Biology subjects

Jones, C. M.

Publications and source records attributed to Jones, C. M..

At least 19 recordsLinked to original sources

bioRxiv2026

The scaffold nucleoporin Nup188 undergoes liquid-liquid phase separation

Components of nuclear pore complexes are broadly classified into two categories: intrinsically disordered FG-repeat nucleoporins such as Nup98, which can undergo liquid-liquid phase separation, and scaffold nucleoporins, which form the NPC's structural framework. The basis for crosstalk of these nucleoporins within NPC and beyond is poorly understood. Here we show that human Nup188, a helical inner-ring scaffold protein, forms condensates both in purified form as well as at endogenous level. This condensate exhibits fusion, dissolved in 1,6-hexanediol and recovered after photobleaching, with dynamics and material properties comparable to those of hNup98 condensates. Moreover, these condensates are not colocalized to annulate lamellae. Our analysis also revealed that hNup188CTD is sufficient to form condensates and MD simulations revealed the key roles of IDR1-3 for condensation. Notably, hNup93 expression along with hNup188 suppressed the condensate formation. Together, these findings indicate that a structured scaffold nucleoporin can adopt a condensate-forming state via its CTD and Nup93 binding can suppress this phenomenon.

biochemistry↗

bioRxiv2026

Unconventional presentation of an immunodominant HLA-DR15-restricted nephritogenic proteinase 3 epitope implicated in vasculitis

Proteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is associated with HLA-DR15, implicating HLA-DR15-restricted CD4 T cell autoimmunity in the disease. However, the PR3 epitopes presented by HLA-DR15 and the autoreactive CD4 T cell responses they elicit are undefined. Using humanized hPR3.DR15+ mice, we identified PR3216-231 as an immunodominant human PR3-derived CD4 T cell epitope presented by HLA-DR15. Immunopeptidomic profiling confirmed the natural processing and HLA-DR15-restricted presentation of PR3216-231. Structural analyses of HLA-DR15-PR3216-231 complexes revealed an unconventional mode of HLA class II antigen presentation, in which a 10 amino acid peptide core occupies the 9 amino acid binding groove, causing a central kink in the bound peptide. PR3216-231-specific CD4 T cells from both hPR3.DR15+ mice and patients with PR3-ANCA-associated vasculitis exhibited convergent T cell receptor features, and patients with active vasculitis displayed a clonally expanded, PR3216-231-specific CD4 TCR repertoire. Immunization of hPR3.DR15 mice with PR3216-231 induced cell-mediated glomerulonephritis characterized by increased renal infiltration of CD4 T cells and macrophages together with segmental glomerular necrosis. These findings identify a nephritogenic PR3-derived CD4 T cell epitope presented by HLA-DR15 in ANCA-associated vasculitis and define a new extended core binding pattern, broadening our understanding of HLA class II peptide presentation.

immunology↗

bioRxiv2026

Assessing the additional effects of piperonyl butoxide (PBO) exposure on Anopheles mosquitoes

Insecticide treated nets (ITNs) remain one the frontline tool in malaria control in Africa. The synergist piperonyl butoxide (PBO) has been incorporated into ITNs to combat pyrethroid resistance and these pyrethroid-PBO ITNs are now in widespread use across Africa. PBO is known to inhibit the degradation of pyrethroids and other insecticide classes, but little is known about other biological or behavioural effects of PBO exposure. This work assessed the impact of PBO on Anopheles gambiae s.l. male longevity as well as female host-seeking and blood feeding behaviours using laboratory assays. PBO had an immediate impact on blood feeding of female An. gambiae s.l. whereas the effect was not observed 24h post-exposure. Kaplan-Meier survival curves showed a significant difference in mosquito longevity post-exposure to PBO with male mosquitoes living nearly three times as long if exposed to control papers compared to PBO. In olfactometer assays, after exposure to control papers, control mosquitoes were significantly more attracted to host-odours, however, this attraction preference was reversed following PBO exposure. This study shows that in experimental assays, PBO has other effects on mosquito physiology and this is likely to contribute to the impact of pyrethroid - PBO ITNs in vector control programmes.

