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Mendoza, S.

Publications and source records attributed to Mendoza, S..

7 recordsLinked to original sources

Selecting methods for draft GEM generation in multicellular eukaryotes: a comparative analysis

Motivated by multiple strategies that have successfully implemented genome-scale models (GEMs) into their pipeline, several approaches have been developed for automatic generation of draft GEMs. However, most of these methods are not optimized for their use for multicellular eukaryotes and their performance for this task is unclear. In this work we present a comparative analysis of seven automated reconstruction tools (AuReMe, carveMe, Merlin, modelSEED, Pathway tools, Raven and Reconstructor) applied to three multicellular eukaryotes: the mosquito Aedes aegypti, the CHO (Chinese Hamster Ovary) cell line from Cricetulus griseus and the brown algae Ectocarpus siliculosus. Evaluation of these tools was based on metrics for network size, functionality, consistency, representation of organelle-specific functions and organism-specific metabolites, annotation quality and execution time. Finding that similarity of obtained metabolic networks is highly influenced by databases in which these methods base their predictions over phylogeny. Our works aims at providing a practical resource to guide researchers in selecting methods for draft generation tailored to organism characteristics and research goals. Author summaryGenome-scale models (GEMs) represent all the potential biochemical transformations that a specific organism can carry out based on the information encoded in its genome. Although these models are a powerful tool for analyzing omics datasets and simulating the metabolic effects of genetic modifications or changing media composition, the process of manually reconstructing a genome-scale model is complex and time-consuming. Motivated by their potential applications, several tools have been developed for the automated generation of draft GEMs, however, most of them are oriented to simpler organisms such as bacteria or single-cell eukaryotes, while their relative performance for modeling multicellular eukaryotes is unclear. In this work, we compared seven tools for draft GEMs reconstruction of three organisms: for the mosquito Aedes aegypti, the brown algae Ectocarpus siliculosus and the CHO cell line from Cricetulus griseus. Our results showed that no tool systematically outperformed others, suggesting that method selection is influenced by several factors such as organism-specific data availability and their intended application.

systems biology↗

Reduced glutathione levels in Enterococcus faecalis trigger metabolic and transcriptional compensatory adjustments during iron exposure.

Enterococcus faecalis, a facultative anaerobic pathogen and common constituent of the gastrointestinal microbiota, must navigate varying iron levels within the host. This study explores its response to iron supplementation in a glutathione-deficient mutant strain ({Delta}gsh). We examined the transcriptomic and metabolic responses of a glutathione synthetase mutant strain ({Delta}gsh) exposed to iron supplementation, integrating these data into a genome-scale metabolic model (GSMM). Our results show that under glutathione deficiency, E. faecalis reduces intracellular iron levels and shifts its transcriptional response to prioritize energy production genes. Notably, basal metabolites, including arginine, increase. The GSMM highlights the importance of arginine metabolism, particularly the arc operon (anaerobic arginine catabolism), as a compensatory mechanism for reduced glutathione during iron exposure. These findings provide insights into how E. faecalis adjusts metal homeostasis and transcriptional/metabolic processes to mitigate the effects of oxidative stress caused by iron. IMPORTANCEIron is essential for bacterial survival, yet its excess can be harmful through increase of oxidative stress. Enterococcus faecalis, a bacterium common member of the human gut, must carefully balance its iron levels in order to survive in changing environments. This study studies how E. faecalis compensates the reduced levels of glutathione --a key antioxidant-- when exposed to high iron concentrations. We discovered that E. faecalis lowers its intracellular iron levels under glutathione decrease and reprograms its metabolism to prioritize energy production. These findings provide valuable insights into bacterial adaptation mechanisms under oxidative stress conditions, which could influence the development of new strategies to combat bacterial infections.

systems biology↗

Genomic epidemiology reveals antibiotic resistance transfer and polyclonal dissemination of Acinetobacter baumannii in a Paraguayan hospital

Acinetobacter baumannii is a major nosocomial pathogen worldwide and, specifically, in Latin America. Genomic epidemiology has been instrumental in determining the transmission dynamics of A. baumannii in many countries of the world, yet some Latin American countries have conducted no genomic epidemiology studies. Here, we conduct the first genomic epidemiology study about this pathogen in Paraguay. We sequenced 43 isolates from a big tertiary hospital in Paraguay collected from different wards in 2021 and 2022. Our genomic epidemiology analyses, including almost 200 genomes and considering the main international clones (ICs), show that IC1, IC2, IC4, IC5 and IC7 were found in the hospital. We found novel genetic variation (3 novel Sequence Types as per the Oxford MLST scheme and one as per the Pasteur scheme) within IC7. Antibiotic susceptibility tests show that all but one of the Paraguayan isolates were resistant to carbapenems. Notably, 98% were classified as multidrug-resistant. We detected plasmids in almost all the Paraguayan isolates. Furthermore, we detected cases of recent horizontal transfer of important antibiotic-resistance genes between different ICs. On a general note, our findings highlight polyclonal spreading across different hospital wards and horizontal transfer of clinically relevant antibiotic-resistance genes among the different clones. On a more local note, this is the first genomic epidemiology study of A. baumannii in Paraguay and will be a reference point for future studies in the country and the region.

