Biology subjects

Capitani, L.

Publications and source records attributed to Capitani, L..

3 recordsLinked to original sources

bioRxiv2026

New Human IPSC Models of Late-onset Alzheimer's Disease Polygenic Risk Identify Multiple Impairments of Microglial Function

Genetic discoveries implicate microglia in late-onset Alzheimers disease (AD). We modelled AD in a powerful study of 51 human induced pluripotent stem cell (iPSC) microglia derived from high-polygenic risk AD or low-risk cognitively well individuals, sampled from a large cohort. We explored mitochondrial function, cytokine secretion, endocytosis, phagocytosis, lipid accumulation, calcium store release, and chemotaxis under basal conditions and immune challenge. High polygenic risk was independently associated with significant functional deficits in iPSC microglia under immune challenge, in mitochondrial ATP production (p=0.005, -13%), and inflammatory cytokine release (IL-6: p=0.018, -42%; TNF p=0.026, -38.5%). Furthermore, a selective deficit in amyloid-{beta} uptake was identified (p=0.00477, -5.9%). Deficits in inflammatory cytokine release were driven by APOE {varepsilon}4. These findings reflect primary changes in AD pathogenesis predating plaque formation and validate a human in vitro platform for late-onset AD to further understand disease mechanisms and screen drug or genetic therapies.

neuroscience↗

bioRxiv2025

Rewilding beyond the wilderness: Beavers can restore stream biodiversity from urban to agricultural to natural landscapes

1 Beavers have been promoted as a cost-effective nature-based solution to restore degraded stream ecosystems and enhance overall biodiversity. However, the extent to which beaver-engineering boosts biodiversity in human-impacted landscapes remains poorly understood. 2 We assessed the responses of aquatic and terrestrial taxa (amphibians, dragonflies, fish, macrophytes, plankton, terrestrial vegetation, bats, aquatic, flying and terrestrial invertebrates) to beaver-engineering along a gradient of human land-use intensity in Switzerland. In 16 streams, we measured species richness, abundance, unique species richness, evenness, beta and gamma diversity in a beaver-engineered site with beaver dams and a control site without beaver activity. 3 Especially aquatic and semi-aquatic species profited from beaver-engineering. In response to beaver-engineering, amphibians, dragonflies, macrophytes, and plankton increased in species richness, abundance and unique species richness, while fish and terrestrial plants increased in species richness and unique species richness. Bats only increased in unique species richness, while for the other terrestrial taxa, we found no difference between beaver-engineered and control sites. Community evenness remained largely unaffected across all groups. 4 Overall, beaver-engineering increased biodiversity across a land-use gradient. For macrophytes and amphibians (species richness, unique species richness and abundance), as well for dragonflies (species richness and unique species richness), increases were smaller under higher land-use intensity. For the remaining taxa and metrics, we found no relationship between land-use intensity and responses to beaver engineering. 5 However, for beta-diversity, we found that sites with a high land-use intensity had a lower component of nestedness and stronger community turnover in comparison to more natural sites, with a significant effect for macrophytes. Gamma species richness was generally unaffected by land- use intensity, except for amphibians, which were often only found in beaver-engineered sites in high- land-use intensity areas. 6 Synthesis and applications. Our findings demonstrate that beaver-engineering significantly enhances local biodiversity across aquatic and terrestrial ecosystems, even at sites with high land-use intensity. Hence, beavers can effectively restore stream biodiversity from urban to agricultural to natural landscapes. Integrating beaver-engineering into river restoration strategies can substantially advance biodiversity goals under frameworks such as the EU Water Framework Directive and national conservation policies.

ecology↗

bioRxiv2019

Rheumatoid arthritis patients express a skewed repertoire of polyclonal, hypomutated B-cell receptors

ObjectivesThe success of B cell depletion therapy in rheumatoid arthritis (RA) therapy testifies to their importance in disease pathogenesis, but the precise B cells mediating this are unclear. For example, it is unknown if RA patients predominantly express a limited number of circulating clonally expanded populations of B cells with highly mutated B cell antigen receptors (BCRs) that would constitute a shared antigen driven response.\n\nMethodsTo address this, we have undertaken the largest study to date utilising next generation sequencing (NGS), to identify the full length of the peripheral blood BCR sequences from the antigen-binding heavy chain. Between 25,000 to 200,000 BCR sequences per patient were analysed from 127 newly diagnosed RA patients, 16 heathy controls, 16 RA patients with established disease and 8 paired blood and synovial samples. This was complemented with B cell subset analysis from an additional 64 RA patients and 22 healthy controls.\n\nResultsRA patients expressed a significantly higher percentage of circulating poorly mutated polyclonal IgG+ve variable heavy (IgG-Vh) BCR sequences, both at the time of diagnosis and following treatment. These sequences resided predominantly within TNF-alpha secreting IgG+veCD27-ve B cells, that were expanded in RA peripheral blood and enriched in the rheumatoid synovium. Surprisingly, peripheral and synovial B cell repertoires of RA patients are quite distinct, sharing very few IgG sequences.\n\nConclusionsThis is the first report to conclusively establish that a substantial component of the peripheral B cell repertoire in RA consists of polyclonal hypomutated IgG+ve BCRs that may play a critical role in driving an autoimmune mediated inflammation.

immunology↗