93 research outputs found

    Les documents spoliĂ©s dĂ©posĂ©s Ă  la BnF : une enquĂȘte en cours

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    Ce colloque s’est tenu les jeudi et vendredi 23 et 24 mars 2017, Ă  la BibliothĂšque universitaire des langues et civilisations et Ă  la BibliothĂšque nationale de France, Il a Ă©tĂ© organisĂ© par le Centre Gabriel NaudĂ© de l\u27Ecole nationale supĂ©rieure des sciences de l\u27information et des bibliothĂšques (ENSSIB), l\u27Institut d\u27histoire du temps prĂ©sent (IHTP, UMR CNRS Paris 8) et l\u27UniversitĂ© Paris Diderot (EA IdentitĂ©s, cultures, territoires), avec le soutien de la BibliothĂšque nationale de France, de la BibliothĂšque universitaire des langues et civilisations (BULAC), de la Fondation pour la MĂ©moire de la Shoah, de la Claims Foundation, de la Fondation Maison des Sciences de l\u27Homme et du Deutscher Akademischer Austauschdienst. Au cours de ce colloque, une douzaine de livres, datant du XVIIe siĂšcle et retrouvĂ©s dans ses collections par la BibliothĂšque centrale et rĂ©gionale de Berlin (Zentral -und Landesbibliothek) ont Ă©tĂ© restituĂ©s Ă  trois ministĂšres français (ministĂšre des Affaires Ă©trangĂšres, ministĂšre de l\u27IntĂ©rieur, ministĂšre de la Justice) auxquels ils avaient Ă©tĂ© spoliĂ©es en juin 1940. Un registre manuscrit d\u27Ă©tat civil des annĂ©es 1751-1771, spoliĂ© Ă  la commune de Verpel (Ardennes) lui sera Ă©galement restituĂ©. AssociĂ© Ă  ce colloque en ligne, les Presses de l’Enssib proposent OĂč sont les bibliothĂšques françaises spoliĂ©es par les nazis ? ouvrage coordonnĂ© par Martine Poulain qui a rassemblĂ© les contributions, enrichies, concernant particuliĂšrement l’histoire d’environ 14 000 livres spoliĂ©s et dĂ©posĂ©s dans une quarantaine de bibliothĂšques françaises entre 1950 et 1953, et leurs caractĂ©ristiques. https://presses.enssib.fr/catalogue/ou-sont-les-bibliotheques-francaises-spoliees-par-les-nazi

    Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming

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    Despite progress, our understanding of psychiatric and neurological illnesses remains poor, at least in part due to the inability to access neurons directly from patients. Currently, there are in vitro models available but significant work remains, including the search for a less invasive, inexpensive and rapid method to obtain neuronal-like cells with the capacity to deliver reproducible results. Here, we present a new protocol to transdifferentiate human circulating monocytes into neuronal-like cells in 20 days and without the need for viral insertion or reprograming. We have thoroughly characterized these monocyte-derived-neuronal-like cells (MDNCs) through various approaches including immunofluorescence (IF), flow cytometry, qRT-PCR, single cell mRNA sequencing, electrophysiology and pharmacological techniques. These MDNCs resembled human neurons early in development, expressed a variety of neuroprogenitor and neuronal genes as well as several neuroprogenitor and neuronal proteins and also presented electrical activity. In addition, when these neuronal-like cells were exposed to either dopamine or colchicine, they responded similarly to neurons by retracting their neuronal arborizations. More importantly, MDNCs exhibited reproducible differentiation rates, arborizations and expression of dopamine 1 receptors (DR1) on separate sequential samples from the same individual. Differentiation efficiency measured by cell morphology was on average 11.9 ± 1.4% (mean, SEM, n = 38,819 cells from 15 donors). To provide context and help researchers decide which in vitro model of neuronal development is best suited to address their scientific question,we compared our results with those of other in vitro models currently available and exposed advantages and disadvantages of each paradigm

    High Titers of Transmissible Spongiform Encephalopathy Infectivity Associated with Extremely Low Levels of PrPSc in Vivo

