Identification of Urine Metabolic Markers of Stroke Risk Using Untargeted Nuclear Magnetic Resonance Analysis.

Stroke remains the second leading cause of mortality worldwide, and the third leading cause of death and morbidity combined, affecting more than 12 million people every year. Stroke pathophysiology results from complex interactions of several risk factors related to age, family history, gender, lifestyle, and the presence of cardiovascular and metabolic diseases. Despite all the evidence, it is not possible to fully prevent stroke onset. In recent years, there has been an exploration of innovative methodologies for metabolite analysis aimed at identifying novel stroke biomarkers. Utilizing Nuclear Magnetic Resonance (NMR) spectroscopy, we investigated small molecule variations in urine across different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCFs) to calculate the probability of suffering a stroke: low stroke risk (LSR, control), moderate stroke risk (MSR), and high stroke risk (HSR). Univariate statistical analysis showed that urinary 4-hydroxyphenylacetate levels increased while glycolate levels decreased across the different stroke risk groups, from the LSR to the HSR groups. Trimethylamine N-oxide (TMAO) had average concentration values that were significantly higher in elderly people in the HSR group, while trigonelline levels were significantly lower in the MSR group. These metabolic markers can be used for early detection and to differentiate stages of stroke risk more efficiently.

MetSCORE: a molecular metric to evaluate the risk of metabolic syndrome based on serum NMR metabolomics.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. METHODS: We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. RESULTS: We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920-0.952, p < 0.001). MetSCORE is also able to discriminate the intermediate phenotypes, identifying the early risk of MetS in a quantitative way and ranking individuals according to their risk of undergoing MetS (for general population) or according to the severity of the syndrome (for MetS patients). CONCLUSIONS: We believe that MetSCORE may be an insightful tool for early intervention and lifestyle modifications, potentially preventing the aggravation of metabolic syndrome.

Searching for Metabolic Markers of Stroke in Human Plasma via NMR Analysis.

More than 12 million people around the world suffer a stroke every year, one every 3 s. Stroke has a variety of causes and is often the result of a complex interaction of risk factors related to age, genetics, gender, lifestyle, and some cardiovascular and metabolic diseases. Despite this evidence, it is not possible to prevent the onset of stroke. The use of innovative methods for metabolite analysis has been explored in the last years to detect new stroke biomarkers. We use NMR spectroscopy to identify small molecule variations between different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCF) to calculate the probability of suffering a stroke. Using this parameter, three study groups were formed: low stroke risk (LSR, control), moderate stroke risk (MSR) and high stroke risk (HSR). Univariate statistical analysis showed seven metabolites with increasing plasma levels across different stroke risk groups, from LSR to HSR: isoleucine, asparagine, formate, creatinine, dimethylsulfone and two unidentified molecules, which we termed "unknown-1" and "unknown-3". These metabolic markers can be used for early detection and to detect increasing stages of stroke risk more efficiently.

HLA-A23/HLA-A24 serotypes and dementia interaction in the elderly: Association with increased soluble HLA class I molecules in plasma.

MHC class I molecules regulate brain development and plasticity in mice and HLA class I molecules are associated with brain disorders in humans. We investigated the relationship between plasma-derived soluble human HLA class I molecules (sHLA class I), HLA class I serotypes and dementia. A cohort of HLA class I serotyped elderly subjects with no dementia/pre-dementia (NpD, n = 28), or with dementia (D, n = 28) was studied. Multivariate analysis was used to examine the influence of dementia and HLA class I serotype on sHLA class I levels, and to compare sHLA class I within four groups according to the presence or absence of HLA-A23/A24 and dementia. HLA-A23/A24 and dementia, but not age, significantly influenced the level of sHLA class I. Importantly, the concurrent presence of HLA-A23/A24 and dementia was associated with higher levels of sHLA class I (p < 0.001). This study has shown that the simultaneous presence of HLA-A23/HLA-A24 and dementia is associated with high levels of serum sHLA class I molecules. Thus, sHLA class I could be considered a biomarker of neurodegeneration in certain HLA class I carriers.

Effects of bisphenol A on human umbilical arteries.

