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Generation of two iPSC lines from patients with Aicardi-Goutières syndrome carrying either biallelic ADAR1 mutations (PC138) or a heterozygous IFIH1 mutation (PC139)
Get PDFMutations in ADAR1 (Adenosine deaminase acting on RNA 1) and IFIH1 (Interferon Induced With Helicase C Domain 1) are associated with Aicardi-Goutières syndrome (AGS), a genetically determined inflammatory disorder particularly affecting the brain and skin. Here, we generated induced pluripotent stem cells (iPSCs) from one patient carrying compound heterozygous loss-of-function mutations in ADAR1 (PC138/AGS0788.1: c.577C>G p.(Pro193Ala) and c.1386_1390del p.(Asp462Glufs*2)), and one individual carrying a heterozygous gain-of-function mutation in IFIH1 (PC139/AGS2177.1: c.2336G>A p.(Arg779His)). Cells from these patients were reprogrammed by episomal transfection, had normal karyotype, expressed pluripotency markers and were able to differentiate into the three germ cell layers
From Scotland to Gaza:A SCALP and Netpol Report on the policing of Palestine solidarity protests in Scotland
Get PDFSOX2 phosphorylation during mitosis limits genomic damage
Get PDFPioneer transcription factors (TFs) such as SOX2 play critical roles in the control of stem cell identity and are dysregulated in many human cancers. For example, SOX2 regulates the self-renewal of neural stem cells (NSCs) and is typically highly expressed in glioblastoma stem cells (GSCs), where it is known to induce an immature NSC-like state. Here, we explored the regulation of SOX2 by phosphorylation during NSC division and identified an unexpected role for excessive SOX2 pioneer activity in driving mitotic damage. We found that SOX2 phosphorylation during mitosis is a key switch that prevents promiscuous chromatin binding across the genome. Without this regulatory control, excessive SOX2 in mitosis triggers chromatin opening, resulting in increased mitotic transit times and increased chromosomal damage. Therefore, elevated levels of SOX2 in cancers may have dual oncogenic roles: inducing stemness during interphase via its well-known transcriptional roles but simultaneously promoting chromosomal disruptions through unconstrained pioneer factor activity.</p
Immigration and Social Systems:Collected Essays of Michael Bommes
No full textMichael Bommes was one of the most brilliant and original migration studies scholars of our time. This posthumous collection brings together a selection of his most important work on immigration, integration, transnationalism, irregular migration and migrant networks. Each essay provides a rigorous and compelling critique of mainstream accounts, building on Bommes' distinctive systems theoretic approach. It will be required reading for all theoretically minded scholars and advanced students of migration studies.</p
Woman-not-woman:Abjection and gender transformation in Las Fiestas de Santiago
No full textDuring the yearly patronal festival las fiestas en honor a Santiago Apóstol (las fiestas), men from Loíza, Puerto Rico, transform themselves to become madwomen whose ribald and bawdy behaviour transgresses personal and religious boundaries of decency. In Christian colonial contexts, ‘decency’ is a racialised way of prescribing gender and sexual norms that posit the white Christian, heterosexual, male as ideal personhood. Known as la loca, this festal personage disrupts this idealised notion of personhood through gender transformations and engagement with repressed human and social behaviour. Historically understood figuratively and affirmatively, this article draws from ethnographic fieldwork with one loca, Carlito, and the work of philosopher and sociologist of religion Georges Bataille to examine the literal and negative aspects of this festival character. I argue that her vulgarity and gender-bending performances are a manifestation of the negative sacred, which has the potential to destabilise Christian colonial notions of personhood.</p
Discovering hidden laws in innovation by recombination
No full textCombining two things can create amazing new things - whether mixing water and flour or feeding large datasets into neural networks. Hypothesizing rules and theories for recombination, testing those hypotheses, and communicating our findings to each other are key cognitive mechanisms that allow us to navigate an open-ended world of possible combinations. However, in contrast to this open-ended and highly-complex search problem, cognition is constrained by its capacity. Using ideas from information theory, we hypothesize that the compressibility of recombination rules predicts how successfully people find and use these rules. In a combinatorial discovery game, we find that people indeed learn quicker and collect more points when the rules are more compressible. Interestingly, people use fewer words to communicate their findings when the rules are either too easy or too hard to compress, revealing an inverse-U shaped relationship between compressibility and communication effort
Using Longitudinal Data of Somatic Cell Counts and Milk Yield to Identify Mastitis-Resilient Cows