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    Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177Diagnosis of transmissible spongiform encephalopathy (TSE) disease in humans and ruminants relies on the detection in post-mortem brain tissue of the protease-resistant form of the host glycoprotein PrP. The presence of this abnormal isoform (PrPSc) in tissues is taken as indicative of the presence of TSE infectivity. Here we demonstrate conclusively that high titers of TSE infectivity can be present in brain tissue of animals that show clinical and vacuolar signs of TSE disease but contain low or undetectable levels of PrPSc. This work questions the correlation between PrPSc level and the titer of infectivity and shows that tissues containing little or no proteinase K-resistant PrP can be infectious and harbor high titers of TSE infectivity. Reliance on protease-resistant PrPSc as a sole measure of infectivity may therefore in some instances significantly underestimate biological properties of diagnostic samples, thereby undermining efforts to contain and eradicate TSEs.https://doi.org/10.1074/jbc.M704329200282pubpub4

    TNF-α mediated keratinocyte expression and release of matrix metalloproteinase 9: putative mechanism of pathogenesis in Stevens-Johnson syndrome/ toxic epidermal necrolysis.

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    Stevens Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse drug reactions (ADRs) characterised by widespread keratinocyte cell-death and epidermal detachment. At present, there is little understanding of how the detachment occurs or how it is abrogated by the TNF-α inhibitor etanercept, an effective SJS/TEN treatment. RNA-sequencing was used to identify upregulated transcripts in formalin-fixed paraffin-embedded SJS/TEN skin biopsies. Epidermal matrix metalloproteinase 9 (MMP9) expression was assessed by immunohistochemistry in skin biopsies and cultured human skin explants exposed to serum from cutaneous ADRs patients. TNF-α-induced MMP9 expression and activity, and its abrogation by etanercept was determined using the HaCaT immortalised keratinocyte cell-line. Epidermal MMP9 expression was significantly higher in SJS/TEN skin (70.6%) vs. healthy control skin (0%, p=0.0098) and non-bullous skin reactions (10.7%, p=0.0002). SJS/TEN serum induced significant MMP9 expression and collagenase activity in healthy skin explants, which was reduced by etanercept. Etanercept was also able negate the TNF-α induced MMP9 expression in the HaCaT cell line. Data suggest that elevated epidermal MMP9 expression and collagenase activity is a putative pathogenic mechanism in SJS/TEN, which is limited by etanercept. Modulation of MMP9 expression and activity represents to our knowledge a previously unreported therapeutic target for the treatment of SJS/TEN

    The POM Monoclonals: A Comprehensive Set of Antibodies to Non-Overlapping Prion Protein Epitopes

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    PrPSc, a misfolded and aggregated form of the cellular prion protein PrPC, is the only defined constituent of the transmissible agent causing prion diseases. Expression of PrPC in the host organism is necessary for prion replication and for prion neurotoxicity. Understanding prion diseases necessitates detailed structural insights into PrPC and PrPSc. Towards this goal, we have developed a comprehensive collection of monoclonal antibodies denoted POM1 to POM19 and directed against many different epitopes of mouse PrPC. Three epitopes are located within the N-terminal octarepeat region, one is situated within the central unstructured region, and four epitopes are discontinuous within the globular C-proximal domain of PrPC. Some of these antibodies recognize epitopes that are resilient to protease digestion in PrPSc. Other antibodies immunoprecipitate PrPC, but not PrPSc. A third group was found to immunoprecipitate both PrP isoforms. Some of the latter antibodies could be blocked with epitope-mimicking peptides, and incubation with an excess of these peptides allowed for immunochromatography of PrPC and PrPSc. Amino-proximal antibodies were found to react with repetitive PrPC epitopes, thereby vastly increasing their avidity. We have also created functional single-chain miniantibodies from selected POMs, which retained the binding characteristics despite their low molecular mass. The POM collection, thus, represents a unique set of reagents allowing for studies with a variety of techniques, including western blotting, ELISA, immunoprecipitation, conformation-dependent immunoassays, and plasmon surface plasmon resonance-based assays

    OĂč sont les bibliothĂšques spoliĂ©es par les nazis ?

