3,060 research outputs found

    Tumor induction by disruption of the Dnmt1, PCNA and UHRF1 interactions.

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    The low level of DNA methylation in tumors compared to the level of DNA methylation in their normal-tissue counterparts or global DNA hypomethylation was one of the first epigenetic alterations to be found in human cancer^1,2^. While the contribution of genome hypomethylation in cancer development and progression is explained by several mechanisms: chromosomal instability, loss of imprinting, and reactivation of transposable elements^3, 4^, the molecular causes of genome hypomethylation remain unclear. Indeed, despite the central roles of the DNA methyltransferases (Dnmts) in the establishment and maintenance of the DNA methylation, no clear consensus appears between the reduction of the Dnmts expression and the genome hypomethylation in human cancers^5^. Nevertheless, the cancer-associated genome hypomethylation could be explained by the disruption of interactions existing between Dnmts and the DNA replication and DNA repair proteins because these interactions play a crucial role in the DNA methylation in mammalian cells^6-8^. We here demonstrate that the disruption of the Dnmt1/PCNA and Dnmt1/UHRF1 interactions induce the genome hypomethylation and act as oncogenic factors promoting the tumorigenesis. We also identify the Akt- and/or PKC-mediated phosphorylations of Dnmt1 as both initiators of these disruptions and as a hallmark conferring poor prognosis in glioma patients

    Sur les quais des précaires

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    Model-based Decentralized Embedded Diagnosis inside Vehicles: Application to Smart Distance Keeping Function

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    International audienceAbstract—In this paper, the deployment of a fault diagnosis strategy in the Smart Distance Keeping (SDK) system with a decentralized architecture is presented. The SDK system is an advanced version of the Adaptive Cruise Control (ACC) system, implemented in a Renault-Volvo Trucks vehicle. The main goal of this work is to analyze measurements, issued from the SDK elements, in order to detect, to localize and to identify some faults that may be produced. Our main contribution is the proposition of a decentralized approach permitting to carry out an on-line diagnosis without computing the global model and to deploy it on several control units. This paper explains the model-based decentralized solution and its application to the embedded diagnosis of the SDK system inside truck with five control units connected via a CAN-bus using ”Hardware In the Loop” (HIL) technique. We also discuss the constraints that must be fulfilled

    Direct Imaging of Protein Organization in an Intact Bacterial Organelle Using High-Resolution Atomic Force Microscopy

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    The function of bioenergetic membranes is strongly influenced by the spatial arrangement of their constituent membrane proteins. Atomic force microscopy (AFM) can be used to probe protein organization at high resolution, allowing individual proteins to be identified. However, previous AFM studies of biological membranes have typically required that curved membranes are ruptured and flattened during sample preparation, with the possibility of disruption of the native protein arrangement or loss of proteins. Imaging native, curved membranes requires minimal tip–sample interaction in both lateral and vertical directions. Here, long-range tip–sample interactions are reduced by optimizing the imaging buffer. Tapping mode AFM with high-resonance-frequency small and soft cantilevers, in combination with a high-speed AFM, reduces the forces due to feedback error and enables application of an average imaging force of tens of piconewtons. Using this approach, we have imaged the membrane organization of intact vesicular bacterial photosynthetic “organelles”, chromatophores. Despite the highly curved nature of the chromatophore membrane and lack of direct support, the resolution was sufficient to identify the photosystem complexes and quantify their arrangement in the native state. Successive imaging showed the proteins remain surprisingly static, with minimal rotation or translation over several-minute time scales. High-order assemblies of RC-LH1-PufX complexes are observed, and intact ATPases are successfully imaged. The methods developed here are likely to be applicable to a broad range of protein-rich vesicles or curved membrane systems, which are an almost ubiquitous feature of native organelles

    Fabrication of Nanometer and Micrometer Scale Protein Structures by Site-Specific Immobilization of Histidine-Tagged Proteins to Aminosiloxane Films with Photoremovable Protein-Resistant Protecting Groups

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    The site-specific immobilization of histidine-tagged proteins to patterns formed by far-field and near-field exposure of films of aminosilanes with protein-resistant photolabile protecting groups is demonstrated. After deprotection of the aminosilane, either through a mask or using a scanning near-field optical microscope, the amine terminal groups are derivatized first with glutaraldehyde and then with N-(5-amino-1-carboxypentyl)iminodiacetic acid to yield a nitrilo triacetic acid (NTA) terminated surface. After complexation with Ni2+, this surface binds histidine-tagged GFP and CpcA-PEB in a site-specific fashion. The chemistry is simple and reliable, and leads to extensive surface functionalization. Bright fluorescence is observed in fluorescence microscopy images of micrometer- and nanometer-scale patterns. X-ray photoelectron spectroscopy is used to study quantitatively the efficiency of photodeprotection and the reactivity of the modified surfaces. The efficiency of the protein binding process is investigated quantitatively by ellipsometry and by fluorescence microscopy. We find that regions of the surface not exposed to UV light bind negligible amounts of His-tagged proteins, indicating that the oligo(ethylene glycol) adduct on the nitrophenyl protecting group confers excellent protein resistance; in contrast, exposed regions bind His-GFP very effectively, yielding strong fluorescence that is almost completely removed on treatment of the surface with imidazole, confirming a degree of site-specific binding in excess of 90%. This simple strategy offers a versatile generic route to the spatially selective site-specific immobilization of proteins at surfaces

    Simple, Direct Routes to Polymer Brush Traps and Nanostructures for Studies of Diffusional Transport in Supported Lipid Bilayers

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    Patterned poly(oligo ethylene glycol) methyl ether methacrylate (POEGMEMA) brush structures may be formed by using a combination of atom-transfer radical polymerization (ATRP) and UV photopatterning. UV photolysis is used to selectively dechlorinate films of 4-(chloromethyl)phenyltrichlorosilane (CMPTS) adsorbed on silica surfaces, by exposure either through a mask or using a two-beam interferometer. Exposure through a mask yields patterns of carboxylic acid-terminated adsorbates. POEGMEMA may be grown from intact Cl initiators that were masked during exposure. Corrals, traps, and other structures formed in this way enable the patterning of proteins, vesicles, and, following vesicle rupture, supported lipid bilayers (SLBs). Bilayers adsorbed on the carboxylic acid-terminated surfaces formed by C–Cl bond photolysis in CMPTS exhibit high mobility. SLBs do not form on POEGMEMA. Using traps consisting of carboxylic acid-functionalized regions enclosed by POEGMEMA structures, electrophoresis may be observed in lipid bilayers containing a small amount of a fluorescent dye. Segregation of dye at one end of the traps was measured by fluorescence microscopy. The increase in the fluorescence intensity was found to be proportional to the trap length, while the time taken to reach the maximum value was inversely proportional to the trap length, indicating uniform, rapid diffusion in all of the traps. Nanostructured materials were formed using interferometric lithography. Channels were defined by exposure of CMPTS films to maxima in the interferogram, and POEGMEMA walls were formed by ATRP. As for the micrometer-scale patterns, bilayers did not form on the POEGMEMA structures, and high lipid mobilities were measured in the polymer-free regions of the channels

    Bien ou mal payés ?:Les travailleurs du public et du privé jugent leurs salaires

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    Le salaire est une composante essentielle du niveau de vie. Son montant présente pour l’immense majorité des travailleurs un enjeu considérable. Comment les différents salariés perçoivent-ils à la fois le salaire qu’ils touchent et les écarts qui le séparent de celui des autres ? Portant sur les modalités subjectives de la perception des salaires ainsi que sur les critères de justice auxquels se réfèrent les individus pour évaluer leur montant, les deux grandes enquêtes dont est issu cet ouvrage mettent au jour les relations que les travailleurs entretiennent avec leur salaire ainsi que le sens qu’ils attribuent à leur rémunération. Un même questionnaire, l’enquête « SalSa » (« les salaires vus par les salariés »), a été administré à un échantillon de salariés des entreprises, privées et publiques, d’un côté, et à un échantillon de salariés de la fonction publique de l’autre. Il ressort de ces enquêtes que, du point de vue des salariés, le salaire ne se réduit jamais à une simple somme d’argent destinée à satisfaire des besoins. C’est aussi une façon de mesurer la valeur du travail accompli, sa reconnaissance par la société et donc la valeur de la personne elle-même, en soi mais aussi en relation avec les autres. C’est pourquoi la façon dont les individus connaissent, appréhendent et jugent leur rémunération et celle des autres est un élément essentiel pour comprendre les procédures de détermination et donc de négociation des salaires, mais aussi le sens que les individus attribuent à leur travail. (Résumé éditeur
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