Frequency of genetic polymorphisms of PXR gene in the Brazilian population

INTRODUCTION: PXR polymorphisms have been implicated in modulating CYP3A4 and PXR expression, potentially accounting for interindividual differences in drug metabolism. The prevalence of PXR polymorphisms varies among ethnic groups and data on the allelic distribution in the highly mixed Brazilian population is lacking. The aim of this study was to analyze genetic variations in the PXR gene in Brazilians and to compare the results to other ethnic groups. METHODS: DNA samples from 117 healthy Brazilians underwent PCR amplification and sequencing. RESULTS: Eleven polymorphisms were identified, 3 of which are highly associated with differences in CYP3A4 expression. We also identified 1 new synonymous variant in 1.3% of the alleles. Among the functional polymorphisms, -25913 C>T and -6994T>C occurred at a higher frequency comparedtothe Africanalleles (p < 0.05) but at a lower frequency compared to Caucasian alleles. The 8055 C>T allele was found at a similar frequency to those described in Caucasians and Africans (p > 0.05). CONCLUSION: We observed that functional variants of the PXR were frequent in our sample of the Brazilian population. Our results suggest that PXR gene variants may be of interest in pharmacogenetic studies involving Brazilians

Frequency of genetic polymorphisms of PXR gene in the Brazilian population

INTRODUCTION: PXR polymorphisms have been implicated in modulating CYP3A4 and PXR expression, potentially accounting for interindividual differences in drug metabolism. The prevalence of PXR polymorphisms varies among ethnic groups and data on the allelic distribution in the highly mixed Brazilian population is lacking. The aim of this study was to analyze genetic variations in the PXR gene in Brazilians and to compare the results to other ethnic groups. METHODS: DNA samples from 117 healthy Brazilians underwent PCR amplification and sequencing. RESULTS: Eleven polymorphisms were identified, 3 of which are highly associated with differences in CYP3A4 expression. We also identified 1 new synonymous variant in 1.3% of the alleles. Among the functional polymorphisms, -25913 C&gt;T and -6994T&gt;C occurred at a higher frequency comparedtothe Africanalleles (p < 0.05) but at a lower frequency compared to Caucasian alleles. The 8055 C&gt;T allele was found at a similar frequency to those described in Caucasians and Africans (p &gt; 0.05). CONCLUSION: We observed that functional variants of the PXR were frequent in our sample of the Brazilian population. Our results suggest that PXR gene variants may be of interest in pharmacogenetic studies involving Brazilians

Crowdsourcing-Based Fingerprinting for Indoor Location in Multi-Storey Buildings

POCI-01-0247-FEDER-033479The number of available indoor location solutions has been growing, however with insufficient precision, high implementation costs or scalability limitations. As fingerprinting-based methods rely on ubiquitous information in buildings, the need for additional infrastructure is discarded. Still, the time-consuming manual process to acquire fingerprints limits their applicability in most scenarios. This paper proposes an algorithm for the automatic construction of environmental fingerprints on multi-storey buildings, leveraging the information sources available in each scenario. It relies on unlabelled crowdsourced data from users&#x2019; smartphones. With only the floor plans as input, a demand for most applications, we apply a multimodal approach that joins inertial data, local magnetic field andWi-Fi signals to construct highly accurate fingerprints. Precise movement estimation is achieved regardless of smartphone usage through Deep Neural Networks, and the transition between floors detected from barometric data. Users&#x2019; trajectories obtained with Pedestrian Dead Reckoning techniques are partitioned into clusters with Wi-Fi measurements. Straight sections from the same cluster are then compared with subsequence Dynamic Time Warping to search for similarities. From the identified overlapping sections, a particle filter fits each trajectory into the building&#x2019;s floor plans. From all successfully mapped routes, fingerprints labelled with physical locations are finally obtained. Experimental results from an office and a university building show that this solution constructs comparable fingerprints to those acquired manually, thus providing a useful tool for fingerprinting-based solutions automatic setup.publishersversionpublishe

Caseinato de sódio como chaperona das proteínas do soro do leite sob aquecimento ôhmico

As caseínas, β- lactoglobulina e α- lactalbumina são as principais proteínas do leite. Quando aquecidas, acima de determinada temperatura, as proteínas globulares agregam-se devido à exposição e agregação de grupos hidrofóbicos, porém na presença de caseínas esta agregação pode ser menor devido à interação entre tais proteínas e as caseínas. Neste trabalho foi observada menor agregação das proteínas sob aquecimento a campos elétricos moderados (4 e 7 V cm-1) possibilitando o uso desta tecnologia para o controle da agregação de proteínas globulares e permitindo vislumbrar a manufatura de produtos com características diferenciadas.info:eu-repo/semantics/publishedVersio

Avaliação da gestão das transferências voluntárias para obras de engenharia da reforma agrária brasileira