Bisphenol A (BPA) is an endocrine-disrupting chemical widely used in the plastics industry, including food container, toys, and medical equipment. We analyzed the effect of BPA in human umbilical artery contractility and expression of some proteins modulating this function, such as ionic channels and proteins involved in the cGMP pathway. Using standard organ bath technique, rings of human umbilical arteries without endothelium were contracted by 5-HT (1 µM) and histamine (10 µM) and the effect of different concentrations of BPA (1 nM-100 µM) was analyzed. The results showed that BPA is a vasodilator of these arteries in a concentration-dependent way. Besides, qPCR studies on human umbilical smooth muscle cells (HUSMC) allowed to analyze the effects of BPA on gene expression. Thus, 12-h exposition to BPA induced reduction of expression of L-type calcium channels (LTCC), alpha subunit of BKCa channels, and Kvß1 and Kvß3 from Kv channels. BPA also decreased the expression of soluble guanylate cyclase (sGC) and natriuretic peptide receptor type A (NPRA), meanwhile increasing that of PKG, proteins involved in vasodilation of human umbilical arteries (HUA) by cGMP. Further studies will be necessary to increase knowledge about the implications of these changes induced by BPA exposure.

The survival, development, and reproduction of Gonipterus platensis (Coleoptera: Curculionidae) on the main Eucalyptus (Myrtaceae) genotypes planted in Brazil.

Background: Gonipterus platensis Marelli (Coleoptera: Curculionidae) is the main defoliating beetle of Eucalyptus L'Hér. (Myrtaceae) plants worldwide. The suitability of Eucalyptus to this pest varies among host plant genotypes. The objective of this study was to evaluate the development, reproduction, and survival of G. platensis on Eucalyptus species and hybrids to assess their suitability to this insect pest in Brazil. Methods: The survival, development, and reproduction parameters were evaluated with G. platensis feeding leaves of Eucalyptus camaldulensis Dehnh., Eucalyptus grandis W. Hill., Eucalyptus urophylla S.T. Blake and on the hybrids of E. grandis ×E. urophylla 'H13' and 'VR3748' in the laboratory. Results: The duration of the larval stage of G. platensis was shorter on E. urophylla. The pupal stage and the period from larva to adult were equally shorter on E. urophylla and E. camaldulensis. The viability of instars of this insect was low on both E. grandis and E. camaldulensis. The complete lifespan, oviposition period and reproduction parameters of G. platensis were greater on E. urophylla, lower on E. camaldulensis and E. grandis, and intermediate on both hybrids tested. Synthesis: Eucalyptus urophylla is the most suitable host for G. platensis survival, development, and reproduction, while E. grandis and E. camaldulensis are the least suitable.

O uso de uma plataforma virtual para mobilização social no enfrentamento de arboviroses e controle do Aedes aegypti / The use of a virtual platform for social mobilization in the confrontation of arboviruses and control of Aedes aegypti / El uso de una plataforma virtual para la movilización social para combatir los arbovirus y el control de Aedes aegypti

A mobilização social para o enfrentamento da dengue, zika, chikungunya e controle do Aedes aegypti tem sido um desafio no país. Esse artigo apresenta o processo de elaboração de uma plataforma virtual, incluindo a composição do seu acervo e a análise exploratória do seu uso, como ferramenta, numa proposta de mobilização social que envolve a criação de comitês populares nos territórios para o enfrentamento das três doenças e vetor. A construção da plataforma considerou: facilidade para usuário; acesso; armazenamento de material; interatividade e banco para monitoramento de dados. A seleção do acervo baseou-se em critérios: técnico, referente à fonte e autoria; acurácia, concordância entre informação e evidência em saúde; e legibilidade, garantindo a compreensão por diferentes grupos. A análise exploratória utilizou o banco de dados da plataforma. Os resultados apontaram a plataforma como uma ferramenta que pode contribuir com a comunicação e informação em saúde nessa proposta de mobilização social.

Social mobilization for dengue, zika and chikungunya prevention and control of Aedes aegypti has been a challenge in the country. This paper presents the process of elaboration of a virtual platform, including the composition of its collection and the exploratory analysis of its use, as a tool in a social mobilization proposal that encompasses the creation of popular committees in the territories for the confrontation of the three diseases and vector. The construction of the platform considered: ease of use; access; material storage; interactivity and database for data monitoring. The selection of the collection was based on the following criteria: technical, considering source and authorship; accuracy, regarding the agreement between health information and evidence; legibility, ensuring the understanding by different groups. The exploratory analysis used the platform database. The results showed the platform as a tool which can contribute to health communication and information in this proposal of social mobilization.

