953 research outputs found

    Encefalopatías espongiformes transmisibles. Bases moleculares, diagnóstico y perspectivas terapéuticas

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    Las encefalopatías espongiformes transmisibles constituyen un grupo de enfermedades neurodegenerativas que estánasociadas a la presencia en el tejido nervioso de agregados insolubles constituidos por una isoforma anómala de unaproteína denominada prión. Esta isoforma se produce por un cambio conformacional en una molécula que puedetransmitirse a otras proteínas priónicas normales. Las proteínas modificadas pierden su actividad biológica, desencadenándosela muerte de las neuronas por apoptosis. Los cambios conformacionales de los priones que derivan enenfermedad pueden deberse a la existencia de mutaciones que disminuyan la estabilidad de las formas celulares.Existe susceptibilidad genética, por tanto, a padecer tipos hereditarios de la enfermedad o adquiridos por infeccióncon isoformas priónicas anormales. En la actualidad se están perfeccionando métodos sensibles de diagnósticobasados en la detección de las isoformas anormales de la proteína priónica. Todavía no existen tratamientos curativospara estas enfermedades aunque se están diseñando métodos terapéuticos que bloqueen los cambios conformacionalesque conducen a la precipitación de la proteína priónica

    Identificación de productos de Triticum aestivum en las pastas alimenticias. II. Determinación colorimétrica del palmitato de sitosterol.

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    Walde y Mangel (1930) estudiaron los extractos acetónicos de las harinas de una variedad de Triticum durum y otra de Triticum aestivum (incl. T. vulgare); encontraron que la sustancia grasa de esta última contenía una cantidad apreciable de sustancia cristalina, mientras que la de T. durum no presentaba cristales y era menos viscosa. Ambos extractos daban reacción positiva de Liebermann-Burchard, pero el desarrollo de color era más lento en el de T. durum. También encontraron estos autores que el extracto de T. aestivum, disuelto en acetona y llevado a 0o C, separaba un precipitado que no aparecía en el de T. durum. Dicho precipitado fue estudiado por Spielman (1933), siendo identificado como el ester palmítico de una mezcla de sitosterol y sitostanol. Walde y Mangel fueron, por tanto, los primeros en sugerir la presencia de palmitato de sitosterol como posible carácter específico de T. aestivum

    Who Are the Workers Who Never Joined a Union? : Empirical Evidence from Western and Eastern Germany

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    "Using representative data from the German social survey ALLBUS 2002 and the European Social Survey 2002/03, this paper provides the first empirical analysis of trade union ‘never-membership’ in Germany. We show that between 54 and 59 percent of all employees in Germany have never been members of a trade union. In western Germany, individuals’ probability of ‘never-membership’ is significantly affected by their personal characteristics, their political orientation and (to a lesser degree) their family background. In addition, the presence of a union at the workplace plays a significant role. While the latter factor is also important in eastern Germany, many of the variables which are relevant for ‘never-membership’ in the west prove to be irrelevant in the east. This difference probably reflects the fact that most employees in eastern Germany did not really have a choice not to become union members during the communist regime." (author's abstract)"Mit Daten des ALLBUS 2002 und des European Social Survey 2002/03 analysiert diese Arbeit erstmalig die ‚Nie-Mitgliedschaft’ in deutschen Gewerkschaften. Wir zeigen, dass 54 bis 59 Prozent aller Beschäftigten in Deutschland niemals Mitglied einer Gewerkschaft waren. Die individuelle Wahrscheinlichkeit einer ‚Nie-Mitgliedschaft’ hängt in Westdeutschland signifikant mit persönlichen Merkmalen, der politischen Ausrichtung und (in geringerem Maße) dem familiären Hintergrund zusammen. Darüber hinaus spielt das Vorhandensein einer Gewerkschaft am Arbeitsplatz eine signifikante Rolle. Während letzteres auch in Ostdeutschland von Bedeutung ist, erweisen sich viele der im Westen relevanten Erklärungsvariablen im Osten als irrelevant. Dieser Unterschied spiegelt wahrscheinlich wider, dass die meisten Arbeitnehmer in Ostdeutschland während des SED-Regimes kaum die Wahl hatten, auf eine Gewerkschaftsmitgliedschaft zu verzichten." (Autorenreferat

    The expression of RUNX3 in colorectal cancer is associated with disease stage and patient outcome

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    RUNX3 is believed to have tumour suppressor properties in several cancer types. Inactivation of RUNX3 has been shown to occur by methylation-induced transcriptional silencing and by mislocalization of the protein to the cytoplasm. The aim of this study was to examine the clinical significance of RUNX3 expression in a large series of colorectal cancers using immunohistochemistry and tissue arrays. With advancing tumour stage, expression of RUNX3 in the nucleus decreased, whereas expression restricted to the cytoplasmic compartment increased. Nuclear RUNX3 expression was associated with significantly better patient survival compared to tumours in which the expression of RUNX3 was restricted to the cytoplasm (P=0.025). These results support a role for RUNX3 as a tumour suppressor in colorectal cancer

    Determinación de los coeficientes de control de flujo en un tramo acotado de la ruta glucolítica

