Biology subjects

Sutherland, C.

Publications and source records attributed to Sutherland, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Single-cell multi-ancestry regulatory map of systemic lupus erythematosus

Integrating genomic and single-cell transcriptomic profiles from patient cohorts can uncover regulatory effects underlying genetic associations with disease. Here we present SLEmap, a multi-ancestry single-cell expression quantitative trait locus (sc-eQTL) map generated from peripheral blood mononuclear cells from 281 patients with systemic lupus erythematosus (SLE). We identified 18,608 independent eQTLs in 5,656 genes, of which 149 signals in 66 genes colocalized with SLE GWAS loci. Nearly half of these colocalizations were detected exclusively through cell type-level analyses, highlighting the importance of cellular context for interpreting disease-associated genetic variation. Multi-ancestry data identified regulatory signals robust across diverse ancestral backgrounds and improved signal resolution. Most colocalizations were undetectable in sc-eQTLs from a healthy cohort (OneK1K), with novel SLE colocalizations highlighting disease-relevant regulatory mechanisms across distinct cell types, including the NF-{kappa}B pathway. These findings demonstrate the value of disease-specific, multi-ancestry single-cell regulatory maps for resolving the genes and cellular mechanisms underlying disease-associated genetic variation.

genetics↗

bioRxiv2026

One scale does not fit all: invasive predator identity determines the impact on native prey

O_LIWhen eradication is unfeasible, invasive predator control should evaluate how removal affects ecological responses by native species. Assessments often use total invasive predator abundance to evaluate prey responses, yet intraspecific variation in diet and space use means that some subgroups cause disproportionate impacts. Identifying these problem individuals, and the spatial scales over which their impacts operate, can enable targeted spatially explicit removal to maximise impact reduction. However, despite individual-level information is often already collected during trapping operations it is seldom included when analysing predator impacts, potentially biasing the conservation outcomes expected under blanket removal. C_LIO_LIWe use a novel framework and two decades of invasive predator control data to estimate how individual variation in residency status influences the distance-dependent impacts of invasive American mink Neogale vison on water vole Arvicola amphibius occupancy across two prey surveys. We also develop a sub-model to predict mink residency status for individuals with missing age data. C_LIO_LIThe probability of capturing adult mink decreased with elevation and years of control, indicating that long-term control altered the resident population and demographic composition of mink around water vole sites. C_LIO_LIDistance-dependent negative impacts of mink varied by residency status, becoming negligible at approximately 20 km from water vole sites for resident mink and 2 km for transient. The spatial scale of mink impacts was largest during the first vole survey when resident mink were more abundant, and declined rapidly for the second survey, when mink were less abundant and spatially clustered. Our results suggest that water voles have benefited mostly from reducing resident mink rather than the total population, especially in early control phases. C_LIO_LIManagers can use our framework to develop spatially explicit and impact-based strategies, not restricted to invasive species control, to construct empirically informed management buffers around populations of conservation concern. Long-term efforts will change the landscape and invasive predator contexts, and thus we recommend iteratively updating and re-evaluating management outcome evaluations. We argue that incorporating individual heterogeneity improves our understanding of ecological mechanisms influencing management success but that the suitability of targeted strategies should be evaluated for target socioecological contexts. C_LI

ecology↗

bioRxiv2026

Applying integrated population models to guide conservation planning: Western Capercaillie in Scotland