La movilización social para combatir el dengue, zika, chikungunya y control de Aedes ha sido un desafío. Este artículo presenta el proceso de elaboración de una plataforma virtual, que incluye la composición de su acervo y el análisis exploratorio de su uso, como herramienta en una propuesta de movilización social que implica la creación de comités populares en los territorios para enfrentar las enfermedades y el vector. La construcción de la plataforma consideró: facilidad para usuario; acceso; almacenamiento de material; interactividad y bases de datos para el monitoreo. La selección del acervo se basó en criterios: técnico, con fuente y autoría; precisión, concordancia entre información y evidencia en salud; legibilidad, para garantizar la comprensión por diferentes grupos. El análisis utilizó datos de la plataforma. Los resultados mostraron que la plataforma puede ser una herramienta para contribuir a la comunicación e información de salud en esta propuesta de movilización social.

Dopamine-Induced Ascorbate Release From Retinal Neurons Involves Glutamate Release, Activation of AMPA/Kainate Receptors and Downstream Signaling Pathways.

Ascorbate, the reduced form of Vitamin C, is one of the most abundant and important low-molecular weight antioxidants in living tissues. Most animals synthesize vitamin C, but some primates, including humans, have lost this capacity due to disruption in L-gulono-gamma-lactone oxidase gene. Because of this incapacity, those animals must obtain Vitamin C from the diet. Ascorbate is highly concentrated in the central nervous system (CNS), including the retina, and plays essential roles in neuronal physiology. Ascorbate transport into cells is controlled by Sodium Vitamin C Co-Transporters (SVCTs). There are four SVCT isoforms and SVCT2 is the major isoform controlling ascorbate transport in the CNS. Regarding ascorbate release from retinal neurons, Glutamate, by activating its ionotropic receptors leads to ascorbate release via the reversion of SVCT2. Moreover, dopamine, via activation of D1 receptor/cyclic AMP/EPAC2 pathway, also induces ascorbate release via SVCT2 reversion. Because the dopaminergic and glutamatergic systems are interconnected in the CNS, we hypothesized that dopamine could regulate ascorbate release indirectly, via the glutamatergic system. Here we reveal that dopamine increases the release of D-Aspartate from retinal neurons in a way independent on calcium ions and dependent on excitatory amino acid transporters. In addition, dopamine-dependent SVCT2 reversion leading to ascorbate release occurs by activation of AMPA/Kainate receptors and downstream ERK/AKT pathways. Overall, our data reveal a dopamine-to-glutamate signaling that regulates the bioavailability of ascorbate in neuronal cells.

Popcorn genotypes resistance to fall armyworm / Genótipos de milho pipoca resistentes à lagarta-do-cartucho

ABSTRACT: The aim of this study was to evaluate popcorn genotypes for resistance to the fall armyworm, Spodoptera frugiperda. The experiment used a completely randomized design with 30 replicates. The popcorn genotypes Aelton, Arzm 05 083, Beija-Flor, Colombiana, Composto Chico, Composto Gaúcha, Márcia, Mateus, Ufvm Barão Viçosa, Vanin, and Viviane were evaluated,along with the common maize variety Zapalote Chico. Newly hatched fall armyworm larvae were individually assessed with regard to biological development and consumption of food. The data were subjected to multivariate analyses of variance and genetic divergence among genotypes was evaluated through the clustering methods of Tocher based on generalized Mahalanobis distances and canonical variable analyses. Seven popcorn genotypes, namely, Aelton, Arzm 05 083, Composto Chico, Composto Gaúcha, Márcia, Mateus, and Viviane,were shown to form a cluster (cluster I) that had antibiosis as the mechanism of resistance to the pest. Cluster I genotypes and the Zapalote Chico genotype could be used for stacking genes for antibiosis and non-preference resistance.

