Patrícia Abrantes

Low-frequency and common genetic variation in ischemic stroke: The METASTROKE collaboration.

Objective: To investigate the influence of common and low-frequency genetic variants on the risk of ischemic stroke (all IS) and etiologic stroke subtypes. Methods: We meta-analyzed 12 individual genome-wide association studies comprising 10,307 cases and 19,326 controls imputed to the 1000 Genomes (1 KG) phase I reference panel. We selected variants showing the highest degree of association (p < 1E-5) in the discovery phase for replication in Caucasian (13,435 cases and 29,269 controls) and South Asian (2,385 cases and 5,193 controls) samples followed by a transethnic meta-analysis. We further investigated the p value distribution for different bins of allele frequencies for all IS and stroke subtypes. Results: We showed genome-wide significance for 4 loci: ABO for all IS, HDAC9 for large vessel disease (LVD), and both PITX2 and ZFHX3 for cardioembolic stroke (CE). We further refined the association peaks for ABO and PITX2. Analyzing different allele frequency bins, we showed significant enrichment in low-frequency variants (allele frequency <5%) for both LVD and small vessel disease, and an enrichment of higher frequency variants (allele frequency 10% and 30%) for CE (all p < 1E-5). Conclusions: Our findings suggest that the missing heritability in IS subtypes can in part be attributed to low-frequency and rare variants. Larger sample sizes are needed to identify the variants associated with all IS and stroke subtypes.

Chloroquine mediated modulation of Anopheles gambiae gene expression.

Background Plasmodium development in the mosquito is crucial for malaria transmission and depends on the parasites interaction with a variety of cell types and specific mosquito factors that have both positive and negative effects on infection. Whereas the defensive response of the mosquito contributes to a decrease in parasite numbers during these stages, some components of the blood meal are known to favor infection, potentiating the risk of increased transmission. The presence of the antimalarial drug chloroquine in the mosquitos blood meal has been associated with an increase in Plasmodium infectivity for the mosquito, which is possibly caused by chloroquine interfering with the capacity of the mosquito to defend against the infection. Methodology/Principal Findings In this study, we report a detailed survey of the Anopheles gambiae genes that are differentially regulated by the presence of chloroquine in the blood meal, using an A. gambiae cDNA microarray. The effect of chloroquine on transcript abundance was evaluated separately for non-infected and Plasmodium berghei-infected mosquitoes. Chloroquine was found to affect the abundance of transcripts that encode proteins involved in a variety of processes, including immunity, apoptosis, cytoskeleton and the response to oxidative stress. This pattern of differential gene expression may explain the weakened mosquito defense response which accounts for the increased infectivity observed in chloroquine-treated mosquitoes. Conclusions/Significance The results of the present study suggest that chloroquine can interfere with several putative mosquito mechanisms of defense against Plasmodium at the level of gene expression and highlight the need for a better understanding of the impacts of antimalarial agents on parasite transmission.

Peri-urban agro-ecosystems in the Mediterranean: diversity, dynamics, and drivers

To address sustainability challenges of agro-ecosystems located in Mediterranean urban regions, this paper focuses on the multidisciplinary subject of urban agricultural systems. To better understand the diversity and dynamics of peri-urban agro-ecosystems and the main drivers of their sustainability, we compare six case studies located in Southern Europe (Montpellier, France; Pisa, Italy; Lisbon, Portugal; Athens, Greece) and the Maghreb (Constantine, Algeria; Meknes, Morocco). The research is based on fieldwork in each urban region (qualitative analysis) and literature analysis aimed to position each case study in its national and Mediterranean contexts. The comparison between local contexts indicates large discrepancies in the integration of environmental focus among the respective urban planning objectives. Generally, urbanization tends to accentuate agricultural diversity. The different forms of peri-urban agriculture evolve despite their persistent decline, and they also show a capacity to resist and even new growth in response to urban demand.

