L’occupation d’un micro-terroir de la Protohistoire à l’Antiquité : le site d’Hérouvillette « Les Pérelles » (Calvados)

La fouille archéologique préventive effectuée sur la commune d’Hérouvillette a mis en évidence un ensemble de vestiges permettant la restitution d’une occupation espacée sur plus de deux mille ans. Les premières installations remontent au Bronze ancien, accompagnant probablement la fondation des premiers chemins et systèmes parcellaires du IIe millénaire. Ces investissements sont matérialisés par la création d’une enceinte fossoyée de plan elliptique, pour laquelle une vocation domestique est supposée. Après un long hiatus, la deuxième étape d’aménagement s’inscrit dans la vague de création d’enclos d’habitats de la fin du vie et du ve siècle av. J.-C. Il s’agit d’un établissement agricole à double ceinture fossoyée qui s’insère dans un aménagement parcellaire environnant. Après l’abandon de cet enclos au tout début du ive siècle av. J.-C., l’occupation perdure dans le secteur, matérialisée par la création d’un chemin conduisant vers une parcelle à vocation indéterminée et datée de La Tène moyenne/finale. L’occupation suivante se place dans une fourchette chronologique de la fin du ier au début du iiie siècle apr. J.-C. Au sein d’un enclos s’organisent divers vestiges domestiques, permettant d’interpréter cette occupation comme un lieu d’habitat, probablement celui d’une petite exploitation familiale.The preventive archaeological excavation conducted in Hérouvillette (Calvados, France) has brought to light features more than 2000 years old. The first installations go back to the Early Bronze Age with the foundation of the first track ways and field systems of the 2nd millennium BC. An elliptical enclosure, probably a settlement was also discovered. The second phase of the site dates of the end of the 6th and the 5th century BC and includes a farming settlement with a double enclosure located within the field system. After the abandonment of this enclosure at the very beginning of the 6th century BC, we see the creation of a track way leading to a field system dated to the late La Tène period, the function of which has not yet been established. The following occupation is dated from the end of the 1st to the beginning of the 3th century AD. The probable enclosed settlement includes various domestic features.Die archäologische Ausgrabung in der Gemeinde Hérouvillette (Calvados, Frankreich) hat es gestattet, Siedlungsspuren freizulegen, die über 2000 Jahre Siedlungsgeschichte in diesem Gebiet dokumentieren. Die ersten Besiedlungsspuren gehören der älteren Bronzezeit an und begleiten vermutlich erste Weganlagen und Flureinteilungen, die dem 2. Jahrtausend vor Chr. angehören. Zu dieser ersten Besiedlungsphase gehört eine erste Wall-Graben-Anlage von elliptischen Grundriss, für die eine Interpretation als Gehöftanlage angenommen werden muss. Nach einer langen Siedlungsunterbrechung kommt es zu einer zweiten Siedlungsphase, die sich in den Rahmen der Anlage von zahlreichen umhegten Gehöftanlagen stellen lässt, die am Ende des 6. und im 5. Jh. v. Chr. entstehen. Es handelt sich um ein landwirtschaftliches Gehöft mit doppelter Grabeneinhegung, das sich in die umgebende Flurparzellierung einfügt. Nach der Aufgabe dieses umhegten Gehöftes unmittelbar am Beginn des 4. Jh. v. Chr. zeigt die Anlage einer Wegeverbindung, die zu einem Flurstück mit unbestimmbarer Nutzung führte und die in die Mittel- bzw. Spätlaténezeit gestellt werden kann, dass die Besiedlung dieses Gebietes weiterhin fortbesteht. Die folgende Besiedlung kann in einen Zeitabschnitt zwischen dem Ende des 1. Jh. und dem 3. Jh. n. Chr. gestellt werden. Innerhalb einer Grabenanlage wurden verschiedene Besiedlungsspuren nachgewiesen, die es gestatten, diese archäologischen Befunde als Siedlung anzusprechen. Es handelt sich vermutlich um ein kleines landwirtschaftliches Gehöft, das von einer Familie bewirtschaftet wurde.La excavación arqueológica preventiva llevada a cabo en el municipio de Hérouvillette destacó un conjunto de restos que permitieron la restitución de una ocupación extendida a lo largo de más de dos mil años. Las primeras instalaciones, fechadas en la Edad del Bronce antiguo, acompañaron probablemente a la fundación de los primeros caminos y sistemas de parcelas del segundo milenio. Estas inversiones se materializan mediante la creación de un recinto de plano elíptico protegido por fosos por lo cual se supone una función doméstica. Después de un largo paréntesis, la segunda etapa del desarrollo se inscribe en la ola de creación de recintos de hábitats que ocurrió desde los finales del siglo VI hasta el siglo V antes de Cristo. Se trata de un establecimiento agrícola con doble cintura de hoyos que se ajusta al desarrollo de la trama de los alrededores. Después del abandono de este recinto a principios del siglo IV antes de Cristo, la ocupación persiste en la área, materializada por la creación de un camino que conduce hacia una parcela de función indeterminada y fechada de La Tène B / La Tène C. La ocupación siguiente se inscribe en un marco cronológico que va de finales del primero siglo a los principios del tercer siglo después de Cristo. Dentro de un recinto, se organizan varios restos domésticos, que permiten interpretar la ocupación como un lugar de hábitat, probablemente el marco de vida de una pequeña granja familiar

