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Biology subjects

Price, C. A.

Publications and source records attributed to Price, C. A..

6 recordsLinked to original sources

Bifidobacterium pseudocatenulatum extracellular vesicles promote Ly6G+ granulocyte infiltration to inhibit melanoma tumour progression

Harnessing the immunomodulatory capacity of commensal bacteria is an emerging avenue in cancer therapy. Bacterial extracellular vesicles (BEVs) provide a non-replicating, nanoscale alternative to live microbes with the potential for safer systemic delivery. Here, we investigated BEVs from a novel Gram-positive strain of Bifidobacterium pseudocatenulatum (Bif-210). Intravenous administration of Bif-210 BEVs reduced B16-F10 melanoma growth in C57BL/6J mice. Mechanistically, BEVs increased tumour-infiltrating Ly6G+ granulocytes in vivo, increased CD11b+Ly6G+ and ICAM-1+Ly6G+ bone marrow populations, and induced production of the neutrophil-attracting chemokines KC/CXCL1 (mouse) and IL-8 (human). Although Ly6G+ depletion independently inhibited tumour growth, it did not combine additively with BEVs, supporting a model in which Bif-210 BEVs alter Ly6G+ granulocyte function rather than simply expanding a conventional pro-tumour granulocyte pool. BEVs activated TLR2, did not activate TLR4, and upregulated TLR2 on Ly6G+ cells, while proxy assays provided no evidence of NETosis-associated activation. Repeated intravenous BEV administration produced no overt toxicity by tissue histology, body temperature, or body weight monitoring. These findings position B. pseudocatenulatum BEVs as a promising systemic immunotherapy that recruits and re-educates granulocytes via a TLR2-centred pathway to restrain melanoma progression. HIGHLIGHTSO_LIIntravenous Bif-210 BEVs reduce established B16-F10 melanoma growth in mice. C_LIO_LIBif-210 BEVs selectively increase tumour-associated Ly6G+ granulocytes. C_LIO_LIBEV treatment and Ly6G depletion are non-additive, linking BEV activity to granulocyte biology. C_LIO_LIBif-210 BEVs expand Ly6G+ bone marrow populations and induce granulocyte-recruiting chemokines. C_LIO_LIBif-210 BEVs engage TLR2 and enhance granulocyte fitness without NETosis-associated activation. C_LI

cancer biology↗

Laser scanning identifies large trees as a major source of uncertainty in mangrove carbon accounting

BackgroundMangrove forests are crucial ecosystems which support biodiversity, protect coastlines and store vast amounts of carbon. Mangrove conservation and protection rely on accurate carbon accounting to unlock investment. However, the allometric equations underpinning these carbon estimates remain poorly constrained, particularly for the large trees. MethodsWe used terrestrial laser scanning (TLS) to estimate the biomass of 187 mangrove stems across Suriname, Panama, Colombia and Jamaica, including 84 stems >20 cm DBH. TLS-derived biomass estimates were used to evaluate local, regional and pantropical allometric equations. ResultsMost diameter-based allometric equations underestimated biomass by 8-65%. Equations additionally incorporating tree height performed better, but still underestimated biomass by 12-16% on average. Applying alternative allometries to a representative mangrove inventory from Panama produced biomass estimates ranging from 80 to 200 Mg ha-{superscript 1}, demonstrating that allometric uncertainty alone can generate more than a two-fold difference in estimated carbon stocks. ConclusionsCurrent allometric equations systematically underestimate the biomass of large mangrove trees and are therefore likely to underestimate mangrove carbon stocks. TLS provides a practical, non-destructive approach for expanding biomass datasets and improving allometric equations. Reducing allometric uncertainty should be a priority for strengthening blue carbon accounting and mangrove conservation.

ecology↗

Bifidobacterium pseudocatenulatum capsular exopolysaccharide enhances systemic anti-tumour immunity in pre-clinical breast cancer

Gut microbes have merged as powerful regulators of cancer responses, with Bifidobacterium species and strains playing a key role in promoting anti-tumour immunity. While they represent promising candidates for cancer therapeutics, the specific underlying microbial mechanisms driving their efficacy remains poorly understood. In this study, we demonstrate the broad potential of Bifidobacterium species to inhibit breast cancer progression across multiple pre-clinical mouse models. We identify a novel strain, Bifidobacterium pseudocatenulatum 210, which induces systemic anti-tumour immunity and enhances responses to standard-of-care therapies via its cell surface capsular exopolysaccharide (EPS). B. pseudocatenulatum 210 EPS promotes dendritic cell activation and increases systemic cDC1 infiltration, leading to robust CD8+ T cell-mediated anti-tumour activity. Our findings position Bifidobacterium EPS as a novel class of therapeutic compounds with significant potential for cancer treatment.

cancer biology↗

Flow similarity model predicts the allometry and allometric covariation of petiole dimensions

Allometric relationships for plants, plant organs and plant parts, have long generated interest among biologists. Several prominent theoretical models based on biomechanical and/or hydraulic arguments, have been introduced with mixed support. Here I test a more recent offering, flow similarity, which is based on the conservation of volumetric flow rate and velocity. Using dimensional data for 935 petioles from 43 angiosperm species, I show that both the intraspecific and interspecific petiole allometries are more closely aligned with the predictions of the flow similarity model than that of elastic or geometric similarity. Further, allometric covariation among empirical scaling exponents falls along predicted functions with clustering around the flow similarity predictions. This work adds to the body of literature highlighting the importance of hydraulics in understanding the physiological basis of plant allometries, identifies previously unknown central tendencies in petiole allometry, and helps to delineate the scope within which the flow similarity model may be applicable.

developmental biology↗

Endothelial neuropilin-1 and neuropilin-2 are essential for tumour angiogenesis

Neuropilin (NRP) expression is highly correlated with poor outcome in multiple cancer subtypes. As known co-receptors for vascular endothelial growth factor receptors (VEGFRs), core drivers of angiogenesis, past investigations have alluded to their functional roles in facilitating tumorigenesis by promoting invasive vessel growth. Despite this, it remains unclear as to whether NRP1 and NRP2 act in a synergistic manner to enhance pathological angiogenesis. Here we demonstrate, using NRP1ECKO, NRP2ECKO and NRP1/NRP2ECKO mouse models, that maximum inhibition of primary tumour development and angiogenesis is only achieved when both endothelial NRP1 and NRP2 are targeted simultaneously. Metastasis and secondary site angiogenesis were also significantly inhibited in NRP1/NRP2ECKO animals. Mechanistic studies revealed that co-depleting NRP1 and NRP2 in mouse-microvascular endothelial cells (ECs) stimulates rapid shuttling of VEGFR-2 to Rab7+ endosomes for proteosomal degradation. Our results highlight the importance of targeting both NRP1 and NRP2 to modulate tumour angiogenesis.

cancer biology↗

Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumour growth via a mast cell-dependent pathway

The diverse community of commensal microbes that comprise the gut microbiota is known to play an integral role in human health, not least through its ability to regulate host immune responses and metabolic pathways. Alterations to the homeostasis of this community, including through the use of broad-spectrum antibiotics, have already been associated with the progression of several cancers, namely melanoma and liver. The aggressive nature of breast cancer (BrCa), largely due to its ability to metastasize early, has ranked the disease with the second highest mortality rate of all cancers globally. Yet the body of research into the complex relationship between the microbiota and BrCa is still limited. This study found that a depletion of the microbiota, through the administration of antibiotics, significantly increased the rate of primary tumour progression in mouse BrCa models. We show that antibiotic-induced microbiota disturbances lead to changes in behaviour of a relatively obscure tumour-immune cell population: mast cells. We observed increases in tumour stroma-associated mast cells in antibiotic treated animals. Moreover, inhibition of mast cell degranulation, via cromolyn, slowed tumour progression in antibiotic treated animals but not in control animals. Thus, it appears that a perturbed microbiota drives stroma-associated mast cell recruitment and activation, which in turn promotes primary tumour growth through an as yet unknown mechanism. One Sentence Summary: We show that breast cancer progression is accelerated through a unique/novel immune response involving mast cells as a result of an antibiotic induced perturbation of the gut microbiota in a mouse model.

cancer biology↗