189 research outputs found
Expression of citrate carrier gene is activated by ER stress effectors XBP1 and ATF6α, binding to an UPRE in its promoter
Get PDFThe Unfolded Protein Response (UPR) is an intracellular signaling pathway which is activated when unfolded or misfolded proteins accumulate in the Endoplasmic Reticulum (ER), a condition commonly referred to as ER stress. It has been shown that lipid biosynthesis is increased in ER-stressed cells. The N(ε)-lysine acetylation of ER-resident proteins, including chaperones and enzymes involved in the post-translational protein modification and folding, occurs upon UPR activation. In both ER proteins acetylation and lipid synthesis, acetyl-CoA is the donor of acetyl group and it is transported from the cytosol into the ER. The cytosolic pool of acetyl-CoA is mainly derived from the activity of mitochondrial citrate carrier (CiC). Here, we have demonstrated that expression of CiC is activated in human HepG2 and rat BRL-3A cells during tunicamycin-induced ER stress. This occurs through the involvement of an ER stress responsive region identified within the human and rat CiC proximal promoter. A functional Unfolded Protein Response Element (UPRE) confers responsiveness to the promoter activation by UPR transducers ATF6α and XBP1. Overall, our data demonstrate that CiC expression is activated during ER stress through the binding of ATF6α and XBP1 to an UPRE element located in the proximal promoter of Cic gene. The role of ER stress-mediated induction of CiC expression has been discussed
HnRNP A1 mediates the activation of the IRES-dependent SREBP-1a mRNA translation in response to endoplasmic reticulum stress.
Get PDFGrowing evidences suggest the involvement of the endoplasmic reticulum (ER) stress in lipid metabolism and in the development of some liver disease such as steatosis. The transcription factor SREBP-1 modulates the expression of several enzymes involved in lipid synthesis. Previously, we showed that ER stress increased the SREBP-1a protein level in Hep G2 cells, by inducing a cap-independent translation of SREBP-1a mRNA, through an internal ribosome entry site (IRES), located in its leader region. Here, we report evidence that the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) interacts with 5’-UTR of SREBP-1a mRNA, as an IRES trans-acting factor (ITAF), regulating SREBP-1a expression in Hep G2 cells and in primary rat hepatocytes. Overexpression of hnRNP A1 in Hep G2 cells and in rat hepatocytes increased both the SREBP-1a IRES activity and SREBP-1a protein level. Knockdown of hnRNP A1 by small interfering RNA reduced either the SREBP-1a IRES activity and SREBP-1a protein level. HnRNP A1 mediates the increase of SREBP-1a protein level and SREBP-1a IRES activity in Hep G2 cells and in rat hepatocytes upon tunicamycin- and thapsigargin-induced ER stress. The induced ER stress triggered the cytosolic relocation of hnRNP A1 and caused the increment of hnRNP A1 bound to the SREBP-1a 5’-UTR. These data indicate that hnRNP A1 participates in the IRES-dependent translation of SREBP-1a mRNA through RNA-protein interaction. Different content of hnRNP A1 was found in nuclei from liver of high fat diet-fed mice versus standard diet fed-mice, suggesting an involvement of ER stress-mediated hnRNP A1 subcellular redistribution on the onset of metabolic disorders
Lipid accumulation stimulates the cap-independent translation of SREBP-1a mRNA by promoting hnRNP A1 binding to its 5'-UTR in a cellular model of hepatic steatosis
Get PDFNon-alcoholic fatty liver disease (NAFLD) is a chronic disease characterized by accumulation of lipid droplets in hepatocytes. Enhanced release of non-esterified fatty acids from adipose tissue accounts for a remarkable fraction of accumulated lipids. However, the de novo lipogenesis (DNL) is also implicated in the etiology of the NAFLD. Sterol Regulatory Element-Binding Protein-1 (SREBP-1) is a transcription factor modulating the expression of several lipogenic enzymes. In the present study, in order to investigate the effect of lipid droplet accumulation on DNL, we used a cellular model of steatosis represented by HepG2 cells cultured in a medium supplemented with free oleic and palmitic fatty acids (FFAs). We report that FFA supplementation induces the expression of genes coding for enzymes involved in the DNL as well as for the transcription factor SREBP-1a. The SREBP-1a mRNA translation, dependent on an internal ribosome entry site (IRES), and the SREBP-1a proteolytic cleavage are activated by FFAs. Furthermore, FFA treatment enhances the expression and the nucleus-cytosolic shuttling of hnRNP A1, a trans-activating factor of SREBP-1a IRES. The binding of hnRNP A1 to the SREBP-1a IRES is also increased upon FFA supplementation. The relocation of hnRNP A1 and the consequent increase of SREBP-1a translation are dependent on the p38 MAPK signal pathway, which is activated by FFAs. By RNA interference approach, we demonstrate that hnRNP A1 is implicated in the FFA-induced expression of SREBP-1a and of its target genes as well as in the lipid accumulation in cells
