164 research outputs found

    Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping

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    ATRX and MeCP2 belong to an expanding group of chromatin-associated proteins implicated in human neurodevelopmental disorders, although their gene-regulatory activities are not fully resolved. Loss of ATRX prevents full repression of an imprinted gene network in the postnatal brain and in this study we address the mechanistic aspects of this regulation. We show that ATRX binds many imprinted domains individually but that transient co-localization between imprinted domains in the nuclei of neurons does not require ATRX. We demonstrate that MeCP2 is required for ATRX recruitment and that deficiency of either ATRX or MeCP2 causes decreased frequency of long-range chromatin interactions associated with altered nucleosome density at CTCF-binding sites and reduced CTCF occupancy. These findings indicate that MeCP2 and ATRX regulate gene expression at a subset of imprinted domains by maintaining a nucleosome configuration conducive to CTCF binding and to the maintenance of higher order chromatin structure

    A review of the dodo and its ecosystem: insights from a vertebrate concentration Lagerstätte in Mauritius

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    The dodo Raphus cucullatus Linnaeus,1758, an extinct and flightless, giant pigeon endemic to Mauritius, has fascinated people since its discovery, yet has remained surprisingly poorly known. Until the mid-19th century, almost all that was known about the dodo was based on illustrations and written accounts by 17th century mariners, often of questionable accuracy. Furthermore, only a few fragmentary remains of dodos collected prior to the bird's extinction exist. Our understanding of the dodo's anatomy was substantially enhanced by the discovery in 1865 of subfossil bones in a marsh called the Mare aux Songes, situated in southeastern Mauritius. However, no contextual information was recorded during early excavation efforts, and the majority of excavated material comprised larger dodo bones, almost all of which were unassociated. Here we present a modern interdisciplinary analysis of the Mare aux Songes, a 4200-year-old multitaxic vertebrate concentration Lagerstätte. Our analysis of the deposits at this site provides the first detailed overview of the ecosystem inhabited by the dodo. The interplay of climatic and geological conditions led to the exceptional preservation of the animal and associated plant remains at the Mare aux Songes and provides a window into the past ecosystem of Mauritius. This interdisciplinary research approach provides an ecological framework for the dodo, complementing insights on its anatomy derived from the only associated dodo skeletons known, both of which were collected by Etienne Thirioux and are the primary subject of this memoir.Additional co-authors: Anneke H. Van Heteren, Vikash Rupear, Gorah Beebeejaun, Alan Grihault, J. (Hans) Van Der Plicht, Marijke Besselink, Juliën K. Lubeek, Max Jansen, Hege Hollund, Beth Shapiro, Matthew Collins, Mike Buckley, Ranjith M. Jayasena, Nicolas Porch, Rene Floore, Frans Bunnik, Andrew Biedlingmaier, Jennifer Leavitt, Gregory Monfette, Anna Kimelblatt, Adrienne Randall, Pieter Floore & Leon P. A. M. Claessen

    Collective Thomson scattering system for determination of ion properties in a high flux plasma beam

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    A collective Thomson scattering system has been developed for measuring ion temperature, plasma velocity and impurity concentration in the high density magnetized Magnum-PSI plasma beam, allowing for measurements at low temperature (4 x 10 20m3,while avoiding laser plasma heating caused by inverse Bremsstrahlung. The collective Thomson scattering system is based on the fundamental mode of a seeded Nd:YAG laser and equipped with an LIVAR M506 camera (EBABS technology). The first collective Thomson scattering measurements are taken at the linear plasma generator Pilot-PSI, 40 mm downstream of the cascaded arc source. At this location, the ion temperature is about equal to the electron temperature in the bulk of the plasma beam

    Robust impurity detection and tracking for tokamaks

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    A robust impurity detection and tracking code, able to generate large sets of dust tracks from tokamak camera footage, is presented. This machine learning–based code is tested with cameras from the Joint European Torus, Doublet-III-D, and Magnum-PSI and is able to generate dust tracks with a 65–100% classification accuracy. Moreover, the number dust particles detected from a single camera shot can be up to the order of 1000. Several areas of improvement for the code are highlighted, such as generating more significant training data sets and accounting for selection biases. Although the code is tested with dust in single two-dimensional camera views, it could easily be applied to multiple-camera stereoscopic reconstruction or nondust impurities.</p

