Targeting intraplaque angiogenesis : imaging and therapeutic interventions

Despite the available treatment options and sophisticated imaging technologies for monitoring lesion development, the morbidity and mortality from acute cardiovascular events remain unacceptably high.While cholesterol-lowering, anti-inflammatory and anti-platelet therapies benefits can increase survival as a primary or secondary prevention, they are not sufficient for plaque rupture prevention. Moreover, the most advance imaging technologies to detect high-risk atherosclerotic patients fail to visualize and explore cellular events in small preclinical models. Therefore, there is a clear need for the development of new therapies and the application of high-resolution imaging modalities.In the current thesis, we evaluated new possibilities to inhibit and image intraplaque angiogenesis.LUMC / Geneeskund

Evaluation of bone mineral density in cystic fibrosis patients

Patients with cystic fibrosis (CF) have an increasing life span and osteoporosis has become a more recognised problem in these patients. The pathogenesis of low bone mineral density (BMD) in CF seems to be multifactorial and the aim of this study was to assess the prevalence of low BMD in a group of CF outpatients and to relate the findings with the variables studied. The study included 22 patients aged between 14 and 45 years (mean age 26.3). Two of the subjects were lung transplant patients. BMD was assessed by dual-energy X-ray absorptiometry (DEXA) at the lumbar spine (LS) and femoral neck (FN). This data was correlated with serum 25-hydroxy vitamin D (25-OHD) levels, BMI and the forced expiratory volume in one second (FEV1). BMD (Z-score and T-score) ranged from 0.6 to -6 and from 0.5 to -6.7 at LS; at FN the scores ranged from 0.6 to -3.9 and from 0.6 to -4.1. The mean serum 25-OHD concentration (12,57 ng/ml) was at the low end of the normal range (10-60 ng/ml). On average patients did not present with malnutrition, however BMI ranged from 15.2 to 33.7 kg/m2. Lung function status was assessed by FEV1; 64% of patients had FEV1 below 80% and within this group four patients had a FEV1 under 40%. There was a positive correlation between low BMD and 25-OHD concentrations and also between BMD and FEV1. There was no linear correlation between BMD and BMI

Plaque angiogenesis and intraplaque hemorrhage in atherosclerosis

Vascular Surger

Atorvastatin pleiotropically decreases intraplaque angiogenesis and intraplaque haemorrhage by inhibiting ANGPT2 release and VE-Cadherin internalization

Objective Statins pleiotropically provide additional benefits in reducing atherosclerosis, but their effects on intraplaque angiogenesis (IPA) and hemorrhage (IPH) remain unclear. Therefore, we discriminated statin's lipid-lowering dependent and independent effects on IPA and IPH. Approach and results ApoE3*Leiden mice are statin-responsive due to ApoE and LDLR presence, but also allow to titrate plasma cholesterol levels by diet. Therefore, ApoE3*Leiden mice were fed a high-cholesterol-inducing-diet (HCD) with or without atorvastatin (A) or a moderate-cholesterol-inducing-diet (MCD). Mice underwent vein graft surgery to induce lesions with IPA and IPH. Cholesterol levels were significantly reduced in MCD (56%) and HCD + A (39%) compared to HCD with no significant differences between MCD and HCD + A. Both MCD and HCD + A have a similar reduction in vessel remodeling and inflammation comparing to HCD. IPA was significantly decreased by 30% in HCD + A compared to HCD or MCD. Atorvastatin treatment reduced the presence of immature vessels by 34% vs. HCD and by 25% vs. MCD, resulting in a significant reduction of IPH. Atorvastatin's anti-angiogenic capacity was further illustrated by a dose-dependent reduction of ECs proliferation and migration. Cultured mouse aortic-segments lost sprouting capacity upon atorvastatin treatment and became 30% richer in VE-Cadherin expression and pericyte coverage. Moreover, Atorvastatin inhibited ANGPT2 release and decreased VE-Cadherin(Y685)-phosphorylation in ECs. Conclusions Atorvastatin has beneficial effects on vessel remodeling due to its lipid-lowering capacity. Atorvastatin has strong pleiotropic effects on IPA by decreasing the number of neovessels and on IPH by increasing vessel maturation. Atorvastatin improves vessel maturation by inhibiting ANGPT2 release and phospho(Y658)-mediated VE-Cadherin internalization.Cardiolog

