1,768,064 research outputs found

    Role and regulation of miR-483 in cancer

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    The hsa-mir-483 locus is located at chromosome 11p15.5 within intron 2 of the IGF2 locus. Because of its location, de-regulated in Wilms’ tumor and other neoplasia, I hypothesized that this microRNA had a potential role in tumors. By analyzing 19 Wilms’ tumors, I proved that miR-483-3p is indeed over-expressed in 100% of the cases and a co-regulation with the over-expression of IGF2 was found. However, several other types of common adult cancers exhibit high or even extremely high levels of miR-483-3p expression without IGF2 over-expression. Indeed, independently from IGF2, the expression of the miR-483-3p could also be induced by the oncoprotein β-catenin through a novel interaction with the basic Helix-Loop-Helix protein upstream stimulatory transcription factor 1 (USF1). I also show that β-catenin itself is a target of miR-483-3p, triggering a negative regulative loop that becomes ineffective in cells harbouring activating mutations of β-catenin pathway. The potential oncogenic role of miR-483-3p was supported by the findings that its ectopic expression protects cells from apoptosis and, conversely, its inhibition increase the level of apoptosis. To understand the mechanisms of its action, I investigated potential gene targets. Among these, an important pro-apoptotic protein, Puma, were inhibited by miR-483-3p. My results indicate that miR-483-3p functions as an anti-apoptotic oncogene, coordinately over-expressed with IGF2 in Wilms’ tumors or induced by β-catenin activation in other tumor types

    The vanishing author in computer-generated works: a critical analysis of recent Australian case law

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    Abstract The use of software is ubiquitous in the creation of many copyright works, yet the requirement in copyright law that every work have a human author who engages in independent intellectual effort means that its use may prevent copyright subsistence. Several recent Australian cases have refocused attention on authorship as an essential criterion of copyright subsistence, and these cases suggest that much computer-produced output may be authorless and thus lack copyright protection. This article, the first in a two-part series, analyses how each case deals with the question of authorship of computer-produced works and why the use of software diminishes copyright protection for a significant number of computer-generated works. The article critiques the application of conventional notions of human authorship developed in the pre-computer age to modern productions and suggests alternative approaches to authorship that satisfy both the major objectives of copyright policy and the need to adapt to the computer age. The article argues that, without a broader judicial approach to authorship of computer-generated works, Parliament must remedy the lacuna in protection for these ‘authorless’ works. Possible solutions for reform are suggested. In a forthcoming article, the author comprehensively examines those reform proposals

    Toponymes (lignes 52 a 63) - CTH 483

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    Notes related to the ritual performed 'when pulling the gods on the roads' based on tablet concordances listed in the CTH 483. Emmanuel Laroche translated this text as "Rituel : 'quand on tire les dieux sur les chemins',” and classified the concordance in the category of Kizzuwatna rituals in ritual texts (Catalogue des textes Hittites, No. 483).Paper (5 sheets

    Toponymes (lignes 52 a 63) - CTH 483

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    Notes related to the ritual performed 'when pulling the gods on the roads' based on tablet concordances listed in the CTH 483. Emmanuel Laroche translated this text as "Rituel : 'quand on tire les dieux sur les chemins',” and classified the concordance in the category of Kizzuwatna rituals in ritual texts (Catalogue des textes Hittites, No. 483).Paper (5 sheets

    Role of mir-483-5p in stress and anxiety

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    Stress and anxiety disorders are often severely debilitating to the individual and contribute immensely to the health care costs. Surveys have estimated that 33.7% of the population is affected by these disorders at least once in their lifetime. Financial burden of anxiety disorders within the European Union is over 41 billion Euros in 2004. A comprehensive understanding of the underlying neuronal and synaptic plasticity mechanisms that contribute to the adaptation and maladaptation to stress and anxiety is essential to offer therapeutic interventions to stress and anxiety disorders. microRNAs (miRs) have been identified to be involved in the orchestration of cellular mechanisms facilitating neuronal and synaptic plasticity. Animal models have been used to understand these mechanisms since they offer flexibility in studying several aspects of these conditions that are unobtainable from human studies due to technical and ethical issues. Here, we have used mice model to study the role of miRs in the amygdala, a brain region implicated in stress, fear and anxiety. We have identified several miRs, one of which is mir-483-5p, that is upregulated in the amygdala following 6hr restraint stress (6hRS). Further investigation revealed that mir-483-5p is enriched and upregulated in synaptosomes of the amygdalar neurons following stress. Moreover, overexpression of mir-483-5p was sufficient to induce changes in dendritic arborisation and spine proportions. Twelve genes were identified as potential targets of mir-483-5p that are expressed in the amygdala and respond to stress using miR target prediction algorithms and gene ontology lists. Out of these twelve in silico predicted targets, three genes (Pgap2, Gpx3 and Macf1) showed down-regulation by mir-483-5p in N2a cells. Furthermore, using luciferase assay, we established a direct interaction of mir-483-5p at the predicted 3’UTR of these three target mRNAs. In vivo experiments showed that these targets are down-regulated in the amygdala following 6hRS where Pgap2 also showed a reduction in synaptosomal compartments. Finally, we assayed the behaviour of mice after bilaterally overexpressing mir-48-5p or knocking down Pgap2 in mice amygdala. Both of these cohorts of animals, relative to their controls, exhibited anxiolytic behaviour. Hitherto, our data suggest that mir-483- 5p, through the downregulation of Pgap2 in the amygdala, contribute to the mediation of anxiolytic behaviour in mice. Understanding the mechanisms and deciphering the molecular partners of mir-483-5p/Pgap2 interaction could advance our understanding of the mechanisms involved in neuronal and synaptic plasticity leading to anxiolytic behaviour and adaptive response to stress

    Magic ritual of Kizzuwatna Rituel magique du Kizzuwatna - CTH 483

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    Notes related to the ritual performed 'when pulling the gods on the roads' based on tablet concordances listed in the CTH 483. Emmanuel Laroche translated this text as "Rituel : 'quand on tire les dieux sur les chemins',” and classified the concordance in the category of Kizzuwatna rituals in ritual texts (Catalogue des textes Hittites, No. 483).Paper (3 sheets

    Resolución UNRN N° 483/2009. Designar docente interina.

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    Fil: Universidad Nacional de Río Negro (U). Universidad Nacional de Río Negro. Río Negro, ArgentinaResolución UNRN N° 483/2009. Designar docente interina.fals
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