5,644 research outputs found

    Terrestrial Very-Long-Baseline Atom Interferometry: Workshop Summary

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    Summary of the Terrestrial Very-Long-Baseline Atom Interferometry Workshop held at CERN: https://indico.cern.ch/event/1208783/This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more km-scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions

    APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints

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    The APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). The contribution of microglial APOE4 to AD pathogenesis is unknown, although APOE has the most enriched gene expression in neurodegenerative microglia (MGnD). Here, we show in mice and humans a negative role of microglial APOE4 in the induction of the MGnD response to neurodegeneration. Deletion of microglial APOE4 restores the MGnD phenotype associated with neuroprotection in P301S tau transgenic mice and decreases pathology in APP/PS1 mice. MGnD–astrocyte cross-talk associated with β-amyloid (Aβ) plaque encapsulation and clearance are mediated via LGALS3 signaling following microglial APOE4 deletion. In the brains of AD donors carrying the APOE4 allele, we found a sex-dependent reciprocal induction of AD risk factors associated with suppression of MGnD genes in females, including LGALS3, compared to individuals homozygous for the APOE3 allele. Mechanistically, APOE4-mediated induction of ITGB8–transforming growth factor-β (TGFβ) signaling impairs the MGnD response via upregulation of microglial homeostatic checkpoints, including Inpp5d, in mice. Deletion of Inpp5d in microglia restores MGnD–astrocyte cross-talk and facilitates plaque clearance in APP/PS1 mice. We identify the microglial APOE4–ITGB8–TGFβ pathway as a negative regulator of microglial response to AD pathology, and restoring the MGnD phenotype via blocking ITGB8–TGFβ signaling provides a promising therapeutic intervention for AD.</p

    Measurement of ultrashort laser pulses with a time-dependent polarization state using the d-scan technique

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    The dispersion scan (d-scan) technique is extended to measurement of the time-dependent polarization state of ultrashort laser pulses. In the simplest implementation for linearly polarized ultrashort pulses, the d-scan technique records the second harmonic generation spectrum as a function of a known spectral phase manipulation. By applying this method to two orthogonally polarized projections of an arbitrary polarized electric field and by measuring the spectrum at an intermediate angle, we can reconstruct the evolution over time of the polarization state. We demonstrate the method by measuring a polarization gate generated from 6 fs6\,\mathrm{fs} pulses with a combination of waveplates. The measurements are compared to simulations, showing an excellent agreement

    bii4africa dataset

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    The bii4africa dataset is presented in a multi-spreadsheet .xlsx file. The raw data spreadsheet (‘Scores_Raw’) includes 31,313 individual expert estimates of the impact of a sub-Saharan African land use on a species response group of terrestrial vertebrates or vascular plants. Estimates are reported as intactness scores - the remaining proportion of an ‘intact’ reference (pre-industrial or contemporary wilderness area) population of a species response group in a land use, on a scale from 0 (no individuals remain) through 0.5 (half the individuals remain), to 1 (same as the reference population) and, in limited cases, to 2 (two or more times the reference population). For species that thrive in human-modified landscapes, scores could be greater than 1 but not exceeding 2 to avoid extremely large scores biasing aggregation exercises. Expert comments are included alongside respective estimates

    Differential metabolic responses in bold and shy sea anemones during a simulated heatwave.

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    As climate change-induced heatwaves become more common, phenotypic plasticity at multiple levels is a key mitigation strategy by which organisms can optimise selective outcomes. In ectotherms, changes to both metabolism and behaviour can help alleviate thermal stress. Nonetheless, no study in any ectotherm has yet empirically investigated how changing temperatures affect among-individual differences in the associations between these traits. Using the beadlet anemone (Actinia equina), an intertidal species from a thermally heterogeneous environment, we investigated how individual metabolic rates, linked to morphotypic differences in A. equina, and boldness were related across changing temperatures. A crossed-over design and a temporal control was used to test the same individuals at a non-stressful temperature, 13oC, and under a simulated heatwave at 21oC. At each temperature, short-term repeated measurements of routine metabolic rate (RMR) and a single measurement of a repeatable boldness-related behaviour, immersion response-time (IRT), were made. Individual differences, but not morphotypic differences, were highly predictive of metabolic plasticity, and the plasticity of RMR was associated with IRT. At 13oC, shy animals had the highest metabolic rates, while at 21oC this relationship was reversed. Individuals that were bold at 13oC also exhibited the highest metabolic rates at 21oC. Additional metabolic challenges during heatwaves could be detrimental to fitness in bold individuals. Equally, lower metabolic rates at non-stressful temperatures could be necessary for optimal survival as heatwaves become more common. These results provide novel insight into the relationship between metabolic and behavioural plasticity, and its adaptive implications in a changing climate

