Biology subjects

Rodriguez, Y.

Publications and source records attributed to Rodriguez, Y..

7 recordsLinked to original sources

bioRxiv2025

Contractility governs cardiomyocyte cell cycle activity

The hearts rhythmic contractions keep blood flowing to deliver the oxygen and nutrients that sustain life, but this very strength may also explain why the heart has so little capacity to regenerate. Whereas embryonic and neonatal hearts can repair themselves, this ability is rapidly lost after birth as heart muscle cells (cardiomyocytes) exit the cell cycle. We tested whether the force-generating machinery of the heart acts as a barrier to regeneration. Across human cardiomyocytes, engineered heart tissue, and myocardial slices, we found that active force generation suppresses proliferation, whereas its inhibition, through chemogenetic or pharmacological modulation, enabled cell cycle re-entry. These findings identify contractility as a central regulator of regenerative potential, highlighting new directions for strategies to restore repair in the diseased heart.

cell biology↗

bioRxiv2025

Joint probabilistic modeling of pseudobulk and single-cell transcriptomics enables accurate estimation of cell type composition

Bulk RNA sequencing provides an averaged gene expression profile of the numerous cells in a tissue sample, obscuring critical information about cellular heterogeneity. Computational deconvolution methods can estimate cell type proportions in bulk samples, but current approaches can lack precision in key scenarios due to simplistic statistical assumptions, limited modeling of cell-type heterogeneity and poor handling of rare populations. We present MixupVI, a deep generative model that learns representations of single-cell transcriptomic data and introduces a mixup-based regularization to enable reference-free deconvolution of bulk samples. Our method creates a latent representation with an additive property, where the representation of a pseudobulk sample corresponds to the weighted sum of its constituent cell types. We demonstrate how MixupVI enables accurate estimation of cell type proportions through benchmarking on pseudobulks simulated from a large immune single-cell atlas. To support reproducibility and foster progress in the field, we also release PyDeconv, a Python library that implements multiple state-of-the-art deconvolution algorithms and provides a comprehensive benchmark on simulated pseudobulk datasets.

bioinformatics↗

bioRxiv2024

Late-Life Alcohol Exposure Does Not Exacerbate Age-Dependent Reductions in Mouse Spatial Memory and Brain TFEB Activity

Alcohol consumption is believed to affect Alzheimers disease (AD) risk, but the contributing mechanisms are not well understood. A potential mediator of the proposed alcohol-AD connection is autophagy, a degradation pathway that maintains organelle and protein homeostasis. Autophagy is in turn regulated through the activity of Transcription factor EB (TFEB), which promotes lysosome and autophagy-related gene expression. To explore the effect of alcohol on brain TFEB and autophagy, we exposed young (3-month old) and aged (23-month old) mice to two alcohol-feeding paradigms and assessed biochemical, transcriptome, histology, and behavioral endpoints. In young mice, alcohol decreased hippocampal nuclear TFEB staining but increased SQSTM1/p62, LC3-II, ubiquitinated proteins, and phosphorylated Tau. Hippocampal TFEB activity was lower in aged mice than it was in young mice, and Gao-binge alcohol feeding did not worsen the age-related reduction in TFEB activity. To better assess the impact of chronic alcohol exposure, we fed young and aged mice alcohol for four weeks before completing Morris Water and Barnes Maze spatial memory testing. The aged mice showed worse spatial memory on both tests. While alcohol feeding slightly impaired spatial memory in the young mice, it had little effect or even slightly improved spatial memory in the aged mice. These findings suggest that aging is a far more important driver of spatial memory impairment and reduced autophagy flux than alcohol consumption.

animal behavior and cognition↗

bioRxiv2022

Effect of intranasal administration of neuroEPO in the histological structure of the olfactory mucosa of rats Wistar

IntroductionStrokes and neurodegenerative diseases are major global health problems. Not only because they cause high mortality and disability, but to the lack of effective therapies. NeuroEPO, a variant of recombinant human erythropoietin (rHu-EPO) with a low sialic acid content, has shown encouraging results as a potential neuroprotective agent when administered intranasally. ObjectiveTo determine the effect of intranasal administration of NeuroEPO on the histological structure of the olfactory mucosa of Wistar rats. Materials and MethodsAn experimental, prospective, and longitudinal study was conducted in Wistar rats. Ten healthy animals were randomly distributed into two groups of five each. The control group received a vehicle (0.3 l/g/day) and the treated group received NeuroEPO (300 g/kg/day). Both treatments were administered intranasally for 28 days. The histological characteristics of the olfactory mucosa were evaluated. The medians of the study groups were compared using the Mann-Whitney U test. ResultsThere were no alterations in the histological characteristics of the olfactory epithelium. However, at the level of the lamina propria in the group treated with NeuroEPO, slight hypertrophy, and hyperplasia of the Bowmans glands was observed. ConclusionsThe administration of the nasal formulation of NeuroEPO did not induce histological alterations of the olfactory mucosa of Wistar rats under the experimental conditions of this research.