No full textBovine mastitis remains a significant concern for the dairy industry, affecting animal welfare, farm profitability, and milk quality. Despite genetic and non-genetic control efforts, its multi-pathogenic nature makes eradication challenging, highlighting the importance of mastitis resilient cows (animals that are minimally affected or recover quickly after a health challenge). Resilience is commonly quantified using resilience indicators (RIs) based on performance deviations from a hypothetical unperturbed trajectory (i.e., the expected performance in the absence of challenges). To date, RIs for dairy cows have been constructed exclusively from time-series performance data (e.g., milk yield). However, to breed for resilience to mastitis, it would be more useful to develop mastitis-specific indicators than general production-based ones. This study explores the use of daily records of somatic cell counts (SCC) and milk yield to identify and characterise potential perturbations associated with mastitis. Specifically, we evaluated alternative statistical approaches for estimating individuals’ unperturbed trajectories and assessed their consistency in detecting periods of systematic deviation. Data from the Swedish University of Agricultural Sciences cattle infrastructure, Gigacow, were used. The dataset includes daily records of milk yield and online SCC from 1,052 dairy cows across up to 7 lactations, from 6 Swedish dairy farms using automatic milking systems with online cell counters. Three methods were applied separately to the milk yield and SCC data: (i) weighted spline, where data points likely associated with perturbations were given lower weights (e.g., milk yield drops or SCC spikes); (ii) quantile regression (targeting the 0.7 quantile for milk yield and 0.3 quantile for SCC); and (iii) iterative polynomial regression, where large negative (milk yield) and large positive residuals (SCC) were progressively removed and the curve refitted to minimise the influence of perturbed observations. Deviations from the estimated trajectories were computed, and potential perturbations characterised. Preliminary findings suggest that quantile regression and weighted spline produce similar trajectories and identify comparable perturbations. In contrast, the iterative polynomial method generates a different trajectory and detects fewer perturbations, reflecting a conservative approach for identifying perturbations. These results can help determine the most appropriate method for detecting mastitisrelated perturbations and, ultimately, identify the most mastitis-resilient animals
Integrative mapping of preexisting influenza immune landscapes predicts vaccine response
No full textBACKGROUNDPredicting individual vaccine responses is a substantial public health challenge. We developed Immunaut, an open-source, data-driven framework for systems vaccinologists to analyze and predict immunological outcomes across diverse vaccination settings, beyond traditional assessments.METHODSUsing a comprehensive live attenuated influenza vaccine (LAIV) dataset from 244 Gambian children, Immunaut integrated prevaccination and postvaccination humoral, mucosal, cellular, and transcriptomic data. Through advanced modeling, our framework provided a holistic, systems-level view of LAIV-induced immunity.RESULTSThe analysis identified 3 distinct immunophenotypic profiles driven by baseline immunity: (a) CD8+ T cell responders with strong preexisting immunity boosting memory T cell responses; (b) mucosal responders with prior influenza A virus immunity developing robust mucosal IgA and subsequent influenza B virus seroconversion; and (c) systemic, broad influenza A virus responders starting from immune naivety who mounted broad systemic antibody responses. Pathway analysis revealed how preexisting immune landscapes and baseline features, such as mucosal preparedness and cellular support, quantitatively dictate vaccine outcomes.CONCLUSIONOur findings emphasize the power of integrative, predictive frameworks for advancing precision vaccinology. The Immunaut framework is a valuable resource for deciphering vaccine response heterogeneity and can be applied to optimize immunization strategies across diverse populations and vaccine platforms.FUNDINGWellcome Trust (110058/Z/15/Z); Bill & Melinda Gates Foundation (INV-004222); HIC-Vac Consortium; NIAID (R21 AI151917); NIAID CEIRR Network (75N93021C00045).</p
Knowledge and priorities of UK and European equine industry stakeholders regarding equine genetics
No full textThe field of equine genetics has progressed considerably in the 21st century (Kalbfleisch et al., 2018, Bailey et al., 2022), with a wide range of genetic tests available and considerable research efforts examining different aspects of genomics and various genetic traits (Hamilton, 2024, McFadden et al., 2024, Puchalska and WitkowskaPiłaszewicz, 2025). A recent survey was conducted in the USA to assess knowledge and priorities of stakeholders in the industry to help direct future research efforts (Hernandez et al., 2025). In this study, we conducted a similar survey in UK and European stakeholders.The survey was run from July to December 2024, targeting horse owners and industry professionals in the UK and mainland Europe using a snowball sampling method. Closed-ended and free text questions regarding their genetics knowledge, their experience and concern around genetic diseases, communication and information sources, and their priorities for genetics research were asked. We also tested respondents’ knowledge by asking 6 genetics questions of approximately secondary school biology level, requesting they answer ‘do not know’ if they were not certain of their answer, and generated a total knowledge score where respondents received 0 for an incorrect answer, 1 for ‘do not know’ and 2 for a correct answer. Descriptive statistics were produced, and closedended questions were analysed using Kruskal-Wallis tests and Spearman’s correlations. The