1,847 research outputs found

    HDAC6 is a bruchpilot deacetylase that facilitates neurotransmitter release

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    Presynaptic densities are specialized structures involved in synaptic vesicle tethering and neurotransmission; however, the mechanisms regulating their function remain understudied. In Drosophila, Bruchpilot is a major constituent of the presynaptic density that tethers vesicles. Here, we show that HDAC6 is necessary and sufficient for deacetylation of Bruchpilot. HDAC6 expression is also controlled by TDP-43, an RNA-binding protein deregulated in amyotrophic lateral sclerosis (ALS). Animals expressing TDP-43 harboring pathogenic mutations show increased HDAC6 expression, decreased Bruchpilot acetylation, larger vesicle-tethering sites, and increased neurotransmission, defects similar to those seen upon expression of HDAC6 and opposite to hdac6 null mutants. Consequently, reduced levels of HDAC6 or increased levels of ELP3, a Bruchpilot acetyltransferase, rescue the presynaptic density defects in TDP-43-expressing flies as well as the decreased adult locomotion. Our work identifies HDAC6 as a Bruchpilot deacetylase and indicates that regulating acetylation of a presynaptic release-site protein is critical for maintaining normal neurotransmission

    Recognition of differences in the capacity to deal with floods—A cross-country comparison of flood risk management

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    Flood risks worldwide are increasing due to climate change. Managing these risks is ever more necessary. Although flood risk management (FRM) is often understood as a technical challenge, it also involves decisions about the distribution of resources and risks in floods, which can be inherently unfair. People are disparately affected by floods due to their location. Because of their various socioeconomic and demographic characteristics, they also differ in their capacity to deal with floods. These differences need to be recognised in FRM to prevent disproportionate impacts on vulnerable communities. However, at present, a knowledge gap exists on how to make FRM more inclusive and just, and discussions on recognition justice in the context of FRM are scarce. This article therefore examines recognition of differences in the capacity of people to deal with floods in FRM in England (United Kingdom), Finland, Flanders (Belgium) and France. We analyse if, and how, these differences are recognised in FRM policy and practice and through decision-making procedures, drawing on examples from the implementation of five FRM strategies in each country (flood risk prevention, flood defence, flood risk mitigation, flood preparation and flood recovery). Furthermore, we aim to highlight opportunity spaces to strengthen recognition justice in future FRM

    MP764: Field Manual for Managing Eastern White Pine Health in New England

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    This manual provides basic information for identifying and evaluating important health problems of eastern white pine in New England. The health problems include: • White pine weevil • White pine blister rust • Caliciopsis canker • White pine bast scale • White pine needle damage • Red rot or Red-ring rot In addition to providing descriptions of symptoms, signs, and risk factors, recommendations for white pine silviculture are described for managing stands for low densities and crop trees.https://digitalcommons.library.umaine.edu/aes_miscpubs/1039/thumbnail.jp

    The time of the Roma in times of crisis: Where has European neoliberal capitalism failed?

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    This paper argues that the economic and financial crisis that has ensnared Europe from the late 2000s has been instrumental in reshaping employment and social relations in a detrimental way for the majority of the European people. It argues that the crisis has exacerbated the socio-economic position of most Roma people, immigrants as well as of other vulnerable groups. This development is approached here as an outcome of the widening structural inequalities that underpin the crisis within an increasingly neoliberalised Europe. Through recent policy developments and public discourses from a number of European countries I show how rising inequalities nurture racialised social tensions. My account draws on classic and contemporary theoretical propositions that have been propounded about the nature of capitalism, its contemporary re-articulation as well as its ramification for the future of Europe

    Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-beta plaques

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    BACKGROUND: Increasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular and functional studies in rodent models. However, these models may not fully recapitulate human disease as human and rodent astrocytes differ considerably in morphology, functionality, and gene expression. RESULTS: To address these challenges, we established an approach to study human astrocytes within the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived astrocyte progenitors into neonatal brains. Xenografted hiPSC-derived astrocyte progenitors differentiated into astrocytes that integrated functionally within the mouse host brain and matured in a cell-autonomous way retaining human-specific morphologies, unique features, and physiological properties. In Alzheimer´s chimeric brains, transplanted hiPSC-derived astrocytes responded to the presence of amyloid plaques undergoing morphological changes that seemed independent of the APOE allelic background. CONCLUSIONS: In sum, we describe here a promising approach that consist of transplanting patient-derived and genetically modified astrocytes into the mouse brain to study human astrocyte pathophysiology in the context of Alzheimer´s disease

    Should We Continue to Measure Endometrial Thickness in Modern-Day Medicine? The Effect on Live Birth Rates and Birth Weight

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    The evaluation of endometrial thickness (EMT) is still part of standard cycle monitoring during IVF, despite the lack of robust evidence of any value of this measurement to predict little revalidation in contemporary medical practice; other tools, however, such as endocrine profile monitoring, have become increasingly popular. The aim of this study was to reassess whether EMT affects the outcome of a fresh embryo transfer in modern-day medicine, using a retrospective, single-centre cohort of 3350 IVF cycles (2827 women) carried out between 2010 and 2014. In the multivariate regression analysis, EMT was non-linearly associated with live birth, with live birth rates being the lowest with an EMT less than 7.0 mm (21.6%; P < 0.001) and then between 7.0 mm and 9.0 mm (30.2%; P = 0.008). An EMT less than 7.0 mm was also associated with a decrease in neonatal birthweight z-scores (-0.40; 95% CI -0.69 to -0.12). In conclusion, these results reaffirm the use of EMT as a potential prognostic tool for live birth rates and neonatal birthweight in contemporary IVF, namely when considered together with other ovarian stimulation monitoring methods, such as the late-follicular endocrine profile.info:eu-repo/semantics/publishedVersio
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