Simultaneous analysis of distinct Omics data sets with integration of biological knowledge: Multiple Factor Analysis approach

<p>Abstract</p> <p>Background</p> <p>Genomic analysis will greatly benefit from considering in a global way various sources of molecular data with the related biological knowledge. It is thus of great importance to provide useful integrative approaches dedicated to ease the interpretation of microarray data.</p> <p>Results</p> <p>Here, we introduce a data-mining approach, Multiple Factor Analysis (MFA), to combine multiple data sets and to add formalized knowledge. MFA is used to jointly analyse the structure emerging from genomic and transcriptomic data sets. The common structures are underlined and graphical outputs are provided such that biological meaning becomes easily retrievable. Gene Ontology terms are used to build gene modules that are superimposed on the experimentally interpreted plots. Functional interpretations are then supported by a step-by-step sequence of graphical representations.</p> <p>Conclusion</p> <p>When applied to genomic and transcriptomic data and associated Gene Ontology annotations, our method prioritize the biological processes linked to the experimental settings. Furthermore, it reduces the time and effort to analyze large amounts of 'Omics' data.</p

Specialized lexicography by means of a conceptual data base: establishing the format for a multilingual marine dictionary

Colloque avec actes et comité de lecture. internationale.International audienceThe Hydrographic Dictionary published by the International Hydrographic Bureau (Monaco) was computerized as part of the European research project Dhydro. The aim of the project was to develop a multilingual electronic dictionary with an interactive editorial infrastructure based on the new information technologies. This paper will firstly provide a summary of the analysis that has resulted in the hitherto followed lexicographical approach being abadoned in favour of a monosemic perspective more suited for the management of a large number of source and target languages. This will be followed by a detailed description of the strategy that has enabled the tagging of the surface structure of each monolingual volume of the dictionary in accordance with the prescriptions of the Text Encoding Initiative, and the subsequent merging of all data in one single multilingual data base which conforms to the ISO 12 200 standard on the exchange of terminological data. Finally, the authors will show how XML records resulting from the retroconversion process will enable the reproduction of numerous variants of the dictionary thanks to the use of stylesheets (XSL Transformations)

Le projet européen DHYDRO : la normalisation à l'épreuve d'un forum terminologique

Colloque avec actes et comité de lecture.The paper will focus on the conceptual and technical design of a terminological forum developed in the context of the European MLIS­DHYDRO project.The aim of this project is to provide an integrated environment giving on-line access to a multilingual terminological database. This database corresponds to the computerisation of the existing Hydrographic Dictionary (HD) which has so far been published in three languages (English, French and Spanish) and is under development for a few additional languages, in particular German and Japanese. The set of functionalities considered for this forum are the following: - on-line and/or off-line editing of the different multilingual records in each language by a certified user; - coordination of the editorial work through a discussion forum; - central validation of a given entry by a co-ordinating supervisor; - on-line access to a larger public through standard web browsers. This is achieved thanks to a Java applet allowing the Internet users to build complex queries on the HD database; - publication of several by-products such as bilingual terminological lists, multicolumn polysemic dictionaries, in various paper and electronic formats (rtf, word, html...); Such a complex project could only be tackled by relying upon some kind of standard representation of the terminological data which would permit us to define a central core representation independently of any specific target format (like html for instance). Furthermore, we aim at identifying a set of generic modules which makes the system architecture flexible enough to be applied in the framework of other terminological projects. These two goals led us first to experiment on the applicability of the MARTIF proposal as defined within TC37 of ISO and second to implement a software platform fully based on the use of XML as the central exchange data format between modules. The paper will first provide arguments supporting our choices. It will also report the strategy used to convert the three monolingual polysemic dictionaries into a unique multilingual terminological database

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

<p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p

Intérêts d'une nouvelle méthode radiologique dans la prise en charge thérapeutique des descellements aseptiques fémoraux des arthroplasties totales de hanche (à propos de 180 cas)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude des mécanismes régulateurs de la réponse immunitaire innée de Drosophila melanogaster

