Involvement of ANXA5 and ILKAP in Susceptibility to Malignant Melanoma

Single nucleotide-polymorphisms (SNPs) are a source of diversity among human population, which may be responsible for the different individual susceptibility to diseases and/or response to drugs, among other phenotypic traits. Several low penetrance susceptibility genes associated with malignant melanoma (MM) have been described, including genes related to pigmentation, DNA damage repair and oxidative stress pathways. In the present work, we conducted a candidate gene association study based on proteins and genes whose expression we had detected altered in melanoma cell lines as compared to normal melanocytes. The result was the selection of 88 loci and 384 SNPs, of which 314 fulfilled our quality criteria for a case-control association study. The SNP rs6854854 in ANXA5 was statistically significant after conservative Bonferroni correction when 464 melanoma patients and 400 controls were analyzed in a discovery Phase I. However, this finding could not be replicated in the validation phase, perhaps because the minor allele frequency of SNP rs6854854 varies depending on the geographical region considered. Additionally, a second SNP (rs6431588) located on ILKAP was found to be associated with melanoma after considering a combined set of 1,883 MM cases and 1,358 disease-free controls. The OR was 1.29 (95% CI 1.12-1.48; p-value= 4x10(-4)). Both SNPs, rs6854854 in ANXA5 and rs6431588 in ILKAP, show population structure, which, assuming that the Spanish population is not significantly structured, suggests a role of these loci on a specific genetic adaptation to different environmental conditions. Furthermore, the biological relevance of these genes in MM is supported by in vitro experiments, which show a decrease in the transcription levels of ANXA5 and ILKAP in melanoma cells compared to normal melanocytes.

Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

Background: Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods: A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results: Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: p(M-H) = 0.0005; ORM-H (95% CI) = 1.27 (1.11-1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [p(M-H) = 0.0003, ORM-H (95% CI) = 1.32 (1.14-1.53)]. Conclusion: Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.

Using productivity and susceptibility indices to assess the vulnerability of United States fish stocks to overfishing

Assessing the vulnerability of stocks to fishing practices in U.S. federal waters was recently highlighted by the National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric Administration, as an important factor to consider when 1) identifying stocks that should be managed and protected under a fishery management plan; 2) grouping data-poor stocks into relevant management complexes; and 3) developing precautionary harvest control rules. To assist the regional fishery management councils in determining vulnerability, NMFS elected to use a modified version of a productivity and susceptibility analysis (PSA) because it can be based on qualitative data, has a history of use in other fisheries, and is recommended by several organizations as a reasonable approach for evaluating risk. A number of productivity and susceptibility attributes for a stock are used in a PSA and from these attributes, index scores and measures of uncertainty are computed and graphically displayed. To demonstrate the utility of the resulting vulnerability evaluation, we evaluated six U.S. fisheries targeting 162 stocks that exhibited varying degrees of productivity and susceptibility, and for which data quality varied. Overall, the PSA was capable of differentiating the vulnerability of stocks along the gradient of susceptibility and productivity indices, although fixed thresholds separating low-, moderate-, and highly vulnerable species were not observed. The PSA can be used as a flexible tool that can incorporate regional-specific information on fishery and management activity.

Aplicação da geocomputação a estudos de susceptibilidade de deslizamentos de terra

Esta tese propôs uma metodologia para detecção de áreas susceptíveis a deslizamentos de terra a partir de imagens aéreas, culminando no desenvolvimento de uma ferramenta computacional, denominada SASD/T, para testar a metodologia. Para justificar esta pesquisa, um levantamento sobre os desastres naturais da história brasileira relacionada a deslizamentos de terra e as metodologias utilizadas para a detecção e análise de áreas susceptíveis a deslizamentos de terra foi realizado. Estudos preliminares de visualização 3D e conceitos relacionados ao mapeamento 3D foram realizados. Estereoscopia foi implementada para visualizar tridimensionalmente a região selecionada. As altitudes foram encontradas através de paralaxe, a partir dos pontos homólogos encontrados pelo algoritmo SIFT. Os experimentos foram realizados com imagens da cidade de Nova Friburgo. O experimento inicial mostrou que o resultado obtido utilizando SIFT em conjunto com o filtro proposto, foi bastante significativo ao ser comparado com os resultados de Fernandes (2008) e Carmo (2010), devido ao número de pontos homólogos encontrados e da superfície gerada. Para detectar os locais susceptíveis a deslizamentos, informações como altitude, declividade, orientação e curvatura foram extraídas dos pares estéreos e, em conjunto com as variáveis inseridas pelo usuário, forneceram uma análise de quão uma determinada área é susceptível a deslizamentos. A metodologia proposta pode ser estendida para a avaliação e previsão de riscos de deslizamento de terra de qualquer outra região, uma vez que permite a interação com o usuário, de modo que este especifique as características, os itens e as ponderações necessárias à análise em questão.