Invasion and Amplification of Endogenous Retroviruses in Dasyuridae Marsupial Genomes.

Retroviruses are an ancient viral family that have globally coevolved with vertebrates and impacted their evolution. In Australia, a continent that has been geographically isolated for millions of years, little is known about retroviruses in wildlife, despite the devastating impacts of a retrovirus on endangered koala populations. We therefore sought to identify and characterize Australian retroviruses through reconstruction of endogenous retroviruses from marsupial genomes, in particular the Tasmanian devil due to its high cancer incidence. We screened 19 marsupial genomes and identified over 80,000 endogenous retrovirus fragments which we classified into eight retrovirus clades. The retroviruses were similar to either Betaretrovirus (5/8) or Gammaretrovirus (3/8) retroviruses, but formed distinct phylogenetic clades compared to extant retroviruses. One of the clades (MEBrv 3) lost an envelope but retained retrotranspositional activity, subsequently amplifying throughout all Dasyuridae genomes. Overall, we provide insights into Australian retrovirus evolution and identify a highly active endogenous retrovirus within Dasyuridae genomes.

Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts.

Osteoarthritis (OA) stands as a prevalent and progressively debilitating clinical condition globally, impacting joint structures and leading to their gradual deterioration through inflammatory mechanisms. While both non-modifiable and modifiable factors contribute to its onset, numerous aspects of OA pathophysiology remain elusive despite considerable research strides. Presently, diagnosis heavily relies on clinician expertise and meticulous differential diagnosis to exclude other joint-affecting conditions. Therapeutic approaches for OA predominantly focus on patient education for self-management alongside tailored exercise regimens, often complemented by various pharmacological interventions primarily targeting pain alleviation. However, pharmacological treatments typically exhibit short-term efficacy and local and/or systemic side effects, with prosthetic surgery being the ultimate resolution in severe cases. Thus, exploring the potential integration or substitution of conventional drug therapies with natural compounds and extracts emerges as a promising frontier in enhancing OA management. These alternatives offer improved safety profiles and possess the potential to target specific dysregulated pathways implicated in OA pathogenesis, thereby presenting a holistic approach to address the condition's complexities.

The devil is in the details: Experiment reveals how a forest-dwelling scavenger, and their excrement, may buffer ecosystem processes from climate change.

This article is an Invited Commentary on Stephenson et al. (2024). This commentary attempts to provide broader context of the research within the body of literature on species loss and ecosystem functioning and highlights its relevance to conservation and global change.

Human habitat modification, not apex scavenger decline, drives isotopic niche variation in a carnivore community.

Top carnivores can influence the structure of ecological communities, primarily through competition and predation; however, communities are also influenced by bottom-up forces such as anthropogenic habitat disturbance. Top carnivore declines will likely alter competitive dynamics within and amongst sympatric carnivore species. Increasing intraspecific competition is generally predicted to drive niche expansion and/or individual specialisation, while interspecific competition tends to constrain niches. Using stable isotope analysis of whiskers, we studied the effects of Tasmanian devil Sarcophilus harrisii declines upon the population- and individual-level isotopic niches of Tasmanian devils and sympatric spotted-tailed quolls Dasyurus maculatus subsp. maculatus. We investigated whether time since the onset of devil decline (a proxy for severity of decline) and landscape characteristics affected the isotopic niche breadth and overlap of devil and quoll populations. We quantified individual isotopic niche breadth for a subset of Tasmanian devils and spotted-tailed quolls and assessed whether between-site population niche variation was driven by individual-level specialisation. Tasmanian devils and spotted-tailed quolls demonstrated smaller population-level isotopic niche breadths with increasing human-modified habitat, while time since the onset of devil decline had no effect on population-level niche breadth or interspecific niche overlap. Individual isotopic niche breadths of Tasmanian devils and spotted-tailed quolls were narrower in human-modified landscapes, likely driving population isotopic niche contraction, however, the degree of individuals' specialisation relative to one another remained constant. Our results suggest that across varied landscapes, mammalian carnivore niches can be more sensitive to the bottom-up forces of anthropogenic habitat disturbance than to the top-down effects of top carnivore decline.

Adaptive UAV Navigation Method Based on AHRS.