O_LIMany conservation interventions prove ineffective because they lack a rigorous evidence-base. Multifactorial drivers and data limitations often hinder anticipatory planning and are difficult to tackle with standard methods. Predictive modelling approaches that integrate diverse data sources with biological hypotheses can bridge this gap by clarifying the drivers of decline and evaluating management options under uncertainty. C_LIO_LI We developed a Bayesian integrated population model (IPM) applicable to lekking species, combining incomplete data from different life stages and seasons while accounting for observation error. IPMs are widely recognised for reducing bias relative to single-data-stream analyses, yet their application in conservation planning remains limited. C_LIO_LIWe applied the model to the threatened Western Capercaillie population in Scotland, which has been declining since at least the 1980s despite decades of conservation efforts, a typical case requiring urgent, evidence-based management. By fitting the model to 30 years of biased and incomplete monitoring data, we investigated associations between demographic processes and their potential drivers, including weather variables, fence collision mortality and a proxy of predation pressure. We used model predictions to evaluate the joint effectiveness of proposed management actions aimed at improving vital rates, including fence management and diversionary feeding. C_LIO_LIData integration improved population estimate precision by 17-49% relative to standalone national survey estimates, confirming that the decline continued from 1990-2023. Reproductive rate was related to the pattern of April warming, negatively affected by pre-breeding precipitation and positively by vole abundance, the latter consistent with the alternative prey hypothesis. Model predictions indicated that combining diversionary feeding with fence removal produced the most favourable conservation outcomes, but growth remained limited and uncertainty included possible continued decline. C_LIO_LI5. This modelling approach forms a key component of Scotlands Capercaillie Emergency Plan 2025-2030, guiding management by assessing population-level responses and predicting conservation intervention outcomes. In future, the model could support formal adaptive management through iterative evaluation of interventions as new data become available. Beyond this case study, our integrated approach offers a transferable framework for managing multifactorial declines in other threatened species under uncertainty. C_LI

ecology↗

bioRxiv2025

CRISPR/Cas9-mediated generation of a de novo C9ORF72 knock-in isogenic iPSC cell bank to model ALS and FTD

BackgroundThe pathogenic G4C2 repeat expansion in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Studies focused on delineating the underlying perturbed mechanisms resulting from this genetic mutation are often confounded by the heterogeneity present in current disease models, such as patient-derived iPSC lines, with estimations of up to 50% of the variation in iPSC cell phenotypes resulting from inter-individual differences. Isogenic models, in which the pathogenic mutation is introduced into a defined genetic background, offer a powerful approach to isolating mutation-specific effects and enable high-resolution comparison across distinct ALS/FTD-associated mutations. Such models are essential for uncovering convergent disease mechanisms and improving reproducibility in ALS/FTD research. MethodsA two-step scarless CRISPR/Cas9 genome editing strategy was used to generate isogenic human iPSC lines carrying a de novo knock-in of a disease-length G4C2 repeat expansion in the C9ORF72 locus. The resulting lines underwent thorough quality control and were differentiated into lower motor neurons and assessed for the presence of key ALS/FTD pathologies, including changes to C9ORF72 mRNA and protein expression, RNA foci and dipeptide repeat proteins. ResultsTwo C9ORF72 knock-in iPSC lines were generated with 631 and 600 G4C2 repeats, alongside an isogenic genome editing control line. The C9ORF72 G4C2 repeat expansion knock-in iPSC lines exhibit both loss-of-function and gain-of-function pathological features characteristic of ALS/FTD. Compared to the parental wild-type KOLF2.1J line and isogenic (wild-type) CRISPR control line, these exhibit a significant reduction in C9ORF72 mRNA and protein levels, the presence of RNA foci accumulation, and a marked increase in poly(GA) and poly(GP) dipeptide repeat protein levels in iPSCs and motor neurons. ConclusionsThis is one of the first reports of a successful knock-in of the pathogenic C9ORF72 G4C2 repeat expansion into a human iPSC line, establishing a genetically defined and physiologically relevant model of ALS/FTD. These isogenic lines recapitulate both key loss- and gain-of-function disease pathologies, providing a crucial complement to existing patient-derived iPSC banks. By eliminating confounding genetic background variability, these cell lines will enable more precise interrogation of C9ORF72-linked pathomechanisms and offer a robust platform for comparative studies across the ALS and FTD spectrum, mechanistic investigations, and future therapeutic targeting with enhanced translational relevance.

neuroscience↗

bioRxiv2024

Empirical evidence that diversionary feeding increases productivity in ground-nesting birds.

The recovery of predator populations can negatively impact other species of conservation concern, leading to conservation conflicts. Evidence-based solutions are needed to resolve such conflicts without sacrificing hard-won gains for recovering species. Well-designed, large-scale field experiments provide the most rigorous evidence to justify new forms of intervention, but they are notoriously hard to implement. Further, monitoring scarce species without negative impacts is challenging, calling for indirect and non-invasive monitoring methods. Uncertainties remain about whether observational monitoring adequately reflects the true processes of interest. Having conducted a well-designed, large-scale, diversionary feeding field experiment that reduced artificial nest depredation, we evaluated whether this translated to capercaillie productivity in the same area. Using camera traps aimed at dust baths, we non-invasively monitored capercaillie hen productivity over 3 years and in 30 1km2 grid cells under a randomised control (un-fed) and treatment (fed) design. Diversionary feeding significantly increased the probability that a detected hen would have a brood. The impact of diversionary feeding did not change over the brooding season, indicating that hens without a brood had failed due to nest depredation rather than predation of chicks. The probability of detecting a hen with a brood was 0.85 (0.65-0.94) in fed locations, more than double that in unfed locations, which was 0.37 (CI 0.2-0.57). The average brood size was reduced over time, but the change did not differ between fed and unfed sites. This is in line with natural mortality occurring independently of diversionary feeding. Importantly, the increased chance of having a brood in the fed areas and the predicted brood size leads to a substantial increase in overall productivity - the expected number of chicks per hen - at the end of the sampling season. This was just 0.82 (0.35 - 1.29) chicks per hen in the unfed sites and more than double 1.90 (1.24 - 2.55) chicks in fed sites. This study provides compelling empirical evidence that diversionary feeding positively affects productivity, offering an effective non-lethal solution to the increasingly common conservation conflict where both predator and prey are afforded protection.

ecology↗

bioRxiv2024

Improving the integration of AI into existing ecological inference workflows

O_LIArtificial Intelligence (AI) has revolutionised the process of identifying species and individuals in audio recordings and camera trap images. However, despite developments in sensor technology, machine learning, and statistical methods, a general AI-assisted data-to-inference pipeline has yet to emerge. C_LIO_LIWe argue that this is, in part, due to a lack of clarity around several decisions in existing workflows, including: the choice of classifier used (e.g., semi- vs. fully automated); how classifier confidence scores are used and interpreted; and the availability and selection of appropriate statistical methods for drawing ecological inferences. C_LIO_LIHere, we attempt to conceptualise a general workflow associated with automated tools in ecology. We motivate this perspective using our experiences with occupancy modelling using monitoring data collected through passive acoustic monitoring and camera trapping, identifying priority areas for future developments. C_LIO_LIWe offer an accessible guide to support the ecological community in navigating and capitalising on rapid technological and methodological advances. We describe how different error types arise from both sensor-based monitoring and from classifiers themselves; how different error types are handled at each stage of the workflow; and finally, implications and opportunities associated with deciding on methods used at each step of the pipeline. C_LIO_LIWe recommend that "black box" tools like neural network classification algorithms should be embraced in ecology, but widespread uptake requires more formal integration of AI into the existing ecological inference workflows. Like ecological AI more broadly, however, successful development of new data-to-inference pipelines is a multidisciplinary endeavour that requires input from everyone invested in collecting, processing, analysing, and using ecological monitoring data. C_LI

ecology↗

bioRxiv2024

Sample size considerations for species co-occurrence models.

