DGH - Materiais de difusão da cultura científica e de formação
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Percorrer DGH - Materiais de difusão da cultura científica e de formação por Domínios Científicos e Tecnológicos (FOS) "Ciências Médicas::Ciências da Saúde"
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- Genome wide analysis of methylation changes in Caco 2 intestinal cells after exposure to undigested and digested titanium dioxide nanoparticlesPublication . Ventura, CéliaTitanium dioxide nanoparticles (TiO2NPs) are nanomaterials with relevant properties for several applications in biomedicine and industry, where they are primarily used as a white pigment to improve the opacity, brightness, and whiteness of several products, such as paint, food, cosmetics, and pharmaceutics. Nevertheless, there are still concerns about its effects on human health, particularly through ingestion of the food-grade TiO2NPs, which caused its ban from all food products in the European Union. Moreover, in recent years, there has been a great interest in the role of epigenetics in the biological response to chemical exposure, including the study of DNA methylation. This study aimed at identifying changes in DNA methylation of Caco-2 intestinal cells caused by exposure to anatase (NM-102), rutile (NM-103) and anatase/rutile (NM-105) TiO2NPs, either after a simulated in vitro digestion or the undigested counterparts. Using Reduced Representative Bissulfite Sequencing, significant differential methylation of 209 and 319 genomic regions in cells exposed to undigested and digested NMs was identified, respectively. These included 48, 41 and 55 differentially methylated genes for undigested NM-102, NM-103 and NM-105, and 71, 65 and 55 for the digested counterparts. Reactome pathways and Gene Ontology (GO) analyses showed that both undigested and digested TiO2NPs have a functional impact on intestinal cells, often cancer-related, and that digestion seems to reduce this impact. Different TiO2NPs caused enrichment of different pathways and GO terms, probably due to their specific physicochemical properties. A trend towards CpG hypermethylation was observed upon NM-105 exposure, unlike the other TiO2NPs. This study highlights the importance of DNA methylation analysis in assessing the adverse effects of nanomaterials on human cells.
- Rastreio Neonatal da Fibrose QuísticaPublication . Marcão, AnaApresentação sobre o rastreio neonatal da fibrose quística no âmbito do Programa Nacional do Rastreio Neonatal (PNRN), inserida em iniciativa promovida pela Unidade de Rastreio Neonatal, Metabolismo e Genética do seu Departamento de Genética Humana, com o objetivo principal de informar os participantes sobre a organização do PNRN, nomeadamente todos os profissionais que intervêm no diagnóstico de doenças incluídas no PNRN. A iniciativa pretende ainda discutir os problemas relacionados com a colheita de sangue, com a conservação e envio das fichas, assim como informar sobre as patologias atualmente rastreadas, os critérios de seleção utilizados e o modo pelo qual deve ser dado conhecimento aos pais sobre os resultados do rastreio.
- Translational regulation of the human PERK by upstream open reading framesPublication . Silvestre, SamuelUpstream open reading frames (uORFs) are cis-acting elements located within the 5’ leader sequence (5’UTR) of transcripts, which can regulate protein synthesis, i.e. mRNA translation, of the correspondent main open reading frame (mORF). During endoplasmic reticulum (ER) stress, the accumulation of unfolded proteins activates the ER-resident PKR-like ER kinase (PERK), which results in phosphorylation of eIF2α to inhibit global mRNA translation, while allowing the selective uORF-mediated translation of downstream effectors responsible for stress resolution or, ultimately, cell death. The dual role of PERK in regulating cell fate was implicated in human diseases, like diabetes, neurodegenerative disorders and cancer. Moreover, mutations in the EIF2AK3 gene (encoding PERK) were associated with the rare genetic disease, Wolcott-Rallison Syndrome (WRS). In this work, we aimed to study the translational regulatory role of 5 AUG- and 3 non-AUG-uORFs identified in the PERK 5’UTR and assess its biological relevance. Altogether, we highlight the importance of including 5’UTRs in the screening of disease-related mutations and the necessity of functional studies to assess their role in pathogenesis.