475 research outputs found

    Tan queridos y tan desaparecidos

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    Clermont-Ferrand – Angles des rues Kessler et Rabanesse et du boulevard Jean-Jaurès

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    Identifiant de l'opération archéologique : 2007/218 Date de l'opération : 2007 (EX) Le projet d’aménagement d’un immeuble dans une zone riche en vestiges archéologiques étant susceptible d’affecter des éléments du patrimoine, une campagne de diagnostic a été prescrite par le service régional de l’archéologie d’Auvergne. Cette opération, menée du 9 au 17 octobre 2007, concerne un projet d’une surface de 2 732 m2 . Le site est localisé dans les quartiers sud de la ville, à l’angle des rues Kes..

    Big metamodels are evil

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    While reuse is typically considered a good practice, it may also lead to keeping irrelevant concerns in derived elements. For instance, new metamodels are usually built upon existing metamodels using additive techniques such as profiling and package merge. With such additive techniques, new metamodels tend to become bigger and bigger, which leads to harmful overheads of complexity for both tool builders and users. In this paper, we introduce ≪ package unmerge≫ - a proposal for a subtractive relation between packages - which complements existing metamodel-extension techniques

    Les espaces de cuisine d’un édifice public ou collectif d’<i>Augustonemetum</i>/Clermont-Ferrand (Puy-de-Dôme)

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    International audienceDuring the excavations of Carré Jaude 2 in Clermont-Ferrand, a building, identified as a schola, has been partially uncovered adjacent to a vast public square. Built in the middle of the 2nd century AD, it was burnt down, during the 3rd quarter of the 3rd century. A series of service rooms located to the south of richly decorated public latrines, with an ornamental basin, are mainly devoted to activities such as cooking: a main kitchen, equipped with two tiled ovens and a rectangular stonework construction which could be a raised hob; a room equipped with a flat tiled hearth and manhole access to a drain; another room with a hydraulic concrete floor probably contained a water tank; a utility room contained a large stone mortar set into the floor; a storeroom for stocking foodstuffs and crockery. The interpretation of this archaeological complex is also documented by a religious inscription uncovered in the demolition layers of one of the rooms and the analysis of the finds and the plant and animal remains.Dans le cadre des fouilles du Carré Jaude 2 à Clermont-Ferrand, a été partiellement reconnu un édifice interprété comme une schola, implanté à proximité d’une grande place publique. Construit vers le milieu du IIe s. apr. J. C., il a été incendié vers le troisième quart du IIIe s. Au sud de latrines collectives richement décorées, associées à un bassin ornemental, se développe une série de pièces de service en grande partie dévolues à la préparation de repas : une cuisine principale équipée de deux fours en tuiles et d’une structure maçonnée rectangulaire pouvant correspondre à la base d’une table de cuisson ; une pièce pourvue d’un foyer plat en tuiles et d’un regard d’accès à l’égout ; une salle dotée d’un sol de béton hydraulique, qui abritait probablement une cuve d’eau ; un local comportant un grand mortier de broyage encastré dans le sol ; une resserre réservée au stockage de denrées et de vaisselle. Cet ensemble est documenté par l’étude d’une inscription religieuse découverte dans les niveaux de destruction de l’une des pièces, ainsi que par l’analyse du mobilier et des restes fauniques et carpologiques

    Cournon-d’Auvergne – Carré du Buisson (lotissement Bois Joli 2)

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    Identifiant de l'opération archéologique : 2006/78 Date de l'opération : 2007 (EX) La commune de Cournon d’Auvergne, située à quelque5km au sud-est de Clermont-Ferrand, s’inscrit entre la grande plaine de La Limagne au nord, la dépression du bassin de Sarliève à l’ouest, bordé lui-même par des collines calcaires et la rivière Allier à l’est. Elle se situe donc au débouché du bassin de l’Allier vers la plaine. Le bassin de Sarliève, qui intéresse plus particulièrement, notre dossier est dominé..

    Lempdes – Les Gibaudonnes et La Ponsole, Fontanille, Croix Saint-Masson (ZAC de la Fontanille II)

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    L’emprise de la future ZAC de la Fontanille à Lempdes est située entre les ronds-points de la Croix Saint-Masson et de Chazal. Les parcelles concernées par l’opération archéologique se trouvent au pied de la butte marnocalcaire de Chambussière, en bordure sud de la grande plaine de La Limagne, dans le secteur communément appelée les Marais. Cette opération, menée du 13 novembre 2006 au 23 décembre 2006 et du 8 au 26 janvier 2007, concerne un projet d’une surface de 375 776 m2 (BSR 2006, p. 10..

    TWIST1 a New Determinant of Epithelial to Mesenchymal Transition in EGFR Mutated Lung Adenocarcinoma

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    Metastasis is a multistep process and the main cause of mortality in lung cancer patients. We previously showed that EGFR mutations were associated with a copy number gain at a locus encompassing the TWIST1 gene on chromosome 7. TWIST1 is a highly conserved developmental gene involved in embryogenesis that may be reactivated in cancers promoting both malignant conversion and cancer progression through an epithelial to mesenchymal transition (EMT). The aim of this study was to investigate the possible implication of TWIST1 reactivation on the acquisition of a mesenchymal phenotype in EGFR mutated lung cancer. We studied a series of consecutive lung adenocarcinoma from Caucasian non-smokers for which surgical frozen samples were available (n = 33) and showed that TWIST1 expression was linked to EGFR mutations (P<0.001), to low CDH1 expression (P<0.05) and low disease free survival (P = 0.044). To validate that TWIST1 is a driver of EMT in EGFR mutated lung cancer, we used five human lung cancer cell lines and demonstrated that EMT and the associated cell mobility were dependent upon TWIST1 expression in cells with EGFR mutation. Moreover a decrease of EGFR pathway stimulation through EGF retrieval or an inhibition of TWIST1 expression by small RNA technology reversed the phenomenon. Collectively, our in vivo and in vitro findings support that TWIST1 collaborates with the EGF pathway in promoting EMT in EGFR mutated lung adenocarcinoma and that large series of EGFR mutated lung cancer patients are needed to further define the prognostic role of TWIST1 reactivation in this subgroup

    Upstream ORF affects MYCN translation depending on exon 1b alternative splicing

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    <p>Abstract</p> <p>Background</p> <p>The <it>MYCN </it>gene is transcribed into two major mRNAs: one full-length (<it>MYCN) </it>and one exon 1b-spliced (<it>MYCN</it><sup>Δ1<it>b</it></sup>) mRNA. But nothing is known about their respective ability to translate the MYCN protein.</p> <p>Methods</p> <p>Plasmids were prepared to enable translation from the upstream (uORF) and major ORF of the two <it>MYCN </it>transcripts. Translation was studied after transfection in neuroblastoma SH-EP cell line. Impact of the upstream AUG on translation was evaluated after directed mutagenesis. Functional study with the two <it>MYCN </it>mRNAs was conducted by a cell viability assay. Existence of a new protein encoded by the <it>MYCN</it><sup>Δ1<it>b </it></sup>uORF was explored by designing a rabbit polyclonal antibody against a specific epitope of this protein.</p> <p>Results</p> <p>Both are translated, but higher levels of protein were seen with <it>MYCN</it><sup>Δ1<it>b </it></sup>mRNA. An upstream ORF was shown to have positive cis-regulatory activity on translation from <it>MYCN </it>but not from <it>MYCN</it><sup>Δ1<it>b </it></sup>mRNA. In transfected SH-EP neuroblastoma cells, high MYCN dosage obtained with <it>MYCN</it><sup>Δ1<it>b </it></sup>mRNA translation induces an antiapoptotic effect after serum deprivation that was not observed with low MYCN expression obtained with <it>MYCN </it>mRNA. Here, we showed that MYCNOT: <it>MYCN </it>Overlap Transcript, a new protein of unknown function is translated from the upstream AUG of <it>MYCN</it><sup>Δ1<it>b </it></sup>mRNA.</p> <p>Conclusions</p> <p>Existence of upstream ORF in <it>MYCN </it>transcripts leads to a new level of MYCN regulation. The resulting MYCN dosage has a weak but significant anti-apoptotic activity after intrinsic apoptosis induction.</p

    EMT Inducers Catalyze Malignant Transformation of Mammary Epithelial Cells and Drive Tumorigenesis towards Claudin-Low Tumors in Transgenic Mice

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    The epithelial-mesenchymal transition (EMT) is an embryonic transdifferentiation process consisting of conversion of polarized epithelial cells to motile mesenchymal ones. EMT–inducing transcription factors are aberrantly expressed in multiple tumor types and are known to favor the metastatic dissemination process. Supporting oncogenic activity within primary lesions, the TWIST and ZEB proteins can prevent cells from undergoing oncogene-induced senescence and apoptosis by abolishing both p53- and RB-dependent pathways. Here we show that they also downregulate PP2A phosphatase activity and efficiently cooperate with an oncogenic version of H-RAS in malignant transformation of human mammary epithelial cells. Thus, by down-regulating crucial tumor suppressor functions, EMT inducers make cells particularly prone to malignant conversion. Importantly, by analyzing transformed cells generated in vitro and by characterizing novel transgenic mouse models, we further demonstrate that cooperation between an EMT inducer and an active form of RAS is sufficient to trigger transformation of mammary epithelial cells into malignant cells exhibiting all the characteristic features of claudin-low tumors, including low expression of tight and adherens junction genes, EMT traits, and stem cell–like characteristics. Claudin-low tumors are believed to be the most primitive breast malignancies, having arisen through transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this prevailing view, we propose that these aggressive tumors arise from cells committed to luminal differentiation, through a process driven by EMT inducers and combining malignant transformation and transdifferentiation

    Evenness mediates the global relationship between forest productivity and richness

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    1. Biodiversity is an important component of natural ecosystems, with higher species richness often correlating with an increase in ecosystem productivity. Yet, this relationship varies substantially across environments, typically becoming less pronounced at high levels of species richness. However, species richness alone cannot reflect all important properties of a community, including community evenness, which may mediate the relationship between biodiversity and productivity. If the evenness of a community correlates negatively with richness across forests globally, then a greater number of species may not always increase overall diversity and productivity of the system. Theoretical work and local empirical studies have shown that the effect of evenness on ecosystem functioning may be especially strong at high richness levels, yet the consistency of this remains untested at a global scale. 2. Here, we used a dataset of forests from across the globe, which includes composition, biomass accumulation and net primary productivity, to explore whether productivity correlates with community evenness and richness in a way that evenness appears to buffer the effect of richness. Specifically, we evaluated whether low levels of evenness in speciose communities correlate with the attenuation of the richness–productivity relationship. 3. We found that tree species richness and evenness are negatively correlated across forests globally, with highly speciose forests typically comprising a few dominant and many rare species. Furthermore, we found that the correlation between diversity and productivity changes with evenness: at low richness, uneven communities are more productive, while at high richness, even communities are more productive. 4. Synthesis. Collectively, these results demonstrate that evenness is an integral component of the relationship between biodiversity and productivity, and that the attenuating effect of richness on forest productivity might be partly explained by low evenness in speciose communities. Productivity generally increases with species richness, until reduced evenness limits the overall increases in community diversity. Our research suggests that evenness is a fundamental component of biodiversity–ecosystem function relationships, and is of critical importance for guiding conservation and sustainable ecosystem management decisions
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