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The antiviral properties of iminosugars have been reported previously in vitro and in small animal models against Ebola virus (EBOV); however, their effects have not been tested in larger animal models such as guinea pigs. We tested the iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)-1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850 mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three times daily, caused no adverse effects and were well tolerated. A pilot study treating infected animals three times within an 8 hour period was promising with 1 of 4 infected NB-DNJ treated animals surviving and the remaining three showing improved clinical signs. MON-DNJ showed no protective effects when EBOV-infected guinea pigs were treated. On histopathological examination, animals treated with NB-DNJ had reduced lesion severity in liver and spleen. However, a second study, in which NB-DNJ was administered at equally-spaced 8 hour intervals, could not confirm drug-associated benefits. Neither was any antiviral effect of iminosugars detected in an EBOV glycoprotein pseudotyped virus assay. Overall, this study provides evidence that NB-DNJ and MON-DNJ do not protect guinea pigs from a lethal EBOV-infection at the dose levels and regimens tested. However, the one surviving animal and signs of improvements in three animals of the NB-DNJ treated cohort could indicate that NB-DNJ at these levels may have a marginal beneficial effect. Future work could be focused on the development of more potent iminosugars.

Toxoplasma gondii is a globally distributed apicomplexan protozoan of zoonotic importance. Domestic cats ( Felis catus ) and related felids constitute its sole definitive hosts, while numerous warm-blooded species serve as intermediate hosts . Infection outcomes for intermediate hosts range from latent toxoplasmosis to behaviour alteration and fatal systemic disease. Oocysts, the lifecycle environmental stage, are often washed into watercourses, making river-dwelling species like Eurasian beavers ( Castor fiber ) particularly at risk. To investigate the presence and impact of T. gondii on beavers in the United Kingdom, archived brain, heart, and liver from 23 beavers necropsied between 2021 and 2023 were screened for T. gondii DNA by nested- and quantitative PCR. Positive samples were genotyped using a panel of six published PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) assays and amplicon sequencing. Sequences were aligned with those reported previously from UK and other wildlife species to assess the occurrence of shared genotypes. Toxoplasma gondii DNA was detected in 19/23 (83%) Eurasian beavers; all consistent with PCR-RFLP ToxoDB#3 with limited genetic diversity, concurring with findings from previous surveillance of UK wildlife species. Following histopathological screening non-suppurative toxoplasmosis was characterised in 3/6 tissues selected from two animals. These results demonstrate a high occurrence of T. gondii infection in UK beavers

Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for animal welfare and wildlife conservation. We build a pan-species cancer digital pathology atlas (panspecies.ai) and conduct a pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). In 18 other vertebrate species (mammalia = 11, reptilia = 4, aves = 2, and amphibia = 1), accuracy (range 0.57–0.94) is influenced by cell morphological similarity preserved across different taxonomic groups, tumour sites, and variations in the immune compartment. Furthermore, a spatial immune score based on artificial intelligence and spatial statistics is associated with prognosis in canine melanoma and prostate tumours. A metric, named morphospace overlap, is developed to guide veterinary pathologists towards rational deployment of this technology on new samples. This study provides the foundation and guidelines for transferring artificial intelligence technologies to veterinary pathology based on understanding of morphological conservation, which could vastly accelerate developments in veterinary medicine and comparative oncology. Artificial Intelligence (AI) has the potential of assisting the study and diagnosis of veterinary cancers. Here, the authors build a cancer digital pathology atlas encompassing multiple animal species and demonstrate an AI approach for comparative pathology, which yields insights about immune response and morphological similarities.

Escherichia albertii is a recently identified gastrointestinal bacterial pathogen of humans and animals which is typically misidentified as pathotypes of diarrhoeagenic Escherichia coli or Shigella species and is generally only detected during genomic surveillance of other Enterobacteriaceae. The incidence of E. albertii is likely underestimated, and its epidemiology and clinical relevance are poorly characterised. Here, we whole genome sequenced E. albertii isolates from humans ( n  = 83) and birds ( n  = 79) isolated in Great Britain between 2000 and 2021 and analysed these alongside a broader public dataset ( n  = 475) to address these gaps. We found human and avian isolates typically (90%; 148/164) belonged to host-associated monophyletic groups with distinct virulence and antimicrobial resistance profiles. Overlaid patient epidemiological data suggested that human infection was likely related to travel and possibly foodborne transmission. The Shiga toxin encoding stx2f gene was associated with clinical disease (OR = 10.27, 95% CI = 2.98–35.45 p  = 0.0002) in finches. Our results suggest that improved future surveillance will further elucidate disease ecology and public and animal health risks associated with E. albertii . Escherichia albertii is an emerging gastrointestinal pathogen that causes disease in humans and animals, notably birds. In this genomic epidemiology study, the authors investigate characteristics of isolates sampled from humans and birds in Great Britain and find that they tend to cluster separately.

Usutu virus (USUV) is an emerging zoonotic flavivirus in Europe and the first zoonotic mosquito-borne virus to be confirmed in animal hosts in the United Kingdom (UK). Repeated detection of USUV in the years following its initial detection in 2020 indicated that the virus is overwintering in the UK and should now be considered endemic within southeast England. Surveillance of avian hosts and mosquito vectors has been insufficient to elucidate the mechanism by which USUV has persisted through temperate winters. Through enhanced targeted vector surveillance at the index site between 2021 and 2024 inclusive, we detected USUV RNA in host-seeking adult female Culex pipiens s.l. as well as in adults reared from field-caught larvae. This is, to our knowledge, the first description of vertical transmission of USUV in an arthropod vector that should consequently be considered a viable mechanism for the persistence of USUV in temperate areas.

Abstract Penguins (Sphenisciformes) are an iconic order of flightless, diving seabirds distributed across a large latitudinal range in the Southern Hemisphere. The extensive area over which penguins are endemic is likely to have fostered variation in pathogen pressure, which in turn will have imposed differential selective pressures on the penguin immune system. At the front line of pathogen detection and response, the Toll-like receptors (TLRs) provide insight into host evolution in the face of microbial challenge. TLRs respond to conserved pathogen-associated molecular patterns and are frequently found to be under positive selection, despite retaining specificity for defined agonist classes. We undertook a comparative immunogenetics analysis of TLRs for all penguin species and found evidence of adaptive evolution that was largely restricted to the cell surface-expressed TLRs, with evidence of positive selection at, or near, key agonist-binding sites in TLR1B, TLR4, and TLR5. Intriguingly, TLR15, which is activated by fungal products, appeared to have been pseudogenized multiple times in the Eudyptes spp., but a full-length form was present as a rare haplotype at the population level. However, in vitro analysis revealed that even the full-length form of Eudyptes TLR15 was nonfunctional, indicating an ancestral cryptic pseudogenization prior to its eventual disruption multiple times in the Eudyptes lineage. This unusual pseudogenization event could provide an insight into immune adaptation to fungal pathogens such as Aspergillus, which is responsible for significant mortality in wild and captive bird populations.

Carnivorans are an important study object for comparative neuroscience, as they exhibit a wide range of behaviours, ecological adaptations, and social structures. Previous studies have mainly examined relative brain size, but a comprehensive understanding of brain diversity requires the investigation of other aspects of their neuroanatomy. Here, we obtained primarily post-mortem brain scans from 26 species of the order Carnivora, spanning across eight families with diverse representatives and including additional individuals for selected species, to create the largest carnivoran brain collection to date. We reconstructed their cortical surfaces and examined neocortical sulcal anatomy to establish a framework for systematic interspecies comparisons, revealing distinct regional variations in sulcal anatomy, potentially related to the species’ behaviour and ecology. Arctoidea species with pronounced forepaw dexterity exhibited complex sulcal configurations in the presumed somatosensory cortex but low sulcal complexity in the presumed visual and auditory occipitotemporal cortex. Canidae had the largest number of unique major sulci, including one in the occipital cortex and highly social canids featuring an additional frontal cortex sulcus. We also observed differentially complex occipitotemporal sulcal patterns in Felidae and Canidae, indicative of changes in auditory and visual areas that may be related to foraging strategies and social behaviour. In conclusion, this study presents an inventory of the sulcal anatomy of a number of rarely studied carnivoran brains including detailed digital atlases and establishes a framework and novel avenues for further investigations employing a variety of neuroimaging modalities to reveal more about carnivoran brain diversity.

Background Through the evolution of novel wing structures, bats (Order Chiroptera) became the only mammalian group to achieve powered flight. This achievement preceded the massive adaptive radiation of bats into diverse ecological niches. We investigate some of the developmental processes that underlie the origin and subsequent diversification of one of the novel membranes of the bat wing: the plagiopatagium, which connects the fore- and hind limb in all bat species. Results Our results suggest that the plagiopatagium initially arises through novel outgrowths from the body flank that subsequently merge with the limbs to generate the wing airfoil. Our findings further suggest that this merging process, which is highly conserved across bats, occurs through modulation of the programs controlling the development of the periderm of the epidermal epithelium. Finally, our results suggest that the shape of the plagiopatagium begins to diversify in bats only after this merging has occurred. Conclusions This study demonstrates how focusing on the evolution of cellular processes can inform an understanding of the developmental factors shaping the evolution of novel, highly adaptive structures.

Background Sindbis virus (SINV) and Batai virus (BATV) are emerging zoonotic arboviruses with a growing number of detections in Europe. Recent SINV outbreaks in northern Europe and high BATV seroprevalence in sheep, goats, and cattle in Germany emphasise the threat they pose to both animal and human health. Despite their presence in countries of similar latitude and climate, neither of these viruses have been detected in the UK. Methods Zoos are strategic sentinel sites for disease surveillance because they are well monitored and possess a high diversity of animal species. Located in southeast England, where the climate and vector prevalence may provide suitable conditions for viral emergence, London Zoo was selected as the sampling site for SINV and BATV prevalence in mosquito samples between September 2022 and January 2024. In 2020, it was also the first location where Usutu virus was detected in the UK. Adult mosquitoes were collected during host-seeking and overwintering seasons while larvae were collected in the summer months. Results A total of 8477 mosquito specimens were analysed, representing all mosquito stages, i.e. including host-seeking and overwintering mosquitoes as well as adults that had emerged from larvae. Mosquitoes of the Culex pipiens / Culex torrentium complex were the most abundant, accounting for 97.5% of the total. Molecular analysis using quantitative polymerase chain reaction was performed to test for SINV and BATV; however, none of the samples tested positive. Conclusions These results suggest that neither SINV nor BATV actively circulated in the sampled area during the study period. The findings provide baseline data for arbovirus surveillance in the UK, particularly at London Zoo, which is home to diverse bird populations that might be potential sentinel populations for viral emergence. Future studies that obtain molecular and serological data on birds or mammals housed at the zoo would complement our surveillance efforts on the emergence or prevalence of SINV and BATV in the UK. This study focused on a single location, but extending sampling and monitoring to other sites across the UK, especially in the southeast, is crucial to strengthening the UK’s preparedness and response strategies in case SINV and BATV emerge in the country in the future.

Following the first detection in the United Kingdom of Usutu virus (USUV) in wild birds in 2020, we undertook a multidisciplinary investigation that combined screening host and vector populations with interrogation of national citizen science monitoring datasets to assess the potential for population impacts on avian hosts. Pathological findings from six USUV-positive wild passerines were non-specific, highlighting the need for molecular and immunohistochemical examinations to confirm infection. Mosquito surveillance at the index site identified USUV RNA in Culex pipiens s.l. following the outbreak . Although the Eurasian blackbird ( Turdus merula ) is most frequently impacted by USUV in Europe, national syndromic surveillance failed to detect any increase in occurrence of clinical signs consistent with USUV infection in this species. Furthermore, there was no increase in recoveries of dead blackbirds marked by the national ringing scheme. However, there was regional clustering of blackbird disease incident reports centred near the index site in 2020 and a contemporaneous marked reduction in the frequency with which blackbirds were recorded in gardens in this area, consistent with a hypothesis of disease-mediated population decline. Combining results from multidisciplinary schemes, as we have done, in real-time offers a model for the detection and impact assessment of future disease emergence events.