Biology subjects

Greco, F.

Publications and source records attributed to Greco, F..

3 recordsLinked to original sources

bioRxiv2024

Asymptomatic infection and antibody prevalence to co-occurring avian influenza viruses vary substantially between sympatric seabird species following H5N1 outbreaks

Emerging infectious diseases are of major concern to animal and human health. Recent emergence of high pathogenicity avian influenza virus (HPAIV) (H5N1 clade 2.3.4.4b) led to substantial global mortality across a range of host species. Co-occurring species showed marked differences in mortality, generating an urgent need for better epidemiological understanding within affected populations. We therefore tested for antibodies, indicative of previous exposure and recovery, and for active viral infection in apparently healthy individuals (n=350) across five co-occurring seabird species on the Isle of May, Scotland, during 2023, following H5N1 HPAIV associated mortality in the preceding summer. Antibody prevalence to AIV subtypes varied substantially between species, ranging from 1.1% in European shags (Gulosus aristotelis) (to H5) to 78.7% in black-legged kittiwakes (Rissa tridactyla) (to H16 or both H13 and H16), and between 31-41% for three auk species (H5, H16 or both). At least 20.4% of auks had antibodies to an as yet unidentified subtype, suggesting further subtypes circulating in the population. We found low levels of active, but asymptomatic, AIV infection in individuals (1.6-4.5%), but excluded this as H5N1. Our results emphasise the importance of testing healthy individuals to understand the prevalence of co-circulating AIV subtypes in wild populations, and the potential for future reassortment events which could alter virus behaviour and impact.

ecology↗

bioRxiv2024

Atlastin-1 regulates endosomal tubulation and lysosomal proteolysis in human cortical neurons

Mutation of the ATL1 gene is one of the most common causes of hereditary spastic paraplegia (HSP), a group of genetic neurodegenerative conditions characterised by distal axonal degeneration of the corticospinal tract axons. Atlastin-1, the protein encoded by ATL1, is one of three mammalian atlastins, which are homologous dynamin-like GTPases that control endoplasmic reticulum (ER) morphology by fusing tubules to form the three-way junctions that characterise ER networks. However, it is not clear whether atlastin-1 is required for correct ER morphology in human neurons and if so what the functional consequences of lack of atlastin-1 are. Using CRISPR-inhibition we generated human cortical neurons lacking atlastin-1. We demonstrate that ER morphology was altered in these neurons, with a reduced number of three-way junctions. Neurons lacking atlastin-1 had longer endosomal tubules, suggestive of defective tubule fission. This was accompanied by reduced lysosomal proteolytic capacity. As well as demonstrating that atlastin-1 is required for correct ER morphology in human neurons, our results indicate that lack of a classical ER-shaping protein such as atlastin-1 may cause altered endosomal tubulation and lysosomal proteolytic dysfunction. Furthermore, they strengthen the idea that defective lysosome function contributes to the pathogenesis of a broad group of HSPs, including those where the primary localisation of the protein involved is not at the endolysosomal system.

cell biology↗

bioRxiv2020

Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration

Intestinal organoids capture essential features of the intestinal epithelium such as folding of the crypt, spatial compartmentalization of different cell types, and cellular movements from crypt to villus-like domains. Each of these processes and their coordination in time and space requires patterned physical forces that are currently unknown. Here we map the three-dimensional cell-ECM and cell-cell forces in mouse intestinal organoids grown on soft hydrogels. We show that these organoids exhibit a non-monotonic stress distribution that defines mechanical and functional compartments. The stem cell compartment pushes the ECM and folds through apical constriction, whereas the transit amplifying zone pulls the ECM and elongates through basal constriction. Tension measurements establish that the transit amplifying zone isolates mechanically the stem cell compartment and the villus-like domain. A 3D vertex model shows that the shape and force distribution of the crypt can be largely explained by cell surface tensions following the measured apical and basal actomyosin density. Finally, we show that cells are pulled out of the crypt along a gradient of increasing tension, rather than pushed by a compressive stress downstream of mitotic pressure as previously assumed. Our study unveils how patterned forces enable folding and collective migration in the intestinal crypt.

cell biology↗