ecology↗

bioRxiv2026

Polyclonal and single clonal patient-derived organoid models of Barrett oesophagus and oesophageal adenocarcinoma establish a platform for the analysis of heterogeneity in disease progression and therapy response

SUMMARY/ABSTRACTOesophageal adenocarcinoma (OAC) is a major cause of morbidity and mortality. OAC and its precursor, Barrett oesophagus (BO), are defined by substantial early heterogeneity, complicating prevention and treatment of OAC and remaining poorly recapitulated by current in vitro and animal model systems. We have generated 116 patient- and healthy donor-derived organoids (PDOs) spanning normal oesophagogastric tissue, BO and OAC. These PDOs capture population diversity and recapitulate phenotypic, genomic and transcriptomic features of their respective disease stages. We develop a single cell-derived clonal organoid approach and show that this enables us to capture the heterogeneity and isolate high-risk, subclonal populations that are difficult to discern and maintain in bulk PDO cultures. Using this platform, we demonstrate functional importance of this biobank across the pre-malignant to invasive disease spectrum, including a role for BO in shaping fibroblast phenotype within assembloids, and diverse responses of OAC to chemotherapy, radiotherapy and targeted CDK4/6 inhibition. HIGHLIGHTSO_LIPatient- and healthy donor-derived organoids (PDOs) provide a functional platform of disease progression and heterogeneity across normal gastric, non-dysplastic and dysplastic Barrett oesophagus (BO) and oesophageal adenocarcinoma (OAC). C_LIO_LIWe provide a quantitative phenotypic and molecular framework to assess the provenance and fidelity of each PDO model given the heterogeneity of this disease. C_LIO_LIPDOs recapitulate key features of non-dysplastic and dysplastic BO, as well as invasive OAC. C_LIO_LISingle cell-derived clonal organoids (sc-organoids) isolate and maintain high-risk subclonal populations. C_LIO_LIOAC PDOs mirror known population level variation in response to systemic anti-cancer therapies. C_LI

cancer biology↗

bioRxiv2025

A nuclease-driven mechanism of post-replicative ssDNA gap suppression.

During replication stress, failure to resolve post-replicative ssDNA gaps generated by PRIMPOL-mediated replication repriming is linked with chemosensitivity, and in all models reported to date the nuclease MRE11 has been implicated as a gap-promoting factor. We have dissected ssDNA gap dynamics following nucleoside analogue-mediated nascent strand termination and report a novel mechanism via which loss of the MRE11 negative regulator MRN-Interacting Protein (MRNIP) leads to MRE11 exonuclease-dependent suppression of post-replicative ssDNA gaps. This process is driven by UBC13 and the B-family TLS polymerase REV3L, suggesting that in the absence of MRNIP, dysregulated MRE11 activity at chain termination sites licenses gap filling via template switching. In the absence of PRIMPOL-dependent repriming, MRNIP loss leads to paradoxical SMARCAL1, MRE11 and primosome-dependent ssDNA gaps, suggesting that nucleolytic digestion of reversed forks generates DNA intermediates that platform primase redundancy in the context of chain termination. We also highlight novel site-specific roles for the anti-resection factor 53BP1 in enabling primase redundancy via suppression of the nuclease EXO1, and in limiting the EXO1-dependent processing of post-replicative ssDNA gaps. Finally, we demonstrate that CDK-dependent MRNIP phosphorylation is required for MRNIP functionality in the regulation of ssDNA gaps and sensitivity to chain terminators. This work represents the first report of nuclease-driven post-replicative gap filling, illuminates an additional level of versatility in the replication stress response, and expands our understanding of the context-dependent links between nuclease regulation and chemoresistance.

cancer biology↗

bioRxiv2025

Best practices and challenges for urban tree detection, classification, and geolocation with street-level images across North American cities