pharmacology and toxicology↗

bioRxiv2022

Antimicrobial Susceptibility Profiles of Bacteria Isolated from The Ozama River in Santo Domingo, Dominican Republic

The dissemination of antimicrobial-resistant bacteria in environmental waters is an emerging concern in medical and industrial settings. In the present study, our research team analyzed superficial water samples from 3 different collection sites along the Ozama River, the most important river in the Dominican metropolitan area. Seventy-six isolates were obtained from culture media previously enriched with cefotaxime and imipenem and subsequently identified by MALDI-ToF. Our isolates spanned 12 genera of bacteria; over 30% were of clinical relevance, and 43% exhibited a phenotype classified as multi-drug resistance. The most frequent species identified as Stenotrophomonas maltophilia (n = 33), an emerging nosocomial pathogen. This study constitutes part of the initiative to understand the profiles of the perils of multi-drug resistance in metropolitan areas of the Dominican Republic: a nation with poor antibiotic use regulation. IMPORTANCENearly two billion people are sourcing their water from low-quality reservoirs world-wide. These reservoirs consist of contaminated waters with anthropogenic pollutants such as antibiotics, disinfectants, and other substances used to treat water in societies with scarce resources and unregulated industries. Furthermore, the exposure of these antibiotics to potable water reservoirs promotes the increase of clinically relevant bacteria with antibiotic-resistance capabilities, becoming a public health crisis. Therefore, treating patients with infectious diseases and providing prophylactic measures against infection-associated conditions (such as post-surgical recovery) has become progressively more difficult. Based on this evidence frame, it is of considerable importance to analyze the bacterial profiles of rivers that fall prey to anthropogenic contamination, as these investigations on antibiotic resistance will, of course, benefit the life of humans.

microbiology↗

bioRxiv2022

A transcriptional mechanism involving R-loop, m6A modification and RNA abasic sites regulates an enhancer RNA of APOE.

The DNA genetic code and the RNA regulatory code determine phenotypes from gene expression to disease susceptibility. DNA sequence variants lead to phenotypic differences among individuals, while within an individual, RNA dynamically confers cell identity and responds to cellular and environmental signals. To provide regulation for different cell types and conditions, the nucleotides of RNA are modified by hundreds of chemical reactions, and RNA folds into innumerable shapes. To decipher the RNA regulatory code is to understand how RNA sequence and structure respond to cellular needs. Here, we deciphered one part of the RNA code where RNA abasic sites in R-loops regulate transcription by pausing RNA polymerase II. We uncovered an enhancer RNA, AANCR, that regulates the transcription and expression of APOE. When AANCR is folded into an R-loop, which is then modified by N6-adenine methylation and N-glycosidic cleavage, it is a partially transcribed nonfunctional enhancer and APOE is not expressed. In contrast, in some cell types and under stress, AANCR does not form a stable R-loop as its sequence is not modified, so it is transcribed into a full-length enhancer that promotes APOE expression. By genetic analysis, we confirmed that AANCR regulates APOE expression. DNA sequence variants in AANCR are associated with APOE expression and also with Alzheimers disease. Our data show that DNA and RNA sequence and structure jointly regulate gene expression that influence disease risk. HighlightsO_LIm6A, RNA abasic sites and R-loops jointly regulate transcription by pausing RNA Polymerase II. C_LIO_LIAn enhancer RNA regulates APOE expression. C_LIO_LIEnhancer RNA of APOE modifies susceptibility to Alzheimers disease. C_LI

molecular biology↗

bioRxiv2019

Perceptions and Prospects in Life Sciences in a Heterogenous Latin American Population

Particular challenges exist for science education in the developing world, where limited resources beget curricula designed to balance state-of-the-art knowledge with practical and political considerations in region-specific contexts. Project-based biology teaching is particularly difficult to execute due to high infrastructural costs and limited teacher training. Here, we report our results implementing short, challenging, and low-cost biology courses to high school and college students in Bolivia, designed and taught in collaboration between scientists from developed nations and local science instructors. We find our approach to be effective at transmitting advanced topics in disease modeling, microscopy, genome engineering, neuroscience, microbiology, and regenerative biology. Importantly, this approach was unaffected by the students backgrounds, education level, socioeconomic status, or initial interest in the course, and increased participants interest in pursuing scientific careers. These results demonstrate efficacy of participatory learning in a developing nation, and suggest that such techniques could drive scientific engagement in other developing economies.

scientific communication and education↗