Role of miRNA in the Regulatory Mechanisms of Estrogens in Cardiovascular Ageing

Cardiovascular diseases are a worldwide health problem and are the leading cause of mortality in developed countries. Together with experimental data, the lower incidence of cardiovascular diseases in women than in men of reproductive age points to the influence of sex hormones at the cardiovascular level and suggests that estrogens play a protective role against cardiovascular disease and that this role is also modified by ageing. Estrogens affect cardiovascular function via their specific estrogen receptors to trigger gene expression changes at the transcriptional level. In addition, emerging studies have proposed a role for microRNAs in the vascular effects mediated by estrogens. miRNAs regulate gene expression by repressing translational processes and have been estimated to be involved in the regulation of approximately 30% of all protein-coding genes in mammals. In this review, we highlight the current knowledge of the role of estrogen-sensitive miRNAs, and their influence in regulating vascular ageing

miRNA as New Regulatory Mechanism of Estrogen Vascular Action

The beneficial effects of estrogen on the cardiovascular system have been reported extensively. In fact, the incidence of cardiovascular diseases in women is lower than in age-matched men during their fertile stage of life, a benefit that disappears after menopause. These sex-related differences point to sexual hormones, mainly estrogen, as possible cardiovascular protective factors. The regulation of vascular function by estrogen is mainly related to the maintenance of normal endothelial function and is mediated by both direct and indirect gene transcription through the activity of specific estrogen receptors. Some of these mechanisms are known, but many remain to be elucidated. In recent years, microRNAs have been established as non-coding RNAs that regulate the expression of a high percentage of protein-coding genes in mammals and are related to the correct function of human physiology. Moreover, within the cardiovascular system, miRNAs have been related to physiological and pathological conditions. In this review, we address what is known about the role of estrogen-regulated miRNAs and their emerging involvement in vascular biology

Impact of the Application of Landfill Leachate on the Germination of Senna macranthera in Different Substrates

Landfill leachate is a potential environmental pollutant. Physicochemical analyses allow identifying its elements while the use of ecotoxicological tests aims to understand the relation with the environment. The germination assay of Senna macranthera in different substrates (filter paper, commercial-SCM, conventional-SCV and organic-SOR) was performed with different doses of leachate. The objective was to identify the potential impact of leachate by determining the concentration able to cause inhibition in 50% of the seeds (LC50) and the values of the no observable effect concentration (NOEC) and the lowest observed effect concentration (LOEC). The LC50 and LOEC occurred in the treatments with 6.25 while NOEC was with 3.125%. The test in substrates, It was not possible to identify the LC50 in the SCM. For the SCV was with 66 and in SOR with 25%. The NOEC and LOEC for SCM and SCV were 25 and 50% and in SOR with 50 and 100%.O lixiviado de aterro é um potencial poluente ambiental. Análises físico-químicas permitem identificar seus elementos enquanto o uso de testes ecotoxicológicos visa compreender a relação com o ambiente. O ensaio de germinação de Senna macranthera em diferentes substratos (papel de filtro, comercial-SCM, convencional-SCV e orgânica-SOR) foi realizada com diferentes doses de lixiviado. O objetivo foi identificar o impacto potencial do lixiviado via determinação da concentração capaz de causar inibição em 50% do sementes (CL50) e os valores da concentração de efeito não observável (CENO) e a concentração de efeitos observados (CEO). A CL50 e a CEO ocorreu nos tratamentos com 6,25% enquanto a CENO ocorreu com 3,125%. Não foi possível identificar o CL50 no SCM. Para o SCV ocorreu com 66% e em SOR com 25%. A CENO e CEO para SCM e SCV foram 25% e 50% e em SOR com 50% e 100%

Estudio de métodos de selección de conceptos

Ponencia presentada en el XI Congreso Internacional de Ingeniería de Proyectos celebrado en Lugo en el año 2007Best product concept selection is of prime importance to direct the marketing launching process. This selection is one of the most difficult and critical decisions for the designer, and an inappropriate concept selection can rarely be compensated on a later stage of the process, increasing the cost of redesign at the same time. Nowadays, there are several concept selection and evaluation methods that allow to reduce the failure risk. The objective of this communication is to carry an analysis of those different methods to evaluate and select concepts, with the aim of reinforcing the methodology developed by the authors on 2006.La elección del mejor concepto de producto es vital para encaminar el proceso de lanzamiento del mismo al mercado. Dicha elección es una de las cuestiones más críticas y difíciles que tiene que tomar el diseñador. Una elección inadecuada de concepto raramente puede ser compensada en posteriores fases del proceso incrementando a su vez el coste de rediseño. En la actualidad existen diferentes métodos de selección y evaluación de concepto que permiten reducir el riesgo de fracaso del proceso. El objetivo de esta comunicación es realizar un estudio de los diferentes métodos que existen en la actualidad para la evaluar y seleccionar conceptos de producto, con el fin de reforzar el método desarrollado por los autores en el año 2006

MicroRNA as crucial regulators of gene expression in estradiol-treated human endothelial cells.

