Biology subjects

Gomez, P.

Publications and source records attributed to Gomez, P..

10 recordsLinked to original sources

bioRxiv2024

The combined effect of viral infection and temperature on the gene response of melon and zucchini plants with different levels of temperature tolerance

Biotic and abiotic environmental factors shape plant responses. As such the interplay between viral infection and heat-stress can trigger specific physiological and metabolic plant responses that lead to gene-specific changes in defense and development. However, although plant gene expression patterns have been thoroughly studied under a single stress, the extent to which the combination of both stressors could modulate common or exclusive signaling pathways remains unclear. In this study, we examined the effects of watermelon mosaic virus infection and diurnal temperature variations (20/14 {degrees}C, 26/20 {degrees}C, and 32/24 {degrees}C) on the gene responses of two plant species (melon and zucchini), each with high- and low-temperature tolerance, using a differential 3mRNA-seq approach. The WMV load was much greater in zucchini than in melon plants, and was also dependent on the temperature conditions and tolerance of each plant species. Our comparative RNA-seq analysis revealed that the percentage of differentially expressed genes (DEGs) was higher in the thermo-susceptible plants of both species under the combination of WMV infection and low temperatures (20 {degrees}C). Among these significantly regulated genes, between 37 % and 45 % were related to biotic and/or abiotic stress. Furthermore, we found that 30 GO terms were involved in the response to both combined stress from low temperatures and 23 GO terms for high temperatures, which were exclusive to the thermotolerant varieties. Together, these findings allowed the identification of two unique orthologous genes linked to temperature and virus infection in melon and zucchini plants. Understanding the effects of biotic and abiotic factors on plant responses is essential for unraveling the complexity of plant-pathogen-environment interactions and developing strategies to enhance plant resilience and productivity under changing climatic conditions.

plant biology↗

bioRxiv2023

Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses

Coxsackievirus B (CVB) infection of pancreatic {beta} cells is associated with {beta}-cell autoimmunity. We investigated how CVB impacts human {beta} cells and anti-CVB T-cell responses. {beta} cells were efficiently infected by CVB in vitro, downregulated HLA Class I and presented few, selected HLA-bound viral peptides. Circulating CD8+ T cells from CVB-seropositive individuals recognized only a fraction of these peptides, and only another sub-fraction was targeted by effector/memory T cells that expressed the exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with the {beta}-cell antigen GAD. Infected {beta} cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Thus, our in-vitro and ex-vivo data highlight limited T-cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8+ T cells recognizing structural and non-structural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.

immunology↗

bioRxiv2022

Neuregulin1 regulates cardiomyocyte dynamics, proliferation, and maturation during ventricular chamber morphogenesis

BACKGROUNDCardiac ventricles are essential for providing the contractile force of the beating heart throughout life. How the primitive endocardium-layered myocardial projections called trabeculae form and mature into the adult ventricles is of great interest for fundamental biology and regenerative medicine. Trabeculation is dependent on the signaling protein Neuregulin-1 (Nrg1). However, the mechanism of action of Nrg1 and its role in ventricular wall maturation are poorly understood. METHODSIn this study we investigated the functions and downstream mechanisms of Nrg1 signaling during ventricular chamber development using confocal imaging, transcriptomics, and biochemical approaches in mice with conditional cardiac-specific inactivation or overexpression of Nrg1. RESULTSAnalysis of cardiac-specific-Nrg1 mutant mice showed that the transcriptional program underlying cardiomyocyte-oriented cell division and trabeculae formation depends on endocardial Nrg1 to myocardial ErbB2 signaling and pErk activation. Early endothelial loss of Nrg1 and below normal pErk activation diminished cardiomyocyte Pard3 and Crumbs2 protein, and altered cytoskeletal gene expression and organization. These changes were associated with aberrant expression of genes involved in mitotic spindle organization and a directional shift from perpendicular to parallel/obliquely-oriented cardiomyocyte division. Further analysis indicated that Nrg1 is required for trabecular growth and ventricular wall thickening by regulating an epithelial-to-mesenchyme transition (EMT)-like process in cardiomyocytes involving migration, adhesion, cytoskeletal actin turnover, and timely progression through the cell cycle G2/M phase. Ectopic cardiac Nrg1 overexpression and high pErk signaling caused S-phase arrest, maintained high EMT-like gene expression and prolonged trabeculation, blocking compact myocardium maturation. Likewise, alterations of myocardial trabecular patterning resulting from above- or below-normal Nrg1-dependent pErk activation were concomitant with disorganization of the sarcomere actin cytoskeleton. The Nrg1 loss- and gain-of-function transcriptomes were enriched for yes-associated protein-1 (Yap1) gene signatures, identifying Yap1 as a potential downstream effector. Biochemical and imaging data showed that pErk activation and nuclear-cytoplasmic distribution of Yap1 during trabeculation are dependent on Nrg1. CONCLUSIONSThese data establish the Nrg1-ErbB2/4-pErk axis as a crucial regulator of cardiomyocyte cell cycle progression and migration during ventricular development. Moreover, our data identify a Nrg1-dependent signaling cascade that could be leveraged for future cardiac regenerative therapies. Novelty and Significance WHAT IS KNOWN?O_LIMyocardial trabeculae play important roles in ventricular chamber growth, development of the conduction system, and formation of the coronary arteries. C_LIO_LITrabeculae are formed through oriented cell division (OCD), and their growth is driven by directional migration. C_LIO_LIThe membrane glycoprotein Neuregulin-1 (Nrg1) mediates cell-cell signaling and is essential for trabecular development. C_LI WHAT NEW INFORMATION DOES THIS ARTICLE CONTRIBUTE?O_LINrg1 signaling is essential for the expression of cardiomyocyte polarity genes and the organization of the cytoskeleton during the oriented cell division process underlying trabeculation. C_LIO_LINrg1 is required for the formation of the inner ventricular wall but not the coronaries. C_LIO_LINrg1 regulates motility and cell-cycle progression during ventricular wall growth. C_LIO_LIEctopic expression of Nrg1 leads to excessive trabeculation of the myocardium and disrupts compaction. C_LIO_LINrg1 regulates ventricular patterning mediated by cytoskeletal dynamics and modulates pErk-dependent Yap1 S274 phosphorylation during trabeculation. C_LIO_LINrg1 is not required for ventricular compaction. C_LI

developmental biology↗

bioRxiv2022

Mutational Analysis and Deep Learning Classification of Uterine and Cervical Cancers

We analyzed tumor mutations of 7 uterine and 2 cervical cancers with the goal of developing a Deep Learning (DL) software tool that can automatically classify tumors based on their somatic mutations. The data were obtained from the AACR Genie Project [1], that has a collection of more than 120,000 tumor samples for more than 750 cancer types. We performed a thorough analysis of the mutational data of tumors of the uterus and uterine cervix, selecting tumors with 3 or more mutations and cancer types with more than 15 cases. For each cancer type we then selected the top 12 most mutated genes among their neoplasms. In the introduction section we summarize our analysis of these nine diseases and in the deep learning section we present a convolutional neural network (CNN) [2] that yields an overall classification accuracy of 94.3% and 89.2% on the train and test datasets, respectively. We hope that this tool can be added to the existing arsenal of histological and immunohistochemical techniques in cases when a precise diagnosis cannot be clearly determined. Each cancer type has a unique somatic mutational profile that can be used to disambiguate two candidate malignancies with similar histologic features.

bioinformatics↗

bioRxiv2021

Exploring the Inner Workings of Neuron Circuits That Exhibit Persistent Activity To Explain How Working Memory and Executive Function Are Implemented in The Brain

In this research we explore in detail how a phenomenon called "sustained persistent activity" is achieved by circuits of interconnected neurons. Persistent activity is a phenomenon that has been extensively studied (Papoutsi et al. 2013; Kaminski et. al. 2017; McCormick et al. 2003; Rahman, and Berger, 2011). Persistent activity consists of neuron circuits whose spiking activity remains even after the initial stimuli are removed. Persistent activity has been found in the prefrontal cortex (PFC) and has been correlated to working memory and decision making (Clayton E. Curtis and Daeyeol Lee, 2010). We go beyond the explanation of how persistent activity happens and show how arrangements of those basic circuits encode and store data and are used to perform more elaborated tasks and computations. The purpose of the model we propose here is to describe the minimum number of neurons and their interconnections required to explain persistent activity and how this phenomenon is actually a fast storage mechanism required for implementing working memory, task processing and decision making.

neuroscience↗

bioRxiv2020

Rethinking glottal midline detection

A healthy voice is crucial for verbal communication and hence in daily as well as professional life. The basis for a healthy voice are the sound producing vocal folds in the larynx. A hallmark of healthy vocal fold oscillation is the symmetric motion of the left and right vocal fold. Clinically, videoendoscopy is applied to assess the symmetry of the oscillation and evaluated subjectively. High-speed videoendoscopy, an emerging method that allows quantification of the vocal fold oscillation, is more commonly employed in research due to the amount of data and the complex, semi-automatic analysis. In this study, we provide a comprehensive evaluation of methods that detect fully automatically the glottal midline. We use a biophysical model to simulate different vocal fold oscillations, extended the openly available BAGLS dataset using manual annotations, utilized both, simulations and annotated endoscopic images, to train deep neural networks at different stages of the analysis workflow, and compared these to established computer vision algorithms. We found that classical computer vision perform well on detecting the glottal midline in glottis segmentation data, but are outper-formed by deep neural networks on this task. We further suggest GlottisNet, a multi-task neural architecture featuring the simultaneous prediction of both, the opening between the vocal folds and the symmetry axis, leading to a huge step forward towards clinical applicability of quantitative, deep learning-assisted laryngeal endoscopy, by fully automating segmentation and midline detection.

