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Arabidopsis thaliana Fanconi Anaemia I (FANCI) has roles in the repair of interstrand crosslinks and CRISPR-Cas9 induced DNA double strand breaks
No full textDNA repair is crucial for genome stability, in particular for plants which are exposed to high levels of damage arising from UV irradiation, soil pollutants and reactive oxygen species. Damage that affects both strands of the DNA duplex is harder to repair due to both the lack of a template strand and the potential for physical separation of fragmented chromosomes. As such, DNA double-strand breaks (DSBs) and interstrand DNA crosslinks (ICL) are particularly cytotoxic forms of damage. Here we report the functions of FANCONI ANAEMIA I (FANCI), an Arabidopsis thaliana homologue of the mammalian ICL repair protein. We show that in plant cells, as in mammals, FANCI forms a nuclear localised complex with FANCD2. Genetic analysis of plants lacking FANCI displays significant hypersensitivity to the DNA crosslinking reagent mitomycin C. Furthermore, mutation of FANCI in combination with mutations in a second ICL repair factor, METHYL METHANESULFONATE AND UV-SENSITIVE PROTEIN 81 (MUS81), results in increased levels of programmed cell death compared to the corresponding single mutants, revealing roles in maintaining plant genome stability. Sequence analysis of mutational repair of CRISPR-Cas9-induced DSBs revealed that FANCI promotes single nucleotide insertions and reduces longer deletions. This pattern of mutations may reflect roles for FA proteins in replication-coupled repair of a subset of DSBs. Taken together, this analysis finds evidence for multiple roles for FANCI in the maintenance of plant genome stability
Colourful Brazilian anurans are preferentially targeted by wildlife trade
Get PDFThe global wildlife trade is a multi-billion-dollar industry, that when poorly managed, can threaten all major terrestrial taxa. Amphibians are currently the most threatened terrestrial vertebrate taxa, due in part to exploitation. Humans place a high value on the aesthetics of nature, with distinctive morphology often a key driver of wildlife trade. Here, we explore the association of colour on the trade of anuran species traded as both pets (traded alive) and products (traded dead) in Brazil, a hotspot of anuran diversity. We collected colour data on all 64 traded Brazilian anurans plus an additional 216 control species not in trade. Our results highlighted more vibrant colours in traded than non-traded species and that the probability of trade increases with the number of colours present. The presence of blue had the strongest effect on trade probability, followed by orange, black, then yellow, with the remaining colours having no effect on the likelihood of trade. Anurans displaying rarer colours are more likely to be traded and more colours increase the likelihood of trade for pets but not for products. Our results provide crucial evidence that colour diversity in amphibians influences the risk of trade and adds to the growing weight of evidence that colour is a key correlate of trade. This points to the need to focus monitoring and protection efforts on colourful species that are at-risk from unsustainable exploitation
Stepping Up, Standing Out: A Case Study on engaging with international student voices through co-creation
Get PDFIn the diverse and dynamic landscape of United Kingdom (UK) Higher Education (HE), the challenges and opportunities faced by international Postgraduate Taught (PGT) students have become a focal point for institutions striving to create an inclusive environment. The influx of international students highlights their importance to the UK HE sector, yet despite HE institutional efforts to provide support, students often report ongoing challenges and feeling limited in their opportunities to share their student voices in shaping institutional actions. This creates gaps in a feedback loop between problem and solution. We report here on a case-study arising from a recent three-year mixed-methods project in a UK university, exploring student engagement with academic support. Based on a participatory approach, we included students in each year of the project through surveys, focus groups and workshops. Findings from each stage were evaluated by students to feed into the next, leading to the co-creation of practical, inclusive, interculturally-aware resources on how to make the most of a Masters’ experience, from the students’ perspective. These resources are now refreshing student recruitment and staff practice at our University, to ensure a welcoming, empathetic, and inclusive environment. This project highlights the importance of a collaborative approach in supporting international PGT students, valuing their unique contributions to the academic community, and demonstrating the central role played by student partners in closing the feedback loop
