Biology subjects

Carver, S.

Publications and source records attributed to Carver, S..

14 recordsLinked to original sources

bioRxiv2026

Decoupled seasonal effects of an environmentally transmitted wildlife disease

O_LISeasonal forcing is a dominant factor shaping host-pathogen interactions and disease dynamics across many wildlife systems, including species impacted by environmentally transmitted parasites. How seasonality in parasite dynamics translates to the host when the infection and disease impacts operate at different timescales, however, remains poorly understood. C_LIO_LIWe investigate how seasonality shapes sarcoptic mange in bare-nosed wombats, Vombatus ursinus, a disease caused by the environmentally transmitted parasitic mite Sarcoptes scabiei, causing a protracted clinical time-course in the host. Using an empirically informed state-based deterministic model we explore how wombat population trajectories are influenced by (i) seasonal constraints to mite survival and (ii) in context of host-pathogen encounter rates, as measured by the ratio of burrows to wombats. C_LIO_LIWe demonstrate three long-term outcomes of wombat-mange: host and parasite extinction, endemic disease, and disease-free. We find seasonal environments narrow the range of host-pathogen encounter rates that support S. scabiei persistence relative to stable environments, and prevalence and population sizes vary more in seasonal compared to stable environments except under moderate host-pathogen encounter rates when seasonal effects are less apparent. We also find that a protracted infectious period is essential for host-parasite coexistence in the wombat-mange system. C_LIO_LIOur seasonal model results are consistent with field observations, such that mange prevalence in natural populations increases during seasons of longer off-host mite survival. Application of these findings suggest management efforts could reduce host population impacts through disease management in seasons with longer off-host parasite survival or reduce the environmental reservoir through disease management in seasons with shorter off-host survival. C_LIO_LIWe provide novel, mechanistic explanations for distinctive population trajectories that arise from a seasonally forced wildlife disease, including climate factors that operate independently on parasites, host demography, and disparate timescales over which seasonality affects parasites and hosts. Broadly, linking seasonality to long-term population dynamics can improve the predictability and management of wildlife diseases, but requires an understanding of how local intrinsic factors interact with seasonal pressures over time. C_LI

ecology↗

bioRxiv2024

Discovery of disease-associated cellular states using ResidPCA in single-cell RNA and ATAC sequencing data

To enhance understanding of cellular heterogeneity and disease from single-cell sequencing data, we introduce ResidPCA, a robust method for cell state identification that models cell type heterogeneity. Simulations demonstrate ResidPCAs efficacy, particularly in complex scenarios, with its accuracy more than four times higher than conventional Principal Component Analysis (PCA) and over three times higher than Non-negative Matrix Factorization (NMF)-based methods in identifying states expressed across multiple cell types. In scRNA-seq data from light-stimulated mouse visual cortex cells, ResidPCA captures stimulus-driven variability with an accuracy more than five times higher than NMF methods. In single nucleus data from an Alzheimers disease cohort, ResidPCA identified 44 snATAC-based and 42 snRNA-based states. 30 snATAC states were significantly enriched for Alzheimers disease heritability and were often more significantly enriched than established cell types such as microglia. The ResidPCA-based snATAC state most significantly enriched for Alzheimers disease heritability further elucidates a recently identified mechanism involving the neuron-ODC-microglial axis. This state links early amyloid production in neurons and oligodendrocytes with later-stage microglial activation and immune response, driving Alzheimers disease progression. These results demonstrate ResidPCAs ability to reveal additional biological variation in single-cell data and uncover disease-relevant cell states.

genomics↗

bioRxiv2024

Impacts of Antiretroviral Therapy on the Oral Microbiome and Periodontal Health of Feline Immunodeficiency Virus Positive Cats