To address the inaccuracy of the Constant Acceleration/Constant Velocity (CA/CV) model as the state equation in describing the relative motion state in UAV relative navigation, an adaptive UAV relative navigation method is proposed, which is based on the UAV attitude information provided by Attitude and Heading Reference System (AHRS). The proposed method utilizes the AHRS output attitude parameters as the benchmark for dead reckoning and derives a relative navigation state equation with attitude error as process noise. By integrating the extended Kalman filter output for relative state estimation and employing an adaptive decision rule designed using the innovation of the filter update phase, the proposed method recalculates motion states deviating from the actual motion using the Tasmanian Devil Optimization (TDO) algorithm. The simulation results show that, compared with the CA/CV model, the proposed method reduces the relative position errors by 12%, 23%, and 32% in the X, Y, and Z directions, respectively, and that it reduces the relative velocity errors by 350%, 330%, and 300%, respectively. There is a significant improvement in the relative navigation accuracy.

New specimens of middle Eocene omomyines (Primates, Omomyoidea) from the Uinta Basin of Utah and the Tornillo Basin of Texas, with clarification of the generic status of Ourayia, Mytonius, and Diablomomys.

In the middle Eocene, multiple lineages of North American omomyoids independently evolved body masses greater than 500 g. Most of these large-bodied omomyoids are known from small sample sizes, which has contributed to a lack of consensus regarding their alpha taxonomy. Here, we describe new Uintan omomyine specimens from the Uinta Basin of Utah and the Tornillo Basin of Texas. These new samples expand the hypodigms of Diablomomys dalquesti, Mytonius hopsoni, and Ourayia uintensis, and favor the recognition of new species of Mytonius and Ourayia based on specimens from the Tornillo Basin. These samples support the recognition of Diablomomys as a valid genus distinct from Omomys, Ourayia as a valid genus distinct from Macrotarsius, and Mytonius as a valid genus distinct from Ourayia. Although Diablomomys and Omomys co-occur in the late Uintan of the Tornillo Basin, Ourayia and Mytonius are time-successive taxa with a wide distribution across multiple Laramide basins. The data presented here reinforce the conclusion that the Uintan was a time period in which omomyines diversified to include a large number of taxa with body masses above Kay's threshold and frugivorous-folivorous diets. These data also provide evidence that North American primate faunas exhibited a shifting pattern of regional endemism during the middle Eocene. By the early Uintan, primate faunas from Southern California were already quite distinct from primate faunas of the central Rocky Mountains or Trans-Pecos Texas. By the late Uintan, primate faunas in all three regions demonstrated greater provincialism, with Trans-Pecos Texas and Southern California both exhibiting a large number of endemic primate taxa and sharing only a single primate genus (Macrotarsius) in common. This increase in primate endemism across the Uintan may be tied to changes in paleohabitats associated with the larger trend toward decreasing temperatures from the Early Eocene Climatic Optimum to the Eocene/Oligocene transition.

Ethyl Acetate Fraction of Harpagophytum procumbens Prevents Oxidative Stress In Vitro and Amphetamine-Induced Alterations in Mice Behavior.

Microglial activation has been associated to the physiopathology of neurodegenerative diseases, such as schizophrenia, and can occur during inflammation and oxidative stress. Pharmacological treatment is associated with severe side effects, and studies for use of plant extracts may offer alternatives with lower toxicity. Harpagophytum procumbens (HP) is a plant known for its anti-inflammatory properties. In the present study, we characterized the ethyl acetate fraction of HP (EAF HP) by ESI-ToF-MS and investigated the effects EAF HP in a lipopolysaccharide (LPS) induced inflammation model on microglial cells (BV-2 lineage). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), DCFH-DA (2',7'-dichlorofluorescein diacetate) and cell cycle flow cytometer analysis were performed. In vivo was investigated the amphetamine-induced psychosis model through behavioral (locomotor and exploratory activities, stereotypies and working memory) and biochemical (DCFH-DA oxidation and protein thiols) parameters in cortex and striatum of mice. EAF HP reduced activation and proliferation of microglial cells in 48 h (300 µg/mL) and in 72 h after treatments (50-500 µg/mL). Reactive oxygen species levels were lower at the concentration of 100 µg/mL EAF HP. We detected a modulatory effect on the cell cycle, with reduction of cells in S and G2/M phases. In mice, the pre-treatment with EAF HP, for 7 days, protected against positive and cognitive symptoms, as well as stereotypies induced by amphetamine. No oxidative stress was observed in this amphetamine-induced model of psychosis. Such findings suggest that EAF HP can modulate the dopaminergic neurotransmission and be a promising adjuvant in the treatment of locomotor alterations, cognitive deficits, and neuropsychiatric disorders.