Malicious attacks for maximising island numbers in cyber-physical power system: a graph-theoretic approach
No full textThis letter proposes an island-maximising attack mechanism to maximise the number of power islands in cyber-physical power systems (CPPS) by disrupting lines. Specifically, a single-level mixed-integer programming (MIP) model is developed with a graph-theoretic approach, which is able to divide CPPS into power islands, while intra-island line overloads are induced in a high-stealth manner with increasing load shedding and economic loss. Case studies conducted on modified IEEE 14-bus and practical 36-zone Great Britain systems validate the effectiveness of our proposed island-maximising approach
Letter to the Editor: Misclassification of fibres in Ramage et al. (2025) and implications for microplastics research
Get PDFAssociations between polygenic risk for Alzheimer’s disease and grey matter volume are dependent on APOE, pathological and diagnostic status
Get PDFBackground/Objectives: Studies have shown that higher polygenic risk scores (PRSs) for Alzheimer’s disease (AD) are associated with smaller volumes in temporal brain regions typically affected by this disease. These effects have also been found in cognitively unimpaired (CU) older adults. This study aimed to investigate the relationship between PRSs and brain volumes in specific areas associated with early AD. Methods: 342 participants were selected from the Alzheimer’s Disease Neuroimaging Initiative and stratified into three groups: 114 amyloid-positive atrophic (A+N+), 114 amyloid-negative non-atrophic (A−N−), and 114 amyloid-positive non-atrophic (A+N−) people. Linear regressions were performed within each group to investigate associations between PRSs and regional grey matter volumes. Analyses were also repeated after stratifying groups by APOE status and clinical diagnosis. Two sensitivity analyses were run to investigate the impact of APOE and amyloid status and concordance across biomarkers. Multiplicity was controlled for using the Benjamini–Hochberg false discovery rate (FDR) approach. Results: Negative associations were observed between PRSs and volumes of the left amygdala and hippocampus in A+N+, right hippocampus in A+N−, and right posterior cingulate cortex in A−N− participants. Associations were found especially in A−N− participants, both ε4 allele carriers and non-carriers, and mostly confirmed in sensitivity analyses. Associations emerged only in CU and AD participants, but not in people with MCI. None of these findings survived correction for FDR. Conclusions: These findings highlight the potential of PRSs as novel biological indicators for a deeper characterisation of AD-related neural alterations
Ultrasound-detected inflammation and structural changes in the joints, tendons and entheses of patients with cancer who developed arthritis or arthralgia after exposure to immune checkpoint inhibitors
Get PDFObjectives
To explore the prevalence and distribution of ultrasound-detected inflammation and structural damage in the joints, tendons and entheses of patients who developed new-onset arthritis or arthralgia following exposure to immune checkpoint inhibitor (ICI) therapy, including a comparison between those with ICI-induced arthritis and those with ICI-induced arthralgia.
Methods
Patients with cancer who developed clinical arthritis or arthralgia (ie, joint pain without clinical synovitis) after receiving ICIs were consecutively recruited from six international centres. Patients underwent a full clinical assessment and ultrasound evaluation of 18 joints, 15 tendons and 5 entheses bilaterally, using the Outcome Measures in Rheumatology definitions.
Results
A total of 101 patients were included: 53 (52.5%) had ICI-arthralgia (absent clinical synovitis). Among them, 25 (47.2%) had ultrasound-detected subclinical synovitis, 10 (18.9%) tenosynovitis, 1 (1.9%) digital extensor peritendinitis and 13 (24.5%) enthesitis. In the 48 patients with ICI-arthritis, ultrasound-detected synovitis was more prevalent than in ICI-arthralgia (93.8% vs 47.2%, p<0.001), particularly in the wrists (56.3% vs 20.8%, p<0.001) and the knees (54.2% vs 13.2%, p<0.001), which were the most frequently affected joints. Tenosynovitis (52.1% vs 18.9%, p<0.001), peritendinitis (10.4% vs 1.9%, p=0.099) and bone erosions (25% vs 7.5%, p=0.027) were also more frequent in ICI-arthritis. ‘Active’ enthesitis was similar between groups (31.3% vs 24.5%), with no significant differences.
