bioRxiv Science⌕ Search

Biology subjects

D'Andrea, M.

Publications and source records attributed to D'Andrea, M..

4 recordsLinked to original sources

Vegetation and fires under climate change: a Mediterranean modelled case study from central Italy

Wildfire regimes in Mediterranean landscapes are undergoing significant changes due to the combined effects of land-use transitions and climate change. In particular, land abandonment increased fuel availability, the expansion of the wildland-urban interface increased ignition frequency, while climate change increases the chances of fire-weather conditions and reduces vegetation recovery capacity. This study presents a modelling framework to investigate the coupled dynamics of fire and vegetation under different fire regimes scenarios, using a case study in central Italy (Monte Pisano). The approach integrates two cellular automata models for vegetation dynamics (Batllori et al., 2017) and for fire-spread (PROPAGATOR; Trucchia et al., 2020). The vegetation model represents succession among six functional classes, including grasslands, shrubs, and trees with different fire-response strategies (seeders and resprouters), while explicitly accounting for post-fire recovery processes. The model was calibrated for the area using historical fire perimeters and vegetation maps over 40 years. Fire spread is simulated probabilistically using PROPAGATOR, driven by fuel types, topography, and weather conditions. A stochastic coupling was implemented by sampling fuel classes from vegetation composition, and by feeding simulated burned areas back into the vegetation model, thus enabling dynamic fire-vegetation feedback. Future wildfire scenarios are constructed by linking ignition probability to fire-weather conditions derived from historical reanalysis data (1981-2023). Extreme fire events are defined based on thresholds of wind speed and fuel moisture, and their probability of occurrence is varied across scenarios to represent increasing climate-driven risk. Simulations are performed over a 100-year horizon starting from current vegetation conditions. Results show that, in the absence of fire, vegetation dynamics lead to dominance of late-successional, fire-resilient species (resprouters). This is particularly evident for low probabilities of extreme fire events, with fire impacts diminishing over time as landscapes become less flammable. However, increasing the frequency of extreme fire conditions resulted in persistent disturbance, maintaining higher proportions of shrubs and early successional vegetation, and sustaining elevated burned areas over time. Overall, the study shows that coupling fire spread and vegetation dynamics provides a useful framework for exploring long-term ecosystem trajectories under climate change. The results highlight the critical role of extreme fire events in shaping landscape resilience and suggest that future management strategies should account for fire-vegetation feedbacks to support more stable and less fire-prone ecosystems.

ecology↗

Differential chromatin accessibility between pre- and post-natal stages highlights putative causal regulatory variants in pig skeletal muscle

Deciphering how chromatin dynamics shape the effects of regulatory variants on complex traits across development remains largely unexplored in farmed animals. Focusing on porcine skeletal muscle, we integrated chromatin accessibility (ATAC-seq), molecular QTL (molQTL), and GWAS data to identify putative stage-specific regulatory variants influencing agronomically important traits. We aggregated and analyzed 202 ATAC-seq libraries spanning prenatal (fetal) and postnatal (piglet) stages. We intersected consensus and differential peaks with cis-molQTLs from the Porcine Genotype-by-Tissue-by-Expression Atlas (PigGTEx) followed by functional enrichment analysis, promoter-focused functional annotation, integration with gene-trait pairs, and intersection with eGenes (i.e., genes whose expression is regulated by at least one cis-eQTL) to link variants previously associated with QTLs for production traits. We identified 132,275 differentially accessible peaks (DAPs) distinguishing fetal and piglet muscle. Fetal DAPs were enriched in promoter and intergenic regions, whereas piglet DAPs were enriched in intronic regions, indicating a shift from transcriptional priming to postnatal regulatory refinement. Overlaps between accessible regions and molQTLs were highly significant (p < 0.001), with the strongest eQTLs predominating in the fetal stage (14 fetal vs. 4 piglet). Gene Ontology analysis of promoter-accessible eGenes revealed enrichment for RNA metabolism and chromatin organization in fetuses, and for muscle contraction and lipid metabolism in piglets. The intersection with colocalized complex traits loci identified 107 fetal- and 30 piglet-stage regulatory elements, with only three eGenes shared between stages. These findings provide insights into developmental chromatin dynamics in skeletal muscle and an effective framework for prioritising putative regulatory variants affecting pig traits at prenatal stages.