Sox2 Is Required for Maintenance and Differentiation of Bronchiolar Clara, Ciliated, and Goblet Cells

The bronchioles of the murine lung are lined by a simple columnar epithelium composed of ciliated, Clara, and goblet cells that together mediate barrier function, mucociliary clearance and innate host defense, vital for pulmonary homeostasis. In the present work, we demonstrate that expression of Sox2 in Clara cells is required for the differentiation of ciliated, Clara, and goblet cells that line the bronchioles of the postnatal lung. The gene was selectively deleted in Clara cells utilizing Scgb1a1-Cre, causing the progressive loss of Sox2 in the bronchioles during perinatal and postnatal development. The rate of bronchiolar cell proliferation was decreased and associated with the formation of an undifferentiated, cuboidal-squamous epithelium lacking the expression of markers of Clara cells (Scgb1a1), ciliated cells (FoxJ1 and α-tubulin), and goblet cells (Spdef and Muc5AC). By adulthood, bronchiolar cell numbers were decreased and Sox2 was absent in extensive regions of the bronchiolar epithelium, at which time residual Sox2 expression was primarily restricted to selective niches of CGRP staining neuroepithelial cells. Allergen-induced goblet cell differentiation and mucus production was absent in the respiratory epithelium lacking Sox2. In vitro, Sox2 activated promoter-luciferase reporter constructs for differentiation markers characteristic of Clara, ciliated, and goblet cells, Scgb1a1, FoxJ1, and Agr2, respectively. Sox2 physically interacted with Smad3 and inhibited TGF-β1/Smad3-mediated transcriptional activity in vitro, a pathway that negatively regulates proliferation. Sox2 is required for proliferation and differentiation of Clara cells that serve as the progenitor cells from which Clara, ciliated, and goblet cells are derived

A complete collection of single-gene deletion mutants of Acinetobacter baylyi ADP1

We have constructed a collection of single-gene deletion mutants for all dispensable genes of the soil bacterium Acinetobacter baylyi ADP1. A total of 2594 deletion mutants were obtained, whereas 499 (16%) were not, and are therefore candidate essential genes for life on minimal medium. This essentiality data set is 88% consistent with the Escherichia coli data set inferred from the Keio mutant collection profiled for growth on minimal medium, while 80% of the orthologous genes described as essential in Pseudomonas aeruginosa are also essential in ADP1. Several strategies were undertaken to investigate ADP1 metabolism by (1) searching for discrepancies between our essentiality data and current metabolic knowledge, (2) comparing this essentiality data set to those from other organisms, (3) systematic phenotyping of the mutant collection on a variety of carbon sources (quinate, 2-3 butanediol, glucose, etc.). This collection provides a new resource for the study of gene function by forward and reverse genetic approaches and constitutes a robust experimental data source for systems biology approaches

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder

Models Contribution to the Understanding of Sarcoidosis Pathogenesis: “Are There Good Models of Sarcoidosis?”

