Biology subjects

Thom, C.

Publications and source records attributed to Thom, C..

5 recordsLinked to original sources

bioRxiv2026

Impaired glycolysis in bone underlies age-related bone loss in mice

Bone loss and metabolic dysregulation often coexist in older adults, yet the relationship between age-related changes in bone cell metabolism and bone-forming activity remains unclear. By modeling both conditions in aged mice and using in vivo stable-isotope tracing, we demonstrated that age-related decline in bone formation was coupled with an intrinsic impairment of glycolysis within bone tissue. Impaired glycolysis was associated with reduced protein levels of key glycolysis enzymes, and transcriptomics analyses revealed compensatory upregulation of glycolysis genes in aged bone. Metabolic intervention through long-term caloric restriction prevented age-related trabecular bone loss. Furthermore, osteoblast-specific genetic enhancement of glycolysis, via overexpression of HIF1 or the rate-limiting enzyme PFKFB3, significantly improved osteoblast function and increased bone mass in aged mice. Together, the study identifies glycolytic decline as a cell-autonomous driver of osteoblast deficiency and provides proof of principle that reactivating glycolysis can promote bone accrual in aging.

physiology↗

bioRxiv2025

IGF-1 from bone marrow Adipoq-lineage cells stimulates endocortical bone formation in mature female mice

Insulin-like growth factor 1 (IGF-1) is an anabolic signal promoting growth, differentiation and function of both embryonic and postnatal tissues. Both endocrine and paracrine functions of IGF-1 have been documented to regulate bone growth and bone marrow hematopoiesis. Local production of IGF-1 from various cell types may contribute differently to the overall bioactivity of IGF-1 in bone, but relevant sources and mechanisms are yet to be fully elucidated. Here we report that the Adipoq+ stromal cells are a notable source of IGF-1 in the bone marrow of postnatal mice. Deletion of IGF-1 with Adipoq-Cre diminished endocortical bone formation and cortical bone mass in mature female mice. On the other hand, the trabecular bone parameters or hematopoietic properties were not affected in mutant mice of either sex. The study uncovers a local source of IGF-1 in the bone marrow microenvironment that contributes to bone anabolic regulation in a site-specific manner. Lay SummaryThe insulin-like growth factor 1 (IGF-1) is known to play important roles in promoting bone growth and in regulating blood stem or progenitor cells. The factor is available both through the blood circulation and from the local production by cells in the bone tissue, but the functional contribution of each source is not well understood. Here we discover the non-blood cells in the bone marrow (bone marrow stromal cells) as a notable source of IGF-1 which specifically stimulates bone formation in the bone shaft of the long bone.

developmental biology↗

bioRxiv2024

Design and testing of a PCR assay to quantify coliform bacteria in drinking water

Here we present an enhanced lacZ qPCR assay targeting {beta}-galactosidase, encoded by lacZ, to assess coliforms in drinking water. Coliform bacteria are a diverse group of over 80 species, commonly found in enteric environments, and act as indicators of water supply contamination. Due to the significant variation among coliforms, and the size of the group designing a single target was challenging, as previous studies have demonstrated. To address this, a coliform lacZ sequence database was created, and the phylogeny of the group was reviewed. The degree of phylogenetic differences both between and among different coliform genera is indeed large, raising questions about their current definition. Using the database, current and new primer sets were tested for specificity and coverage both in silico and in vitro. The de novo primer set, LZ1, was found to be the most effective for qPCR. When compared directly with traditional culture-based methods and flow cytometry total cell counts, the LZ1 lacZ qPCR assay quantified E. coli in drinking water down to a concentration of 1.82 x 103 cfu/100mL, equivalent to 360 cfu per qPCR reaction. ImportanceColiform bacteria and E. coli are key indicators of faecal contamination in drinking water. Compliance with U.K., U.S.A., or European regulations requires that drinking water be free of these organisms. However, the culture-based methods used to quantify these bacteria have remained unchanged for over 100 years, relying on the culturability of the organisms, sampling only a small volume at a single time point, and lacking direct correlation to pathogenic microbes. There is a pressing need for a rapid, high-throughput analysis capable of detecting coliforms more representatively, without relying solely on culturability. By analysing larger volumes or more replicates, this qPCR assay could potentially be used to assess the risk of drinking water contamination over longer periods of time, offering a more comprehensive evaluation compared to traditional, culture-dependent methods.

microbiology↗

bioRxiv2022

Structural basis for the activation and ligand recognition of the human oxytocin receptor

The small cyclic neuropeptide hormone oxytocin (OT) and its cognate receptor play a central role in the regulation of social behaviour and sexual reproduction. Here we report the single-particle cryo-electron microscopy structure of the active oxytocin receptor (OTR) in complex with its cognate ligand oxytocin. Our structure provides high-resolution insights into the OT binding mode, the OTR activation mechanism as well as the subtype specificity within the oxytocin/vasopressin receptor family.

biochemistry↗

bioRxiv2021

Microbiomes in drinking water treatment and distribution: a critical review and meta-analysis from source to tap

A meta-analysis of existing and available Illumina 16S rRNA datasets from drinking water source, treatment and drinking water distribution systems (DWDS) were collated to compare changes in abundance and diversity throughout. Samples from bulk water and biofilm were used to assess principles governing microbial community assembly and the value of amplicon sequencing to water utilities. Individual phyla relationships were explored to identify competitive or synergistic factors governing DWDS microbiomes. The relative importance of stochasticity in the assembly of the DWDS microbiome was considered to identify the significance of source and treatment in determining communities in DWDS. Treatment of water significantly reduces overall species abundance and richness, with chlorination of water providing the most impact to individual taxa relationships. The assembly of microbial communities in the bulk water of the source, primary treatment process and DWDS is governed by more stochastic processes, as is the DWDS biofilm. DWDS biofilm is significantly different from bulk water in terms of local contribution to beta diversity, type and abundance of taxa present. Water immediately post chlorination has a more deterministic microbial assembly, highlighting the significance of this process in changing the microbiome, although elevated levels of stochasticity in DWDS samples suggest that this may not be the case at customer taps. 16S rRNA sequencing is becoming more routine, and may have several uses for water utilities, including: detection and risk assessment of potential pathogens such as those within the genera of Legionella and Mycobacterium; assessing the risk of nitrification in DWDS; providing improved indicators of process performance and monitoring for significant changes in the microbial community to detect contamination. Combining this with quantitative methods like flow cytometry will allow a greater depth of understanding of the DWDS microbiome.

microbiology↗