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    Reduced osmoresponsiveness in magnocellular neuroendocrine neurones during chronic salt-loading

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    Here, we studied the effects of salt-loading in rats on the electrophysiological behaviour of neurones that secrete oxytocin and vasopressin. After 7 days of salt-loading, the basal firing rate of both vasopressin cells and oxytocin cells in urethane-anaesthetized rats was increased by less than 1 spike s -1, which is much less than expected from the hyperosmolality induced by saltloading. The neuronal responsiveness to acute osmotic stimuli was also markedly impaired, with no change in their responses to non-osmotic stimuli. We then undertook a systematic search of the literature for studies in salt-loaded rats that had measured oxytocin or vasopressin secretion, plasma osmolality, haematocrit or pituitary hormone content, and reviewed them in light of our electrophysiological findings. The prevailing understanding is that salt loading induces plastic changes in neuronal behaviour to promote exaggerated vasopressin secretion, but the conclusions that we draw from our electrophysiological findings in urethane-anaesthetized rats and the literature review suggest the converse - that vasopressin neurones selectively habituate to osmotic stimuli, presumably to conserve diminished pituitary stores of vasopressin while sustaining enough secretion for maximal renal effects. KEY POINTS: Seven days of 'salt-loading' produces a large increase in plasma osmolality and depletes the pituitary content of vasopressin and oxytocin, apparently reflecting enhanced secretion. Using in vivo electrophysiological recordings in urethane-anaesthetized rats, we show that, after 7 days of salt loading, the basal firing rate of both vasopressin and oxytocin cells was increased to a much lesser extent than expected from the hyperosmolality induced by acute osmotic stimuli. The neuronal responsiveness to acute osmotic stimuli was also markedly impaired with no change in their responses to non-osmotic stimuli. Our results show that these neurones strongly and selectively habituate to chronic osmotic stimuli, presumably to conserve diminished pituitary stores of hormone. Our conclusions contradict the prevailing understanding that salt loading promotes an exaggerated hyperexcitability of the hypothalamo-neurohypophysial system. </p

    Use of generative AI in postgraduate taught programmes at a UK vet school: a moment in time

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    IntroductionThe rapid rise in the use of generative artificial intelligence (GenAI) models in society is having a marked impact on universities. Studies have been conducted looking at perceptions of AI of UK students but little research has been conducted in the veterinary space, let alone in postgraduate veterinary curricula. Flexible online postgraduate courses such as PGCerts and MSc programmes are popular with vets as they fit in around their demanding clinical work, but the extent of GenAI use by students in these programmes is not well understood.MethodsA survey of postgraduate taught students at a UK vet school was conducted between May and late July 2025. Demographic data including programme of study, age, gender, country of residence, and native English language status were collected, and students were asked about their experience of using GenAI, their confidence in various aspects of GenAI knowledge and application, and how useful they would find teaching in this area. Descriptive statistics were collated, Spearman’s correlations and Kruskal-Wallis tests performed between variables, and principal components analysis (PCA) performed.Results87 students responded to the survey from 13 programmes. Most respondents were from the UK (24, 27.6%) and USA (20, 23.0%) with 25 other countries represented, and the majority of respondents were in the 26-35 (24, 27.6%), 36-45 (22, 25.3%) and 46-55 (25, 28.7%) age ranges. The majority of students (56, 64.4%) were using GenAI in the workplace, and a similar number were using it in their studies (59, 67.8%) with a strong correlation between the frequency of usage in each (Spearman’s ρ=0.672, p=1E-12). The modal score for confidence (of a 1-5 low-high scale) was 4 for fundamental knowledge of AI, ethics, assessing AI accuracy and professionalism in relation to AI, with a score of 3 most common for application to clinical care and 2 in data privacy and security. When asked about usefulness of teaching in these same areas (1-4 low-high scale), the modal score was 4 for all areas aside from fundamental knowledge of AI, where modal score was 3. Kruskal-Wallis tests were conducted for the confidence variables, teaching variables and employment and studies use of GenAI against programme, country, gender, and English language status, and Spearman’s correlations calculated against age. No comparisons were significant after Benjamini-Hochberg control, and no correlations were significant. PCA did not illustrate clear grouping of variables to allow identification of user profiles.ConclusionsThe majority of students on postgraduate programmes at the vet school are using GenAI in their studies, and this correlates strongly with their use in the workplace. They feel confident in their knowledge of AI and its application but need to develop confidence around clinical application and data privacy and security, and they strongly value teaching across these areas on their programmes. There is not a clear profile of a typical GenAI user – usage is widespread, and likely to increase as Gen AI becomes more embedded in the workplace. The findings provide an opportunity for reflecting on current student support and the curriculum in order to better equip students to feel confident in today’s world