La défense des animaux contre les infections repose sur une réponse immunitaire innée, immédiate, complétée par une réponse adaptative chez les vertébrés. L activation des facteurs NF- B est le principal signe de la réponse immunitaire innée dans tout le règne animal. La plupart des éléments impliqués au niveau des voies d activations des facteurs NF- B sont hautement conservés depuis les insectes jusqu à l homme. Cette conservation évolutive ainsi qu un grand nombre d outils disponibles et en particulier la génétique font de la Drosophile un excellent modèle pour l analyse de la réponse immunitaire innée. Mon projet a consisté en la caractérisation des mécanismes régulant la réponse immunitaire innée chez Drosophila melanogaster. Pour cela ma thèse a été divisée en trois axes, traitant chacun un aspect différent de la réponse immunitaire innée. Nous avons tout d abord analysé les mécanismes moléculaires mis à l oeuvre dans la voie de transduction du signal de la voie Imd, similaire à celle en aval du récepteur au TNFa. A cette occasion un site de clivage entre les résidus 30 et 31 de la protéine Imd a été mis en évidence à la fois in vitro et in vivo. Le clivage d Imd en cette position permet la liaison de DIAP2 et la polyubiquitination de la protéine Imd pour activer en aval les autres composants de la voie puis in fine la transcription des PAM. Dans un second temps, nous avons montré que le mutant Methuselah, dont l espérance de vie est supérieure de 35% aux drosophiles sauvages, résiste beaucoup mieux aux infections que des mouches sauvages. Afin de mieux comprendre les raisons de cette résistance, nous avons analysé l influence de cette mutation sur l activation de la réponse immunitaire. De manière surprenante, nous avons observé un sauvetage de la mutation Imd. Il semblerait que celui ci soit dû au rétablissement de l expression des PAM après infection. Et pour finir, toujours dans le registre de la régulation de l immunité innée chez la drosophile, nous avons étudié le rôle des voies impliqués dans la biosynthèse des petits ARN non codant. Il a été établi que leur absence affecte la survie des Drosophiles infectées par voie naturelle, principalement au niveau de l intestin. C est la première fois que l on attribue une fonction à une classe de petits ARN non codant endogènes, dits endo-siARN.The innate immune system constitutes the first line of defence against pathogens and is preserved in many animal phyla. NF- B factor activation represents a hallmark of innate immune responses among the animal kingdom. Most of the components involved in the activation of NF- B are highly conserved between insects and vertebrates. Conservation and the number of genetic tools available make the fruit fly Drosophila melanogaster an excellent model to study innate immune responses. My project focused on the characterization of mechanisms that are implicated in regulating the innate immune response in Drosophila melanogaster. I divided my thesis manuscript into three parts: First, we analyzed the molecular mechanisms involved in the IMD signal transduction pathway. We showed both in vitro and in vivo, that the cleavage side of the Imd protein is between the amino acid residues 30 and 31. This cleavage allows the binding of DIAP2 and polyubiquitination of the Imd protein in order to activate other downstream components of the Imd pathway resulting in the transcription of antimicrobial peptides. Second, we showed that the mutant Methuselah is more resistant to infections with Gramnegative bacteria compared to wild type flies. To characterize this phenotype in more detail, we analyzed the influence of this mutation on the activation of the innate immune response. Interestingly, the methuselah null mutant was able to restore the functionality of the IMD pathway. Finally, we studied the role of small non-coding RNA upon bacterial infections. We showed that the absence of functional non-coding RNA pathway affects the survival of the fly upon bacterial feeding. To the best of our knowledge, we provide for the first time evidence that a class of small endogenous non-coding RNA or endo-siRNAs may have a role in fighting bacterial infections.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Secondary structure conformation of hydroperoxide lyase from green bell pepper, cloned in Yarrowia lipolytica, and its activity in selected media

International audienceCircular dichroism (CD) spectroscopy of secondary structure conformation of the purified green bell pepper hydroperoxide lyase (HPL), cloned in the yeast Yarrowia lipolytica, was investigated. The CD spectra of HPL in iso-octane, obtained at 60 °C, in the presence of the reducing agent dithiothreitol showed dramatic increase in α-helix content. The enzyme conformation remained unchanged over a range of pH values of 5.0–7.0. Using 13-hydroperoxide of linoleic acid (13-HPOD) as substrate, the biocatalysis of HPL in organic solvent media, including chloroform, dichloromethane, hexane, iso-octane, octane and toluene, was investigated. The results indicated an increase in HPL activity in the biphasic hexane medium

Predicted secondary structure of hydroperoxide lyase from green bell pepper cloned in the yeast Yarrowia lipolytica

International audienceFatty acid hydroperoxide lyase (HPL) is a member of the cytochrome P450 family acting on fatty acid hydroperoxides in many organisms. The active green bell pepper HPL, cloned and expressed in the yeast Yarrowia lipolytica, was purified by immobilized metal-ion affinity chromatography (IMAC) in the presence of 2% of Triton X-100R. The secondary structure prediction by bioinformatics servers of HPL was realized by ANTHEPROT software, using the GOR, DPM and Predator methods. The theoretical results which are average values obtained from three different calculation methods showed 33% α-helix, 18% β-sheet, 7% turn and 42% coil. On the other hand, the secondary structure approach of the purified active HPL (specific activity of 2.94 U/mg protein) was realized by differential scanning calorimetry (DSC) and circular dichroism (CD) spectroscopy, and showed 13% α-helix, 29% β-sheet, 5% turn and 53% random coil

Les unités paysagères : une méthode et un outil pour spatialiser des risques de pollution des eaux superficielles. Applications concrètes a un sous bassin de la Zone Atelier Moselle (Z.A.M)

L'évolution de l'organisation des paysages ruraux et des parcellaires agricoles est étroitement reliée, solidaire de la préservation de la ressource en eau. Aujourd'hui, de nombreuses démarches visent à étudier les liens et synergies reliant les paysages et agrosystèmes et leurs hydrosystèmes traversés, afin de répondre aux nouvelles attentes qualitatives qui concernent des territoires, où il est ambitionné de mettre en place des modèles d'organisation des activités rurales vivables, viables, équitables et transmissibles. La démonstration tente de montrer les répercussions, appréciées à des échelles emboîtées, des assolements sur la qualité des eaux. Par la suite, cet exposé de recherche analyse les stratégies agricoles qui façonnent le paysage par la méthode des U.A.P. (unité agro-physionomiques), reflets des organisations de territoire à un instant donné. Les U.A.P. sont une méthode de spatialisation qui s'adapte à la géographie des risques qui concernent les ressources en eau. C'est un outil d'évaluation, de suivi de l'hydrosystème, objet essentiel pour concevoir des aménagements cohérents, paisibles, partagés, acceptés par tous.Changes in land use and landscape are linked to water resources preservation. Number of studies pointed out the linkage between landscape, farming systems and hydrosystems. The aim is to develop sustainable activities taking into account new objectives of rural stakeholders. We focus our work on land use impacts on water quality at different scales : field, landscape units, watershed. The landscape units (U.A.P.) are studied as a result of former activities. On the other hand, U.A.P. are modelized as a factor of water resources quality. U.A.P. is identified as a tool of territory evaluation to design new landscape managements

Production, caractérisation et étude structurale de l Hydroperoxyde lyase du poivron vert exprimée par la levure Yarrowia lipolytica (optimisation de la production d hexanal)

L hydroperoxyde lyase du poivron vert exprimée par la levure Y. lipolytica permet la transformation des acides gras poly-insaturés en aldéhydes et alcools, famille d arômes à notes vertes . Cette enzyme a été purifiée puis caractérisée : elle génère un radical alkyl ou alkoxyl qui semble se lier à l enzyme pendant la catalyse et qui altère le site actif de l enzyme, la rendant inactive. L activité de l enzyme augmente significativement (42%) à potentiel d oxydo-réduction bas en présence de dithiotréitol. La structure secondaire de l enzyme a été déterminée ; elle est composée de 13% d hélices a et 29% de feuillets b et la perte d hélices a conduit à une perte de l activité enzymatique. Un plan d expérience factoriel a permis de déterminer les facteurs influant sur la production d hexanal : hydroperoxydes d acides gras (100 mM) et dithiotréitol (100 mM).The green bell pepper Hydroperoxide lyase enzyme expressed by the yeast Yarrowia lipolytica allows the hydroperoxide fatty acids transformation to aldehydes and alcohols. In this word, the purification and characterization of enzyme were realized: the participation of radicals during the catalysis of hydroperoxide lyase was founded and it has been observed that the radical species might be an alkyl or alkoxyl radical linked to the enzyme, which affected the active site of the enzyme losing his activity. The enzymatic activity enhanced significantly (42%) at low oxido-reduction potential. The secondary structure of enzyme is composed by 13% a-helix and 29% b-sheet. Moreover the loss of a-helix decreased the activity enzymatic. A factorial plan was applied to determine the factors influent on the production of hexanal: fatty acids hydroperoxides (100 mM) and dithiothreitol (100 mM).DIJON-BU Sciences Economie (212312102) / SudocSudocFranceF