Biology subjects

McCloskey, E.

Publications and source records attributed to McCloskey, E..

3 recordsLinked to original sources

bioRxiv2024

HSV-1 ICP0 Dimer Domain Adopts a Novel β-barrel Fold

Infected cell protein 0 (ICP0) is an immediate-early regulatory protein of herpes simplex virus 1 (HSV-1) that possesses E3 ubiquitin ligase activity. ICP0 transactivates viral genes, in part, through its C-terminal dimer domain (residues 555-767). Deletion of this dimer domain results in reduced viral gene expression, lytic infection, and reactivation from latency. Since ICP0s dimer domain is associated with its transactivation activity and efficient viral replication, we wanted to determine the structure of this specific domain. The C-terminus of ICP0 was purified from bacteria and analyzed by X-ray crystallography to solve its structure. Each subunit or monomer in the ICP0 dimer is composed of nine {beta}-strands and two -helices. Interestingly, two adjacent {beta}-strands from one monomer "reach" into the adjacent subunit during dimer formation, generating two {beta}-barrel-like structures. Additionally, crystallographic analyses indicate a tetramer structure is formed from two {beta}-strands of each dimer, creating a "stacking" of the {beta}-barrels. The structural protein database searches indicate the fold or structure adopted by the ICP0 dimer is novel. The dimer is held together by an extensive network of hydrogen bonds. Computational analyses reveal that ICP0 can either form a dimer or bind to SUMO1 via its C-terminal SUMO-interacting motifs but not both. Understanding the structure of the dimer domain will provide insights into the activities of ICP0 and, ultimately, the HSV-1 life cycle.

microbiology↗

bioRxiv2023

Invasive traits of freshwater fish database (ITOFF)

AIMSpecies invasions are a major driver of global biodiversity loss, but only a minority of invasions are successful. Evidence suggests that invasive success is linked to life-history traits. Yet, data on invasive success and species traits remain fragmented across multiple sources. Here we present the Invasive Traits of Freshwater Fish (ITOFF) database, an interdisciplinary framework that integrates multiple datasets to elucidate the role of life-history traits in shaping invasive success. ITOFF allows seamless access to invasive species data and fosters collaborative actions through knowledge sharing. ITOFF is supported by an innovative web-application that makes complex relationships between invasive and native species accessible to a broad audience. The scientific contribution of ITOFF is illustrated by examining the role of life-history traits and phylogeny in invasion success. LOCATIONGlobal. METHODSGeneralized linear models were used to test the contribution of generation time, trophic level, longevity, and temperature range to invasive success. Through divisive cluster analysis we investigate the role of multiple traits in determining invasive success. Finally, we construct phylogenetic trees to investigate the role of evolutionary history in the invasion process. RESULTSITOFF unifies data for 1917 freshwater fish species representative of invasive species, those species they endanger, and species impacted by invasives but not considered endangered. Invasive species are generally characterized by greater temperature ranges, but are indistinguishable from impacted, endangered, and critically endangered species for the remaining life-history traits. Further, we show that invasive species are generally not distinct from impacted or endangered species when considering multiple traits or phylogeny. MAIN CONCLUSIONSITOFF provides an accessible platform for the improved forecasting of species invasions. ITOFF data shows that classical predictions of life-history traits determining invasive success do not hold amongst freshwater fish species. Forecasting of invasive species must therefore shift towards a wholistic approach encompassing the species and the environment.

ecology↗

bioRxiv2021

miR-24:Prdx6 interactions regulate oxidative stress and viability of myogenic progenitors during ageing

microRNAs regulate a myriad of physiological processes, including skeletal muscle regeneration and homeostasis. During ageing, changes in muscle fibre microenvironment contribute to the capability of satellite cells to regenerate the muscle in response to injury and loading stressors. In this study, we isolated murine satellite cells and primary myogenic progenitors from mice and humans to demonstrate that the microRNA miR-24-3p and its target peroxiredoxin 6 (Prdx6) play an important role in muscle regeneration during ageing, regulating satellite cell viability and their differentiation potential. Our results show upregulation of miR-24 during early stages of muscle regeneration in vivo in adult mice, suggesting a potential role of miR-24 at the early stages of muscle injury. On contrary, miR-24 was downregulated during regeneration of muscle of old mice. miR-24 was also downregulated, whereas its target gene Prdx6 was upregulated, in satellite cells isolated from old mice. miR-24 consistently regulated viability and myogenic potential of myogenic progenitors from both humans and old mice, suggesting that changes in miR-24 levels during ageing may contribute to defective early stages of muscle regeneration during ageing through affecting satellite cell viability and myogenic potential. This regulation likely occurs via miR-24 counteracting the generation of reactive oxygen species through Prdx6 de-repression in primary myogenic progenitors isolated from humans and old mice. We propose that downregulation of miR-24 in muscle of old mice following injury may be a protective mechanism against elevated ROS levels to maintain satellite cell viability and myogenic potential, acting through Prdx6 upregulation. However, as miR-24 is a regulator of p16 and p21, this downregulation may lead to increased satellite cell senescence, therefore representing an age-related failed compensatory mechanism.

cell biology↗