119 research outputs found

    Un groupe statuaire complexe à Autun : essai d’identification

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    Au cours d’un diagnostic rĂ©alisĂ© au nord-ouest de la ville d’Autun, Ă  proximitĂ© du rempart d’origine augustĂ©enne, un fragment de groupe statuaire a Ă©tĂ© trouvĂ© au croisement de deux rues antiques. Reposant sur le sol de circulation, il semble avoir Ă©tĂ© abandonnĂ© au cours de l’AntiquitĂ© tardive ou du haut Moyen Age. Il se compose d’un personnage cuirassĂ© (cuirasse musclĂ©e) vraisemblablement reprĂ©sentĂ© de dos. Il s’agirait d’une gigantomachie, en ronde-bosse (sculptĂ© sur trois cotĂ©s), la face principale a Ă©tĂ© dĂ©litĂ©e par la cassure de l’arkose taillĂ©e en dĂ©lit (les bancs gĂ©ologiques locaux sont impuissants Ă  fournir la hauteur nĂ©cessaire Ă  ce groupe). Sur ce drapĂ©, on voit se lover dans une attitude agressive une tĂȘte de serpent, tous crocs sortis : plusieurs possibilitĂ©s d’interprĂ©tation s’offrent Ă  nous, le serpent terminant les jambes d’un gĂ©ant, ou le serpent fĂ©tiche et protecteur de Minerve, qui serait donc notre dĂ©esse cuirassĂ©e. La cassure latĂ©rale (Ă  droite) laisse voir la suite de la cuirasse Ă  festons et un arrachement sur toute la hauteur pourrait aisĂ©ment correspondre Ă  l’arrachement d’un bouclier qui servirait en plus d’élĂ©ment de stabilitĂ©. Enfin, le dernier Ă©lĂ©ment Ă  gauche est une sorte de torse musclĂ© de gĂ©ant vraisemblablement dĂ©sarticulĂ©, peut-ĂȘtre AlcyonĂ©e, dĂ©membrĂ© par Minerve.During an archaeological investigation in the northwest of Autun, near the Augustan rampart, a fragment of a statuary group was found in the intersection of two ancient streets. Resting on the road surface, it seems to have been abandoned during Late Antiquity or the high Middle Ages. It consists of a cuirassed figure likely represented from behind. It was a gigantomachy carved in the round (on three sides), the principal side was damaged by the fracture of the cut arkose (the local geological beds are unable to provide the height needed for this group). On the drapery, we can see the head of a snake coiled in an aggressive attitude, with its fangs bared. Several interpretations are available to us : the snake is the end of a giant’ s legs or it is the lucky snake of Minerva, who would be our armored goddess. The lateral fissure (to the right) reveals the path of the cuirass’s festoons and tear along the entire height could easily match the removal of a shield that would have added an element of stability. Finally, the last item on the left is a kind of disarticulated muscular torso of a giant, perhaps Alcyoneus, who was dismembered by Minerva

    Une <i>schola</i> monumentale découverte boulevard Frédéric-Latouche à <i>Augustodunum</i>/Autun (SaÎne-et-Loire)

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    International audienceIn 2011, an archaeological evaluation was carried out in the centre of the Roman city of Augustodunum (Autun) on a plot of over 1 ha. This operation afforded the opportunity to explore parts of two insulae along the main street, the so-called cardo maximus, an area that has benefited from recent advances in knowledge. The first insula hosts a high-status domus strongly resembling those of "Balbius Iassus" and the "Étui d’Or", excavated in the vicinity in the 1970s; the second, addressed in this paper, contains the remains of a vast monumental complex covering approximately 900 m2. Most probably built at the beginning of the 2nd c. on the ruins of earlier houses, it was thoroughly restructured at the end of the 3rd c. or the beginning of the 4th and seems to have been abandoned then partly dismantled from the start of the 5th c. To judge by its plan and its situation within a residential area located in the immediate vicinity of the monumental centre, the building of the beginning of the late-antique period exhibits the functional and topographical features of a schola of exceptional size. Comparison with literary sources would seem to indicate that the remains are those of the scholae Maenianae, known from a speech delivered in AD 298 by Eumenius, a local notable, in the presence of the governor of Gallia Lugdunensis. Only further excavation and the discovery of an inscription could definitively prove this initial hypothesis. The discovery of such a vast complex, whatever function is assigned to it, vividly illustrates the importance of the monumental equipment of Autun under the Early Empire as well as the restoration work that took place in the city at the turn of the 300s.Un diagnostic d’archĂ©ologie prĂ©ventive a Ă©tĂ© rĂ©alisĂ© en 2011 dans le centre de la ville antique d’Augustodunum sur une parcelle de plus d’un hectare. Cette opĂ©ration a Ă©tĂ© l’occasion d’explorer partiellement deux Ăźlots longeant la rue principale, dite « cardo maximus », un secteur qui bĂ©nĂ©ficie d’avancĂ©es rĂ©centes de la recherche. Le premier Ăźlot accueille un habitat de fort statut qui prĂ©sente de remarquables similitudes avec les maisons dites de Balbius Iassus et Ă  l’Étui d’Or fouillĂ©es Ă  proximitĂ© dans les annĂ©es 1970 ; le second Ăźlot recĂšle les vestiges d’un vaste complexe monumental, dĂ©gagĂ©s sur prĂšs de 900 m2, qui fait l’objet du prĂ©sent article. Vraisemblablement construit au dĂ©but du IIe s. sur les ruines d’anciennes maisons, il fut profondĂ©ment restructurĂ© Ă  la fin du IIIe s. ou au dĂ©but du IVe s. et semble avoir Ă©tĂ© abandonnĂ© puis en partie dĂ©mantelĂ© Ă  partir du dĂ©but du Ve s. L’édifice du dĂ©but de l’AntiquitĂ© tardive, par son plan et sa localisation dans un quartier rĂ©sidentiel situĂ© Ă  proximitĂ© immĂ©diate du centre monumental, rĂ©pond aux caractĂ©ristiques fonctionnelle et topographique d’une schola de taille exceptionnelle. La confrontation avec les sources littĂ©raires suggĂšre d’identifier nos vestiges comme ceux des scholae Maenianae connues par un discours prononcĂ© en 298 apr. J. C., par un notable originaire de la citĂ©, EumĂšne, en prĂ©sence du gouverneur de Lyonnaise. Seule une fouille complĂ©mentaire et la dĂ©couverte d’un texte Ă©pigraphique sont Ă  mĂȘme dĂ©sormais de valider dĂ©finitivement ces premiĂšres hypothĂšses. Quelle que soit la fonction assignĂ©e Ă  ce vaste complexe, sa dĂ©couverte illustre avec Ă©clat Ă  la fois l’importance de la parure monumentale d’Autun sous le Haut-Empire ainsi que l’entreprise de restauration intervenue sur place au tournant des annĂ©es 300