microbiology↗

Occurrence of the Humboldt Penguin (Spheniscus humboldti, Meyen, 1834) in El Ferrol Bay, Chimbote, Peru, and strategies for its conservation

The Humboldt penguin is an emblematic species of the Humboldt ecosystem of Peru and Chile, declared as vulnerable in The IUCN Red List of Threatened Species in 2020. By 2023, its population was estimated around 9,900 pairs, which means a decrease of 93% of its population in 70 years. In response to a warning of its occurrence on the Guaneras Islands located in El Ferrol Bay (Chimbote, Peru), the objective of this study was to verify its presence in situ. Between October and November 2024, four expeditions were carried out on the leeward side of the Islote Pena Blanca (White Rock Islet), Isla Blanca (White Island), Isla Ferrol del Norte (Northern Ferrol Island), Isla Ferrol del Centro (Central Ferrol Island), and Isla Ferrol del Sur (Southern Ferrol Island). The presence of 149 individuals, 5 of them juveniles, and one chick accompanied by its parent, was verified on Northern Ferrol Island, Central Ferrol Island, and Southern Ferrol Island. It is estimated that the presence of these organisms is explained by the improvement of oceanographic conditions in this bay. Considering the high vulnerability of the species, the local community must articulate efforts to guarantee the establishment of its population in this particular habitat.

ecology↗

Oxytocin Neurons Enable Social Transmission of Maternal Behavior

Maternal care is profoundly important for mammalian survival, and non-biological parents can express it after experience with infants. One critical molecular signal for maternal behavior is oxytocin, a hormone centrally released by hypothalamic paraventricular nucleus (PVN). Oxytocin enables plasticity within the auditory cortex, a necessary step for responding to infant vocalizations. To determine how this change occurs during natural experience, we continuously monitored homecage behavior of female virgin mice co-housed for days with an experienced mother and litter, synchronized with recordings from virgin PVN cells, including from oxytocin neurons. Mothers engaged virgins in maternal care by ensuring their nest presence, and demonstrated maternal behavior in self-generated pup retrieval episodes. These social interactions activated virgin PVN and gated behaviorally-relevant cortical plasticity for pup vocalizations. Thus rodents can acquire maternal behavior by social transmission, and our results describe a mechanism for adapting brains of adult caregivers to infant needs via endogenous oxytocin. One Sentence SummaryMother mice help co-housed virgins become maternal by enacting specific behaviors that activate virgin oxytocin neurons.

neuroscience↗

Alpha/Beta Hydrolase Domain-Containing Protein 2 regulates the rhythm of follicular maturation and estrous stages of the female reproductive cycle

Therian female fertility is defined by a successful and strictly periodic ovarian cycle, which is under the control of gonadotropins and steroid hormones, particularly progesterone and estrogen. The latter two are produced by the ovaries that are engaged in controlled follicular growth, maturation and release of the eggs, i.e. ovulation. It is well known that steroid hormones regulate ovarian cycles via genomic signaling, by altering gene transcription and protein synthesis. However, despite this well-studied mechanism, steroid hormones can also signal via direct, non-genomic action, by binding to their membrane receptors. Here we show, that the recently discovered sperm membrane progesterone receptor /{beta} hydrolase domain-containing protein 2 (ABHD2) is highly expressed in mammalian ovaries where the protein plays a novel regulatory role in follicle maturation and the sexual cycle of females. Ablation of Abhd2 caused a dysregulation of the estrous cycle rhythm with females showing shortened luteal stages while remaining in the estrus stage for a longer time. Interestingly, the ovaries of Abhd2 knockout (KO) females resemble polycystic ovary morphology with a high number of atretic antral follicles that could be rescued with injection of gonadotropins. Such a procedure also allowed Abhd2 KO females to ovulate a significantly increased number of mature and fertile eggs in comparison to their wild-type littermates. These results suggest a novel regulatory role of ABHD2 as an important factor in non-genomic steroid regulation of the female reproductive cycle.

physiology↗

Asymmetrically Positioned Flagellar Control Units Regulate Human Sperm Rotation

The ability of sperm to fertilize an egg is controlled by ion channels, one of which is the pH-dependent calcium channel of sperm CatSper. For CatSper to be fully activated, the cytoplasmic pH must be alkaline, which is accomplished by either proton transporters, or a faster mechanism, such as the voltage-gated proton channel Hv1. To ensure effective regulation, these channels and regulatory proteins must be tightly compartmentalized. Here, we characterize human sperm nanodomains that are comprised of Hv1, CatSper and regulatory protein ABHD2. Super-resolution microscopy revealed that Hv1 forms asymmetrically positioned bilaterally distributed longitudinal lines that span the entire length of the sperm tail. Such a distribution provides a direct structural basis for the selective activation of CatSper, and subsequent flagellar rotation along the long axis that, together with hyperactivated motility, enhances sperm fertility. Indeed, Hv1 inhibition leads to a decrease in sperm rotation. Thus, sperm ion channels are organized in distinct regulatory nanodomains that control hyperactivated motility and rotation.

cell biology↗