Feline immunodeficiency virus (FIV) is the domestic cat analogue of HIV infection in humans. Both viruses induce oral disease in untreated individuals, with clinical signs that include gingivitis and periodontal lesions. Oral disease manifestations in HIV patients are abated by highly effective combination antiretroviral therapy (cART), though certain oral manifestations persist despite therapy. Microorganisms associated with oral cavity opportunistic infections in patients with HIV cause similar pathologies in cats. To further develop this model, we evaluated characteristics of feline oral health and oral microbiome during experimental FIV infection over an 8-month period following cART. Using 16S metagenomics sequencing, we evaluated gingival bacterial communities at four timepoints in uninfected and FIV-infected cats treated with cART or placebo. Comprehensive oral examinations were also conducted by a veterinary dental specialist over the experimental period. Gingival inflammation was higher in FIV-infected cats treated with placebo compared to cART-treated cats and controls at study endpoint. Oral microbiome alpha diversity increased in all groups, while beta diversity differed among treatment groups, documenting a significant effect of cART therapy on microbiome community composition. This finding has not previously been reported and indicates cART ameliorates immunodeficiency virus-associated oral disease via preservation of oral mucosal microbiota. Further, this study illustrates the value of the FIV animal model for investigations of mechanistic associations and therapeutic interventions for HIV oral manifestations. IMPORTANCEFeline Immunodeficiency Virus (FIV) is the viral analogue to HIV in humans, and both infections are associated with oral disease. Our study explored how antiretroviral treatment affects the oral health and microbiome of domestic cats infected with FIV. Cats treated with antiretroviral therapy had less gum inflammation and a different community of oral bacteria compared to untreated FIV-positive cats. This suggests that antiretroviral therapy not only helps in controlling FIV infection but also benefits feline oral health. These findings advance our understanding of antiretroviral treatment for lentiviral-associated oral disease and highlight FIV as a valuable experimental model for the similar condition in humans.

microbiology↗

bioRxiv2024

Liver-specific Mettl14 deletion induces nuclear heterotypia and dysregulates RNA export machinery

Modification of RNA with N6-methyladenosine (m6A) has gained attention in recent years as a general mechanism of gene regulation. In the liver, m6A, along with its associated machinery, has been studied as a potential biomarker of disease and cancer, with impacts on metabolism, cell cycle regulation, and pro-cancer state signaling. However these observational data have yet to be causally examined in vivo. For example, neither perturbation of the key m6A writers Mettl3 and Mettl14, nor the m6A readers Ythdf1 and Ythdf2 have been thoroughly mechanistically characterized in vivo as they have been in vitro. To understand the functions of these machineries, we developed mouse models and found that deleting Mettl14 led to progressive liver injury characterized by nuclear heterotypia, with changes in mRNA splicing, processing and export leading to increases in mRNA surveillance and recycling.

molecular biology↗

bioRxiv2022

The spectral underpinnings of pathogen spread on animal networks

Predicting what factors promote or protect populations from infectious disease is a fundamental epidemiological challenge. Social networks, where nodes represent hosts and edges represent direct or indirect contacts between them, are important in quantifying these aspects of infectious disease dynamics. However, how network structure and epidemic parameters interact in empirical networks to promote or protect animal populations from infectious disease remains a challenge. Here we draw on advances in spectral graph theory and machine learning to build predictive models of pathogen spread on a large collection of empirical networks from across the animal kingdom. We show that the spectral features of an animal network are powerful predictors of pathogen spread for a variety of hosts and pathogens and can be a valuable proxy for the vulnerability of animal networks to pathogen spread. We validate our findings using interpretable machine learning techniques and provide a flexible web application for animal health practitioners to assess the vulnerability of a particular network to pathogen spread.

ecology↗

bioRxiv2021

Characterising the spatio-temporal threats, conservation hotspots, and conservation gaps for the most extinction-prone bird family (Aves: Rallidae)

