77 research outputs found

    Nanodevices for correlated electrical transport and structural investigation of individual carbon nanotubes

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    We report a new approach to the correlation of the structural properties and the transport properties of carbon nanotubes. Through an original combination of UV lithography, custom-made photosensitive sol–gel resist and deep reactive ion etching (RIE), we have successfully integrated membrane technology and nanodevice fabrication for the electrical connection of individual carbon nanotubes. After single wall nanotube (SWNT) deposition by molecular combing and contacting using high resolution electron beam lithography, we obtain a device that allows both the investigation of the nanotubes and the contact regions by transmission electron microscopy (TEM) and the measurement of the electronic transport properties of the same individual nano-object. The whole fabrication process is detailed and the demonstration that the micro membranes are suitable for both TEM inspection and nanoelectrode fabrication is given

    Midbody and primary cilium of neural progenitors release extracellular membrane particles enriched in the stem cell marker prominin-1

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    Expansion of the neocortex requires symmetric divisions of neuroepithelial cells, the primary progenitor cells of the developing mammalian central nervous system. Symmetrically dividing neuroepithelial cells are known to form a midbody at their apical (rather than lateral) surface. We show that apical midbodies of neuroepithelial cells concentrate prominin-1 (CD133), a somatic stem cell marker and defining constituent of a specific plasma membrane microdomain. Moreover, these apical midbodies are released, as a whole or in part, into the extracellular space, yielding the prominin-1–enriched membrane particles found in the neural tube fluid. The primary cilium of neuroepithelial cells also concentrates prominin-1 and appears to be a second source of the prominin-1–bearing extracellular membrane particles. Our data reveal novel origins of extracellular membrane traffic that enable neural stem and progenitor cells to avoid the asymmetric inheritance of the midbody observed for other cells and, by releasing a stem cell membrane microdomain, to potentially influence the balance of their proliferation versus differentiation

    Release of extracellular membrane vesicles from microvilli of epithelial cells is enhanced by depleting membrane cholesterol

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    AbstractWe previously reported on the occurrence of prominin-1-carrying membrane vesicles that are released into body fluids from microvilli of epithelial cells. This release has been implicated in cell differentiation. Here we have characterized these vesicles released from the differentiated Caco-2 cells. We find that in these vesicles, prominin-1 directly interacts with membrane cholesterol and is associated with a membrane microdomain. The cholesterol depletion using methyl-ÎČ-cyclodextrin resulted in a marked increase in their release, and a dramatic change in the microvillar ultrastructure from a tubular shape to a “pearling” state, with multiple membrane constrictions, suggesting a role of membrane cholesterol in vesicle release from microvilli

    MoccaDB - an integrative database for functional, comparative and diversity studies in the Rubiaceae family

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    <p>Abstract</p> <p>Background</p> <p>In the past few years, functional genomics information has been rapidly accumulating on Rubiaceae species and especially on those belonging to the <it>Coffea </it>genus (coffee trees). An increasing number of expressed sequence tag (EST) data and EST- or genomic-derived microsatellite markers have been generated, together with Conserved Ortholog Set (COS) markers. This considerably facilitates comparative genomics or map-based genetic studies through the common use of orthologous loci across different species. Similar genomic information is available for e.g. tomato or potato, members of the Solanaceae family. Since both Rubiaceae and Solanaceae belong to the Euasterids I (lamiids) integration of information on genetic markers would be possible and lead to more efficient analyses and discovery of key loci involved in important traits such as fruit development, quality, and maturation, or adaptation. Our goal was to develop a comprehensive web data source for integrated information on validated orthologous markers in Rubiaceae.</p> <p>Description</p> <p>MoccaDB is an online MySQL-PHP driven relational database that houses annotated and/or mapped microsatellite markers in Rubiaceae. In its current release, the database stores 638 markers that have been defined on 259 ESTs and 379 genomic sequences. Marker information was retrieved from 11 published works, and completed with original data on 132 microsatellite markers validated in our laboratory. DNA sequences were derived from three <it>Coffea </it>species/hybrids. Microsatellite markers were checked for similarity, <it>in vitro </it>tested for cross-amplification and diversity/polymorphism status in up to 38 Rubiaceae species belonging to the Cinchonoideae and Rubioideae subfamilies. Functional annotation was provided and some markers associated with described metabolic pathways were also integrated. Users can search the database for marker, sequence, map or diversity information through multi-option query forms. The retrieved data can be browsed and downloaded, along with protocols used, using a standard web browser. MoccaDB also integrates bioinformatics tools (CMap viewer and local BLAST) and hyperlinks to related external data sources (NCBI GenBank and PubMed, SOL Genomic Network database).</p> <p>Conclusion</p> <p>We believe that MoccaDB will be extremely useful for all researchers working in the areas of comparative and functional genomics and molecular evolution, in general, and population analysis and association mapping of Rubiaceae and Solanaceae species, in particular.</p

