Biology subjects

Chaves, S.

Publications and source records attributed to Chaves, S..

4 recordsLinked to original sources

bioRxiv2024

MHC heterozygosity may increase subordinate but not alpha male siring success in white-faced capuchin monkeys (Cebus imitator)

The genes of the major histocompatibility complex (MHC) are vital to vertebrate immunity and may influence mate choice in several species. The extent to which the MHC influences female mate choice in primates remains poorly understood, and studies of MHC-based mate choice in platyrrhines are especially rare. White-faced capuchin monkeys (Cebus imitator) reside in multimale-multifemale groups where alpha males sire most of the offspring. In this study, we investigated the roles of social dominance, relatedness, and MHC genotypes in determining which mating pairs produced offspring in wild white-faced capuchins in the Sector Santa Rosa (SSR), Area de Conservacion Guanacaste, Costa Rica. We find that males in this population do not differ significantly in MHC metrics based on their social status or siring success. Using mixed conditional logit models and generalized linear models, we find that alpha males that are distantly related to reproducing females are significantly more likely to sire offspring while MHC metrics do not predict the probability of siring offspring, or becoming an alpha male. However, we do find some evidence that subordinate males heterozygous at MHC loci sire significantly more offspring than homozygous subordinates. Further, one-sided binomial simulations reveal that offspring are more frequently heterozygous at MHC loci than expected given the gene pool. We conclude that in this population with limited genomic variation, females may preferentially mate with MHC-diverse subordinate males when related to the alpha, leading to increased probabilities of MHC-diverse offspring.

evolutionary biology↗

bioRxiv2024

Diseased skin dermal proteomic profiles reflect shared extracellular matrix dysregulation patterns

Extracellular matrix (ECM) plays a major role in the maintenance of skin homeostasis and modifications in its structure are commonly linked with skin diseases of different origins. Recent evidence shows that epidermal fibroblasts can be important regulators of epidermal pathology. However, despite recent advances, the intricate mechanisms responsible for the ECM defects in a wide range of skin pathologies are still evasive. In this work we used Dystrophic Epidermolysis Bullosa, Pemphigus vulgaris and Squamous Cell Carcinoma, as the models for epidermal diseases of distinct etiology, in order to explore potential shared alterations in diseased dermal fibroblasts. Our proteome analysis revealed that differentially expressed proteins in all diseases are commonly enriched in processes related to supramolecular fiber organization, complex of collagen trimers and actomyosin, however with opposite patterns. Nevertheless, Collagen XII is significantly downregulated in all diseases. Additionally, an algorithmic pipeline predicts that MAPKs and CDKs are major regulators of dermal proteome alterations across all diseases. Altogether, our results highlight a possible shared mechanism where downregulation of Collagen XII mediates ECM organization disruption leading to diverse disease phenotypes.

cell biology↗

bioRxiv2024

The widely used cymoxanil fungicide impairs respiration in Saccharomyces cerevisiae via cytochrome c oxidase inhibition

Cymoxanil (CYM) is a synthetic acetamide fungicide that has been widely used to combat downy mildew diseases in grapevine cultures and late blight diseases in tomato and potato caused by the oomycetes Plasmopara viticola and Phytophthora infestans, respectively. Despite its extensive application, the biochemical mode of action of CYM remains elusive. Previous reports indicate that CYM affects growth, DNA and RNA synthesis in Phytophthora and inhibits cell growth, biomass production and respiration rate in the well-characterized fungal model Saccharomyces cerevisiae. We therefore used this model to further characterize the effect of CYM on mitochondria. We found that CYM inhibits oxygen consumption in whole cells after 3 h of exposure, which persists over time. Using isolated mitochondria, we demonstrated that CYM specifically inhibits cytochrome c oxidase (CcO) activity during oxidative phosphorylation. Based on molecular docking algorithms, we propose that CYM acts by blocking the interaction of cytochrome c (cyt c) with CcO, hampering electron transfer and inhibiting CcO catalytic activity. Although other targets cannot be excluded, our data offer valuable insights into the mode of action of CYM that can be instrumental to drive informed management of the use of this fungicide.

biochemistry↗

bioRxiv2024

The antifungal activity of cymoxanil is associated with proton pump inhibition and disruption of plasma membrane potential

Worldwide use of agrochemicals, particularly pesticides, is necessary to increase agricultural production to feed the ever-growing population. However, despite widespread use, the biochemical mode of action of many agrochemicals and their potential deleterious effects on the environment are poorly characterized. Cymoxanil (CYM) is a fungicide used to combat downy mildew diseases in grapevine cultures and late blight diseases in tomato and potato cultures caused by the oomycetes Plasmopara viticola and Phytophthora infestans, respectively. Previous reports indicate that CYM affects growth, DNA and RNA synthesis in Phytophthora and inhibits cell growth, biomass production and respiration rate in the well-characterized fungal model Saccharomyces cerevisiae. We therefore used this model to further dissect mechanisms underlying the toxicological effects of CYM. We found that CYM induced genome-wide alterations, particularly in membrane transporter systems. These alterations were associated with perturbations in lipid-raft organization and inhibition of Pma1p, leading to a decrease in plasma membrane potential and intracellular acidification. Altogether, these findings identify the plasma membrane as one of the targets of CYM and proposes a mode of action underlying its antifungal activity.

cell biology↗