Mortalidade por câncer de boca e condição sócio-econômica no Brasil

BORGES,D. M. L.et al. Mortalidade por câncer de boca e condição sócio-econômica no Brasil.Cad. Saúde Pública, Rio de Janeiro, v.25,n.2, p.321-327, fev, 2009

The metabolic and epigenetic effects of the isocitrate dehydrogenase-1 mutation in glioma

Cancer cells have been noted to have an altered metabolic phenotype for over ninety years. In the presence of oxygen, differentiated cells predominately utilise the tricarboxylic acid (TCA) cycle and oxidative phosphorylation to efficiently produce energy and the metabolites necessary for protein and lipid synthesis. However, in hypoxia, this process is altered and cells switch to a higher rate of glycolysis and lactate production to maintain their energy and metabolic needs. In cancer cells, glycolysis is maintained at a high rate, even in the presence of oxygen; a term described as “aerobic glycolysis”. Tumour cells are rapidly dividing and have a much greater need for anabolism compared to normal differentiated cells. Rapid glucose metabolism enables faster ATP production as well as a greater redistribution of carbons to nucleotide, protein, and fatty acid synthesis, thus maximising cell growth. Recently, other metabolic changes, driven by mutations in genes related to the TCA cycle, indicate an alternative role for metabolism in cancer, the “oncometabolite”. This is where a particular metabolite builds up within the cell and contributes to the tumorigenic process. One of these genes is isocitrate dehydrogenase (IDH) IDH is an enzyme that forms part of the tricarboxylic acid (TCA) cycle and converts isocitrate to α-ketoglutarate (α-KG). It exists in three isoforms; IDH1, IDH2 and IDH3 with the former present in the cytoplasm and the latter two in the mitochondria. Point mutations have been identified in the IDH1 and IDH2 genes in glioma which result in a gain of function by converting α-KG to 2-hydroxyglutarate (2HG), an oncometabolite. 2HG acts as a competitive inhibitor of the α-KG dependent dioxygenases, a superfamily of enzymes that are involved in numerous cellular processes such as DNA and histone demethylation. It was hypothesised that the IDH1 mutation would result in other metabolic changes in the cell other than 2HG production, and could potentially identify pathways which could be targeted for therapeutic treatment. In addition, 2HG can act as a potential competitive inhibitor of α-KG dependent dioxygenases, so it was hypothesised that there would be an effect on histone methylation. This may alter gene expression and provide a mechanism for tumourogenesis and potentially identify further therapeutic targets. Metabolic analysis of clinical tumour samples identified changes associated with the IDH1 mutation, which included a reduction in α-KG and an increase in GABA, in addition to the increase in 2HG. This was replicated in several cell models, where 13C labelled metabolomics was also used to identify a possible increase in metabolic flux from glutamate to GABA, as well as from α-KG to 2HG. This may provide a mechanism whereby the cell can bypass the IDH1 mutation as GABA can be metabolised to succinate in the mitochondria by GABA transaminase via the GABA shunt. JMJ histone demethylases are a subset of the α-KG dependent dioxygenases, and are involved in removing methyl groups from histone tails. Changes in histone methylation are associated with changes in gene expression depending on the site and extent of chemical modification. To identify whether the increase in 2HG and fall in α-KG was associated with inhibition of histone demethylases a histone methylation screen was used. The IDH1 mutation was associated with an increase in methylation of H3K4, which is associated with gene activation. ChiP and RNA sequencing identified an increase in H3K4me3 at the transcription start site of the GABRB3 subunit, resulting in an increase in gene expression. The GABRB3 subunit forms part of the GABA-A receptor, a chloride channel, which on activation can reduce cell proliferation. The IDH1 mutation was associated with an increase in GABA and GABRB3 subunit of the GABA-A receptor. This raises the possibility of GABA transaminase as a potential therapeutic target. Inhibition of this enzyme could reduce GABA metabolism, potentially reducing any beneficial effect of the GABA shunt in IDH1 mutant tumours, and increasing activation of the GABA-A receptor by increasing the concentration of GABA in the brain. This in turn may reduce cell proliferation, and could be achieved by using Vigabatrin, a GABA transaminase inhibitor licensed for use in epilepsy.

Diversité phénotypique dans la population d’anchois commun (Engraulis encrasicolus) du golfe de Gascogne

With the constant rising of the human population, it is essential to assess and manage the exploitation of the marine species for human consumption such as the anchovy of Bay of Biscay. Thanks to the PELGAS annual surveys, stocks of each species are estimated (biomass, repartition) and studies are undertaken to improve our knowledge about these species. Allozymic studies realized on the anchovy allowed to find a correlation between 2 alleles of the locus IDH and the habitat (depth). This allozyme has a key role in Krebs’ cycle,being speed limiting.. It enables to tolerate variations of temperature and dissolved oxygen. It would be interesting to do new research on variations in the anchovy’s environment and its migrations.

