RESUMEN
Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orthologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.
Asunto(s)
Redes Reguladoras de Genes , Fenoles/farmacología , Saccharomyces cerevisiae/efectos de los fármacos , Schizosaccharomyces/efectos de los fármacos , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/toxicidad , Hidroxianisol Butilado/farmacología , Hidroxianisol Butilado/toxicidad , Hidroxitolueno Butilado/farmacología , Hidroxitolueno Butilado/toxicidad , Puntos de Control del Ciclo Celular , Reparación del ADN , Estrés del Retículo Endoplásmico , Genómica , Fenoles/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/fisiología , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Schizosaccharomyces/fisiología , Respuesta de Proteína DesplegadaRESUMEN
Young children with multiple disabilities have unique needs and challenges. Many of these young children struggle to communicate their wants and needs, to freely move their body to access and engage their world, and to learn abstract concepts and ideas. Professionals and families working together must identify the individual supports each child needs to ensure that the young child with multiple disabilities is an active participant in all aspects of their lives and makes meaningful progress toward valued life outcomes.