Educación Jurídica Internacional
Get PDF"Originally published as International Legal Education, in 26 Harv. Int'l L. J. 361 (1985). Translation by Public Translator Romina Redondo. The editors gratefully acknowledge the generosity of the author and the authorities of the Harvard International Law Journal in allowing the translation and reproduction of the article."Fil: Kennedy, David. Harvard University. Law School. Institute for Global Law and Policy. Cambridge, Estados Unidos"Publicado originalmente como International Legal Education, en 26 Harv. Int'l L. J. 361 (1985). Traducción a cargo de la Trad. Públ. Romina Redondo. Los editores agradecen la generosidad del autor y de las autoridades del Harvard International Law Journal al permitir la traducción y reproducción del artículo"
Pathways of Peace. The Philosophy and Sociology of Peace and Nonviolence.
No full textThis book explores the close interconnection that exists between sociological and philosophical scholarship in relation to peace studies. Through an examination of the thought of nine leading philosophers and sociologists in their historical and geographical context, the author considers notions of nonviolent resistance, pacifism and reverse strike, as well as violence theories of conflict, theories of conflict resolution, the problem of war, and political transitions towards democratization. Engaging with the work of Thoreau, Gandhi, Ghaffar Khan, Capitini, Dolci, Bobbio, Galtung, Sharp and Weil, and considering the institutionalisation of peace research, this volume will appeal to scholars and students of sociology, politics and philosophy with interest in peace and security studies, and conflict
Determinants of farm diversification and interaction with the CAP. An application to FADN of Marche region (Italy)
Get PDFThis work analyzes farm diversification activities in an Italian region (Marche). The study examines 387 farms from Farm Accountancy Data Network (FADN) over a six-year period (2000-2005), applying Discrete Choice Models to identify their business. Recognizing the driving forces of such diversification strategy can be useful to better design those agricultural policies explicitly aimed at promoting agricultural multifunctionality as well as social and environmental sustainability. The linkage between diversification choices and CAP payments is thus also investigated.Farm diversification, Discrete Choice Models, Multifunctionality, Agricultural and Food Policy, Farm Management,
Translational control of human acetyl-CoA carboxylase 1 mRNA is mediated by an internal ribosome entry site in response to ER stress, serum deprivation or hypoxia mimetic CoCl2.
No full textAcetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate limiting step in de novo fatty acid biosynthesis. There is mounting evidence showing that ACC1 is susceptible to dysregulation and that it is over-expressed in liver diseases associated with lipid accumulation and in several cancers. In the present study, ACC1 regulation at the translational level is reported. Using several experimental approaches, the presence of an internal ribosome entry site (IRES) has been established in the 5' untranslated region (5' UTR) of the ACC1 mRNA. Transfection experiments with the ACC1 5' UTR inserted in a dicistronic reporter vector show a remarkable increase in the downstream cistron translation, through a cap-independent mechanism. The endoplasmic reticulum (ER) stress condition and the related unfolded protein response (UPR), triggered by treatment with thapsigargin and tunicamycin, cause an increase of the cap-independent translation of ACC1 mRNA in HepG2 cells, despite the overall reduction in global protein synthesis. Other stress conditions, such as serum starvation and incubation with hypoxia mimetic agent CoCl2, up-regulate ACC1 expression in HepG2 cells at the translational level. Overall, these findings indicate that the presence of an IRES in the ACC1 5' UTR allows ACC1 mRNA translation in conditions that are inhibitory to cap-dependent translation. A potential involvement of the cap-independent translation of ACC1 in several pathologies, such as obesity and cancer, has been discussed
El arte como alienación en la teoría Macuseana de la cultura