Automated Analysis of PD1 and PDL1 Expression in Lymph Nodes and the Microenvironment of Transmissible Tumors in Tasmanian Devils.

The wild Tasmanian devil (Sarcophilus harrisii) population has suffered a devastating decline due to two clonal transmissible cancers. The first devil facial tumor 1 (DFT1) was observed in 1996, followed by a second genetically distinct transmissible tumor, the devil facial tumor 2 (DFT2), in 2014. DFT1/2 frequently metastasize, with lymph nodes being common metastatic sites. MHC-I downregulation by DFT1 cells is a primary means of evading allograft immunity aimed at polymorphic MHC-I proteins. DFT2 cells constitutively express MHC-I, and MHC-I is upregulated on DFT1/2 cells by interferon gamma, suggesting other immune evasion mechanisms may contribute to overcoming allograft and anti-tumor immunity. Human clinical trials have demonstrated PD1/PDL1 blockade effectively treats patients showing increased expression of PD1 in tumor draining lymph nodes, and PDL1 on peritumoral immune cells and tumor cells. The effects of DFT1/2 on systemic immunity remain largely uncharacterized. This study applied the open-access software QuPath to develop a semiautomated pipeline for whole slide analysis of stained tissue sections to quantify PD1/PDL1 expression in devil lymph nodes. The QuPath protocol provided strong correlations to manual counting. PD-1 expression was approximately 10-fold higher than PD-L1 expression in lymph nodes and was primarily expressed in germinal centers, whereas PD-L1 expression was more widely distributed throughout the lymph nodes. The density of PD1 positive cells was increased in lymph nodes containing DFT2 metastases, compared to DFT1. This suggests PD1/PDL1 exploitation may contribute to the poorly immunogenic nature of transmissible tumors in some devils and could be targeted in therapeutic or prophylactic treatments.Abbreviations: PD1: programmed cell death protein 1; PDL1: programmed death ligand 1; DFT1: devil facial tumor 1; DFT2: devil facial tumor 2; DFTD: devil facial tumor disease; MCC: Matthew's correlation coefficient; DAB: diaminobenzidine; ROI: region of interest.

Classification of brain tumours from MRI images using deep learning-enabled hybrid optimization algorithm.

Brain tumours are produced by the uncontrolled, and unusual tissue growth of brain. Because of the wide range of brain tumour locations, potential shapes, and image intensities, segmentation of the brain tumour by magnetic resonance imaging (MRI) is challenging. In this research, the deep learning (DL)-enabled brain tumour detection is developed by hybrid optimization method. The pre-processing stage used adaptive Wiener filter for minimizing the noise from input image. After that, the abnormal section of the image is segmented using U-Net. Afterwards, the data augmentation is accomplished to recover the random erasing, brightness, and translation characters. The statistical, shape, and texture features are extracted in feature extraction process. In first-level classification, the abnormal section of the image is sensed as brain tumour or not. Here, the Red Deer Tasmanian Devil Optimization (RDTDO) trained DenseNet is hired for brain tumour detection process. If tumour is identified, then second-level classification provides the brain tumour classification, where deep residual network (DRN)-enabled RDTDO is employed. Furthermore, the system performance is assessed by accuracy, true positive rate (TPR), true negative rate (TNR), positive predictive value (PPV), and negative predictive value (NPV) with the maximum values of 0.947, 0.926, 0.950, 0.937, and 0.926 are attained.

A Novel IoT-Enabled Healthcare Monitoring Framework and Improved Grey Wolf Optimization Algorithm-Based Deep Convolution Neural Network Model for Early Diagnosis of Lung Cancer.