RESUMO: O objetivo do estudo foi avaliar genótipos de milho pipoca para resistência à lagarta-do-cartucho, Spodoptera frugiperda. O experimento foi conduzido em delineamento inteiramente casualizado com 30 repetições. Foram avaliados os genótipos de milho pipoca Aelton, Arzm 05 083, Beija-Flor, Colombiana, Composto Chico, Composto Gaúcha, Márcia, Mateus, Ufvm Barão Viçosa, Vanin, Viviane e Zapalote Chico. Larvas recém-eclodidas foram individualizadas para avaliação do desenvolvimento biológico e consumo alimentar. Os dados foram submetidos à análise multivariada de variância e a divergência genética entre genótipos foi avaliada através dos métodos de agrupamento de Tocher, com base na distância generalizada de Mahalanobis e análise de variáveis canônicas. Sete genótipos,Aelton, Arzm 05 083, Composto Chico, CompostoGaúcha, Márcia, Mateus e Viviane formaram um cluster (cluster I) que apresentaram antibiose com o mecanismo de resistência à praga. Os genótipos do cluster I e Zapalote Chico podem ser usados para empilhar genes para resistência por antibiose e não-preferência.

Effects of cardiotonic steroids on isolated perfused kidney and NHE3 activity in renal proximal tubules.

Cardiotonic steroids (CS) are known as modulators of sodium and water homeostasis. These compounds contribute to the excretion of sodium under overload conditions due to its natriuretic property related to the inhibition of the renal Na+/K+-ATPase (NKA) pump α1 isoform. NHE3, the main route for Na+ reabsorption in the proximal tubule, depends on the Na+ gradient generated by the NKA pump. In the present study we aimed to investigate the effects of marinobufagin (MBG) and telocinobufagin (TBG) on the renal function of isolated perfused rat kidney and on the inhibition of NKA activity. Furthermore, we investigated the mechanisms for the cardiotonic steroid-mediated natriuretic effect, by evaluating and comparing the effects of bufalin (BUF), ouabain (OUA), MBG and TBG on NHE3 activity in the renal proximal tubule in vivo. TBG significantly increased GFR, UF, natriuresis and kaliuresis in isolated perfused rat kidney, and inhibits the activity of NKA at a much higher rate than MBG. By stationary microperfusion technique, the perfusion with BUF, OUA, TBG or MBG promoted an inhibitory effect on NHE3 activity, whereas BUF was the most effective agent, and demonstrated a dose-dependent response, with maximal inhibition at 50nM. Furthermore, our data showed the role of NKA-Src kinase pathway in the inhibition of NHE3 by CS. Finally, a downstream step, MEK1/2-ERK1/2 was also investigated, and, similar to Src inhibition, the MEK1/2 inhibitor (U0126) suppressed the BUF effect. Our findings indicate the involvement of NKA-SRc-Kinase-Ras-Raf-ERK1/2 pathway in the downregulation of NHE3 by cardiotonic steroids in the renal proximal tubule, promoting a reduction of proximal sodium reabsorption and natriuresis.

O encontro entre o desenvolvimento rural sustentável e a promoção da saúde no Guia Alimentar para a População Brasileira / The meeting between sustainable rural development and health promotion in Food Guide for the Brazilian Population

Resumo O Guia Alimentar é documento que aborda os princípios e as recomendações de uma alimentação adequada e saudável para a população brasileira, tendo como propósito apoiar a educação alimentar e nutricional e subsidiar políticas e programas nacionais de alimentação e nutrição no setor de saúde e também em outros setores. O objetivo deste estudo foi identificar a interseção entre a promoção da saúde e o desenvolvimento rural sustentável no Guia Alimentar para a População Brasileira. Realizou-se análise do texto do Guia através de temas previstos a partir dos conceitos de promoção da saúde e desenvolvimento rural sustentável. Posteriormente, revisou-se o texto e foram identificados temas emergentes expressos pela interseção dos conceitos, sendo, então, discutidos à luz do referencial bibliográfico dos campos da segurança alimentar e nutricional, do desenvolvimento rural e da epidemiologia nutricional. Sete temas previstos e seis temas emergentes foram identificados e relacionados a quatro dimensões explicativas dos seis temas de interseção relacionados aos conceitos, os quais foram identificados a partir dos elementos constitutivos dos itens: princípios e diretrizes do Guia Alimentar; dez passos para uma alimentação saudável; superação de obstáculos para a realização desses dez passos. O Guia Alimentar propõe a produção social da saúde na interação entre as noções de alimentação adequada e saudável, segurança alimentar e nutricional, e desenvolvimento rural. Destacam-se as recomendações e orientações que dialogam com a produção de alimentos de base agroecológica e com a garantia da biodiversidade alimentar na agricultura familiar, bem como a perspectiva de relação com os sistemas alimentares locais.