Multispecies occupancy models are widely applied to infer interactions in the occurrence of different species, but convergence and estimation issues under realistic sample sizes are common. We conducted a simulation study to evaluate the ability of a recently developed model to recover co-occurrence estimates under varying sample size and interaction scenarios while increasing model complexity in two dimensions: the number of interacting species and the number of covariates. Using both standard and penalized likelihood, we demonstrate that the ability to quantify interactions in species occupancy using this model is highly sensitive to sample size, detection probability and interaction strength. In the simplest scenario, there is high bias in the interaction parameter (used for co-occurrence inference) with less than 100 sites at high detection, and 400-1000 sites at low detection, depending on interaction strength. Strong co-occurrence is detected consistently above 200 sites with high detection probabilities, but weak co-occurrence is never consistently detected even with 2980 sites. We demonstrate that mean predictive ability of the co-occurrence model is less affected by sample size, with low bias in derived probabilities at 50 sites. Our results highlight that while occupancy patterns are often robust to sample size limitations, reliable inference about co-occurrence demands substantially larger datasets than many studies currently achieve. We caution the interpretation of model output in small datasets or when co-occurrence is expected to be weak, but show methods are suitable to quantify strong co-occurrence in larger datasets and generate predictions of site occupancy states.

ecology↗

bioRxiv2024

Elraglusib induces cytotoxicity via microtubule destabilisation independently of GSK3 inhibition

AO_SCPLOWBSTRACTC_SCPLOWElraglusib (9-ING-41) is an ATP-competitive inhibitor of glycogen synthase kinase-3 (GSK3) with pre-clinical studies demonstrating broad activity against many tumour types. Promising early-phase clinical trial data led to FDA orphan drug status, and a randomized phase 2 study in combination with cytotoxic chemotherapy in pancreatic cancer has recently completed its recruitment. Similarly, single-agent responses in adult T-cell leukaemia/lymphoma and melanoma, and combination treatment data in several other tumour types have been encouraging. The elraglusib mechanism of action is unknown, but it is unlikely to act through GSK3 inhibition because cytotoxicity is observed below the IC50 for GSK3 and other small molecule GSK3 inhibitors do not produce cytotoxic effects, at least in lymphoma cells. We show here that elraglusib perturbs chromosomal alignment to cause a mitotic arrest in multiple tumour lines. This arrest is caused by direct microtubule depolymerisation, which prevents the attachment of kinetochores to microtubules. At clinically relevant doses, these mitotically arrested cells eventually undergo mitotic slippage, leading to gross chromosome missegregation, DNA damage and apoptosis. These effects explain the cytotoxicity of elraglusib because temporarily pausing cell cycle progression with the CDK4/6 inhibitor palbociclib abolishes any drug-induced genotoxicity and apoptosis. In summary, elraglusib acts as a potent direct microtubule destabilizer both in vitro and across multiple cancer types, resulting in mitotic arrest, DNA damage and apoptosis. These effects likely account for its broad pan-cancer activity, which does not rely upon GSK3 inhibition as they are not replicated by other GSK3 inhibitors.

cancer biology↗

bioRxiv2024

Population genomics of Plasmodium ovale species in sub-Saharan Africa

Plasmodium ovale curtisi (Poc) and Plasmodium ovale wallikeri (Pow) are relapsing malaria parasites endemic to Africa and Asia that were previously thought to represent a single species. Amid increasing detection of ovale malaria in sub-Saharan Africa, we performed a population genomic study of both species across the continent. We conducted whole-genome sequencing of 25 isolates from Central and East Africa and analyzed them alongside 20 previously published African genomes. Isolates were predominantly monoclonal (43/45), with their genetic similarity aligning with geography. Pow showed lower average nucleotide diversity (1.8x10-4) across the genome compared to Poc (3.0x10-4) (p < 0.0001). Signatures of selective sweeps involving the dihydrofolate reductase gene were found in both species, as were signs of balancing selection at the merozoite surface protein 1 gene. Differences in the nucleotide diversity of Poc and Pow may reflect unique demographic history, even as similar selective forces facilitate their resilience to malaria control interventions.