Sarcoidosis is a systemic, granulomatous, and noninfectious disease of unknown etiology. The clinical heterogeneity of the disease (targeted tissue(s), course of the disease, and therapy response) supports the idea that a multiplicity of trigger antigens may be involved. The pathogenesis of sarcoidosis is not yet completely understood, although in recent years, considerable efforts were put to develop novel experimental research models of sarcoidosis. In particular, sarcoidosis patient cells were used within in vitro 3D models to study their characteristics compared to control patients. Likewise, a series of transgenic mouse models were developed to highlight the role of particular signaling pathways in granuloma formation and persistence. The purpose of this review is to put in perspective the contributions of the most recent models in the understanding of sarcoidosis

Some side-effects of change

Avalaible on: http://www.crc.ensmp.fr/~denis.besnard/Publications/Sanseverino-Besnard--Side-effects-change-2010.pdfInternational audienc

La teneur en lipides du régime affecte les capacités d'absorption intestinale et la triglycéridémie post-prandiale (contribution du récepteur nucléaire PPARb ?)

L absorption intestinale des acides gras à longue chaines (AGLC) est très efficace. En revanche, on ignore si ce phénomène est inné ou adaptatif. C est pourquoi, des souris ont été soumises à un régime hyperlipidique (40% m/m) pendant 21 jours. Nous avons constaté une induction du captage des AGLC, de l activité proliférative et de la masse relative de la muqueuse, de l expression des gènes impliqués dans les différentes étapes du processus d absorption intestinale des AGLC. Ce phénomène est adaptatif puisque ces régulations retournent aux valeurs des témoins lorsque les souris sont renourries avec un régime normolipidique. Ces modifications s accompagnent d une augmentation de la clairance plasmatique des lipoprotéines riches en triglycérides. Le Peroxisome Proliferator-Activated ReceptorB (PPARB) pourrait être à l origine de cette adaptation intestinale. Les données obtenues ont montré que la sur-expression intestinale de PPARB engendre une adaptation moins efficace des capacités d absorption.It is well known that intestinal fat absorption is efficient. However, we don t if the high triglycerides bioavailability of gut is attributable to inborn properties or to acquired properties. To answer this question, mice were subjected to a high-fat diet (40%, w/w) during 21 days. We have shown that high-fat induces intestinal LCFA uptake, intestinal mitotic index which leads to an increase of intestinal relative mass, expression of genes involved in fatty uptake, trafficking and lipoprotein synthesis. These changes were lipid-mediated, in that they were fully abolished in mice refed the control diet. Moreover, these changes induces a higher efficiency of triglycerides clearance in blood. The molecular mechanism at the origin of this intestinal adaptation could be the nuclear receptor, Peroxisome Proliferator-Activated Receptor B PPARB). Our data have shown that the intestinal overexpression of PPARB led to a low fat-mediated adaptation.DIJON-BU Sciences Economie (212312102) / SudocSudocFranceF

Absorption intestinale des acides gras: faits et incertitudes

VIIe Symposium nutrition – « L'intervention nutritionnelle » : de la prévention à la thérapeutique – Brest, 8 novembre 2006International audienceOver the two last decades, isolation and characterization of proteins involved in transport and metabolic fate of long-chain fatty acids have provided new insights on the molecular basis of fat absorption. This systematic cloning period has been followed by the functional genomics time which led to surprises. Indeed, disruption of several genes, thought to be crucial for long-chain fatty acid absorption, did not lead to clear phenotypes. This observation raises the question about the real physiological role of several lipid-binding proteins and enzymes found in the enterocyte. This mini-review assesses the present knowledge concerning the main steps of intestinal fat absorption: the cellular uptake and trafficking of long-chain fatty acids and the lipoprotein synthesis.Les deux dernières décennies ont été marquées par une accumulation de connaissances nouvelles concernant les aspects moléculaires de l'absorption des lipides alimentaires avec l'isolement et la caractérisation de protéines potentiellement impliquées dans le transport et le devenir entérocytaires des acides gras à longue chaîne. À cette période de clonage systématique a succédé celle de la génomique fonctionnelle qui s'avère pleine de surprise puisque l'invalidation de nombreux gènes considérés jusqu'alors comme essentiels pour l'absorption intestinale des lipides ne s'accompagne pas d'un phénotype clair. Ce constat amène à reconsidérer le rôle physiologique exercé, notamment, par les nombreux transporteurs de lipides (lipid-binding proteins) et certaines enzymes exprimés au niveau entérocytaire. Cette mini-revue se propose de faire un état des lieux des faits et incertitudes concernant les principales étapes de l'absorption des acides gras, à savoir leur captage et trafic cellulaire et la synthèse des lipoprotéines intestinales