Abstract The Food Guide is a document that addresses the principles and recommendations of an adequate and healthy food for the Brazilian population, with the purpose to support food and nutrition education, and support national policies and food and nutrition programs in the health sector and also in other sectors. The objective of this study is to identify the intersection between health promotion and sustainable rural development in the Food Guide for the Brazilian population. We conducted an analysis of the Guide text from the provided themes established by the concepts of health promotion and sustainable rural development, and subsequently identified emerging themes expressed by the intersection of the concepts, and then discussed in the light of the nutrition and food security, rural development, and nutritional epidemiology bibliography. Seven expected themes and six emerging themes were identified and related to four explanatory dimensions of the six intersection of issues related to the concepts, which were identified from the constitutive elements of items: principles and guidelines of the Food Guide; ten steps to a healthy diet; overcoming obstacles to achieving the ten steps. The Food Guide suggests the social promotion of health in the interaction between the notions of proper nutrition and healthy food and nutritional security, and rural development. Highlight the recommendations and guidelines that dialogue with the production of agroecological basis of food and ensuring food biodiversity in family farming, as well as the prospect of relationship with local food systems.

Multi-matrix quantification and risk assessment of pesticides in the longest river of the Iberian peninsula.

The distribution of pesticides in dissolved aqueous phase (DAP), suspended particulate matter (SPM) and Scrobicularia plana soft tissues from the Tagus River estuary was determined to evaluate the chemicals pollution status and their hazard potential in this area. Samples were collected in 6 campaigns (December 2012-October 2013), from 3 strategical sites, and analysed via different extraction procedures followed by gas chromatography tandem mass spectrometry (GC-MS/MS) determination. The contamination profile among matrices (DAP, SPM, and soft tissue from bivalves (STB)) was marked by average concentrations of 345ng/L, 0.51mg/kg, and 0.02mg/kg, respectively, with several samples above the 2013/39/EU Directive of environmental quality standards (EQS); no differences were observed between sex. A wider range of pesticides was present in STB (n=53) than in SPM (n=36) and DAP (n=19) matrices. Sediment-water partition coefficient, bioaccumulation factor in both DAP and SPM fraction were estimated ranging between 2.5 and 4.4 and 0.008-2799, respectively. The spatial distribution of most pesticides and physicochemical parameters were consistent, indicating a pollution pattern primarily near the Trancão River mouth. Due to the presence of the target compounds, calculated risk quotients pointed out potential hazards for aquatic organisms, mainly to invertebrates. The estimated average daily intake, theoretical maximum daily intake, and hazard quotient of the studied pesticides-via bivalve ingestion-indicated no risk for human health, although it is important to note possible biomagnification processes that may happen along the estuarine food-chain.

O indigesto sistema do alimento mercadoria / The indigestible system of food as commodity

A caracterização do alimento enquanto mercadoria surge por meio de um sistema alimentar cada vez mais concentrado e determinado por poucas empresas transnacionais, sendo essa uma das consequências da crise estrutural do capitalismo. Entender como a alimentação está dominada pela lógica privada do capital e como o alimento virou mercadoria é uma das chaves para explicar o atual cenário produtor de doenças e de desigualdades econômicas e sociais. A metodologia utilizada neste artigo partiu da perspectiva teórica marxista determinada pela concepção crítica-dialética e de outras abordagens heterodoxas sobre a fase atual do capitalismo. Propõe-se uma discussão sobre o contexto recente do sistema alimentar global e o processo de massificação do alimento em mercadoria, sobre os traços gerais da dinâmica do capitalismo contemporâneo e sua crise com impactos sobre o sistema alimentar e sobre como esse novo contexto constrange o Estado brasileiro na garantia da Segurança Alimentar e Nutricional e no Direito Humano à Alimentação Adequada, impondo desafios importantes no campo da saúde pública e na garantia de direitos humanos.

The characterization of food as a consumable commodity emerges from a food system which is becoming increasingly concentrated and determined by few multinational corporations. This is one of the consequences of the capitalist structural crisis. Understanding how the production of food is dominated by the logics of private property and how food has become a commodity is essential in explaining the current context, which is leading to more diseases and social-economic inequalities. The methodology used in this article is based on the perspective of Marxist theory, determined by the emergence of dialectical criticism, as well as on heterodox approaches towards the current state of capitalism. This article proposes a discussion about the recent context of the global food system and the process of mass production of food as commodity, the general lines of the contemporary capitalist dynamics and its crisis with the impact on the food system. Moreover, how this new context is restricting Brazil in guaranteeing food and nutrition safety, as well as the Human Right to Adequate Food, thus giving rise to new and notable challenges in the field of public health and in securing human rights to citizens.