    Low circulating miR-190a-5p predicts progression of chronic kidney disease

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    MicroRNAs may act as diagnostic and prognostic biomarkers of chronic kidney disease and are functionally important in disease pathogenesis. To identify novel microRNA biomarkers, we performed small RNA-sequencing on plasma from individuals with type 2 diabetes, with and without chronic kidney disease. MiR-190a-5p abundance was significantly lower in the circulation of type 2 diabetic patients with reduced function compared to those with normal kidney function. In an independent cohort of patients with chronic kidney disease of diverse aetiology, miR-190a-5p abundance predicted disease progression in individuals with no or moderate albuminuria (&lt; 300 mg/mmol). miR-190a-5p expression in kidney biopsy tissue correlated with the level of miR-190a-5p in the circulation and with estimated glomerular filtration rate, tubular mass and negatively with histological fibrosis. Administration of a miR-190a-5p mimic in a murine ischaemia-reperfusion injury model in male mice reduced tubular injury and fibrosis and increased expression of genes associated with tubular health. Our analyses suggest that miR-190a-5p is a biomarker of tubular cell health, low circulating levels may predict chronic kidney disease progression independent of existing risk factors and strategies to preserve miR-190a-5p may be an effective treatment for restoring tubular cell health following kidney injury.</p

    Chromosome-level genome assembly of the hamour (orange-spotted grouper), Epinephelus coioides

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    We present a chromosome-level genome assembly and annotation of the hamour, or orange-spotted grouper ( Epinephelus coioides), a high-value and significant teleost fish species across West Indo-Pacific regions of the Middle East, South Africa, and Australia. This species is a popular target for both commercial and recreational fishing and it is widely cultured around the world, particularly in the Asia-Pacific region. The hamour genome was sequenced from one individual male originating from a wild population in the Arabian Gulf and assembled into a 1.07 Gb assembly, the largest 24 superscaffolds making up 99.9% of the assembly. Annotation of the genome identified 28,384 protein-coding genes, with 98.9% single-copy BUSCO gene completeness (Actinopterygii database). These data will support further studies on functional ecological and evolutionary genomics of this species, enhancing the understanding of its biology and its responses to stressors including pathogens.</p

    Synovial Fluid and Serum MicroRNA Signatures in Equine Osteoarthritis

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    The aim of this study was to identify differentially expressed microRNAs (miRNAs) in serum and synovial fluid (SF) samples of control horses and those with osteoarthritis (OA) to identify potential candidates for biomarkers of disease. Total RNA was extracted from serum and SF samples of control (n = 4) and OA (n = 9) horses and sequenced. Differential expression analysis, pathway analysis and miRNA target prediction were performed. A group of six miRNAs (eca-miR-199a-3p, eca-miR-148a, eca-miR-99b, eca-miR-146a, eca-miR-423-5p and eca-miR-23b) was selected for validation in an independent cohort (serum, n = 46; SF, n = 88). The effect of clinical variables on miRNA expression was also assessed. Sequencing analyses found 43 and 23 differentially expressed miRNAs in serum and SF samples, respectively. Pathway analysis showed miRNAs were involved in inflammatory disease/response and associated with OA pathways. miRNA expression in serum was strongly associated with the horses' workload, while age had a pronounced influence on miRNA expression in SF. Distinct patterns of miRNA differential expression were observed in serum and SF samples from horses with OA compared to controls. miR-199a-3p and miR-148a warrant further investigation as potential biomarkers of equine OA. Further characterization of these molecular changes could provide novel insights into the mechanisms of early OA.</p

    SciBlend: Advanced data visualization workflows within Blender

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    Scientific data visualization is essential for analysis, communication, and storytelling in research. While Blender offers a powerful rendering engine and a flexible 3D environment, its steep learning curve and general-purpose interface can hinder scientific workflows. To address this gap, we present SciBlend, a Python-based toolkit that extends Blender for data visualization. It provides specialized add-ons for multiple computational data files import, annotation, shading, and scene composition, enabling both photorealistic (Cycles) and real-time (EEVEE) rendering of large-scale and time-varying data. By combining a streamlined workflow with physically based rendering, SciBlend supports advanced visualization tasks while preserving essential scientific attributes. Comparative evaluations across multiple case studies show improvements in rendering performance, clarity, and reproducibility relative to traditional tools. This modular and user-oriented design offers a robust solution for creating publication-ready visuals of complex computational data