(I)Migrantes, diversidades e desigualdades no sistema educativo português : balanço e perspectivas

O objectivo do presente artigo consiste em procurar transmitir um olhar sociologicamente informado no que concerne à situação portuguesa no domínio das políticas educativas públicas e investigações produzidas relacionadas com o sistema educativo e a (i)migração, ou seja, com a tentativa de construção de uma educação intercultural. Neste sentido, será realizada uma análise descritiva e compreensivo-interpretativa da evolução desta problemática em Portugal desde que a mesma se tornou objecto de reflexão por parte de investigadores/as e políticos nos finais da década de oitenta, início da década de noventa do século XX. Nesta análise, será dada ênfase às investigações e quadros teóricos produzidos e às medidas legislativas e políticas educativas no domínio do tratamento da diferença cultural dentro do sistema educativo português.The aim of this article consists in attempting to transmit a sociologically informed view in what the Portuguese situation in the field of public policies and research related to the educational system and (im)migration are concerned, that is, in attempting to construct an intercultural education. In this way, a descriptive and comprehensiveinterpretative analysis of the evolution of this problem in Portugal will be realized, since the latter became an object of reflection on the part of researchers and politicians towards the end of the 80s, the beginning of the 90s of the XXth century. In this analysis, emphasis will be given on the research and theoretical frameworks produced and on the legislative measures and educational policies in the field of treating cultural difference in the Portuguese educational system

New Emigration and Portuguese Society: Transnationalism and Return

This chapter addresses the theme of transnationalism and return in recent Portuguese emigration, namely the flows that occurred after the turn of the century. It starts with a brief theoretical overview on those topics, which constitute two relatively neglected characteristics of Portuguese emigration. Next, based on a survey carried out in 2014–2015 to more than 6000 recent emigrants, it reveals some of the links that they maintain with their home country, as well as their plans for the future, which include settlement in the destination country, return and re-emigration. Lastly, it examines data on returning emigrants – especially those that returned between 2001 and 2011 – extracted from the 2011 Census. The evidence reveals a significant number of returns, including individuals at both working and retirement ages and at all skill levels, thus exposing the unexpected complexity of movements. The results are based on the research project “Back to the future: new emigration and links with Portuguese society” (REMIGR), which aimed to ascertain the extent and characteristics of the new emigration wave. The project included an overview of emigration and return to and from all regions of the world, as well as case studies in UK, France, Luxembourg, Angola, Mozambique and Brazil.info:eu-repo/semantics/publishedVersio

Origin and history of Phoxinus (Cyprinidae) introductions in the Douro basin (Iberian Peninsula): an update inferred from genetic data