Development and application of a QuEChERS-based extraction method for the analysis of 55 pesticides in the bivalve Scrobicularia plana by GC-MS/MS.

A method for quantitative determination of 55 pesticides in a bivalve matrix was established, based on QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) extraction and using gas chromatography (GC)-ion trap (IT) mass spectrometry (MS/MS). Accomplishing the European SANCO guidelines, this method was validated using 5 g of homogenized soft tissue, allowing the quantification of pesticides at ng/g of wet weight (ww). Quantification limits and recovery rates ranged from 0.33 to 10.3 µg/L and from 78 to 119 %, respectively. As an important mollusc, not only from an ecological perspective but also for food consumption, the peppery furrow shell (Scrobicularia plana) was sampled at three strategical sites (Ria Formosa Lagoon, in the south of Portugal) during 2012-2013, over six campaigns. A total of 2160 animals were pooled by place and sex. No statistical differences were found among sites or between sexes. Forty percent of the sampled pools were above quantification limits, reaching total annual average concentrations of ∑800 ng/g ww. Additionally, 83 % of the selected compounds showed concentrations above the legal limits set by the European Directive 2013/39/EU. In conclusion, the applied method was successful and proved that bivalves were contaminated by the selected pesticides. In future work, this methodology can be used to monitor body burdens and obtain data for predicting impacts in shellfish consumers. Graphical Abstract Resume of pesticides extraction and analyses process from S. plana.

A mollusk VDR/PXR/CAR-like (NR1J) nuclear receptor provides insight into ancient detoxification mechanisms.

The origin and diversification of the metazoan endocrine systems represents a fundamental research issue in biology. Nuclear receptors are critical components of these systems. A particular group named VDR/PXR/CAR (NR1I/J) is central in the mediation of detoxification responses. While orthologues have been thoroughly characterized in vertebrates, a sparse representation is currently available for invertebrates. Here, we provide the first isolation and characterization of a lophotrochozoan protostome VDR/PXR/CAR nuclear receptor (NR1J), in the estuarine bivalve the peppery furrow shell (Scrobicularia plana). Using a reporter gene assay, we evaluated the xenobiotic receptor plasticity comparing the human PXR with the S. plana NR1Jß. Our results show that the molluscan receptor responds to a natural toxin (okadaic acid) in a similar fashion to that reported for other invertebrates. In contrast, the pesticide esfenvalerate displayed a unique response, since it down regulated transactivation at higher concentrations, while for triclosan no response was observed. Additionally, we uncovered lineage specific gene duplications and gene loss in the gene group encoding NRs in protostomes with likely impacts on the complexity of detoxification mechanisms across different phyla. Our findings pave the way for the development of multi-specific sensor tools to screen xenobiotic compounds acting via the NR1I/J group.

Educação alimentar e nutricional no contexto do desenvolvimento rural: estudo de caso do Rio Grande do Sul / Food and nutrition education in the context of rural development a case study of Rio Grande do Sul

