Biology subjects

Atkinson, J.

Publications and source records attributed to Atkinson, J..

15 recordsLinked to original sources

bioRxiv2026

Nutrient enrichment and herbivore exclusion disrupt the climate-driven balance between C3 and C4 plants in grasslands

The distribution of plants with different photosynthetic pathways is strongly structured by climate, with C3 plants favoured in cooler temperate regions and C4 plants in hotter, high-light conditions. The relative abundance of C3 and C4 plants across the world has cascading impacts on local food webs, decomposition, productivity and other vital ecosystem processes. Human impacts, including climate change, changes to herbivore assemblages, and increased nutrient availability, are shifting the optimal conditions for important C3 and C4-dominated ecosystems and crops. Using 3,184 plot-level observations from 112 sites across six continents, we reveal how chronic nutrient enrichment disrupts the climate-driven balance between C3 and C4 plants in grasslands. We found that, consistent with expectations, the global distribution of C4 plants was strongly related to climate. However, experimental nutrient addition reduced the relative cover of C4 species, with the strongest declines found when nitrogen and phosphorus were added together. Herbivore exclusion had no consistent effect on C4 plants. Our results provide global experimental evidence that elevated nutrients, particularly nitrogen, alter competitive outcomes among plant functional types to suppress C4 grasses, even in climatically optimal conditions. This has major implications for predicting vegetation responses to global change, with consequences for carbon cycling, primary productivity, herbivore dynamics, and food security.

ecology↗

bioRxiv2026

Chromosome-scale genome assembly of diploid halophyte Thinopyrum bessarabicum excludes J genome from polyploid Thinopyrum ancestry

Wild relatives of wheat harbour genetic diversity essential for improving resilience to climate-driven stresses, yet their deployment is hampered by unresolved evolutionary relationships and the absence of reference genomes. Here we present a chromosome-scale reference genome for Thinopyrum bessarabicum, a diploid halophyte and high-priority donor for wheat salt tolerance breeding. A key unresolved question is whether the diploid J genome contributed directly to the subgenome composition of extant polyploid Thinopyrum species, and which genomic features underpin its exceptional salt tolerance. Using this resource, we show that the diploid J genome of Th. bessarabicum is not represented among the subgenomes of polyploid Thinopyrum species, resolving a long-standing ambiguity in Triticeae genomics. Gene-level resolution of the reciprocal 4/5 chromosomal translocation across six related Triticeae species identifies conserved breakpoint gene pairs, supporting a single ancestral rearrangement. Genome-wide gene content analysis shows that halophytic capacity is underpinned by quantitative expansion of conserved stress-response gene families. Salt tolerance phenotyping validates chromosome 5J as a tolerance locus in both Th. bessarabicum and wheat introgression lines. A physically anchored marker framework and dual-reference skim-sequencing pipeline enable precise megabase-resolution characterisation of Th. bessarabicum introgressions in wheat, providing a genomic foundation for deploying J-genome diversity in crop improvement.

plant biology↗

bioRxiv2026

Adipose-driven complement-lipid reprogramming controls nociceptive vulnerability in obesity-associated osteoarthritis

Obesity amplifies osteoarthritis (OA) pain disproportionately to joint damage, creating a major unmet clinical need for non-opioid interventions that act beyond the joint. Using OA as a translational model, we integrated serum multi-omics in obese mice with surgically induced OA and genetic and adipose-reconstitution models of complement factor D (FD). In humans, we analyzed longitudinal metabolomics data from the IDEA weight-loss trial and conducted functional studies in dorsal root ganglion (DRG) neurons. Adipose-derived FD emerged as a regulator of systemic immunometabolic state: FD deficiency in obese mice worsened pain sensitivity whereas restoring circulating FD normalized pain and inflammatory markers without altering joint structure. Cross-species lipid profiling identified conserved shifts in linoleic acid versus arachidonic acid-derived lipids that were associated with pain phenotypes in mice and with pain improvement in humans. Defined lipid cocktails modulated excitability and TRPV1 sensitivity in human DRG neurons, and transcriptomics of knee-innervating DRGs revealed diet and FD-dependent activation of complement and neuronal excitability pathways. Together, these findings define an adipose-complement-lipid axis that regulates nociceptive vulnerability independent of joint damage and identify extra-articular targets for translational, non-opioid OA pain therapies. One Sentence SummaryWe identify an adipose-complement-lipid axis that systemically regulates sensory neuron sensitization, providing a mechanistic basis for pain-structure discordance in obesity-associated osteoarthritis.

physiology↗

bioRxiv2026

Estrogen receptor-positive cell line xenograft models recapitulate metastatic dissemination and endocrine response of invasive lobular breast carcinoma

HighlightsO_LIER+, CDH1-deficient ILC xenografts recapitulate single-file histology in vivo C_LIO_LISpontaneous metastases faithfully mirror unique ILC clinical dissemination patterns C_LIO_LIER+ leptomeningeal metastases confirmed histologically in ILC xenograft models C_LIO_LIFulvestrant inhibits ILC tumor growth and metastatic burden, improving survival C_LIO_LIER signaling is enriched in ILC brain metastases, with upregulation of RET C_LI Invasive lobular breast carcinoma (ILC), the most common special histological subtype of breast cancer, is characterized by nearly universal expression of estrogen receptor alpha (ER) and unique sites of metastases, neither of which is fully recapitulated by genetically engineered mouse models. Using reporter-labeled ILC mouse xenografts, herein we used mammary fat pad, tail vein and intracardiac orthotopic growth to analyze spontaneous and experimental metastasis and gene expression. We observed ER-positive primary tumors with single-file histology and collagen deposition, and spontaneous metastasis from the mammary fat pad to bones, ovaries, and brain including the leptomeninges, thereby closely mirroring the growth and metastatic spread of human ILC. Brain metastases showed strong ER staining, confirmed by sequencing analyses which identified estrogen signaling as top activated pathway, and the lesions exhibited robust response to endocrine therapy. In summary, we report endocrine responsive mammary fat pad, tail vein and intracardiac xenografts that faithfully demonstrate unique ILC features and can serve as invaluable pre-clinical translational platforms for validating candidate ILC genetic drivers and testing novel therapeutics.

cancer biology↗

bioRxiv2025

Caspase-11 Mediated Hyperinflammation Impairs CD8⁺ T Cell Immunity and Viral Clearance in Severe SARS-CoV-2 Infection

Severe SARS-CoV-2 infection is characterized by lung hyperinflammation, impaired interferon responses, and defective T-cell activation, yet the molecular drivers of these immune dysregulations remain incompletely understood. Caspase-11 (CASP11), a key mediator of the non-canonical inflammasome, has been shown to mediate an innate hyperinflammatory response and cytokine release in a non-severe, non-lethal SARS-CoV-2 infection model. However, the role played by CASP11 in severe SARS-CoV-2 disease and how it impacts adaptive immunity is not identified. Here, we newly discover that CASP11 exacerbates severe SARS-CoV-2 pathogenesis by amplifying early innate immune responses while concurrently impairing antiviral CD8 T-cell immunity. Using global knockouts, reciprocal bone marrow chimeras, and phagocyte-monocyte system (PMS) cell-specific CASP11 deletion models, we show that CASP11 deletion in monocyte-derived cells reduces lung inflammation, enhances type I and II interferon signaling, and promotes robust virus-specific effector CD8 T-cell response. This was associated with enhanced viral clearance and improved survival, even under lethal infection conditions. Importantly, CASP11 KO mice also exhibited faster resolution of post-viral inflammation, suggesting a role in long-term immune remodeling. These findings position CASP11 as a promising immunomodulatory target for acute and delayed manifestations of severe SARS-CoV-2.

microbiology↗

bioRxiv2025

Defining the transmission parameters of lumpy skin disease virus by the three model insect vector species Aedes aegypti, Stomoxys calcitrans and Culicoides nubeculosus reveals important differences in their likely role in transmission

Lumpy skin disease virus (LSDV) is a poxvirus that can cause severe, systemic disease in cattle. By far the most important route of transmission of LSDV is mechanical transmission via haematophagous arthropod vectors. However we lack detailed information on this process including the likelihood of transmission by different vector species. This study used an experimental bovine model of LSDV transmission to quantify the transmission of LSDV from an infected donor to a naive recipient calf. Three species of Diptera representing different vector groups were included (Stomoxys calcitrans, Aedes aegypti and Culicoides nubeculosus, respectively a large biting fly, a mosquito and a midge), and the clinical, virological and immunological outcomes in the recipient calves studied. The ability of Ae. aegypti to mechanically transmit LSDV following feeding on an artificial membrane feeding system was also examined. Both Ae. aegypti and S. calcitrans were able to transmit LSDV, resulting in disease in recipient calves. Bites from virus-positive C. nubeculosus did not result in disease in recipient calves, though the presence of neutralising antibodies in these recipients indicated exposure to virus or virus components. Ae. aegypti successfully transmitted LSDV following feeding on LSDV-spiked blood through an artificial membrane feeding system, validating this laboratory model as a future replacement for donor cattle. Mathematical models of the data were generated and predicted S. calcitrans to be the most efficient vector of LSDV of the insects tested with a reproduction number (R0) of 5.8. Impact statementLumpy skin disease virus (LSDV) is a neglected, rapidly emerging pathogen of cattle that has spread into Europe and throughout the Middle East and Asia over the past ten years. Lack of understanding of the mechanism of transmission of LSDV has hampered efforts to control its rapid spread. This study compares the ability of three model species of Diptera (Stomoxys calcitrans, Aedes aegypti and Culicoides nubeculosus) to mechanically transmit the virus to cattle, generating high quality quantitative data to facilitate mathematical modelling of virus transmission. S. calcitrans was identified as a potential driver of LSDV transmission with a R0 of 5.8. This work provides new insights into the vector transmission of LSDV that can be used to design more targeted and effective disease control programmes.

microbiology↗

bioRxiv2025

The Rapid Anatomics Tool (RAT): A low-cost root anatomical phenotyping pipeline reveals changes in root anatomy along the root axis

Root anatomical phenotyping has become a demonstrably essential part of investigating root physiology and in acquiring a holistic understanding of plant development. However, accessible high throughput methods for root anatomical analysis are still lacking. Here, we present the Rapid Anatomics Tool (RAT), a novel, low-cost system for high throughput root anatomical imaging with a shallow learning curve for obtaining high quality images suitable for comparative analysis across a number of plant species. Its efficiency comes from combining blockface-like imaging and stain-free imaging using near-ultraviolet (nUV) autofluorescence utilising a combination of low-cost commercial equipment, readily available mechanical components, and custom designed and 3D printed tools. Using this system, we investigated the anatomy of mature tissue along the axis of wheat crown roots, revealing a tendency of reduction in vascular complexity (expressed through a reduction in metaxylem number, area, and mean area per metaxylem file) from the basal to the distal region of the root. This study highlights the importance of thorough sampling strategies for investigating root anatomy in relation to organ function and introduces an accessible, relatively high-throughput method to support such research.

plant biology↗

bioRxiv2025

Mechanisms of ATM Inhibitor AZD1390-Mediated Radiosensitization by Comparing DNA DSB Formation and Repair in 4T1 Cells