Habitat selection and phenotypic diversity in the anchovy of the Bay of Biscay

Diversity among individuals in a population is an important feature linking vital rates with behaviour and spatial occupation. We measured the growth increments in the otolith of individual fishes collected on the annual fisheries survey PELGAS from 2001 to 2015. Individuals who grew larger at juvenile stage occupied later in life more off-shore habitats. Further, we analysed the allozymes of 13 different loci from 2001 to 2006. Alleles of the enzyme IDH showed different frequencies in inshore and offshore habitats. The population spatially segregates along a coast to off-shore gradient with individuals showing different early growth and allele frequencies. Results show how individuals in a population segregate spatially in different habitats in relation with phenotypic diversity. This implies modelling the population with individual-based and physiological approaches to fully grasp its dynamics. It also implies developing management strategies to conserve infra-population diversity as a means to garantee the occupation of the full range of habitats.

Justicia restaurativa: un estudio sobre su influencia en los procesos de reparación ante el Consejo de Estado colombiano

24 p.

La exigibilidad del control de convencionalidad de las sentencias de la Corte Interamericana de Derechos Humanos: el principio de subsidiariedad en el ordenamiento jurídico colombiano

92 p.

Avaliação dos principais programas de boas práticas agropecuárias implantados no Brasil para promover a sustentabilidade da cadeia leiteira

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Agronomia e Medicina Veterinária, 2016.

Asymptomatic intradialytic hypotension: the need for pre-emptive intervention

Intradialytic hypotension (IDH) remains the most common severe side effect of hemodialysis despite numerous technological advancements. Recent evidence emphasises the significance of asymptomatic hypotensive episodes, as well as the hypoperfusive consequences of both relative blood pressure drops and repetitive, symptomatic events. This article reviews the physiological importance of rapid blood pressure decrease during hemodialysis, and highlights the pathological consequences of repeated asymptomatic and symptomatic hypoperfusive episodes. In proposing a view concerned with asymptomatic IDH, a practicalpre-emptive intervention is offered to improve the long-term outcomes of patients on hemodialysis. Ongoing monitoring of individual patient's mean arterial pressure (MAP) throughout the dialysis treatment can facilitate the identification of an asymptomatic hypotensive episode. A brief pause in ultrafiltration enables vascular refill and subsequent increase in MAP, allowing resumption of safe fluid removal. Such enhanced assessment results in a reduction off patient risk, allowing safe and optimal fluid removal.

Defining Īśvara: A New Perspective in the Hermeneutics of Classical Yoga

The mere presence of the term īśvara in Patañjali’s Yogasūtra has come to affect the meaning of both the path and the goal of Classical Yoga as well as the meaning of the term Yoga itself. The frequent translation of the term īśvara as God leads to the system of Classical Yoga to be labeled as theistic, particularly obscuring the interpretation of īśvarapraṇidhāna, a functional component of the system, as well as perpetuating a syncretic trend that has led to the popular understanding of Yoga as ‘union with the divine’. From identifying problematic hermeneutical trends and their underlying causes, as well as understanding the term within the constraints of the original text in its original Sanskrit, the term īśvara emerges as the archetype of an ultimate reality functioning as a practical and experiential tool providing the yogi with a direct glimpse of its true nature.

América Latina y el Caribe: Variables de competitividad para la dinámica empresarial 2007 - 2014

Este estudio realiza una categorización regional de los países en América Latina con respecto de las categorizaciones globales teniendo en cuenta los índices de competitividad, crecimiento económico y desarrollo humano. El objetivo es actualizar los análisis sobre la situación regional de forma cuantitativa involucrando el grado de asimetría en la competitividad. Esta relación entre el posicionamiento global y regional ha influenciado directamente la evolución del tejido empresarial

El concepto de duelo en los familiares de los desaparecidos : una revisión de la literatura

Este trabajo de grado tiene por objetivo realizar una revisión de literatura que dé cuenta de las características conceptuales del duelo que viven los familiares de los desaparecidos, en un contexto de desaparición forzada de personas como ilícito internacional de los derechos humanos. Para ello se exploraron libros de consulta reconocidos en el tema, artículos de revistas indexadas de los últimos diez años, y jurisprudencia de la Corte Interamericana de Derechos Humanos de casos de desapariciones forzada. Se presenta la definición de la desaparición forzada como ilícito internacional en DDHH, una categorización de víctimas, el desarrollo del concepto de duelo general y para estos casos y su aplicabilidad a los casos de la Corte IDH. Se encontró que los hallazgos dados por la teoría son aplicados en los dictámenes de esta corte, con un discurso de reivindicación de derechos y reparación integral. Se recomiendan futuras investigaciones en propuestas terapéuticas.