Molecular basis of the non-classical hereditary hemochromatosis in Portugal

A Hemocromatose Hereditária (HH) é uma doença autossómica recessiva caracterizada pela absorção excessiva de ferro a nível intestinal e sua acumulação em órgãos vitais, podendo originar cardiomiopatia, cirrose e carcinoma hepatocelular. O correspondente diagnóstico molecular é obtido pela associação com genótipos específicos no gene HFE (homozigotia para p.Cys282Tyr ou heterozigotia composta p.Cys282Tyr/p.His63Asp). Contudo, nos países do sul da Europa, cerca de um terço dos doentes com diagnóstico clínico de HH não apresenta os referidos genótipos. Para identificar a base molecular da HH não-clássica em Portugal usaram-se metodologias de pesquisa geral de variantes genéticas (SSCP e dHPLC), Next-Generation Sequencing (NGS) e sequenciação de Sanger, cobrindo seis genes relacionados com o metabolismo do ferro em 303 doentes. Identificaram-se 69 variantes diferentes e de vários tipos, por ex. missense, nonsense, de splicing, que perturbam a transcrição do gene ou a regulação da tradução do mRNA. Seguidamente, realizaram-se estudos in silico e in vitro para esclarecer o significado etiológico de algumas das novas variantes. Concluiu-se que a base molecular desta patologia é bastante heterogénea e que a NGS é uma ferramenta adequada para efetuar a análise simultânea dos vários genes num grande número de amostras. Contudo, o estabelecimento da relevância clínica de algumas variantes requer a realização de estudos funcionais.Hereditary Hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive intestinal iron absorption and deposition in vital organs leading to cardiac failure, cirrhosis and hepatocellular carcinoma. Molecular diagnosis of common HH is made by the presence of specific genotypes in HFE gene (p.Cys282Tyr homozygosity or p.Cys282Tyr/p.His63Asp compound heterozygosity). However, in Southern European countries up to one third of the patients with a clinical diagnosis of HH do not have these genotypes. In order to identify the molecular basis of the non-classical HH in Portugal, we used genetic screening methods for the detection of unknown mutations (SSCP and dHPLC), Next-Generation Sequencing (NGS) and/or Sanger sequencing in six HH-related genes in 303 patients. Sixty-nine different variants were identified, including missense, nonsense and splicing variants, and variants that impair gene transcription or mRNA translation regulation. In silico and in vitro studies were performed to know the likely etiologic significance of some of the novel variants found. We can conclude that the molecular basis of the non-classical HH in Portuguese population is largely heterogeneous. NGS revealed to be an appropriate tool for fast analysis of the HH-related genes in a large number of samples. However, establishing the clinical relevance of some novel variants requires further functional studies

Next-generation sequencing of hereditary hemochromatosis-related genes: novel likely pathogenic variants found in the Portuguese population

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism-related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1GNC)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5′-UTR of HAMP gene(c.-25GNA). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism-related disorders

Mídia e política no Brasil: textos e agenda de pesquisa Midia and politics in Brazil: texts and research agenda

Um especialista em estudos de comunicação e um cientista político apresentam conjuntamente um panorama da pesquisa sobre as relações entre os meios de comunicação e os processos políticos no Brasil. Uma agenda de pesquisa é proposta e um elenco de textos nessa área é apresentado.<br>A specialist in communication studies and a political scientist present together a panorama of research on the relations between communication midia and political processes in Brazil A research agenda is proposed and a list of texts in this area is presented

Comentarios a una sentencia anunciada : el proceso Lula

El centenar de textos que conforman este libro -escritos por un movimiento de prestigiosos/as juristas y abogados- desgranan el procedimiento al que fue sometido Lula. En la opinión de las y los autores de los artículos las normas no fueron observadas, y su inobservancia llevó a que se dictaminase una decisión injusta. Frases del estilo "Voy a tomar una decisión revolucionaria, dejando de lado la ley, porque por la ley no se puede condenarlo de ninguna manera”, dichas en los juicios por las más altas autoridades judiciales militares y civiles, hoy son conocidas gracias a quienes se abocaron al trabajo de escuchar los audios de aquellas sesiones, nutriendo las reflexiones que argumentan sobre el imperativo de la hora: restablecer el estado de derecho y absolver al presidente Lula Da Silva

Comenta&#769;rios a uma sentenc&#807;a anunciada : o processo Lula

“Comentários a uma sentença: o Caso Lula” é talvez o mais importante documento jurídico publicado no Brasil em décadas. A presente coletânea de artigos nasceu de um movimento espontâneo e bastante significativo de juristas brasileiros e estrangeiros que examinaram cuidadosamente a sentença proferida no âmbito do processo que tramitou na 13ª Vara Federal de Curitiba, no caso que ficou conhecido na mídia como o do “tríplex do Guarujá”. <br>De la presentación de Geraldo Prad

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved

Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora