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Biology subjects

Richards, S. J.

Publications and source records attributed to Richards, S. J..

3 recordsLinked to original sources

Phylogenomic assessment of microhylid frogs reveals widespread taxonomic confusion in the Asterophryinae and establishes the timing of diversification in Australia

Microhylid frogs are a hyper-diverse family thought to have radiated explosively around the Cretaceous-Paleogene boundary. Roughly half of microhylid species richness is concentrated into a single subfamily, the Asterophryinae, which is centered in New Guinea and surrounds, and has been a rich source for species discovery over the past 50 years. However, resolving Asterophryinae phylogenetics has remained a challenge, with frequent taxonomic reshuffling. To address this instability, we generated a sequence-capture molecular dataset to investigate the phylogenetics of the group. This included 71 species of Asterophryinae, across 13 of 17 recognized genera representing extensive sampling of the New Guinea radiation and full sampling of Australian microhylid species. Our dated species tree supports an explosive diversification of microhylids in New Guinea near the start of the Miocene, approximately 20 million years ago. Asterophryinae expansion into northern Australia occurred much later ([~]10 ma) and is marked by well supported clades of Austrochaperina and Cophixalus that show temporally consistent splits from their New Guinea sister taxa. Our phylogeny allows us to identify several instances of polyphyly, which are at odds with our current understanding of intergeneric relationships within the Asterophryinae. We suggest that this confusion is a result of rapid radiation and morphological variability across some poorly defined genera. This work establishes a reliable phylogenetic framework that can form a foundation for a more stable taxonomy of the Asterophryinae. HighlightsO_LIA phylogenomic assessment of the globally distributed frog family Microhylidae C_LIO_LIThe subfamily Asterophryinae radiated explosively in New Guinea C_LIO_LIAustralian species represent two distinct clades C_LIO_LIAssignments of species to genera by morphological means are often unreliable C_LI

evolutionary biology↗

Comparative genomic and crystal structure analyses identify a collagen glucosyltransferase from Acanthamoeba Polyphaga Mimivirus

Humans and Acanthamoeba Polyphaga Mimivirus share numerous homologous genes, including collagens and collagen-modifying enzymes. To explore the homology, we performed a genome-wide comparison between human and mimivirus using DELTA-BLAST (Domain Enhanced Lookup Time Accelerated BLAST) and identified 52 new mimiviral proteins that are homologous with human proteins. To gain functional insights into mimiviral proteins, their human protein homologs were organized into Gene Ontology (GO) and REACTOME pathways to build a functional network. Collagen and collagen-modifying enzymes form the largest subnetwork with most nodes. Further analysis of this subnetwork identified a putative collagen glycosyltransferase R699. Protein expression test suggested that R699 is highly expressed in E coli, unlike the human collagen-modifying enzymes. Enzymatic activity assays showed that R699 catalyzes the conversion of unique galactosylhydroxylysine within the GXXXUG motif (U=galactosylhydroxylysine) to glucosylgalactosylhydroxylysine on collagen using uridine diphosphate glucose (UDP-Glc) as a sugar donor, suggesting R699 is a mimiviral collagen galactosylhydroxylysyl glucosyltransferase (GGT) with defined substrate specificity. Structural study of R699 produced the first crystal structure of a collagen GGT with a visible UDP-Glc. Sugar moiety of the UDP-Glc resides in a previously unrecognized pocket. Mn2+ coordination and nucleoside-diphosphate binding site are conserved among GGT family members and critical for R699s collagen GGT activity. To facilitate further analysis of human and mimiviral homologous proteins, we presented an interactive and searchable genome-wide comparison website for quickly browsing human and Acanthamoeba Polyphaga Mimivirus homologs, which is available at RRID Resource ID: SCR_022140 or https://guolab.shinyapps.io/app-mimivirus-publication/.

biochemistry↗

The CXCR6/CXCL16 axis links inflamm-aging to disease severity in COVID-19 patients

Advancing age and chronic health conditions, significant risk factors for severe COVID-19, are associated with a pro-inflammatory state, termed inflamm-aging. CXCR6+ T cells are known to traffic to the lung and have been reported to increase with age. The ligand of CXCR6, CXCL16, is constitutively expressed in the lung and upregulated during inflammatory responses and the CXCR6/CXCL16 axis is associated with severe lung disease and pneumonia. Genome-wide association studies have also recently identified 3p21.31, encompassing the CXCR6 gene, as a susceptibility locus for severe COVID-19. We assessed numbers T cells expressing the chemokine receptor CXCR6 and plasma levels of CXCL16, in control and COVID-19 patients. Results demonstrated that circulating CD8+CXCR6+ T cells were significantly elevated with advancing age, yet virtually absent in patients with severe COVID-19. Peripheral levels of CXCL16 were significantly upregulated in severe COVID-19 patients compared to either mild COVID-19 patients or SARS-CoV-2 negative controls. This study supports a significant role of the CXCR6/CXCL16 axis in the immunopathogenesis of severe COVID-19.

immunology↗