    Deep mutational scanning of the human insulin receptor ectodomain to inform precision therapy for insulin resistance

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    The insulin receptor entrains tissue growth and metabolism to nutritional conditions. Complete loss of function in humans leads to extreme insulin resistance and infantile mortality, while loss of 80-90% function permits longevity of decades. Even low-level activation of severely compromised receptors, for example by anti-receptor monoclonal antibodies, thus offers the potential for decisive clinical benefit. A barrier to genetic diagnosis and translational research is the increasing identification of variants of uncertain significance in the INSR gene, encoding the insulin receptor. By coupling saturation mutagenesis to flow-based assays, we stratified approximately 14,000 INSR extracellular missense variants by cell surface expression, insulin binding, and insulin- or monoclonal antibody-stimulated signalling. Resulting function scores correlate strongly with clinical syndromes, offer insights into dynamics of insulin binding, and reveal novel potential gain-of-function variants. This INSR sequence-function map has biochemical, diagnostic and translational utility, aiding rapid identification of variants amenable to activation by non-canonical INSR agonists.</p

    MRI signal void in degenerated canine intervertebral disks may represent mineralization or gas.

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    Accurate interpretation of intradiskal signal voids on magnetic resonance imaging (MRI) is essential to avoid misdiagnosis and improve diagnostic decision-making in canine spinal imaging. Gas accumulation within the degenerated canine intervertebral disk (IVD), known as vacuum phenomenon (VP), and IVD mineralization are common findings in computed tomography (CT), with distinctly different x-ray attenuation characteristics. In MRI, both appear as a signal void, which can complicate interpretation. We hypothesized that gas and mineralization would not differ in intensity values on MRI but would differ in location and shape when compared to CT. This exploratory retrospective multicenter study aims to assess the characteristics of VPs and mineralization in MRI, using CT as the gold standard. Imaging archives were searched for matching canine spinal CT and MRI performed within 48 h. Inclusion criteria included mineralization or gas in the IVD on CT images and available sagittal T2W-sequence MRI images of the same vertebral segment. Twenty-six studies were included, contributing 32 IVD spaces. The presence of IVD mineralization and gas in CT, along with the location, shape, and pixel-value of MRI signal intensity in IVD spaces, was recorded. No statistical differences were identified in pixel values between the groups (p = 0.5). However, there were significant changes in the location of the signal void compared to the recorded location in CT, particularly in VP (p = 0.03). These results emphasize that MRI T2 signal voids in canine IVDs may represent gas. No specific MRI characteristics allowed reliable prioritization of VP versus mineralization; therefore, both should be considered differential diagnoses when encountering intradiskal signal voids on MRI.</p

    Transcriptome-wide mRNP condensation precedes stress granule formation and excludes new mRNAs

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    Stress-induced messenger ribonucleoprotein (mRNP) condensation is conserved across eukaryotes, resulting in stress granule formation under intense stresses, yet the mRNA composition and function of these condensates remain unclear. Exposure of ribosome-free mRNA following stress is thought to cause condensation and stress granule formation through mRNA-sequence-dependent interactions, leading to disproportionate condensation of long mRNAs. Here, we show that, by contrast, virtually all mRNAs condense in response to multiple stresses in budding yeast with minor length dependence and often without stress granule formation. New transcripts escape mRNP condensation, enabling their selective translation. Inhibiting translation initiation causes formation of mRNP condensates distinct from stress granules and processing bodies (P bodies), and these translation-initiation-inhibited condensates (TIICs) are omnipresent, even in unstressed cells. Stress-induced mRNAs are excluded from TIICs due to the timing of their expression, indicating determinants of escape that are independent of sequence. Together, our results reveal a previously undetected level of translation-linked molecular organization and stress-responsive regulation

    The capacious companion:Law, lawyers and the legal on ethics advisory groups

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    This article asks whether and how law matters in ethics advisory work in the fields of health, medicine and science, and whether it is law or legal knowledge, or both, that matters. Written from the perspective of four law professors, each with first-hand experience of ethics advisory groups, it examines the framing of academic legal expertise on ethics advisory groups and explains why this framing requires ongoing negotiation

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