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    Ce colloque s’est tenu les jeudi et vendredi 23 et 24 mars 2017, Ă  la BibliothĂšque universitaire des langues et civilisations et Ă  la BibliothĂšque nationale de France, Il a Ă©tĂ© organisĂ© par le Centre Gabriel NaudĂ© de l\u27Ecole nationale supĂ©rieure des sciences de l\u27information et des bibliothĂšques (ENSSIB), l\u27Institut d\u27histoire du temps prĂ©sent (IHTP, UMR CNRS Paris 8) et l\u27UniversitĂ© Paris Diderot (EA IdentitĂ©s, cultures, territoires), avec le soutien de la BibliothĂšque nationale de France, de la BibliothĂšque universitaire des langues et civilisations (BULAC), de la Fondation pour la MĂ©moire de la Shoah, de la Claims Foundation, de la Fondation Maison des Sciences de l\u27Homme et du Deutscher Akademischer Austauschdienst. Au cours de ce colloque, une douzaine de livres, datant du XVIIe siĂšcle et retrouvĂ©s dans ses collections par la BibliothĂšque centrale et rĂ©gionale de Berlin (Zentral -und Landesbibliothek) ont Ă©tĂ© restituĂ©s Ă  trois ministĂšres français (ministĂšre des Affaires Ă©trangĂšres, ministĂšre de l\u27IntĂ©rieur, ministĂšre de la Justice) auxquels ils avaient Ă©tĂ© spoliĂ©es en juin 1940. Un registre manuscrit d\u27Ă©tat civil des annĂ©es 1751-1771, spoliĂ© Ă  la commune de Verpel (Ardennes) lui sera Ă©galement restituĂ©. Les vidĂ©os du colloque sont disponibles Ă  l\u27adresse suivante : https://www.enssib.fr/bibliotheque-numerique/notices/67542-ou-sont-les-bibliotheques-spoliees-par-les-nazis-tentatives-d-identification-et-de-restitution-un-chantier-en-cours AssociĂ©e Ă  ce colloque, la publication "Le MystĂšre de la boĂźte verte" est accessible Ă  l\u27adresse suivante : https://www.enssib.fr/bibliotheque-numerique/notices/68714-le-mystere-de-la-boite-vert

    Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

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    BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≄week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

    Governing the Internet : mobilizations, expertise and bureaucracies in the making of digital policies (1969-2017)

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    La thĂšse porte sur l’émergence et la transformation des politiques numĂ©riques, plus particuliĂšrement en France Ă  partir des annĂ©es 1990. Face Ă  la concurrence des acteurs techniques et aux institutions d’une gouvernance multipartite des rĂ©seaux, elle propose d’élucider les conditions de possibilitĂ© (et d’impossibilitĂ©) d’une intervention publique sur internet. Alors que les travaux sur la rĂ©volution numĂ©rique ont souvent nĂ©gligĂ© le rĂŽle qu’y ont jouĂ© les acteurs publics, cette recherche rĂ©inscrit l’étude du gouvernement de l’internet dans l’espace administratif, en tenant compte de ses luttes internes et de ses Ă©changes avec les univers militants, Ă©conomiques ou scientifiques. L’enquĂȘte multi-site combine ainsi l’observation de collectifs d’internautes mobilisĂ©s Ă  celle de l’État au quotidien, Ă  partir d’un cabinet ministĂ©riel. Elle articule de nombreux entretiens avec l’analyse quantitative des rĂ©seaux d’action publique et s’appuie Ă©galement sur l’étude de rapports publics et des archives du web. On montre alors comme les agents bureaucratiques se sont progressivement appropriĂ© la rĂ©volution numĂ©rique, l’ont accompagnĂ©e et en ont importĂ© les logiques au sein de l’État, participant Ă  la transformation plus gĂ©nĂ©rale de l’action publique. Contribution Ă  l’analyse des politiques publiques et Ă  l’étude des recompositions de l’État, la thĂšse permet ainsi d’éclairer les mĂ©canismes et les stratĂ©gies par lesquelles les Ă©lites prĂ©servent leur capacitĂ© d’action dans une sociĂ©tĂ© bouleversĂ©e par la diffusion des nouvelles technologies.This research deals with the conception and evolution of Internet policies, more specifically in France from the mid-1990’s onwards. It investigates the possibility of government intervention in a social space marked by decentralized governance and strong technical impediments. To this day, little attention has been devoted to the part played by state elites in governing the digital revolution : this research hence studies internet policies in the light of bureaucratic mechanisms at stake in internet policies, taking into account conflicts within the administration and the relationships of public actors with activists, scientists or private interests. The fieldwork combines the observation of digital protest groups and an account of a government cabinet’s everyday life. This dissertation also relies on a network analysis, the study of administrative reports and Web archives as well as on numerous interviews. It evidences how public actors have adapted to the Internet revolution, by contributing to this phenomenon and spreading its logics inside the bureaucratic structures, and how they have finally changed the design and implementation of public policies in the digital age. The dissertation offers a contribution to the analysis of modern state transformation and policy change, as it clarifies the ways in which state elites preserve their ability to govern a society transformed by technology

    Avancées sur la transmission, l'épidémiologie et le diagnostic des maladies à prions

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    CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

    Introduction

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