    The N-terminal domains of TRF1 and TRF2 regulate their ability to condense telomeric DNA

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    TRF1 and TRF2 are key proteins in human telomeres, which, despite their similarities, have different behaviors upon DNA binding. Previous work has shown that unlike TRF1, TRF2 condenses telomeric, thus creating consequential negative torsion on the adjacent DNA, a property that is thought to lead to the stimulation of single-strand invasion and was proposed to favor telomeric DNA looping. In this report, we show that these activities, originating from the central TRFH domain of TRF2, are also displayed by the TRFH domain of TRF1 but are repressed in the full-length protein by the presence of an acidic domain at the N-terminus. Strikingly, a similar repression is observed on TRF2 through the binding of a TERRA-like RNA molecule to the N-terminus of TRF2. Phylogenetic and biochemical studies suggest that the N-terminal domains of TRF proteins originate from a gradual extension of the coding sequences of a duplicated ancestral gene with a consequential progressive alteration of the biochemical properties of these proteins. Overall, these data suggest that the N-termini of TRF1 and TRF2 have evolved to finely regulate their ability to condense DNA

    An Epigenetic Switch Involving Overlapping Fur and DNA Methylation Optimizes Expression of a Type VI Secretion Gene Cluster

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    Type VI secretion systems (T6SS) are macromolecular machines of the cell envelope of Gram-negative bacteria responsible for bacterial killing and/or virulence towards different host cells. Here, we characterized the regulatory mechanism underlying expression of the enteroagregative Escherichia coli sci1 T6SS gene cluster. We identified Fur as the main regulator of the sci1 cluster. A detailed analysis of the promoter region showed the presence of three GATC motifs, which are target of the DNA adenine methylase Dam. Using a combination of reporter fusion, gel shift, and in vivo and in vitro Dam methylation assays, we dissected the regulatory role of Fur and Dam-dependent methylation. We showed that the sci1 gene cluster expression is under the control of an epigenetic switch depending on methylation: fur binding prevents methylation of a GATC motif, whereas methylation at this specific site decreases the affinity of Fur for its binding box. A model is proposed in which the sci1 promoter is regulated by iron availability, adenine methylation, and DNA replication

    Genetic Variation in the Familial Mediterranean Fever Gene (MEFV) and Risk for Crohn's Disease and Ulcerative Colitis

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    BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene. METHODOLOGY AND RESULTS: MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p<0.0003; DSS p<0.006), in biopsies from CD (p<0.02) and severe ulcerative colitis (UC) patients (p<0.008). Comprehensive genetic screening of the MEFV region in the Belgian exploratory sample set (440 CD trios, 137 UC trios, 239 CD cases, 96 UC cases, and 107 healthy controls) identified SNPs located in the MEFV 5' haplotype block that were significantly associated with UC (rs224217; p = 0.003; A allele frequency: 56% cases, 45% controls), while no CD associations were observed. Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p = 0.0005; A allele frequency: 32% in cases, 23% in controls). No consistent associations were observed in additional Canadian (256 CD trios, 91 UC trios) and Scottish (495 UC, 370 controls) sample sets. We note that rs224222 showed marginal association (p = 0.012; G allele frequency: 82% in cases, 70% in controls) in the Canadian sample, but with a different risk allele. None of the NLRP3 common variants were associated with UC in the Belgian-Canadian UC samples and no significant interactions were observed between NLRP3 and MEFV that could explain the observed flip-flop of the rs224222 risk allele. CONCLUSION: The differences in association levels observed between the sample sets may be a consequence of distinct founder effects or of the relative small sample size of the cohorts evaluated in this study. However, the results suggest that common variants in the MEFV region do not contribute to CD and UC susceptibility.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

