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Étude mécaniste des complexes du divisome corynébacterien impliqués dans la séparation cellulaire
No full textChez les bactéries, la division cellulaire est un processus coordonné par un complexe multiprotéique appelé divisome. L'assemblage du divisome s'effectue à partir d'une protéine bactérienne très conservée, FtsZ, un homologue de la tubuline qui polymérise pour former une structure annulaire dynamique, le Z-ring, marquant le futur site de division. Le Z-ring recrute alors de manière séquentielle les protéines structurales et auxiliaires qui constitueront la machinerie de division à même de réorganiser la paroi cellulaire. Ce complexe de protéines transmembranaires coordonne d'une part la synthèse centripète de peptidoglycane (le composant majeur de la paroi cellulaire des bactéries) par les penicillin-binding proteins, et d'autre part la dégradation périphérique du peptidoglycane par des enzymes autolytiques, pour permettre la séparation de deux cellules filles viables (septation). Malgré un schéma général d'assemblage et de fonctionnement du divisome très conservé, d'importantes spécificités existent au sein des bactéries, vraisemblablement pour accommoder leur richesse caractéristique en termes de morphologies, de modes de croissance, et de compositions de paroi cellulaire. C'est particulièrement vrai chez les Corynebacteriales, un groupe d'actinomycètes incluant d'importants pathogènes comme Mycobacterium tuberculosis et Corynebacterium diphtheriae. Les Corynebacteriales présentent un mode de croissance polaire et une paroi à l'organisation complexe, entourée d'une couche d'acides mycoliques. La septation se fait chez les Corynebacteriales via un processus de rupture rapide et brutale des parois des deux cellules filles appelé V-snapping. L'objectif de cette thèse est la caractérisation structurale et fonctionnelle du divisome chez les Corynebacteriales. Nous nous sommes ici concentrés sur RipA, une enzyme clef de la séparation cellulaire chez les Corynebacteriales. RipA est une autolysine qui catalyse le clivage des liaisons peptidiques transversales au sein du peptidoglycane, et qui a été montrée comme importante dans les mécanismes de virulence de M. tuberculosis et C. diphtheriae. Nous avons caractérisé la structure complète de l'homologue de RipA chez Corynebacterium glutamicum, qui montre l'enzyme dans une conformation auto-inhibée assurée par son domaine N-terminal en superhélice. Nous avons pu ensuite montrer que RipA fonctionne en synergie avec deux protéines nouvellement caractérisées impliquées dans la division cellulaire et spécifiques des Corynebacteriales, SteA et SteB. La structure crystalline du domaine extracytosolique de SteB nous a permis de construire un modèle putatif d'interaction avec RipA. Nous avons généré une souche de C. glutamicum délétée de steA, ce qui nous a permis de de reconstituer le protéome de SteA par immuno-précipitation. L'analyse du protéome de SteA nous a permis d'émettre des hypothèses quant à l'intégration de SteA et SteB dans le processus de division cellulaire chez les Corynebacteriales. Étant donné que les déplétions des différentes protéines impliquées dans la division cellulaire sont connues pour augmenter la sensibilité aux antibiotiques des Corynebacteriales, nous espérons que ces travaux pourront conduire à l'avenir à la conception rationnelle de nouveaux médicaments qui pourraient agir en synergie avec les antibiotiques existants.Bacterial cell division is a temporally and spatially regulated process coordinated by a multiprotein complex called the divisome. The assembly of the divisome is initiated and organized by the highly conserved bacterial tubulin homologue FtsZ, which polymerizes to form a dynamic ring structure (Z-ring) that marks the site of cell division. Following ring assembly, FtsZ recruits structural and accessory proteins in an ordered manner to form the functional cell division machinery that will rearrange the cell wall. This transmembrane protein complex will coordinate the inward synthesis of peptidoglycan (the major component of the cell wall) by penicillin-binding proteins with its peripheral degradation by autolytic enzymes to allow the separation of two viable daughter cells (septation). Although the general scheme of divisome assembly and function seems to be widely conserved in bacteria, important species-specific differences exist to satisfy different morphologies, growth modes and cell wall compositions. This is particularly true in Corynebacteriales, an order of Actinobacteria including important human pathogens such as Mycobacterium tuberculosis and Corynebacterium diphtheriae. Corynebacteriales have an unusual polar elongation mode and a complex cell wall surrounded by a mycolic acid layer. Corynebacteriales septation is performed through a fast, brutal rupture of the cell walls of the two daughter cells called V-snapping. The goal of the present thesis was the structural and functional characterization of the divisome in Corynebacteriales. We focused on RipA, a key enzyme for cell separation in Corynebacteriales. RipA is an autolysin which catalyzes the cleavage of the peptidic cross-links of peptidoglycan and has been shown to be important for virulence of M. tuberculosis and C. diphtheriae. We characterized the structure of the full-length Corynebacterium glutamicum homologue of RipA, which revealed the enzyme in an auto-inhibited conformation mediated by its N-terminal coiled-coil domain. Further work allowed us to show that RipA works in synergy with the newly characterized, Corynebacteriales-specific division proteins SteA-SteB. The crystal structure of the extracytosolic domain of SteB allowed us to build a putative mode of interaction with RipA. We generated a C.glutamicum strain knocked-out for steA which allowed us to reconstitute the proteome of SteA by immunoprecipitation. The analysis of the proteome of SteA gave us insights into how SteA and SteB are integrated into the cell division process in Corynebacteriales. Since depletions of the different proteins involved in cell separation are known to increase antibiotics susceptibility in Corynebacteriales, we hope this work could lead in the future to the rational design of new drugs which could act in synergy with existing antibiotics
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Face aux « revues prédatrices », comment cesser d’être des lapins ?
No full textInternational audienceNo abstract availabl
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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