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    The Flux Control Theory has been applied successfully to the study of the regulation of metabolism. There have been described several methods for the determination of the flux control coefficients in different metabolic pathways. In this work, we describe an experimental method for the determination of these coefficients in the earlier glycolytic steps in rat-kidney cortex, their change caused by AMP and the possible application to the study of the metabolic importance of the substrate cycle established between fructose 6-phosphate and fructose             1,6-bisphosphate.La Teoría de Control de Flujo ha demostrado ser útil en el estudio de la regulación del metabolismo. Han sido descritos varios métodos para la determinación de los coeficientes de control de flujo en diferentes rutas metabólicas. En este trabajo describimos un método experimental para la determinación de estos coeficientes en las primeras etapas de las glucolisis en corteza renal de rata, su modificación en presencia de AMP y la posible aplicación al estudio de la importancia metabólica del ciclo de sustrato establecido entre fructosa 6-fosfato y fructosa 1,6-bisfosfato

    Determinación de los coeficientes de control de flujo en un tramo acotado de la ruta glucolítica

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    La Teoría de Control de Flujo ha demostrado ser útil en el estudio de la regulación del metabolismo. Han sido descritos varios métodos para la determinación de los coeficientes de control de flujo en diferentes rutas metabólicas. En este trabajo describimos un método experimental para la determinación de estos coeficientes en las primeras etapas de las glucolisis en corteza renal de rata, su modificación en presencia de AMP y la posible aplicación al estudio de la importancia metabólica del ciclo de sustrato establecido entre fructosa 6-fosfato y fructosa 1,6- bisfosfato.The Flux Control Theory has been applied successfully to the study of the regulation of metabolismo There have been described several methods for the determination of the flux control coefficients in different metabolic pathways. In this work, we describe an experimental method for the determination of these coefficients in the earlier glycolytic steps in rat-kidney cortex, their change caused by AMP and the possible application to the study of the metabolic importance of the substrate cycle established between fructose 6-phosphate and fructose 1,6- bisphosphate

    Efecto de cationes divalentes sobre la actividad fructosa 1,6-bisfosfatasa purificadas de corteza renal de rata

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    Fructose 1,6-bisphosphatse is an enzyme that plays an important physiological role, especially in the gluconeogenic tissues, as kidney-cortex. There are several mechanisms to guarantee a strict regulation of its activity. We will emphasize the importance of divalent cations as enzyme effectors, leaving aside their role as catalytic ions. In this work we describe the kinetic characteristics of the purified enzyme from rat-kidney cortex, as a functions of the concentrations of the most important cations for the enzyme activity, magnesium and manganese.La fructosa 1,6-bisfosfatasa es un enzima de gran importancia fisiológica, sobre todo en los tejidos gluconeogénicos como la corteza renal, por lo que existen diversos mecanismos para ejercer una estricta regulación de su actividad. Entre ellos, destacamos el papel de diversos cationes divalentes como efectores del enzima, al margen de que, también, sean imprescindibles para la catálisis. En este trabajo, se estudian las características cinéticas del enzima purificado a partir de corteza renal de rata, en función de la concentración de dos de los cationes más importantes para la actividad del enzima, magnesio y manganeso

    Gastrointestinal tissue‐based molecular biomarkers: A practical categorization based on the 2019 WHO Classification of Epithelial Digestive Tumours

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    Molecular biomarkers have come to constitute one of the cornerstones of oncological pathology. The method of classification not only directly affects the manner in which patients are diagnosed and treated, but also guides the development of drugs and of artificial intelligence tools. The aim of this article is to organise and update gastrointestinal molecular biomarkers in order to produce an easy-to-use guide for routine diagnostics. For this purpose, we have extracted and reorganised the molecular information on epithelial neoplasms included in the 2019 World Health Organization classification of tumours. Digestive system tumours, 5th edn

    Ultra-low DNA input into whole genome methylation assays and detection of oncogenic methylation and copy number variants in circulating tumour DNA

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    Background: Abnormal CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide coverage. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) biopsy specimens from clinical trials or circulating tumour DNA is challenging at the genome-wide level because of lack of available input. We present the results of low input experiments into the Illumina Infinium HD methylation assay on FFPE specimens and ctDNA samples. Methods: For all experiments, the Infinium HD assay for methylation was used. In total, forty-eight FFPE specimens were used at varying concentrations (lowest input 50 ng); eighteen blood derived specimens (lowest input 10 ng) and six matched ctDNA input (lowest input 10 ng)/fresh tumour specimens (lowest input 250 ng) were processed. Downstream analysis was performed in R/Bioconductor for quality control metrics and differential methylation analysis as well as copy number calls. Results: Correlation coefficients for CpG methylation were high at the probe level averaged R2 = 0.99 for blood derived samples and R2 > 0.96 for the FFPE samples. When matched ctDNA/fresh tumour samples were compared, R2 > 0.91 between the two. Results of differential methylation analysis did not vary significantly by DNA input in either the blood or FFPE groups. There were differences seen in the ctDNA group as compared to their paired tumour sample, possibly because of enrichment for tumour material without contaminating normal. Copy number variants observed in the tumour were generally also seen in the paired ctDNA sample with good concordance via DQ plot. Conclusions: The Illumina Infinium HD methylation assay can robustly detect methylation across a range of sample types, including ctDNA, down to an input of 10 ng. It can also reliably detect oncogenic methylation changes and copy number variants in ctDNA. These findings demonstrate that these samples can now be accessed by methylation array technology, allowing analysis of these important sample types
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