Lung cancer is a high-risk disease that causes mortality worldwide; nevertheless, lung nodules are the main manifestation that can help to diagnose lung cancer at an early stage, lowering the workload of radiologists and boosting the rate of diagnosis. Artificial intelligence-based neural networks are promising technologies for automatically detecting lung nodules employing patient monitoring data acquired from sensor technology through an Internet-of-Things (IoT)-based patient monitoring system. However, the standard neural networks rely on manually acquired features, which reduces the effectiveness of detection. In this paper, we provide a novel IoT-enabled healthcare monitoring platform and an improved grey-wolf optimization (IGWO)-based deep convulution neural network (DCNN) model for lung cancer detection. The Tasmanian Devil Optimization (TDO) algorithm is utilized to select the most pertinent features for diagnosing lung nodules, and the convergence rate of the standard grey wolf optimization (GWO) algorithm is modified, resulting in an improved GWO algorithm. Consequently, an IGWO-based DCNN is trained on the optimal features obtained from the IoT platform, and the findings are saved in the cloud for the doctor's judgment. The model is built on an Android platform with DCNN-enabled Python libraries, and the findings are evaluated against cutting-edge lung cancer detection models.

A human adenovirus encoding IFN-γ can transduce Tasmanian devil facial tumour cells and upregulate MHC-I.

The devil facial tumour disease (DFTD) has led to a massive decline in the wild Tasmanian devil (Sarcophilus harrisii) population. The disease is caused by two independent devil facial tumours (DFT1 and DFT2). These transmissible cancers have a mortality rate of nearly 100 %. An adenoviral vector-based vaccine has been proposed as a conservation strategy for the Tasmanian devil. This study aimed to determine if a human adenovirus serotype 5 could express functional transgenes in devil cells. As DFT1 cells do not constitutively express major histocompatibility complex class I (MHC-I), we developed a replication-deficient adenoviral vector that encodes devil interferon gamma (IFN-γ) fused to a fluorescent protein reporter. Our results show that adenoviral-expressed IFN-γ was able to stimulate upregulation of beta-2 microglobulin, a component of MHC-I, on DFT1, DFT2 and devil fibroblast cell lines. This work suggests that human adenoviruses can serve as a vaccine platform for devils and potentially other marsupials.

Transmissible cancer and longitudinal telomere dynamics in Tasmanian devils (Sarcophilus harrisii).

A plethora of intrinsic and environmental factors have been shown to influence the length of telomeres, the protector of chromosome ends. Despite the growing interest in infection-telomere interactions, there is very limited knowledge on how transmissible cancers influence telomere maintenance. An emblematic example of transmissible cancer occurs in the Tasmanian devil (Sarcophilus harrisii), whose populations have been dramatically reduced by infectious cancer cells. To investigate associations between telomere dynamics and the transmissible cancer, we used longitudinal data from a Tasmanian devil population that has been exposed to the disease for over 15 years. We detected substantial temporal variation in individual telomere length (TL), and a positive significant association between TL and age, as well as a marginally significant trend for devils with devil facial tumour disease (DFTD) having longer telomeres. A proportional hazard analysis yielded no significant effect of TL on the development of DFTD. Like previous studies, we show the complexity that TL dynamics may exhibit across the lifetime of organisms. Our work highlights the importance of long-term longitudinal sampling for understanding the effects of wildlife diseases on TL.

A field experiment characterizing variable detection rates during plant surveys.

Surveys aimed at finding threatened and invasive species can be challenging due to individual rarity and low and variable individual detection rates. Detection rate in plant surveys typically varies due to differences among observers, among the individual plants being surveyed (targets), and across background environments. Interactions among these 3 components may occur but are rarely estimated due to limited replication and control during data collection. We conducted an experiment to investigate sources of variation in detection of 2 Pilosella species that are invasive and sparsely distributed in the Alpine National Park, Australia. These species are superficially similar in appearance to other yellow-flowered plants occurring in this landscape. We controlled the presence and color of flowers on target Pilosella plants and controlled their placement in plots, which were selected for their variation in cover of non-target yellow flowers and dominant vegetation type. Observers mimicked Pilosella surveys in the plots and reported 1 categorical and 4 quantitative indicators of their survey experience level. We applied survival analysis to detection data to model the influence of both controlled and uncontrolled variables on detection rate. Orange- and yellow-flowering Pilosella in grass- and heath-dominated vegetation were detected at a higher rate than nonflowering Pilosella. However, this detection gain diminished as the cover of other co-occurring yellow-flowering species increased. Recent experience with Pilosella surveys improved detection rate. Detection experiments are a direct and accessible means of understanding detection processes and interpreting survey data for threatened and invasive species. Our detection findings have been used for survey planning and can inform progress toward eradication. Interaction of target and background characteristics determined detection rate, which enhanced predictions in the Pilosella eradication program and demonstrated the difficulty of transferring detection findings into untested environments.

