126 research outputs found

    Size and polydispersity effect on the magnetization of densely packed magnetic nanoparticles

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    The magnetic properties of densely packed magnetic nanoparticles (MNP) assemblies are investigated from Monte Carlo simulations. The case of iron oxide nanoparticles is considered as a typical example of MNP. The main focus is put on particle size and size polydispersity influences on the magnetization curve. The particles are modeled as uniformly magnetized spheres isolated one from each other by a non magnetic layer representing the organic coating. A comparison with recent experimental results on γ\gamma-Fe2_2O3_3 powder samples differing by their size is given.Comment: To be published in the Journal of Applied Physics, to be found at http://jap.aip.org

    Insights into nuclear organization in plants as revealed by the dynamic distribution of Arabidopsis SR splicing factors

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    Serine/arginine-rich (SR) proteins are splicing regulators that share a modular structure consisting of one or two N-terminal RNA recognition motif domains and a C-terminal RS-rich domain. We investigated the dynamic localization of the Arabidopsis thaliana SR protein RSZp22, which, as we showed previously, distributes in predominant speckle-like structures and in the nucleolus. To determine the role of RSZp22 diverse domains in its nucleolar distribution, we investigated the subnuclear localization of domain-deleted mutant proteins. Our results suggest that the nucleolar localization of RSZp22 does not depend on a single targeting signal but likely involves different domains/motifs. Photobleaching experiments demonstrated the unrestricted dynamics of RSZp22 between nuclear compartments. Selective inhibitor experiments of ongoing cellular phosphorylation influenced the rates of exchange of RSZp22 between the different nuclear territories, indicating that SR protein mobility is dependent on the phosphorylation state of the cell. Furthermore, based on a leptomycin B- and fluorescence loss in photobleaching-based sensitive assay, we suggest that RSZp22 is a nucleocytoplasmic shuttling protein. Finally, with electron microscopy, we confirmed that RSp31, a plant-specific SR protein, is dynamically distributed in nucleolar cap-like structures upon phosphorylation inhibition. Our findings emphasize the high mobility of Arabidopsis SR splicing factors and provide insights into the dynamic relationships between the different nuclear compartments

    Homology modeling and in vivo functional characterization of the zinc permeation pathway in a heavy metal P-type ATPase

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    The P1B ATPase Heavy Metal ATPase 4 (HMA4) is responsible for zinc and cadmium translocation from roots to shoots in the plant Arabidopsis thaliana. It couples ATP hydrolysis to cytosolic domain movements enabling metal transport across the membrane. Thanks to high conservation level within the P-type ATPase family, the role of the HMA4 cytoplasmic catalytic domains can be inferred from well characterized pumps. In contrast, the function of its terminal cytosolic extensions as well as the metal permeation mechanism through the membrane remains elusive. Here, homology modeling of the HMA4 transmembrane region was conducted based on the crystal structure of a ZntA bacterial homolog. The analysis highlighted amino acids forming a metal permeation pathway, whose importance was subsequently investigated functionally through mutagenesis and complementation experiments in plants. Although the zinc pathway displayed overall conservation among the two proteins, significant differences were observed, especially in the entrance area with altered electronegativity and the presence of a salt bridge/H-bond network. The analysis also newly identified amino acids whose mutation results in total or partial loss of the protein function. In addition, comparison of zinc and cadmium accumulation in shoots of A. thaliana complemented lines revealed a number of HMA4 mutants exhibiting different abilities in zinc and cadmium translocation. These observations could be instrumental to design low cadmium accumulating crops, hence decreasing human cadmium exposure

    Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

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    BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices

    Prognostic impact of vitamin B6 metabolism in lung cancer

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    Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.publishedVersio

    Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

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    Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

    Organisation et propriétés de structures mésoscopiques constituées de nanocristaux

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    PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

    Le système complexe des hiéroglyphes, entre texte, image et symbole

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    Après une brève présentation des écritures égyptiennes et une introduction au fonctionnement des hiéroglyphes, la langue sacrée des Égyptiens, cette conférence explore les liens qui unissent texte et image. Elle évoque en outre quelques cas particuliers où l’écriture est utilisée de manière symbolique

    Plantes, transferts et résistances. Le Jardin des cultures guyanaises, reflet d'un métissage à l'œuvre sur les marchés de la Guyane française

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    La Guyane est une mosaïque de populations d'origines et de cultures diverses, façonnée par des siècles d'arrivées successives. Les Créoles guyanais (issus des anciens esclaves et affranchis créoles), largement majoritaires jusqu'aux années 70, ne constituent plus qu'une minorité qui, même si elle est encore importante, se trouve confrontée à d'autres minorités dont certaines sont en pleine expansion démographique1. Ces autres minorités sont constituées par les différents groupes amérindiens (Kali'na, Palikur, Wayampi, etc.), les Bushinenge ou Noirs-Marrons (descendants d'esclaves ayant fui les plantations hollandaises du Suriname), les Chinois, arrivés après l'abolition de l'esclavage, les Haïtiens de culture créole, les Hmong et Laotiens arrivés à la fin des années 70, les Brésiliens, groupe en forte augmentation, les Français de l'Hexagone et les Indonésiens. Jusqu'à une date assez récente, les différents modes de vie de ces minorités ont été en grande partie préservés grâce à la difficulté des communications. Le désenclavement de certaines régions a changé la donne et les effets en sont perceptibles sur les marchés, lieux d'échanges entre les différents groupes. À travers l'étude de la diversité biologique des plantes vendues sur les marchés de Guyane, nous analyserons les métissages (adoptions d'espèces, de la façon de les nommer, de les utiliser, de les cultiver). Quels éléments de culture matérielle y sont diffusés ? Par quelles minorités ? Ces marchés peuvent-ils également révéler des particularismes identitaires résistants ? Notre recherche sera centrée sur des produits alimentaires puisqu'il s'agit d'un domaine particulièrement saillant de l'identité d'une population. Les produits considérés seront des produits de base comme l'igname, mais aussi des produits considérés comme mineurs, par exemple les herbes aromatiques qui traduisent de façon signifiante une appartenance culturelle. 1 Cf. Équipe du PRNG, Région Guyane, 2006, Projet de Charte (consultable sur Internet http://www.cr-guyane.fr/ressources/File/region_dyn/communiques_manif/charteEP131106.pdf)
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