knowledge test score and self-reported knowledge scores were also transformed to a common percentile scale for analysis of over- and under-estimation of knowledge. Thematic analysis of free text responses is ongoing.There were 177 responses, with the largest age category being 31-50 years old (n=94, 53%). The most common industry role was owner (n=78, 44%) followed by breeder (n=36, 20%), and the primary horse type worked with was sports horses (n=96, 54%) and native ponies (n=29, 16%). Respondents typically owned/cared for 1-5 horses (n=108, 61%), and their main activity was leisure riding (n=46, 26%), breeding (n=35, 20%) or dressage (n=26, 15%). The most common primary horse breeds worked with were warmbloods (n=63, 36%), other breeds (n=15, 8%) and a combination of breeds (n=11, 6%).The majority of respondents (n=119, 67%) felt they had a ‘solid’ understanding of genetics (rank 3 of 4), and the lowest mean ranked information source was breed/discipline organisations (mean rank=2.59, SD=1.98), followed by universities (mean rank=3.16, SD=2.27), however respondents reported preferring to receive information via magazines/newsletters (n=103, 58%). The top three genetic diseases respondents were concerned about were osteochondritis dissecans (OCD) (n=65, 37%), polysaccharide storage myopathy type 1 (PSSM1) (n=55, 31%) and cervical vertebral stenotic myelopathy (CVSM) (n=54, 31%), whilst the disease most encountered by participant was none (n=103, 58%) followed by OCD (n=60, 34%). Respondents were interested in knowing the level of geneticdiversity in their horses (n=117, 68%) and in testing for performance genes (n=91, 51%). The mean genetics knowledge score was 8.67 out of 12 (SD=2.47) – the only significant difference in score between industry roles were in scientists, who had higher scores than breeders (U=209, p=0.033) and trainers (U=48, p=0.035).There was a significant but moderate correlation between self-reported genetics knowledge level and the test score (ρ=0.33, p=5.95e-6). When compared on a common percentile scale, 46.9% (n=83) overestimated their own knowledge, whilst 53.1% (n=94) underestimated, showing no evidence of a skew to overconfidence (binomial p=0.816). However, lower performing respondents were more likely to overestimate than higher performing respondents: 69% of the lowest quartile and 74% of Q2 overestimated their knowledge, compared to 14% in Q3 and 23% in Q4.Overall, our responding stakeholders had both knowledge and interest in equine genetics, with key priorities for future research in genetic disease, genetic diversity and performance traits identified. Future opportunity for outreach and communication of ongoing research to industry is also clear. However, we also present evidence of a pattern consistent with a Dunning-Kruger effect in our sample.References:Kalbfleisch TS, Rice ES, DePriest Jr MS, Walenz BP, Hestand MS, Vermeesch JR, O′ Connell BL, Fiddes IT, Vershinina AO and Saremi NF 2018. Improved reference genome for the domestic horse increases assembly contiguity and composition. Communications Biology 1, 197.Bailey E, Petersen JL and Kalbfleisch TS 2022. Genetics of Thoroughbred Racehorse Performance. Annual review of animal biosciences 10, 131-150. DOI: https://doi.org/10.1146/annurev-animal-020420-035235Hamilton NA 2024. Genetic Basis of Equine Performance. In Equine Sports Medicine and Surgery, pp. 114-127, Elsevier.McFadden A, Vierra M, Martin K, Brooks SA, Everts RE and Lafayette C 2024. Spotting the pattern: A review on white coat color in the domestic horse. Animals 14, 451.Puchalska M and Witkowska-Piłaszewicz O 2025. Gene doping in horse racing and equine sports: Current landscape and future perspectives. Equine Veterinary Journal 57, 312-324.Hernandez S, Nastrini E, Norton E, McCoy AM, Brooks SA and Mienaltowski MJ 2025. U.S. stakeholder survey examining understanding of equine genetics and concerns for genetic diseases. Journal of Equine Veterinary Science 148, 105508.DOI: https://doi.org/10.1016/j.jevs.2025.105508<br/
Tissue resident colonic macrophages persist through acute inflammation and adapt to aid tissue repair
No full textMacrophages are crucial for the maintenance of intestinal homeostasis, are considered key proinflammatory effector cells during intestinal inflammation and are implicated in tissue repair following injury or inflammation. Whether these roles are attributed to distinct subsets of macrophages or if macrophages retain a degree of plasticity in the intestine remains poorly understood. Here, through a combination of single cell RNA sequencing, lineage-tracing and immunofluorescence imaging, we define three major subpopulations of murine, colonic macrophages on the basis of CD11c and CD163 expression. These macrophages occupy discrete anatomical niches and display distinct replenishment kinetics. They all accumulate during acute colitis and Cx3cr1--based fate mapping shows that they persist through to inflammation resolution. Moreover, marked transcriptional differences exist between the macrophages present in health and their counterparts in the post-inflammation environment, demonstrating that inflammation leads to transcriptional rewiring of the resident macrophages in a subset-specific manner. Intriguingly, there were minimal transcriptional changes between long-lived macrophages and their recently differentiated counterparts, indicating the environment exerted a greater influence than ontogeny or the time of residency on their functional states in inflammation resolution.</p
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