Aterosclerose e doença cardiovascular : o problema do colesterol elevado

A secção Biologia é coordenada pelo Professor Universitário Armindo Rodrigues.A aterosclerose é a principal causa de patologia cardiovascular. A Hipercolesterolemia Familiar é uma doença genética, e um factor de risco para a aterosclerose

Familial hypercholesterolemia: Molecular characterization of possible cases from the Azores Islands (Portugal)

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of the cholesterol metabolism, which constitutes a risk factor for coronary arterial disease (CAD). In the Azores Islands (Portugal), where mortality from CAD doubles its rate comparatively to the rest of the country and where a high frequency of dyslipidemia has been reported, the prevalence and distribution of FH remain unknown. The molecular characterization of a group of 33 possible cases of FH of Azorean background was undertaken in this study. A DNA array was initially used to search mutations in the LDLR, APOB and PCSK9 loci in 10 unrelated possible cases of FH. No mutations were detected in the array; after sequencing the full LDLR gene, 18 variants were identified, corresponding to two missense (c.806G > A; c.1171G > A) and sixteen synonymous alterations. Six of the synonymous variants which are consistently described in the literature as associated with altered cholesterol levels were used to build haplotypes. The most frequent haplotype corresponded to TTCGCC (45%), a "risk" haplotype, formed exclusively by alleles that were reported to increase cholesterol levels. Some of the variants detected in the full sequencing of the LDLR gene fell within the ligand-binding domain of this gene, defined by exons 2 to 6. To add information as to the role of such variants, these exons were sequenced in the remaining 23 possible FH cases. Two missense alterations (c.185C > T; c.806G > A) were found in this subset of possible FH cases. The missense alteration c.185C > T, identified in one individual, is novel for the Portuguese population. In silico analysis was not conclusive for this alteration, whose role will have to be further investigated. This study represents the first approach to the establishment of the mutational profile of FH in the Azores Islands.This work was supported by the project entitled “High prevalence pathologies in the Azores: genetic and biochemical markers” with reference (M2.1.2/I/026/2008) funded by SRCTE. M. R. receives a PhD fellowship (M3.1.2/F/006/2011) from Fundo Regional para a Ciência. T.C. receives a post-doctoral fellowships from Fundação para a Ciência e a Tecnologia (SFRH/BPD/38659/ 2007) and N. K. (M3.1.7/F/002/2008) and A. R. (M3.1.7/F/031/2011) both receives post-doctoral fellowships from Fundo Regional para a Ciência

Implementation of the Water Framework Directive in an outermost EU region : the case of Azores archipelago

The Azores Water Plan (AWP) came to force in year 2003 in order to provide a coherent set of measures to protect and enhance water resources in the archipelago. The AWP was developed according to EU Water Framework Directive (WFD) and a close relationship can be found between goals on both documents. The evaluation of results associated to AWP implementation, made possible through a consultation procedure described in the present paper, provides an indirect assessment of the implementation of the WFD in an EU outermost region such as the Azores. The analysis suggests that major constrains to the full implementation of the AWP and WFD are associated with administrative arrangements, reflected in a lack of coordination, as well as adequate funding and cost recovery and strategies for public participation and information provision. Instead, water quality monitoring is already fully operational showing a strong relationship between science and water policy

Patterns of mitochondrial DNA damage in blood and brain tissues of a transgenic mouse model of Machado-Joseph disease