Un Experimento de Campo que Caracteriza las Tasas Variables de Detección en los Censos de Plantas Resumen Los censos enfocados en encontrar especies amenazadas e invasoras pueden ser un reto debido a la rareza individual y las tasas bajas y variables de detección individual. Las tasas de detección en los censos botánicos varían comúnmente por las diferencias entre los observadores, entre las plantas individuales que se están censando (objetivo de búsqueda) y en el entorno ambiental. La interacción entre estos tres componentes puede ocurrir, pero rara vez se calcula debido a la replicación y control limitados durante la recolección de datos. Realizamos un experimento para investigar el origen de las variaciones en la detección de dos especies de Pilosella que son invasoras y están distribuidas escasamente en el Parque Nacional Alpino en Australia. Estas especies son superficialmente similares en apariencia a otras plantas de flores amarillas que habitan este paisaje. Controlamos la presencia y el color de las flores en las plantas de Pilosella, así como su colocación en lotes, los cuales fueron seleccionados por su variación en la cobertura de flores amarillas y tipos de vegetación circundantes. Los observadores imitaron los censos de Pilosella en los lotes y reportaron un indicador categórico y cuatro cuantitativos de su nivel de experiencia en censos. Aplicamos el análisis de supervivencia a los datos de detección para modelar la influencia de las variables controladas y no controladas sobre la tasa de detección. Las plantas de Pilosella con flores amarillas y anaranjadas en la vegetación dominada por pastos y brezales fueron detectadas con una tasa mayor que las plantas de Pilosella sin flores. Sin embargo, esta ganancia en la detección disminuyó conforme incrementó la cobertura de otras plantas con flores amarillas. La experiencia reciente de los observadores con censos de Pilosella aumentó la tasa de detección. Los experimentos de detección son un medio directo y accesible para entender los procesos de detección e interpretar los datos de los censos de especies amenazadas e invasoras. Nuestros resultados en la detección han sido utilizados para la planeación de censos y pueden guiar el progreso hacia la erradicación. La interacción de las características diana y del entorno determinaron la tasa de detección, la cual mejoró las predicciones en el programa de erradicación de Pilosella y demostró la dificultad de transferir los resultados de detección hacia ambientes sin ensayos.

Solanum linnaeanum Leaves: Chemical Profiling of VOCs and Effects on Seed Germination and Early Growth of Monocots and Dicots.

Some Solanaceae plants are a rich source of sesquiterpenoid phytoalexins with allelopathic potential. Powder and aqueous extract obtained from the leaves of Solanum linnaeanum Hepper & P.M.L. Jaeger were used to treat the seeds of three target species (Lolium multiflorum Lam., Sinapis alba L. and Trifolium incarnatum L.). Both matrices were evaluated along with untreated controls to determine their toxicity on germination and seedling growth. The results revealed that the pre-emergence treatments were able to be very effective against all three species in the filter paper test by inhibiting the germination up to 100 %. The effectiveness was reduced by the interaction with soil. Despite this, significant data were obtained, albeit different according to the applied matrix. In general, L. multiflorum was the most sensitive to both the action of the leaf powder and aqueous extract while S. alba was found to be the most resistant to powder activity and T. incarnatum had the strongest response to the extract. For the first time, SPME-GC/MS technique was used to characterize the volatile chemical profile of S. linnaeanum leaves. The analyses highlighted the presence of different classes of compounds including terpenoids and sesquiterpenoids potentially useful in the fight against noxious plants both in natural and cultivated ecosystems.

The Fight against Infection and Pain: Devil's Claw (Harpagophytum procumbens) a Rich Source of Anti-Inflammatory Activity: 2011-2022.

