20 research outputs found
Imitations d'opus sectile et décors à réseau : essai de terminologie
Ce document de travail d'équipe, dont la parution est ancienne, sera corrigé et enrichi.Le Bulletin de liaison / Centre d'étude des peintures murales romaines : n° 12 contient un glossaire, des références bibliographiques et un index des noms de lieux.This bulletin is based on drawings and schemes which is referred to the description of two decorations in the ancient wall-painting. Each note contains the decorative scheme terminology from the archaeological site and the bibliography.Le bulletin de liaison est basé sur des croquis et des schémas couplés à une description normalisée de deux types de décors de la peinture murale antique. La terminologie des compositions géométriques et de leur remplissage est regroupée sous forme de notices, renvoyant à un exemple-type avec référence bibliographique
XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining
International audienceThe Ku70-Ku80 (Ku) heterodimer binds rapidly and tightly to the ends of DNA double-strand breaks and recruits factors of the non-homologous end-joining (NHEJ) repair pathway through molecular interactions that remain unclear. We have determined crystal structures of the Ku-binding motifs (KBM) of the NHEJ proteins APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex. The two KBM motifs bind remote sites of the Ku80 alpha/beta domain. The X-KBM occupies an internal pocket formed by an unprecedented large outward rotation of the Ku80 alpha/beta domain. We observe independent recruitment of the APLF-interacting protein XRCC4 and of XLF to laser-irradiated sites via binding of A- and X-KBMs, respectively, to Ku80. Finally, we show that mutation of the X-KBM and A-KBM binding sites in Ku80 compromises both the efficiency and accuracy of end joining and cellular radiosensitivity. A- and X-KBMs may represent two initial anchor points to build the intricate interaction network required for NHEJ
Multigenerational study of the obesogen effects of bisphenol S after a perinatal exposure in C57BL6/J mice fed a high fat diet
International audienceBackground : Bisphenol S is an endocrine disruptor exhibiting metabolic disturbances, especially following perinatal exposures. To date, no data are available on the obesogen effects of BPS in a mutligenerational issue.Objectives : We investigated obesogen effects of BPS in a multigenerational study by focusing on body weight, adipose tissue and plasma parameters in male and female mice.Methods : Pregnant C57BL6/J mice were exposed to BPS (1.5 ÎŒg/kg bw/day ie a human equivalent dose of 0.12 ÎŒg/kg bw/day) by drinking water from gestational day 0 to post natal day 21. All offsprings were fed with a high fat diet during 15 weeks. Body weight was monitored weekly and fat mass was measured before euthanasia. At euthanasia, blood glucose, insuline, triglyceride, cholesterol and no esterified fatty acid plasma levels were determined and gene expressions in visceral adipose tissue were assessed. F1 males and females were mated to obtain the F2 generation. Likewise, the F2 mice were cross-bred to obtain F3. The same analyses were performed.Results : In F1 BPS induced an overweight in male mice associated to lipolysis gene expressions upregulation. In F1 females, dyslipidemia was observed. In F2, BPS exposure was associated to an increase in body weight, fat and VAT masses in males and females. Several plasma parameters were increased but with a sex related pattern (blood glucose, triglycerides and cholesterol in males and NEFA in females). We observed a down-regulation in mRNA expression of gene involved in lipogenesis and in lipolysis for females but only in the lipogenesis for males. In F3, a decrease in VAT mass and an upregulation of lipogenesis gene expression occurred only in females.Conclusions : BPS perinatal exposure induced sex-dependent obesogen multigenerational effects, the F2 generation being the most impacted. Transgenerational disturbances persisted only in females
Building the Data Management Plan of Observatoire de Paris
International audienceDuring the last decade, the production of science data increased in parallel with the decreasing cost of digital storage and the increase of data processing and computation capabilities. Science institute have to find a way to manage and preserve this data inflow. Most of the calls of funding agencies now require to provide a description of how the data produced in the projet will be managed (archiving, curation, distribution...) and published. This usually takes the form of a Data Management Plan. Funding agency also required more and more to select open source licences for any production of the project, for instance by enforcing FAIR (Findable, Accessible, Interoperable, Reusable) principles.Founded in 1667, the Observatoire de Paris is the largest French national research center for astronomy. Nearly a third of all French astronomers are working in its five laboratories and institute. Located in Paris, Meudon and Nançay, they are all associated with CNRS (National Center for Scientific Research) and with the major scientific universities in the Paris and Orléans area. The research conducted at the Paris observatory covers all the fields of contemporary astronomy and astrophysics: the study of the Sun and Sun-Earth relations, planets and planetary systems, star formation, the interstellar medium, the formation and evolution of galaxies, astroparticles and cosmology, time and space metrology as well as the history and philosophy of science. The Library of the Observatoire is a service entirely devoted to research. Its two missions are to provide scientists with the most complete and pertinent documentation, and to enrich a 350 year old heritage, while at the same time thinking about what today's heritage will be, and what the future will bring. Although mainly destined for the scientists of the Observatoire, it is nevertheless also open to others: scientists from different disciplines and all countries, students, school children, the general public, who are welcome and for whom it organizes scientific and technical outreach activities.Observatoire de Paris has listed a few services that needed to set up a way to formally manage their data more formally: the Informatics Department of the Observatory (DIO), which is hosting scientific computing servers and data storage facilities for the sciences teams of the observatory; the Paris Astronomical Data Centre (PADC), which provides interoperable access on data collections produced within the observatory; the Library of the observatory. Several teams (linked with projects funded by EU or space agencies) showed interest as well.Several actions have now been started by the working group: Identification of the various sources of data and data collection in each department of the Observatory; Identification of the needs in term of citation (data collections, artifacts, documents, software...) and licences; study of possible authoritative delegations (e.g., on DOI attribution, long term preservation...) and to whom; proposing a Data Management Plan template to support science teams when applying for fundings. Those actions are all aiming at building a generic Data Management Plan for the Observatory, that would propose rules and practices for preserving, distribution and sharing science products.The PADC team is deeply involved in data-related international data alliances, such as the International Virtual Observatory Alliance (IVOA), the International Planetary Data Alliance (IPDA), and the Research Data Alliance (RDA). This is ensuring that: (a) this study is conducted with up-to-date technologies and concepts, and that (b) the results of the study will be discussed and advertised in those international contexts
Nutrient shortage triggers the hexosamine biosynthetic pathway via the GCN2-ATF4 signalling pathway
