Biology subjects

Castaldo, G.

Publications and source records attributed to Castaldo, G..

5 recordsLinked to original sources

bioRxiv2020

Long-chain polyphosphates impair SARS-CoV-2 infection and replication: a route for therapy in man

Anti-viral activities of long-chain inorganic polyphosphates (PolyPs) against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection were investigated. In molecular docking analyses, PolyPs interacted with several conserved angiotensin-converting enzyme (ACE)2 and RNA-dependent RNA polymerase (RdRp) amino acids. We thus tested PolyPs for functional interactions in vitro in SARS-CoV-2-infected Vero E6, Caco2 and human primary nasal epithelial cells. Immunofluorescence, qPCR, direct RNA sequencing, FISH and Immunoblotting were used to determine virus loads and transcription levels of genomic(g)RNAs and sub-genomic(sg)RNAs. We show that PolyP120 binds to ACE2 and enhances its proteasomal degradation. PolyP120 shows steric hindrance of the genomic Sars-CoV-2-RNA/RdRP complex, to impair synthesis of positive-sense gRNAs, viral subgenomic transcripts and structural proteins needed for viral replication. Thus, PolyP120 impairs infection and replication of Korean and European (containing non-synonymous variants) SARS-CoV-2 strains. As PolyPs have no toxic activities, we envision their use as a nebulised formula for oropharyngeal delivery to prevent infections of SARS-CoV-2 and during early phases of antiviral therapy.

genetics↗

bioRxiv2019

Impaired cholesterol metabolism in the mice model of cystic fibrosis. A vicious circle?

Patients with cystic fibrosis (CF) have low cholesterol absorption and, despite enhanced endogenous biosynthesis, low serum cholesterol. Herein, we investigated cholesterol metabolism in a murine CF model in comparison to wild type (WT) testing serum and liver surrogate biomarkers together with the hepatic expression of genes involved in cholesterol metabolism. CF mice display lower sterols absorption and increased endogenous biosynthesis. Subsequently, we evaluated the effects of a cholesterol-supplemented diet on cholesterol metabolism in CF and WT mice. The supplementation in WT mice determines biochemical changes similar to humans. Instead, CF mice with supplementation did not show significant changes, except for serum phytosterols (-50%), liver cholesterol (+35%) and TNF mRNA expression, that resulted 5-fold higher than in CF without supplementation. However, liver cholesterol in CF mice with supplementation resulted significantly lower compared to WT supplemented mice. This study shows that in CF mice there is a vicious circle in which the altered bile salts synthesis/secretion contribute to reduce cholesterol digestion/absorption. The consequence is the enhanced liver cholesterol biosynthesis that accumulates in the cell triggering inflammation.

biochemistry↗

bioRxiv2019

Environmental plasticity and colonisation history in the Atlantic salmon microbiome: a translocation experiment

Microbial communities associated with the gut and the skin are strongly influenced by environmental factors, and can rapidly adapt to change. Historical processes may also affect the microbiome. In particular, variation in microbial colonisation in early life has the potential to induce lasting effects on microbial assemblages. However, little is known about the relative extent of microbiome plasticity or the importance of historical colonisation effects following environmental change, especially for non-mammalian species. To investigate this we performed a reciprocal translocation of Atlantic salmon between captive and semi-natural conditions. Wild and hatchery-reared fry were transferred to three common garden experimental environments for six weeks: standard hatchery conditions, hatchery conditions with an enriched diet, and simulated wild conditions. We characterised the faecal and skin microbiome of individual fish before and after the environmental translocation, using a BACI (before-after-control-impact) design. We found evidence of extensive plasticity in both gut and skin microbiota, with the greatest changes in alpha and beta diversity associated with the largest changes in environment and diet. Microbiome richness and diversity were entirely determined by environment, with no detectable historical effects of fish origin. Microbiome structure was also strongly influenced by current environmental conditions but, for the first time in fish, we also found evidence of colonisation history, including a number of OTUs characteristic of captive rearing. These results may have important implications for host adaptation to local selective pressures, and also highlight how conditions during early life can have a long-term influence on the microbiome and, potentially, host health.

microbiology↗

bioRxiv2018

Density-dependent changes in neophobia and stress-coping styles in the worlds oldest farmed fish

Farmed fish are typically reared at densities much higher than those observed in the wild, but to what extent crowding results in abnormal behaviours that can impact welfare and stress coping styles is subject to debate. Neophobia (i.e. fear of the new) is thought to be adaptive under natural conditions by limiting risks, but it is potentially maladapted in captivity, where there are no predators or novel foods. We reared juvenile Nile tilapia (Oreochromis niloticus) for six weeks at either high (50g/L) or low density (14g/L), assessed the extent of skin and eye darkening (two proxies of chronic stress), and exposed them to a novel object in an open-test arena, with and without cover, to assess the effects of density on neophobia and stress coping styles. Fish reared at high density were darker, more neophobic, less aggressive, less mobile and less likely to take risks than those reared at low density, and these effects were exacerbated when no cover was available. Thus, the reactive coping style shown by fish at high density was very different from the proactive coping style shown by fish at low density. Our findings provide novel insights into the plasticity of fish behaviour and the effects of aquaculture intensification on one of the worlds oldest farmed and most invasive fish, and highlight the importance of considering context. Crowding could have a positive effect on the welfare of tilapia by reducing aggressive behaviour, but it can also make fish chronically stressed and more fearful, which could make them less invasive.

animal behavior and cognition↗

bioRxiv2017

The Parasite Extinction Assessment & Red List: an open-source, online biodiversity database for neglected symbionts

Parasite conservation is a rapidly growing field at the intersection of ecology, epidemiology, parasitology, and public health. The overwhelming diversity of parasitic life on earth, and recent work showing that parasites and other symbionts face severe extinction risk, necessitates infrastructure for parasite conservation assessments. Here, we describe the release of the Parasite Extinction Assessment & Red List (PEARL) version 1.0, an open-access database of conservation assessments and distributional data for almost 500 macroparasitic invertebrates. The current approach to vulnerability assessment is based on range shifts and loss from climate change, and will be expanded as additional data (e.g., host-parasite associations and coextinction risk) is consolidated in PEARL. The web architecture is also open-source, scalable, and extensible, making PEARL a template for more eZcient red listing for other high-diversity, data-de1cient groups. Future iterations will also include new functionality, including a user-friendly open data pository and automated assessment and re-listing.

ecology↗