    Methylation-associated PHOX2B gene silencing is a rare event in human neuroblastoma.

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    International audienceNeuroblastoma (NB), an embryonic tumour originating from neural crest cells, is one of the most common solid tumours in childhood. Although NB is characterised by numerous recurrent, large-scale chromosome rearrangements, the genes targeted by these imbalances have remained elusive. We recently identified the paired-like homeobox 2B (PHOX2B, MIM 603851) gene as disease-causing in dysautonomic disorders including Congenital Central Hypoventilation Syndrome (CCHS), Hirschsprung disease (HSCR) and NB in various combinations. Most patients with NB due to a germline heterozygous PHOX2B gene mutation are familial and/or syndromic. PHOX2B, at chromosome 4p12, does not lie in a commonly rearranged locus in NB. To evaluate the role of PHOX2B in sporadic, isolated NB, we analysed 13 NB cell lines and 45 tumours for expression, mutations of coding and promoter sequences, loss of heterozygosity (LOH), or aberrant hypermethylation of PHOX2B (13 cell lines and 18 tumours). We didn't identify any mutation but LOH in about 10% of the cases and aberrant CpG dinucleotide methylation of the 500 bp PHOX2B promoter region in 4/31 tumours and cell lines (12.9%). Altogether, both germinal and somatic anomalies at the PHOX2B locus are found in NB

    CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder

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    Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder with unclear underlying mechanisms. Here, the authors unravel the contribution of a stress-responsive pathway to RSTS where impaired HSF2 acetylation, due to RSTS-associated CBP/EP300 mutations, alters the expression of neurodevelopmental players, in keeping with hallmarks of cell-cell adhesion defects.Patients carrying autosomal dominant mutations in the histone/lysine acetyl transferases CBP or EP300 develop a neurodevelopmental disorder: Rubinstein-Taybi syndrome (RSTS). The biological pathways underlying these neurodevelopmental defects remain elusive. Here, we unravel the contribution of a stress-responsive pathway to RSTS. We characterize the structural and functional interaction between CBP/EP300 and heat-shock factor 2 (HSF2), a tuner of brain cortical development and major player in prenatal stress responses in the neocortex: CBP/EP300 acetylates HSF2, leading to the stabilization of the HSF2 protein. Consequently, RSTS patient-derived primary cells show decreased levels of HSF2 and HSF2-dependent alteration in their repertoire of molecular chaperones and stress response. Moreover, we unravel a CBP/EP300-HSF2-N-cadherin cascade that is also active in neurodevelopmental contexts, and show that its deregulation disturbs neuroepithelial integrity in 2D and 3D organoid models of cerebral development, generated from RSTS patient-derived iPSC cells, providing a molecular reading key for this complex pathology.</p