We thank the Dr. J.D. Minna (University of Texas Southwestern Medical Center, Dallas, USA) for the HBEC 3KT-RL cell line. We are grateful to Dr. D. Ron (Institute of Metabolic Science, Cambridge, UK) for GCN2 deficient Mouse Embryonic Fibroblasts and for the F2vE-PERK construct. The authors thank the Dr. B. Manship for language editing and manuscript corrections. C. Chaveroux. is the recipient of the program for fundamental and clinical research on cancer from the "Fondation de France". S. Manie is supported by the foundation "Association pour la Recherche sur le Cancer" (PJA20131200334), and by the "Programme INCA" (INCA_7981)The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. Despite its biological significance, little is known about the regulation of HBP flux during nutrient limitation. Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2 alpha signalling pathway. The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked beta-N-acetylglucosamine protein modifications. Taken together, these findings demonstrate that ATF4 provides a link between nutritional stress and the HBP for the regulation of the O-GlcNAcylation-dependent cellular signallin
Building the Data Management Plan of Observatoire de Paris
International audienceDuring the last decade, the production of science data increased in parallel with the decreasing cost of digital storage and the increase of data processing and computation capabilities. Science institute have to find a way to manage and preserve this data inflow. Most of the calls of funding agencies now require to provide a description of how the data produced in the projet will be managed (archiving, curation, distribution...) and published. This usually takes the form of a Data Management Plan. Funding agency also required more and more to select open source licences for any production of the project, for instance by enforcing FAIR (Findable, Accessible, Interoperable, Reusable) principles.Founded in 1667, the Observatoire de Paris is the largest French national research center for astronomy. Nearly a third of all French astronomers are working in its five laboratories and institute. Located in Paris, Meudon and Nançay, they are all associated with CNRS (National Center for Scientific Research) and with the major scientific universities in the Paris and Orléans area. The research conducted at the Paris observatory covers all the fields of contemporary astronomy and astrophysics: the study of the Sun and Sun-Earth relations, planets and planetary systems, star formation, the interstellar medium, the formation and evolution of galaxies, astroparticles and cosmology, time and space metrology as well as the history and philosophy of science. The Library of the Observatoire is a service entirely devoted to research. Its two missions are to provide scientists with the most complete and pertinent documentation, and to enrich a 350 year old heritage, while at the same time thinking about what today's heritage will be, and what the future will bring. Although mainly destined for the scientists of the Observatoire, it is nevertheless also open to others: scientists from different disciplines and all countries, students, school children, the general public, who are welcome and for whom it organizes scientific and technical outreach activities.Observatoire de Paris has listed a few services that needed to set up a way to formally manage their data more formally: the Informatics Department of the Observatory (DIO), which is hosting scientific computing servers and data storage facilities for the sciences teams of the observatory; the Paris Astronomical Data Centre (PADC), which provides interoperable access on data collections produced within the observatory; the Library of the observatory. Several teams (linked with projects funded by EU or space agencies) showed interest as well.Several actions have now been started by the working group: Identification of the various sources of data and data collection in each department of the Observatory; Identification of the needs in term of citation (data collections, artifacts, documents, software...) and licences; study of possible authoritative delegations (e.g., on DOI attribution, long term preservation...) and to whom; proposing a Data Management Plan template to support science teams when applying for fundings. Those actions are all aiming at building a generic Data Management Plan for the Observatory, that would propose rules and practices for preserving, distribution and sharing science products.The PADC team is deeply involved in data-related international data alliances, such as the International Virtual Observatory Alliance (IVOA), the International Planetary Data Alliance (IPDA), and the Research Data Alliance (RDA). This is ensuring that: (a) this study is conducted with up-to-date technologies and concepts, and that (b) the results of the study will be discussed and advertised in those international contexts