BACKGROUND: Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia caused by a CAG tract expansions in the ATXN3 gene. Patterns of mitochondrial damage associated with pathological findings of brain tissues could provide molecular biomarkers of this disorder. OBJECTIVE: The potential of mitochondrial DNA (mtDNA) damage as a biomarker of MJD progression was investigated using a transgenic mouse model. METHODS: DNA was obtained from affected (pontine nuclei) and nonaffected tissues (hippocampus and blood) of transgenic animals of three distinct age groups: 8 weeks, before onset of the phenotype; 16 weeks, at onset, and 24 weeks, at well-established phenotype. Wild-type littermate mice, serving as controls, were analyzed for the same tissues and age groups. mtDNA damage was studied by fluorescence-based quantitative PCR in 84 transgenic and 93 wild-type samples. RESULTS: A clear pattern of decrease in mtDNA copy number with age and accumulation of 3,867-bp deletions at the initial stages (both being more pronounced in transgenic mice) was observed. Pontine nuclei, the affected tissue in transgenic mice, displayed 1.5 times less copies of mtDNA than nonaffected brain tissue hippocampus (odds ratio = 1.21). Pontine nuclei displayed the highest percentage of mtDNA deletions (6.05% more in transgenic mice). CONCLUSION: These results suggest that mtDNA damage is related to the initiation of the phenotype in transgenic mice; mtDNA 3,867-bp deletions may be a biomarker of the initial stages of the disease.This study was supported by the following grants: DRCT Postdoctoral fellowship to N.K. (M3.1.7/F/002/2008), FCT Postdoctoral fellowship to T.C. (SFRH/BPD/38659/2007) and C.B. (SFRH/BPD/63121/2009), FCT research grants to S.S. (PTDC/SAU-GMG/64076/2006) and A.S.F. (PIC/IC/83013/2007)

A Partial African Ancestry for the Creole Cattle Populations of the Caribbean

Seventy-eight cattle samples from three Creole Caribbean islands and one Brazilian breed were analyzed for sequence variation in the hypervariable segment of the mitochondrial DNA control region. Seventy-three samples displayed Bos taurus haplotypes, and five samples exhibited haplotypes that were of Bos indicus ancestry. Phylogenetic analysis revealed that all sampled B. taurus sequences fell into two distinct clusters with separate African and European origins. European sequences were encountered in each population; however, the distribution of African haplotypes was uneven, with the highest proportion of African influence found in the Guadeloupe Creole. The reduced levels of African haplotypic variation within the Caribbean and Brazilian are consistent with prior founder effects. Additionally, genetic variation at three microsatellite loci illustrated African influence uniquely in the Guadeloupe Creole. Collectively, the data suggest that this African influence is, at least in part, attributable to the historical importation of African cattle to the Americas. Furthermore, alleles of B. indicus ancestry were detected at appreciable frequencies in all Caribbean Creole populations and may reflect zebu introgressions from either West Africa or the Indian subcontinen

On the Breeds of Cattle—Historic and Current Classifications

Classification of cattle breeds contributes to our understanding of the history of cattle and is essential for an effective conservation of genetic diversity. Here we review the various classifications over the last two centuries and compare the most recent classifications with genetic data. The classifications devised during the 19th to the late 20th century were in line with the Linnaean taxonomy and emphasized cranial or horn morphology. Subsequent classifications were based on coat color, geographic origin or molecular markers. Several theories were developed that linked breed characteristics either to a supposed ancestral aurochs subspecies or to a presumed ethnic origin. Most of the older classifications have now been discarded, but have introduced several Latin terms that are still in use. The most consistent classification was proposed in 1995 by Felius and emphasizes the geographic origin of breeds. This is largely in agreement with the breed clusters indicated by a biochemical and molecular genetic analysis, which reflect either groups of breeds with a common geographic origin or single breeds that have expanded by export and/or crossbreeding. We propose that this information is also relevant for managing the genetic diversity of cattl

Reflexiones sobre música y espacio atlántico en el siglo XIX: intercambios ibéricos e iberoamericanos

En la historiografía actual, el concepto de ‘espacio atlántico’, que parte de un campo de estudio más amplio —la llamada Historia del Atlántico—, ha sido utilizado particularmente para el estudio del Antiguo Régimen. Este concepto tiene también puntos de contacto con los estudios transnacionales y solo recientemente comienza a ser aplicado al estudio de la música. Nada impide, sin embargo, que se parta de él para estudiar las relaciones transatlánticas en la música del siglo XIX, una época en la que las relaciones entre España, Portugal y sus antiguas colonias americanas habían ya evolucionado hacia una diplomacia entre naciones independientes (dos de ellas antiguas y las otras, jóvenes) y durante la cual, la emigración transatlántica fue un fenómeno de gran impacto en distintos niveles. Partiendo de un conjunto de testimonios documentales encontrados en las Azores, un pequeño archipiélago en el Atlántico Norte por el que, al menos desde el siglo XVII, pasaban las rutas que conectaban las áreas geográficas de lengua y cultura castellana y portuguesa, este artículo discute fenómenos como los ritmos e imágenes sonoras de la música nacional y/o cosmopolita entre España, Portugal y las Américas hispana y portuguesa (a partir de los ejemplos del lundum y del tango-habanera), los ideales de la ópera nacional y del cosmopolitismo (a través del proyecto de invención de una ópera nacional portuguesa apoyado por la comunidad de emigrantes portugueses en el Brasil que se materializó en Beatriz de Portugal de Francisco de Sá Noronha o del estreno de I vespri siciliani de Verdi en los teatros ibéricos).