The number of non-native freshwater fishes in the Iberian Peninsula has been greatly increasing. In this study, individuals of the genus Phoxinus were detected in 18 out of 138 stream sites sampled across the Douro Basin in 2017 and 2018. A total of 26 individuals were barcoded using partial cytochrome c oxidase subunit I (COI) and cytochrome b (cytb) genes for species identification and determination of geographical origin. Molecular data provided the first record of a second Phoxinus species in western Douro (Portugal, Iberian Peninsula), with haplotypes closely matching those found in the Charente River (southern France). This species is suspected to be a recent introduction associated with the use of minnows as live bait by freshwater anglers, which was facilitated by human movements between France and Portugal. Individuals from watercourses in eastern Douro (Spain) were genetically assigned to Phoxinus bigerri, an introduced species previously known for that region, which confirms reports of introduction events from Ebro to Douro Basin probably also related to freshwater angling and facilitated by geographic proximity. The potential ecological impacts of this genus in the region are unknown and need further investigation.We acknowledge Fernando Teixeira, Fernando Miranda, Mario Ferreira, Sara Carona, Jose Pedro RamiAo and Francisco Carvalho for the valuable assistance during fieldwork. We specially thank Maria Filomena MagalhAes for previous fruitful discussions and logistic support. We are grateful to Matthias F. Geiger and Andrea Corral Lou for facilitating genetic data and coordinates of sampling sites. Finally, we appreciate the comments of the three anonymous reviewers that improved the quality of the manuscript. AFF and AGR were supported by the project FRESHING founded by the Portuguese Foundation for Science and Technology (FCT) and COMPETE (PTDC/AAGMAA/2261/2014 - POCI-01-0145-FEDER-356016824). FMSM was supported by the FCT PhD grant SFRH/BD/104703/2014. This study was conducted as part of the projects FRESHING and FRESHCO. The latter is also supported by FCT and COMPETE (PTDC/AGR-FOR/1627/2014 - 04/SAICT/2015) and UID/AGR/04033/2019. Logistic support was also facilitated by the ENVMETAGEN - Capacity Building at InBIO for Research and Innovation Using Environmental Metagenomics project at CIBIO laboratories (668981; EUH2020-WIDESPREAD-2014-2)

Adenosine-to-inosine editing of vasoactive microRNAs alters their targetome and function in ischemia

Adenosine-to-inosine (A-to-I) editing in the seed sequence of microRNAs can shift the microRNAs' targetomes and thus their function. Using public RNA-sequencing data, we identified 35 vasoactive microRNAs that are A-to-I edited. We quantified A-to-I editing of the primary (pri-)microRNAs in vascular fibroblasts and endothelial cells. Nine pri-microRNAs were indeed edited, and editing consistently increased under ischemia. We determined mature microRNA editing for the highest expressed microRNAs, i.e., miR-376a-3p, miR-376c3p, miR-381-3p, and miR-411-5p. All four mature microRNAs were edited in their seed sequence. We show that both ADAR1 and ADAR2 (adenosine deaminase acting on RNA 1 and RNA 2) can edit pri-microRNAs in a microRNA-specific manner. MicroRNA editing also increased under ischemia in vivo in a murine hindlimb ischemia model and ex vivo in human veins. For each edited microRNA, we confirmed a shift in targetome. Expression of the edited microRNA targetomes, not the wild type targetomes, was downregulated under ischemia in vivo. Furthermore, microRNA editing enhanced angiogenesis in vitro and ex vivo. In conclusion, we show that microRNA A-to-I editing is a widespread phenomenon, induced by ischemia. Each editing event results in a novel microRNA with a unique targetome, leading to increased angiogenesis.Vascular Surger

Portuguese emigration to Angola (2000-2015): Strengthening a specific postcolonial relationship in a new global framework?

Outflows to the Portuguese-speaking countries, although not dominant, played an important role in the growth of Portuguese emigration during the economic recession and austerity period, between 2010 and 2016. This chapter examines this migration process, considering that contemporary migration from Portugal to Angola is an example of reverse post-colonial migration within the framework of North-South movements. It presents the historical and socio-demographic background of Angola and some theoretical insights on the issue of North-South migration. The analyses of the migration process and the emigrants’ profiles rely in statistics and academic literature but especially on data gathered in a direct survey. Attention is given to indicators of integration, relations with Portugal and the post-colonial nature of the process. The profile of Portuguese in Angola shows an overrepresentation of highly skilled males over 35 years old, which migrated for professional reasons and sustain relations with Portugal through diverse transnational practices. This supports explanations for the emergence of North-South migration by appeal to economic expansion associated to the increasing insertion of several developing countries into global networks. However, the analysis fails to back up the hypothesis that Portuguese emigration to Angola is a form of reverse post-colonial migration based in ancestral return.info:eu-repo/semantics/publishedVersio