Biology subjects

Payo-Payo, A.

Publications and source records attributed to Payo-Payo, A..

3 recordsLinked to original sources

bioRxiv2025

CB2R-induced differentiation epigenetically restrains cancer plasticity enabling adaptive therapy

Cellular plasticity enables cancer cells to escape therapy by adopting stem-like or alternate lineage states. Here, we identify a mechanism by which cannabinoid receptor 2 (CB2R) activation promotes irreversible lineage commitment in breast cancer. Using patient-derived and murine organoids, we show that brief, low-dose exposure to CB2R agonists--either phytogenic or synthetic--induces a basal-to-luminal transition, accompanied by reduced self-renewal, invasiveness, and tumor-initiating potential. These changes are retained under conditions that normally promote dedifferentiation, including fibroblast co-culture, immune pressure, and mechanical shear stress. Mechanistically, CB2R engagement initiates a transient chromatin remodeling program, marked by early expression of pluripotency-associated genes followed by silencing and differentiation commitment. This epigenetically stabilized state renders tumor cells more responsive to tamoxifen and limits the emergence of resistant clones. Our findings uncover a previously unrecognized role for CB2R in modulating cancer cell identity and suggest new opportunities to constrain tumor plasticity by directing differentiation through a drug-responsive pathway.

cancer biology↗

bioRxiv2023

Eco-evolutionary dynamics of partially migratory metapopulations in spatially and seasonally varying environments

Predicting population responses to environmental changes requires understanding interactions among environmentally induced phenotypic variation, selection, demography and genetic variation, and thereby predicting eco-evolutionary dynamics emerging across diverse temporal and spatial scales. Partially migratory metapopulations (PMMPs), featuring seasonal coexistence of resident and migrant individuals across multiple spatially distinct subpopulations, have clear potential for complex spatio-seasonal eco-evolutionary dynamics through impacts of selection on migration on spatial population dynamics, and feedbacks resulting from ongoing micro-evolution. However, the key genetic and environmental conditions that maintain migratory polymorphisms, and eco-evolutionary dynamics of PMMPs under stochastic environmental variation and strong seasonal perturbations, have not yet been resolved. Accordingly, we present a general individual-based model that tracks eco-evolutionary dynamics in PMMPs inhabiting spatially structured, seasonally varying landscapes, with migration formulated as a quantitative genetic threshold trait. Our simulations show that such genetic and landscape structures, which commonly occur in nature, can readily produce a variety of stable partially migratory systems given diverse regimes of spatio-seasonal environmental variation. Typically, partial migration is maintained whenever sites differ in non-breeding season suitability resulting from variation in density-dependence, causing ideal free non-breeding distributions where residents and migrants occur with frequencies that generate similar survival probabilities. Yet, stable partial migration can also arise without any fixed differences in non-breeding season density-dependence among sites, and even without density-dependence at all, through risk-spreading given sufficiently large stochastic environmental fluctuations among sites and years. Finally, we show that local non-breeding season mortality events, as could result from extreme climatic events, can generate eco-evolutionary dynamics that ripple out to affect breeding and non-breeding season space use of subpopulations throughout the PMMP, on both short and longer timeframes. Such effects result from spatially divergent selection on both the occurrence and destinations of migration. Our model thus shows how facultative seasonal migration can act as a key mediator of eco-evolutionary dynamics in spatially and seasonally structured environments, providing key steps towards predicting responses of natural partially migratory populations to ongoing changes in spatio-seasonal patterns of environmental variation.

evolutionary biology↗

bioRxiv2023

Evaluating diversionary feeding as a method to resolve conservation conflicts in a recovering ecosystem

1. The recovery of mammalian predators of conservation concern in Europe is a success story, but their impact on some prey species of conservation concern may cause conservation dilemmas. This calls for effective intervention strategies that mitigate predator impacts without compromising their recovery. 2. We evaluated diversionary feeding as a management intervention tool to reduce depredation on nests of rapidly declining Western capercaillies in Scotland. We studied the influence of diversionary feeding provision on the fates of artificial nests deployed using a replicated and representative randomised landscape-scale experiment. This comprised 30 paired control (no diversionary feeding) and treatment (diversionary feeding applied) sites, 60 in total, each containing six artificial nests distributed across 600 km2. The experiment was replicated over two years, and in the second year, the control-treatment pairs were reversed, yielding 60 treatment and 60 control sites and 720 artificial nests. 3. Diversionary feeding substantially reduced depredation of artificial nests, translating into an 83% increase in predicted nest survival over 28 days of incubation. The increase in survival was mostly accounted for by a reduction in the probability that a pine marten, the main nest predator, consumed or cached eggs. Diversionary food also significantly reduced nest predation by badgers, although the magnitude of this effect varied by year. 4. Diversionary feeding is an easily employable method shown in this study to reduce predator impact (functional) without lethal (numerical) intervention. Managers should proceed with its application for conserving capercaillie in Scotland without delay.

ecology↗