Accurate, up-to-date catalogs of urban tree populations are crucial for quantifying ecosystem services and enhancing the quality of life in cities. However, mapping tree species cost-effectively remains challenging. In response, remote sensing researchers are developing general-purpose tools to survey plant populations across broad spatial scales. In this study, we developed computer vision models to detect, classify, and map 100 tree genera across 23 cities in North America using Google Street View (GSV) and iNaturalist images. We validated our predictions in independent portions of each city. We then compared our predictions to existing street tree records to evaluate the spatial context of errors using generalized linear mixed-effects models. Our computer vision models identified most ground-truthed street trees (67.1%). Performance varied across the 23 cities (67.4% {+/-} 9.3%) and 100 genera (50.9% {+/-} 23.0%) and improved denser street-view coverage, simpler stand structure, and greater training representation, particularly from the focal city. We found that genus classification performed better in continental cities with lower relative diversity, and that seasonal changes in the appearance of trees provided visual cues that moderate classification rates. Using widely available street-level imagery is a generalizable and promising avenue for mapping tree distributions across urban environments.

ecology↗

bioRxiv2025

Mechanics regulate the postembryonic developmental maturation and function of sensory neurons in a pre-vertebrate chordate.

Physical forces are emerging as important contributors to a wide diversity of biological processes across multiple scales and contexts. The development of the nervous system is infuenced by mechanical forces exerted on neurons and glia by the surrounding environment. However, the extent to which tissue mechanics influence the function and morphology of the post-embryonic nervous system remains unclear. Here we leverage the post-embryonic larval period of the pre-vertebrate chordate Ciona intestinalis to study the dynamic interplay between nervous system mechanics, cellular and nuclear morphology and neuronal function. During this post-embryonic period the larval head undergoes substantial stretching along the anterior-posterior axis. We show that this macroscopic morphological change is associated with a significant change in cell and nuclear shape (stretching) of the polymodal sensory neurons located in the papillar organs. Using FRET based genetically encoded tension sensors we show that mechanical tension at the focal adhesions and the nuclear envelope of these papillar sensory neurons increases with time. At the functional level Ca2+ imaging experiments reveal that presentation and removal of a chemosensory stimulus that promotes settlement and metamorphosis elicits significantly stronger responses in late swimming larvae papillar neurons compared to those newly hatched ones. Finally, by combining optoGEF-RhoA dependent control of cellular forces and Ca2+ imaging we demonstrate that the strength of chemosensory responses and settlement behavior can be modulated by mechanical forces.

developmental biology↗

bioRxiv2025

IFI16 senses and protects stalled replication forks

Replication stress is a key driver of DNA damage and genome instability. Replication stress-induced fork remodelling generates a new DNA end that is vulnerable to the action of nucleases, and which is protected by a range of factors including the canonical tumour suppressors BRCA1 and BRCA2. Here we report that replication stress drives elevated production of cytokines and chemokines in the absence of DNA damage. The DNA sensor IFI16 binds nascent DNA at stalled replication forks and signals via the DNA sensing adaptor STING, to induce the activation of NF-{kappa}B and the production of pro-inflammatory cytokines in response to replication stress. IFI16 also acts directly at stalled replication forks to protect nascent DNA from degradation by the nucleases MRE11 and DNA2. Furthermore, IFI16 is required for the interferon-mediated rescue of fork protection in BRCA-deficient cells, highlighting the critical role of IFI16 in the cross-talk between innate immunity and fork protection during replication stress. HighlightsO_LIReplication stress induces an early innate immune response, which is dependent on the DNA sensing factors IFI16 and STING, but not cGAS C_LIO_LIIFI16 binds directly to nascent DNA at stalled replication forks C_LIO_LIIFI16 prevents nucleolytic degradation of reversed forks C_LIO_LIIFI16 is required for interferon-mediated fork protection in BRCA-deficient cells C_LI

cancer biology↗

bioRxiv2025

FlickerPrint: An Analysis Package for Measuring Interfacial Tension and Bending Rigidity of Biomolecular Condensates and Vesicles at Scale

1 In BriefWilliamson, Law et. al. present FlickerPrint, a computational analysis tool which can be used for measuring the interfacial tension and bending rigidity of soft fluctuating bodies, including biomolecular condensates, droplets or vesicles, from confocal microscopy images using flicker spectroscopy. This method is highly scalable so can be used to analyse the properties of whole populations of thousands of such soft bodies. 2 MotivationBiomolecular condensates play fundamental roles in sub-cellular organisation and it is well-known that the composition of condensates can affect their function. Measuring the conden-sates mechanical properties (for example, interfacial tension and bending rigidity) can aid the understanding of their biomolecular composition and cellular functions. However, measuring the properties of individual condensates under physiological conditions is very challenging and cum-bersome to scale to the population level using traditional methods. To overcome these issues, we have developed a software package to run flicker spectroscopy analysis of condensates at scale, to determine their interfacial tension and bending rigidity. At the same time, FlickerPrint can be harnessed to analyse other soft, fluctuating bodies such as lipid vesicles. 3 SummaryAccurate measurement of the mechanical properties of biomolecular condensates is an essential step in understanding their behaviour within cells. We present FlickerPrint, an open-source Python package to determine the interfacial tension and bending rigidity of thousands of biomolecular condensates using flicker spectroscopy by analysing their shape fluctuations in confocal microscopy images. We detail the workflow used by FlickerPrint to scale up these individual measurements to the population level and the computational requirements to run Flicker-Print. We provide examples of experiments in live cells and in vitro which are suitable for analysis with FlickerPrint as well as scenarios where the package cannot be used. Using these examples, we show that the results obtained from the analysis are robust to changes in the imaging setup, including frame rate. This implementation enables a step-change in the capability to measure two key properties of biomolecular condensates, the interfacial tension and bending rigidity. Moreover, the tools in FlickerPrint are also applicable for analysing other soft, fluctuating bodies, which we demonstrate here using vesicles.

cell biology↗

bioRxiv2025

Distribution of alternative routes for completing denitrification in microbial genomes and metagenomes of global biomes

Diverse microorgani sms can execute one or more steps in denitrification, during which nitrate or nitrite is successively reduced into nitric oxide, nitrous oxide, and ultimately dinitrogen. Many of the best-characterized denitrifiers are "complete" denitrifiers capable of executing all steps in the pathway, but whether they dominate in natural communities and what metabolic traits and environmental factors drive the global distribution of complete vs. partial denitrifiers remains to be determined. To address this, we conducted a comparative analysis of denitrification genes in 61,293 genomes, 3,991 metagenomes covering all major biomes, and 413 terrestrial and aquatic metatranscriptomes. We show that partial denitrifiers outnumber complete denitrifiers and the potential to initiate denitrification is more common than the potential to terminate it, both among genomes and at the community level across most biomes, particularly in nutrient rich environments. These patterns were also reflected in the metatranscriptomes. Our results further indicate that complete denitrifiers are more likely to be fast-growing organisms, favoring organic acid over sugar metabolism, and encoding the ability to oxidize and reduce a broader range of organic and inorganic compounds compared to partial denitrifiers. This suggests complete denitrifiers are metabolically flexible opportunists. Together, our results indicate an environmental footprint on the presence of denitrification genes which favors the genomic potential for partial over complete denitrification in most biomes and highlight that completion of the denitrification pathway is a community effort.

microbiology↗

bioRxiv2024

In situ, High-Resolution Quantification of CO2 Uptake Rates via Automated Off-Gas Analysis Illuminates Carbon Uptake Dynamics in Cyanobacterial Cultures