Generation of llama single-domain antibodies against methotrexate, a prototypical hapten.
Single-domain antibodies specific to methotrexate (MTX) were obtained after immunization of one llama (Llama glama). Specific VHH domains (V-D-J-REGION) were selected by panning from an immune-llama library using phage display technology. The antibody fragments specific to MTX were purified from Escherichia coli (C41 strain) periplasm by immobilized metal affinity chromatography with an expression level of around 10mg/L. A single band around 16,000Da corresponding to VHH fragments was found after analysis by SDS-PAGE and Western blotting, while competition ELISA demonstrated selective binding to soluble MTX. Surface plasmon resonance (SPR) analysis showed that anti-MTX VHH domains had affinities in the nanomolar range (29-515nM) to MTX-serum albumin conjugates. The genes encoding anti-MTX VHH were found by IMGT/V-QUEST to be similar to the previously reported llama and human IGHV germline genes. The V-D and D-J junction rearrangements in the seven anti-MTX CDR3 sequences indicate that they were originated from three distinct progenitor B cells. Our results demonstrate that camelid single-domain antibodies are capable of high affinity binding to low molecular weight hydrosoluble haptens. Furthermore, these anti-MTX VHH give new insights on how the antigen binding repertoire of llama single-domain antibody can provide combining sites to haptens in the absence of a VL. This type of single-domain antibodies offers advantages compared to murine recombinant antibodies in terms of production rate and sequence similarity to the human IGHV3 subgroup genes
ATF4-Dependent NRF2 Transcriptional Regulation Promotes Antioxidant Protection during Endoplasmic Reticulum Stress
International audienceEndoplasmic reticulum (ER) stress generates reactive oxygen species (ROS) that induce apoptosis if left unabated. To limit oxidative insults, the ER stress PKR-like endoplasmic reticulum Kinase (PERK) has been reported to phosphorylate and activate nuclear factor erythroid 2-related factor 2 (NRF2). Here, we uncover an alternative mechanism for PERK-mediated NRF2 regulation in human cells that does not require direct phosphorylation. We show that the activation of the PERK pathway rapidly stimulates the expression of NRF2 through activating transcription factor 4 (ATF4). In addition, NRF2 activation is late and largely driven by reactive oxygen species (ROS) generated during late protein synthesis recovery, contributing to protecting against cell death. Thus, PERK-mediated NRF2 activation encompasses a PERK-ATF4-dependent control of NRF2 expression that contributes to the NRF2 protective response engaged during ER stress-induced ROS production
Hauts-de-France, Nord, Lille, rue Malpart, rue Lydéric et place Gentil Muiron : rapport de diagnostic
Les sondages rĂ©alisĂ©s mettent en Ă©vidence une occupation continue de la parcelle Ă partir de la fin du XIIe - dĂ©but de XIIIe siĂšcle. La premiĂšre phase sâĂ©tablit entre la fin du XIIe siĂšcle ou le dĂ©but du XIIIe et le XIVe siĂšcle et correspond Ă lâoccupation prĂ©cĂ©dant la fondation de lâhospice en 1460. Les niveaux archĂ©ologiques de cette premiĂšre phase sont prĂ©sents dans lâensemble des sondages. Ils sont en gĂ©nĂ©ral assez bien conservĂ©s. Ces vestiges permettent dâavoir des indications sur lâorganisation de lâĂźlot urbain dans son ensemble, et ouvrent de nombreuses interrogations. Ils se composent de niveaux de rue appartenant Ă la rue du Bois Saint-Sauveur (supprimĂ©e en 1960) et de niveaux dâhabitats et de jardins dans la partie haute. Dans la partie basse, des niveaux dâĂ©pandages et de remblais scellent de larges fosses au comblement organique et phosphatĂ©. Deux fossĂ©s bordant les limites de lâĂźlot mĂ©diĂ©val sont mis en place au moins au cours du XIIIe siĂšcle. Ă lâintĂ©rieur de lâĂźlot, le fossĂ© 1240 dĂ©finit une limite parcellaire qui semble se maintenir dans les phases dâhabitat postĂ©rieures. Il est probable quâune zone dâhabitat se mette en place en front de rue du cĂŽtĂ© de la rue du Bois Saint-Sauveur dĂšs le dĂ©but du XIIIe siĂšcle. Bien