genomics↗

bioRxiv2024

Detection of naturally acquired, strain-transcending antibodies against rosetting Plasmodium falciparum strains in humans

Strain-transcending antibodies against subsets of P. falciparum blood stage surface antigens could protect children from severe malaria. However, the evidence supporting the existence of such antibodies is incomplete and inconsistent. One subset of surface antigens associated with severe malaria, rosette-mediating Plasmodium falciparum Erythrocyte Membrane Protein one (PfEMP1) variants, cause infected erythrocytes to bind to uninfected erythrocytes to form clusters of cells (rosettes) that contribute to microvascular obstruction and pathology. Here, using flow cytometry of live infected erythrocytes, we tested plasma from 80 individuals living in malaria-endemic regions for IgG recognition of the surface of four P. falciparum rosetting strains. Broadly-reactive plasma samples were then used in antibody elution experiments in which intact IgG was eluted from the surface of infected erythrocytes and transferred to heterologous rosetting strains to look for strain-transcending antibodies. We found that seroprevalence (percentage of samples that recognised each strain) against allopatric rosetting strains was high in adults (58% - 93%), but lower in children (5%-30%). Strain-transcending antibodies were present in nine out of eleven eluted antibody experiments, with six of these recognising multiple heterologous rosetting parasite strains. One eluate had rosette disrupting activity against heterologous strains, suggesting PfEMP1 as the likely target of the strain-transcending antibodies. Naturally acquired strain-transcending antibodies to rosetting P. falciparum strains in humans have not been directly demonstrated previously. Their existence suggests that such antibodies could play a role in clinical protection and raises the possibility that conserved epitopes recognised by strain-transcending antibodies could be targeted therapeutically.

microbiology↗

bioRxiv2023

Evaluating diversionary feeding as a method to resolve conservation conflicts in a recovering ecosystem

1. The recovery of mammalian predators of conservation concern in Europe is a success story, but their impact on some prey species of conservation concern may cause conservation dilemmas. This calls for effective intervention strategies that mitigate predator impacts without compromising their recovery. 2. We evaluated diversionary feeding as a management intervention tool to reduce depredation on nests of rapidly declining Western capercaillies in Scotland. We studied the influence of diversionary feeding provision on the fates of artificial nests deployed using a replicated and representative randomised landscape-scale experiment. This comprised 30 paired control (no diversionary feeding) and treatment (diversionary feeding applied) sites, 60 in total, each containing six artificial nests distributed across 600 km2. The experiment was replicated over two years, and in the second year, the control-treatment pairs were reversed, yielding 60 treatment and 60 control sites and 720 artificial nests. 3. Diversionary feeding substantially reduced depredation of artificial nests, translating into an 83% increase in predicted nest survival over 28 days of incubation. The increase in survival was mostly accounted for by a reduction in the probability that a pine marten, the main nest predator, consumed or cached eggs. Diversionary food also significantly reduced nest predation by badgers, although the magnitude of this effect varied by year. 4. Diversionary feeding is an easily employable method shown in this study to reduce predator impact (functional) without lethal (numerical) intervention. Managers should proceed with its application for conserving capercaillie in Scotland without delay.

ecology↗

bioRxiv2023

A comprehensive analysis of rheumatoid arthritis B cells reveals the importance of CD11c+ve double-negative-2 B cells as the major synovial plasma cell precursor.

B cells are key pathogenic drivers of chronic inflammation in rheumatoid arthritis (RA). There is limited understanding of the relationship between synovial B cell subsets and pathogenic antibody secreting cells (ASCs). This knowledge is crucial for the development of targeted therapies. Here, we combine flow cytometry of circulating B cells with single-cell RNA and paired repertoire sequencing of over 27,000 synovial B cells from patients with established RA. Twelve B cell clusters were identified including previously recognised subsets, and a novel cluster that strongly expressed heat shock proteins. All lineages identified by trajectory analysis contribute to the DN2 B cell population, which is the major precursor to synovial ASCs. This was further supported by B cell receptor (BCR) lineage analysis, which revealed clonal relationships between DN2 cells and ASCs. This study advances our understanding of B cells in RA and reveals the origin of pathogenic ASCs in the RA synovium.

immunology↗

bioRxiv2022

AIRRSHIP: simulating human B cell receptor repertoire sequences

Adaptive Immune Receptor Repertoire Sequencing is a rapidly developing field that has advanced understanding of the role of the adaptive immune system in health and disease. Numerous tools have been developed to analyse the complex data produced by this technique but work to compare their accuracy and reliability has been limited. Thorough, systematic assessment of their performance is dependent on the ability to produce high quality simulated datasets with known ground truth. We have developed AIRRSHIP, a flexible and fast Python package that produces synthetic human B cell receptor sequences. AIRRSHIP uses a comprehensive set of reference data to replicate key mechanisms in the immunoglobulin recombination process, with a particular focus on junctional complexity. Repertoires generated by AIRRSHIP are highly similar to published data and all steps in the sequence generation process are recorded. These data can be used to not only determine the accuracy of repertoire analysis tools but can also, by tuning of the large number of user-controllable parameters, give insight into factors that contribute to inaccuracies in results. Availability and ImplementationAIRRSHIP is implemented in Python. It is available via https://github.com/Cowanlab/airrship and on PyPI at https://pypi.org/project/airrship/. Documentation can be found at https://airrship.readthedocs.io. Contactgraeme.cowan@ed.ac.uk

bioinformatics↗

bioRxiv2022

Death-associated protein kinase 3 (DAPK3) regulates the myogenic reactivity of cerebral arterioles

The vascular smooth muscle (VSM) of resistance blood vessels displays intrinsic autoregulatory responses to increased intraluminal pressure, the myogenic response. In the brain, the myogenic responses of cerebral arterioles are critical to homeostatic blood flow regulation. Here we provide the first evidence to link the death-associated protein kinase 3 (DAPK3) to the myogenic response of rat and human cerebral arterioles. DAPK3 is a Ser/Thr kinase involved in Ca2+- sensitization mechanisms of VSM contraction. Ex vivo administration of a specific DAPK3 inhibitor (i.e., HS38) could attenuate vessel constrictions invoked by serotonin as well as intraluminal pressure elevation. The HS38-dependent dilation was not associated with any change in myosin light chain (LC20) phosphorylation. The results suggest that DAPK3 does not regulate Ca2+ sensitization pathways during the myogenic response of cerebral vessels but rather operates to control the actin cytoskeleton. Finally, a slow return of myogenic tone was observed during the sustained exposure of cerebral arterioles to a suite of DAPK3 inhibitors. Recovery of tone was associated with greater LC20 phosphorylation that suggests intrinsic signaling compensation in response to attenuation of DAPK3 activity. The translational importance of DAPK3 to the human cerebral vasculature was noted, with robust expression of the protein kinase and significant HS38-dependent attenuation of myogenic reactivity found for human pial vessels.

physiology↗

bioRxiv2021

GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans

Chronically elevated intraocular pressure (IOP) is the major risk factor of primary open- angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of aqueous humor (AqH) from the anterior chamber, is the major cause of elevated IOP. Here, we demonstrate that mice deficient in the Kruppel- like zinc finger transcriptional factor GLI-similar-1 (GLIS1) develop chronically elevated IOP. Magnetic resonance imaging and histopathological analysis reveal that deficiency in GLIS1 expression induces progressive degeneration of the TM, leading to inefficient AqH drainage from the anterior chamber and elevated IOP. Transcriptome and cistrome analyses identified several glaucoma- and extracellular matrix-associated genes as direct transcriptional targets of GLIS1. We also identified a significant association between GLIS1 variant rs941125 and glaucoma in humans (P=4.73x10-6), further supporting a role for GLIS1 into glaucoma etiology. Our study identifies GLIS1 as a critical regulator of TM function and maintenance, AqH dynamics, and IOP.

molecular biology↗

bioRxiv2021

Defining dual-axis landscape gradients of human influence for studying ecological processes

Ecological processes are strongly shaped by human landscape modification, and understanding the reciprocal relationship between ecosystems and modified landscapes is critical for informed conservation. Single axis measures of spatial heterogeneity proliferate in the contemporary gradient ecology literature, though they are unlikely to capture the complexity of ecological responses. Here, we develop a standardized approach for defining multi-dimensional gradients of human influence in heterogeneous landscapes and demonstrate this approach to analyze landscape characteristics of ten ecologically distinct US cities. Using occupancy data of a common human-adaptive songbird collected in each of the cities, we then use our dual-axis gradients to evaluate the utility of our approach. Spatial analysis of landscapes surrounding ten US cities revealed two important axes of variation that are intuitively consistent with the characteristics of multi-use landscapes, but are often confounded in single axis gradients. These were, a hard-to-soft gradient, representing transition from developed areas to non-structural soft areas; and brown-to-green, differentiating between two dominant types of soft landscapes: agriculture (brown) and natural areas (green). Analysis of songbird data demonstrated that occupancy responds to both hard-to-soft (decreasing with development intensity) and brown-to-green gradient (increasing with more natural area). Overall, our results reveal striking consistency in the dominant sources of variation across ten geographically distinct cities and suggests that our approach advances how we relate variation in ecological responses to human influence. Our case study demonstrates this: robins show a remarkably consistent response to a gradient differentiating agricultural and natural areas, but city-specific responses to the more traditional gradient of development intensity, which would be overlooked with a single gradient approach. Managing ecological communities in human dominated landscapes is extremely challenging due to a lack of standardized approaches and a general understanding of how socio-ecological systems function, and our approach offers promising solutions.

ecology↗

bioRxiv2020

A Conserved TCRβ signature dominates a highly polyclonal T-cell expansion during the acute phase of a murine malaria infection

CD4+ {beta} T-cells are key mediators of the immune response to a first Plasmodium infection, undergoing extensive activation and splenic expansion during the acute phase of an infection. However, the clonality and clonal composition of this expansion has not previously been described. Using a comparative infection model, we sequenced the splenic CD4+ T-cell receptor repertoires generated over the time-course of a Plasmodium chabaudi infection. We show through repeat replicate experiments, single-cell RNA-seq, and analyses of independent RNA-seq data, that following a first infection - within a highly polyclonal expansion - T-effector repertoires are consistently dominated by TRBV3 gene usage. Clustering by sequence similarity, we find the same dominant clonal signature is expanded across replicates in the acute phase of an infection, revealing a conserved pathogen-specific T-cell response that is consistently a hallmark of a first infection, but not expanded upon re-challenge. Determining the host or parasite factors driving this conserved response may uncover novel immune targets for malaria therapeutic purposes.

immunology↗

bioRxiv2020

Towards optimal sampling design for spatial capture-recapture

Spatial capture-recapture (SCR) has emerged as the industry standard for estimating population density by leveraging information from spatial locations of repeat encounters of individuals. The precision of density estimates depends fundamentally on the number and spatial configuration of traps. Despite this knowledge, existing sampling design recommendations are heuristic and their performance remains untested for most practical applications. To address this issue, we propose a genetic algorithm that minimizes any sensible, criteria-based objective function to produce near-optimal sampling designs. To motivate the idea of optimality, we compare the performance of designs optimized using three model-based criteria related to the probability of capture. We use simulation to show that these designs out-perform those based on existing recommendations in terms of bias, precision, and accuracy in the estimation of population size. Our approach allows conservation practitioners and researchers to generate customized and improved sampling designs for wildlife monitoring.

ecology↗