Radioresistant cancers often exhibit upregulated DNA damage response (DDR) proteins including ataxia telangiectasia mutated (ATM), recovering more readily from radiation-induced DNA double-strand breaks (DSBs). ATM inhibitors (ATMi) are therefore being explored as adjuvants in radiotherapy to both enhance radiosensitivity and minimise normal tissue complications. The molecule AZD1390 has been developed as an inhibitor of ATM and is undergoing assessment in clinical trials. However, traditional markers of DNA DSB repair, such as {gamma}H2AX, represent stages of DDR downstream from the action of ATM. The ATMi AZD1390, developed by AstraZeneca, ultimately prevents phosphorylation of the H2AX histone variant. In order to quantify ATMi AZD1390 action, the novel and highly complementary assay SensiTive Recognition of Individual DNA Ends (STRIDE) was employed to directly quantify DSBs in comparison to {gamma}H2AX after X-ray irradiation of 4T1 cells. Findings revealed that ATM inhibition via AZD1390 delays DSB repair initiation and appears to play a greater role in suppressing DDR beyond ATM inhibition alone. In X-ray irradiated conditions, obfuscation of DSBs commenced between 30- to 45-minutes post-irradiation without AZD1390 versus 45 to 60-minutes for cells pretreated with AZD1390 and entirely prevented {gamma}H2AX in the majority of cells. STRIDE and {gamma}H2AX exhibited almost no co-localization indicating that they provide distinct and complementary information. DSB formation was also assessed in cells fixed pre-insult to minimise any biological response, providing unprecedented assessment of DSB formation. These results highlight the potential of STRIDE to accurately measure DNA damage response kinetics, paving the way for more precise mechanistic studies into the role of ATM in radiotherapy.

cancer biology↗

bioRxiv2025

pyRootHair: Machine Learning Accelerated Software for High-Throughput Phenotyping of Plant Root Hair Traits

1Root hairs play a key role in plant nutrient and water uptake. Historically, root hair traits have been largely quantified manually. As such, this process has been laborious and low-throughput. However, given their importance for plant health and development, high-throughput quantification of root hair morphology could help underpin rapid advances in the genetic understanding of these traits. With recent increases in the accessibility and availability of artificial intelligence (AI) and machine learning techniques, the development of tools to automate plant phenotyping processes has been greatly accelerated. Here, we present pyRootHair, a high-throughput, AI-powered software application to automate root hair trait extraction from images of plant roots grown on agar plates. pyRootHair is capable of batch processing over 600 images per hour without manual input from the end user. In this study, we deploy pyRootHair on a panel of 24 diverse wheat cultivars and uncover a large, previously unresolved amount of variation in many root hair traits. We show that the overall root hair profile falls under two distinct shape categories, and that different root hair traits often correlate with each other. We also demonstrate that pyRootHair can be deployed on a range of plant species, including arabidopsis (Arabidopsis thaliana), brachypodium (Brachypodium distachyon), medicago (Medicago truncatula), oat (Avena sativa), rice (Oryza sativa), teff (Eragostis tef) and tomato (Solanum lycopersicum). The application of pyRootHair enables users to rapidly screen large numbers of plant germplasm resources for variation in root hair morphology, supporting high-resolution measurements and high-throughput data analysis. This facilitates downstream investigation of the impacts of root hair genetic control and morphological variaton on plant performance.

bioinformatics↗

bioRxiv2023

Engineering Human Pluripotent Stem Cell Lines to Evade Xenogeneic Transplantation Barriers

Allogeneic human pluripotent stem cell (hPSC)-derived cells and tissues for therapeutic transplantation must necessarily overcome immunological rejection by the recipient. To define these barriers and to create cells capable of evading rejection for preclinical testing in immunocompetent mouse models, we genetically ablated {beta}2m, Tap1, Ciita, Cd74, Mica, and Micb to limit expression of HLA-I, HLA-II, and natural killer cell activating ligands in hPSCs. Though these and even unedited hPSCs readily formed teratomas in cord blood-humanized immunodeficient mice, grafts were rapidly rejected by immunocompetent wild-type mice. Transplantation of these cells that also expressed covalent single chain trimers of Qa1 and H2-Kb to inhibit natural killer cells and CD55, Crry, and CD59 to inhibit complement deposition led to persistent teratomas in wild-type mice. Expression of additional inhibitory factors such as CD24, CD47, and/or PD-L1 had no discernible impact on teratoma growth or persistence. Transplantation of HLA-deficient hPSCs into mice genetically deficient in complement and depleted of natural killer cells also led to persistent teratomas. Thus, T cell, NK cell, and complement evasion are necessary to prevent immunological rejection of hPSCs and their progeny. These cells and versions expressing human orthologs of immune evasion factors can be used to refine tissue- and cell type-specific immune barriers, and to conduct preclinical testing in immunocompetent mouse models.

immunology↗

bioRxiv2023

Glutaredoxin regulation of primary root growth confers early drought stress tolerance in pearl millet

Seedling root traits impact plant establishment under challenging environments. Pearl millet is one of the most heat and drought tolerant cereal crops that provides a vital food source across the sub-Saharan Sahel region. Pearl millets early root system features a single fast-growing primary root which we hypothesize is an adaptation to the Sahelian climate. Using crop modelling, we demonstrate that early drought stress is an important constraint in agrosystems in the Sahel where pearl millet was domesticated. Furthermore, we show that increased pearl millet primary root growth is correlated with increased early water stress tolerance in field conditions. Genetics including GWAS and QTL approaches identify genomic regions controlling this key root trait. Combining gene expression data, re-sequencing and re-annotation of one of these genomic regions identified a glutaredoxin-encoding gene PgGRXC9 as the candidate stress resilience root growth regulator. Functional characterization of its closest Arabidopsis homolog AtROXY19 revealed a novel role for this glutaredoxin (GRX) gene clade in regulating cell elongation. In summary, our study suggests a conserved function for GRX genes in conferring root cell elongation and enhancing resilience of pearl millet to its Sahelian environment.

plant biology↗

bioRxiv2022

Duckweed roots are dispensable and are on a trajectory toward vestigiality

Duckweeds are morphologically simplified, free floating aquatic monocots comprising both rooted and rootless genera. This has led to the idea that roots in these species may be vestigial, but empirical evidence supporting this is lacking. Here we show that duckweed roots are no longer required for their ancestral role of nutrient uptake. Comparative analyses of nearly all rooted duckweed species revealed a highly reduced anatomy, with greater simplification in the more recently diverged genus Lemna. A series of root excision experiments demonstrated that roots are dispensable for normal growth in Spirodela polyrhiza and Lemna minor. Furthermore, ionomic analyses of fronds in these two species showed little difference in the elemental composition of plants in rooted versus root-excised samples. In comparison, another free-floating member of the Araceae, Pistia stratiotes, which colonized the aquatic environment independently of duckweeds, has retained a more complex root anatomy. Whilst Pistia roots were not absolutely required for growth, their removal inhibited plant growth and resulted in a broad change in the mineral profile of aerial tissues. Collectively, these observations suggest that duckweeds and Pistia may be different stages along a trajectory towards root vestigialization Given this, along with the striking diversity of root phenotypes, culminating in total loss in the most derived species, we propose that duckweed roots are a powerful system with which to understand organ loss and vestigiality. One sentence summaryThrough their adaption to the aquatic environment, duckweed roots have progressively become structurally reduced making them an ideal plant model with which to study vestigiality.

evolutionary biology↗

bioRxiv2021

Ex Vivo and In Vivo CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26)

Human adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against SARS-CoV-2 and HIV-1. Yet, its primary receptor portfolio remains controversial, potentially including sialic acid, CAR, integrins, and CD46. We and others have shown that Ad26 can use CD46, but these observations were questioned by the inability to co-crystallize Ad26 fiber with CD46. Recent work demonstrated that Ad26 binds CD46 with its hexon protein rather than its fiber. We examined the functional consequences of Ad26 for infection in vitro and in vivo. Ectopic expression of human CD46 on Chinese hamster ovary cells increased Ad26 infection significantly. Deletion of the complement control protein domains CCP1 or CCP2 or the serine-threonine-proline (STP) region of CD46 reduced infection. Comparing wild type and sialic acid-deficient CHO cells, we show that the usage of CD46 is independent of its sialylation status. Ad26 transduction was increased in CD46 transgenic mice after intramuscular (IM) injection, but not after intranasal (IN) administration. Ad26 transduction was 10-fold lower than Ad5 after intratumoral (IT) injection of CD46-expressing tumors. Ad26 transduction of liver was 1000-fold lower than Ad5 after intravenous (IV) injection. These data demonstrate the use of CD46 by Ad26 under certain situations, but also show that the receptor has little consequence by other routes of administration. Finally, IV injection of high doses of Ad26 into CD46 mice induced release of liver enzymes in the bloodstream and reduced white blood cell counts, but did not induce thrombocytopenia. This suggests that Ad26 virions do not induce direct clotting side effects seen during COVID-19 vaccination with this serotype of adenovirus. IMPORTANCEHuman species D Ad26 is being pursued as a low seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection, and its role in virus biology, vaccine efficacy, and importantly, in vaccine safety.

