Biology subjects

Price, C.

Publications and source records attributed to Price, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Evidence for fungivory in Proctotydaeus furnarius, a brood mite of the Australian stingless bee Tetragonula carbonaria

Mites are common but poorly understood associates of stingless bee nests. The brood mite Proctotydaeus furnarius inhabits brood cells of Tetragonula carbonaria and was hypothesised to feed on fungi. We tested this hypothesis using electron microscopy, ITS amplicon sequencing, dye-based feeding trials, and brood-cell culturing. The unarmed, needle-like stylets of P. furnarius resembled those of fungivorous mites. In feeding trials, P. furnarius consumed a yeast isolate (Zygosaccharomyces sp.) cultured from brood cells, although also consumed crushed bee pupae. Mite presence did not detectably alter the culturable brood-cell microbial community. These findings suggest that P. furnarius feeds on fungi inside host nests but could shift its diet to feed on host brood according to resource availability.

ecology↗

bioRxiv2026

Gluconate acts as a signal to induce biofilm in Bacillus subtilis

Bacillus subtilis is the best-studied Gram-positive microorganism, but little is known about how the presence and utilization of diverse carbon sources impacts its production of biofilm. Here, we have identified gluconate as a carbon source that induces biofilm wrinkling in B. subtilis colony biofilms. Targeted phenotypic analysis revealed that the genes encoding the canonical structural biofilm components (tasA, epsA-O, and bslA) are required for this response. Import and metabolism of gluconate, however, are not required to induce these phenotypic changes. We show that the effect of gluconate on B. subtilis is linked to iron availability: production of the siderophore bacillibactin is decreased by gluconate and B. subtilis mutants unable to import bacillibactin grow better and wrinkle more in the presence of gluconate. In addition, supplementation of single-carbon media with iron dramatically increased growth and wrinkling of a B. subtilis bacillibactin mutant grown on gluconate but did not impact B. subtilis grown on glucose. We conclude that gluconate acts as a signal to increase biofilm in B. subtilis and increases iron availability in a bacillibactin-independent manner.

microbiology↗

bioRxiv2026

Systemically delivered Bacteroides thetaiotaomicron-derived bacterial extracellular vesicles inhibit primary and metastatic melanoma growth

The gut microbiome can contribute to anti-tumour immunity and cancer therapy responses, but translating live microbe-based interventions remains challenging due to safety, controllability, and delivery constraints. Bacterial extracellular vesicles (BEVs) are an attractive cell-free alternative, as they package bacterial cargo into a nanoscale format capable of host-cell engagement, immunological activation, and systemic distribution. Here, we investigated the anti-tumour potential of BEVs derived from the human gut commensal Bacteroides thetaiotaomicron (Bt). We show that delivery route is a major determinant of efficacy. Intravenous, but not intraperitoneal, administration produced robust anti-tumour activity in a B16F10 melanoma mouse model. Intravenously delivered Bt BEVs suppressed primary tumour growth in a dose-dependent manner and reduced metastatic outgrowth in the lung. Bt BEVs did not directly impair tumour-cell viability in vitro, but they activated NF-{kappa}B and Toll-like receptor signalling in innate immune reporter systems and localised to tumour tissue following systemic administration. Together, these data support a model in which Bt BEVs act via host immune modulation rather than direct tumour cytotoxicity. These findings identify naturally produced commensal-derived Bt BEVs as a potential microbial therapeutic modality and as an alternative to the use of live bacterial administration in cancer therapy.

cancer biology↗

bioRxiv2025

The Nicotinamide Salvage Pathway is a Metabolic Vulnerability of High-Risk MDS Stem Cells

High-risk myelodysplastic syndrome (HR-MDS) is a malignant clonal disorder originating in hematopoietic stem and progenitor cells (HSPCs). The current standard of care for HR-MDS patients is hypomethylating agents; however, the response rate is poor. There is thus a need to explore vulnerabilities of HR-MDS HSPCs for better clinical outcomes. We demonstrate that HR-MDS HSPCs have significant upregulation of metabolic proteins required for glycolysis, citric acid cycle, and oxidative phosphorylation. Consistently, we see increased oxygen consumption rate in HR-MDS HSPCs compared to healthy, suggesting an increased metabolic rate. Corroboratively, compared to healthy HSPCs, HR-MDS HSPCs have increased abundance of mitochondrial complex I proteins, which are NADH dehydrogenases, and crucial for energy production. Therefore, we investigated whether HR-MDS HSPCs are functionally reliant on NAMPT, the rate-limiting enzyme in the nicotinamide salvage pathway of NAD anabolism. NAMPT inhibition significantly decreased NAD(H) in HR-MDS HSPCs. Consequently, NAMPT inhibition reduced the oxygen-consuming capacity of HR-MDS-HSPCs compared to healthy. Importantly, NAMPT inhibition significantly impaired the self-renewal and colony-forming potential, increased cell death and reduced disease burden specifically of HR-MDS HSPCs, compared to healthy controls. Collectively, our data suggest that NAMPT is selectively required for the function and survival of HR-MDS HSPCs representing a promising therapeutic target.