With thousands of vertebrate species now threatened with extinction, there is an urgent need to understand and mitigate the causes of wildlife collapse. As distinct evolutionary clades can follow different routes to endangerment, there is value in taxon-specific analyses when assessing species vulnerability to threats and identifying gaps in conservation actions. Rails (Aves: Rallidae), being the most extinction-prone bird Family globally, and with one third of extant rail species now threatened or near-threatened, are an emphatic case in point. Yet even for this well-studied group, there is uncertainty in our understanding of what factors might be causing this vulnerability, whether the current threats are consistent with those that led to recent extinctions, and ultimately, what conservation actions might be necessary to mitigate further losses. Here, we undertook a global synthesis of the temporal and spatial threat patterns for Rallidae and determined conservation priorities and gaps. We found two key pathways in the threat pattern for rails. One follows the same trajectory as extinct rails, where island endemic and flightless rails are most threatened, mainly due to invasive predators. The second, created by the recent diversification of anthropogenic activities, involves continental rails (generally in the Neotropics), threatened most commonly by agriculture, natural-system modifications and residential and commercial development. Conservation efforts around most-at-risk species should be adapted according to the most relevant geographic scale (bioregions or countries), and principal locality type of the population (continental or island endemic). Indonesia, the U.S.A., the United Kingdom, New Zealand, and Cuba were the priority countries identified by our classification system incorporating species unique evolutionary features and level of endangerment, but also among the countries that lack conservation actions the most. Future efforts should predominantly target improvements in ecosystem protection and management, as well as ongoing research and monitoring. Forecasting the impacts of climate change on island endemic rails and disentangling the specific roles of extrinsic and intrinsic traits (like flightlessness), will be particularly valuable avenues of research for improving our forecasts of rail vulnerability.

ecology↗

bioRxiv2021

Transmission of one predicts another: Apathogenic proxies for transmission dynamics of a fatal virus

Identifying drivers of transmission prior to an epidemic--especially of an emerging pathogen--is a formidable challenge for proactive disease management efforts. We tested a novel approach in the Florida panther, hypothesizing that apathogenic feline immunodeficiency virus (FIV) transmission could predict transmission dynamics for pathogenic feline leukemia virus (FeLV). We derived a transmission network using FIV whole genome sequences, and used exponential random graph models to determine drivers structuring this network. We used these drivers to predict FeLV transmission pathways among panthers and compared predicted outbreak dynamics against empirical FeLV outbreak data. FIV transmission was primarily driven by panther age class and distances between panther home range centroids. Prospective FIV-based modeling predicted FeLV dynamics at least as well as simpler, often retrospective approaches, with evidence that FIV-based predictions captured the spatial structuring of the observed FeLV outbreak. Our finding that an apathogenic agent can predict transmission of an analogously transmitted pathogen is an innovative approach that warrants testing in other host-pathogen systems to determine generalizability. Use of such apathogenic agents holds promise for improving predictions of pathogen transmission in novel host populations, and could thereby provide new strategies for proactive pathogen management in human and animal systems.

ecology↗

bioRxiv2020

Post release immune responses of Tasmanian devils vaccinated with an experimental devil facial tumour disease vaccine

Disease is increasingly becoming a driver of wildlife population declines and extinction risk. Vaccines have been one of the most successful health interventions in human history, but few have been tested for mitigating wildlife disease. The transmissible cancer, devil facial tumour disease (DFTD), triggered the Tasmanian devils (Sarcophilus harrisii) inclusion on the international endangered species list. Development of a protective DFTD vaccine would provide a valuable management approach for conservation of the species. In 2016, 33 devils from a DFTD-free insurance population were given an experimental DFTD vaccination prior to their release on the north coast of Tasmania. The release site was already home to an incumbent population of devils, including some individuals with DFTD. To determine the efficacy of the vaccination protocol and the longevity of the response it induced, six trapping trips took place at the site over the 2.5 years following release. Eight of the 33 vaccinated devils were re-trapped, and six of those developed DFTD within the monitoring period. Despite the apparent lack of protection provided by the vaccine for the re-trapped devils, we observed several signs of immune activation not usually found in unvaccinated devils. Firstly, sera collected from the eight devils showed that anti-DFTD antibodies persisted for up to two years post vaccination. Secondly, tumour infiltrating lymphocytes were found in three out of four biopsies collected from vaccinated devils which contrasts with the "immune deserts" typical of DFTs; only one out of twenty incumbent devils with DFTD trapped during the same period had a tumour biopsy exhibiting immune cell infiltrate. Thirdly, immunohistochemical analysis of tumour biopsies from the vaccinated devils identified the functional immune molecules associated with antigen presenting cells (MHC-II) and T cells (CD3), and the immune checkpoint molecule PD-1, all associated with anti-tumour immunity in other species. These results correlate with our previous study on captive devils in which a prophylactic vaccine primed the devil immune system and, following DFTD challenge and tumour growth, immunotherapy induced complete tumour regressions. The field trial results presented here provide further evidence that the devil immune system can be primed to recognise DFTD cells, but additional immune manipulation could be needed for complete protection or induction of tumour regressions.

