A Customized Pigmentation SNP Array Identifies a Novel SNP Associated with Melanoma Predisposition in the SLC45A2 Gene

As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date

Profilage et Visualisation de Datasets d’Applications Android Malveillantes

Mobile devices are ubiquitous: nowadays most people own a mobile telephone.Because of this, it is a target of interest for attackers.Researchers in malware analysis put their effort to recognize these types of programs before they are installed on a user device.To do this, they perform experiments to automatically detect malware, for example with machine learning, where they use sets of already known malware and goodware.Depending on their choice of datasets, the evaluation of the experiments can yield acceptable results, or outstanding but overestimated results.Consequently, datasets with malware and benign samples are important elements to consider when designing an experiment.This thesis presents, first, a method to evaluate the quality of datasets based on a statistical test that helps to compare a crafted dataset against a large set of applications such as markets.We show that historical datasets of the literature are of low quality, which justifies the need to create new up-to-date datasets.Second, we introduce an algorithm to update mixed datasets of malware/goodware of low quality in order to resemble a target dataset that cannot be used directly, \eg a market.We evaluate the updated mixed datasets using a machine learning algorithm and we show that the detection of malware in our up-to-date dataset becomes a more difficult problem to solve.Lastly, we introduce DaViz, a dataset visualization tool for exploring and comparing Android malware datasets, which enables researchers to visualize the biases in datasets of the literature, and obtain useful information from them.Les dispositifs mobiles sont ubiquitaires: aujourd’hui la majorité des gens possèdent un téléphone mobile. A cause de ce fait, ces dispositifs sont une cible d’intérêt pour les attaquants. Ces attaques sont véhiculées au travers des applications malveillantes qui peuvent nuire aux dispositifs mobiles. Les chercheurs en analyse de malware travaillent à reconnaître ces types de programmes avant qu’ils soient installés sur un dispositif utilisateur. Pour faire cela, ils réalisent des expériences pour automatiquement détecter ces malware, où ils utilisent des ensembles de malware et des applications bénignes déjà connues. Selon le dataset choisi, les résultats des expériences peuvent être acceptables ou bien exceptionnellement bons parce que surestimés. Par conséquent, les datasets de malware et applications bénignes sont des éléments importants à considérer quand nous élaborons une expérience. Cette thèse présente, premièrement, une méthode pour évaluer la qualité des datasets basée sur un test statistique qui aide à comparer un dataset créé avec un grand ensemble d’applications par exemple issu d’un magasin d’applications. Nous montrons alors que les datasets historiques de la littérature sont de mauvaise qualité, ce qui justifie le besoin de créer des nouveaux datasets plus à jour. Deuxièmement, nous introduisons un algorithme pour mettre à jour des datasets mixtes de malware/goodware de mauvaise qualité afin de ressembler à un dataset cible qui ne peut pas être utilisé directement, e.g. un magasin d’applications. Nous évaluons les datasets mixtes mis à jour en utilisant un algorithme d’apprentissage automatique et nous montrons que la détection de malware sur notre dataset mis à jour devient un problème plus difficile à résoudre. Enfin, nous introduisons DaViz, un outil de visualisation de datasets pour explorer et comparer des datasets d’applications Android. Cet outil permet aux chercheurs de visualiser les biais dans les datasets de la littérature, et d’obtenir des informations utiles à leur propos

Profilage et Visualisation de Datasets d’Applications Android Malveillantes

Mobile devices are ubiquitous: nowadays most people own a mobile telephone.Because of this, it is a target of interest for attackers.Researchers in malware analysis put their effort to recognize these types of programs before they are installed on a user device.To do this, they perform experiments to automatically detect malware, for example with machine learning, where they use sets of already known malware and goodware.Depending on their choice of datasets, the evaluation of the experiments can yield acceptable results, or outstanding but overestimated results.Consequently, datasets with malware and benign samples are important elements to consider when designing an experiment.This thesis presents, first, a method to evaluate the quality of datasets based on a statistical test that helps to compare a crafted dataset against a large set of applications such as markets.We show that historical datasets of the literature are of low quality, which justifies the need to create new up-to-date datasets.Second, we introduce an algorithm to update mixed datasets of malware/goodware of low quality in order to resemble a target dataset that cannot be used directly, \eg a market.We evaluate the updated mixed datasets using a machine learning algorithm and we show that the detection of malware in our up-to-date dataset becomes a more difficult problem to solve.Lastly, we introduce DaViz, a dataset visualization tool for exploring and comparing Android malware datasets, which enables researchers to visualize the biases in datasets of the literature, and obtain useful information from them.Les dispositifs mobiles sont ubiquitaires: aujourd’hui la majorité des gens possèdent un téléphone mobile. A cause de ce fait, ces dispositifs sont une cible d’intérêt pour les attaquants. Ces attaques sont véhiculées au travers des applications malveillantes qui peuvent nuire aux dispositifs mobiles. Les chercheurs en analyse de malware travaillent à reconnaître ces types de programmes avant qu’ils soient installés sur un dispositif utilisateur. Pour faire cela, ils réalisent des expériences pour automatiquement détecter ces malware, où ils utilisent des ensembles de malware et des applications bénignes déjà connues. Selon le dataset choisi, les résultats des expériences peuvent être acceptables ou bien exceptionnellement bons parce que surestimés. Par conséquent, les datasets de malware et applications bénignes sont des éléments importants à considérer quand nous élaborons une expérience. Cette thèse présente, premièrement, une méthode pour évaluer la qualité des datasets basée sur un test statistique qui aide à comparer un dataset créé avec un grand ensemble d’applications par exemple issu d’un magasin d’applications. Nous montrons alors que les datasets historiques de la littérature sont de mauvaise qualité, ce qui justifie le besoin de créer des nouveaux datasets plus à jour. Deuxièmement, nous introduisons un algorithme pour mettre à jour des datasets mixtes de malware/goodware de mauvaise qualité afin de ressembler à un dataset cible qui ne peut pas être utilisé directement, e.g. un magasin d’applications. Nous évaluons les datasets mixtes mis à jour en utilisant un algorithme d’apprentissage automatique et nous montrons que la détection de malware sur notre dataset mis à jour devient un problème plus difficile à résoudre. Enfin, nous introduisons DaViz, un outil de visualisation de datasets pour explorer et comparer des datasets d’applications Android. Cet outil permet aux chercheurs de visualiser les biais dans les datasets de la littérature, et d’obtenir des informations utiles à leur propos