in search of a transnational approach

UID/EAT/00693/2013In Portugal, an old popular saying states that "From Spain, neither a good wind nor a good marriage". This proverb reflects an anti-castilianism that hasn’t always been shared by the whole Portuguese society. But the message it expressed, even if decontextualized, allows us to understand the distances that were forged, for centuries, between the two states that make up the peninsula. In the 19th-Century, however, when perceived from Italy and by opera producing agents, the political-administrative divisions within the Iberian peninsula appeared blurred. This suggests the outset of a transnational approach. Nevertheless, neither Portuguese nor Spanish Musicology seem so far to have been interested in this type of approach. The main exception is David Cranmer’s article, “Intercâmbio entre Portugal e Espanha no campo da ópera entre 1793 e 1828” (Revista Portuguesa de Musicologia, 1 (1991), pp. 205-210), where he discusses the relationship between the theatres of the two countries and the circulation of repertoires, singers and other theatre professionals. Starting from an opera like Donizetti’s Il furioso all'Isola di San Domingo, which was premiered in Rome in 1833 and had a wide circulation in Italian theatres, this paper aims to explain the reasons and conditions that characterized its success in this geographical space. These are: 1) the fact that in some cities Rossini’s heritage enjoyed a larger acceptance than the Romantic models; 2) in Spain, the fact that the opera is based on an episode of Don Quijote; 3) in the Portuguese reception, the attempt to adapt it both to the demands of a prima donna and a more openly Romantic taste; 4) in both countries, the fascination with tropical environments, in a context of strong colonial connections with Central and South America. Finally, the opera's Iberian dissemination and reception reveals a set of regional circuits inside the Península which ultimately allows us to overcome political boundaries.publishersversionpublishe

recezione verdiana e rifiuto della storia nazionale

UID/EAT/00693/2013authorsversionpublishe

The APOE ε2 allele increases the risk of Earlier Age at onset in Machado-Joseph disease

Background. Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder of late onset, caused by a (CAG)n expansion at the ATXN3 gene (14q32.1). Variation in age-at-onset is partially explained by the size of the (CAG)n tract in expanded alleles. The remaining variation should be the product of other factors, namely modifier genes. The genotype at the APOE locus has been described as a possible modifier in different neurological disorders, namely Parkinson (PD) and Huntington disease (HD). In the CNS, apolipoprotein E constitutes an important mediator of cholesterol transport/metabolism, which is essential for synaptic integrity and neuronal function. Objective. To investigate a modulating effect of the APOE polymorphism on age-at-onset of MJD. Design and Subjects. The APOE polymorphism was typed in a series of 192 MJD patients. Results. Cases with the ε2/ε3 genotype presented an earlier onset, when compared with those with ε3/ε3 or ε3/ε4. In this series of patients, the presence of an APOE ε2 allele implies a decrease of nearly 5 years in the age-at-onset. When combining, in a general linear model, several other predictors, namely the presence/absence of the APOE ε2 allele, with the size of the (CAG)n in expanded alleles, the model was significantly improved and the explanation of onset variance was raised from 59.8% to 66.5%. Furthermore, the presence of the ε2 allele was associated with an onset below 39 years (OR=5.00; 95% CI: 1.18-21.14). Conclusions. These findings indicate that the polymorphism at the APOE gene plays a role as a genetic modifier of MJD phenotype.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BPD/63121/2009, SFRH/BPD/38659/2007, M3.1.3/F/004/2009, “Secretaria Regional da Ciência, Tecnologia e Equipamentos”.Fundação para a Ciência e a Tecnologia (FCT) - “Transcriptional variation of the ATXN3 gene as modulator of the clinical heterogeneity in Machado-Joseph disease (MJD)” (PIC/IC/83074/2007)Institute of Biotechnology and Biomedicine (IBBA) - “High prevalence diseases in the Azores Islands” (M2.1.2/I/026/2008