22 research outputs found

    La tradición política Portaliana: Chile siglos XIX y XX

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    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Filosofía y Letras, Departamento de Historia Contemporanea. Fecha de Lectura: 07-09-2022La vida y obra del ministro Diego Portales (1793-1837) tiene en Chile una numerosa bibliografía. Los más destacados historiadores chilenos se han pronunciado sobre él, ya sea resaltándolo como el forjador de la república chilena del siglo XIX y otros criticándolo por encarnar la figura del líder conservador-autoritario por excelencia, que habría dirigido una especie de reacción colonial post independencia de Chile. Lo anterior, además, cruzado de fuertes disputas sobre la real influencia para la historia de Chile de su legado. El presente trabajo no intenta resolver la extensa disputa historiográfica sobre Diego Portales, sino que intenta, en primer lugar, definir un núcleo portaliano, es decir, el conjunto ideas, creencias e imágenes más permanentes asociadas a su figura y obra a lo largo de los siglos XIX y XX y como ese núcleo evolucionó hasta construir la primera y más permanente tradición política de tipo republicano en la historia de Chile. No es, por tanto, un trabajo tanto de “hechos” como de “ideas” sobre Diego Portales y como esas ideas y creencias han determinado, en diversas circunstancias históricas de Chile, el actuar o la justificación de sus protagonistas. Al respecto cabe señalar que Diego Portales, como hombre esencialmente volcado a la acción, no desarrollo una exposición sistemática y clara del contenido de sus ideales políticos, los que es necesario desentrañar a través de sus actuaciones y sus obras, además de su nutrida correspondencia privada. Por otra parte, desde el instante mismo de su muerte, sus partidarios y seguidores fueron elaborando, dependiendo de las necesidades políticas del momento, una serie de principios e ideas en torno al buen gobierno republicano que también pasaron a formar parte, -algunos con más mérito que otros-, del supuesto legado portaliano. En tal sentido, nuestro trabajo intenta estudiar la evolución a través de los siglos XIX y XX, de un conjunto de ideas, imágenes o conductas, que fueron capaces de condensar y simbolizar toda una idea del buen gobierno republicano, personificado a su vez, en la vida y obra de Diego Portale

    Genome-wide identification of new Wnt/β-catenin target genes in the human genome using CART method

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    <p>Abstract</p> <p>Background</p> <p>The importance of <it>in silico </it>predictions for understanding cellular processes is now widely accepted, and a variety of algorithms useful for studying different biological features have been designed. In particular, the prediction of <it>cis </it>regulatory modules in non-coding human genome regions represents a major challenge for understanding gene regulation in several diseases. Recently, studies of the Wnt signaling pathway revealed a connection with neurodegenerative diseases such as Alzheimer's. In this article, we construct a classification tool that uses the transcription factor binding site motifs composition of some gene promoters to identify new Wnt/β-catenin pathway target genes potentially involved in brain diseases.</p> <p>Results</p> <p>In this study, we propose 89 new Wnt/β-catenin pathway target genes predicted <it>in silico </it>by using a method based on multiple Classification and Regression Tree (CART) analysis. We used as decision variables the presence of transcription factor binding site motifs in the upstream region of each gene. This prediction was validated by RT-qPCR in a sample of 9 genes. As expected, LEF1, a member of the T-cell factor/lymphoid enhancer-binding factor family (TCF/LEF1), was relevant for the classification algorithm and, remarkably, other factors related directly or indirectly to the inflammatory response and amyloidogenic processes also appeared to be relevant for the classification. Among the 89 new Wnt/β-catenin pathway targets, we found a group expressed in brain tissue that could be involved in diverse responses to neurodegenerative diseases, like Alzheimer's disease (AD). These genes represent new candidates to protect cells against amyloid β toxicity, in agreement with the proposed neuroprotective role of the Wnt signaling pathway.</p> <p>Conclusions</p> <p>Our multiple CART strategy proved to be an effective tool to identify new Wnt/β-catenin pathway targets based on the study of their regulatory regions in the human genome. In particular, several of these genes represent a new group of transcriptional dependent targets of the canonical Wnt pathway. The functions of these genes indicate that they are involved in pathophysiology related to Alzheimer's disease or other brain disorders.</p

    A rapid preparative-TLC/GC-MS methodology for discriminating between two filmy ferns (Hymenophyllaceae) native from the temperate rain forest of Southern Chile based on their soluble carbohydrates

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    Filmy ferns are a conspicuous epiphytic component of the temperate rain forest of southern Chile and the more abundant genus is Hymenophyllum represented by 19 species, they are a primitive fern family sharing their limited water lost control (poikilohydricity) with lower non-vascular plants, such as bryophytes and lichens. Because, carbohydrate accumulation is a desiccation tolerance mechanism proposed for desiccation-tolerant vascularized plants, the aim of this investigation was to propose a methodology for soluble carbohydrate analysis in native ferns. Preparative- TLC showed to be a simple and rapid technique for separating Hymenophyllum sugars. GC-MS analysis allowed identifying glucitol (2.0%), sucrose (2.0%),  or -melibiose (5.0%) and salidroside (4.4%) in H. cruentum carbohydrate profile from H. dentatum showed significant differences presenting only two sugars sucrose (1.4%) and  or -melibiose (3.2%). Furthermore, salidroside, an antioxidant compound, was identified only in H. cruentum. Our results suggest that H. cruentum, has higher preventive mechanisms than H. dentatum; that would allow delay the effects of desiccation (prevent a rapid dehydration) and thus survive to short periods of drought present in the study area. Due to the presence of salidroside in H. cruentum this species should be more resistant to oxidative stress that H. dentatum