genomics↗

Ribosomal protein L5 (RPL5/uL18) I60V mutation is associated to increased translation and modulates drug sensitivity in T-cell acute lymphoblastic leukemia cells

Somatic mutations in ribosomal proteins (RPs), including RPL5, have been reported in approximately 10% of pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL). In cancer, the incorporation of mutant RPs into ribosomes often disrupts canonical ribosome function, thereby contributing to disease development. In this study, we aimed to characterize the effects of the RPL5-I60V mutation in the context of T-ALL, focusing on its impact on translation and cellular responses to a panel of compounds in vitro. Using CRISPR-Cas9, we generated a homozygous knock-in mutant in Jurkat cells and investigated its effects on ribosome biogenesis. We observed both quantitative and qualitative alterations in the production of the large ribosomal subunit. Ribosomes containing the mutant RPL5 protein exhibited intrinsically increased protein synthesis activity, which correlated with enhanced cellular proliferation. We then evaluated the response of these mutant cells to a panel of compounds targeting protein synthesis at various levels--including an MNK1 inhibitor, metformin, silvestrol, homoharringtonine, anisomycin, resveratrol, and hygromycin B--as well as cytarabine, a chemotherapeutic agent commonly used in T-ALL treatment. Our results showed that the RPL5-I60V mutation confers increased sensitivity to most of these compounds, with the exception of hygromycin B. This study advances our understanding of how oncoribosomes contribute to cancer pathogenesis and highlights the therapeutic potential of directly or indirectly targeting altered ribosomes, offering insights for the development of personalized treatment strategies. HighlightsO_LIRPL5 mutations have been reported in T-ALL C_LIO_LIRibosomes containing the RPL5 I60V mutation exhibit increased translational activity C_LIO_LIIncreased proliferation is observed in cells harboring the RPL5-I60V mutation C_LIO_LIRPL5-I60V confers a specific drug sensitivity profile C_LI Statements and DeclarationsCompeting interests: The authors declare that they have no conflict of interest.

cancer biology↗

Outcome of radial scar/complex sclerosing lesion associated with epithelial proliferations with atypia diagnosed on breast core biopsy - Results from a multicentric UK based study

AIMS: The clinical significance of radial scar/complex sclerosing lesion (RS/CSL) with high risk lesions (epithelial atypia) diagnosed on needle core biopsy (NCB) is not well defined. We aimed at assessing the upgrade rate to carcinoma in-situ (DCIS) and invasive on the surgical excision specimen in a large cohort of RS/CSL associated with atypia. METHODS: 161 women with NCB diagnosis of a RS/CSL with atypia and follow-up histology were studied. Histological findings including different forms of the atypical lesions and final histological outcome in the excision specimens were retrieved and analysed and the upgrade rate for malignancy and invasive carcinoma calculated. RESULTS: 76% of the cases were associated with an atypical ductal hyperplasia (ADH) whereas lobular neoplasia was seen in 24%. On final histology 38 cases were malignant (overall upgrade rate of 25%); 12 invasive and 27 DCIS. The upgrade differed according to the type of atypia and was highest for ADH (35%). When associated with lobular neoplasia the upgrade rate was 12%. The upgrade rates variability was also considerably lower and showing less variability when considering the upgrade to invasive carcinoma alone. CONCLUSION: The upgrade rate for ADH diagnosed on NCB with RS is similar to that of ADH without RS and therefore should be managed similarly. RS associated with LN is less frequently associated with malignant outcome. Most lesions exhibiting some degree of atypia showed similar upgrade rate to invasive carcinoma. Management of RS should be based on the concurrent atypical lesion.

pathology↗