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Synthèse d'un α-AApeptide dérivé d'un peptide RNase antibiofilm
No full textLe biofilm microbien est un problème de santé publique selon l'Organisation mondiale de la santé, lié à 75 % des infections humaines. Les biofilms sont des associations microbiennes bien organisées dans une matrice extracellulaire complexe. Les biofilms jouent le rôle de pool de bactéries et de barrière contre les antibiotiques ou pour héberger les cellules immunitaires. Les peptides ont été étudiés au cours des dernières décennies et ont montré une activité antibiofilm considérable même sur des micro-organismes résistants. Bien que très prometteuses, ces biomolécules présentent certaines limites in vivo, telles qu'une sensibilité protéolytique et une faible stabilité. Les peptidomimétiques, comme les AApeptides, sont une alternative viable pour résoudre ces limitations avec une plus grande résistance à la dégradation protéolytique. Objectif : Synthèse d’un α-AApeptide à partir d'un peptide 11-mer naturel hautement actif conçu à partir de plusieurs séquences génétiques du système de défense humain, montrant 50 % d'activité d'inhibition du biofilm à 15 μM vis-à-vis de Staphylococcus epidermidis. Méthode : La synthèse chimique est du type peptidique et a reposé sur la préparation d’unités AAdipeptidiques puis à la conjugaison de celles-ci selon um processus convergent. Résultats : Le 11-mer α-AApeptide a été synthétisé avec succès. La molécule peptidomimétique n'a en revanche pas démontré d'activité vis-à-vis des souches bactériennes étudiées en comparaison avec le peptide naturel Conclusions : Des études supplémentaires devront être menées sur le peptide et son peptidomimétique afin de justifier de cette différence d’effet. Une attention particulière sera portée à la structuration tridimensionnelle de ceux-ci.Background: Microbial biofilm is a public health concern according to the World Health Organization, linked to 75% of human infections. Biofilms are well-organized microbial association in a complex extracellular matrix. Biofilms play as a pool of bacteria and as a barrier to antibiotics or to host immune cells. Peptides have been studied in recent decades and have shown considerable antibiofilm activity even on resistant microorganisms. Although quite promising, these biomolecules have some limitations in vivo, such as proteolytic susceptibility and low stability. Peptidomimetics, like AApeptide, are a viable alternative for solving these limitations with higher resistance to proteolytic degradation. Objective: Synthesize an α-AApeptide from a highly active natural 11-mer peptide designed from several genetical sequences of the human host defense system, showing 50% of biofilm inhibition activity at 15 μM for Staphylococcus epidermidis stains. Methods: All the chemical synthesis has been performed in solution. A convergent synthetical approach was designed to reach the targeted peptidomimetic. Results: The 11-mer α-AApeptide was successfully synthesized. However, it did not show any antibiofilm activity compared to the original peptide. Conclusions: Despite the achievement of the targeted compound, it did not present the expected activity compared to its natural counterpart on the strains assessed. Some studies have to be envisioned in order to understand this result
Peptides and peptidomimetics obtention from Capsicum baccatum var. pendulum (Solanaceae) aiming to the antibiofilm activity
No full textLe biofilm confère aux bactéries de nombreux avantages en tant que matrice qui améliore leur résistance et tolérance aux antibiotiques. Staphylococcus epidermidis est l'une des bactéries cliniques les plus importantes en raison de sa capacité à former des biofilms sur des dispositifs médicaux, notamment les stimulateurs cardiaques, les cathéters urinaires et les prothèses. Dans ce contexte, les peptides ont été proposés comme une alternative importante, que ce soit en tant que traitement médicamenteux ou en tant qu’agents de surfaces anti-infectieux. Cette étude porte sur l’identification de nouveaux peptides naturels et synthetiques antibiofilm issus du piment Capsicum baccatum var. pendulum. Un peptide majeur responsable de l'activité antibiofilm contre S. epidermidis a été sélectionné et étudié de manière approfondie. Il agit par un nouveau mécanisme d'action que nous nommons « anti-assemblage de la matrice » (AAM). Dans le premier chapitre, nous décrivons le lien entre les peptides, les biofilms pathogènes et l'activité antibiofilm. Le chapitre 2 est consacré aux principaux résultats expérimentaux de cette thèse. Il intégre la caractérisation antibiofilm du peptide majeur, agissant par le nouveau mécanisme d'action AAM, indépendant de la régulation cellulaire. Des tests de cytotoxicité sont également présentés. Ces résultats nous ont permis de breveter le peptide en question, référencé au chapitre 3. Le dernier chapitre décrit la possible utilisation de peptidomimétiques antibiofilm en tant que perspective. La stratégie consiste à créer de petites molécules analogues à des peptides. Ces peptidomimétiques conservent les capacités inhérentes au peptide