The Central Role of Cytochrome P450 in Xenobiotic Metabolism—A Brief Review on a Fascinating Enzyme Family

Funding: The elaboration of this manuscript was in part funded by grant UID/BIM/0009/2020 of the Portuguese Fundação para a Ciência e a Tecnologia (FCT) for the Research Center for Toxicogenomics and Human Health (ToXomics).publishersversionpublishe

Non-receptor Tyrosine Kinases Role and Significance in Hematological Malignancies

This chapter presents a review about non-receptor tyrosine kinases, their structure, mechanisms of action and physiopathology, and how they are regulated and interact with other molecules and other signaling pathways, contributing to the regulation of fundamental cellular functions such as cell division and differentiation, stress responses, apoptosis, survival, and proliferation, gene expression, immune response, inter alia. Special emphasis will be assigned to the JAK family, the processes whereby it can be mutated/regulated and aberrantly activated, clinical significance and association with hematological disease progression and malignancy, mainly in myeloproliferative neoplasms. Consideration of these mechanisms may have important implications for selection of anti-cancer targeted therapies

mRNA therapy at the convergence of genetics and nanomedicine

OKJ.C. acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325).publishersversionpublishe

Classe de Ciências

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Classe de Ciências

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Classe de Ciências

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Elogio histórico do académico professor João Fraga de Azevedo

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O ensino da Medicina – Algumas Premissas em Busca de Uma Epistemologia do Ensino Médico

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Copy number variations and constitutional chromothripsis (Review)

Both copy number variations (CNVs) and chromothripsis are phenomena that involve complex genomic rearrangements. Chromothripsis results in CNVs and other structural changes. CNVs are frequently observed in the human genome. Studies on CNVs have been increasing exponentially; the Database of Genomic Variants shows an increase in the number of data published on structural variations added to the database in the last 15 years. CNVs may be a result of replicative and non-replicative mechanisms, and are hypothesized to serve important roles in human health and disease. Chromothripsis is a phenomena of chromosomal rearrangement following chromosomal breaks at multiple locations and involves impaired DNA repair. In 2011, Stephens et al coined the term chromothripsis for this type of fragmenting event. Several proposed mechanisms have been suggested to underlie chromothripsis, such as p53 inactivation, micronuclei formation, abortive apoptosis and telomere fusions in telomere crisis. Chromothripsis gives rise to normal or abnormal phenotypes. In this review, constitutional chromothripsis, which may coexist with multiple de novo CNVs are described and discussed. This reviews aims to summarize recent advances in our understanding of CNVs and chromothripsis, and describe the effects of these phenomena on human health and birth defects.publishersversionpublishe

A novel heterozygous missense mutation in the UMOD gene responsible for Familial Juvenile Hyperuricemic Nephropathy

Background: Familial Juvenile Hyperuricemic Nephropathy is an autosomal dominant nephropathy, characterized by decreased urate excretion and progressive interstitial nephritis. Mutations in the uromodulin coding UMOD gene have been found responsible for the disease in some families. Case presentation: We here describe a novel heterozygous p. K307T mutation in an affected female with hyperuricemia, renal cysts and renal failure. The proband's only son is also affected and the mutation was found to segregate with the disease. Conclusions: This mutation is the fourth reported in exon 5. Initial studies identified a mutation clustering in exon 4 and it has been recommended that sequencing this exon alone should be the first diagnostic test in patients with chronic interstitial nephritis with gout or hyperuricemia. However, regarding the increasing number of mutations being reported in exon 5, we now suggest that sequencing exon 5 should also be performed.publishersversionpublishe