Harpagophytum procumbens subsp. procumbens (Burch.) DC. ex Meisn. (Sesame seed Family-Pedaliaceae) is a popular medicinal plant known as Devil's claw. It is predominantly distributed widely over southern Africa. Its impressive reputation is embedded in its traditional uses as an indigenous herbal plant for the treatment of menstrual problems, bitter tonic, inflammation febrifuge, syphilis or even loss of appetite. A number of bioactive compounds such as terpenoids, iridoid glycosides, glycosides, and acetylated phenolic compounds have been isolated. Harpagoside and harpagide, iridoid glycosides bioactive compounds have been reported in countless phytochemical studies as potential anti-inflammatory agents as well as pain relievers. In-depth studies have associated chronic inflammation with various diseases, such as Alzheimer's disease, obesity, rheumatoid arthritis, type 2 diabetes, cancer, and cardiovascular and pulmonary diseases. In addition, 60% of chronic disorder fatalities are due to chronic inflammatory diseases worldwide. Inflammation and pain-related disorders have attracted significant attention as leading causes of global health challenges. Articles published from 2011 to the present were obtained and reviewed in-depth to determine valuable data findings as well as knowledge gaps. Various globally recognized scientific search engines/databases including Scopus, PubMed, Google Scholar, Web of Science, and ScienceDirect were utilized to collect information and deliver evidence. Based on the literature results, there was a dramatic decrease in the number of studies conducted on the anti-inflammatory and analgesic activity of Devil's claw, thereby presenting a potential research gap. It is also evident that currently in vivo clinical studies are needed to validate the prior massive in vitro studies, therefore delivering an ideal anti-inflammatory and analgesic agent in the form of H. procumbens products.

Quantifying 25 years of disease-caused declines in Tasmanian devil populations: host density drives spatial pathogen spread.

Infectious diseases are strong drivers of wildlife population dynamics, however, empirical analyses from the early stages of pathogen emergence are rare. Tasmanian devil facial tumour disease (DFTD), discovered in 1996, provides the opportunity to study an epizootic from its inception. We use a pattern-oriented diffusion simulation to model the spatial spread of DFTD across the species' range and quantify population effects by jointly modelling multiple streams of data spanning 35 years. We estimate the wild devil population peaked at 53 000 in 1996, less than half of previous estimates. DFTD spread rapidly through high-density areas, with spread velocity slowing in areas of low host densities. By 2020, DFTD occupied >90% of the species' range, causing 82% declines in local densities and reducing the total population to 16 900. Encouragingly, our model forecasts the population decline should level-off within the next decade, supporting conservation management focused on facilitating evolution of resistance and tolerance.

The immunopeptidomes of two transmissible cancers and their host have a common, dominant peptide motif.

Transmissible cancers are malignant cells that can spread between individuals of a population, akin to both a parasite and a mobile graft. The survival of the Tasmanian devil, the largest remaining marsupial carnivore, is threatened by the remarkable emergence of two independent lineages of transmissible cancer, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to major histocompatibility complex class I (MHC-I) molecules from Tasmanian devil cells and representative cell lines of each transmissible cancer. Here, we show that DFT1 + IFN-γ and DFT2 cell lines express a restricted repertoire of MHC-I allotypes compared with fibroblast cells, potentially reducing the breadth of peptide presentation. Comparison of the peptidomes from DFT1 + IFNγ, DFT2 and host fibroblast cells demonstrates a dominant motif, despite differences in MHC-I allotypes between the cell lines, with preference for a hydrophobic leucine residue at position 3 and position Ω of peptides. DFT1 and DFT2 both present peptides derived from neural proteins, which reflects a shared cellular origin that could be exploited for vaccine design. These results suggest that polymorphisms in MHC-I molecules between tumours and host can be 'hidden' by a common peptide motif, providing the potential for permissive passage of infectious cells and demonstrating complexity in mammalian histocompatibility barriers.

Mesenchymal plasticity of devil facial tumour cells during in vivo vaccine and immunotherapy trials.

Immune evasion is critical to the growth and survival of cancer cells. This is especially pertinent to transmissible cancers, which evade immune detection across genetically diverse hosts. The Tasmanian devil (Sarcophilus harrisii) is threatened by the emergence of Devil Facial Tumour Disease (DFTD), comprising two transmissible cancers (DFT1 and DFT2). The development of effective prophylactic vaccines and therapies against DFTD has been restricted by an incomplete understanding of how allogeneic DFT1 and DFT2 cells maintain immune evasion upon activation of tumour-specific immune responses. In this study, we used RNA sequencing to examine tumours from three experimental DFT1 cases. Two devils received a vaccine prior to inoculation with live DFT1 cells, providing an opportunity to explore changes to DFT1 cancers under immune pressure. Analysis of DFT1 in the non-immunised devil revealed a 'myelinating Schwann cell' phenotype, reflecting both natural DFT1 cancers and the DFT1 cell line used for the experimental challenge. Comparatively, immunised devils exhibited a 'dedifferentiated mesenchymal' DFT1 phenotype. A third 'immune-enriched' phenotype, characterised by increased PDL1 and CTLA-4 expression, was detected in a DFT1 tumour that arose after immunotherapy. In response to immune pressure, mesenchymal plasticity and upregulation of immune checkpoint molecules are used by human cancers to evade immune responses. Similar mechanisms are associated with immune evasion by DFTD cancers, providing novel insights that will inform modification of DFTD vaccines. As DFT1 and DFT2 are clonal cancers transmitted across genetically distinct hosts, the Tasmanian devil provides a 'natural' disease model for more broadly exploring these immune evasion mechanisms in cancer.

First evidence of deviation from Mendelian proportions in a conservation programme.

Classic Mendelian inheritance is the bedrock of population genetics and underpins pedigree-based management of animal populations. However, assumptions of Mendelian inheritance might not be upheld in conservation breeding programmes if early viability selection occurs, even when efforts are made to equalise genetic contributions of breeders. To test this possibility, we investigated deviations from Mendelian proportions in a captive metapopulation of the endangered Tasmanian devil. This marsupial population is ideal for addressing evolutionary questions in conservation due to its large size, range of enclosure types (varying in environmental conditions), good genomic resources (which aid interpretation), and the species' biology. Devil mothers give birth to more offspring than they can nurse in the pouch, providing the potential for intense viability selection amongst embryos. We used data from 140 known sire-dam-offspring triads to isolate within-family selection from population-level mechanisms (such as mate choice or inbreeding), and compared observed offspring genotypes at 123 targeted SNPs to neutral (i.e., Mendelian) expectations. We found lower offspring heterozygosity than expected, and subtle patterns that varied across a gradient of management intensity from zoo-like enclosures to semi-wild environments for some loci. Meiotic drive or maternal-foetal incompatibilities are consistent with our results, although we cannot statistically confirm these mechanisms. We found some evidence that maternal genotype affects annual litter size, suggesting that family-level patterns are driven by differential offspring mortality before birth or during early development. Our results show that deviations from Mendelian inheritance can occur in conservation programmes, despite best-practice management to prevent selection.

Two of a kind: transmissible Schwann cell cancers in the endangered Tasmanian devil (Sarcophilus harrisii).

Devil facial tumour disease (DFTD) comprises two genetically distinct transmissible cancers (DFT1 and DFT2) endangering the survival of the Tasmanian devil (Sarcophilus harrisii) in the wild. DFT1 first arose from a cell of the Schwann cell lineage; however, the tissue-of-origin of the recently discovered DFT2 cancer is unknown. In this study, we compared the transcriptome and proteome of DFT2 tumours to DFT1 and normal Tasmanian devil tissues to determine the tissue-of-origin of the DFT2 cancer. Our findings demonstrate that DFT2 expresses a range of Schwann cell markers and exhibits expression patterns consistent with a similar origin to the DFT1 cancer. Furthermore, DFT2 cells express genes associated with the repair response to peripheral nerve damage. These findings suggest that devils may be predisposed to transmissible cancers of Schwann cell origin. The combined effect of factors such as frequent nerve damage from biting, Schwann cell plasticity and low genetic diversity may allow these cancers to develop on rare occasions. The emergence of two independent transmissible cancers from the same tissue in the Tasmanian devil presents an unprecedented opportunity to gain insight into cancer development, evolution and immune evasion in mammalian species.