Grounded Theory : A Methodology Choice to Investigating Labia Minora Elongation Among Zambians in South Africa

A study on how Zambian migrants living in Cape Town perceive and experience the implications of labial elongation on women's health was conducted. Labia minora elongation (LME) is a genital modification that some women in east and southern Africa practice. This tradition is not common in Western Cape province (southwestern part of South Africa). The aim of this article is to discuss the methodological choices made in the design and conduct of this study, in which a White European male interviewed the female study participants on the health implications of a practice that is considered a woman's private issue. Constructivist grounded theory informed by a feminist perspective was chosen as the most suitable methodological approach to enable cogeneration of knowledge with the female participants. The methods and tools used by the lead investigator facilitated access to the participants' emic views. Grounded theory methodology holds the potential to be an appropriate methodological approach for researchers who seek to erode the power imbalances influencing research processes that aim to explore the associated meanings and health implications of female genital modifications, such as LME, as narrated by the women who practice them

A Qualitative study on sports gambling among regular high-stakes undergraduate gamblers

The study aimed to examine the gambling process among regular high-stakes undergraduate gamblers. It analyzed the gambling process from the initiation phase all the way to the decision to either quit or continue gambling. It discussed how sports gambling among regular high-stakes undergraduate gambler affect the four aspects taken considerations in this study, namely everyday activities, academic performance and career goals, emotional stability and family and peer relationships. Ten undergraduates from different universities in Metro Manila, who were regular high-stakes gamblers, took part in the semi-structured interview. And a separate group of ten undergraduates, who were former sports gamblers, took part in another semi-structured interview. The findings of the study show that the participants peer and friends are the biggest reason for the initiation into sports gambling. Experiences of this kind of gambling have many factors which can lead to confusion although practice of it will eventually remove the confusion in it. The effects of gambling to the participants show that there are no alarming effects that need special attention. Quitting is also relevant to the result of the betting of the participants. Lastly, participant response show no change in their self-perceptions

Orally administered Polypodium leucotomos extract decreases psoralen-UVA-induced phototoxicity, pigmentation, and damage of human skin

BACKGROUND: The use of psoralen-UVA (PUVA) in patients of skin phototype I to II is limited by side effects of acute phototoxicity and possible long-term carcinogenesis. OBJECTIVE: We sought to assess oral Polypodium leucotomos (PL) extract in decreasing PUVA-induced phototoxicity of human skin on a clinical and histologic level. METHODS: A total of 10 healthy patients with skin phototypes II to III were exposed to PUVA alone (using 0.6 mg/kg oral 8-methoxypsoralen) and to PUVA with 7.5 mg/kg of oral PL. RESULTS: Clinically, phototoxicity was always lower in PL-treated skin after 48 to 72 hours (P <.005), and pigmentation was also reduced 4 months later. Histologically, PL-treated skin showed a significant numeric reduction of sunburn cells (P=.05), preservation of Langerhans cells (P <or =.01), decrease of tryptase-positive mast cell infiltration (P <.05), and decrease of vasodilation (P <or =.01). No differences were found in Ki-67+ proliferating cells. CONCLUSIONS: PL is an effective chemophotoprotector against PUVA-induced skin phototoxicity and leads to substantial benefits of skin protection against damaging effects of PUVA as evidenced by histolog

G308A polymorphism of TNF-alpha gene is associated with insulin resistance and histological changes in non alcoholic fatty liver disease patients