que cet habitat nâait Ă©tĂ© mis au jour clairement que dans le sondage 4, la multiplication des fosses de rejets domestiques de la mĂȘme pĂ©riode dans la tranchĂ©e 3 laisse prĂ©sager une occupation plus dense que celle perçue dans ce seul sondage. Ces fosses pourrait offrir par ailleurs des ensembles clos permettant une approche fine de la culture matĂ©rielle. La rue du Bois Saint-Sauveur qui desservait ces habitations est dâune grande qualitĂ© pour la pĂ©riode et compte tenu de sa situation. Il sâagit en effet dâune voie secondaire Ă la rue des Malades (actuellement rue de Paris).En contrebas des habitats et de leurs jardins, on trouve de larges fosses quadrangulaires comblĂ©es par un sĂ©diment phosphatĂ©, des niveaux de jardins non bioturbĂ©s et Ă©galement phosphatĂ©s, ainsi que des rejets de forges dans le fossĂ© 1029. Ces Ă©lĂ©ments sont autant dâindices dâune activitĂ© non dĂ©finie (artisanat ?) qui longerait la rue Malpart et lâemplacement supposĂ© des terreaux de la muraille mĂ©diĂ©vale. Lâensemble donne lâimpression dâune rĂ©partition bien diffĂ©renciĂ© des activitĂ©s et de lâhabitat entre le cĂŽtĂ© rue du Bois Saint-Sauveur et le cĂŽtĂ© rue Malpart.Si les limites nord et sud de la parcelle semblent claires, la limite ouest vers la terrĂ©e du rempart mĂ©diĂ©val nâa pas Ă©tĂ© mise en Ă©vidence dans le cadre du diagnostic. La position mĂȘme de ce rempart est difficile Ă Ă©valuer. La prĂ©sence du fossĂ© 1029 en tranchĂ©e 1 repousse le dĂ©part dâune Ă©ventuelle levĂ©e de terre au moins sous la rampe dâaccĂšs du chantier, zone inaccessible au moment de lâopĂ©ration.La seconde phase commence Ă la fondation de lâhospice Gantois et couvre le XVIe siĂšcle. La fondation de lâhospice Gantois en lieu et place de la cense de Georges de Bruges en 1460 marque un tournant important dans lâoccupation des lieux. En transformant les terrains en jardins et cimetiĂšre, lâhospice arrĂȘte la densification de la parcelle.LâĂ©tude cĂ©ramique montre un hiatus chronologique pour le XVe siĂšcle, peut-ĂȘtre liĂ© Ă lâinstallation de lâhospice. Dans la zone basse, cĂŽtĂ© rue Malpart, le cimetiĂšre des chartriers est installĂ©. Bien que le cimetiĂšre nâait Ă©tĂ© dĂ©gagĂ© que sur 44 mÂČ, il est probable quâil soit plus Ă©tendu. Lors de la fouille de lâhospice Gantois en 2002, deux sĂ©pultures avaient Ă©tĂ© retrouvĂ©es sur lâemplacement de lâextension de lâhĂŽtel. Il est donc possible que des sĂ©pultures se trouvent Ă©galement conservĂ©es entre la clĂŽture de lâhĂŽtel Gantois et le sous-sol de la maternitĂ©. La zone dĂ©couverte montre quant Ă elle un cimetiĂšre dense avec de frĂ©quents recoupements. Celui-ci nous permet dâapprĂ©hender la population hĂ©bergĂ©e par lâhospice. Si les statuts de 1467 dĂ©signe une population mixte, pauvre et ĂągĂ©e, les sĂ©pultures testĂ©es dans ce cimetiĂšre montrent des individus, certes ĂągĂ©s, mais avec des pathologies visibles aux yeux de leurs contemporains. LâĂ©tude biologique de cette population complĂ©tĂ©e par une Ă©tude dâarchives pourrait apporter des Ă©lĂ©ments significatifs sur les conditions de vie et sur la prise en charge de cette population dans la sociĂ©tĂ© mĂ©diĂ©vale et moderne.Durant cette seconde phase, des maisons de louage construites sur le cĂŽtĂ© nord maintiennent une occupation uniquement en front de rue et la rue du Bois Saint-Sauveur continue dâĂȘtre entretenue rĂ©guliĂšrement. Vers lâouest, les vestiges dĂ©couverts ne permettent pas dâĂ©tablir la limite de lâĂźlot.La derniĂšre large phase couvre la pĂ©riode allant du XVIIe siĂšcle au XXe siĂšcle et est marquĂ© par la construction du rempart moderne, modifiĂ© par Vauban et son dĂ©mantĂšlement. De nombreux changements interviennent alors sur la bordure ouest de lâemprise qui sont dus Ă lâĂ©volution de la muraille. Les vestiges de cette phase se concentrent dans la partie basse du terrain. Dans la zone haute, les terrains toujours contenus dans lâenclos de lâhospice, sont prĂ©servĂ©s de la densification du quartier pendant le XIXe siĂšcle. Le rempart moderne mis au jour, qui pourrait ĂȘtre celui de lâextension de 1603 est trĂšs altĂ©rĂ©. Toutefois, son tracĂ© rentrant ne trouve pas de solution de continuitĂ© dans la tranchĂ©e 1, la question de son lien avec la fortification du bas Moyen Ăge reste donc ouverte