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Paterson, E.

Publications and source records attributed to Paterson, E..

4 recordsLinked to original sources

Soil microenvironment and microbial community composition jointly regulate carbon accrual in agricultural soils

Much of the persistent soil organic carbon (SOC) pool is microbial in origin: microorganisms process plant carbon into biomass and their necromass can associate with mineral surfaces, contributing to long-term carbon persistence. This has generated interest in microbial interventions such as inoculation to restore carbon in degraded croplands, yet their efficacy remains uncertain. The uncertainty reflects a more fundamental, unresolved question: are microbially-mediated carbon transformations governed principally by the composition of the microbial community or by the soil microenvironment? To disentangle these drivers, we conducted a reciprocal microbial community transplant experiment, introducing communities of contrasting origin from locally adjacent grassland and cropland soils into sterilised grassland and cropland soils, and incubating them for eight months with regular organic inputs. This design decouples the inoculum from the microenvironment, allowing their individual and interactive contributions to be quantified. Fungal assembly was influenced more by the inoculum, consistent with dispersal limitation, whereas bacterial assembly was governed more by the microenvironment, consistent with environmental selection. Despite receiving the same organic carbon inputs, grassland and cropland recipient soils showed distinct SOC trajectories, indicating that the soil microenvironment strongly constrained net carbon retention. Within this constraint, community composition also mattered: introducing grassland rather than cropland communities increased fungal diversity and fungal necromass and led to better SOC outcomes, expressed as net gain or reduced loss. These results show that SOC accrual emerges from interactions between the soil microenvironment and microbial community composition, with fungal community assembly particularly associated with necromass accumulation and carbon retention. They highlight the need to consider both soil conditions and microbial community composition when developing strategies to enhance SOC accrual.

ecology↗

Preclinical efficacy and safety of Tegavivint in Wnt-activated hepatocellular carcinoma

Background & AimsHepatocellular carcinoma (HCC), a predominant form of liver cancer, remains a significant clinical unmet need. Given that 30-50% of HCC cases harbour mutations in the Wnt/{beta}-catenin signalling pathway, targeting this cascade represents a promising therapeutic strategy. However, the clinical translation of Wnt inhibitors has been hindered by severe adverse events observed in preclinical models and early-phase clinical trials, primarily due to the essential role of Wnt signalling in maintaining normal tissues such as the intestine and bone. MethodsWe examined the efficacy of Tegavivint, a first-in-class Wnt pathway inhibitor that targets TBL1, against HCC to elucidate its underlying mechanism of action. We evaluated the dose-response of Tegavivint and its effects on the cell cycle, apoptosis, and Wnt target gene expression using HepG2, HUH6, and HUH7 cell lines in vitro. Furthermore, we employed an orthotopic xenograft transplant model using HepG2 cells in immunodeficient mice to assess the safety profile and on-target anti-cancer efficacy of Tegavivint in vivo. ResultsTegavivint exhibited potent Wnt pathway-suppressing effects in cancer cells with constitutive Wnt pathway activation. Notably, Tegavivint displayed robust anti-tumour activity across a broad range of HCC cell lines, regardless of their Wnt pathway activation status. While Tegavivint inhibited the Wnt pathway and triggered the activation of apoptotic pathways in most cell lines, our findings suggest that it also can induce cell death by activating alternative non-apoptotic pathways in apoptosis-resistant cancer cells. In an orthotopic transplant mouse model, Tegavivint significantly downregulated Wnt pathway target genes, inhibited cell proliferation, induced apoptosis and suppressed growth in tumours. ConclusionsTaken together, our data establish a robust foundation for evaluating Tegavivint as a novel therapeutic option, specifically tailored for HCC patients harbouring Wnt-driven hepatic malignancies.

cancer biology↗

A footptrint of plant eco-geographic adaptation on the composition of the barley rhizosphere bacterial microbiota

The microbiota thriving in the rhizosphere, the thin layer of soil surrounding plant roots, plays a critical role in plants adaptation to the environment. Domestication and breeding selection have progressively differentiated the microbiota of modern crops from the ones of their wild ancestors. However, the impact of eco-geographical constraints faced by domesticated plants and crop wild relatives on recruitment and maintenance of the rhizosphere microbiota remains to be fully elucidated. Here we performed a comparative 16S rRNA gene survey of the rhizosphere of 4 domesticated and 20 wild barley (Hordeum vulgare) genotypes grown in an agricultural soil under controlled environmental conditions. We demonstrated the enrichment of individual bacteria mirrored the distinct eco-geographical constraints faced by their host plants. Unexpectedly, Elite varieties exerted a stronger genotype effect on the rhizosphere microbiota when compared with wild barley genotypes adapted to desert environments with a preferential enrichment for members of Actinobacteria. Finally, in wild barley genotypes, we discovered a limited, but significant, correlation between microbiota diversity and host genomic diversity. Our results revealed a footprint of the hosts adaptation to the environment on the assembly of the bacteria thriving at the root-soil interface. In the tested conditions, this recruitment cue layered atop of the distinct evolutionary trajectories of wild and domesticated plants and, at least in part, is encoded by the barley genome. This knowledge will be critical to design experimental approaches aimed at elucidating the recruitment cues of the barley microbiota across a range of soil types.

plant biology↗

Nitrogen Availability Modulates the Host Control of the Barley Rhizosphere Microbiota.

The microbiota populating the rhizosphere, the interface between roots and soil, can modulate plant growth, development and health. These microbial communities are not stochastically assembled from the surrounding soil but their composition and putative function are controlled, at least partially, by the host plant. Here we use the staple cereal barley as a model to gain novel insights into the impact of differential applications of nitrogen, a rate-limiting step for global crop production, on the host genetic control of the rhizosphere microbiota. Using a high-throughput amplicon sequencing survey, we determined that nitrogen availability for plant uptake is a factor promoting the selective enrichment of individual taxa in the rhizosphere of wild and domesticated barley genotypes. Shotgun sequencing and metagenome-assembled genomes revealed that this taxonomic diversification is mirrored by a functional specialisation, manifested by the differential enrichment of multiple GO-terms, of the microbiota of plants exposed to nitrogen conditions limiting barley growth. Finally, a plant soil feedback experiment revealed that the host control on the barley microbiota underpins the assembly of a phylogenetically diverse group of bacteria putatively required to sustain plant performance under nitrogen-limiting supplies. Taken together, our observations indicate that under nitrogen conditions limiting plant growth, plant-microbe and microbe-microbe interactions fine-tune the host genetic selection of the barley microbiota at both taxonomic and functional levels. The disruption of these recruitment cues negatively impacts plant growth. ImportanceThe microbiota inhabiting the rhizosphere, the thin layer of soil surrounding plant roots, can promote the growth, development, and health of their host plants. Previous research indicated that differences in the genetic composition of the host plant coincide with differences in the composition of the rhizosphere microbiota. This is particularly evident when looking at the microbiota associated to input-demanding modern cultivated varieties and their wild relatives, which have evolved under marginal conditions. However, the functional significance of these differences remains to be fully elucidated. We investigated the rhizosphere microbiota of wild and cultivated genotypes of the global crop barley and determined that nutrient conditions limiting plant growth amplify the host control on microbes at the root-soil interface. This is reflected in a plant- and genotype-dependent functional specialisation of the rhizosphere microbiota which appears required for optimal plant growth. These findings provide novel insights into the significance of the rhizosphere microbiota for plant growth and sustainable agriculture

plant biology↗