    Maskrey et al. 2024 (data and code)

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    Data associated with the paper "Differential metabolic responses in bold and shy sea anemones during a simulated heatwave"</p

    bi4africa dataset - open source

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    The bii4africa dataset is presented in a multi-spreadsheet .ods file. The raw data spreadsheet (‘Scores_Raw’) includes 31,313 individual expert estimates of the impact of a sub-Saharan African land use on a species response group of terrestrial vertebrates or vascular plants. Estimates are reported as intactness scores - the remaining proportion of an ‘intact’ reference (pre-industrial or contemporary wilderness area) population of a species response group in a land use, on a scale from 0 (no individuals remain) through 0.5 (half the individuals remain), to 1 (same as the reference population) and, in limited cases, to 2 (two or more times the reference population). For species that thrive in human-modified landscapes, scores could be greater than 1 but not exceeding 2 to avoid extremely large scores biasing aggregation exercises. Expert comments are included alongside respective estimates

    Influence of Trimethylamine N-Oxide on Platelet Activation

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    Microbiome-derived trimethylamine N-oxide (TMAO) has been associated with platelet hyperreactivity and subsequent atherogenesis. Whether physiological TMAO-levels influence plateletderived lipid mediators remains unknown. Little is known about pre-analytic factors potentially influencing TMAO concentrations. We aimed at developing a quantitative LC-MS/MS method to investigate in-vivo and in-vitro pre-analytical factors in TMAO analysis to properly assess the proposed activating effect of TMAO on platelets. TMAO, betaine, carnitine, and choline were analyzed by HILIC-ESI-MS/MS within 6 min total run time. Method validation included investigation of reproducibility, recovery, sensitivity, and in-vitro pre-analytical factors. A 24-h monitoring experiment was performed, evaluating in-vivo pre-analytical factors like daytime or diet. Finally, the effects of different TMAO concentrations on platelet activation and corresponding alterations of plateletderived eicosanoid release were analyzed. The method showed high reproducibility (CVs 5.3%), good recovery rates (96–98%), and negligible in-vitro pre-analytical effects. The influence of in-vivo pre-analytical factors on TMAO levels was not observable within the applied experimental conditions. We did not find any correlation between TMAO levels and platelet activation at physiological TMAO concentrations, whereas platelet-derived eicosanoids presented activation of the cyclooxygenase and lipoxygenase pathways. In contrast to previously published results, we did not find any indications regarding diet dependency or circadian rhythmicity of TMAO levels. Our results do not support the hypothesis that TMAO increases platelet responsiveness via the release of lipid-mediators

    Estimating dose—response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and revised Mendelian randomization analyses

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    Background Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Methods Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Findings Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically predicted 25(OH)D with coronary heart disease (odds ratio [OR] per 10 nmol/L higher genetically-predicted 25(OH)D concentration 0·98, 95% CI 0·95–1·01), stroke (1·01, [0·97–1·05]), or all-cause mortality (0·99, 0·95–1·02). Null findings were also observed in genetic analyses for cause-specific mortality outcomes, and in stratified genetic analyses for all outcomes at all observed levels of 25(OH)D concentrations. Interpretation Stratified Mendelian randomisation analyses suggest a lack of causal relationship for 25(OH)D concentrations with both cardiovascular and mortality outcomes for individuals at all levels of 25(OH)D. Our findings suggest that substantial reductions in mortality and cardiovascular morbidity due to long-term low-dose vitamin D supplementation are unlikely even if targeted at individuals with low vitamin D status
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