Metropolitan Dynamics Typology of the Portuguese Urban System

The metropolitan dynamics typology of the Portuguese urban system is the product of a methodology based on Geographic Information Systems (GIS). A GIS data describes six dimensions of metropolisation (population, economy, urban organisation, society and culture, networks and territorial organisation), based on a matrix of entities or indicators. Such a matrix has been subjected to treatment by neuronal networks through a Self-Organising Map (SOM). The method is robust in order to obtain a typology designated as DYMET (Metropolitan Dynamics Typology). As a result of the application of SOM’s classification algorithm ten types of areas were identified (metropolis core of Lisbon and of Porto, suburbanised area, suburbanised area in consolidation, potential metropolis centre, metropolisation area, area of urban dynamics, area of local centrality, peri-urbanised area, area with weak urban dynamics, area without urban dynamics) and compared to the typologies based on empirical studies of the Portuguese urban network developed mainly in the nineties. The identified types are described and characterised with some global dimension indicators.

Genetic Variants Underlying Risk of Intracranial Aneurysms: Insights from a GWAS in Portugal.

Subarachnoid hemorrhage (SAH) is a life-threatening event that most frequently leads to severe disability and death. Its most frequent cause is the rupture of a saccular intracranial aneurysm (IA), which is a blood vessel dilation caused by disease or weakening of the vessel wall. Although the genetic contribution to IA is well established, to date no single gene has been unequivocally identified as responsible for IA formation or rupture. We aimed to identify IA susceptibility genes in the Portuguese population through a pool-based multistage genome-wide association study. Replicate pools were allelotyped in triplicate in a discovery dataset (100 IA cases and 92 gender-matched controls) using the Affymetrix Human SNP Array 6.0. Top SNPs (absolute value of the relative allele score difference between cases and controls |RASdiff|≥13.0%) were selected for technical validation by individual genotyping in the discovery dataset. From the 101 SNPs successfully genotyped, 99 SNPs were nominally associated with IA. Replication of technically validated SNPs was conducted in an independent replication dataset (100 Portuguese IA cases and 407 controls). rs4667622 (between UBR3 and MYO3B), rs6599001 (between SCN11A and WDR48), rs3932338 (214 kilobases downstream of PRDM9), and rs10943471 (96 kilobases upstream of HTR1B) were associated with IA (unadjusted allelic chi-square tests) in the datasets tested (discovery: 6.84E-04≤P≤1.92E-02, replication: 2.66E-04≤P≤2.28E-02, and combined datasets: 6.05E-05≤P≤5.50E-04). Additionally, we confirmed the known association with IA of rs1333040 at the 9p21.3 genomic region, thus validating our dataset. These novel findings in the Portuguese population warrant further replication in additional independent studies, and provide additional candidates to more comprehensively understand IA etiopathogenesis.

Effect of chloroquine on gene expression of Plasmodium yoelii nigeriensis during its sporogonic development in the mosquito vector

BackgroundThe anti-malarial chloroquine can modulate the outcome of infection during the Plasmodium sporogonic development, interfering with Plasmodium gene expression and subsequently, with transmission. The present study sets to identify Plasmodium genes that might be regulated by chloroquine in the mosquito vector.MethodsDifferential display RT-PCR (DDRT-PCR) was used to identify genes expressed during the sporogonic cycle that are regulated by exposure to chloroquine. Anopheles stephensi mosquitoes were fed on Plasmodium yoelii nigeriensis-infected mice. Three days post-infection, mosquitoes were fed a non-infectious blood meal from mice treated orally with 50 mg/kg chloroquine. Two differentially expressed Plasmodium transcripts (Pyn_chl091 and Pyn_chl055) were further characterized by DNA sequencing and real-time PCR analysis.ResultsBoth transcripts were represented in Plasmodium EST databases, but displayed no homology with any known genes. Pyn_chl091 was upregulated by day 18 post infection when the mosquito had a second blood meal. However, when the effect of chloroquine on that transcript was investigated during the erythrocytic cycle, no significant differences were observed. Although slightly upregulated by chloroquine exposure the expression of Pyn_chl055 was more affected by development, increasing towards the end of the sporogonic cycle. Transcript abundance of Pyn_chl055 was reduced when erythrocytic stages were treated with chloroquine.ConclusionChloroquine increased parasite load in mosquito salivary glands and interferes with the expression of at least two Plasmodium genes. The transcripts identified contain putative signal peptides and transmembrane domains suggesting that these proteins, due to their location, are targets of chloroquine (not as an antimalarial) probably through cell trafficking and recycling.

