Mehun-sur-Yèvre – Le Château

Date de l'opération : 1989 (FP) ; 1986 (SD) ; 1985 (SD) ; 1984 (SU) Inventeur(s) : Delmarre P ; Bon Philippe En 1984, la fouille a porté sur une fosse de plan rectangulaire (1,70 m x 1,80 m), construite en appareil cyclopéen dont le mur nord-est a servi de fondation au mur de la courtine édifié au XIe s., tandis que le mur nord-ouest a été incorporé à la base du donjon édifié au XIIIe s. Dans un premier temps, cette fosse a pu servir de puits, par l'utilisation d'une source résurgente à fleur..

Is Early Puberty Triggered by Catch-Up Growth Following Undernutrition?

Undernutrition during fetal and postnatal life is still a major problem in many low- and middle-income countries. Even in high-income countries malnutrition may exist in cases of intrauterine growth retardation, as well as in chronic conditions such as anorexia nervosa and inflammatory bowel disease. Children adopted from developing countries are often chronically malnourished. Nutritional rehabilitation, resulting in catch-up growth, is often complicated by influences originating in fetal life as well as during postnatal growth. This may result in hormonal and metabolic changes as well as alterations in pubertal development. The present review focuses on fetal, postnatal and fetal-postnatal undernutrition and subsequent catch-up growth as well as catch-up growth in relation to pubertal development. Catch-up growth in children can be associated with early puberty following fetal or combined fetal-postnatal undernutrition. However, early puberty does not seem to occur following catch-up growth after isolated postnatal undernutrition. Gonadotropins have been reported to be elevated in prepubertal adopted girls as well as during catch-up growth in animals. Even if other factors may contribute, linear catch-up growth seems to be associated with the timing of pubertal development. The mechanisms behind this are still unknown. Future research may elucidate how to carry out nutritional rehabilitation without risk for early pubertal development

The Epigenetic Trans-Silencing Effect in Drosophila Involves Maternally-Transmitted Small RNAs Whose Production Depends on the piRNA Pathway and HP1

BACKGROUND: The study of P transposable element repression in Drosophila melanogaster led to the discovery of the Trans-Silencing Effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin (Telomeric Associated Sequences, "TAS") has the capacity to repress in trans, in the female germline, a homologous P-lacZ transgene located in euchromatin. Phenotypic and genetic analysis have shown that TSE exhibits variegation in ovaries, displays a maternal effect as well as epigenetic transmission through meiosis and involves heterochromatin (including HP1) and RNA silencing. PRINCIPAL FINDINGS: Here, we show that mutations in squash and zucchini, which are involved in the piwi-interacting RNA (piRNA) silencing pathway, strongly affect TSE. In addition, we carried out a molecular analysis of TSE and show that silencing is correlated to the accumulation of lacZ small RNAs in ovaries. Finally, we show that the production of these small RNAs is sensitive to mutations affecting squash and zucchini, as well as to the dose of HP1. CONCLUSIONS AND SIGNIFICANCE: Thus, our results indicate that the TSE represents a bona fide piRNA-based repression. In addition, the sensitivity of TSE to HP1 dose suggests that in Drosophila, as previously shown in Schizosaccharomyces pombe, a RNA silencing pathway can depend on heterochromatin components

Telomeric Trans-Silencing in Drosophila melanogaster: Tissue Specificity, Development and Functional Interactions between Non-Homologous Telomeres

BACKGROUND: The study of P element repression in Drosophila melanogaster led to the discovery of the telomeric Trans-Silencing Effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin (Telomeric Associated Sequences, "TAS") has the capacity to repress in trans, in the female germline, a homologous P-lacZ transgene located in euchromatin. TSE can show variegation in ovaries, displays a maternal effect as well as an epigenetic transmission through meiosis and involves heterochromatin and RNA silencing pathways. PRINCIPAL FINDINGS: Here, we analyze phenotypic and genetic properties of TSE. We report that TSE does not occur in the soma at the adult stage, but appears restricted to the female germline. It is detectable during development at the third instar larvae where it presents the same tissue specificity and maternal effect as in adults. Transgenes located in TAS at the telomeres of the main chromosomes can be silencers which in each case show the maternal effect. Silencers located at non-homologous telomeres functionally interact since they stimulate each other via the maternally-transmitted component. All germinally-expressed euchromatic transgenes tested, located on all major chromosomes, were found to be repressed by a telomeric silencer: thus we detected no TSE escaper. The presence of the euchromatic target transgene is not necessary to establish the maternal inheritance of TSE, responsible for its epigenetic behavior. A single telomeric silencer locus can simultaneously repress two P-lacZ targets located on different chromosomal arms. CONCLUSIONS AND SIGNIFICANCE: Therefore TSE appears to be a widespread phenomenon which can involve different telomeres and work across the genome. It can explain the P cytotype establishment by telomeric P elements in natural Drosophila populations

