Biology subjects

Garcia-Fernandez, J.

Publications and source records attributed to Garcia-Fernandez, J..

5 recordsLinked to original sources

bioRxiv2026

Coronavirus circulation and cross-species transmission in European bats: a new paradigm in betacoronaviruses

Bats are major reservoir hosts of coronaviruses (CoVs), yet the ecological mechanisms governing CoV circulation and cross-species transmission remain poorly understood, particularly in Europe. Here, we investigated the diversity, host associations, and interspecific transmission dynamics of alpha- and betacoronaviruses in European bats using an integrated phylogenetic and network-based approach. We analysed 835 guano samples collected from 31 bat roosts in Catalonia and the Balearic Islands (Spain) between 2020 and 2024, encompassing 14 bat species from three families. CoV RNA was detected in 18.9% of samples, with five alphacoronavirus and two betacoronavirus subgenera identified. Virus-host networks were highly structured and non-random, with strong modularity and specialization, and a small subset of bat species occupying central connector roles. Notably, we report the first confirmed detection of sarbecoviruses in Miniopterus schreibersii, expanding their known host range beyond Rhinolophidae, and identify merbecoviruses in Rhinolophus euryale for the first time. Phylogenetic and seasonal patterns suggest that these associations reflect ecologically mediated cross-species transmission facilitated by mixed roosting, synchronized colony phenology, and spatial overlap. Our findings reveal greater permeability of coronavirus host boundaries than previously assumed and highlight multi-species bat colonies and ecological networks as key contexts for understanding and anticipating viral emergence.

ecology↗

bioRxiv2025

Mechanistic Insights into Sphingomyelin Nanoemulsions as Drug Delivery Systems for Non-Small Cell Lung Cancer Therapy

Sphingomyelin Nanoemulsions (SNs) are promising drug delivery systems with potential for treating challenging tumors, including Non-Small Cell Lung Cancer (NSCLC), which has poor prognosis and a 5-year survival rate below 5%. Understanding the toxicity mechanisms and intracellular behavior of SNs is crucial for optimizing their therapeutic application. This study aims to investigate the interaction between SNs and A549 lung adenocarcinoma cells, focusing on their cytotoxic effects and mechanisms of cellular toxicity. SNs were synthesized and characterized for size, surface charge, and stability. A549 cells were treated with varying concentrations of SNs, and cellular uptake pathways were assessed using inhibitors of energy-dependent processes. Cytotoxicity was evaluated through an MTT assay to determine the IC50 value after 24 hours. Mechanisms of toxicity, including lysosomal and mitochondrial involvement, were examined using co-localization studies, mitochondrial membrane potential assays, and markers of apoptosis. SNs exhibited rapid cellular uptake via energy-dependent pathways. The IC50 concentration for A549 cells was 0.89 {+/-} 0.15 mg/mL, suggesting favorable cytocompatibility compared to other nanocarriers. At IC50, SNs induced apoptosis characterized by lysosomal damage, mitochondrial membrane permeabilization, and release of apoptotic factors. These effects disrupted autophagic flux and contributed to cell death, demonstrating potential for overcoming drug resistance. Resveratrol-loaded SNs showed enhanced cytotoxicity, supporting their application as targeted drug delivery vehicles. This study highlights the potential of SNs as efficient drug delivery systems for NSCLC therapy, offering insights into their cellular interactions and toxicity mechanisms. These findings pave the way for the rational design of SN-based therapeutic platforms for cancer and other mitochondria-related diseases.

pharmacology and toxicology↗

bioRxiv2023

Exploring functional conservation in silico: a new machine learning approach to RNA-editing

Around 50 years from now, molecular biology opened the path to understand changes in forms, adaptations, complexity, or the basis of human diseases, through myriads of reports on gene birth, gene duplication, gene expression regulation, and splicing regulation, among other relevant mechanisms behind gene function. Here, with the advent of big data and artificial intelligence (AI), we focus on an elusive and intriguing mechanism of gene function regulation, RNA editing, in which a single nucleotide from an RNA molecule is changed with a remarkable impact in the increase of the complexity of transcriptome and proteome. We present a new generation approach to assess the functional conservation of the RNA-editing targeting mechanism using two AI learning algorithms, random forest (RF) and bidirectional long short-term memory (biLSTM) neural networks with attention layer. These algorithms combined with RNA-editing data coming from databases and variant calling from same-individual RNA and DNA-seq experiments from different species, allowed us to predict RNA-editing events using both primary sequence and secondary structure. Then, we devised a method for assessing conservation or divergence in the molecular mechanisms of editing completely in silico: the cross-training analysis. This novel method not only helps to understand the conservation of the editing mechanism through evolution but could set the basis for understanding how it is involved in several human diseases.