Quantification of CO2 fixation rates by cyanobacteria is vital to determining their potential as industrial strains in a circular bioeconomy. Currently, however, CO2 fixation rates are most often determined through indirect and/or low-resolution methods, resulting in an incomplete picture of both dynamic behaviors and total carbon fixing potential. To address this, we developed a novel, low-cost system for in situ off-gas analysis which supports the automated acquisition of high-resolution and CO2 uptake rates from cyanobacterial cultures. Carbon fixation data obtained via this system was independently verified by elemental analysis of cultivated biomass. Using Synechococcus sp. PCC 7002 and Synechocystis sp. PCC 6803, we demonstrate that phototrophic CO2 uptake rates accelerate linearly to a maximum before then decaying monotonically to cessation by stationary phase. Furthermore, consistent with the expected stoichiometry, we found that strong correlations exist between both the rates and total levels of cell growth and carbon fixation. This system simultaneously provides a high-resolution growth curve, accurate carbon fixation rates, as well as the total amount of carbon fixed in a cyanobacterial batch culture, thus illuminating the parameters with which cyanobacterial researchers can exploit use to realize their full potential in industrial applications.

microbiology↗

bioRxiv2024

Affinity purification mass spectrometry characterization of the interactome of receptor tyrosine kinase proline rich motifs in cancer

Receptor tyrosine kinase (RTK) overexpression is linked to the development and progression of multiple cancers. RTKs are classically considered to initiate cytoplasmic signalling pathways via ligand-induced tyrosine phosphorylation, however recent evidence points to a second tier of signalling contingent on interactions mediated by the proline-rich motif (PRM) regions of non-activated RTKs. The presence of PRMs on the C-termini of >40% of all RTKs and the abundance of PRM-binding proteins encoded by the human genome suggests that there is likely to be a large number of previously unexplored interactions which add to the RTK intracellular interactome. Here, we explore the RTK PRM interactome and its potential significance using affinity purification mass spectrometry and in silico enrichment analyses. Peptides comprising PRM-containing C-terminal tail regions of EGFR, FGFR2 and HER2 were used as bait to affinity purify bound proteins from different cancer cell line lysates. 490 unique interactors were identified, amongst which proteins with metabolic, homeostatic and migratory functions were overrepresented. This suggests that PRMs from RTKs may sustain a diverse interactome in cancer cells. Since RTK overexpression is common in cancer RTK PRM-derived signalling may be an important, but as yet underexplored, contributor to negative cancer outcomes including resistance to kinase inhibitors.

cell biology↗

bioRxiv2024

MYC is sufficient to generate mid-life high-grade serous ovarian and uterine serous carcinomas in a p53-R270H mouse model

Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment is understood. However, previous GEMMs of high-grade serous ovarian cancer (HGSOC) have had to utilize genetics rarely or never found in human HGSOC to yield ovarian cancer within the lifespan of a mouse. MYC, an oncogene, is amongst the most amplified genes in HGSOC, but it has not previously been utilized to drive HGSOC GEMMs. We coupled Myc and dominant negative mutant p53-R270H with a fallopian tube epithelium-specific promoter Ovgp1 to generate a new GEMM of HGSOC. Female mice developed lethal cancer at an average of 15.1 months. Histopathological examination of mice revealed HGSOC characteristics including nuclear p53 and nuclear MYC in clusters of cells within the fallopian tube epithelium and ovarian surface epithelium. Unexpectedly, nuclear p53 and MYC clustered cell expression was also identified in the uterine luminal epithelium, possibly from intraepithelial metastasis from the fallopian tube epithelium (FTE). Extracted tumor cells exhibited strong loss of heterozygosity at the p53 locus, leaving the mutant allele. Copy number alterations in these cancer cells were prevalent, disrupting a large fraction of genes. Transcriptome profiles most closely matched human HGSOC and serous endometrial cancer. Taken together, these results demonstrate the Myc and Trp53-R270H transgene was able to recapitulate many phenotypic hallmarks of HGSOC through the utilization of strictly human-mimetic genetic hallmarks of HGSOC. This new mouse model enables further exploration of ovarian cancer pathogenesis, particularly in the 50% of HGSOC which lack homology directed repair mutations. Histological and transcriptomic findings are consistent with the hypothesis that uterine serous cancer may originate from the fallopian tube epithelium.

cancer biology↗

bioRxiv2023

Small dams drive Anopheles abundance during the dry season in a high malaria burden area of Malawi

This study explores the influence of small dams on the exposure to malaria vectors during the dry season in Kasungu district, Malawi, an area recently identified as high priority for malaria interventions by the National Malaria Control Programme. Small dam impoundments provide communities with a continuous supply of water for domestic and agricultural activities across sub-Saharan Africa and are considered vital to food security and climate change resilience. However, these permanent water bodies also create ideal breeding sites for mosquitoes in typically arid landscapes. The study focuses on a specific dam impoundment and its vicinity, aiming to assess its spatial and temporal influence on indoor vector densities. Throughout May to August 2021, CDC light traps were used to measure indoor mosquito densities for two consecutive nights per month in three communities located at increasing distances from the dam (0km, [~]1km, [~]2km). Simultaneously, drone imagery was captured for each community, enabling the identification of additional standing water within approximately 400 meters of selected households. Larval sampling was carried out within the impoundment periphery and in additional water bodies identified in the drone imagery. Generalised linear mixed models (GLMMs) were employed to analyse the indoor Anopheles abundance data, estimating the effects of household structure (open/closed eaves), month, temperature, and water proximity on malaria vector exposure. Throughout 685 trapping nights, a total of 1,256 mosquitoes were captured, with 33% (412) being female Anopheles. Among these, 91% were morphologically identified as An. funestus s.l., and 5% as An. gambiae s.l. Catches progressively declines in each consecutive trapping month as the environment became drier. This decline was much slower in Malangano, the community next to the dam, with abundance being notably higher in June and July. Further, the majority of An. gambiae s.l. were caught in May, with none identified in July and August. Anopheles larvae were found both in the impoundment and other smaller water bodies such as irrigation wells in each survey month, however the presence of these smaller water bodies did not have a significant impact on adult female mosquito catches in the GLMM. The study concludes that proximity to the dam impoundment was the primary driver of differences between survey communities with the abundance in Chikhombwe ([~]1km away) and Chiponde ([~]2km away) being 0.35 (95% CI 0.19-0.66) and 0.28 (95% CI 0.16-0.47) lower than Malangano respectively after adjusting for other factors. These findings underscore the importance of targeted interventions, such as larval source management or housing improvements, near small dams to mitigate malaria transmission risks during the dry season. Further research is needed to develop cost-effective strategies for vector control within and around these impoundments.

ecology↗

bioRxiv2023

Predicting genomic traits in ammonia-oxidizing archaea using phylogenetic signals

Phylogenetic conservatism of microbial traits has paved the way for phylogeny-based predictions, allowing us to move from descriptive to predictive functional microbial ecology. Here, we applied phylogenetic eigenvector mapping, an approach not previously used for microorganisms, to predict key traits of ammonia-oxidizing archaea (AOA), which are important players in nitrogen cycling. Using 168 nearly complete AOA genomes and metagenome assembled genomes from public databases, we predicted the distribution of 18 ecologically relevant genes across an updated amoA gene phylogeny, including a novel variant of an ammonia transporter found in this study. Of the selected genes, 94% displayed a significant phylogenetic signal and gene presence was predicted with >88% accuracy, >88% sensitivity, and >80% specificity. The phylogenetic eigenvector approach performed equally well as ancestral state reconstruction of traits. We implemented the predictive models on an amoA sequencing dataset of AOA soil communities and show key ecological predictions, e.g., that AOA communities in nitrogen rich soils have capacity for ureolytic metabolism while those adapted to low pH soils have the high affinity ammonia transporter (amt2). Predicting genomic traits can shed light on the potential functions that microbes perform across earth biomes, further contributing to a better mechanistic understanding of their community assembly.

ecology↗

bioRxiv2023

Phyloecology of nrfA-ammonifiers and their relative importance with denitrifiers in global terrestrial biomes

