Reclassification of the intermediate group classified according to heartscore taking in considertaion individual genetic predisposition to coronary artery disease

PosterIntroduction: Cardiovascular risk stratification has included traditional cardiovascular risk factors (TRF) including tobacco, cholesterol and blood pressure adjusted to age and sex. The utility of genetic risk scores (GRS) as predictors of cardiovascular risk remains inconclusive. Objective: We intended to evaluate the ability of a multilocus GRS within the intermediate risk subgroup, defined by the European Heart score, to add predictive power for the association with coronary artery arterial disease (CAD). Methods: After applying European SCORE (ES) stratification to a total population of 2703 Portuguese individuals, 639 individuals with 59.0 ± 4.3 years were considered to be at intermediate risk subgroup (2 Results: GRS was an independent predictor for CAD (OR=2.411; pinfo:eu-repo/semantics/publishedVersio

Application of Bioactive Thermal Proteome Profiling to Decipher the Mechanism of Action of the Lipid Lowering 132-Hydroxy-pheophytin Isolated from a Marine Cyanobacteria

The acceleration of the process of understanding the pharmacological application of new marine bioactive compounds requires identifying the compound protein targets leading the molecular mechanisms in a living cell. The thermal proteome profiling (TPP) methodology does not fulfill the requirements for its application to any bioactive compound lacking chemical and functional characterization. Here, we present a modified method that we called bTPP for bioactive thermal proteome profiling that guarantees target specificity from a soluble subproteome. We showed that the precipitation of the microsomal fraction before the thermal shift assay is crucial to accurately calculate the melting points of the protein targets. As a probe of concept, the protein targets of 132-hydroxy-pheophytin, a compound previously isolated from a marine cyanobacteria for its lipid reducing activity, were analyzed on the hepatic cell line HepG2. Our improved method identified 9 protein targets out of 2500 proteins, including 3 targets (isocitrate dehydrogenase, aldehyde dehydrogenase, phosphoserine aminotransferase) that could be related to obesity and diabetes, as they are involved in the regulation of insulin sensitivity and energy metabolism. This study demonstrated that the bTPP method can accelerate the field of biodiscovery, revealing protein targets involved in mechanisms of action (MOA) connected with future applications of bioactive compounds.This project received funding from the ERA-NET Marine Biotechnology project CYANOBESITY that it is cofounding from FORMAS, Sweden grant nr. 2016-02004 (SC), FCT Foundation of Science and Technology, Portugal, grant number ERA-MBT/0001/2015 (RU). This work has also been funded by IKERBASQUE (SC), Basque Government grant IT-971-16 (SC and OF), and FCT grants SFRH/BPD/112287/2015, SFRH/BD/116009/2016, FCT strategic fund (UID/Multi/04423/2019) (RU and SF)

Peritoneal fluid modulates the sperm acrosomal exocytosis induced by N-acetylglucosaminyl neoglycoprotein

The effect of peritoneal fluid (PF) on the human sperm acrosome reaction (AR) was tested. Sperm was pre-incubated with PF and the AR was induced by calcium ionophore A23187 and a neoglycoprotein bearing N-acetylglycosamine residues (NGP). The AR induced by calcium ionophore was inhibited 40% by PF from controls (PFc) and 50% by PF from the endometriosis (PFe) group, but not by PF from infertile patients without endometriosis (PFi). No significant differences were found in the spontaneous AR. When the AR was induced by NGP, pre-incubation with PFc reduced (60%) the percentage of AR, while PFe and PFi caused no significant differences. The average rates of acrosome reactions obtained in control, NGP- and ionophore-treated sperm showed that NGP-induced exocytosis differed significantly between the PFc (11%) and PFe/PFi groups (17%), and the ionophore-induced AR was higher for PFi (33%) than PFc/PFe (25%). The incidence of the NGP-induced AR was reduced in the first hour of pre-incubation with PFc and remained nearly constant throughout 4 h of incubation. The present data indicate that PF possesses a protective factor which prevents premature AR.Hospital de Clínicas de Porto AlegreUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Associação independente da variante rs1333049, no locus 9p21, com a doença coronária, numa população portuguesa

