Biology subjects

Suarez, G.

Publications and source records attributed to Suarez, G..

4 recordsLinked to original sources

bioRxiv2025

Early impairment in dentate pattern separation in a rodent model of temporal lobe epilepsy.

The dentate gyrus of the hippocampal formation utilizes sparse neural coding to support memory formation. In temporal lobe epilepsy (TLE), the dentate undergoes extensive restructuring, including loss of local inhibition. It is unknown how circuit changes impact dentate network computations in awake behaving animals. Here we perform high-density tetrode recordings from the dentate in male rats treated with systemic kainic acid (KA) to induce TLE. In KA-treated rats, dentate spatial representations were less precise at the single neuron level, however the stability of the spatial code in representing repeated visits to the same location was retained at the population level. Despite spared spatial representation, the network computations for pattern separation were disrupted. The reorganized dentate network in KA-treated rats generated less distinct population activity patterns for different environments, specifically as a result of impaired rate-remapping. Changes in network computations paralleled impairments in a dentate-dependent memory task, potentially providing a link between altered pattern separation and behavioral discrimination. These deficits were present in animals with confirmed dentate circuit reorganization that had not yet developed spontaneous seizures - suggesting that the dentate network changes underlying altered rate-remapping and impaired dentate-dependent memory occur early in epileptogenesis.

neuroscience↗

bioRxiv2024

Epigenetic control of CD8+ T cell tissue homing and tissue resident memory T cell precursors by the histone methyltransferase SUV39H1

Activation of CD8+ T cells leads to the differentiation of short-lived terminal effectors and memory precursors. Some of these memory precursors remain in lymphoid organs and become long-lived central memory T cells (TCM), while others home to non-lymphoid peripheral tissues early after antigen recognition and differentiate into tissue resident memory T cells (TRM). The early stages of memory precursor tissue homing and TRM differentiation remain poorly understood. We show here that at steady state, during space-induced "homeostatic" expansion, and after flu infection, deletion of the histone 3-lysine 9 methyltransferase SUV39H1 in CD8+ T cells, increases the homing to non-lymphoid tissues (including liver, lungs, gut and skin). SUV39H1-defective cells in tissues express CD49d and differentiate into CD69+/CD103-TRM after adoptive transfer or Flu infection. SUV39H1-defective T cells that accumulate in lungs are fully functional in both Flu re-infection and lung tumor models. We conclude that SUV39H1 restrains CD8+ T cell tissue homing and TRM differentiation in WT mice. These results should encourage the use of SUV39H1-depletion in the context of adoptive T cell therapies to enhance tissue homing, thereby optimizing the efficiency of target cell eradication and long-term protection in the context of infection and cancer.

immunology↗

bioRxiv2022

A study of thermally-induced sex reversal in casque-headed lizards

Non-avian reptiles, unlike mammals and birds, have undergone numerous sex determination turnovers. For example, casque-headed lizards replaced the ancestral XY system shared across pleurodonts with a new pair of XY chromosomes. However, the evolutionary forces that triggered this transition have remained unclear. An interesting evolutionary hypothesis suggests that species with intermediate states, with sex chromosomes but also thermal-induced sex reversal at specific incubation temperatures, could be more susceptible to sex determination turnovers. We contrasted genotypic data (presence/absence of the Y chromosome) against the histology of gonads of embryos from stages 35-37 incubated at various temperatures, including typical male-producing (26{degrees}C) and female-producing (32{degrees}C) temperatures. We observed perfect concordance between genotype and phenotype at all temperatures. However, analysis of transcriptomic data from embryos incubated at 26{degrees}C and 32{degrees}C identified transcript variants of the chromatin modifiers JARID2 and KDM6B that have been linked to temperature-dependent sex determination in other reptiles. Besides, our work reports for the first time to our knowledge the histology of gonads, including morphological changes, from stages 35-37 of development in the Corytophanidae family. We also observed that all embryos developed hemipenes, suggesting sex-linked developmental heterochrony.Our work tested the validity of a mixed sex determination system in the Corytophanidae family. We showed that XY chromosomes are dominant, however, our work supports the hypothesis of a conserved transcriptional response to incubation temperatures across non-avian reptiles that could be the reminiscence of an ancestral sex determination system.

developmental biology↗

bioRxiv2021

How public reaction to disease information across scales and the impacts of vector control methods influence disease prevalence and control efficacy

With the development of social media, the information about vector-borne disease incidence over broad spatial scales can cause demand for local vector control before local risk exists. Anticipatory intervention may still benefit local disease control efforts; however, infection risks are not the only focal concerns governing public demand for vector control. Concern for environmental contamination from pesticides and economic limitations on the frequency and magnitude of control measures also play key roles. Further, public concern may be focused more on ecological factors (i.e., controlling mosquito populations) or on epidemiological factors (i.e., controlling infection-carrying mosquitoes), which may lead to very different control outcomes. Here we introduced a generic Ross-MacDonald model, incorporating these factors under three spatial scales of disease information: local, regional, and global. We tailored and parameterized the model for Zika virus transmitted by Aedes aegypti mosquito. We found that overreaction caused by larger-scale incidence information could decrease average human infections per patch breeding capacity, however, the associated increase in total control effort plays a larger role, which leads to an overall decrease in control efficacy. The shift of focal concerns from epidemiological to ecological risk could relax the negative effect of overreaction on control efficacy when mosquito breeding capacity populations are expected to be large. This work demonstrates that, depending on expected total mosquito breeding capacity population size, and weights of different focal concerns, large-scale disease information can reduce disease infections without lowering control efficacy. Our findings provide guidance for vector-control strategies by considering public reaction through social media.

ecology↗