Nitrate ammonification is important for soil nitrogen retention. However, the ecology of nitrate ammonifiers and their prevalence compared with denitrifiers, being competitors for nitrate, are overlooked. Here, we screened more than 1 million genomes for nrfA, encoding the nitrite reductase in nitrate ammonification. Nearly 50% of the nitrate ammonifier assemblies carry at least one denitrification gene and, contrary to the current paradigm, have higher potential for nitrous oxide production than reduction. We then used a phylogeny-based approach to recruit nrfA and denitrification nitrite reductase gene fragments in 1,861 metagenomes covering the major terrestrial biomes. Denitrification genes dominated, except in tundra, and random forest modelling teased apart the influence of the soil C/N on nitrate ammonifier vs denitrifier abundances, showing an effect of nitrate rather than carbon content. This study demonstrates the multiple roles nitrate ammonifiers play in nitrogen cycling and the factors ultimately controlling the fate of nitrate in soil.

microbiology↗

bioRxiv2022

Distribution and environmental drivers of fungal denitrifiers in global soils

The microbial process denitrification is the primary source of the greenhouse gas nitrous oxide (N2O) from terrestrial ecosystems. Fungal denitrifiers, unlike many bacteria, lack the N2O reductase and are potential sources of N2O. Still, their diversity, distribution, and environmental determinants in terrestrial ecosystems remain unresolved. We used a phylogenetically informed approach to screen 1 980 soil and rhizosphere metagenomes representing 608 globally distributed sampling sites for the denitrification marker gene nirK, coding for nitrite reductase. We show that fungal denitrifiers are sparse, yet cosmopolitan and dominated by saprotrophs and opportunistic plant pathogens. Few showed biome-specific distribution patterns. However, members of the Fusarium oxysporum species complex, known to produce substantial amounts of N2O, were proportionally more abundant and diverse in the rhizosphere than in other biomes. Fungal denitrifiers were most frequently detected in croplands but were most abundant in forest soils. The overall low abundance of fungal relative to bacterial and archaeal denitrifiers suggests that their role in denitrification and contribution to soil N2O emissions may be less important than previously suggested. Nevertheless, in relative terms, they could play a role in soils characterized by high carbon to nitrogen ratio and low pH, especially in tundra and boreal and temperate coniferous forests. Our results further indicate that plant-pathogen interactions may favor fungal denitrifiers. Thus, increasing global warming with predicted proliferation of pathogens and the fact that many of the fungi with nirK detected in the metagenomes are stress-tolerant cosmopolitans suggest that fungal denitrifier abundance may increase in terrestrial ecosystems.

microbiology↗

bioRxiv2022

TCR_Explore: a novel webtool for T cell receptor repertoire analysis

T cells expressing either alpha-beta or gamma-delta T cell receptors (TCR) are critical sentinels of the adaptive immune system, with receptor diversity being essential for protective immunity against a broad array of pathogens and agents. Programs available to profile TCR clonotypic signatures can be limiting for users with no coding expertise. Current analytical pipelines can be inefficient due to manual processing steps, open to data transcription errors and have multiple analytical tools with unique inputs that require coding expertise. Here we present a bespoke webtool designed for users irrespective of coding expertise, coined TCR_Explore, incorporating automated quality control steps that generates a single output file for creation of flexible and publication ready figures. TCR_Explore will elevate a users capacity to undertake in-depth TCR repertoire analysis of both new and pre-existing datasets for identification of T cell clonotypes associated with health and disease. The web application is located at https://tcr-explore.erc.monash.edu for users to interactively explore TCR repertoire datasets. Key PointsO_LIBespoke program for non-specialists in computerised methodologies for deep exploration of TCR repertoire analysis C_LIO_LIAutomated QC and analysis pipelines for Sanger based TCR sequencing coupled with immunophenotyping, with the capacity for integration of other sequencing platform outputs C_LIO_LIAutomated summary processes to aid data visualisation and generation of publication-ready graphical displays C_LI

bioinformatics↗