    Genes encoding novel secreted and transmembrane proteins are temporally and spatially regulated during <it>Drosophila melanogaster </it>embryogenesis

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    <p>Abstract</p> <p>Background</p> <p>Morphogenetic events that shape the <it>Drosophila melanogaster </it>embryo are tightly controlled by a genetic program in which specific sets of genes are up-regulated. We used a suppressive subtractive hybridization procedure to identify a group of developmentally regulated genes during early stages of <it>D. melanogaster </it>embryogenesis. We studied the spatiotemporal activity of these genes in five different intervals covering 12 stages of embryogenesis.</p> <p>Results</p> <p>Microarrays were constructed to confirm induction of expression and to determine the temporal profile of isolated subtracted cDNAs during embryo development. We identified a set of 118 genes whose expression levels increased significantly in at least one developmental interval compared with a reference interval. Of these genes, 53% had a phenotype and/or molecular function reported in the literature, whereas 47% were essentially uncharacterized. Clustering analysis revealed demarcated transcript groups with maximum gene activity at distinct developmental intervals. <it>In situ </it>hybridization assays were carried out on 23 uncharacterized genes, 15 of which proved to have spatiotemporally restricted expression patterns. Among these 15 uncharacterized genes, 13 were found to encode putative secreted and transmembrane proteins. For three of them we validated our protein sequence predictions by expressing their cDNAs in <it>Drosophila </it>S2R+ cells and analyzed the subcellular distribution of recombinant proteins. We then focused on the functional characterization of the gene CG6234. Inhibition of CG6234 by RNA interference resulted in morphological defects in embryos, suggesting the involvement of this gene in germ band retraction.</p> <p>Conclusion</p> <p>Our data have yielded a list of developmentally regulated <it>D. melanogaster </it>genes and their expression profiles during embryogenesis and provide new information on the spatiotemporal expression patterns of several uncharacterized genes. In particular, we recovered a substantial number of unknown genes encoding putative secreted and transmembrane proteins, suggesting new components of signaling pathways that might be incorporated within the existing regulatory networks controlling <it>D. melanogaster </it>embryogenesis. These genes are also good candidates for additional targeted functional analyses similar to those we conducted for CG6234.</p> <p>See related minireview by Vichas and Zallen: <url>http://www.jbiol.com/content/8/8/76</url></p

    UFR2709, an Antagonist of Nicotinic Acetylcholine Receptors, Delays the Acquisition and Reduces Long-Term Ethanol Intake in Alcohol-Preferring UChB Bibulous Rats

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    Alcoholism is a worldwide public health problem with high economic cost and which affects health and social behavior. It is estimated that alcoholism kills 3 million people globally, while in Chile it is responsible for around 9 thousand deaths per year. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels expressed in the central nervous system, and they were suggested to modulate the ethanol mechanism involved in abuse and dependence. Previous work demonstrated a short-term treatment with UFR2709, a nAChRs antagonist, which reduced ethanol intake using a two-bottle free-choice paradigm in University of Chile bibulous (UChB) rats. Here, we present evidence of the UFR2709 efficacy in reducing the acquisition and long-term ethanol consumption. Our results show that UFR2709 (2.5 mg/kg i.p.) reduces the seek behavior and ethanol intake, even when the drug administration was stopped, and induced a reduction in the overall ethanol intake by around 55%. Using naïve UChB bibulous rats, we demonstrate that UFR2709 could delay and reduce the genetically adaptive impulse to seek and drink ethanol and prevent its excessive intake

    Nicotinic antagonist UFR2709 inhibits nicotine reward and decreases anxiety in zebrafish

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    Zebrafish is becoming a popular animal model in neuropharmacology and drug discovery, mainly due to its ease of handling and low costs involved in maintenance and experimental work. This animal displays a series of complex behaviours that makes it useful for assessing the e ects of psychoactive drugs. Here, adult zebrafish were used for assessment of the anxiolytic and anti-addictive properties of UFR2709, a nicotinic receptor (nAChR) antagonist, using two behavioural paradigms to test for addiction, the novel tank diving test to assess anxiety and the conditioned place preference (CPP). Furthermore, the expression of nAChR subunits 4 and 7 was measured in the zebrafish brain. The results show that UFR2709 exhibits an anxiolytic e ect on zebrafish and blocks the e ect evoked by nicotine on CPP. Moreover, UFR2709 significantly decreased the expression of 4 nicotinic receptor subunit. This indicates that UFR2709 might be a useful drug for the treatment of nicotine addiction.National Agency of Research and Development, Chile 115-0615 117-0662 120-047
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