Myelinolyse centro et extrapontine et syndrome des buveurs de bière (à propos d'un cas à l'hopital de Laon en 2002)

La myélinolyse centro et extrapontine ou syndrome de démyélinisation osmotique (ODS) est une maladie rare découverte en 1959 par Adams,Mancall et Victor chez quatre de leurs patients éthyliques chroniques consistant en des foyers de démyélinisation bien limités et symétriques situés dans la partie centrale du pont dans des régions qui présentent une forte intrication de substance blanche et grise richement vascularisée . Le facteur causal clef, la correction de l hyponatrémie, fut suggéré par Tomlinson en 1976 puis démontré de manière convaincante chez l animal par Norenberg-Paapendick (rat) et Karp-Laureno (chien) en 1982 . Il s avéra par la suite que la transition entre deux états osmolaires différents constitue la cause de ces lésions .De la l évolution du concept de CPM/EPM vers celui de syndrome de démyélinisation osmotique (ODS) . En effet cette transition est à l origine d une déshydratation cellulaire et d une peine métabolique auxquelles les cellules gliales, très sensibles aux contraintes énergétiques sont incapables de faire face et, ce particulièrement dans des conditions comme, entre autres l alcoolisme chronique ou elles ont subi préalablement un stress métabolique chronique . Tel fut le cas de notre patient qui fut hospitalisé d urgence face à des troubles de la vigilance ( état de confusion ) imputables à une encéphalopathie métabolique métabolique liée à l hyponatrémie, à la suite d un syndrome de potomanie à la bière sans alcool, une cause connue mais peu fréquente d hyponatrémie sur ce terrain .L évolution chez ce patient après correction des désordres hydroélectrolytiques se fit vers le syndrome de démyélinisation osmotique . Le cas dont nous discuterons est intéressant à plusieurs titres .Il est tout à fait révélateur de la difficulté de poser le diagnostic en milieu de réanimation et de l intérêt et des limites des examens de neuro-imagerie conventionnelle pour le confirmer .Il nous permet d évoquer la discussion ayant cours entre les auteurs quant à la manière de corriger l encéphalopathie hyponatrémique symptomatique .A central pontine and extrapontine myelinolysis is a rare desease discovered in 1959 by Adams, Victor and Mancall in four of their alcoholic patients consisting in well delimited and symetrical foci of demyelination confined in the center of the basis pontis but also out of the pontis in a region of maximal admixture of grey and white matter elements. The triggered key factor, the hyponatremia's correction was suggested by Tomlinson in 1976 then convincingley demonstrated in animals by Norenberg-Papendick (in rats) and Karp-Laureno (in dogs) in 1982. It turned out, later, that the transition between two different osmolar states are responsible for these brain damages. Hence, the evolution of the CPM/EPM concept towards the osmotic demyelination syndrome (ODS) one. In fact this transition is the source of cell's dehydration and of a metabolic penalty for which glial cells are unable to cope up and this, particularly in conditions like, among others, chronic alcoholism although they already suffured from a chronic metabolic stress. So it was for our patient who was rushed to hospital in a state of mental confusion due to an hyponatrémia linked metabolic encephalopathy, following a alcohol free beer potomania syndrom, a well know but un common cause of hyponatremia in this context. The evolution in this patient after the electrolytic disturbance correction led to the osmotic demyelination syndrome (ODS). The case we will talk about is interesting in many ways. It's really telling of the difficulty to diagnose in the intensive care unit and of the interest of imits of the neuroradiologic examination early in the clinical course to confirm it. It allows us the possibility to refer to the current discussion between authors concerning the way to correct hyponatremia.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Les tumeurs intra-canalaires mucineuses et papillaires du pancréas (intérêt de la mini sonde d'échoendoscopie de hautes fréquences dans le diagnostic de lésions débutantes à travers une observation clinique et revue de la littérature)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Toxicité hépatique et traitement par azathioprine au cours des maladies inflammatoires chroniques intestinales

Introduction : L'azathioprine (AZA) et son métabolite, la 6-mercaptopurine (6-MP), sont des immunosuppresseurs utilisés chez les patients atteints de maladie inflammatoire chronique intestinale, corticodépendants ou corticorésistants. Ces analogues des bases puriques sont responsables d'effets indésirables chez environ 15% des patients, d'origine allergique ou non. La toxicité hépatique est décrite dans 0,3 à 5% des cas. La 6-thioguanine (6-TG), un métabolite de l'azathioprine, offre une alternative thérapeutique efficace chez les patients résistants ou intolérants à l'AZA. Cependant, des études récentes ont mis en évidence une hépatotoxité majeure de la 6-TG, en particulier à type d'hyperplasie nodulaire régénérative. But : Le but de notre étude était de déterminer si des doses croissantes d'AZA, conduisant à des taux élevé de 6-thioguanine nucléotides (6-TGN), induisaient des lésions hépatiques. Méthodes : Des biopsies hépatiques ont été réalisées chez 25 patients atteints de maladie inflammatoire chronique intestinale : 14 patients (groupe A) recevaient des doses croissantes d'azathioprine >= 3 mg/kg/j pendant une durée de 6 mois à 2 ans, afin d'obtenir une rémission clinique. Les dosages des métabolites de l'AZA, 6-TGN et 6-méthylmercaptopurine (6-MMP) ont été réalisés au moment de la biopsie dans le groupe A. Un groupe témoin de 11 patients (groupe B) sans traitement immunosupppresseur a eu une biopsie hépatique, soit en raison d'anomalie du bilan biologique hépatique, soit en peropératoire. Résultats : Aucun cas d'hyperplasie nodulaire régénérative n'a été trouvé après coloration spécifique à la réticuline, malgré les taux élevés de 6-TGN. Une fibrose portale minime était présente dans les 2 groupes sans différence significative. Dans le groupe A, les dilatations sinusoïdales et les manifestations extra-digestives étaient significativement moins fréquentes chez les patients répondeurs que chez les non répondeurs. Les taux de 6-TGN et de 6-MMP étaient significativement plus élevés dans le groupe des patients répondeurs. Conclusion : Ces résultats suggèrent que l'azathioprine à posologie élevée n'est pas responsable de lésions hépatiques sévères telle que l'hyperplasie nodulaire régénérative. Les lésions hépatiques trouvées, fibrose et dilatations sinusoïdales, paraissent plus liées à la maladie inflammatoire chronique intestinale qu'au traitement par azathioprine.AMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Deciphering single yeast wall elasticity with flat microlever compression.

Single cell organisms such as yeast can survive in very different environments thanks to a polysaccharide wall that reinforces their extracellular membrane. This wall is not a static structure since it is expected to remodel dynamically depending on the stage of growth, division cycle, environmental osmotic pressure and aging. Probing the mechanics of these organisms is therefore of strong interest, however it implies some more difficulties as compared to other mammal cells, in particular because of their small size (radius of a few microns) and their lack of an adhesion machinery. Using flat cantilevers, we perform compression experiments of single yeast cells (S. cerevisiae) on poly-L-lysine coated glass plates, in the limit of small deformation with an atomic force microscope (AFM). We compare the mechanical response of single yeast cells grown in different culture media, with different carbon sources to address different energetic metabolisms and at different stages of their proliferation (initial, intermediary and final stationary stages). We develop a multi-scale nonlinear analysis of AFM force-displacement curves that provides evidences for non stationary scaling laws. We propose to model this phenomena based on a multilayered elastic system, each layer following a different scaling law.Analyse et modélisation temps fréquence de la rhéologie des systèmes vivant

Two-layer elastic models for single-yeast compressibility with flat microlevers.

Unicellular organisms such as yeast can survive in very different environments thanks to a polysaccharide wall that reinforces their extracellular membrane. This wall is not a static structure, as it is expected to be dynamically remodeled according to growth stage, division cycle, environmental osmotic pressure and ageing. It is therefore of great interest to study the mechanics of these organisms, but they are more difficult to study than other mammalian cells, in particular because of their small size (radius of a few microns) and their lack of an adhesion machinery. Using flat cantilevers, we perform compression experiments on single yeast cells (S. cerevisiae) on poly-L-lysine-coated grooved glass plates, in the limit of small deformation using an atomic force microscope (AFM). Thanks to a careful decomposition of force-displacement curves, we extract local scaling exponents that highlight the non-stationary characteristic of the yeast behavior upon compression. Our multi-scale nonlinear analysis of the AFM force-displacement curves provides evidence for non-stationary scaling laws. We propose to model these phenomena based on a two-component elastic system, where each layer follows a different scaling law

Two-layer elastic models for single-yeast compressibility with flat microlevers.

Unicellular organisms such as yeast can survive in very different environments thanks to a polysaccharide wall that reinforces their extracellular membrane. This wall is not a static structure, as it is expected to be dynamically remodeled according to growth stage, division cycle, environmental osmotic pressure and ageing. It is therefore of great interest to study the mechanics of these organisms, but they are more difficult to study than other mammalian cells, in particular because of their small size (radius of a few microns) and their lack of an adhesion machinery. Using flat cantilevers, we perform compression experiments on single yeast cells (S. cerevisiae) on poly-L-lysine-coated grooved glass plates, in the limit of small deformation using an atomic force microscope (AFM). Thanks to a careful decomposition of force-displacement curves, we extract local scaling exponents that highlight the non-stationary characteristic of the yeast behavior upon compression. Our multi-scale nonlinear analysis of the AFM force-displacement curves provides evidence for non-stationary scaling laws. We propose to model these phenomena based on a two-component elastic system, where each layer follows a different scaling law.Analyse et modélisation temps fréquence de la rhéologie des systèmes vivant