Introdução: A educação alimentar e nutricional (EAN) é campo de prática e reflexão de diversos atores sociais envolvidos na promoção da saúde, entre eles, os serviços de Assistência Técnica e Extensão Rural, que se relacionam com ações de desenvolvimento local e promoção da alimentação adequada e saudável e de segurança alimentar e nutricional das populações rurais. Objetivo: Analisar percepções e práticas sobre o processo de educação alimentar e nutricional no contexto do Desenvolvimento Rural no RS. Metodologia: Artigo 1: Realizou-se análise do texto do Guia Alimentar para a População Brasileira, discutindo-se os temas previstos e os temas emergentes a partir da intersecção dos conceitos de promoção da saúde e de desenvolvimento rural sustentável. Artigo 2: Investigaramse normas estabelecidas nos documentos de âmbito nacional e estadual e práticas executadas pelos extensionistas rurais a partir de busca em Sistema de Registros Administrativos que continham a descrição das atividades realizadas. Os dados foram tabulados e processados por meio da estatística descritiva, com o apoio do programa Microsoft Office Excel, versão 2007, em relação à produção e análise qualitativa dos dados; investigaram-se, na periodicidade histórica, rupturas e permanências contidas no material, com apoio do software NVivo 10 for Windows. Artigo 3: Realizaram-se 18 entrevistas individuais para produção de narrativas com os diferentes atores sociais envolvidos na Assistência Técnica e Extensão Rural no RS. Foi realizada a análise das narrativas a partir da perspectiva teórica e das categorias analíticas emergentes, sendo os dados interpretados, sistematizados e analisados em seu conjunto, com apoio do software NVivo 10 for Windows. Resultados: Artigo 1: Identificou 13 temas relacionados a quatro dimensões explicativas da interseção dos conceitos, os quais foram identificados a partir dos elementos constitutivos dos itens princípios e diretrizes do Guia Alimentar, dez passos para uma alimentação saudável; superação de obstáculos para realização dos dez passos. Artigo 2: Oito documentos e 212.502 atividades foram analisadas, sendo 11,13 por cento relacionadas à EAN. As normas determinaram número mínimo de atividades a serem realizadas por meio de metas estabelecidas nos contratos de serviços, em contrapartida, as práticas derivaram, majoritariamente, das demandas das famílias assessoradas ligados aos temas da Segurança Alimentar e Nutricional, Produção de Cuidados em Saúde, e Alimentação Adequada e Saudável. Artigo 3: A compreensão e a estrutura de significações da EAN foram visualizadas sob três eixos: reconhecimento e não reconhecimento da EAN na ATES; a EAN como um dos temas da dimensão social; a EAN como sinônimo de Segurança Alimentar e Nutricional. Conclusão: Existe uma polissemia de percepções sobre a educação alimentar e nutricional e um espaço permanente de tensões entre as normas e as práticas. Existe uma orientação normativa para a promoção da alimentação adequada e saudável, principalmente na perspectiva de relação com os sistemas alimentares locais. As práticas em educação alimentar e nutricional e as percepções sobre elas se estruturam em um conjunto de valores, signos e sentidos nos quais o alimento é visto como elemento aglutinador-compreensivo de um modelo de extensão rural que é reivindicado

Introduction: Food and nutrition education (FNE) is a field of practice and reflection of various social actors involved in health promotion, including the Technical Assistance and Rural Extension Services, which relate to local development actions and to the promotion of adequate and healthy food, as well as to food and nutrition security of rural populations. Objective: To analyze perceptions and practices about the process of food and nutrition education in the context of Rural Development in RS. Methodology: Article 1: We analyzed the text of the Food Guide for the Brazilian population, discussing the intended and the emerging themes from the intersection of the concepts of health promotion and sustainable rural development. Article 2: We investigated the rules established in the national and state level documents and practices implemented by rural extension agents from a search in Administrative Records System containing the description of activities. The data were compiled and processed through descriptive statistics, with the support of Microsoft Office Excel 2007 concerning the production and qualitative analysis; we investigated, in the historical basis, ruptures and continuities contained in the material, with the support of the software NVivo 10 for Windows. Article 3: We conducted 18 individual interviews to produce narratives with the different social actors involved in the Technical Assistance and Rural Extension in RS. The analysis of the narratives was performed from the theoretical perspective and emerging analytical categories; the data were interpreted, systematized and analyzed as a whole with the support of NVivo 10 for Windows. Results: Article 1: We identified 13 themes related to four explanatory dimensions of the intersection of the concepts, which were identified from the constituent elements of the items principles and guidelines of the Food Guide, ten steps to a healthy diet; overcoming obstacles to achieving the ten steps. Article 2: Eight documents and 212,502 activities were analyzed, being 11.13 per cent related to FNE. The rules determined minimum number of activities to be performed by goals established in service contracts, in contrast, the practices mainly come from the demands of advised families linked to the themes of Food and Nutritional Security, Care Production in Health, and Adequate and Healthy Food. Article 3: The understanding and the structure of meanings of FNE were viewed under three axes: recognition and non-recognition of FNE in TSEA; EAN as one of the themes of the social dimension; FNE as a synonym for Food and Nutrition Security. Conclusion: There is a polysemic perception about food and nutrition education and a permanent space of tensions between rules and practices. There is a normative guidance to promote adequate and healthy food, especially from the perspective of relationship with local food systems. The practices in food and nutrition education and the perceptions about them are structured in a set of values, signs and meanings in which food is seen as a unifying-understanding element of a claimed rural extension model

Adenosine transporters and receptors: key elements for retinal function and neuroprotection.

