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Biology subjects

Mellanby, R. J.

Publications and source records attributed to Mellanby, R. J..

3 recordsLinked to original sources

Modelling sterilisation strategies to maximise population impact and cost-efficiency in free-roaming dog populations

Free-roaming dog populations pose challenges to public health and animal welfare, and their management and protection is legally mandated in many countries to control zoonotic diseases such as rabies, reduce bites, mitigate fear of aggressive dogs, and preserve animal welfare. Although international organisations recommend holistic dog population management with surgical sterilisation as a key component, stakeholders report a lack of evidence-based guidance on effective and cost-efficient strategies. To address this, we developed a deterministic model of a closed free-roaming dog (FRD) population, including dogs dependent on and independent of humans, parameterised using data from southern India. We evaluated a wide range of sterilisation strategies varying duration, interval, frequency, intensity, targeting different population subsets, and fixed or responsive approaches. Strategies were assessed based on their effects on independent FRD population size and implementation costs. Female sterilisation coverage (FSC) strongly determined population reduction and cost-effectiveness. Repeated, short sterilisation periods with appropriately timed intervals and high early intensity best balanced population reduction and cost-efficiency. Excluding dependent dogs (cared for by humans) severely constrained population reduction, while male sterilisation enhanced impact at little extra cost, assuming direct effects on pregnancy rates. Costs and population impacts can be visualised on an interactive web application (https://field.shinyapps.io/DogPopSimApp), allowing practitioners and policymakers to explore sterilisation strategy outcomes. Overall, cost-effective population reduction required sustained commitment and coverage-driven strategies that balance welfare, population reduction and the operational needs of dog-mediated rabies control. Author SummaryFree-roaming street dogs live closely with people. While these animals are often valued members of the community, they can raise public health and safety concerns, including disease transmission, bites, and traffic accidents. To protect both human and animal health, many regions use surgical sterilisation to humanely manage street dog populations. However, running these programmes is complex and expensive, and community managers often lack clear guidance on how to maximise their limited resources. To address this, we used data from southern India to create a mathematical model of a street dog population. We simulated thousands of different sterilisation strategies to see how factors like campaign length, frequency, and targeted sub-groups impacted population size and total costs. We found that short, repeated sterilisation campaigns offer the best balance of population reduction and cost-efficiency. Crucially, these programmes must include dogs that are partially cared for by humans; otherwise, their puppies will continually replenish the street population. Although sterilisation of females drives population reduction, sterilising males alongside females enhanced the overall impact. Ultimately, our study provides practical, evidence-based guidance to help communities design effective and financially sustainable dog management programmes that improve public health and animal welfare.

ecology↗

Vitamin D status is heritable and under environment-dependent selection in the wild.

Vitamin D has a well-established role in skeletal health and is increasingly linked to chronic disease and mortality in humans and companion animals. Despite the clear significance of vitamin D for health and obvious implications for fitness under natural conditions, no longitudinal study has tested whether the circulating concentration of vitamin D is under natural selection in the wild. Here, we show that concentrations of dietary-derived vitamin D2 and endogenously-produced vitamin D3 metabolites are heritable and largely polygenic in a wild population of Soay sheep (Ovis aries). Vitamin D2 status was positively associated with female adult survival, and vitamin D3 status predicted female fecundity in particular, good environment years. Our study provides evidence that vitamin D status has the potential to respond to selection, as well as new insights into how vitamin D metabolism is associated with fitness in the wild.

evolutionary biology↗

Direct detection of circulating microRNA-122 using dynamic chemical labelling with single molecule detection overcomes stability and isomiR challenges for biomarker qualification

Circulating microRNAs are biomarkers reported to be stable and translational across species. miR-122 (miR-122-5p) is a hepatocyte-specific microRNA biomarker for drug-induced liver injury (DILI). Our objective was to develop an extraction-free and amplification-free detection method for measuring miR-122 that has translational utility in context of DILI. We developed a single molecule dynamic chemical labelling (DCL) assay based on miR-122 hybridization to an abasic peptide nucleic acid probe that contained a reactive amine instead of a nucleotide at a specific position in the sequence. The single molecule DCL assay specifically measured miR-122 directly from 10 {micro}L of serum or plasma without any extraction steps, with a fit-for-purpose limit of detection of 1.32 pM. In 192 human serum samples, DCL accurately identified patients at risk of DILI (area under ROC curve 0.98 (95%CI 0.96-1), P<0.0001). The miR-122 assay also quantified liver injury in rats and dogs. When DCL beads were added to serum, the miR-122 signal was stabilised (no loss of signal after 14 days at room temperature). By contrast, there was substantial degradation of miR-122 in the absence of beads ({approx}60% lost in 1 day). RNA sequencing demonstrated the presence of multiple miR-122 isomiRs with DILI that were at low concentration or not present in healthy patient serum. Sample degradation over time produced more isomiRs, particularly rapidly with DILI. PCR was inaccurate when analysing miR-122 isomiRs, whereas the DCL assay demonstrated accurate quantification. In summary, the DCL assay can accurately measure miR-122 directly from serum and plasma to diagnose liver injury in humans and other species, and can overcome important microRNA biomarker analytical and biological challenges.

pharmacology and toxicology↗