Immune interactions and heterogeneity in transmission drives the pathogen-mediated invasion of grey squirrels in the UK

Mathematical models highlighted the importance of pathogen-mediated invasion, with the replacement of red squirrels by squirrelpox virus (SQPV) carrying grey squirrels in the UK, a well-known example. In this study, we combine new epidemiological models, with a range of infection characteristics, with recent longitudinal field and experimental studies on the SQPV dynamics in red and grey squirrel populations to better infer the mechanistic basis of the disease interaction. A key finding is that a model with either partial immunity or waning immunity and reinfection, where individuals become seropositive on the second exposure to infection, that up to now has been shown in experimental data only, can capture the key aspects of the field study observations. By fitting to SQPV epidemic observations in isolated red squirrel populations, we can infer that SQPV transmission between red squirrels is significantly (4×) higher than the transmission between grey squirrels and as a result our model shows that disease-mediated replacement of red squirrels by greys is considerably more rapid than replacement in the absence of SQPV. Our findings recover the key results of the previous model studies, which highlights the value of simple strategic models that are appropriate when there are limited data, but also emphasise the likely complexity of immune interactions in wildlife disease and how models can help infer disease processes from field data.</p

The Molecular Switch of Telomere Phages: High Binding Specificity of the PY54 Cro Lytic Repressor to a Single Operator Site

Temperate bacteriophages possess a molecular switch, which regulates the lytic and lysogenic growth. The genomes of the temperate telomere phages N15, PY54 and ɸKO2 harbor a primary immunity region (immB) comprising genes for the prophage repressor, the lytic repressor and a putative antiterminator. The roles of these products are thought to be similar to those of the lambda proteins CI, Cro and Q, respectively. Moreover, the gene order and the location of several operator sites in the prototype telomere phage N15 and in ɸKO2 are also reminiscent of lambda-like phages. By contrast, in silico analyses revealed the presence of only one operator (O$_{\rm{R}}$3) in PY54. The purified PY54 Cro protein was used for EMSA studies demonstrating that it exclusively binds to a 16-bp palindromic site (O$_{\rm{R}}$3) upstream of the prophage repressor gene. The O$_{\rm{R}}$3 operator sequences of PY54 and ɸKO2/N15 only differ by their peripheral base pairs, which are responsible for Cro specificity. PY54 cI and cro transcription is regulated by highly active promoters initiating the synthesis of a homogenious species of leaderless mRNA. The location of the PY54 Cro binding site and of the identified promoters suggests that the lytic repressor suppresses cI transcription but not its own synthesis. The results indicate an unexpected diversity of the growth regulation mechanisms in lambda-related phages

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

Egocentric bias across mental and non-mental representations in the Sandbox Task

In the Sandbox Task, participants indicate where a protagonist who has a false belief about the location of an object will look for that object in a trough filled with a substrate that conceals the hidden object’s location. Previous findings that participants tend to indicate a location closer to where they themselves know the object to be located have been interpreted as evidence of egocentric bias when attributing mental states to others. We tested the assumption that such biases occur as a result of reasoning about mental states specifically. We found that participants showed more egocentric bias when reasoning from a protagonist’s false belief than from their own memory, but found equivalent levels of bias when they were asked to indicate where a false film would depict the object as when they were asked about a protagonist’s false belief. Our findings suggest that that egocentric biases found in adult false belief tasks are more likely due to a general difficulty with reasoning about false representations than a specialised difficulty with reasoning about false mental states. </jats:p

Pathogenic Polyglutamine Tracts Are Potent Inducers of Spontaneous Sup35 and Rnq1 Amyloidogenesis