    Rejets médicamenteux dans les eaux

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    La pollution de l'environnement, et plus particuliĂšrement des eaux, par les micropolluants d'origine pharmaceutique n'est pas un phĂ©nomĂšne rĂ©cent. Chaque annĂ©e, des milliers de tonnes de substances pharmacologiquement actives sont utilisĂ©es afin de traiter les maladies humaines et animales. Ce sont les rejets de ces substances qui penvent se retrouver, sous des formes plus ou moins actives dans les eaux. Il devient urgent d'Ă©valuer les risques dont ils peuvent ĂȘtre responsables, sur la faune et la flore aquatiques, mais Ă©galement sur l'homme. Il est nĂ©cessaire de mettre au point des mĂ©thodes d'Ă©valuation qualitative et quantitative des diffĂ©rentes substances. Les rĂ©sidus mĂ©dicamenteux ont Ă©tĂ© incriminĂ©s dans des phĂ©nomĂšnes d'antibio-rĂ©sistance ou encore de modulations endocriniennes sur des espĂšces aquatiques. De tels efforts doivent ĂȘtre pris en charge rapidement afin de prĂ©server notre environnement. L'Ă©valuation des impacts Ă©cologiques des substances prĂ©sentes Ă  faibles concentrations est en plein dĂ©veloppement et reprĂ©sente un enjeu majeur Ă  l'Ă©chelle nationale et internationale. En effet, de nombreux programmes d'Ă©valuation ont Ă©tĂ© initiĂ©s durant cette derniĂšre dĂ©cennie, notamment au niveau europĂ©en. En novembre 2009, le gouvernement français intĂ©grait le Plan National sur les RĂ©sidus MĂ©dicamenteux (PNRM) Ă  son projet de Plan National SantĂ© Environnement 2(PNSE 2) lancĂ© en juin 2009.ANGERS-BU MĂ©decine-Pharmacie (490072105) / SudocSudocFranceF

    Variabilité interannuelle des dates de début et de fin de la saison des pluies dans l'arc de déforestation amazonien

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    International audienceIn Amazonia global downward trend in rainfall is observed throughout the basin, particularly in the south. Onset and end trends of the rainy season are poorly documented, and are thus studied here on the arc of Amazon deforestation from 1982 to 2012, using daily rainfall data. Several methods of detecting dates are compared; nevertheless, Liebmann's method is retained. Trend tests of Mann-Kendall and test break of Pettitt are applied on these dates. No trend to global shift to the entire arc of deforestation is highlighted by the tests, either at the beginning or at the end of the season. In contrast, linear regressions reveal trends on a regional scale.En Amazonie une tendance gĂ©nĂ©rale Ă  la baisse des prĂ©cipitations est avĂ©rĂ©e sur l'ensemble du bassin et particuliĂšrement au sud. Les tendances au dĂ©calage des dates de dĂ©but et fin de saison des pluies en Amazonie, peu documentĂ©es, sont ici Ă©tudiĂ©es sur l'arc de dĂ©forestation amazonien de 1982 Ă  2012. Des donnĂ©es pluviomĂ©triques quotidiennes sont utilisĂ©es. Plusieurs mĂ©thodes de dĂ©tection des dates sont comparĂ©es, celle de Liebmann est retenue. Les tests de tendance de Mann-Kendall et de rupture de Pettitt sont appliquĂ©s sur ces dates. Aucune tendance au retard ou Ă  la prĂ©cocitĂ© en dĂ©but et fin de saison ne peut ĂȘtre gĂ©nĂ©ralisĂ©e Ă  l'ensemble de l'arc de dĂ©forestation. Les rĂ©gressions linĂ©aires font apparaĂźtre des tendances de quelques jours Ă  une Ă©chelle rĂ©gionale

    Monitoring Rainfall Patterns in the Southern Amazon with PERSIANN-CDR Data: Long-Term Characteristics and Trends

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    Satellite-derived estimates of precipitation are essential to compensate for missing rainfall measurements in regions where the homogeneous and continuous monitoring of rainfall remains challenging due to low density rain gauge networks. The Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks—Climate Data Record (PERSIANN-CDR) is a relatively new product (released in 2013) but that contains data since 1983, thus enabling long-term rainfall analysis. In this work, we used three decades (1983–2014) of PERSIANN-CDR daily rainfall data to characterize precipitation patterns in the southern part of the Amazon basin, which has been drastically impacted in recent decades by anthropogenic activities that exacerbate the spatio-temporal variability of rainfall regimes. We computed metrics for the rainy season (onset date, demise date and duration) on a pixel-to-pixel basis for each year in the time series. We identified significant trends toward a shortening of the rainy season in the southern Amazon, mainly linked to earlier demise dates. This work thus contributes to monitoring possible signs of climate change in the region and to assessing uncertainties in rainfall trends and their potential impacts on human activities and natural ecosystems
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