125 research outputs found

    Dégradation de l’absorptance solaire de matériaux thermo-optiques contaminés par la propulsion électrique

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    International audienceOne of the objectives of this work was to contaminate samples by the erosion of different targets in order to study the effect of this contamination on their thermo-optical properties. The second objective was to validate the Spacecraft Plasma Interaction System (SPIS) module dedicated to simulation of erosion and contamination.First, experiments were conducted in IDEFIXe chamber at ONERA to expose OSR and SSM to contamination created by the erosion of targets representing elements of a spacecraft using electric propulsion, subject to ions bombardment. The targets were submitted to Xe+ ions beam. Samples were placed facing the target and were then submitted to the contamination by erosion products. The quantity of contaminants was estimated through a quartz micro-balance. Reflectance of the contaminated samples was then measured to evaluate the effect on their solar absorptance and their surface was characterized by XPS.Different targets and different samples were used allowing us to extract general tendencies and phenomenology.In a second time, simulations of the test were performed with SPIS. These simulations have allowed us reproducing experimental results, validating the code and proposing erosion mechanisms for polymeric materials

    Transmission of oocyte DNA damage to preimplantation embryos after in vivo mouse exposure to daunorubicin and cytarabine.

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    International audienceStudy question: Does oocyte DNA damage induced by a previous in vivo mouse exposure to chemotherapy agents is transmissible to preimplantation embryos?Summary answer: DNA damage was observed in preimplantation embryos issued from mice previously exposed to daunorubicin and cytarabine.What is known already: In acute leukemia, the emergency to start a chemotherapydon’t allow a fertility preservation at the time of diagnosis. Some authors have proposed to cryopreserve mature oocytes or embryos after a controlled ovarian stimulation applied shortly after the induction chemotherapy,which is mainly composed by daunorubicin and cytarabine, and reputated to be less gonadotoxic than alkylant agents. We previously observed DNA damage on mouse oocytes issued from antral follicles exposed in vivo to daunorubicin and cytarabine.Little is known about the risk of transmission of oocyte DNA damage to preimplantation embryos after fecundation of oocytes recently exposed to chemotherapy.Study design, size, duration: By three time, two groups of mice (n = 11) were exposed for four days to cytarabine (10 mg/kg IP) or every two days to daunorubicin (1 mg/kg IV). Each group was compared with a negative control group (n = 11) and with a positive control group (n = 11) injected with cyclophosphamide(75 mg/kg IP). Females were mated one week after exposure and preimplantation embryos were collected by flushing the oviducts.Participants/materials, setting, methods: 4 weeks female CD1 mice were mated one week after exposure for studying embryos conceived from oocytes exposed to chemotherapy at late pre-antral stage of follicular development.Cytotoxicity has been assessed by ovulation and fertilization rates and by embryo morphology. DNA embryonic damage was assessed by: (i) alkaline comet assay to quantify the tail DNA (ii) fluorescent immunohistochemical staining in blastomeres to quantify accumulating γH2AX foci.Main results and the role of chance: In mouse, a recent exposure to daunorubicin and cytarabine did not alter the ovarian response to controlled ovarian stimulation with no adverse impact on the fertilization rate and the number of embryo conceived. Ovulation and fertilization rates in mice previouslyexposed to daunorubicin and cytarabine were similar to those in our negative control group. One week after exposure, we observed with the comet assay a significant increase of embryonic DNA damage after exposure to daunorubicin (16.57 ± 1.3, p = 0.0003) and cytarabine (16.46 ± 1.4, p =0.0003) Vs 26.16 ± 2.5 after cyclophosphamide exposure (p < 0.0001) and 7,01 ± 1,1 in negative control group exposed to an injection of sterile saline solution. The analysis γ-H2AX on embryos showed a significant increase of foci corresponding to DNA double-strand breaks, after exposure to daunorubicin (7.97 ± 1.1; p = 0.001), cytarabine (6.47 ± 0.7, p = 0.0039), cyclophosphamide (5.92 ± 0.9; p = 0.0148) compared with negative control group (2,8 ±0,7).Limitations, reasons for caution: Mouse oocyte DNA is not exactly similar to human oocyte DNA, and would be more sensitive to genotoxic effects of chemotherapy agents. After chemotherapy, the kinetic of DNA repair before and after fertilization has to be studied by further assays in exposed oocyte andin embryos.Wider implications of the findings: DNA damage in preimplantation embryos conceived from oocytes exposed to chemotherapy at late pre-antral stage of follicular development lead us to hypothese a transmission of oocyte DNA damage to preimplantation embryo. In acute leukemia, we strongly adviseto not cryopreserve mature oocytes or embryo early after induction chemotherapy.Trial registration number: Experimental protocols and animal handling procedures were reviewed by the French National Ethics Committee on Animal Experimentation (N° 2017033010523688)

    La France du Centre-Est (Auvergne, Bourgogne, Franche-Comté, Rhône-Alpes)

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    International audienceDie Region liefert einen zahlenmäβig bisher noch kleinen Bestand an Befunden, die zur Hauptsache den letzten Jahrhunderten vor der Zeitenwende angehören. Zahlreiche alte und neue Entdeckungen von Weihefunden illustrieren die groβe Bandbreite der Kultorte (Flüsse, Quellen, Höhlen, gewisse Siedlungsplätze usw.). Die jüngeren Forschungen belegen auch die Existenz planmäβig errichteter gallischer Kultstätten an Zentralorten oder im ländlichen Bereich. Sie sind aber oft durch kaiserzeitliche Heiligtümer verdeckt. Insgesamt scheint sich die Region Centre-Est vom Beispiel der Belgica durch eine geringere Präsenz von Elementen der Bewaffnung zu unterscheiden. Dies schlägt zugunsten der Nachweise von Weinamphoren und sonstiger Gefäβkeramik, häuslichem Werkzeug und Gerät, Schmuck oder auch Münzen zu Buche. Weil es an entsprechenden Darstellungen und Inschriften mangelt, bleiben die hier verehrten gallischen Gottheiten jedoch anonym.zu Buche. Weil es an entsprechenden Darstellungen und Inschriften mangelt, bleiben die hier verehrten gallischen Gottheiten jedoch anonym.The amount of cult testimonies collected in this area is still thin and, for the most part, they are dated from the last centuries BC. The impressive finding, recent or previous, of votive deposits illustrates the varying kinds and multiplicity of sacred places (rivers, springs, caves, various settlements...). Recent investigations have provided conclusive evidence for Gallic central or rural organized cult sites, often sealed beneath Roman sanctuaries. On the whole, the central-eastern part of Gaul apparently differs from the Belgic pattern by the paucity of weapons compared to the frequency of wine amphorae, pottery, instrumentum domesticum, ornaments and even coins. Yet, Gaulish deities remain anonymous for lack of representations and inscriptions.La région Centre-Est livre un ensemble numériquement encore faible, appartenant essentiellement aux derniers siècles avant le changement d'ère. Les découvertes nombreuses, anciennes ou récentes, de dépôts à caractère votif, illustrent la variété et la multiplicité des lieux cultuels (rivières, sources, grottes, habitats divers, etc.). Les recherches récentes attestent la réalité de lieux de cultes gaulois centraux ou ruraux organisés, souvent masqués par des sanctuaires d 'époque impériale. Globalement, le Centre-Est semble se distinguer du « modèle belge » par une représentation plutôt faible de l'armement au profit des amphores vinaires, de la céramique, de l'instrumentum domestique, de la parure, voire des monnaies... Les divinités gauloises honorées restent anonymes, faute de figurations et d'inscriptions

    Long and short-term trends of stream hydrochemistry and high frequency surveys as indicators of the influence of climate change, agricultural practices and internal processes (Aurade agricultural catchment, SW France)

