Vienne – Église Saint-André-le-Haut

Depuis une quinzaine d’années, plusieurs opérations archéologiques ont été réalisées dans l’ancienne abbaye de Saint-André-le-Haut à Vienne. À la fin des années 1990, des sondages dans l’église et dans le cloître, placés sous la direction de B. Helly, et une première étude des élévations, menée par M. Zannettacci, avaient montré l’intérêt du site. À partir de 2003, des campagnes de fouilles ont été menées avec les étudiants d’archéologie de l’Université Lyon 2, dans le cadre d’un chantier éco..

Oxydation biocatalytique de liaison C-H non activée pour la synthèse de dérivés bêta-hydroxylamines (application à la synthèse d'acides aminés non protéinogènes)

Le travail présenté dans ce manuscrit porte sur la recherche de nouveaux membres de la famille des dioxygénases a-cétoglutarate et fer dépendantes (a-KAO) et leur application en synthèse organique. Dans un premier, ce travail a consisté à chercher de nouvelles enzymes selon une approche génomique basée sur l homologie de séquence et le partage d un motif InterPro. Deux criblages haut débit avec 79 et 127 enzymes candidates ont ensuite été effectués sur des panels constitués respectivement de 23 et 36 substrats, structurellement plus ou moins proches des substrats métaboliques. Huit nouvelles a-KAO ont ainsi pu être découvertes. Parmi ces huit nouvelles a-KAO, quatre ont été étudiées plus en détail. Après optimisation des conditions de réaction pour chaque enzyme, des montées en échelle ont été réalisées pour caractériser les produits formés. A partir de ces quatre enzymes, la (3S)-3-hydroxy-L-lysine, un dérivé cyclisé de la (4R)-4-hydroxy-L-lysine, (3S)-3-hydroxy-L-ornithine et un dérivé de la (3S)-3-hydroxy-L-arginine ont pu être produits. Nous avons proposé une synthèse biocatalytique de mono et dihydroxydiamines en couplant une ou deux a-KAO avec une décarboxylase. Les (2S)-1,5-diamino-2-pentanol, 1,5-diamino-3-pentanol, (2S)-1,4-diamino-2-butanol et (2S,3S)-1,5-diamino-2,3-pentanediol ont ainsi été obtenus avec de bonnes conversions.The work described in this manuscript deals with the search of new members of the a-ketoglutarate and Iron-dependent dioxygenases family (a-KAO) and their applications in organic synthesis. The first part of this work presents the search of new enzymes through a genomic approach based on sequence homology and InterPro motif sharing. Two high-throughput screenings with 79 and 127 candidate enzymes have been performed on 23 and 36 substrates more or less structurally close to known metabolic substrates. 8 new a-KAOs have been discovered. Among these new enzymes, four were studied in more details. After optimization of the enzymatic reaction conditions for each enzyme, scale-up allowed to obtain compounds for isolation and characterization. With these four enzymes, (3S)-3-hydroxy-L-lysine, (4R)-4-hydroxy-L-lysine as its cyclic derivative, (3S)-3-hydroxy-L-ornithine and a derivative of (3S)-3-hydroxy-L-arginine were produced. Two of the new a-KAO were combined in a cascade process to afford the (3R,4R)-3,4-dihydroxy-L-lysine as its cyclic derivative. We proposed a biocatalytic synthesis of mono and hydroxydiamines by coupling one or two a-KAO with a decarboxylase enzyme. (2S)-1,5-diamino-2-pentanol, 1,5-diamino-3-pentanol, (2S)-1,4-diamino-2-butanol and (2S,3S)-1,5-diamino-2,3-pentanediol were obtained with good overall conversions.EVRY-Bib. électronique (912289901) / SudocSudocFranceF

La découverte du Trésor de Cluny. Premiers résultats et perspectives de recherche

La nouvelle campagne de fouille, qui s’est déroulée dans l’abbaye de Cluny durant l’automne 2017, a donné lieu à la découverte exceptionnelle d’un trésor monétaire, comprenant également une bague sigillaire et un petit carré d’or. Il s’agissait de la troisième opération sur le site de l’ancienne infirmerie. Celle-ci, complètement détruite à l’occasion des grands travaux de reconstruction au milieu du xviiie siècle, était essentiellement connue par le plan anonyme daté de 1700 (fig. 1). Fig. 1..

Premières observations sur la découverte d’un trésor dans l’abbaye de Cluny (Saône-et-Loire)

Depuis 2014, un nouveau programme de fouille dans l’ancienne abbaye de Cluny fait suite aux opérations archéologiques réalisées entre 2011 et 2013 en collaboration avec Christian Sapin et le CEM (BAUD, FLAMMIN, 2017). La zone impactée se situe dans les jardins, à l’est des bâtiments conventuels reconstruits au XVIIIe siècle à l’emplacement de l’ancienne infirmerie. Le premier programme archéologique s’articulait autour de la demeure aristocratique carolingienne et de la chapelle mariale. Dans..

Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm.

IMPORTANCE: Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. OBJECTIVE: Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. MATERIALS AND METHODS: The study included 412 infants born at 23-28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. RESULTS: After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). CONCLUSIONS: Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities

L'échafaudage dans le chantier médiéval

Pour un professionnel qui taille la pierre depuis près de quarante ans, comment ne pas être reconnaissant à ceux qui, professeurs ou archéologues, recherchent avec tant de conviction la mémoire des techniques de la construction médiévale, ces techniques presque oubliées depuis l’abandon total de la construction en pierre. Nous avons de la peine à imaginer ces époques, car nous n’avons plus sous les yeux ni les chantiers, ni l’habileté des hommes de métier. De cette industrie de la pierre, la ..

Lack of Renal 11 Beta-Hydroxysteroid Dehydrogenase Type 2 at Birth, a Targeted Temporal Window for Neonatal Glucocorticoid Action in Human and Mice

International audienceBackground Glucocorticoid hormones play a major role in fetal organ maturation. Yet, excessive glucocorticoid exposure in utero can result in a variety of detrimental effects, such as growth retardation and increased susceptibility to the development of hypertension. To protect the fetus, maternal glucocorticoids are metabolized into inactive compounds by placental 11beta-hydroxysteroid dehydrogenase type2 (11βHSD2). This enzyme is also expressed in the kidney, where it prevents illicit occupation of the mineralocorticoid receptor by glucocorticoids. We investigated the role of renal 11βHSD2 in the control of neonatal glucocorticoid metabolism in the human and mouse. Methods Cortisol (F) and cortisone (E) concentrations were measured in maternal plasma, umbilical cord blood and human newborn urine using HPLC. 11βHSD2 activity was indirectly assessed by comparing the F/E ratio between maternal and neonatal plasma (placental activity) and between plasma and urine in newborns (renal activity). Direct measurement of renal 11βHSD2 activity was subsequently evaluated in mice at various developmental stages. Renal 11βHSD2 mRNA and protein expression were analyzed by quantitative RT-PCR and immunohistochemistry during the perinatal period in both species. Results We demonstrate that, at variance with placental 11βHSD2 activity, renal 11βHSD2 activity is weak in newborn human and mouse and correlates with low renal mRNA levels and absence of detectable 11βHSD2 protein. Conclusions We provide evidence for a weak or absent expression of neonatal renal 11βHSD2 that is conserved among species. This temporal and tissue-specific 11βHSD2 expression could represent a physiological window for glucocorticoid action yet may constitute an important predictive factor for adverse outcomes of glucocorticoid excess through fetal programming

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria