Biology subjects

Benson, R.

Publications and source records attributed to Benson, R..

3 recordsLinked to original sources

bioRxiv2024

IL-6 and IL-27 negatively regulate CRTAM-expressing CD4+ T-cells associated with lymphoid-driven synovitis.

ABSTRACT-Joint pathology in rheumatoid arthritis is heterogeneous, with histology providing evidence of fibroblast-driven, myeloid-driven, and lymphoid-driven synovitis. However, the immuno-modulatory pathways underlying their development remain unclear. Profiling synovial tissues from rheumatoid arthritis patients and mice with antigen-induced arthritis, we identified a subset of synovial infiltrating CD4+ T-cells expressing CRTAM (class-I MHC-restricted T-cell-associated molecule). In human synovial biopsies, CRTAM correlated with the expression of effector cytokines (IL21, IFNG), chemokine receptors (CXCR3, CXCR4, CCR5), granzymes (GZMA, GZMB, GZMK), and regulatory factors (TIGIT, EOMES, BATF) linked with T-cell-mediated immunity. Studies of antigen-induced arthritis showed that CRTAM+CD4+ T-cells accumulate in the inflamed synovium following disease onset. CRTAM+CD4+ T-cells were particularly abundant in synovial tissue from Il27ra-/- mice displaying ectopic lymphoid-like structures. CADM1 (cell adhesion molecule-1), the endogenous ligand for CRTAM, was also expressed in human synovitis and synovial tissues from wild-type, Il6ra-/-, and Il27ra-/- mice with antigen-induced arthritis. Cells expressing human CADM1 included synovial fibroblasts and subsets of monocytic and CD19+ cells. Considering the ex vivo regulation of CRTAM, we identified that activation of naive CD4+ T-cell increased CRTAM expression. This induction was blocked by IL-6 and IL-27, with further studies identifying a role for STAT3 in controlling the CRTAM transcriptional repressor, ZEB1. These results provide insights into the cytokine control of CRTAM on CD4+ T-cells and support the involvement of CRTAM+CD4+ T-cells in lymphoid-driven synovitis.

immunology↗

bioRxiv2023

A whole-body micro-CT scan library that captures the skeletal diversity of Lake Malawi cichlid fishes

Here we describe a dataset of freely available, readily processed, whole-body CT-scans of 56 species (116 specimens) of Lake Malawi cichlid fishes that captures a considerable majority of the morphological variation present in this remarkable adaptive radiation. We contextualise the scanned specimens within a discussion of their respective ecomorphological groupings and suggest possible macroevolutionary studies that could be conducted with these data. We also describe a methodology to efficiently CT-scan (on average) 23 specimens per hour, limiting scanning time and alleviating the financial cost whilst maintaining high resolution. We demonstrate the utility of this method by reconstructing 3D models of multiple bones from multiple specimens within the dataset. We hope this dataset will enable further morphological study of this fascinating system and permit wider-scale comparisons with other cichlid adaptive radiations.

evolutionary biology↗

bioRxiv2023

Macroevolutionary drivers of morphological disparity in the avian quadrate

In birds, the quadrate bone acts as a hinge between the lower jaw and the skull, playing an important role in cranial kinesis. As such, the evolution of avian quadrate morphology may plausibly be assumed to have been influenced by selective pressures related to feeding ecology. However, variation in quadrate morphology across living birds and its potential relationship with ecology have never been quantitatively characterised. Here, we used three-dimensional geometric morphometrics and phylogenetic comparative methods to quantify morphological variation of the quadrate and its relationship with an array of key ecological features across 200 bird species covering all major extant lineages. We found non-significant associations between quadrate shape and several aspects of feeding and foraging ecology across different scales of phylogenetic comparison. By contrast, allometry and phylogeny exhibit stronger relationships with quadrate shape than other ecological features. We show that the avian quadrate evolves as an integrated unit and exhibits strong associations with the morphologies of neighbouring bones. Our results collectively suggest a macroevolutionary scenario in which the shape of the quadrate evolved jointly with other elements of the avian kinetic system, with the major lineages of birds exploring alternative quadrate morphologies--highlighting the potential diagnostic value of quadrate morphology in investigations of fossil bird systematics.

paleontology↗