Adenosine is an important neuroactive substance in the central nervous system, including in the retina where subclasses of adenosine receptors and transporters are expressed since early stages of development. Here, we review some evidence showing that adenosine plays important functions in the mature as well as in the developing tissue. Adenosine transporters are divided into equilibrative and concentrative, and the major transporter subtype present in the retina is the ENT1. This transporter is responsible for a bidirectional transport of adenosine and the uptake or release of this nucleoside appears to be regulated by different signaling pathways that are also controlled by activation of adenosine receptors. Adenosine receptors are also key players in retina physiology regulating a variety of functions in the mature and developing tissue. Regulation of excitatory neurotransmitter release and neuroprotection are the main functions played be adenosine in the mature tissue, while regulation of cell survival and neurogenesis are some of the functions played by adenosine in developing retina. Since adenosine is neuroprotective against excitotoxic and metabolic dysfunctions observed in neurological and ocular diseases, the search for adenosine-related drugs regulating adenosine transporters and receptors can be important for advancement of therapeutic strategies against these diseases.

c-Src function is necessary and sufficient for triggering microglial cell activation.

Microglial cells are the resident macrophages of the central nervous system. Their function is essential for neuronal tissue homeostasis. After inflammatory stimuli, microglial cells become activated changing from a resting and highly ramified cell shape to an amoeboid-like morphology. These morphological changes are associated with the release of proinflammatory cytokines and glutamate, as well as with high phagocytic activity. The acquisition of such phenotype has been associated with activation of cytoplasmic tyrosine kinases, including those of the Src family (SFKs). In this study, using both in vivo and in vitro inflammation models coupled to FRET-based time-lapse microscopy, lentiviruses-mediated shRNA delivery and genetic gain-of-function experiments, we demonstrate that among SFKs c-Src function is necessary and sufficient for triggering microglia proinflammatory signature, glutamate release, microglia-induced neuronal loss, and phagocytosis. c-Src inhibition in retinal neuroinflammation experimental paradigms consisting of intravitreal injection of LPS or ischemia-reperfusion injury significantly reduced microglia activation changing their morphology to a more resting phenotype and prevented neuronal apoptosis. Our data demonstrate an essential role for c-Src in microglial cell activation.

c-Src deactivation by the polyphenol 3-O-caffeoylquinic acid abrogates reactive oxygen species-mediated glutamate release from microglia and neuronal excitotoxicity.

3-O-caffeoylquinic acid (3-CQA) is an isomer of chlorogenic acid, which has been shown to regulate lipopolysaccharide-induced tumor necrosis factor production in microglia. Whereas overactivation of microglia is associated with neuronal loss in brain diseases via reactive oxygen species (ROS) production and glutamate excitotoxicity, naïve (nonactivated) microglia are believed to generate little ROS under basal conditions, contributing to the modulation of synaptic activity and nerve tissue repair. However, the signaling pathways controlling basal ROS homeostasis in microglial cells are still poorly understood. Here we used time-lapse microscopy coupled with highly sensitive FRET biosensors (for detecting c-Src activation, ROS generation, and glutamate release) and lentivirus-mediated shRNA delivery to study the pathways involved in antioxidant-regulated ROS generation and how this associates with microglia-induced neuronal cell death. We report that 3-CQA abrogates the acquisition of an amoeboid morphology in microglia triggered by Aß oligomers or the HIV Tat peptide. Moreover, 3-CQA deactivates c-Src tyrosine kinase and abrogates c-Src activation during proinflammatory microglia stimulation, which shuts off ROS production in these cells. Moreover, forced increment of c-Src catalytic activity by overexpressing an inducible c-Src heteromerization construct in microglia increases ROS production, abrogating the 3-CQA effects. Whereas oxidant (hydrogen peroxide) stimulation dramatically enhances glutamate release from microglia, such release is diminished by the 3-CQA inhibition of c-Src/ROS generation, significantly alleviating cell death in cultures from embryonic neurons. Overall, we provide further mechanistic insight into the modulation of ROS production in cortical microglia, indicating antioxidant-regulated c-Src function as a pathway for controlling microglia-triggered oxidative damage.