Some studies have pointed to a role of TNF-alpha in pathogenesis of non alcoholic fatty liver disease (NAFLD). The aim of our study was to investigate the influence of G308A polymorphism TNF alpha gene on the histological changes, insulin resistance and TNF-alpha levels in overweight patients. A population of 66 patients with NAFLD was recruited in a cross sectional study. A biochemical analysis of serum was measured. Genotype of TNF alpha gene G308A was studied. Fifteen patients (22.7%) had the genotype G308A (mutant type group) and 51 patients (77.3%) G308G (wild type group). Patients with mutant type group presented more moderate-severe portal inflammation (86.7%) in liver biopsy compared to patient with wild genotype (19.7%). Mutant type group had more moderate-severe fibrosis (73.3%) than wild type group (51.3%). The multivariate analysis adjusted by age, sex, BMI and genotype with the dependent variable (fibrosis) showed that HOMA remained in the model, with an increase of the probability to develop fibrosis of 1.78 (CI95%:1.06-3.2) and develop moderate-severe inflammation of 1.45 (CI95%:1.02-2.1) with each increase of one unit on HOMA levels. In conclusion, Patients with mutant genotype have more frequently moderate-severe portal inflammation and fibrosis than wild type genotype

UV irradiation accelerates amyloid precursor protein (APP) processing and disrupts APP axonal transport.

Overexpression and/or abnormal cleavage of amyloid precursor protein (APP) are linked to Alzheimer's disease (AD) development and progression. However, the molecular mechanisms regulating cellular levels of APP or its processing, and the physiological and pathological consequences of altered processing are not well understood. Here, using mouse and human cells, we found that neuronal damage induced by UV irradiation leads to specific APP, APLP1, and APLP2 decline by accelerating their secretase-dependent processing. Pharmacological inhibition of endosomal/lysosomal activity partially protects UV-induced APP processing implying contribution of the endosomal and/or lysosomal compartments in this process. We found that a biological consequence of UV-induced γ-secretase processing of APP is impairment of APP axonal transport. To probe the functional consequences of impaired APP axonal transport, we isolated and analyzed presumptive APP-containing axonal transport vesicles from mouse cortical synaptosomes using electron microscopy, biochemical, and mass spectrometry analyses. We identified a population of morphologically heterogeneous organelles that contains APP, the secretase machinery, molecular motors, and previously proposed and new residents of APP vesicles. These possible cargoes are enriched in proteins whose dysfunction could contribute to neuronal malfunction and diseases of the nervous system including AD. Together, these results suggest that damage-induced APP processing might impair APP axonal transport, which could result in failure of synaptic maintenance and neuronal dysfunction

Normal or High Polyphenol Concentration in Orange Juice Affects Antioxidant Activity, Blood Pressure, and Body Weight in Obese or Overweight Adults1,2,3,4

[Background] The consumption of orange juice may lead to reduced oxidative stress and may enhance the antioxidant defense system.[Objective] The aim was to evaluate the effects of the intake of orange juice containing either normal (NPJ) or high (HPJ) concentrations of polyphenols (299 and 745 mg/d, respectively) on the antioxidant defense system, oxidative stress biomarkers, and clinical signs of metabolic syndrome in 100 nonsmoking subjects who were either overweight or obese.[Methods] A randomized, double-blind crossover study was conducted over two 12-wk periods with a 7-wk washout period. The effects on enzymatic and nonenzymatic blood antioxidant defense systems, urinary and plasma oxidative stress biomarkers, and clinical signs of metabolic syndrome were evaluated before and after an intervention with both of the orange juices. Paired t tests and linear mixed-effects models were used to evaluate the effects of juice, time, and interactions.[Results] The intake of either NPJ or HPJ led to a decrease in urinary 8-hydroxy-2′-deoxyguanosine (NPJ: 935 ± 134 to 298 ± 19 ng/mg creatinine; HPJ: 749 ± 84 to 285 ± 17 ng/mg creatinine), 8-iso-prostaglandin F2α (NPJ: 437 ± 68 to 156 ± 14 ng/mg creatinine; HPJ: 347 ± 43 to 154 ± 13 ng/mg creatinine), erythrocyte catalase, and glutathione reductase activities. A decrease was also observed in body mass index, waist circumference, and leptin (all P < 0.05). The NPJ intervention decreased systolic and diastolic blood pressures (systolic blood pressure: 128 ± 1 to 124 ± 2 mm Hg; diastolic blood pressure: 79 ± 1 to 76 ± 1 mm Hg), whereas the HPJ intervention increased erythrocyte superoxide dismutase (SOD) activity (17.7 ± 1.5 to 23.1 ± 1.7 U/mg hemoglobin).[Conclusions] Our results show that the consumption of either NPJ or HPJ protected against DNA damage and lipid peroxidation, modified several antioxidant enzymes, and reduced body weight in overweight or obese nonsmoking adults. Only blood pressure and SOD activity were influenced differently by the different flavanone supplementations. This trial was registered at clinicaltrials.gov as NCT01290250.Peer reviewe