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Genome-wide analysis identifies novel shared loci between depression and white matter microstructure
Depression, a complex and heritable psychiatric disorder, is associated with alterations in white matter microstructure, yet their shared genetic basis remains largely unclear. Utilizing the largest available genome-wide association study (GWAS) datasets for depression (N = 674,452) and white matter microstructure (N = 33,224), assessed through diffusion tensor imaging metrics such as fractional anisotropy (FA) and mean diffusivity (MD), we employed linkage disequilibrium score regression method to estimate global genetic correlations, local analysis of [co]variant association approach to pinpoint genomic regions with local genetic correlations, and conjunctional false discovery rate analysis to identify shared variants. Our findings revealed that depression showed significant local genetic correlations with FA in 37 genomic regions and with MD in 59 regions, while global genetic correlations were weak. Variant-level analysis identified 78 distinct loci jointly associated with depression (25 novel loci) and FA (35 novel loci), and 41 distinct loci associated with depression (17 novel loci) and MD (25 novel loci). Further analyses showed that these shared loci exhibited both concordant and discordant effect directions between depression and white matter traits, as well as distinct yet overlapping hemispheric patterns in their genetic architecture. Enrichment analysis of these shared loci implicated biological processes related to metabolism and regulation. This study provides evidence of a mixed-direction shared genetic architecture between depression and white matter microstructure. The identification of specific loci and pathways offers potential insights for developing targeted interventions to improve white matter integrity and alleviate depressive symptoms.
Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease
Alzheimer’s disease (AD) therapies utilizing amyloid-β (Aβ) immunization have shown potential in clinical trials. Yet, the mechanisms driving Aβ clearance in the immunized AD brain remain unclear. Here, we use spatial transcriptomics to explore the effects of both active and passive Aβ immunization in the AD brain. We compare actively immunized patients with AD with nonimmunized patients with AD and neurologically healthy controls, identifying distinct microglial states associated with Aβ clearance. Using high-resolution spatial transcriptomics alongside single-cell RNA sequencing, we delve deeper into the transcriptional pathways involved in Aβ removal after lecanemab treatment. We uncover spatially distinct microglial responses that vary by brain region. Our analysis reveals upregulation of the triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E (APOE) in microglia across immunization approaches, which correlate positively with antibody responses and Aβ removal. Furthermore, we show that complement signaling in brain myeloid cells contributes to Aβ clearance after immunization. These findings provide new insights into the transcriptional mechanisms orchestrating Aβ removal and shed light on the role of microglia in immune-mediated Aβ clearance. Importantly, our work uncovers potential molecular targets that could enhance Aβ-targeted immunotherapies, offering new avenues for developing more effective therapeutic strategies to combat AD.
Direct observation of the topological pruning in silica glass network; the key for realizing extreme transparency
The optical transparency of silica glass significantly improves when subjected to compression at its melting temperature. Using a rare hydrostatic iso-pressure apparatus capable of reaching 0.98 GPa at 1800 °C with Ar gas as the pressure medium, we obtained centimeter-sized glass samples, allowing us to measure various properties. Both the density and refractive index increased with pressure, while the refractive index dispersion decreased monotonically. However, Rayleigh scattering intensity, and small ring structures show a minimum around 0.8 GPa. High-energy X-ray scattering analysis indicates that the short-range structure, around 4 Å, governs the monotonic trends in the averaged physical properties, such as density and refractive index. In contrast, non-monotonic changes are observed with the disappearance of intermediate-range order at around 8 Å. This simplification of structural ordering is crucial for achieving extreme transparency in silica glass. The effect of suppression of the 8 Å order is well explained by the predicted topological pruning phenomenon, where large voids and small unstable ring structures vanish, leading to the minimal light scattering under high pressure. Our experimental findings also reveal that the optimal pressure for achieving this transparency is much lower than previously predicted, which makes the process more feasible for mass-production applications.
Improved radicchio seedling growth under CsPbI3 perovskite rooftop in a laboratory-scale greenhouse for Agrivoltaics application
Agrivoltaics, integrating photovoltaic systems with crop cultivation, demands semitransparent solar modules to mitigate soil shadowing. Perovskite Solar Cells (PSC) offer competitive efficiency, low fabrication costs, and high solar transmittance, making them suitable for agrivoltaic applications. However, the impact of PSC light filtering on plant growth and transcriptomics remains underexplored. This study investigates the viability and agronomic implications of the growth of radicchio seedlings (Cichorium intybus var. latifolium) in laboratory-scale greenhouses integrating Perovskites-coated rooftops. Eu-enriched CsPbI3 layers are chosen to provide semi-transparency and phase stability while radicchio has limited size and grows in pots. Despite the reduced light exposure, radicchio seedlings exhibit faster growth and larger leaves than in the reference, benefiting from specific spectral filtering. RNA-sequencing reveals differential gene expression patterns reflecting adaptive responses to environmental changes. Simulations of full PSC integration demonstrate a positive energy balance in greenhouses to cover annual energy needs for lighting, irrigation, and air conditioning.
Transition from irrigation with untreated wastewater to treated wastewater and associated benefits and risks
Investments in “Clean water and sanitation” drive a transition from irrigation with untreated to irrigation with treated wastewater. While this transition reduces many health risks, it may decrease crop yields, and soil carbon storage, cause a release of accumulated pollutants from soils, and increase the spread of antibiotic resistance in the environment. A holistic view on multiple SDGs is necessary to maximize benefits and minimize risks of wastewater treatment for irrigation.
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