Background/Aims: Estrogen signalling plays an important role in vascular biology as it modulates vasoactive and metabolic pathways in endothelial cells. Growing evidence has also established microRNA (miRNA) as key regulators of endothelial function. Nonetheless, the role of estrogen regulation on miRNA profile in endothelial cells is poorly understood. In this study, we aimed to determine how estrogen modulates miRNA profile in human endothelial cells and to explore the role of the different estrogen receptors (ERα, ERβ and GPER) in the regulation of miRNA expression by estrogen. Methods: We used miRNA microarrays to determine global miRNA expression in human umbilical vein endothelial cells (HUVEC) exposed to a physiological concentration of estradiol (E2; 1 nmol/L) for 24 hours. miRNA-gene interactions were computationally predicted using Ingenuity Pathway Analysis and changes in miRNA levels were validated by qRT-PCR. Role of ER in the E2-induced miRNA was additionally confirmed by using specific ER agonists and antagonists. Results: miRNA array revealed that expression of 114 miRNA were significantly modified after E2 exposition. Further biological pathway analysis revealed cell death and survival, lipid metabolism, reproductive system function, as the top functions regulated by E2. We validated changes in the most significantly increased (miR-30b-5p, miR-487a-5p, miR-4710, miR-501-3p) and decreased (miR-378h and miR-1244) miRNA and the role of ER in these E2-induced miRNA was determined. Results showed that both classical, ERα and ERβ, and membrane-bound ER, GPER, differentially regulated specific miRNA. In silico analysis of validated miRNA promoters identified specific ER binding sites. Conclusion: Our findings identify differentially expressed miRNA pathways linked to E2 in human endothelial cells through ER, and provide new insights by which estrogen can modulate endothelial function

Regulatory network analysis in estradiol-treated human endothelial cells.

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a com-prehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miR-NA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17ß- Estradiol (E2) (1 nmol/lL, 24 h). miRNA--mRNA pairings and their associated canonical pathways were determined using Ingenuity Pathway Analysis software. Transcription factors were identified among the miR-NA-regulated genes. Transcription factor downstream target genes were predicted by consensus transcription factor binding sites in the promoter region of E2-regulated genes by using JASPAR and TRANSFAC tools in Enrichr software. Results: miRNA--target pairings were filtered by using differentially expressed miRNAs and mRNAs characterized by a regulatory relationship accord-ing to miRNA target prediction databases. The analysis identified 588 miRNA--target interactions between 102 miRNAs and 588 targets. Specifically, 63 up-regregulated miRNAs interacted with 295 down-regregulated targets, while 39 down-regregulated miRNAs were paired with 293 up-regregulated mRNA targets. Functional characterization of miRNA/mRNA association analy-sis highlighted hypoxia signallignaling, integrin, ephrin receptor signaling, and regulation of actin-based motility by Rho among the canonical pathways regulated by E2 in HUVEC. Tran-scription factors and downstream genes analysis revealed a total of eight networks, including those mediated by JUN and REPIN1, which are associated with cadherin binding and cell adhe-sion molecule binding pathways. Conclusion: This study identifies regulatory networks obtained by integrative microarray analysis and provides additional insights into the way estradiol could regulate endothelial function in human endothelial cells

Relações solo-fauna durante sucessão florestal em áreas de clareiras por movimento de massa em Mata Atlântica.

Os movimentos de massa são feições naturais do Ambiente de Mata Atlântica, trazendo diversas transformações na paisagem, tanto do ponto de vista ecológico como hidrológico. O presente trabalho observou como se dá a recuperação dos nutrientes do solo e da fauna de microartrópodes em três áreas de deslizamento, levando em conta as características morfológicas de cada uma, que variam em tamanho e forma, sempre as comparando com uma área de floresta clímax local. Observou-se que as clareiras de maior porte apresentam condições menos favoráveis a sucessão, assim como maior propagação de efeito de borda. A densidade da fauna diferiu sensivelmente entre as áreas de clareira e a da floresta, assim como os principais nutrientes do solo, com maiores teores na floresta e no topo do solo, principalmente o fósforo. A diversidade de habitats que são criados por estas clareiras pode estar fortemente associada à biodiversidade elevada típica destes ecossistemas, influenciando diretamente na sua dinâmica na resiliência deste

Broad band analysis of arbitrarily shaped microwave filters using a novel singular value decomposition technique

A new full-wave electromagnetic analysis method based on the Boundary Integral Resonant Mode Expansion (BI-RME) is presented in this paper. The technique allows the computation of the broad band circuital response of arbitrarily shaped cavity filters. The coaxial excitation of this kind of filters is rigorously modeled by taking into account the high order modes on the coaxial aperture. A singular decomposition algebraic procedure has been implemented in order to obtain the solenoidal and non-solenoidal counterparts contributions of the electric current density inside the cavity needed by the BI-RME formulation. This method is simple and avoids some issues associated to star and loop based functions which are typically used for the same purpose.This work has been developed with financial support fromSENECA project Ref. 08833/PI/08, and CICYT project Ref.TEC2007-67630-C03