cancer biology↗

bioRxiv2025

TREM2 macrophages are associated with enhanced response to PD-1 blockade in human hepatocellular carcinoma

Macrophages are known to dampen tumor immunity. However, identifying druggable targets that modulate these cells to improve existing immunotherapies has been limited by a dearth of studies identifying macrophages that associate with pathological response to immune checkpoint blockade. To fulfill this unmet clinical need, we leveraged transcriptional and spatial profiling of specimens collected from a Phase II clinical trial studying neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC). We determined that the intratumoral abundance of TREM2-expressing macrophages and serological levels of soluble TREM2 are elevated in patients who responded to PD-1 blockade, compared to non-responders. We validated these findings in a second HCC cohort and in the IMbrave150 trial. These highlight the robust potential for TREM2 macrophages to predict therapeutic responses of HCC to immunotherapy. Therefore, our study provides a novel basis for the use of TREM2 macrophages to strategize treatment for patients with HCC to maximize therapeutic benefit.

immunology↗

bioRxiv2025

Evaluating tree biomass estimation in trans-Atlantic mangrove species: comparing bole diameter measurements for improved accuracy

Estimating the biomass of terrestrial forests generally, and mangrove forests in particular, is an area of considerable interest. Most approaches rely on empirically derived allometric models to predict tree biomass. The single parameter with the strongest predictive ability in most studies is diameter at breast height (DBH), however the use of DBH arose primarily out of convenience, not from an analysis of tree form. While DBH explains a lot of variability in other tree metrics such as height or above ground biomass, its utility in smaller species is uncertain. Here we used measurements from 302 destructively sampled mangrove trees of four species to test which of three bole diameter measurements, basal stem diameter (BSD), diameter at 30 cm (D30), and DBH, is the best predictor of above ground biomass. D30 had the highest mean coefficient of determination (R2) and lowest mean root mean squared error (RMSE) across all site/species combinations. However, the improvement over DBH was modest, with a mean across all site/species combinations of 1.58 kg RMSE and R2 of 0.948 for D30, compared to 1.63 kg RMSE and R2 of 0.917 for DBH. Nevertheless, D30 may have utility in future studies as it allows for lower size thresholds and has better overall explanatory power than DBH.

plant biology↗

bioRxiv2025

Neuropilin 2 stabilises adherens junctions and protects against endothelial activation by promoting the interaction between VE cadherin and p120 catenin

The mechanosensing properties of endothelial cell-cell junctions are essential for vascular beds to respond to the mechanical forces exerted by blood flow. In states of disturbed flow, endothelial cells (ECs) become activated and transition to a pro-inflammatory, atheroprone phenotype. Here, we investigated the role of transmembrane glycoprotein neuropilin 2 (NRP2) in maintaining adherens junction integrity using cultured immortalised mouse ECs and a genetically modified mouse model to demonstrate the effects of an endothelial-specific deletion of Nrp2 in vivo. We reveal that, akin to its ortholog, Nrp1, Nrp2 exists as a constituent of adherens junctions, maintaining surface availability of VE cadherin by promoting its interaction with p120 catenin. As a consequence, endothelial knockout mice (Nrp2flfl.ECKO) display hyperpermeable retinal vasculature during development. Nrp2 depletion was subsequently found to activate key pro-inflammatory cytokines and adhesion molecules known to participate in the progression of atherogenesis, in addition to increased immune cell attachment aortic plaque development. These findings describe a role for Nrp2 in maintaining junctional signalling in ECs, protecting against endothelial activation during a state of vascular disease.

cell biology↗

bioRxiv2025

Flow similarity model predicts allometric relationships among Acer platanoides branches

Using physical models to predict patterns of plant growth has been a long-standing goal for biologists. Most approaches invoke either biomechanical or hydraulic principles and assume the mechanism of interest applies similarly throughout the plant branching architecture. A recent effort, the flow similarity model, predicts numerous aspects of branching physiology and morphology and argues that the physiological constraints experienced by plants change as a function of branch order and size, with more basal portions satisfying more biomechanical constraints, and more distal portions, hydraulic ones. Distal branches are expected to have a strong influence on allometric relationships within plants due to their numerical abundance. Here we evaluate the predictions of the flow similarity model and a well-known alternative fractal branching model, using data on the dimensions of 3,484 individual stem internodes across four individual Acer platanoides trees. Overall, we find strong agreement between model predictions and the allometric exponents describing tree branch allometry. Further the predicted curvature in allometric relationships is found in all 24 cases examined and the frequency distributions of branch lengths and diameters are consistent with model expectations in 6/8 cases. We also find the area ratios are consistent with the model assumption of area-preserving branching. Collectively, our data and analysis provides strong support for the flow similarity model, and identifies several areas in need of subsequent inquiry.

plant biology↗

bioRxiv2024

Integrating spatial transcriptomics count data with Crescendo improves visualization and detection of spatial gene patterns

Spatial transcriptomics allows for the analysis of a cells gene expression in the context of its physical location. With spatial transcriptomics data, investigators often want to find genes of interest whose spatial patterns are biologically relevant in multiple samples. However, due to confounding factors in spatial data that produce noise across samples, datasets, and technologies, it is challenging to visualize genes and their spatial patterns across samples. We present Crescendo, an integration algorithm that performs correction directly on gene expression counts to reduce variation from technical confounders. We first apply Crescendo to a 3-sample spatial transcriptomics mouse brain dataset to show how Crescendo enables accurate visualization of gene expression across these spatial transcriptomic samples. We then demonstrate Crescendos scalability by integrating a 16-sample immuno-oncology dataset of 7 million cells. Finally, we show that Crescendo can perform cross-technology integration by merging a colorectal cancer (CRC) scRNA-seq dataset with two CRC spatial transcriptomics samples. By transferring information between technologies, Crescendo can impute poorly expressed genes to improve detection of gene-gene colocalization, such as ligand-receptor interactions.

bioinformatics↗

bioRxiv2023

Spatial analysis of human lung cancer reveals organized immune hubs enriched for stem-like CD8 T cells and associated with immunotherapy response

The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially-localized multicellular immunity hubs defined by expression of the T cell-attracting chemokines CXCL10/CXCL11 and abundant T cells. Here, we examined immunity hubs in human pre-immunotherapy lung cancer specimens, and found that they were associated with beneficial responses to PD-1-blockade. Immunity hubs were enriched for many interferon-stimulated genes, T cells in multiple differentiation states, and CXCL9/10/11+ macrophages that preferentially interact with CD8 T cells. Critically, we discovered the stem-immunity hub, a subtype of immunity hub strongly associated with favorable PD-1-blockade outcomes, distinct from mature tertiary lymphoid structures, and enriched for stem-like TCF7+PD-1+ CD8 T cells and activated CCR7+LAMP3+ dendritic cells, as well as chemokines that organize these cells. These results elucidate the spatial organization of the human intratumoral immune response and its relevance to patient immunotherapy outcomes.

immunology↗

bioRxiv2022

Intratumoral mregDC and CXCL13 T helper niches enable local differentiation of CD8 T cells following PD-1 blockade

Here, we leveraged a large neoadjuvant PD-1 blockade trial in patients with hepatocellular carcinoma (HCC) to search for correlates of response to immune checkpoint blockade (ICB) within T cell-rich tumors. We show that ICB response correlated with the clonal expansion of intratumoral CXCL13+ CH25H+ IL-21+ PD-1+ CD4 T helper cells (CXCL13+ Th) and Granzyme K+ PD-1+ effector-like CD8 T cells, whereas terminally exhausted CD39hi TOXhi PD-1hi CD8 T cells dominated in non-responders. Strikingly, most T cell receptor (TCR) clones that expanded post-treatment were found in pre-treatment biopsies. Notably, PD-1+ TCF-1+ progenitor-like CD8 T cells were present in tumors of responders and non-responders and shared clones mainly with effector-like cells in responders or terminally differentiated cells in non-responders, suggesting that local CD8 T cell differentiation occurs upon ICB. We found that these progenitor CD8 T cells interact with CXCL13+ Th cells within cellular triads around dendritic cells enriched in maturation and regulatory molecules, or "mregDC". Receptor-ligand analysis revealed unique interactions within these triads that may promote the differentiation of progenitor CD8 T cells into effector-like cells upon ICB. These results suggest that discrete intratumoral niches that include mregDC and CXCL13+ Th cells control the differentiation of tumor-specific progenitor CD8 T cell clones in patients treated with ICB.