A Bottom Up Approach to Modeling Habitat Connectivity Dynamics Through Networks Analysis

© 2012 Morgado et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A Bottom Up Approach to Modeling Habitat Connectivity Dynamics Through Networks Analysis

Metropolitan Dynamics Typology of the Portuguese Urban System~!2009-04-07~!2009-05-15~!2010-03-02~!

The metropolitan dynamics typology of the Portuguese urban system is the product of a methodology based on Geographic Information Systems (GIS). A GIS data describes six dimensions of metropolisation (population, economy, urban organisation, society and culture, networks and territorial organisation), based on a matrix of entities or indicators. Such a matrix has been subjected to treatment by neuronal networks through a Self-Organising Map (SOM). The method is robust in order to obtain a typology designated as DYMET (Metropolitan Dynamics Typology). As a result of the application of SOM’s classification algorithm ten types of areas were identified (metropolis core of Lisbon and of Porto, suburbanised area, suburbanised area in consolidation, potential metropolis centre, metropolisation area, area of urban dynamics, area of local centrality, peri-urbanised area, area with weak urban dynamics, area without urban dynamics) and compared to the typologies based on empirical studies of the Portuguese urban network developed mainly in the nineties. The identified types are described and characterised with some global dimension indicators.

The Integration Between Mediterranean Cities and Agriculture in Local Projects. A Conceptual Framework

The return of agriculture as a subject of debate in the realm of urban sustainable development is a recent phenomenon. Its presence is anchored in the recognition of the multifunctional role of agriculture and its importance in the conception and success of a more sustainable city. This study proposes a conceptual framework to analyse the socio-spatial integration between cities and agriculture in Mediterranean countries. The concept of integration is seen as a temporal process that articulates the actors, the spaces, and the resources linked by a project. Using a collection of local projects that explore the interactive dynamics of urban and agricultural relationships, the authors propose a conceptual framework, which reveals four aspects of socio-spatial integration. The first aspect encompasses socio-spatial integration through agricultural practices within the city. The second aspect includes integration processes through a pivotal actor playing as an interface between agriculture and the city. The third aspect concerns the flows and mobilities of resources and actors between cities and agricultural countryside. The fourth aspect deals with planning processes where the construction of networks of actors, spaces and resources are significant. These categories highlight the multidimensional processes of integration and the differentiated effects. The analysis is based on case studies situated in France, Italy, Portugal, Algeria, and Morocco.

GIS Graph Tool for Modeling: Urban–Rural Relationships

As the world is becoming increasingly more urbanized and built-up areas (that have an artificial cover as a result of human activities such as: urban fabric, industrial, commercial and transport units, mine, dump and construction sites, sports and leisure facilities) are endangering functional diversity, several environmental and spatial planning problems arise, such as urban sprawl, city food safety, community vulnerability to climate change, coastal erosion, and pollution (air, water, and noise). Lately, urban–rural relationships have attracted a lot of attention from both national and international community governance, hoping to mitigate and combat some of these problems. Although the necessary steps are known, it is unclear how to address the problems. A good understanding of how actors relate to each other in urban–rural relationships is fundamental. This paper introduces a novel GIS graph-based model tool (Geo_ graph ) for mapping and measuring urban–rural relationships through an actor’s network. The GIS graph model tool contributes to a better understanding of the relationships being built over the years under government supervision, and it also shows the relationships’ resilience and how many of these relationships are vulnerable to setbacks. The GIS graph tool provides decision makers with a visual image and numeric indicators of the relative role played by each of the actors. The methodology is grounded in graph theory and it results in a data-driven form of modeling using preprocessed data in a GIS environment.