As transferências voluntárias e as obras de engenharia desempenham um papel importante na viabilização de infraestruturas no Brasil, especialmente nas zonas rurais. Porém, observam-se poucos resultados efetivos na implementação dessas políticas. O artigo teve por objetivo estudar o desempenho de implementação e execução de transferências voluntárias para obras de engenharia em áreas de reforma agrária, a partir da investigação de índices de desempenho e avaliação política. Os programas foram avaliados por meio de uma pesquisa aplicada e documental do tipo quantitativa descritiva em ações do plano plurianual 2012-2015. A investigação de índices, realizada por meio de uma pesquisa exploratória, sugere que as transferências voluntárias apresentam desempenho com pouca eficácia, frustrando expectativas geradas em torno da formalização dos instrumentos. Como contribuição destaca-se a identificação de padrões de comportamento que expõem fragilidades dos programas e que podem auxiliar na compreensão de sucessos e fracassos para melhorias das políticas públicas.Voluntary transfers and engineering works play an important role in enabling infrastructures in Brazil, especially in rural areas. However, there are few effective results in implementing these policies. The main objective of this article was to study the implementation performance and execution of voluntary transfers for engineering works in agrarian reform areas, based on the investigation of performance indices and political evaluation. The programs were evaluated through an applied and documental research of quantitative descriptive type in actions of the multiannual plan 2012-2015. Index research, conducted through exploratory research, suggests that voluntary transfers present a poor effectiveness, frustrating expectations generated by the formalization of the instruments. As a contribution, the identification of behavioral patterns stands out exposing weaknesses of the programs which can aid in the understanding of successes and failures to improve public policies.Este estudo foi realizado no Centro de Investigação em Ciência Política (UID/CPO/00758/2013), Universidade do Minho e apoiado pela Fundação para a Ciência e a Tecnologia e pelo Ministério da Educação e Ciência através de fundos nacionais.info:eu-repo/semantics/publishedVersio

Varietal thiols in white wines from portuguese grape varieties

Wines from Antão Vaz, Arinto, Fernão Pires, Verdelho da Madeira and Viosinho grape cultivars, from 2009 and 2010 vintages, were studied in order to characterize the volatile thiols profile, namely 4-mercapto-4-methyl-pentan-2-one (4MMP), 3-mercaptohexan-1-ol (3MH) and 3-mercaptohexyl acetate (3MHA). Volatile thiols profile of these wines was also compared to a Sauvignon blanc wine produced in Portugal. Besides sensory analysis, all wines were analyzed using GC coupled to different detectors, namely FID, FPD, MS and Olfactometry (GC-O). In all wines, GC-O analyses showed the existence of two olfactory zones related to the presence of 4MMP and 3MH. A third olfactory zone for 3MHA was only observed for the youngest wines. The wines produced from Portuguese cultivars presented aromatic intensities comparable or even higher than those obtained in the Sauvignon blanc wine. Indeed, 3MH was found in all wines and the highest amounts were observed in Antão Vaz, Arinto and Viosinho wines. In general, these findings are in agreement with those obtained by sensory analysis

Myocardial stretch-induced compliance is abrogated under ischemic conditions and restored by cGMP/PKG-related pathways

Introduction: Management of acute myocardial infarction (MI) mandates careful optimization of volemia, which can be challenging due to the inherent risk of congestion. Increased myocardial compliance in response to stretching, known as stretch-induced compliance (SIC), has been recently characterized and partly ascribed to cGMP/cGMP-dependent protein kinase (PKG)-related pathways. We hypothesized that SIC would be impaired in MI but restored by activation of PKG, thereby enabling a better response to volume loading in MI.Methods: We conducted experiments in ex vivo rabbit right ventricular papillary muscles under ischemic and non-ischemic conditions as well as pressure–volume hemodynamic evaluations in experimental in vivo MI induced by left anterior descending artery ligation in rats.Results: Acutely stretching muscles ex vivo yielded increased compliance over the next 15 min, but not under ischemic conditions. PKG agonists, but not PKC agonists, were able to partially restore SIC in ischemic muscles. A similar effect was observed with phosphodiesterase-5 inhibitor (PDE5i) sildenafil, which was amplified by joint B-type natriuretic peptide or nitric oxide donor administration. In vivo translation revealed that volume loading after MI only increased cardiac output in rats infused with PDE5i. Contrarily to vehicle, sildenafil-treated rats showed a clear increase in myocardial compliance upon volume loading.Discussion: Our results suggest that ischemia impairs the adaptive myocardial response to acute stretching and that this may be partly prevented by pharmacological manipulation of the cGMP/PKG pathway, namely, with PDE5i. Further studies are warranted to further elucidate the potential of this intervention in the clinical setting of acute myocardial ischemia

Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

INTRODUCTION: 21-hydroxylase deficiency is an autosomal recessive disorder that causes glucocorticoid deficiency and increased androgen production. Treatment is based on glucocorticoid replacement; however, interindividual variability in the glucocorticoid dose required to achieve adequate hormonal control has been observed. OBJECTIVE: The present study aimed to evaluate the association between polymorphic variants involved inglucocorticoid action and/or metabolism and the mean daily glucocorticoid dose in 21-hydroxylase deficiency patients. METHODS: We evaluated 53 patients with classical forms of 21-hydroxylase deficiency who were receiving cortisone acetate. All patients were between four and six years of age and had normal androgen levels. RESULTS: The P450 oxidoreductase A503V, HSD11B1 rs12086634, and CYP3A7*1C variants were found in 19%, 11.3% and 3.8% of the patients, respectively. The mean ± SD glucocorticoid dose in patients with the CYP3A7*1C and wild-type alleles was 13.9 ± 0.8 and 19.5 ± 3.2 mg/m²/d, respectively. We did not identify an association between the P450 oxidoreductase or HSD11B1 allelic variants and the mean glucocorticoid dose. CONCLUSION: Patients carrying the CYP3A7*1C variant required a significantly lower mean glucocorticoid dose. Indeed, the CYP3A7*1C allele accounted for 20% of the variability in the cortisone acetate dose. The analysis of genes involved in glucocorticoid metabolism may be useful in the optimization of treatment of 21-hydroxylase deficiency

Impact of Glucocorticoid Receptor Gene Polymorphisms on the Metabolic Profile of Adult Patients with the Classical Form of 21-Hydroxylase Deficiency

Background: CAH patients have an increased risk of cardiovascular disease, and it remains unknown if lifelong glucocorticoid (GC) treatment is a contributing factor. In the general population, glucocorticoid receptor gene (NR3C1) polymorphisms are associated with an adverse metabolic profile. Our aim was to analyze the association between the NR3C1 polymorphisms and the metabolic profile of CAH patients. Methodology: Sixty-eight adult patients (34SV/34SW) with a mean age of 28.4 +/- 9 years received dexamethasone (mean 0.27 +/- 0.11 mg/day) to obtain normal androgen levels. SW patients also received fludrocortisone (50 mu g/day). Metabolic syndrome (MetS) was defined by the NCEP ATPIII criteria and obesity by BMI &gt;= 30 kg/m(2). NR3C1 alleles were genotyped, and association analyses with phenotype were carried out with Chi-square, t-test and regression analysis. Results: Obesity and MetS were observed in 23.5% and 7.3% of patients, respectively, and were not correlated with GC doses and treatment duration. BMI was positively correlated with blood pressure (BP), triglycerides (TG), LDL-c levels and HOMA-IR and inversely correlated with HDL-c levels. BclI and A3669G variants were found in 26.4% and 9.6% of alleles, respectively. Heterozygotes for the BclI polymorphism presented with higher BMI (29 kg/m(2) +/- 5.3 vs. 26 kg/m(2) +/- 5.3, respectively) and waist circumference (89 cm +/- 12.7 vs. 81 cm +/- 13, respectively) compared to wild-type subjects. Hypertension was found in 12% of patients and heterozygotes for the BclI polymorphism presented higher systolic BP than wild type subjects. Low HDL-c and high TG levels were identified in 30% and 10% of patients, respectively, and were not associated with the NR3C1 polymorphisms. A3669G carriers and non-carriers did not differ. Conclusion: In addition to GC therapy, the BclI GR variant might play an important role in obesity susceptibility in CAH patients. Genotyping of GR polymorphisms could result in the identification of a subgroup at risk patients, allowing for the establishment of personalized treatment and the avoidance of long-term adverse consequences.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP [09/54394-4, 09/54238-2]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq [305117/2009-2, 301339/2008-9]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq

Preparation and microstructural characterization of a high-Cr white cast iron reinforced with WC particles

High-chromium white cast iron (WCI) specimens locally reinforced with WC–metal matrix composites were produced via an ex situ technique: powder mixtures of WC and Fe cold-pressed in a pre-form were inserted in the mold cavity before pouring the base metal. The microstructure of the resulting reinforcement is a matrix of martensite (α’) and austenite (γ) with WC particles evenly distributed and (Fe,W,Cr)6C carbides that are formed from the reaction between the molten metal and the inserted pre-form. The (Fe,W,Cr)6C precipitation leads to the hypoeutectic solidification of the matrix and the final microstructure consists of martensite, formed from primary austenite during cooling and eutectic constituent with (Fe,Cr)7C3 and (Fe,W,Cr)6C carbides. The presence of a reaction zone with 200 µm of thickness, between the base metal and the composite should guarantee a strong bonding between these two zones.This research was funded by FEDER through the program P2020 |COMPETE, Projetos em Copromocao (project POCI-01-0247-FEDER-033417), and the program P2020|Norte2020, Programas doutorais (NORTE-08-5369-FSE-000051)