891 research outputs found

    Geoheritage, a National Inventory in France

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    International audienceGood protection measures for geological heritage should begin with an inventory of geosites. In France, for example, a law enacted in 2002 grants formal recognition to the notion of geological heritage. An inventory and evaluation were then established on a region-by-region basis. By April 2007, the French Ministry of Environment launched the inventory programme for the nation’s geological heritage and the data are now being collected at a regional scale. The data are being gathered and homogenised, and then transferred to the French National Museum of Natural History for examination.The ratified site data are stored and available for public use on a website (http://inpn.mnhn.fr) in a similar structure to natural data that are also processed and stored (flora, fauna, ecosystems, habitats). Today, protecting global heritage is understood as a dynamic process. Instead of placing objects beneath a display case, the conservation approach is now a more modern, active effort, which facilitates access for knowledge and researc

    Measuring indirect transmission-reducing effects in tuberculosis vaccine efficacy trials: why and how?

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    Tuberculosis is the leading bacterial cause of death globally. In 2021, 10·6 million people developed symptomatic tuberculosis and 1·6 million died. Seven promising vaccine candidates that aim to prevent tuberculosis disease in adolescents and adults are currently in late-stage clinical trials. Conventional phase 3 trials provide information on the direct protection conferred against infection or disease in vaccinated individuals, but they tell us little about possible indirect (ie, transmission-reducing) effects that afford protection to unvaccinated individuals. As a result, proposed phase 3 trial designs will not provide key information about the overall effect of introducing a vaccine programme. Information on the potential for indirect effects can be crucial for policy makers deciding whether and how to introduce tuberculosis vaccines into immunisation programmes. We describe the rationale for measuring indirect effects, in addition to direct effects, of tuberculosis vaccine candidates in pivotal trials and lay out several options for incorporating their measurement into phase 3 trial designs

    A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of diffuse large B-cell lymphoma.

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    Dysregulated expression of factors that control protein synthesis is associated with poor prognosis of many cancers, but the underlying mechanisms are not well defined. Analysis of the diffuse large B-cell lymphoma (DLBCL) translatome revealed selective upregulation of mRNAs encoding anti-apoptotic and DNA repair proteins. We show that enhanced synthesis of these proteins in DLBCL is mediated by the relief of repression that is normally imposed by structure in the 5'-untranslated regions of their corresponding mRNAs. This process is driven by signaling through mammalian target of rapamycin, resulting in increased synthesis of eukaryotic initiation factor (eIF) 4B complex (eIF4B), a known activator of the RNA helicase eIF4A. Reducing eIF4B expression alone is sufficient to decrease synthesis of proteins associated with enhanced tumor cell survival, namely DAXX, BCL2 and ERCC5. Importantly, eIF4B-driven expression of these key survival proteins is directly correlated with patient outcome, and eIF4B, DAXX and ERCC5 are identified as novel prognostic markers for poor survival in DLBCL. Our work provides new insights into the mechanisms by which the cancer-promoting translational machinery drives lymphomagenesis

    Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions

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    We report on a search for metastable positively and negatively charged states of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864. We have sampled approximately six billion 10% most central Au+Pb interactions and have observed no strangelet states (baryon number A < 100 droplets of strange quark matter). We thus set upper limits on the production of these exotic states at the level of 1-6 x 10^{-8} per central collision. These limits are the best and most model independent for this colliding system. We discuss the implications of our results on strangelet production mechanisms, and also on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover memorial edition

    Physiological Biomimetic Culture System for Pig and Human Heart Slices

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    RATIONALE: Preclinical testing of cardiotoxicity and efficacy of novel heart failure therapies faces a major limitation: the lack of an in situ culture system that emulates the complexity of human heart tissue and maintains viability and functionality for a prolonged time. OBJECTIVE: To develop a reliable, easily reproducible, medium-throughput method to culture pig and human heart slices under physiological conditions for a prolonged period of time. METHODS AND RESULTS: Here, we describe a novel, medium-throughput biomimetic culture system that maintains viability and functionality of human and pig heart slices (300 µm thickness) for 6 days in culture. We optimized the medium and culture conditions with continuous electrical stimulation at 1.2 Hz and oxygenation of the medium. Functional viability of these slices over 6 days was confirmed by assessing their calcium homeostasis, twitch force generation, and response to β-adrenergic stimulation. Temporal transcriptome analysis using RNAseq at day 2, 6, and 10 in culture confirmed overall maintenance of normal gene expression for up to 6 days, while over 500 transcripts were differentially regulated after 10 days. Electron microscopy demonstrated intact mitochondria and Z-disc ultra-structures after 6 days in culture under our optimized conditions. This biomimetic culture system was successful in keeping human heart slices completely viable and functionally and structurally intact for 6 days in culture. We also used this system to demonstrate the effects of a novel gene therapy approach in human heart slices. Furthermore, this culture system enabled the assessment of contraction and relaxation kinetics on isolated single myofibrils from heart slices after culture. CONCLUSIONS: We have developed and optimized a reliable medium-throughput culture system for pig and human heart slices as a platform for testing the efficacy of novel heart failure therapeutics and reliable testing of cardiotoxicity in a 3D heart model

    Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study

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    Objectives: Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods: In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results: In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion: 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/ carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists
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