Get PDFEl artículo propone una revisión de la teoría de la cultura de Herbert Marcuse, desde sus escritos tempranos hasta algunas tesis de sus últimas obras. La idea fundamental del texto es que la concepción del arte y la experiencia estética que el autor sostiene presenta elementos para una comprensión más compleja de su teoría de la cultura afirmativa y para la negación de la idea de su eliminación radical.The article proposes a revision of the theory of the culture of Herbert Marcuse, from its early writings until some theses of its last Works. The fundamental idea of the text is that the conception of art and the aesthetic experience that the author maintains presents elements for a more complex comprensión of his theory of affirmative culture and for the negation of the idea of its radical elimination.Fil: Conti, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata; Argentin
Posmodernidad e individuo en la novela Agosto de Romina Paula
No full textRomina Paula, one of the young authors of contemporary argentine literature, in her novel Agosto, tells the story of a woman in her short journey from Buenos Aires to Esquel, the town where she was born and raised. In this study, Paula’s novel, which can be considered experimental, has been analyzed as a postmodern work. The structure and style of the novel allows it to be thought within the context of postmodernism. In the novel, which consists of short texts in the style of letters, the sequence of sentences and word groups and the repetition of certain expressions in similar ways is considered as a postmodern feature. In addition, Emilia, the protagonist of the novel, has features in order to be examined as a postmodern individual. Leaving her little town and trying to find her own existence in the heterogeneous crowd of the cosmopolitan city Buenos Aires, the young woman sheds light on the unstable, slippery, variable and versatile aspect of the postmodern world with her hesitations and uncertainty. It is observed that there is a postmodern alienation towards both herself and her surroundings in the young woman who hesitates between leaving and staying. While Emilia is created by the author Romina Paula as a traveling individual with her disorganized, restless and volatile thoughts, it is seen that there is actually a tidal state in the spiritual sense. In the study, it is argued that this novel, in which it becomes clear that the individual cannot feel belonging and is alienated in this way, is a postmodern work in terms of both its structure, style and the way it handles the individual.Romina Paula es una de las jóvenes autoras de la literatura argentina contemporánea que, en su novela Agosto, cuenta la historia de una mujer que realiza un breve viaje desde Buenos Aires hasta Esquel, la ciudad en la que nació y creció. El objeto de este estudio es analizar la novela de Paula, considerada experimental, como una obra posmoderna, dado que su estructura y estilo permiten pensarla en el contexto de la posmodernidad. En la novela, que consta de textos cortos a modo de carta, la secuencia de oraciones y grupos de palabras, así como la repetición de ciertas expresiones similares, se valoran como características posmodernas. Además, su protagonista, Emilia, tiene rasgos para ser examinada como un individuo posmoderno. Esta mujer, al salir de su pequeña ciudad y tratar de encontrar su propia existencia en la heterogénea multitud de la cosmopolita Buenos Aires, arroja luz sobre el aspecto inestable, resbaladizo, variable y versátil del mundo posmoderno, con sus vacilaciones e incertidumbres. Se observa, entonces, la existencia de una alienación posmoderna en la protagonista hacia sí misma y hacia su entorno, una vez que duda entre irse o quedarse. Con pensamientos des-organizados, inquietos y volátiles, Emilia es retratada por la escritora Romina Paula como una persona viajera, al mismo tiempo que se percibe una especie de estado de marea del que goza en el sentido espiritual. Por ende, en este estudio se argumenta la idea de que las situaciones en las que el individuo no puede sentir pertenencia social, y, por lo tanto, se aliena de la sociedad, son las que conducen a considerar esta novela como posmoderna, teniendo en cuenta la estructura, el estilo y la forma de manejar al individu
Take the Law
Get PDFEn el marco de la discusión acerca de la relación entre el derecho y la enseñanza en la actualidad, la autora introduce tres reflexiones tangenciales: en primer lugar, el derecho en la generación de la desigualdad; en segundo, la enseñanza jurídica de la jerarquía; finalmente, la arquitectura legal androcéntrica.Within the framework of the discussion on the relationship between law and education today, the author introduces three tangential reflections: firstly, law in the generation of
inequality; secondly, the legal teaching of hierarchy; and finally, the androcentric legal architecture.Fil: Lerussi, Romina Carla. Universidad Nacional de Cordoba. Facultad de Filosofia y Humanidades. Cent.de Invest. Maria Saleme de Burnichon; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin
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