immunology↗

bioRxiv2022

A mixed generative model of auditory word repetition

In this paper, we introduce a word repetition generative model (WORM), which--when combined with an appropriate belief updating scheme--is capable of inferring the word that should be spoken when presented with an auditory cue. Our generative model takes a deep temporal form, combining both discrete and continuous states. This allows a (synthetic) WORM agent to perform categorical inference on continuous acoustic signals, and--based on the same model--to repeat heard words at the appropriate time. From the perspective of word production, the model simulates how high-level beliefs about discrete lexical, prosodic and context attributes give rise to continuous acoustic signals at the sensory level. From the perspective of word recognition, it simulates how continuous acoustic signals are recognised as words and, how (and when) they should be repeated. We establish the face validity of our generative model by simulating a word repetition paradigm in which a synthetic agent or a human subject hears a target word and subsequently reproduces that word. The repeated word should be the target word but differs acoustically. The results of these simulations reveal how the generative model correctly infers what must be repeated, to the extent it can successfully interact with a human subject. This provides a formal process theory of auditory perception and production that can be deployed in health and disease. We conclude with a discussion of how the generative model could be scaled-up to include a larger phonetic and phonotactic repertoire, complex higher-level attributes (e.g., semantic, concepts, etc.), and produce more elaborate exchanges.

neuroscience↗

bioRxiv2022

Intestinal Bacteroides Modulates Systemic Inflammation and the Microbial Ecology in a Mouse Model of CF: Evidence for Propionate and other Short Chain Fatty Acids Reducing Systemic Inflammatory Cytokines

Persons with cystic fibrosis, starting in early life, have intestinal microbiome dysbiosis characterized in part by a decreased relative abundance of the genus Bacteroides. Bacteroides is a major producer of the intestinal short chain fatty acid (SCFA) propionate. We demonstrate here that CFTR-/- Caco-2 intestinal epithelial cells are responsive to the anti-inflammatory effects of propionate. Furthermore, Bacteroides isolates inhibit the IL-1{beta}-induced inflammatory response of CFTR-/- Caco-2 intestinal epithelial cells and do so in a propionate-dependent manner. Bacteroides isolates also produce low levels of butyrate; this SCFA is positively correlated with inhibition of the inflammatory response. Finally, the introduction of Bacteroides-supplemented stool from infants with CF into the gut of CftrF508del mice results in an increase in propionate in the stool as well as the reduction in several systemic pro-inflammatory cytokines. Bacteroides supplementation also reduced the fecal relative abundance of E. coli, indicating a potential interaction between these two microbes, consistent with previous clinical studies. Together, our data indicate the important role of Bacteroides and Bacteroides-derived propionate in the context of the developing microbiome in infants and children with CF, which could help explain the observed gut-lung axis in CF.

microbiology↗

bioRxiv2021

Dynamic Self-Reinforcement of Gene Expression Determines Acquisition and Retention of Cellular Mechanical Memory

Mechanotransduction describes activation of gene expression by changes in the cells physical microenvironment. Recent experiments show that mechanotransduction can lead to long-term "mechanical memory", where cells cultured on stiff substrates for sufficient time (priming phase) maintain altered phenotype after switching to soft substrates (dissipation phase), as compared to unprimed controls. The timescale of memory acquisition and retention is orders of magnitude larger than the timescale of mechanosensitive cellular signaling, and memory retention time changes continuously with priming time. We develop a model that captures these features by accounting for positive reinforcement in mechanical signaling. The sensitivity of reinforcement represents the dynamic transcriptional state of the cell composed of protein lifetimes and 3D chromatin organization. Our model provides a single framework connecting microenvironment mechanical history to cellular outcomes ranging from no memory to terminal differentiation. Predicting cellular memory of environmental changes can help engineer cellular dynamics through changes in culture environments.

systems biology↗

bioRxiv2021

Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection.

