Squirrelpox in a red squirrel in Fife

SQUIRRELPOX has been identified as a key factor in red squirrel (Sciurus vulgaris) decline in the UK.1 Grey squirrels (Sciurus carolinensis) are thought to act as reservoir hosts for squirrelpox virus (SQPV), the causative agent of squirrelpox, with a reported asymptomatic seroprevalence of 61 per cent.2SQPV is implicated in the complete replacement of red squirrels by grey squirrels throughout mainland England and Wales,1 and poses a major threat to Scottish red squirrel populations since being first detected in 2007.3 To combat this threat, an mortality surveillance programme has been established at the Royal (Dick) School of Veterinary Studies, University of Edinburgh, using opportunistic sampling of red squirrel carcases. This has been ongoing for several years, including a summary publication covering 262 cases submitted from 2005 to 2009.4As part of this monitoring programme, an adult female red squirrel carcase was submitted by a member of the public, after having been found in Townhall Wood (NT110894), on the outskirts of Dunfermline, Fife, in March 2024. Postmortem examination identified multiple lesions typically associated with squirrelpox, including ulcerative and exudative dermatitis of the periocular and perioral skin (Fig 1). Histopathology of the affected skin identified extensive ulceration alongside remnant areas of epithelium with marked ballooning degeneration and eosinophilic intracytoplasmic inclusion bodies. Transmission electron microscopy of the affected tissue also identified numerous pox virions within the affected tissue, which through their size, shape and available surface morphology (Fig 2), were consistent with those of SQPV. In Britain there have been no additional identified diseases in red squirrels that present with periocular or perioral, ulcerative to exudative dermatitis due to a poxvirus,5indicating this case is highly likely due to SQPV.This finding represents the first identification of squirrelpox north of the central belt and is consistent with the predictions of previous modelling, which identified a high risk of northern SQPV spread from 2023 onwards.6 This modelling also suggests a rapid increase and spread of squirrelpox into more northerly and naive red squirrel populations is likely following establishment north of the central belt in central Scotland.6This case and modelling supports an increased requirement for targeted investigations, ongoing monitoring and grey squirrel interventions both around Dunfermline itself and within adjacent areas to establish the disease burden in this locality and limit further northerly squirrelpox spread.LA Wilson, veterinary pathology lecturer, M Marr, postdoctoral research fellow, C Logie, postmortem room technician, K Beckmann, conservation medicine lecturer, PWW Lurz, squirrel ecologist, R Ogden, director of conservation science, E Milne, professor emerita of veterinary clinical pathology Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG email: [email protected] DJ Everest, pathology scientist APHA Weybridge, Addlestone, Surrey KT15 3NBReferences1 Tompkins DM, White AR, Boots M. Ecological replacement of native red squirrels by invasive greys driven by disease. Ecol Lett2003;6:189–962 Sainsbury AW, Nettleton P, Gilray J, et al. Grey squirrels have high seroprevalence to a parapoxvirus associated with deaths in red squirrels. Anim Conserv2000;3:229–33 3 Mclnnes CJ, Coulter L, Dagleish MP, et al. First cases of squirrelpox in red squirrels (Sciurus vulgaris) in Scotland. Vet Rec2009;164:528–314 LaRose JP, Meredith AL, Everest DJ, et al. Epidemiological and postmortem findings in 262 red squirrels (Sciurus vulgaris) in Scotland, 2005 to 2009. Vet Rec2010;167:297–3025 Everest DJ, Tolhurst-Cherriman DAR, Davies H, et al. Assessing a potential non-invasive method for viral diagnostic purposes in European squirrels. Hystrix 2019;30:44–506 White A, Lurz PWW. A modelling assessment of control strategies to prevent/reduce squirrelpox spread. 2014. Scottish Natural Heritage Commissioned Report No 627. https://bit.ly/441TOgM (accessed 8 April 2024)PROFESSIONHistory of the veterinary professionI WRITE in response to the debate article by Bruce Vivash Jones (VR, 16/23 March 2024, vol 194, p 236). As a PhD researcher on the history of the RCVS and veterinary regulation, and a veterinary nurse, I would like to raise some issues with Vivash Jones’ historical evidence. He states that changes to the council structure would create an oligarchy. From his interpretation of an oligarchy I can assure him and our profession that the first RCVS council did work as This finding represents the first identification of squirrelpox north of the central belt20/27 April 2024 | VET RECORD312Fig 2: Squirrelpox virus virions detected in the affected tissue. Bar = 200 nmFig 1: Macroscopic lesions of ulcerative and exudative dermatitis surrounding the eye in a red squirrel (Sciurus vulgaris)Letters 20 April.indd 312Letters 20 April.indd 31216/04/2024 12:4816/04/2024 12:4

CARMENES input catalogue of M dwarfs IV. New rotation periods from photometric time series

Aims. The main goal of this work is to measure rotation periods of the M-type dwarf stars being observed by the CARMENES exoplanet survey to help distinguish radial-velocity signals produced by magnetic activity from those produced by exoplanets. Rotation periods are also fundamental for a detailed study of the relation between activity and rotation in late-type stars. Methods. We look for significant periodic signals in 622 photometric time series of 337 bright, nearby M dwarfs obtained by long-time baseline, automated surveys (MEarth, ASAS, SuperWASP, NSVS, Catalina, ASAS-SN, K2, and HATNet) and for 20 stars which we obtained with four 0.2-0.8 m telescopes at high geographical latitudes. Results. We present 142 rotation periods (73 new) from 0.12 d to 133 d and ten long-term activity cycles (six new) from 3.0 a to 11.5 a. We compare our determinations with those in the existing literature; we investigate the distribution of P rot in the CARMENES input catalogue,the amplitude of photometric variability, and their relation to vsin i and pEW(Halfa); and we identify three very active stars with new rotation periods between 0.34 d and 23.6 d.Comment: 34 pages, 43 figures, 2 appendix table

Environment and Rural Affairs Monitoring & Modelling Programme - ERAMMP Year 1 Report 22: A Review of the contribution of species records held by Local Environmental Record Centres in Wales to ERAMMP Evidence Needs

I. Better use of Local Environmental Record Centre (LERC) data in delivering biodiversity objectives is stated explicitly in the Nature Recovery Action Plan for Wales. Consistent with this aspiration we carried out two quantitative assessments of LERC data to determine the availability of species records at the resolution required for ERAMMP and WFG (Indicator 44) evidence needs; <=1km. II. A comparison of the availability of 1km square records for section 7 reptiles, amphibians and mammals between LERC and NBN Atlas showed that LERC data were more numerous in every case and sometimes markedly so (on average 17 times as many 1km square records in LERC data). For these species the NBN Atlas tends to have a greater number of records available at 10 rather than 1km square resolution. III. An assessment of the contribution of LERC 1km square records to national trends modelling demonstrated that substantial benefits in increased species coverage and precision of modelled trends are likely to arise by including additional LERC data alongside surveillance scheme data already used for trends modelling. By combining datasets the number of species that could be modelled increased by 267% on average across all the taxonomic groups previously modelled. IV. The design of the new Wales-only Indicator 44 “status of biological diversity” is currently under consultation. Our results show that species coverage for this indicator will benefit from combining multiple datasets with the current analytical state-of-the-art for trends modelling. While results are always dependent on sufficient data, there would seem to be scope for exploring how an ecologically more comprehensive Indicator 44 could be developed in partnership with Wales LERC and others. V. Our assessment also suggests that exploiting the more numerous 1km square records for section 7 species will increase the chances of detecting legacy and future effects of management scheme interventions for biodiversity and resilience objectives. A strategy for extracting the most biodiversity understanding for time spent would most likely involve applying state-of-the-art spatio-temporal modelling in collaboration with the Wales LERC and surveillance schemes. VI. A key benefit of working more closely with LERC is their ability to identify recording gaps and to mobilise new recording effort among the interested public as well as scholarly recording societies. This kind of reactive engagement activity could also contribute to efficient risk-based surveillance but with the proviso that voluntary effort typically exhibits strong spatial bias and variation in recording quality. VII. Further evidence needs driven by recent legislation and policy in Wales are likely to become clearer as indicators for SoNaRR, in particular the resilience objective of SMNR evolve in the near future

A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation

BACKGROUND: Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 μl/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. RESULTS: Geltrex™ basement matrix at 5 μl/cm(2) in 24-well (10 μl) or 96-well (2 μl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix. CONCLUSIONS: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-014-0041-5) contains supplementary material, which is available to authorized users

Questioning context: a set of interdisciplinary questions for investigating contextual factors affecting health decision making

Objective  To combine insights from multiple disciplines into a set of questions that can be used to investigate contextual factors affecting health decision making. Background  Decision‐making processes and outcomes may be shaped by a range of non‐medical or ‘contextual’ factors particular to an individual including social, economic, political, geographical and institutional conditions. Research concerning contextual factors occurs across many disciplines and theoretical domains, but few conceptual tools have attempted to integrate and translate this wide‐ranging research for health decision‐making purposes. Methods  To formulate this tool we employed an iterative, collaborative process of scenario development and question generation. Five hypothetical health decision‐making scenarios (preventative, screening, curative, supportive and palliative) were developed and used to generate a set of exploratory questions that aim to highlight potential contextual factors across a range of health decisions. Findings  We present an exploratory tool consisting of questions organized into four thematic domains – Bodies, Technologies, Place and Work (BTPW) – articulating wide‐ranging contextual factors relevant to health decision making. The BTPW tool encompasses health‐related scholarship and research from a range of disciplines pertinent to health decision making, and identifies concrete points of intersection between its four thematic domains. Examples of the practical application of the questions are also provided. Conclusions  These exploratory questions provide an interdisciplinary toolkit for identifying the complex contextual factors affecting decision making. The set of questions comprised by the BTPW tool may be applied wholly or partially in the context of clinical practice, policy development and health‐related research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86973/1/j.1369-7625.2010.00618.x.pd

Mouse hypothalamic GT1-7 cells demonstrate AMPK-dependent intrinsic glucose-sensing behaviour.

AIMS/HYPOTHESIS: Hypothalamic glucose-excited (GE) neurons contribute to whole-body glucose homeostasis and participate in the detection of hypoglycaemia. This system appears defective in type 1 diabetes, in which hypoglycaemia commonly occurs. Unfortunately, it is at present unclear which molecular components required for glucose sensing are produced in individual neurons and how these are functionally linked. We used the GT1-7 mouse hypothalamic cell line to address these issues. METHODS: Electrophysiological recordings, coupled with measurements of gene expression and protein levels and activity, were made from unmodified GT1-7 cells and cells in which AMP-activated protein kinase (AMPK) catalytic subunit gene expression and activity were reduced. RESULTS: Hypothalamic GT1-7 neurons express the genes encoding glucokinase and ATP-sensitive K(+) channel (K(ATP)) subunits K ( ir ) 6.2 and Sur1 and exhibit GE-type glucose-sensing behaviour. Lowered extracellular glucose concentration hyperpolarised the cells in a concentration-dependent manner, an outcome that was reversed by tolbutamide. Inhibition of glucose uptake or metabolism hyperpolarised cells, showing that energy metabolism is required to maintain their resting membrane potential. Short hairpin (sh)RNA directed to Ampkα2 (also known as Prkaa2) reduced GT1-7 cell AMPKα2, but not AMPKα1, activity and lowered the threshold for hypoglycaemia-induced hyperpolarisation. shAmpkα1 (also known as Prkaa1) had no effect on glucose-sensing or AMPKα2 activity. Decreased uncoupling protein 2 (Ucp2) mRNA was detected in AMPKα2-reduced cells, suggesting that AMPKα2 regulates UCP2 levels. CONCLUSIONS/INTERPRETATION: We have demonstrated that GT1-7 cells closely mimic GE neuron glucose-sensing behaviour, and reducing AMPKα2 blunts their responsiveness to hypoglycaemic challenge, possibly by altering UCP2 activity. These results show that suppression of AMPKα2 activity inhibits normal glucose-sensing behaviour and may contribute to defective detection of hypoglycaemia.This study was funded by: grants from the Wellcome Trust (grant numbers 068692 and 086989) and Diabetes UK (grant number RD08/0003681) to M.L.J. Ashford; a Juvenile Diabetes Research Foundation (JDRF) Postdoctoral Fellowship to C. Beall (grant number 3-576-2010); grants from JDRF and European Foundation for the study of Diabetes to R.J. McCrimmon, and from the British Heart Foundation to A. Jovanović

Memory for pitch in congenital amusia: Beyond a fine-grained pitch discrimination problem

Congenital amusia is a disorder that affects the perception and production of music. While amusia has been associated with deficits in pitch discrimination, several reports suggest that memory deficits also play a role. The present study investigated short-term memory span for pitch-based and verbal information in 14 individuals with amusia and matched controls. Analogous adaptive-tracking procedures were used to generate tone and digit spans using stimuli that exceeded psychophysically measured pitch perception thresholds. Individuals with amusia had significantly smaller tone spans, whereas their digits spans were a similar size to those of controls. An automated operation span task was used to determine working memory capacity. Working memory deficits were seen in only a small subgroup of individuals with amusia. These findings support the existence of a pitch-specific component within short-term memory and suggest that congenital amusia is more than a disorder of fine-grained pitch discrimination

Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity

Advancing age is the greatest risk factor for developing multiple age-related diseases. Therapeutic approaches targeting the underlying pathways of ageing, rather than individual diseases, may be an effective way to treat and prevent age-related morbidity while reducing the burden of polypharmacy. We harness the Open Targets Genetics Portal to perform a systematic analysis of nearly 1,400 genome-wide association studies (GWAS) mapped to 34 age-related diseases and traits, identifying genetic signals that are shared between two or more of these traits. Using locus-to-gene (L2G) mapping, we identify 995 targets with shared genetic links to age-related diseases and traits, which are enriched in mechanisms of ageing and include known ageing and longevity-related genes. Of these 995 genes, 128 are the target of an approved or investigational drug, 526 have experimental evidence of binding pockets or are predicted to be tractable, and 341 have no existing tractability evidence, representing underexplored genes which may reveal novel biological insights and therapeutic opportunities. We present these candidate targets for exploration and prioritisation in a web application

The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver

LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver