Biology subjects

Nieto, A.

Publications and source records attributed to Nieto, A..

4 recordsLinked to original sources

bioRxiv2025

Performance of Sequential Markovian Coalescence Methods when Populations are Structured

Sequentially Markovian Coalescent (SMC) methods are widely used to reconstruct demographic histories from genomic data, yet their accuracy in the presence of population structure has not been systematically evaluated. Here we assessed the performance of two popular SMC based algorithms (PSMC and SMC++) in retrieving the inverse instantaneous coalescent rate (IICR) simulated under two structured equilibrium scenarios, namely the finite island (FIM) and the two-dimensional stepping-stone (2D-SST). Looking backward in time, the IICR of a couple of lineages collected in a deme is characterized by a short period of constant value (the scattering phase) followed by an increase over time (the transition phase) up to a plateau (the collecting phase). Both algorithms recovered the IICR at the collecting phase but significantly deviated from the values expected during the transition phase under specific parameters combination. Specifically, the total error increased with the number of demes and the abruptness of the transition phase, which in turn is related to the extent of between demes connectivity. Moreover, each algorithm displayed a specific bias, corresponding backward in time to an artificial expansion either at the beginning of the collecting phase (PSMC) or of the transition phase (SMC++). Our results demonstrate that the observed systematic biases carry information about metapopulation dynamics, rather than being simple artefacts. Moreover, combining the results obtained from the two algorithms will increase our understanding of the historical demography of the metapopulations and help to put forward specific evolutionary scenarios to be tested with model-based algorithms using SFS or LD statistics.

evolutionary biology↗

bioRxiv2024

A probabilistic view of forbidden links: their prevalence and their consequences for the robustness of mutualistic networks

The presence in ecological communities of unfeasible species interactions, termed forbidden links, due to physiological or morphological exploitation barriers has been long debated, but little direct evidence has been found. Forbidden links are likely to make ecological communities less robust to species extinctions, stressing the need to assess their prevalence. Here, we used a dataset of plant-hummingbird interactions, coupled with a Bayesian hierarchical model, to assess the importance of exploitation barriers in determining species interactions. We found evidence for exploitation barriers between flowers and hummingbirds across the 32 studied communities, however, the proportion of forbidden links changed drastically among communities, because of changes in trait distributions. The higher the proportion of forbidden links, the more they decreased network robustness, because of constraints on interaction rewiring. Our results suggest that exploitation barriers are not rare in plant-hummingbird communities and have the potential to limit the rescue of species experiencing partner extinction.

ecology↗

bioRxiv2022

Microenvironmental Snail1 is a driver of immunosuppression in melanoma

Melanoma is an aggressive form of skin cancer due to its high metastatic abilities and resistance to therapies. Melanoma cells reside in a heterogeneous tumour microenvironment that acts as a crucial regulator of its progression. Snail1 is an epithelial-to-mesenchymal transition transcription factor expressed during development and reactivated in pathological situations including fibrosis and cancer. In this work, we show that Snail1 is activated in the melanoma microenvironment, particularly in fibroblasts. Analysis of murine models that allow stromal Snail1 depletion and therapeutic Snail1 blockade indicate that targeting Snail1 activation in the tumour microenvironment decreases melanoma growth and lung metastatic burden, extending mice survival. Transcriptomic analysis of melanoma-associated fibroblasts and analysis of the tumours indicate that stromal Snail1 induces melanoma growth by promoting an immunosuppressive microenvironment and pro-tumour immunity. This study unveils a novel role of Snail1 in melanoma biology and supports its potential as a therapeutic target.

cancer biology↗

bioRxiv2022

Pro-tumor and prothrombotic activities of hepsin in colorectal cancer cells and suppression by venetoclax

Hepsin is a type II transmembrane serine protease whose expression has been linked to greater tumorigenicity and worse prognosis in different tumors such as prostate and gastric cancer. Recently, our group described hepsin expression in the primary biopsy as a potential biomarker of thrombosis and metastasis in localized colorectal cancer patients. Here we explored the role of hepsin in this tumor. Hepsin overexpression increased Caco-2 cell migration and invasion, higher phosphorylation of Erk1/2 and STAT3 and led to more thrombin generation in plasma. Indeed, our study revealed higher plasma levels of hepsin in metastatic colorectal cancer patients, which was associated with a greater tendency toward thrombosis. By virtual screening of a FDA-approved drug library, we identified venetoclax as a potent hepsin inhibitor, reducing the metastatic and prothrombotic phenotype of Caco-2 cells, but not of other colorectal cancer cells without hepsin expression. Interestingly, pre-treating Caco-2 cells overexpressing hepsin with venetoclax reduced its in vivo invasiveness. Taken together, our results demonstrate that elevated hepsin levels correlate with a more aggressive and prothrombotic tumor phenotype. Likewise, they evidence an antitumor role for venetoclax as a hepsin inhibitor. This lays the groundwork for molecular targeted therapy for colorectal cancer.

cancer biology↗