97 research outputs found

    RIPK3-mediated cell death is involved in DUX4-mediated toxicity in facioscapulohumeral dystrophy

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    BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is caused by mutations leading to the aberrant expression of the DUX4 transcription factor in muscles. DUX4 was proposed to induce cell death, but the involvement of different death pathways is still discussed. A possible pro‐apoptotic role of DUX4 was proposed, but as FSHD muscles are characterized by necrosis and inflammatory infiltrates, non‐apoptotic pathways may be also involved. METHODS: We explored DUX4‐mediated cell death by focusing on the role of one regulated necrosis pathway called necroptosis, which is regulated by RIPK3. We investigated the effect of necroptosis on cell death in vitro and in vivo experiments using RIPK3 inhibitors and a RIPK3‐deficient transgenic mouse model. RESULTS: We showed in vitro that DUX4 expression causes a caspase‐independent and RIPK3‐mediated cell death in both myoblasts and myotubes. In vivo, RIPK3‐deficient animals present improved body and muscle weights, a reduction of the aberrant activation of the DUX4 network genes, and an improvement of muscle histology. CONCLUSIONS: These results provide evidence for a role of RIPK3 in DUX4‐mediated cell death and open new avenues of research

    Plant-dominated assemblage and invertebrates from the lower Cenomanian of Jaunay-Clan, western France

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    International audienceTwo fossil localities are reported on the "LGV SEA" railroad from the Lower Cenomanianof Jaunay-Clan (JC), near Poitiers, western France. The laminated mudstones yielded plantfossils including ferns (Cladophlebis, Osmundophyllum, Ruffordia goeppertii, Sphenopteris),conifers (Brachyphyllum, Dammarophyllum, Pagiophyllum), and terrestrial and aquaticfreshwater angiosperms (Eucalyptolaurus depreii, Ploufolia). They are associated with acoleopteran insect that shows systematic affinities to the modern subfamily Chrysomeli-nae (Chrysomelidae). This assemblage suggests connections with arborescent vegetationgrowing in calm freshwater environment. Brackish to marine invertebrates also occurand include a dakoticancroid crab (Brachyura, Podotremata, Dakoticancroidea) and a fewbivalves (Brachidontes). They suggest brackish episodes during pond sedimentation in acoastal environment. Lastly, vertebrates are represented by an isolated feather

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    Role and regulation of the avian uncoupling protein in bird mitochondrial metabolism

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    La protéine découplante aviaire (avUCP), majoritairement exprimée dans le muscle, pourrait être impliquée dans le transport de substrats énergétiques, la limitation de la production de radicaux libres et/ou la thermogenèse sans frisson. La stimulation in vivo chez le poulet du système ß-adrénergique par l’isoprotérénol augmente l’expression d’avUCP. Cette régulation pourrait faire intervenir la voie de signalisation post-ß2-adrénorécepteur des cellules musculaires, mais aussi des modifications du statut thyroïdien, des métabolismes du glucose et des acides gras. Sur myoblastes de poussin en culture primaire, nous mettons en évidence l’implication de l’AMPK et du facteur de transcription PPARa dans la régulation de l’expression d’avUCP, qui est modulée par l’isoprotérénol et les acides gras. L’expression d’avUCP diffère en fonction du type contractile et métabolique de muscle, ce qui pourrait être lié à un rôle dans l’utilisation des substrats énergétiques par le muscle.Avian uncoupling protein (avUCP), mainly expressed in muscle, could be involved in energy substrates transport, limitation of reactive oxygen species production and/or non-shivering thermogenesis. The in vivo stimulation of the ß-adrenergic system by isoproterenol increased avUCP expression in chicken. This regulation may involve the post-ß2-adrenoreceptor signaling pathway in muscle cells, but also modulations of thyroid status, glucose and fatty acid metabolisms. By using primary culture of chick myoblasts, we showed the involvement of AMPK and of the transcription factor PPARa in the regulation of avUCP expression, that was controlled by isoproterenol and fatty acids. AvUCP expression depended on the contractile and the metabolic types of chicken muscles, which could be related to a role of avUCP in the regulation of fuel substrate utilisation in chicken muscles

    Airtight container for the transfer of atmosphere-sensitive materials into vacuum-operated characterization instruments

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    This paper describes the design and operation of a simple airtight container devised to facilitate the transfer of atmosphere-sensitive samples from a glovebox to the vacuum chamber of an analytical instrument such as a scanning electron microscope. The use of this device for characterizing the microstructure of highly hygroscopic strontium iodide ceramics by scanning electron microscopy is illustrated as an application example

    Rôles et régulations de la protéine découplante aviaire dans le métabolisme mitochondrial de l'oiseau

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    La protéine découplante aviaire (avUCP), majoritairement exprimée dans le muscle, pourrait être impliquée dans le transport de substrats énergétiques, la limitation de la production de radicaux libres et/ou la thermogenèse sans frisson. La stimulation in vivo chez le poulet du système ß-adrénergique par l isoprotérénol augmente l expression d avUCP. Cette régulation pourrait faire intervenir la voie de signalisation post-ß2-adrénorécepteur des cellules musculaires, mais aussi des modifications du statut thyroïdien, des métabolismes du glucose et des acides gras. Sur myoblastes de poussin en culture primaire, nous mettons en évidence l implication de l AMPK et du facteur de transcription PPARa dans la régulation de l expression d avUCP, qui est modulée par l isoprotérénol et les acides gras. L expression d avUCP diffère en fonction du type contractile et métabolique de muscle, ce qui pourrait être lié à un rôle dans l utilisation des substrats énergétiques par le muscle.Avian uncoupling protein (avUCP), mainly expressed in muscle, could be involved in energy substrates transport, limitation of reactive oxygen species production and/or non-shivering thermogenesis. The in vivo stimulation of the ß-adrenergic system by isoproterenol increased avUCP expression in chicken. This regulation may involve the post-ß2-adrenoreceptor signaling pathway in muscle cells, but also modulations of thyroid status, glucose and fatty acid metabolisms. By using primary culture of chick myoblasts, we showed the involvement of AMPK and of the transcription factor PPARa in the regulation of avUCP expression, that was controlled by isoproterenol and fatty acids. AvUCP expression depended on the contractile and the metabolic types of chicken muscles, which could be related to a role of avUCP in the regulation of fuel substrate utilisation in chicken muscles.TOURS-Bibl.électronique (372610011) / SudocSudocFranceF

    Study and Design of an Integrated CMOS Laser Diode Driver for an iToF-based 3D Image Sensor

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    International audienceThis paper presents a study of two architectures for designing an integrated CMOS Laser Diode Driver (LDD) intended for a 3D image sensor used in mobile applications and based on the indirect Time-of-Flight (iToF) measurement. Architectures are focused on two different driving topologies: series and shunt which means the laser diode is connected either in series or parallel with a switching element in order to provide laser pulses. Two LDD prototypes implemented in a 130 nm CMOS technology are able to provide programmable current pulses up to 3 A with a 2.5 ns pulse width at a maximum 200 MHz Pulse Repetition Frequency (PRF)

    IBM ILOG Graph Layout for Eclipse

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