majeur, mais sont plus résistants aux protéases et/ou plus actifs.Biofilm confers to bacteria many benefits due to the production of a matrix that improves their resistance and tolerance to antibiotics. Staphylococcus epidermidis is one of the most important clinical bacteria, able to form biofilm on medical devices such as pacemakers, urinary catheters and prostheses. In this context, peptides have been proposed as an important alternative as a treatment or as anti-infective surface agents. This study focuses on the identification of new antibiofilm natural and synthetic peptides from the Capsicum baccatum var. pendulum pepper. As a result, a lead peptide responsible for the antibiofilm activity against S. epidermidis was selected and extensively studied. It acts by a new mechanism of action that we call "matrix anti-assembly" (MAA). In the first chapter, we explore the link between peptides, pathogenic biofilms and the antibiofilm activity. Chapter 2 consists of the main experimental results of this thesis. It describes the antibiofilm characterization of the lead peptide acting by the AAM new mechanism of action, independent of cell regulation. Cytotoxicity tests are also presented. These results allowed us to patent this peptide, referenced in Chapter 3. The last chapter presents the possible use of antibiofilm peptidomimetics as a perspective. The strategy is to create small peptide-like molecules. These peptidomimetics retain the inherent capabilities of the lead peptide, but are more resistant to proteases and / or more active.O biofilme apresenta vários benefícios às bactérias devido à existência de uma matriz que confere resistência e tolerância aos antibioticos. O Staphylococcus epidermidis é uma das bactérias com maior relevância clínica devido à sua capacidade de formar biofilmes em dispositivos médicos, tais como, marca-passos, cateteres urinários e próteses. Neste contexto, os peptídeos têm sido propostos como uma alternativa importante, tanto como tratamento, quanto como agentes anti-infecciosos de superfície. Este estudo consiste na identificação de novos peptídeos naturais e sintéticos, derivados da pimenta Capsicum baccatum var. pendulum, com atividade antibiofilme. Por conseguinte, foi selecionado e estudado extensivamente um peptídeo de referência que apresentou a melhor atividade antibiofilme contra S. epidermidis. Este peptídeo atua através de um novo mecanismo de ação que descrevemos e chamamos de "anti-montagem de matriz" (AMM). No primeiro capítulo deste trabalho foi abordado a ligação entre peptídeos, biofilmes patogênicos e a atividade antibiofilme. O Capítulo 2 consiste nos principais resultados experimentais desta tese como a caracterização da atividade antibiofilme do peptídeo de referência, que age através do novo mecanismo de ação AMM independente da regulação celular e os testes de citotoxicidade. Esses resultados nos permitiram patentear o peptídeo em questão, referenciado no Capítulo 3. Finalmente, o último capítulo descreve o possível uso de peptidomiméticos antibiofilme como uma perspectiva. A estratégia é criar pequenas moléculas semelhantes ao peptídeo de referência. Estes peptidomiméticos mantêm as capacidades inerentes ao peptídeo principal, porém são mais resistentes a proteases e / ou mais ativos
Conception et synthèse de nouveaux dérivés de génines triterpéniques d'Ilex à visée antipaludique
No full textLe paludisme est une maladie endémique sérieuse qui représente une menace importante de santé publique en Afrique, en Asie, Océanie, et en Amérique latine. Suite à la recrudescence de la résistance du parasite, à l origine du paludisme, aux molécules actuellement commercialisées, il devient primordial de disposer de nouvelles molécules antipaludiques. Ce travail de thèse avait pour but l extraction, l hémisynthèse d analogues de l acide ursolique et enfin l évaluation de l activité antipaludique des composés ainsi obtenus. Sept produits naturels ont e té extraits et purifiés à partir d espèces sud américaines Ilex paraguariensis et Ilex dumosa. Il s agit des triterpénes de l acide ursolique et de l acide oléanolique et les saponosides matésaponines peracetylées ou non. L optimisation de l'activité antipaludique de l acide ursolique, initialement décrite, a été réalisée par pharmacomodulation du noyau triterpénique en position 3 et 28. Parmi les différents analogues de l acide ursolique obtenus, certains ont démontré des activités intéressantes de l'ordre de nanomolaire (IC50 78 to 964 nM). Ainsi, nous avons démontré l importance du noyau triterpénique, du groupement acétyle en C-3 et l importance des substitutions au niveau de l azote terminal de la chaine bis-(3-aminopropyl)pipérazine pour l activité antipaludique. Et ceci notamment à travers des études de relation structure-activité. Enfin, l hypothèse que ces composés agissent sur l inhibition de la formation de b-hémazoïne a été confirmée par des études in vitro (inhibition de la formation de la b-hématine) et de modélisation moléculaireAMIENS-BU Santé (800212102) / SudocSudocFranceF
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
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