Biology subjects

Greco, S.

Publications and source records attributed to Greco, S..

4 recordsLinked to original sources

bioRxiv2024

The proteotranscriptomic characterization of venom in the white seafan Eunicella singularis elucidates the evolution of Octocorallia arsenal

All the members of the phylum Cnidaria are characterized by the production of venom in specialized structures, the nematocysts. Venom of jellyfish (Medusozoa) and sea anemones (Anthozoa) has been investigated since the 1970s, revealing a remarkable molecular diversity. Specifically, sea anemones harbour a rich repertoire of neurotoxic peptides, some of which have been developed in drug leads. However, venoms of the vast majority of Anthozoa species remain uncharacterized, particularly in the class Octocorallia. To fill this gap, we applied a proteo-transcriptomic approach to investigate the venom composition in Eunicella singularis, a gorgonian species common in Mediterranean hard-bottom benthic communities. Our results highlighted the peculiarities of the venom of E. singularis with respect to sea anemones, which is reflected in the presence of several toxins with novel folds, worthy of functional characterization. A comparative genomic survey across the octocoral radiation allowed us to generalize these findings and provided insights into the evolutionary history, molecular diversification patterns and putative adaptive roles of venom toxins. A comparison of whole-body and nematocyst proteomes revealed the presence of different cytolytic toxins inside and outside the nematocysts. Two instances of differential maturation patterns of toxin precursors were also identified, highlighting the intricate regulatory pathways underlying toxin expression.

evolutionary biology↗

bioRxiv2023

Gene expression shifts in Emperor penguin adaptation to the extreme Antarctic environment

Gene expression can accelerate ecological divergence by rapidly tweaking the response of an organism to novel environments, with more divergent environments exerting stronger selection and supposedly, requiring faster adaptive responses. Organisms adapted to extreme environments provide ideal systems to test this hypothesis, particularly when compared to related species with milder ecological niches. The Emperor penguin (Aptenodytes forsteri) is the only warm-blooded vertebrate breeding in the harsh Antarctic winter, in stark contrast with the less cold-adapted sister species, the King penguin (A. patagonicus). Assembling the first de novo transcriptomes and analysing multi-tissue (brain, kidney, liver, muscle, skin) RNAseq data from natural populations of both species, we quantified the shifts in tissue-enhanced genes, co-expression gene networks, and differentially expressed genes characterising Emperor penguin adaptation to extreme Antarctic ecology. Our analyses revealed the crucial role played by muscle and liver in temperature homeostasis, fasting and whole-body energy metabolism (glucose/insulin regulation, lipid metabolism, fatty acid beta-oxidation, and blood coagulation). Repatterning at the regulatory level appears as more important in the brain of the Emperor penguin, showing the lowest signature of differential gene expression but the largest co-expression gene network shift. Nevertheless, over-expressed genes related to mTOR signalling in the brain and the liver support their central role in cold and fasting responses. Besides contributing to understanding the genetics underlying complex traits, like body energy reservoir management, our results provide a first insight into the role of gene expression in adaptation to one of the most extreme environmental conditions endured by an endotherm.

evolutionary biology↗

bioRxiv2023

Interleukin 11-induced microRNAs as functional mediators and circulating biomarkers of cardiac fibrosis

BackgroundCardiac fibrosis can be triggered by several pathologies, including ischemic heart disease and aortic stenosis (AS). Cardiac fibrosis is brought about by uncontrolled extracellular matrix (ECM) deposition by myofibroblasts. Interleukin-11 (IL-11) has been firmly demonstrated to be a major trigger of multi-organ fibrosis. However, the molecular mechanisms underpinning IL-11-induced fibrosis requires further characterisation. Recent studies indicate that microRNA (miRNA) dysregulation contributes to the pathogenesis of cardiac fibrosis and can be targeted therapeutically. In this study, we explored the hypothesis that miRNAs act as downstream effectors of IL-11-induced cardiac fibrosis. Moreover, we investigated the translational potential of IL-11-regulated miRNAs as circulating biomarkers of cardiac fibrosis in AS patients. Methods and ResultsUsing computational approaches, we identified miRNA-497-5p and miRNA-27b-5p as potential new downstream profibrotic effectors of IL-11 in fibroblasts. We next confirmed that both miRNAs increased in healthy rat CF stimulated with IL-11 and in CF derived from post-infarction failing hearts. At the functional level, miRNA-497-5p and miRNA-27b-5p inhibition indirectly reduced the mRNA expression of collagen 1 (Col1a1). Conversely, transfection of CFs with mimics for each of the two miRNAs promoted fibroblast-to-myofibroblast transition and increased Col1a1 levels. We provided evidences that miRNA-27b-5p and miRNA-497-5p converge to promote hypoxia-inducible factor 1 signalling, by targeting its regulator EGLN (PHD) family members. The clinical relevance of our findings was confirmed using left ventricle (LV) specimens obtained from surgical patients with AS. The miRNA-27b-5p and miRNA-497-5p measured in the LV, peripheral plasma and plasma extracellular vesicles correlated with the severity of LV fibrosis, indicating these miRNAs potential as new circulating biomarkers of cardiac fibrosis. ConclusionsIn this study, we have newly identified the potential value of miRNA-27b-5p and miRNA-497-5p as actionable biomarkers of the profibrotic response to IL-11 in the heart. Future studies should validate the translational potential of the miRNAs as new clinical biomarkers and therapeutic targets.

molecular biology↗

bioRxiv2022

Independent acquisition of short insertions at the RIR1 site in the spike N-terminal domain of the SARS-CoV-2 BA.2 lineage

Although the SARS-CoV-2 variants BA.1 and BA.2 share over 30 non-synonymous substitutions in the spike glycoprotein, they show several unique mutations that were likely acquired after the split between these two major omicron lineages. One of the most intriguing mutations associated with BA.1 is the presence of the inserted tripeptide Glu-Pro-Glu within the N-terminal domain. While the functional implications of this insertion are still unclear, several other SARS-CoV-2 lineages had previously independently acquired similarly short insertions at the very same site, named RIR1. We have previously identified this site, located approximately between codon 212 and codon 216, as a hotspot of insertions, which usually involve small nucleotide sequences including three or four codons. Here we show that similar insertion events have independently occurred at least 13 times in early 2022 within the BA.2 lineage, being occasionally associated with significant community transmission. One of these omicron sublineages, characterized by a Ser-Gly-Arg insertion in position 212, is responsible of over 2% of all SARS-CoV-2 cases recorded in Denmark, as of early April 2022. Molecular surveillance data highlight a slow but steady growth compared with the parental BA.2 lineage in all Danish regions, suggesting that the RIR1 insertion may confer a selective advantage. We report the identification of other currently circulating BA.2 sublineages showing similar insertions, whose spread should be therefore carefully monitored in the upcoming months.

genomics↗