Funding: This study was supported by the European Regional Development Fund’s Operational Programme for the Enhancement of Economic Potential and Territorial Cohesion for the Autonomous Region of Madeira (INTERVIR+).Introduction: Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations. Aim: To investigate whether the SNP rsl333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population. Methods: We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.7±8.9 years, 79.9% male) and 683 controls without coronary disease (mean age 53.3±10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD. Results: The C allele was found in 60% of the CAD patients and 53% of the controls, with OR=1.33; p=0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR=1.34, p=0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR=1.05, p=0.670). After logistic regression analysis, the CC genotype remained in the equation with 0R=1.7; p=0.018 and CG with OR=I.5, p=0.048. Conclusion: In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.publishersversionpublishe

Growth of arabica coffee cultivars submitted to glyphosate doses

Avaliaram-se, neste trabalho, os efeitos do glyphosate sobre o crescimento de três cultivares de café arábica. Utilizou-se o esquema fatorial (3 x 5) em delineamento de blocos casualizados, com quatro repetições, sendo os tratamentos compostos por três cultivares de café: Catucaí Amarelo (2 SL), Oeiras (MG-6851) e Topázio (MG-1190) e cinco doses de glyphosate (0; 57,6; 115,2; 230,4; e 460,8 g ha-1). O herbicida foi aplicado quando as plantas de café se apresentavam com 21 pares de folhas e de forma que não atingisse o terço superior delas. Aos 45 e 120 dias após a aplicação do glyphosate (DAA), avaliaram-se os incrementos na altura, na área foliar, no diâmetro do caule, no número de folhas e nos ramos plagiotrópicos, sendo eles mensurados inicialmente no dia da aplicação do herbicida; aos 10, 45 e 120 DAA, avaliou-se a porcentagem de intoxicação das plantas. A massa da matéria seca de folhas, raízes e caule, a densidade e o comprimento radicular foram avaliados aos 120 DAA. Os sintomas de intoxicação das plantas de café causados pelo glyphosate foram semelhantes nos diferentes cultivares, sendo caracterizados por clorose e estreitamento do limbo foliar. Os incrementos no número de folhas e ramos plagiotrópicos e no diâmetro do caule, independentemente do cultivar, não foram alterados pelo glyphosate. O cultivar Topázio foi o mais sensível ao glyphosate quanto a acúmulo de área foliar, de massa de matéria seca e densidade radicular.This study evaluated the effects of glyphosate on the growth of three arabica coffee cultivars. A factorial (3 x 5) was arranged in a randomized block design with four replications, with treatments consisting of three coffee varieties: Catucaí Amarelo (2 SL), Oeiras (MG-6851) and Topázio (MG-1190) and five glyphosate doses (0, 57.6, 115.2, 230.4 and 460.8 g ha-1 ). The herbicide was applied when the coffee plants reached 21 pairs of leaves, before reaching their upper third ones. At 45 and 120 days after glyphosate application (DAA), increase in leaf area, stem diameter, number of leaves and plagiotropic branches was evaluated, being initially measured on the day the herbicide was applied, and plant intoxication rate at 10, 45 and 120 DAA. Dry matter of leaves, roots and stem, and root length and density were measured at 120 DAA. Symptoms of coffee plant intoxication caused by glyphosate were similar in different cultivars, being characterized by chlorosis and leaf narrowing. Increase in the number of leaves, plagiotropic branches and stem diameter, regardless of the cultivar, was not affected by glyphosate. Cultivar Topázio was the most sensitive to glyphosate, in terms of accumulation of leaf area, root dry matter and root density.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)(FAPEMIG) Fundação de Amparo à Pesquisa do Estado de Minas Gerai

Visualizing Structures in Confocal Microscopy Datasets Through Clusterization: A Case Study on Bile Ducts