    La sculpture romaine en Occident

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    Cet ouvrage rĂ©unit les rĂ©sultats de deux manifestations complĂ©mentaires  : d’une part, la table ronde intitulĂ©e «  Rendre Ă  CĂ©sar  », organisĂ©e le mercredi 20 juin 2012, Ă  Paris, au MusĂ©e du Louvre et, d’autre part, les «  Rencontres autour de la sculpture romaine conservĂ©e en France  » qui ont eu lieu du 18 au 20 octobre 2012 au MusĂ©e dĂ©partemental Arles antique. La richesse des interventions lors de ces deux manifestations permet de restituer un ouvrage composĂ© de trente-huit articles, rĂ©partis en trois parties et une conclusion. La premiĂšre partie, en Ă©cho et en dĂ©veloppement de la table ronde du Louvre, porte sur le portrait du «  CĂ©sar du RhĂŽne  », aussi bien que sur «  Le portrait romain en Gaule  ». La deuxiĂšme partie publie cinq Ă©tudes autour des «  nouvelles techniques d’investigations scientifiques  » et prĂ©sente l’analyse des matĂ©riaux des sculptures en pierre et en bronze, dĂ©couvertes dans le RhĂŽne Ă  Arles, ainsi qu’une Ă©tude ethnoarchĂ©ologique sur les techniques de production du portrait. Enfin une troisiĂšme partie prĂ©sente les «  dĂ©couvertes rĂ©centes et les nouvelles recherches  », dĂ©clinĂ©es en seize Ă©tudes qui sont consacrĂ©es Ă  des Ă©tudes de cas (Autun, Vaison-la-Romaine, NĂźmes, Metz-Divodurum, Apt), ainsi qu’à des relectures novatrices de sculptures mĂ©connues (Plouarzel, Langres, Avignonet-Lauragais, VernĂšgues, vallĂ©e de l’Ubaye, Besançon, Lyon). Robert Turcan signe la conclusion. Ainsi, «  La sculpture romaine en Occident. Nouveaux regards   » reflĂšte la variĂ©tĂ© et l’intĂ©rĂȘt des questionnements actuels dans ce domaine

    Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

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    RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≄60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    Structure and function of the type vi secretion system tail

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    RĂ©sumĂ© : La comprĂ©hension des contraintes qui rĂ©gissent l'assemblage des machineries supramolĂ©culaires – qu'elles soient solubles ou bien ancrĂ©es dans les membranes biologiques – est un enjeu scientifique majeur.Le systĂšme de de sĂ©crĂ©tion type VI (T6SS) est un organelle bactĂ©rien rĂ©cemment mis en Ă©vidence qui a pour particularitĂ© de possĂ©der une origine Ă©volutive commune avec le bactĂ©riophage T4. En raison de cette origine Ă©volutive commune, certaines sous unitĂ©s du T6SS et du bactĂ©riophage T4 prĂ©sentent des structures comparables. Cependant, un grand nombre des sous unitĂ©s du T6SS reste Ă  caractĂ©riser. Parmi celles-ci, les protĂ©ines SciB et SciC sont retrouvĂ©es dans tous les systĂšmes de sĂ©crĂ©tion de type VI suggĂ©rant que ces deux protĂ©ines participent Ă  la formation du "core-complexe": le complexe minimal requis pour le fonctionnement du T6SS.The recently identified type VI secretion system has been demonstrated to be involved in most of these processes. The T6SS is a highly complex macromolecular machine that allows Gram-negative bacteria to deliver effector proteins to both prokaryotic and eukaryotic cells in a contact-dependent manner. The T6SS promotes therefore antibacterial competition, virulence towards eukaryotes or even both. The T6SS is composed of a minimal set of 13 subunits, which are currently believed to form the core apparatus. They assemble two distinct sub-complexes: one is a cytosolic contractile structure related to the tail of contractile bacteriophages, whereas the other spans the whole cell envelope. Therefore, the T6SS is generally depicted as an inverted phage tail anchored to the cell envelope through its membrane-associated complex. Contractile tails are currently thought to assemble from four structural elements: the baseplate, the internal tube, the contractile sheath and the tail terminator. The aim of my Ph.D. work was to further characterize the assembly and function of the T6SS phage tail-like complex in enteroaggregative E. coli. In this thesis document, I provide evidence that the internal tube assembles from Hcp hexamers stacked in a head-to-tail manner and that this internal cylinder is used as a template during sheath assembly. I also characterized a sub-complex of three proteins (TssEFG) that forms the baseplate of the T6SS and controls the polymerization of the tube and sheath. Finally, I recently showed that the T6SS functions like a nano-crossbow to kill target cells as the contraction of the T6SS results in prey cell death during interbacterial competition

    Un groupe statuaire complexe à Autun : essai d’identification

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