Biology subjects

Bolton, C.

Publications and source records attributed to Bolton, C..

7 recordsLinked to original sources

bioRxiv2026

Exercise induces Skeletal Muscle Methylome and Transcriptome changes, regardless of Age and COPD

Skeletal muscle atrophy and deconditioning contribute to functional limitation and disability in COPD. While transcriptome and DNA methylation changes accompany exercise in healthy muscle, their interaction with COPD status and ageing, and integrative analyses of methylome-transcriptome responses have not been explored. We performed gene expression and DNA methylation profiling in skeletal muscle of sedentary volunteers with COPD, age-matched older adults, and younger healthy individuals, before and during (1,4 and 8 weeks) supervised aerobic exercise training and after four weeks of detraining. Exercise induced transcriptomic and DNA methylation changes, but these responses were unaffected by COPD status or age. Subsequent analysis focusing on temporal exercise effects independent of disease or age revealed differential transcriptomic changes across time points, a subset of which significantly associated with DNA methylome alterations. Transient transcriptomic changes not linked to DNA methylation were enriched for inflammatory and oxidative stress pathways, whereas persistent methylation-associated adaptations were related to immunomodulation and tissue remodelling. Together, this study provides insight into molecular mechanisms contributing to skeletal muscle adaptation to aerobic exercise training in sedentary individuals.

genomics↗

bioRxiv2025

Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases

Regulatory T cells (Tregs), characterized by FOXP3 expression, are essential for maintaining immune homeostasis by controlling inflammation. However, in autoimmune diseases such as rheumatoid arthritis (RA), impaired Treg function contributes to immune dysregulation and disease pathology. While most studies of human Tregs have focused on blood, here we analyzed Tregs in synovial tissues from RA patients using single cell RNA sequencing (scRNAseq). We identified two predominant Treg states, CD25hiCXCR6pos Tregs with strong suppressive function, and CD25loAREGpos Tregs, a dysfunctional state exclusively enriched in synovial tissues but not in blood. Computational and in vitro analyses revealed that cortisol induced AREG expression, suppressed glycolysis, and impaired the suppressive function of CD25loAREGpos Tregs. In turn, AREG promoted an IL-33+ inflammatory phenotype in synovial fibroblasts. Importantly, we found that TNFR2 engagement can prevent or reverse this dysfunctional Treg state. In contrast to CD25loAREGpos Tregs, CD25hiCXCR6pos Tregs were highly suppressive, showed coordinated abundance with macrophages in synovial tissue, and functionally interacted with membrane-bound TNF expressed by macrophages, which promoted their functional suppressive state. These two Treg subsets were similarly found in the synovial tissue in Juvenile Idiopathic Arthritis (JIA), another inflammatory arthritic disorder, indicating conserved mechanisms across arthritic diseases. Together, our findings define distinct pathways driving divergent functional and dysfunctional Treg states in inflamed tissues and point to interventions that may prevent or reverse the development of the dysfunctional state.

immunology↗

bioRxiv2025

DNA Divers: volunteer-based eDNA capture for local and global marine biodiversity monitoring

Volunteer-based biodiversity recording is a powerful source of scalable data yet to be used to its full potential by the scientific community. Coastal ecosystems are varied and diverse, making it difficult for managers to identify flexible methods for monitoring biological components. Emerging technologies such as environmental DNA (eDNA) analysis are promising for measuring aquatic biodiversity, yet most management organizations lack personnel and capacity to collect molecular data. Here we investigate, together as professional and non-professional scientists, the efficacy of a quasi-passive eDNA capture technique. Volunteer SCUBA divers and snorkelers used low-cost materials, namely cotton medical gauze, to capture eDNA via swimming. We compared this method to conventional eDNA capture techniques in an aquarium and nature, collectively iterating the field and laboratory procedures to improve feasibility. With a small (< 30) network of volunteers, we detected 275 unique teleost and elasmobranch species from varied marine habitats spanning 90 degrees of latitude. The swimming motion of divers was more effective than stationary soaking and the fish communities sampled by divers were comparable to that of conventional eDNA samples. The ease of this technique matched by the eagerness and generosity of volunteers presents an untapped, viable approach for scaling multi-species marine eDNA monitoring as well as an avenue for improving science literacy. Data availabilityhttps://zenodo.org/records/14853820?token=eyJhbGciOiJIUzUxMiJ9.eyJpZCI6ImYxMTlhODFiLTI3NGYtNDQ2Ni05MDYyLTIyOTlkNWVhY2FkNiIsImRhdGEiOnt9LCJyYW5kb20iOiIwYmZlMzJhMWU0YWZkM2ZhMWEwYTE0NmY0ZWM5YWZkNSJ9.0R7GJjVJLEuq-UJVKA1CcMT8LCTamv3GEvPl-5ItzP10pFRd-cAzAr_Q5ggjEewZUtByHjBu-eSegWWlLAx_Rw

ecology↗

bioRxiv2024

Spatial programming of fibroblasts promotes resolution of tissue inflammation through immune cell exclusion