    5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells

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    YesMammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC) locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac) revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene promoters and enhancers at the multi-TAD EDC locus in skin epithelial cells are cell type-specific and involve extensive contacts within TADs as well as between different gene-rich TADs, forming the framework for lineage-specific transcription.This study was supported by the grants 5R01AR064580 and 1RO1AR071727 to VAB, TKS and AAS, as well as by the grants from MRC (MR/ M010015/1) and BBSRC (BB/K010050/1) to VAB

    Inter-MAR Association Contributes to Transcriptionally Active Looping Events in Human β-globin Gene Cluster

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    Matrix attachment regions (MARs) are important in chromatin organization and gene regulation. Although it is known that there are a number of MAR elements in the β-globin gene cluster, it is unclear that how these MAR elements are involved in regulating β-globin genes expression. Here, we report the identification of a new MAR element at the LCR(locus control region) of human β-globin gene cluster and the detection of the inter-MAR association within the β-globin gene cluster. Also, we demonstrate that SATB1, a protein factor that has been implicated in the formation of network like higher order chromatin structures at some gene loci, takes part in β-globin specific inter-MAR association through binding the specific MARs. Knocking down of SATB1 obviously reduces the binding of SATB1 to the MARs and diminishes the frequency of the inter-MAR association. As a result, the ACH establishment and the α-like globin genes and β-like globin genes expressions are affected either. In summary, our results suggest that SATB1 is a regulatory factor of hemoglobin genes, especially the early differentiation genes at least through affecting the higher order chromatin structure

    Plasma-wall interaction studies within the EUROfusion consortium: Progress on plasma-facing components development and qualification

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    This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 under grant agreement No 633053. The views and opinions expressed herein do not necessarily reflect those of the European Commission.The provision of a particle and power exhaust solution which is compatible with first-wall components and edge-plasma conditions is a key area of present-day fusion research and mandatory for a successful operation of ITER and DEMO. The work package plasma-facing components (WP PFC) within the European fusion programme complements with laboratory experiments, i.e. in linear plasma devices, electron and ion beam loading facilities, the studies performed in toroidally confined magnetic devices, such as JET, ASDEX Upgrade, WEST etc. The connection of both groups is done via common physics and engineering studies, including the qualification and specification of plasma-facing components, and by modelling codes that simulate edge-plasma conditions and the plasma-material interaction as well as the study of fundamental processes. WP PFC addresses these critical points in order to ensure reliable and efficient use of conventional, solid PFCs in ITER (Be and W) and DEMO (W and steel) with respect to heat-load capabilities (transient and steady-state heat and particle loads), lifetime estimates (erosion, material mixing and surface morphology), and safety aspects (fuel retention, fuel removal, material migration and dust formation) particularly for quasi-steady-state conditions. Alternative scenarios and concepts (liquid Sn or Li as PFCs) for DEMO are developed and tested in the event that the conventional solution turns out to not be functional. Here, we present an overview of the activities with an emphasis on a few key results: (i) the observed synergistic effects in particle and heat loading of ITER-grade W with the available set of exposition devices on material properties such as roughness, ductility and microstructure; (ii) the progress in understanding of fuel retention, diffusion and outgassing in different W-based materials, including the impact of damage and impurities like N; and (iii), the preferential sputtering of Fe in EUROFER steel providing an in situ W surface and a potential first-wall solution for DEMO.European Commission; Consortium for Ocean Leadership 633053; Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART

    Denial of long-term issues with agriculture on tropical peatlands will have devastating consequences

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    Long-term thermal sensitivity of Earth’s tropical forests

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    The sensitivity of tropical forest carbon to climate is a key uncertainty in predicting global climate change. Although short-term drying and warming are known to affect forests, it is unknown if such effects translate into long-term responses. Here, we analyze 590 permanent plots measured across the tropics to derive the equilibrium climate controls on forest carbon. Maximum temperature is the most important predictor of aboveground biomass (−9.1 megagrams of carbon per hectare per degree Celsius), primarily by reducing woody productivity, and has a greater impact per °C in the hottest forests (>32.2°C). Our results nevertheless reveal greater thermal resilience than observations of short-term variation imply. To realize the long-term climate adaptation potential of tropical forests requires both protecting them and stabilizing Earth’s climate
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