genetics↗

bioRxiv2021

Cardiopharyngeal deconstruction and ancestral tunicate sessility

A key problem in understanding chordate evolution has been the origin of sessility of ascidians, and whether the appendicularian free-living style represents a primitive or derived condition of tunicates. To address this problem, we performed comprehensive developmental and genomic comparative analyses of the cardiopharyngeal gene regulatory network (GRN) between appendicularians and ascidians. Our results reveal that the cardiopharyngeal GRN has suffered a process of evolutionary deconstruction with massive ancestral losses of genes (Mesp, Ets1/2, Gata4/5/6, Mek1/2, Tbx1/10, and RA- and FGF-signaling related genes) and subfunctions (e.g. FoxF, Islet, Ebf, Mrf, Dach and Bmp signaling). These losses have led to the deconstruction of two modules of the cardiopharyngeal GRN that in ascidians are related to early and late multipotent state cells involved in lineage fate determination towards first and secondary heart fields, and siphon muscle. Our results allow us to propose an evolutionary scenario, in which the evolutionary deconstruction of the cardiopharyngeal GRN has had an adaptive impact on the acceleration of the developmental cardiac program, the redesign of the cardiac architecture into an open-wide laminar structure, and the loss of pharyngeal muscle. Our findings, therefore, provide evidence supporting that the ancestral tunicate had a sessile ascidian-like lifestyle, and points to the deconstruction of the cardiopharyngeal GRN in appendicularians as a key event that facilitated the evolution of their pelagic free-living style connected to the innovation of the house.

evolutionary biology↗

bioRxiv2020

Analysis of Fox genes in Schmidtea mediterranea reveals new families and a conserved role of Smed-foxO in controlling cell death.

The forkhead box (Fox) genes encode transcription factors that control several key aspects of development. Present in the ancestor of all eukaryotes, Fox genes underwent several duplications followed by loss and diversification events that gave rise to the current 25 families. However, few Fox members have been identified from the Lophotrochozoa clade, and specifically from planarians, which are a unique model for understanding development, due to the striking plasticity of the adult. The aim of this study was to identify and perform evolutionary and functional studies of the Fox genes of lophotrochozoan species and, specifically, of the planarian Schmidtea mediterranea. Generating a pipeline for identifying Forkhead domains and using phylogenetics allowed us the phylogenetic reconstruction of Fox genes. We corrected the annotation for misannotated genes and uncover a new family, the QD, present in all metazoans. According to the new phylogeny, the 27 Fox genes found in Schmidtea mediterranea were classified into 12 families. In Platyhelminthes, family losses were accompanied by extensive gene diversification and the appearance of specific families, the A(P) and N(P). Among the newly identified planarian Fox genes, we found a single copy of foxO, which shows an evolutionary conserved role in controlling cell death. Author summaryTranscription factors are the key elements that regulate gene expression in the nucleus. The forkhead box (Fox) transcription factors are one of the most numerous and they control key aspects of development. Fox genes were already present in the ancestor of all eukaryotes, and then underwent several duplications followed by loss and diversification events that gave rise to the current Fox families in the different species. The available data classifies Fox genes in 25 families, but they include few members corresponding to Lophotrocozoa, one of the two invertebrate phyla that includes annelids, molluscs or platyhelmintes. In this study we identify and perform evolutionary studies of the Fox genes of several lophotrochozoan species and, specifically, of the planarian Schmidtea mediterranea. The result is the correction of the annotation of Fox genes from many species, proposing a new nomenclature, and the identification of new families; the QD family, present in all metazoans, and the A(P) and N(P) families, specific of Platyhelminthes. We also study the function of Schmidtea mediterranea foxO, a gene involved in aging and cancer in other species, showing its evolutionary conserved role in controlling cell death according to cell metabolism.

developmental biology↗