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    The hydrochemical time series of stream water from a cultivated catchment were investigated at different time scales and survey frequencies. A 35-year time series of nitrate concentration and discharge, a 15-year time series of major elements and dissolved organic carbon (DOC) concentrations were analysed from a yearly to a daily/hourly basis during discharge recession after storm event periods, to determine the origin of elements, the time trends and the main controlling factors of the trends. A significant decrease over time of nitrate, base cations and other major anions was observed. These trends were controlled by agricultural practice changes (decrease of N-fertiliser input, grass-band set up) and discharge increase, especially in the last years of the period. On the other hand, K and DOC increased over the 15-year period. This increase might result from both 1) organic matter eroded from the soil surface by runoff during flood events and 2) an increase in mineralisation with increasing temperature. Seasonal variations and nycthemeral cycles indicated either calcite precipitation and nitrification processes and/or evapotranspiration, water and/or vegetation uptake during the day with increasing temperature. This paper highlights that the hydrochemical parameters measured at various time scales and frequencies can be used as powerful indicators of catchment internal processes, and of changes in agricultural management and climate change. Particularly, the multivariate high-resolution survey has shown its ability to evidence very tenuous processes not detectable by discrete sampling. The recent observed changes in hydrology argue for the need to continue the hydrochemical survey over decades

    The three-dimensional organization of telomeres in the nucleus of mammalian cells

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    BACKGROUND: The observation of multiple genetic markers in situ by optical microscopy and their relevance to the study of three-dimensional (3D) chromosomal organization in the nucleus have been greatly developed in the last decade. These methods are important in cancer research because cancer is characterized by multiple alterations that affect the modulation of gene expression and the stability of the genome. It is, therefore, essential to analyze the 3D genome organization of the interphase nucleus in both normal and cancer cells. RESULTS: We describe a novel approach to study the distribution of all telomeres inside the nucleus of mammalian cells throughout the cell cycle. It is based on 3D telomere fluorescence in situ hybridization followed by quantitative analysis that determines the telomeres' distribution in the nucleus throughout the cell cycle. This method enables us to determine, for the first time, that telomere organization is cell-cycle dependent, with assembly of telomeres into a telomeric disk in the G2 phase. In tumor cells, the 3D telomere organization is distorted and aggregates are formed. CONCLUSIONS: The results emphasize a non-random and dynamic 3D nuclear telomeric organization and its importance to genomic stability. Based on our findings, it appears possible to examine telomeric aggregates suggestive of genomic instability in individual interphase nuclei and tissues without the need to examine metaphases. Such new avenues of monitoring genomic instability could potentially impact on cancer biology, genetics, diagnostic innovations and surveillance of treatment response in medicine

    Bibliothécaire jeunesse : quel métier ?

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    Journée d\u27étude organisée le 21 octobre 2010 par le Centre national de la littérature jeunesse - La Joie par les livres / Bibliothèque nationale de France et l\u27enssi

    Brain Responses to Violet, Blue, and Green Monochromatic Light Exposures in Humans: Prominent Role of Blue Light and the Brainstem

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    BACKGROUND: Relatively long duration retinal light exposure elicits nonvisual responses in humans, including modulation of alertness and cognition. These responses are thought to be mediated in part by melanopsin-expressing retinal ganglion cells which are more sensitive to blue light than violet or green light. The contribution of the melanopsin system and the brain mechanisms involved in the establishment of such responses to light remain to be established. METHODOLOGY/PRINCIPAL FINDINGS: We exposed 15 participants to short duration (50 s) monochromatic violet (430 nm), blue (473 nm), and green (527 nm) light exposures of equal photon flux (10(13)ph/cm(2)/s) while they were performing a working memory task in fMRI. At light onset, blue light, as compared to green light, increased activity in the left hippocampus, left thalamus, and right amygdala. During the task, blue light, as compared to violet light, increased activity in the left middle frontal gyrus, left thalamus and a bilateral area of the brainstem consistent with activation of the locus coeruleus. CONCLUSION/SIGNIFICANCE: These results support a prominent contribution of melanopsin-expressing retinal ganglion cells to brain responses to light within the very first seconds of an exposure. The results also demonstrate the implication of the brainstem in mediating these responses in humans and speak for a broad involvement of light in the regulation of brain function

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

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    Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock
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