Review of harm-benefit analysis in the use of animals in research

This is the final version of the report. Available from the Home Office via the link in this recordReport of our review of the processes of harm-benefit analysis (HBA) carried out under the UK Animals (Scientific Procedures) Act 1986 (A(SP)A).Report of the Animals in Science Committee Harm-Benefit Analysis Sub-Group chaired by Professor Gail Davies. The Animals in Science Committee Harm-Benefit Analysis subgroup, chaired by Professor Gail Davies, has produced a review of the harm-benefit analysis (HBA). This review is an analysis of the underpinnings and implementation of the HBA which remains a crucial step in the justification of the use of animals in science. It is published in response to a ministerial commission.Animals in Science Committe

A framework linking ecosystem services and human well‐being: Saltmarsh as a case study

1. The ecosystem services approach is based on the interdependencies between nature and human well‐being. However, while the ecosystem services aspect of this approach is well‐developed, the human well‐being aspect remains unstructured and vaguely defined. 2. An integrated conceptual framework was developed by adapting and linking the UK National Ecosystem Assessment‐Follow On framework with human well‐being domains. 3. As well as benefits, the notion of disbenefits was incorporated to recognise the potentially detrimental effects from interacting with nature. Benefits and disbenefits occur at the social–ecological interface and are classified by the seven domains of human well‐being they affect. 4. The framework is applied to saltmarsh habitat as a case study, highlighting knowledge gaps and the potential applicability and usefulness of the framework. In saltmarsh, benefits mainly accrue at larger scales with a greater impact affecting local to global individuals, while disbenefits tend to occur at a smaller scale and impact in‐situ individuals. 5. The framework provides in‐depth insight into links, trade‐offs and dichotomies between benefits and disbenefits and human well‐being, and improves accessibility to the complex research area of human well‐being. 6. This research can be a useful tool to guide environmental and health policy and management, as well as stakeholder engagement

Neuropathological characterisation of a novel TBK1 loss of function mutation associated with amyotrophic lateral sclerosis

Mutations in TANK binding kinase gene (TBK1) have been identified as causative in amyotrophic lateral sclerosis (ALS). Here, we examine the spectrum of TBK1 mutations in a cohort of ALS patients from Northern England, comparing missense and loss of function mutations with clinical phenotype. Analysis of 290 ALS cases identified seven variants, including one novel in-frame deletion (p.Ile85del). In silico analysis and review of the literature suggested that four variants, one nonsense mutation (p.Glu2Ter), two in-frame deletions (p.Ile85del, p.Glu643del) and one missense mutation (p.Gln565Pro) were pathogenic, whilst the remaining three missense mutations were variants of uncertain significance or benign. Post-mortem material was available from the patient with the novel in-frame deletion. Neuropathological examination established this individual had classical ALS pathology, with moderate phosphorylated TDP-43 neuronal and glial cytoplasmic inclusions in the motor cortex, skein-like inclusions in the lower motor neurons and “pre-inclusions” in the medulla. This corresponds to Type B FTLD-TDP pathology and is consistent with previously published literature on TBK1 mutants. In addition to demonstrating no changes in TBK1 staining, we are the first to show there was no differential expression of interferon regulatory factor IRF3, a downstream effector of TBK1 in the innate immunity pathway, in the TBK1-mutant tissue compared to controls. Comparison of clinical and neuropathological data, however, suggests that TBK1-ALS cases show classical ALS pathology but no specific phenotype

Are Some Natural Environments More Psychologically Beneficial Than Others? The Importance of Type and Quality on Connectedness to Nature and Psychological Restoration

Exposure to nature can strengthen an individual’s sense of connectedness (i.e., emotional/cognitive bonds to the natural world) and enhance psychological restoration (e.g., feeling relaxed/refreshed). To date, there have been few large studies looking at the role that type and quality of natural environments may have on these outcomes. The present study used data from a large survey in England (sample analyzed = 4,515), which asked participants to recall a recent visit to nature. After controlling for covariates, respondents recalled greater connectedness to nature and restoration following visits to rural and coastal locations compared with urban green space, and to sites of higher environmental quality (operationalized by protected/designated area status, for example, nature reserves). A series of structural equation analyses provided evidence for a bidirectional association between connectedness and restoration. Consideration of the psychological benefits associated with different types and quality of environment has implications for human health, environmental management, and conservation

Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry

Hepatitis C virus (HCV) is one of the leading causes of liver diseases and transplantation worldwide. The current available therapy for HCV infection is based on interferon-α, ribavirin and the new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of drug design, severe side effects and HCV resistance presented by the existing treatments demonstrate the need for developing more efficient anti-HCV agents. This study aimed to evaluate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids from Pterogyne nitens on the HCV replication cycle. These compounds were investigated for their anti-HCV activities using genotype 2a JFH-1 subgenomic replicons and infectious virus systems. Flavonoids 1 and 2 inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic concentrations. The mechanism of the flavonoid 2 block to virus entry was demonstrated to be by both the direct action on virus particles and the interference on the host cells. Alternatively, the flavonoid 1 activity was restricted to its virucidal effect. Additionally, no inhibitory effects on HCV replication and release were observed by treating cells with these flavonoids. These data are the first description of 1 and 2 possessing in vitro anti-HCV activity

Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma

\ua9 2024 National Academy of Sciences. All rights reserved.Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this, we have created a multiscale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single-cell RNA sequencing, spatial global transcriptional profiling, and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community

The co-development of HedgeDATE, a public engagement and decision support tool for air pollution exposure mitigation by green infrastructure

There is a lack of clear guidance regarding the optimal configuration and plant composition of green infrastructure (GI) for improved air quality at local scale. This study aimed to co-develop (i.e. with feedback from end-users) a public engagement and decision support tool, to facilitate effective GI design and management for air pollution abatement. The underlying model uses user-directed input data (e.g. road type) to generate output recommendations (e.g. plant species) and pollution reduction projections. This model was computerised as a user-friendly tool named HedgeDATE (Hedge Design for Abatement of Traffic Emissions). A workshop generated feedback on HedgeDATE, which we also discuss. We found that data from the literature can be synthesised to predict air pollutant exposure and abatement in open road environments. However, further research is required to describe pollutant decay profiles under more diverse roadside scenarios (e.g. split-level terrain) and to strengthen projections. Workshop findings validated the HedgeDATE concept and indicated scope for uptake. End-user feedback was generally positive, although potential improvements were identified. For HedgeDATE to be made relevant for practitioners and decision-makers, future iterations will require enhanced applicability and functionality. This work sets the foundation for the development of advanced GI design tools for reduced pollution exposure

Microplastics in personal care products: Exploring perceptions of environmentalists, beauticians and students

Microplastics enter the environment as a result of larger plastic items breaking down (‘secondary’) and from particles originally manufactured at that size (‘primary’). Personal care productsare an important contributor of secondary microplastics (typically referred to as ‘microbeads’), for example in toothpaste, facial scrubs and soaps. Consumers play an important role in influencing the demand for these products and therefore any associated environmental consequences. Hence we need to understand public perceptions in order to help reduce emissions of microplastics. This study explored awareness of plastic microbeads in personal care products in three groups: environmental activists, trainee beauticians and university students in South West England. Focus groups were run, where participants were shown the quantity of microbeads found in individual high-street personal care products. Qualitative analysis showed that while the environmentalists were originally aware of the issue, it lacked visibility and immediacy for the beauticians and students. Yet when shown the amount of plastic in a range of familiar everyday personal care products, all participants expressed considerable surprise and concern at the quantities and potential impact. Regardless of any perceived level of harm in the environment, the consensus was that their use was unnatural and unnecessary. This research could inform future communications with the public and industry as well as policy initiatives to phase out the use of microbeads

Oxysterol Binding Protein-dependent Activation of Sphingomyelin Synthesis in the Golgi Apparatus Requires Phosphatidylinositol 4-Kinase IIα

The study identifies a sterol- and oxysterol binding protein (OSBP)-regulated phosphatidylinositol 4-kinase that regulates ceramide transport protein (CERT) activity and sphingomyelin (SM) synthesis. RNA interference silencing experiments identify PI4KIIα; as the mediator of Golgi recruitment of CERT, providing a potential mechanism for coordinating assembly of SM and cholesterol in the Golgi or more distal compartments