Biology subjects

McBride, S.

Publications and source records attributed to McBride, S..

3 recordsLinked to original sources

bioRxiv2026

Sleep quality and quantity and their associations with age, salivary cortisol and abnormal behaviours: a preliminary field study in racing thoroughbreds.

Sleep plays a key role in both physical recovery and welfare. However, sleep patterns remain poorly documented in animals, particularly in athletic horses. This study aimed to provide a detailed description of sleep quantity and quality in training Thoroughbred racehorses and to investigate their relationships with age, abnormal behaviours, and cortisol. Thirteen Thoroughbreds (2-7 years old) were continuously monitored in their home environment over three consecutive days. An ethogram was used to quantify the two main phases of sleep: Non Rapid Eye Movement sleep (NREM) and Rapid Eye Movement sleep (REM), as well as sleep interruptions (from day 1 at 12:00 a.m. to day 3 at 12:00 a.m.). Sleep Quality Indices (SQI), defined as the quantity of sleep divided by the number of sleep interruptions (SI), were calculated. Behavioural observations of four indicators of poor welfare (alertness, stereotypies, inactivity, aggressiveness towards humans) were performed using scan sampling, and salivary cortisol was measured each morning. Linear models were used to assess the links between sleep quantity and quality, age, mean cortisol, and abnormal behaviours. Sleep quantity was significantly associated with age: positively for total NREM sleep (ANOVA: {chi}{superscript 2} = 5.26, p < 0.05) and, negatively for total REM sleep (ANOVA: {chi}{superscript 2} = 4.46, p <0.05) and total recumbency duration (ANOVA: {chi}{superscript 2} = 5.68, p < 0.05), suggesting an age-related shift favouring NREM over REM. Morning cortisol concentrations and the frequency of abnormal behaviours were significantly higher in horses with lower sleep quality (cortisol: Total SQI, ANOVA: F = 5.26, p < 0.05; Combined SQI, ANOVA: F = 5.40, p < 0.05; abnormal behaviours: Total SQI, ANOVA: F = 4.07, p = 0.074), pointing to a potential link between stress or altered welfare and poorer sleep quality. These findings suggest that, whilst the type and duration of equine sleep may be mainly affected byage, sleep quality is associated with both cortisol levels and the expression of abnormal behaviours, indicating that poor sleep quality may be linked to poor welfare in this population of horses. Thus, sleep appears to be closely linked with racehorse welfare, highlighting the need for further investigation into how it is influenced by factors such as husbandry, training load, recovery, and performance.

animal behavior and cognition↗

bioRxiv2023

Use of Epivolve phage display to generate a monoclonal antibody with opsonic activity directed against a subdominant epitope on extracellular loop 4 of Treponema pallidum BamA (TP0326)

Syphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum (Tp), is resurging globally. Opsonic antibodies (Abs) targeting surface-exposed epitopes of the spirochetes outer membrane proteins (OMPs) are believed to promote macrophage-mediated clearance of the bacterium during infection and are presumed to be key to vaccine development. Tps repertoire of outer membrane proteins includes BamA ({beta}-barrel assembly machinery subunit A/TP0326), the central component of the molecular machine that inserts newly exported OMP precursors into the OM lipid bilayer. BamA is a bipartite protein consisting of an 18-stranded {beta}-barrel with nine extracellular loops (ECLs) and five periplasmic POTRA (polypeptide transport-associated) domains. Antisera directed against BamA ECL4 promote internalization of Tp by rabbit peritoneal macrophages. Herein, we employed a novel two-stage, phage display strategy, termed "Epivolve" (for epitope evolution), to generate five site-directed murine monoclonal Abs (mAbs) targeting a centrally located peptide (S2) of BamA ECL4. Each of the five mAbs demonstrated reactivity by immunoblotting and ELISA to nanogram amounts of BamA ECL4 displayed by a Pyrococcus furiosus thioredoxin (PfTrx) scaffold (PfTrxBamA/ECL4). One mAb containing a unique amino acid sequence in both light and heavy chains showed activity in an opsonophagocytosis assay employing murine bone marrow-derived macrophages. Mice and rabbits hyperimmunized with PfTrxBamA/ECL4 produced opsonic antisera that strongly recognized the ECL presented in a heterologous scaffold and overlapping ECL4 peptides including S2. In contrast, Abs generated during Tp infection of mice and rabbits poorly recognized the peptides, indicating that S2 contains a subdominant epitope. Epivolve, which circumvents the natural immune response, can be utilized for the generation of mAbs that target subdominant opsonic epitopes in ECLs of Tp OMPs.

immunology↗

bioRxiv2019

Phase variation of a signal transduction system controls Clostridioides difficile colony morphology, motility, and virulence

Recent work has revealed that Clostridioides difficile, a major cause of nosocomial diarrheal disease, exhibits phenotypic heterogeneity within a clonal population as a result of phase variation. Many C. difficile strains representing multiple ribotypes develop two colony morphotypes, termed rough and smooth, but the biological implications of this phenomenon have not been explored. Here, we examine the molecular basis and physiological relevance of the distinct colony morphotypes produced by this bacterium. We show that C. difficile reversibly differentiates into rough and smooth colony morphologies, and that bacteria derived from the isolates display opposing surface and swimming motility behaviors. We identified an atypical phase-variable signal transduction system consisting of a histidine kinase and two response regulators, named herein CmrRST, which mediates the switch in colony morphology and motility behaviors. The CmrRST-regulated surface motility is independent of Type IV pili, suggesting a novel mechanism of surface expansion in C. difficile. Microscopic analysis of cell and colony structure indicates that CmrRST promotes the formation of elongated bacteria arranged in bundled chains, which may contribute to bacterial migration. In a hamster model of acute C. difficile disease, colony morphology correlates with virulence, and the CmrRST system is required for disease development. Furthermore, we provide evidence that CmrRST phase varies during infection, suggesting that the intestinal environment impacts the proportion of CmrRST-expressing C. difficile. Our findings indicate that C. difficile employs phase variation of the CmrRST signal transduction system to generate phenotypic heterogeneity during infection, with concomitant effects on bacterial physiology and pathogenesis.\n\nSignificance StatementPhenotypic heterogeneity within a genetically clonal population allows many mucosal pathogens to survive within their hosts, balancing the need to produce factors that promote colonization and persistence with the need to avoid the recognition of those factors by the host immune system. Recent work suggests that the human intestinal pathogen Clostridium difficile employs phase variation during infection to generate a heterogeneous population differing in swimming motility, toxin production, and more. This study identifies a signal transduction system that broadly impacts C. difficile physiology and behavior in vitro and in an animal model. Phase variation of this system is therefore poised to modulate the coordinated expression of multiple mechanisms influencing C. difficile disease development.

microbiology↗