Conclusions
This multicentre study reveals a higher burden of ultrasound-detected changes in ICI-arthritis compared with ICI-arthralgia, with diverse patterns across joints, tendons and entheses in both subtypes. Significant subclinical inflammation suggests that many cases of non-specific ICI-arthralgia may benefit from targeted interventions
Phenotypic and genomic analysis of the emerging poultry pathogen Enterococcus cecorum in UK isolates
Get PDFThe rate of Enterococcus cecorum infections within poultry (e.g. chickens, racing pigeons and Pekin ducks) has rapidly increased since they were initially reported in the UK and the Netherlands in 2002. E. cecorum can infect the free thoracic vertebra of chickens, often leading to carcass rejection at processing plants, incurring large economic costs to farmers. The environmental spread of this pathogen has been facilitated by high levels of antimicrobial resistance, as well as the emergence of divergent clonal lines with a higher pathogenic potential within poultry. Previous genomic studies have explored these characteristics within E. cecorum populations in both the USA and France. However, whether E. cecorum isolates in other countries show the same genomic traits remains unknown. In the present study, we investigate the properties of 190 E. cecorum isolates collected from UK broiler farms between 2021 and 2022. We report the MICs and epidemiological cutoff values for 32 antibiotics and analyse the genome sequence of 39 representative organisms from diseased or healthy broiler farms. We show that UK isolates present phenotypic signs of resistance for 26 antibiotics tested and show that clinical isolates are enriched in a single clade. These strains share properties with pathogenic strains from France and the USA, including conserved cell wall biosynthesis loci, as well as mobile genetic elements involved in the propagation of antibiotic resistance genes. Our results support the idea of a cross-continental spread of virulent E. cecorum
Industrial-scale fractionation of fava bean, chickpea, and red lentil: A comparative analysis of composition, antinutrients, nutrition, structure, and functionality
Get PDFLegumes are emerging as sustainable protein sources that can replace animal proteins and help meet global dietary needs. This study systemically compared the compositional profiles, antinutritional factors, amino acid profiles, protein quality, structural characteristics, and techno-functional properties of fava bean, chickpea, and red lentil flours, along with their dry- and wet-fractionated protein-enriched fractions (PFs). Wet-fractionated PFs exhibited higher protein content (58.36 – 83.79 g/100 g), while dry-fractionated PFs retained more total dietary fibre (7.62 – 14.64 g/100 g). Wet-fractionated fava bean (84.12 %) and red lentil (84.06 %) showed the highest in vitro protein digestibility (IVPD), while dry-fractionated chickpea showed the highest IVPDCAAS at 62.43 %. The protein composition was generally preserved after fractionation, though changes in secondary structure varied depending on legume source. Surface hydrophobicity (H₀ 62,739 – 99,381) increased following wet fractionation. In terms of functionality, wet-fractionated PFs showed the highest water-holding capacity (2.83 g/g, red lentil), foaming capacity (139.1 %, fava bean) and emulsifying capacity (108.1 m²/g, red lentil), but with relatively poor foaming and emulsifying stability. Conversely, dry-fractionated PFs exhibited higher protein solubility, lower least gelation concentration (8–10 %), and superior oil-holding capacity (3.98 g/g, Chickpea), likely due to reduced structural disruption, which limited protein aggregation and denaturation. Despite higher levels of antinutritional factors, dry fractionation emerges as a promising, cost-effective, and sustainable technology to produce legume protein concentrates with improved functionality and nutritional quality comparable to those obtained by wet-fractionated
Investigating the ageing-Parkinson’s disease nexus: standardisation of in vitro models and techniques by the PD-AGE network
Get PDFAgeing is the primary risk factor for Parkinson’s disease, yet the intricate interplay between these processes remains ambiguous. This position paper, a collaborative output from the PD-AGE consortium, addresses the urgent need for standardising methods in in vitro modelling. A panel of international experts recommends human induced pluripotent stem cell (iPSC)-derived models, with chemically induced ageing methods, such as the SLO cocktail, as a robust system. Furthermore, the consortium highlights the value of direct and semi-direct reprogramming for retaining donor-specific ageing phenotypes. The paper also outlines a prioritised panel of measurable parameters, categorised into senescence, inflammaging, omics profiling, and mitochondrial dysfunction, providing a consistent framework to enhance research reproducibility, investigating the nexus of ageing and Parkinson’s. In addition, we provide links to SOPs to measure the key measurable ageing parameters outlined in this review to facilitate consistency and reproducibility within the field
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