bioengineering↗

bioRxiv2020

Increasing growth temperature alters the within-host competition of viral strains and influences virus genetic variation

The emergence of viral diseases in plant crops hamper the sustainability of food production, and this may be boosted by global warming. Concurrently, mixed viral infections are becoming common in plants, of which epidemiology are unpredictable due to within-host virus-virus interactions. However, the extent in which the combined effect of variations in the abiotic components of the plant ecological niche (e.g., temperature) and the prevalence of mixed infections (i.e., within-host interactions among viruses) affect the evolutionary dynamics of viral populations is not well understood. Here, we explore the interplay between ecological and evolutionary factors during viral infections, and show that two individual strains of pepino mosaic virus (PepMV) coexisted in a temperature-dependent continuum between neutral and antagonistic interactions in tomato plants. After a long-term infection, the mutational analysis of the evolved viral genomes revealed strain-specific single-nucleotide polymorphisms that were modulated by the interaction between the type of infection and temperature. Mathematical modeling allowed us to asses a thermal reaction norm for both strains, which indicated that viral replication rates were increased along with increasing temperature in mixed infections, with a remarkable strain-dependent effect. These results suggest that the growth temperature is an ecological driver of virus-virus interactions, with an effect on the genetic diversity of individual viruses co-infecting a host. This research provides insights into the effect that climate change will have on the evolutionary dynamics of viral populations.

evolutionary biology↗

bioRxiv2019

Spatial heterogeneity of an ecologically relevant environment accelerates diversification and adaptation.

Spatial heterogeneity is a key driver for the evolution of resource specialists and has been shown to both promote and constrain the rate of adaptation. However, direct empirical support for these evolutionary consequences of spatial heterogeneity comes from simplified laboratory environments. Here we address how spatial structure, through its effect on resource heterogeneity, alters diversification and adaptive evolution of the soil bacterium Pseudomonas fluorescens in an ecologically relevant context: soil-based compost. Our data show that environmental heterogeneity can both promote phenotypic diversification and accelerate adaptation. These results suggest that environmental disturbance, which can decrease spatial heterogeneity, may limit diversification and adaptation of microbial populations.

ecology↗

bioRxiv2019

Forest canopy, a proxi of light intensity, arrests Pinus radiata invasion: basic science to conserve the Coastal Maulino forest, Central Chile.

Coastal Maulino forest is an endemic forest of central Chile, which has suffered a large history of disturbance, being replaced by large extensions of Pinus radiata plantations. This land transformation conveys high rates of pines invasion into native remnants. In this study we examined to what extent structural features of forest patches explains invisibility of this forest-type. Within eight forest fragments, we sampled 162 plots (10 x 10 m2 each). We quantified seedling pine density and related this estimates with tree cover, litter depth, PAR radiation, and diversity of the resident community. Our results indicate that canopy cover was the most important variable to determine seedling pine density within forest fragments. To preserve the Coastal Maulino forest and the biodiversity containing on it, it seems to be necessary to maintain the native canopy cover. These actions can be highly effective even if we cannot avoid a massive seed arrival from pine plantations which will be unable to regenerate under well conserved native forests.

ecology↗

bioRxiv2017

De-novo assembly of zucchini genome reveals a whole genome duplication associated with the origin of the Cucurbita genus

The Cucurbita genus (squashes, pumpkins, gourds) includes important domesticated species such as C. pepo, C. maxima and C. moschata. In this study, we present a high-quality draft of the zucchini (C. pepo) genome. The assembly has a size of 263 Mb, a scaffold N50 of 1.8 Mb, 34,240 gene models, includes 92% of the conserved BUSCO core gene set, and it is estimated to cover 93.0% of the genome. The genome is organized in 20 pseudomolecules, that represent 81.4% of the assembly, and it is integrated with a genetic map of 7,718 SNPs. Despite its small genome size three independent evidences support that the C. pepo genome is the result of a Whole Genome Duplication: the topology of the gene family phylogenies, the karyotype organization, and the distribution of 4DTv distances. Additionally, 40 transcriptomes of 12 species of the genus were assembled and analyzed together with all the other published genomes of the Cucurbitaceae family. The duplication was detected in all the Cucurbita species analyzed, including C. maxima and C. moschata, but not in the more distant cucurbits belonging to the Cucumis and Citrullus genera, and it is likely to have happened 30 {+/-} 4 Mya in the ancestral species that gave rise to the genus.

genomics↗