Aiming at a better result from previous works, we employed some heuristics found in the literature to determine the appropriate parameters for the clustering. We proposed our methodology by adding some steps to be performed before the clustering phase: one step for pre-processing the volumetric dataset and another to analyzing candidate features to guide the clustering. In this latter aspect, we provide an interesting contribution: we have explored the gradient magnitude as a feature that allowed to extract relevant information from the density-based spatial clustering. Besides the fact that DBSCAN allows easy detection of noise points, an interesting result for both datasets was that the first and largest cluster found as significant for the visualization represents the structure of interest. In the red channel, this cluster represents the most prominent vessels, while in the green channel, the peribiliary glands were made more evident.Abstract—Three-dimensional datasets from biological tissues have increased with the evolution of confocal microscopy. Hepatology researchers have used confocal microscopy for investigating the microanatomy of bile ducts. Bile ducts are complex tubular tissues consisting of many juxtaposed microstructures with distinct characteristics. Since confocal images are difficult to segment because of the noise introduced during the specimen preparation, traditional quantitative analyses used in medical datasets are difficult to perform on confocal microscopy data and require extensive user intervention. Thus, the visual exploration and analysis of bile ducts pose a challenge in hepatology research, requiring different methods. This paper investigates the application of unsupervised machine learning to extract relevant structures from confocal microscopy datasets representing bile ducts. Our approach consists of pre-processing, clustering, and 3D visualization. For clustering, we explore the density-based spatial clustering for applications with noise (DBSCAN) algorithm, using gradient information for guiding the clustering. We obtained a better visualization of the most prominent vessels and internal structures.info:eu-repo/semantics/publishedVersio

A landscape ecological vegetation map of Sint Eustatius (Lesser Antilles)

A semi-detailed landscape-based vegetation map (scale: 1: 37,500) based on field data from 1999 has been available as an update of Stoffers’ 1956 map of the Lesser Antillean island of St. Eustatius, Netherlands Caribbean, but up to now was never finalized or published. In this report we complete the documentation of that map to provide new insights into vegetation change over a period of more than 40 years, and a quantitative reference point for future studies on landscape-level vegetation development for the island

Numerical convergence of the block-maxima approach to the Generalized Extreme Value distribution

In this paper we perform an analytical and numerical study of Extreme Value distributions in discrete dynamical systems. In this setting, recent works have shown how to get a statistics of extremes in agreement with the classical Extreme Value Theory. We pursue these investigations by giving analytical expressions of Extreme Value distribution parameters for maps that have an absolutely continuous invariant measure. We compare these analytical results with numerical experiments in which we study the convergence to limiting distributions using the so called block-maxima approach, pointing out in which cases we obtain robust estimation of parameters. In regular maps for which mixing properties do not hold, we show that the fitting procedure to the classical Extreme Value Distribution fails, as expected. However, we obtain an empirical distribution that can be explained starting from a different observable function for which Nicolis et al. [2006] have found analytical results.Comment: 34 pages, 7 figures; Journal of Statistical Physics 201

Ligand-Free Palladium-Catalyzed Oxyarylation of Dihydronaphthal­enes and Chromenequinone with o-Iodophenols and 3-Iodolawsone in PEG-400: An Efficient Synthesis of 5-Carbapterocarpans and Pterocarpanquinones

Dihydronaphthalenes were oxyarylated with o-iodophenols, in PEG-400 at 140 or 170 °C, leading regio- and stereoselectively to 5-carbapterocarpans. By using Pd(OAc)2 (5–10 mol%) as precatalyst and Ag2CO3 (1.1 equiv) as base (conditions A), products were obtained in good to excellent chemical yields, in 5–30 minutes, irrespective of the pattern of substitution the starting materials. Alternatively, when p-hydroxyacetophenone oxime derived palladacycle (1 mol%) was used as precatalyst, and dicyclohexylamine (2 equiv) was used as base (silver-free, conditions B), the corresponding adducts were obtained in moderate to good yields, in 0.5 to 4 hours. Finally, the oxyarylation of dihydronaphthalenes­ and chromenquinone with o-iodophenols and 3-iodolawsone in PEG-400 under conditions A led regio- and stereoselectively to the formation of carbapterocarpanquinones and pterocarpanquinones in moderate yield.Financial support from Brazilian agencies CAPES-DGU (Project 200/09), CNPq, FAPERJ and UFRJ are acknowledged. Spanish MICINN (Projects PHB2008-0037-PC, CTQ2007-62771/BQU, CTQ2010-20387, Consolider INGENIO 2010 CSD2007-00006), FEDER, Generalitat Valenciana (Project PROMETEO/2009/038), and the University of Alicante are acknowledged