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19). It is also unclear which pathways are contributing to complement activation in COVID-19, and, if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability. To address these questions, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers. We compared our patients to two non-COVID cohorts: (a) patients hospitalized with influenza, and (b) patients admitted to the intensive care unit (ICU) with acute respiratory failure requiring invasive mechanical ventilation (IMV). We demonstrate that circulating markers of complement activation (i.e., sC5b-9) are elevated in patients with COVID-19 compared to those with influenza and to patients with non-COVID-19 respiratory failure. Further, the results facilitate distinguishing those who are at higher risk of worse outcomes such as requiring ICU admission, or IMV. Moreover, the results indicate enhanced activation of the alternative complement pathway is most prevalent in patients with severe COVID-19 and is associated with markers of endothelial injury (i.e., Ang2) as well as hypercoagulability (i.e., thrombomodulin and von Willebrand factor). Our findings identify complement activation to be a distinctive feature of COVID-19, and provide specific targets that may be utilized for risk prognostication, drug discovery and personalized clinical trials. SUMMMARYComplement has been implicated in COVID-19. However, whether this is distinctive of COVID-19 remains unanswered. Ma et al report increased complement activation in COVID-19 compared to influenza and non-COVID respiratory failure, and demonstrate alternative pathway activation as a key marker of multiorgan failure and death.

immunology↗

bioRxiv2021

Simulating lesion-dependent functional recovery mechanisms

Functional recovery after brain damage varies widely and depends on many factors, including lesion site and extent. When a neuronal system is damaged, recovery may occur by engaging residual (e.g., perilesional) components. When damage is extensive, recovery depends on the availability of other intact neural structures that can reproduce the same functional output (i.e., degeneracy). A systems response to damage may occur rapidly, require learning or both. Here, we simulate functional recovery from four different types of lesions, using a generative model of word repetition that comprised a default premorbid system and a less used alternative system. The synthetic lesions (i) completely disengaged the premorbid system, leaving the alternative system intact, (ii) partially damaged both premorbid and alternative systems, and (iii) limited the experience-dependent plasticity of both. The results, across 1000 trials, demonstrate that (i) a complete disconnection of the premorbid system naturally invoked the engagement of the other, (ii) incomplete damage to both systems had a much more devastating long-term effect on model performance and (iii) the effect of reducing learning capacity within each system. These findings contribute to formal frameworks for interpreting the effect of different types of lesions.

neuroscience↗

bioRxiv2021

Comparative and Stability Study of Glucose Concentrations Measured in Sodium Fluoride and Serum Separator tubes

IntroductionSodium fluoride/potassium oxalate (NaF/KOx) tubes were once regarded as the gold-standard tubes for glucose analysis. Even though their ineffectiveness in immediately inhibiting glycolysis has been reported in several studies especially in the first 1-4hours, they are still used in our clinical Biochemistry laboratory for glucose measurement. However in its absence, only SSTs are employed for glucose measurement. AimTo determine whether SSTs can replace NaF/KOx tubes for laboratory-based measurement of blood glucose and to assess the stability of glucose concentrations for 3 days period MethodsDuring the study period (1 March to 11 April, 2015), a total of 50 paired samples collected separately in NaF/KOx tubes and SSTs from healthy adult participants in the Gambia Adults Reference Intervals Study (GARIS) project were used as the project sample size. The samples were analysed within 2hours, and at 24hours, 42hours and 72hours time-points following blood collection and separation using Vitros 350 dry chemistry analyser. The GARIS samples were treated as clinical samples. ResultsThere was no significant difference in the mean glucose concentrations between the two tubes (Mean difference= 0.06mmol/L; P=0.38) recorded in the different time-points. Using growth trajectory and mixed effects model, the study data showed no significant change in the glucose concentrations (p=0.25) for three days period. ConclusionsThe study confirms that SSTs can produce similar glucose results when employed in the absence of NaF/KOx tubes. Besides, the glucose concentrations were stable in both tubes for three days when the samples were separated within two hours and refrigerated in 2-8{degrees}C.

biochemistry↗

bioRxiv2019

Generation and Trapping of a Mesoderm Biased State of Human Pluripotency

We postulate that exit from pluripotency involves intermediates that retain pluripotency while simultaneously exhibiting lineage-bias. Using a MIXL1 reporter, we explored mesoderm lineage-bias within the human pluripotent stem cell compartment. We identified a substate, which at the single cell level coexpresses pluripotent and mesodermal gene expression programs. Functionally these cells could initiate stem cell cultures and exhibited mesodermal bias in differentiation assays. By promoting mesodermal identity through manipulation of WNT signalling while preventing exit from pluripotency using lysophosphatidic acid, we could trap and maintain cells in a lineage-biased stem cell state through multiple passages. These cells correspond to a normal state on the differentiation trajectory, the plasticity of which is evidenced by their reacquisition of an unbiased state upon removal of differentiation cues. The use of cross-antagonistic signalling to trap pluripotent stem cell intermediates with different lineage-bias may have general applicability in the efficient production of cells for regenerative medicine.

cell biology↗