© 2010 Goehler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedDOI:10.1371/journal.pone.0009642The glutamine/asparagine (Q/N)-rich yeast prion protein Sup35 has a low intrinsic propensity to spontaneously self-assemble into ordered, β-sheet-rich amyloid fibrils. In yeast cells, de novo formation of Sup35 aggregates is greatly facilitated by high protein concentrations and the presence of preformed Q/N-rich protein aggregates that template Sup35 polymerization. Here, we have investigated whether aggregation-promoting polyglutamine (polyQ) tracts can stimulate the de novo formation of ordered Sup35 protein aggregates in the absence of Q/N-rich yeast prions. Fusion proteins with polyQ tracts of different lengths were produced and their ability to spontaneously self-assemble into amlyloid structures was analyzed using in vitro and in vivo model systems. We found that Sup35 fusions with pathogenic (≥54 glutamines), as opposed to non-pathogenic (19 glutamines) polyQ tracts efficiently form seeding-competent protein aggregates. Strikingly, polyQ-mediated de novo assembly of Sup35 protein aggregates in yeast cells was independent of pre-existing Q/N-rich protein aggregates. This indicates that increasing the content of aggregation-promoting sequences enhances the tendency of Sup35 to spontaneously self-assemble into insoluble protein aggregates. A similar result was obtained when pathogenic polyQ tracts were linked to the yeast prion protein Rnq1, demonstrating that polyQ sequences are generic inducers of amyloidogenesis. In conclusion, long polyQ sequences are powerful molecular tools that allow the efficient production of seeding-competent amyloid structures

On deflationary accounts of human action understanding

A common deflationary tendency has emerged recently in both philosophical accounts and comparative animal studies concerned with how subjects understand the actions of others. The suggestion emerging from both arenas is that the default mechanism for understanding action involves only a sensitivity to the observable, behavioural (non-mental) features of a situation. This kind of ‘smart behaviour reading’ thus suggests that, typically, predicting or explaining the behaviour of conspecifics does not require seeing the other through the lens of mental state attribution. This paper aims to explore and assess this deflationary move. In §1 I clarify what might be involved in a smart behaviour reading account via looking at some concrete examples. Then in §2 I critically assess the deflationary move, arguing that, at least in the human case, it would in fact be a mistake to assume that our default method of action understanding proceeds without appeal to mental state attribution. Finally in §3 I consider briefly how the positive view proposed here relates to discussions about standard two-system models of cognition

Climate Change Mitigation: An Analysis of Advanced Technology Scenarios

This report documents a scenario analysis that explores three advanced technology pathways toward climate stabilization using the MiniCAM model

Conservation of genetic uniqueness in remaining populations of red squirrels (Sciurus vulgaris L.) in the South of England

The Eurasian red squirrel (Sciurus vulgaris) is an emblematic species for conservation, and its decline in the British Isles exemplifies the impact that alien introductions can have on native ecosystems. Indeed, red squirrels in this region have declined dramatically over the last 60 years due to the spread of squirrelpox virus following the introduction of the gray squirrel (Sciurus carolinensis). Currently, red squirrel populations in Britain are fragmented and need to be closely monitored in order to assess their viability and the effectiveness of conservation efforts. The situation is even more dramatic in the South of England, where S. vulgaris survives only on islands (Brownsea Island, Furzey Island, and the Isle of Wight). Using the D‐loop, we investigated the genetic diversity and putative ancestry of the squirrels from Southern England and compared them to a European dataset composed of 1,016 samples from 54 populations. We found that our three populations were more closely related to other squirrels from the British Isles than squirrels from Europe, showed low genetic diversity, and also harbored several private haplotypes. Our study demonstrates how genetically unique the Southern English populations are in comparison with squirrels from the continental European range. We report the presence of four private haplotypes, suggesting that these populations may potentially harbor distinct genetic lineages. Our results emphasize the importance of preserving these isolated red squirrel populations for the conservation of the species

Magnetic resonance imaging of abnormal ventricular septal motion in heart diseases: a pictorial review

The purpose of this article is to illustrate the usefulness of MR imaging in the clinical evaluation of congenital and acquired cardiac diseases characterised by ventricular septal wall motion abnormality. Recognition of the features of abnormal ventricular septal motion in MR images is important to evaluate the haemodynamic status in patients with congenital and acquired heart diseases in routine clinical practice