pharmacology and toxicology↗

bioRxiv2020

Quantifying the acquisition and retention of lumpy skin disease virus by haematophagus insects and the implications for transmission and control.

Lumpy skin disease virus (LSDV), a poxvirus that causes severe disease in cattle, has in the last few years rapidly extended its distribution from Africa and the Middle East into Europe, Russia, and across Asia. LSDV is believed to be primarily spread mechanically by blood-feeding arthropods, however the exact mode of arthropod transmission, the relative ability of different arthropod species to acquire and retain the virus, as well as their comparative importance for LSDV transmission, remain poorly characterised. Since the vector-borne nature of LSDV transmission is believed to have enabled the rapid geographic expansion of this virus, the lack of quantitative evidence on LSDV transmission has impeded effective control of the disease during the current epidemic. Obtaining high quality data on virus transmission by arthropods is challenging, and practical limitations often result in inadequate arthropod numbers or model hosts, limiting the transferability of experimental findings to the natural transmission scenario. We have addressed these limitations in this study. Using a highly representative bovine experimental model of lumpy skin disease we allowed four representative vector species (Aedes aegypti, Culex quinquefasciatus, Stomoxys calcitrans and Culicoides nubeculosus) to blood-feed on LSDV-inoculated cattle in order to examine the acquisition and retention of LSDV by these species in unprecedented detail. We found the probability of LSDV transmission from clinical cattle to vector correlated with disease severity. Subclinical disease was more common than clinical disease in the inoculated cattle, however the probability of vectors acquiring LSDV from subclinical animals was very low. All four potential vector species studied had a similar rate of acquisition of LSDV after feeding on the host, but Aedes aegypti and Stomoxys calcitrans retained the virus for a longer time, up to 8 days. There was no evidence of virus replication in the vector, consistent with mechanical rather than biological transmission. The parameters obtained in the in-vivo transmission experiments subsequently enabled enhanced modelling approaches to determine the basic reproduction number of LSDV in cattle mediated by each of the insect species. This was highest for Stomoxys calcitrans (19.1), C. nubeculosus (7.4), and Ae. aegypti (2.4), surprisingly indicating these three species are all potentially efficient transmitters of LSDV. These results reveal that currently applied LSDV control measures such as stamping out of all cattle on affected premises or insect control measures targeting single species need to be urgently reconsidered. Overall our studies have highlighted that the combination of highly relevant in-vivo experiments and mathematical modelling can be directly applied to devise evidence-based proportionate and targeted control programmes.

microbiology↗

bioRxiv2017

The complement system supports normal postnatal development and gonadal function in both sexes

Male and female infertility are clinically managed and classified as distinct diseases, and relatively little is known about mechanisms of gonadal function common to both sexes. We used genome-wide genetic analysis on 74,896 women and men to find rare genetic variants that modulate gonadal function in both sexes. This uncovered an association with variants disrupting CSMD1, a complement regulatory protein located on 8p23, in a genomic region with an exceptional evolution. We found that Csmd1 knockout mice display a diverse array of gonadal defects in both sexes, and in females, impaired mammary gland development that leads to increased offspring mortality. The complement pathway is significantly disrupted in Csmd1 mice, and further disruption of the complement pathway from joint inactivation of C3 leads to more extreme reproductive defects. Our results can explain a novel human genetic association with infertility and implicate the complement system in the normal development of postnatal tissues.

developmental biology↗