immunology↗

bioRxiv2020

Emerging phylogenetic structure of the SARS-CoV-2 pandemic

Since spilling over into humans, SARS-CoV-2 has rapidly spread across the globe, accumulating significant genetic diversity. The structure of this genetic diversity, and whether it reveals epidemiological insights, are fundamental questions for understanding the evolutionary trajectory of this virus. Here we use a recently developed phylodynamic approach to uncover phylogenetic structures underlying the SARS-CoV-2 pandemic. We find support for three SARS-CoV-2 lineages co-circulating, each with significantly different demographic dynamics concordant with known epidemiological factors. For example, Lineage C emerged in Europe with a high growth rate in late February, just prior to the exponential increase in cases in several European countries. Mutations that characterize Lineage C in particular are non-synonymous and occur in functionally important gene regions responsible for viral replication and cell entry. Even though Lineages A and B had distinct demographic patterns, they were much more difficult to distinguish. Continuous application of phylogenetic approaches to track the evolutionary epidemiology of SARS-CoV-2 lineages will be increasingly important to validate the efficacy of control efforts and monitor significant evolutionary events in the future.

genetics↗

bioRxiv2019

Kinship and social organization in Copper Age Europe. A cross-disciplinary analysis of archaeology, DNA, isotopes, and anthropology from two Bell Beaker cemeteries

We present a high-resolution cross-disciplinary analysis of kinship structure and social institutions in two Late Copper Age Bell Beaker culture cemeteries of South Germany containing 24 and 18 burials, of which 34 provided genetic information. By combining archaeological, anthropological, genetic and isotopic evidence we are able to document the internal kinship and residency structure of the cemeteries and the socially organizing principles of these local communities. The buried individuals represent four to six generations of two family groups, one nuclear family at the Alburg cemetery, and one seemingly more extended at Irlbach. While likely monogamous, they practiced exogamy, as six out of eight non-locals are women. Maternal genetic diversity is high with 23 different mitochondrial haplotypes from 34 individuals, whereas all males belong to one single Y-chromosome haplogroup without any detectable contribution from Y-chromosomes typical of the farmers who had been the sole inhabitants of the region hundreds of years before. This provides evidence for the society being patrilocal, perhaps as a way of protecting property among the male line, while in-marriage from many different places secured social and political networks and prevented inbreeding. We also find evidence that the communities practiced selection for which of their children (aged 0-14 years) received a proper burial, as buried juveniles were in all but one case boys, suggesting the priority of young males in the cemeteries. This is plausibly linked to the exchange of foster children as part of an expansionist kinship system which is well attested from later Indo-European-speaking cultural groups.

genetics↗

bioRxiv2019

Host relatedness and landscape connectivity shape pathogen spread in a large secretive carnivore

Urban expansion can fundamentally alter wildlife movement and gene flow, but how urbanization alters pathogen spread is poorly understood. Here we combine high resolution host and viral genomic data with landscape variables to examine the context of viral spread in puma from two contrasting regions: one bounded by the wildland urban interface (WUI) and one unbounded with minimal anthropogenic development. We found landscape variables and host gene flow explained significant amounts of variation of feline immunodeficiency virus (FIV) spread in the WUI, but not in the unbounded region. The most important predictors of viral spread also differed; host spatial proximity, host relatedness, and mountain ranges played a role in FIV spread in the WUI, whereas unpaved roads were more important in the unbounded region. Our research demonstrates how anthropogenic landscapes can alter pathogen spread, providing a more nuanced understanding of host-pathogen relationships to inform disease ecology in free-ranging species.

ecology↗

bioRxiv2019

Urbanization impacts apex predator gene flow but not genetic diversity across an urban-rural divide

Apex predators are important indicators of intact natural ecosystems. They are also sensitive to urbanization because they require broad home ranges and extensive contiguous habitat to support their prey base. Pumas (Puma concolor) can persist near human developed areas, but urbanization may be detrimental to their movement ecology, population structure, and genetic diversity. To investigate potential effects of urbanization in population connectivity of pumas, we performed a landscape genomics study of 134 pumas on the rural Western Slope and more urbanized Front Range of Colorado, USA. Over 12,000 single nucleotide polymorphisms were genotyped using double-digest, restriction site-associated DNA sequencing (ddRADseq). We investigated patterns of gene flow and genetic diversity, and tested for correlations between key landscape variables and genetic distance to assess the effects of urbanization and other landscape factors on gene flow. Levels of genetic diversity were similar for the Western Slope and Front Range, but effective population sizes were smaller, genetic distances were higher, and there was more overall population substructure in the more urbanized Front Range. Forest cover was strongly positively associated with puma gene flow on the Western Slope, while impervious surfaces restricted gene flow and more open, natural habitats enhanced gene flow on the Front Range. Landscape genomic analyses revealed differences in puma movement and gene flow patterns in rural versus urban settings. Our results highlight the utility of dense, genome-scale markers to document subtle impacts of urbanization on a wide-ranging carnivore living near a large urban center.

genomics↗

bioRxiv2019

How to make more from exposure data? An integrated machine learning pipeline to predict pathogen exposure

O_LIPredicting infectious disease dynamics is a central challenge in disease ecology. Models that can assess which individuals are most at risk of being exposed to a pathogen not only provide valuable insights into disease transmission and dynamics but can also guide management interventions. Constructing such models for wild animal populations, however, is particularly challenging; often only serological data is available on a subset of individuals and non-linear relationships between variables are common.\nC_LIO_LIHere we take advantage of the latest advances in statistical machine learning to construct pathogen-risk models that automatically incorporate complex non-linear relationships with minimal statistical assumptions from ecological data with missing values. Our approach compares multiple machine learning algorithms in a unified environment to find the model with the best predictive performance and uses game theory to better interpret results. We apply this framework on two major pathogens that infect African lions: canine distemper virus (CDV) and feline parvovirus.\nC_LIO_LIOur modelling approach provided enhanced predictive performance compared to more traditional approaches, as well as new insights into disease risks in a wild population. We were able to efficiently capture and visualise strong non-linear patterns, as well as model complex interactions between variables in shaping exposure risk from CDV and feline parvovirus. For example, we found that lions were more likely to be exposed to CDV at a young age but only in low rainfall years.\nC_LIO_LIWhen combined with our data calibration approach, our framework helped us to answer questions about risk of pathogen exposure which are difficult to address with previous methods. Our framework not only has the potential to aid in predicting disease risk in animal populations, but also can be used to build robust predictive models suitable for other ecological applications such as modelling species distribution or diversity patterns.\nC_LI

ecology↗

bioRxiv2017

The Beaker Phenomenon And The Genomic Transformation Of Northwest Europe

Bell Beaker pottery spread across western and central Europe beginning around 2750 BCE before disappearing between 2200-1800 BCE. The mechanism of its expansion is a topic of long-standing debate, with support for both cultural diffusion and human migration. We present new genome-wide ancient DNA data from 170 Neolithic, Copper Age and Bronze Age Europeans, including 100 Beaker-associated individuals. In contrast to the Corded Ware Complex, which has previously been identified as arriving in central Europe following migration from the east, we observe limited genetic affinity between Iberian and central European Beaker Complex-associated individuals, and thus exclude migration as a significant mechanism of spread between these two regions. However, human migration did have an important role in the further dissemination of the Beaker Complex, which we document most clearly in Britain using data from 80 newly reported individuals dating to 3900-1200 BCE. British Neolithic farmers were genetically similar to contemporary populations in continental Europe and in particular to Neolithic Iberians, suggesting that a portion of the farmer ancestry in Britain came from the Mediterranean rather than the Danubian route of farming expansion. Beginning with the Beaker period, and continuing through the Bronze Age, all British individuals harboured high proportions of Steppe ancestry and were genetically closely related to Beaker-associated individuals from the Lower Rhine area. We use these observations to show that the spread of the Beaker Complex to Britain was mediated by migration from the continent that replaced >90% of Britains Neolithic gene pool within a few hundred years, continuing the process that brought Steppe ancestry into central and northern Europe 400 years earlier.

genomics↗