76 research outputs found

    Genetically enhanced asynapsis of autosomal chromatin promotes transcriptional dysregulation and meiotic failure

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    During meiosis, pairing of homologous chromosomes and their synapsis are essential prerequisites for normal male gametogenesis. Even limited autosomal asynapsis often leads to spermatogenic impairment, the mechanism of which is not fully understood. The present study was aimed at deliberately increasing the size of partial autosomal asynapsis and analysis of its impact on male meiosis. For this purpose, we studied the effect of t12 haplotype encompassing four inversions on chromosome 17 on mouse autosomal translocation T(16;17)43H (abbreviated T43H). The T43H/T43H homozygotes were fully fertile in both sexes, while +/T43H heterozygous males, but not females, were sterile with meiotic arrest at late pachynema. Inclusion of the t12 haplotype in trans to the T43H translocation resulted in enhanced asynapsis of the translocated autosome, ectopic phosphorylation of histone H2AX, persistence of RAD51 foci, and increased gene silencing around the translocation break. Increase was also on colocalization of unsynapsed chromatin with sex body. Remarkably, we found that transcriptional silencing of the unsynapsed autosomal chromatin precedes silencing of sex chromosomes. Based on the present knowledge, we conclude that interference of meiotic silencing of unsynapsed autosomes with meiotic sex chromosome inactivation is the most likely cause of asynapsis-related male sterility

    The power of comparative and developmental studies for mouse models of Down syndrome

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    Since the genetic basis for Down syndrome (DS) was described, understanding the causative relationship between genes at dosage imbalance and phenotypes associated with DS has been a principal goal of researchers studying trisomy 21 (Ts21). Though inferences to the gene-phenotype relationship in humans have been made, evidence linking a specific gene or region to a particular congenital phenotype has been limited. To further understand the genetic basis for DS phenotypes, mouse models with three copies of human chromosome 21 (Hsa21) orthologs have been developed. Mouse models offer access to every tissue at each stage of development, opportunity to manipulate genetic content, and ability to precisely quantify phenotypes. Numerous approaches to recreate trisomic composition and analyze phenotypes similar to DS have resulted in diverse trisomic mouse models. A murine intraspecies comparative analysis of different genetic models of Ts21 and specific DS phenotypes reveals the complexity of trisomy and important considerations to understand the etiology of and strategies for amelioration or prevention of trisomic phenotypes. By analyzing individual phenotypes in different mouse models throughout development, such as neurologic, craniofacial, and cardiovascular abnormalities, greater insight into the gene-phenotype relationship has been demonstrated. In this review we discuss how phenotype-based comparisons between DS mouse models have been useful in analyzing the relationship of trisomy and DS phenotypes

    Current Wildland Fire Patterns and Challenges in Europe: A Synthesis of National Perspectives

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    Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009–2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action “Fire and the Earth System: Science & Society” funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence

    Blood coagulation and beyond: Position paper from the Fourth Maastricht Consensus Conference on Thrombosis

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    The 4th Maastricht Consensus Conference on Thrombosis (MCCT), included the following themes: Theme 1: The coagulome as a critical driver of cardiovascular disease Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infections associated-coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies This theme included state of the art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: how to utilize ex vivo models? Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularised organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation (ECMO) associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management Plenary presentations addressed controversial areas, ie thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies and clinically tested factor XI(a) inhibitors,both possibly with reduced bleeding risk. Finally, Covid-19 associated coagulopathy is revisited

    Review. Supporting problem structuring with computerbased tools in participatory forest planning

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    Aim of study: This review presents the state-of-art of using computerized techniques for problem structuring (PS) in participatory forest planning. Frequency and modes of using different computerized tool types and their contribution for planning processes as well as critical observations are described, followed by recommendations on how to better integrate PS with the use of forest decision support systems.Area of study: The reviewed research cases are from Asia, Europe, North-America, Africa and Australia.Materials and methods: Via Scopus search and screening of abstracts, 32 research articles from years 2002–2011 were selected for review. Explicit and implicit evidence of using computerized tools for PS was recorded and assessed with content-driven qualitative analysis.Main results: GIS and forest-specific simulation tools were the most prevalent software types whereas cognitive modelling software and spreadsheet and calculation tools were less frequently used, followed by multi-criteria and interactive tools. The typical use type was to provide outputs of simulation–optimization or spatial analysis to negotiation situations or to compile summaries or illustrations afterwards; using software during group negotiation to foster interaction was observed only in a few cases.Research highlights: Expertise in both decision support systems and group learning is needed to better integrate PS and computerized decision analysis. From the knowledge management perspective, it is recommended to consider how the results of PS – e.g. conceptual models – could be stored into a problem perception database, and how PS and decision making could be streamlined by retrievals from such systems.Keywords: facilitated modeling; group negotiation; knowledge management; natural resource management; PSM; soft OR; stakeholders.</p

    Review. Supporting problem structuring with computer-based tools in participatory forest planning

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    <p><em>Aim of study:</em> This review presents the state-of-art of using computerized techniques for problem structuring (PS) in participatory forest planning. Frequency and modes of using different computerized tool types and their contribution for planning processes as well as critical observations are described, followed by recommendations on how to better integrate PS with the use of forest decision support systems.</p><p><em>Area of study:</em> The reviewed research cases are from Asia, Europe, North-America, Africa and Australia.</p><p><em>Materials and methods:</em> Via Scopus search and screening of abstracts, 32 research articles from years 2002–2011 were selected for review. Explicit and implicit evidence of using computerized tools for PS was recorded and assessed with content-driven qualitative analysis.</p><p><em>Main results:</em> GIS and forest-specific simulation tools were the most prevalent software types whereas cognitive modelling software and spreadsheet and calculation tools were less frequently used, followed by multi-criteria and interactive tools. The typical use type was to provide outputs of simulation–optimization or spatial analysis to negotiation situations or to compile summaries or illustrations afterwards; using software during group negotiation to foster interaction was observed only in a few cases.</p><p><em>Research highlights:</em> Expertise in both decision support systems and group learning is needed to better integrate PS and computerized decision analysis. From the knowledge management perspective, it is recommended to consider how the results of PS – e.g. conceptual models – could be stored into a problem perception database, and how PS and decision making could be streamlined by retrievals from such systems.</p><p><strong>Keywords</strong>: facilitated modeling; group negotiation; knowledge management; natural resource management; PSM; soft OR; stakeholders.</p
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