Biology subjects

Torres, N.

Publications and source records attributed to Torres, N..

6 recordsLinked to original sources

bioRxiv2025

MICOMWeb: a website for microbial community metabolic modeling of the human gut

SummaryMICOMWeb is a user-friendly website for easy microbial community metabolic modeling of the human gut. This website tackles three constraints when generating in silico metagenome-scale metabolic models: (i) the prior Python user knowledge for metabolic modeling using flux balance analysis with MICOM Python package, (ii) predefined and user-defined diets to generate ad hoc metabolic models, and (iii) the high- throughput computational infrastructure required to obtain the simulated growth and metabolic exchange fluxes, using real abundance from metagenomic shotgun or 16S amplicon sequencing; we present MICOMWebs features to easily run in silico experiments as a functional hypothesis generator for experimental validation on previously published data. Availability and ImplementationMICOMWeb is freely accessible for academic purposes at https://micomweb.c3.unam.mx.

systems biology↗

bioRxiv2024

Metabolic reprogramming and synergistic cytotoxicity of genistein and chemotherapy in human breast cancer cells

Breast cancer (BCa) is a heterogeneous disease, initially responsive to hormone therapy but often developing resistance to both hormonal and chemotherapy treatments. Novel therapeutic strategies are needed for drug-resistant BCa. Genistein, a phytoestrogen structurally similar to estrogen, competes with estrogen for receptor binding and exhibits anti-cancer effects. In this study, we investigated the cellular and metabolic impacts of genistein, alone or in combination with chemotherapy, in two human BCa cell lines--one estrogen receptor-positive (ER+) and one estrogen receptor-negative (ER-). We observed a strong synergistic effect on cell viability at low concentrations of genistein and chemotherapy, resulting in reduced clonogenic capacity and impaired cell migration. Genistein alone modulated cellular energy metabolism, notably reducing ATP production in MCF7 (ER+) cells. This metabolic shift was linked to a decreased dependence on fatty acids for energy, coupled with a decrease in the rate-limiting mitochondrial translocase CPT1 required for fatty acid oxidation, alongside with an increase in intracellular fatty acid levels. While the most significant changes occurred in ER+ cells, ER- cells also showed responses to genistein treatment. Collectively, our findings suggest that low dose genistein, in combination with conventional chemotherapy, induces synergistic anti-cancer effects, promoting cellular senescence. This effect may be partly mediated by a reduced reliance on fatty acid metabolism in BCa cells.

cancer biology↗

bioRxiv2024

A three-country analysis of the gut microbiome indicates taxon associations with diet vary by location and strain

Emerging research suggests that diet plays a vital role in shaping the composition and function of the gut microbiota. While significant efforts have been made to identify general patterns linking diet to the gut microbiome, much of this research lacks representation from low- and middle-income countries such as Mexico. Additionally, both diet and the gut microbiome have highly complex and individualized configurations, and there is growing evidence that tailoring diets to individual gut microbiota profiles may optimize the path toward improving or maintaining health and preventing disease. Using fecal metagenomic data from 1,291 individuals across three countries, we examine two bacterial genera prevalent in the human gut, Prevotella and Faecalibacterium, which have gained significant attention due to their potential roles in human health. We find that they show significant associations with many aspects of diet, but that these associations vary in scale and direction, depending on the level of metagenomic resolution and the contextual population. These results highlight the growing importance of assembling metagenomic datasets that are standardized, comprehensive, and representative of diverse populations to increase our ability to tease apart the complex relationship between diet and the microbiome.

microbiology↗

bioRxiv2020

Calories delivered by nonhuman primate foraging enrichment: Data and methods to inform decisions concerning the dietary consequences of enrichment

Foraging opportunities are a key component of enrichment in captive nonhuman primates providing manipulative opportunities in which animals can engage in species-typical behaviors. Recent studies suggest captive NHP populations have increased body weight over time leading to negative health outcomes. Increasing food foraging opportunities provides added calories that can be estimated but often are not directly measured. We assessed 10 commonly used foraging puzzles for the amount of foraging material they held; evaluated the range of caloric content delivered; and determine the labor and usage cost of each. Five preparation areas were sampled. The amount of foraging material contained in each prepared puzzle was calculated by subtracting the average empty puzzle weight from the loaded puzzle weight. A detailed description of food content was used to illustrate caloric content. Larger prepared puzzles held more food (M=104.9 g) as compared to small volumes puzzles (M=59.8 g). Analysis of the weight of food applied and caloric content suggest larger puzzles do have the potential to provide increased caloric load; however, the added food from large foraging puzzles constitutes only 5%-10% of the daily k/cal dietary requirement. The study illustrates the importance of considering puzzle characteristics when selecting foraging toys and discusses the considerations of cost of puzzle deployment, maintenance and interactive benefit. The broad significance of our assessment suggests that calories from foraging opportunities are not excessive and can be managed by adopting standard serving sizes and scheduling intermitted presentation of non-nutritive enrichment options.

animal behavior and cognition↗

bioRxiv2018

Individual response to mTOR inhibition in delaying replicative senescence of mesenchymal stromal cells

Background aimsDelaying replicative senescence and extending lifespan of human mesenchymal stromal cells (MSCs) may enhance their potential for tissue engineering and cell based therapies. Accumulating evidence suggests that inhibitors of the mTOR signaling pathway, such as rapamycin, constitute promising pharmacological agents to retard senescence and extend stemness properties of various progenitor cell types. Here, we investigated whether the ability of rapamycin to postpone replicative senescence varies among bone marrow MSC samples (BM-MSCs) derived from different healthy donors, and explored the molecular mechanisms that drive rapamycin-mediated lifespan increment.\n\nMethodsBM-MSCs at early passages were serially passaged either in absence or continuous presence of rapamycin and the number of cell population doublings until growth arrest was measured. The inhibition of mTOR signaling was assessed by the phosphorylation status of the downstream target RPS6. The expression levels of several senescence and pluripotency markers at early and late/senescent passages were analyzed by RT-qPCR, flow cytometry and western blot.\n\nResultsWe found that the lifespan extension in response to the continuous rapamycin treatment was highly variable among samples, but effective in most BM-MSCs. Despite all rapamycin-treated cells secreted significantly reduced levels of IL6, a major SASP cytokine, and expressed significantly higher levels of the pluripotency marker NANOG, the expression patterns of these markers were not correlated with the rapamycin-mediated increase in lifespan. Interestingly, rapamycin-mediated life-span extension was significantly associated only with repression of p16INK4A protein accumulation.\n\nConclusionsTaken together, our results suggest that some, but not all, BM-MSC samples would benefit from using rapamycin to postpone replicative arrest and reinforce a critical role of p16INK4A protein downregulation in this process.

cell biology↗

bioRxiv2017

Functional Annotation of Chemical Libraries across Diverse Biological Processes

Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells to a compound, revealing chemical-genetic interactions that can elucidate a compounds mode of action. We developed a highly parallel and unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized, diagnostic mutant collection that is predictive all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode sequencing protocol, enabling assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened 7 different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.

systems biology↗