The role of fibroblasts in determining tissue topography and immune cell organisation within chronically inflamed tissues is poorly understood. Herein, we use multi-omic spatial analysis to define the cellular zonation pattern of the synovium in patients with inflammatory arthritis, identifying discrete tissue niches underpinned by spatially programmed subsets of synovial fibroblasts. We observe that perivascular fibroblasts switch on distinct matrix programs in response to cytokine signalling from neighbouring cells, forming adapted tissue niches that either permit or restrict immune cell trafficking. Specifically, IFN-{gamma}-responsive fibroblasts form a pathogenic lymphocyte-permissive niche that supports the persistence of leukocytes in the tissue, whilst TGF-{beta}-responsive, matrix-synthesising fibroblasts comprise a reparative niche, composed of a collagen-rich barrier around blood vessels that restricts leukocyte migration and promotes resolution of tissue inflammation. Augmentation of such endogenous pathways to promote resolution of inflammation may offer therapeutically tractable approaches for restoration of tissue homeostasis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/614064v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1e6e4dborg.highwire.dtl.DTLVardef@1baee04org.highwire.dtl.DTLVardef@1608a1forg.highwire.dtl.DTLVardef@10c1edb_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGRAPHICAL ABSTRACTC_FLOATNO C_FIG

immunology↗

bioRxiv2021

Regulating peroxisome-ER contacts via the ACBD5-VAPB tether by FFAT motif phosphorylation and GSK3β

Peroxisomes and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism. They form membrane contacts through interaction of the peroxisomal membrane protein ACBD5 [acyl-coenzyme A-binding domain protein 5] and the ER-resident protein VAPB [vesicle-associated membrane protein-associated protein B]. ACBD5 binds to the major sperm protein domain of VAPB via its FFAT-like [two phenylalanines (FF) in an acidic tract] motif. However, molecular mechanisms, which regulate formation of these membrane contact sites, are unknown. Here, we reveal that peroxisome-ER associations via the ACBD5-VAPB tether are regulated by phosphorylation. We show that ACBD5-VAPB binding is phosphatase-sensitive and identify phosphorylation sites in the flanking regions and core of the FFAT-like motif, which alter interaction with VAPB and thus, peroxisome-ER contact sites differently. Moreover, we demonstrate that GSK3{beta} [glycogen synthase kinase-3 beta] regulates this interaction. Our findings reveal for the first time a molecular mechanism for the regulation of peroxisome-ER contacts in mammalian cells and expand the current model of FFAT motifs and VAP interaction. SUMMARYKors et al. reveal that peroxisome-ER associations via the ACBD5-VAPB tether are regulated by phosphorylation and GSK3{beta} in mammalian cells. Phosphorylation sites in the FFAT-like motif of ACBD5 affect the binding to VAPB and thus, peroxisome-ER contact sites, differently.

cell biology↗

bioRxiv2021

Coral settlement and recruitment responses to reef fish foraging and trait diversity

The process of coral recruitment is crucial to the functioning of coral reef ecosystems, as well as recovery of coral assemblages following disturbances. Fishes can be key mediators of this process by removing benthic competitors like algae, but their foraging impacts are capable of being facilitative or harmful to coral recruits depending on species traits. Reef fish assemblages are highly diverse in foraging strategies and the relationship between this diversity with coral settlement and recruitment success remains poorly understood. Here, we investigate how foraging trait diversity of reef fish assemblages covaries with coral settlement and recruitment success across multiple sites at Lizard Island, Great Barrier Reef. Using a multi-model inference approach incorporating six metrics of fish assemblage foraging diversity (foraging rates, trait richness, trait evenness, trait divergence, herbivore abundance, and sessile invertivore abundance), we found that herbivore abundance was positively related to both coral settlement and recruitment success. However, the correlation with herbivore abundance was not as strong in comparison with foraging trait diversity metrics. Coral settlement and recruitment exhibited a negative relationship with foraging trait diversity, especially with trait divergence and richness in settlement. Our findings provide further evidence that fish play a role in making benthic habitats more conducive for coral settlement and recruitment. Because of their ability to shape the reef benthos, the variation of fish biodiversity is likely to contribute to spatially uneven patterns of coral recruitment and reef recovery.

ecology↗

bioRxiv2021

Rhythmic clock gene expression in Atlantic salmon parr brain

To better understand the complexity of clock genes in salmonids, a taxon with an additional whole genome duplication, an analysis was performed to identify and classify gene family members (clock, arntl, period, cryptochrome, nr1d, ror, and csnk1). The majority of clock genes, in zebrafish and Northern pike, appeared to be duplicated. In comparison to the 29 clock genes described in zebrafish, 48 clock genes were discovered in salmonid species. There was also evidence of species-specific reciprocal gene losses conserved to the Oncorhynchus sister clade. From the six period genes identified three were highly significantly rhythmic, and circadian in their expression patterns (per1a.1, per1a.2, per1b) and two was significantly rhythmically expressed (per2a, per2b). The transcriptomic study of juvenile Atlantic salmon (parr) brain tissues confirmed gene identification and revealed that there were 2,864 rhythmically expressed genes (p < 0.001), including 1,215 genes with a circadian expression pattern, of which 11 were clock genes. The majority of circadian expressed genes peaked two hours before and after daylight. These findings provide a foundation for further research into the function of clock genes circadian rhythmicity and the role of an enriched number of clock genes relating to seasonal driven life history in salmonids.

physiology↗