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Biology subjects

Keen, N.

Publications and source records attributed to Keen, N..

2 recordsLinked to original sources

Independent colonisations of serpentine habitats highlight species-specific evolutionary histories of lineage diversification

Serpentine soils are characterized by high levels of heavy metals, low nutrient availability, and water scarcity, presenting significant ecological challenges for plant species. Nonetheless, some species have adapted successfully to these conditions. We investigate the population genomic structure, evolutionary history and phenotypic differentiation of three diploid generalist plant species, Lavandula stoechas L., Halimium atriplicifolium (Lam) Spach. subsp. atriplicifolium, and Phlomis purpurea L., all of which inhabit adjacent serpentine and non-serpentine soils in the Malaga region in the southern Iberian Peninsula (Spain). We explore whether populations from serpentine and non-serpentine soils represent distinct evolutionary lineages and whether there is genomic and phenotypic differentiation associated with serpentine conditions. We measured plant height and specific leaf area (SLA) to detect potential ecotypic variation associated with soil type. A ddRADseq SNP dataset was generated for each species, representing 10 populations from serpentine and 10 from non-serpentine soils. We ordinated genotype data to assess genomic variation, conducted an ADMIXTURE analysis to infer ancestral groups, and used Treemix analyses to investigate phylogenetic relationships and gene flow events between populations. Isolation by distance (IBD) analyses evaluated the role of geographic separation in observed genomic differentiation. Our results reveal species-specific patterns of genomic, and to some extent phenotypic, differentiation between serpentine and non-serpentine populations, with evidence of multiple colonisations of serpentine sites in all three species. The study highlights the role of historical differentiation and subsequent gene flow in shaping the genomic structure of plant populations, alongside observed variation in phenotypic traits across environments.

evolutionary biology↗

Conditional activation of NK cell function using chemically synthetic constrained bicyclic peptides directed against NKp46 and tumor-expressed antigens

Natural killer (NK) cells have the unique potential to recognize and kill tumor cells independently of MHC-I presentation of antigens, as well as to secrete cytokines that engage adaptive anti-tumor immunity and the function of cytolytic T cells. We have discovered and characterized chemically synthetic, constrained bicyclic peptides that bind with high affinity and specificity to NKp46, an activating receptor expressed selectively on NK cells in the tumor microenvironment. Chemical coupling to other bicyclic peptides specific for the tumor antigens EphA2 or MT-1 created NKp46 agonists whose function was completely conditional on binding to the tumor antigen. These chemical conjugates effectively convert the tumor antigen into a "kill me" signal for NK cells. Not only did these newly created tumor-immune cell agonists (TICAs) direct potent and efficient killing of human tumor cells by primary human NK cells in vitro, but they also caused secretion of the pro-inflammatory cytokines TNF and IFN{gamma}. Importantly, the TICAs directed production of FLT3 ligand, an essential mitogen for conventional dendritic cells which are central to the development of anti-tumor immunity in cancer. We illustrate the TICA-directed interaction of NK cells with tumor cells using confocal microscopy and we show that TICAs enable sustained function over multiple rounds of killing. These novel tools are well positioned to harness the potential of NK cells in the treatment of cancer.

cancer biology↗