Dissertations / Theses on the topic 'Diverse Interactions'
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Petrou, Georgia. "Investigating mucin interactions with diverse surfaces for biomedical applications." Licentiate thesis, KTH, Glykovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-249469.
Full textSlemhinnor täckts av slem, en viskoelastisk hydrogel som spelar en viktig roll för att skydda mot mekanisk nötning och patogener. Muciner, en grupp av tätt glykosylerade proteiner, spelar en viktig roll i viskoelasticiteten av slem. Eftersom muciner kan interagera med diverse ytor är det av stort intresse att utforska och manipulera sådana interaktioner för biomedicinska tillämpningar. Denna avhandling presenterar undersökningar av mucininteraktioner med hydrofoba ytor för att identifiera de viktigaste egenskaperna hos mucinsmörjning, samt beskriver utveckling av material som optimerades för att interagera med muciner. I Artikel I undersökte vi de domäner som bidrar till mucinernas enastående kapacitet som smörjmedel. Resultaten visade att mucinernas hydrofoba terminaldomäner spelar en avgörande roll vid adsorption och smörjning på hydrofoba ytor. Mer specifikt, proteasklyvning av svinmagemuciner och salivmuciner resulterade i klyvningen av dessa domäner och förlust av smörjning och ytadsorption. Genom att länka hydrofobiska fenylgrupper till de uppbrutna mucinerna, lyckades deras smörjningsegenskaper förbättras. Denna strategi förbättrade också smörjningsegenskaper hos andra polymerer som annars har dåliga smörjningsegenskaper. I Artikel II utvecklade vi mukoadhesiva material baserade på genetiskt modifierade partiella spindelsilkeproteiner. Spindelsilkeproteinet 4RepCT funktionaliserades framgångsrikt med tillsats av sex lysiner (pLys-4RepCT), eller den mänskliga Galectin-3 karbohydrat igenkänningsdomänen (hGal3-4RepCT). Syftet med dessa strategier var antingen att öka ospecifika elektrostatiska interaktioner mellan de positiva lysinerna och de negativa mucinerna, eller den specifika bindningen mellan hGal3 och mucin-glykanerna. Beläggningar, fibrer, nät och skum framställdes från de nya silkeproteinerna. Efter att adsorption av svinmagsmuciner och bovina submaxillära muciner uppmätts, visade de nya silkeproteinerna förbättrad mucin adsorption. Detta arbete visar hur interaktioner mellan mucin-material kan bidra med värdefull information för utvecklingen av nya biomaterial. Mucinbaserade och mucininspirerade smörjmedel kan ge önskad smörjning till ett brett spektrum av ytor, medan vår nya silkesbaserad material kan vara ett värdefullt verktyg för utvecklingen av slemhinneförband.
QC 20190412
Schmitt, Anita Maria. "Gifted students in diverse environments an analysis of interactions and perceptions /." [Pensacola, Fla.] : University of West Florida, 2009. http://purl.fcla.edu/fcla/etd/WFE0000160.
Full textHaider, Mohammed Jassim. "Characterisation of FcRy-coupled phagocytic interactions between macrophages and taxonomically diverse fungi." Thesis, University of Aberdeen, 2017. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=233453.
Full textBarile, John P. "Health Disparities in a Diverse County: Investigating Interactions between Residents and Neighborhoods." Digital Archive @ GSU, 2010. http://digitalarchive.gsu.edu/psych_diss/80.
Full textSuetsugu, Kenji. "Diverse interactions of heterotrophic plants with their hosts, pollinators and seed dispersers." Kyoto University, 2014. http://hdl.handle.net/2433/192205.
Full text0048
新制・課程博士
博士(人間・環境学)
甲第18605号
人博第701号
新制||人||167(附属図書館)
26||人博||701(吉田南総合図書館)
31505
京都大学大学院人間・環境学研究科相関環境学専攻
(主査)教授 加藤 眞, 教授 市岡 孝朗, 教授 瀬戸口 浩彰, 教授 宮本 嘉久, 教授 新宮 一成
学位規則第4条第1項該当
Simmons, Noreen Rosalind. "Barriers, bridges and beyond : understanding perspectives in linguistically and culturally diverse clinical interactions." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31524.
Full textMedicine, Faculty of
Audiology and Speech Sciences, School of
Graduate
Gomez-Lopez, Iris Nelly. "Simulating the Spread of Infectious Diseases in Heterogeneous Populations with Diverse Interactions Characteristics." Thesis, University of North Texas, 2013. https://digital.library.unt.edu/ark:/67531/metadc407831/.
Full textMoller, Abraham Ghoreishi. "Mapping ecologically important virus-host interactions in geographically diverse solar salterns with metagenomics." Miami University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=miami1461841762.
Full textBarman, Biraj Kumar. "Investigation of diverse interactions and inclusion complexation in different environment by physicochemical methodology." Thesis, University of North Bengal, 2018. http://ir.nbu.ac.in/handle/123456789/2622.
Full textDutta, Ashutosh. "Exploration of diversified interactions of some significant compounds prevalent in several environments by physicochemical contrivance." Thesis, University of North Bengal, 2018. http://ir.nbu.ac.in/handle/123456789/2787.
Full textRay, Samapika. "Study to explore inclusion complexations and assorted interactions of some industrially and biologically significant molecules in diverse systems." Thesis, University of North Bengal, 2022. http://ir.nbu.ac.in/handle/123456789/4789.
Full textYates, Ronald John. "Symbiotic interactions of geographically diverse annual and perennial Trifolium spp. with Rhizobium leguminosarum bv. trifolii /." Murdoch University Digital Theses Program, 2008. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20100330.93305.
Full textau, ronald yates@agric wa gov, and Ronald John Yates. "Symbiotic Interactions of Geographically Diverse Annual and Perennial Trifolium spp. with Rhizobium leguminosarum bv. trifolii." Murdoch University, 2008. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20100330.93305.
Full textYates, Ronald. "Symbiotic Interactions of Geographically Diverse Annual and Perennial Trifolium spp. with Rhizobium leguminosarum bv. trifolii." Thesis, Yates, Ronald (2008) Symbiotic Interactions of Geographically Diverse Annual and Perennial Trifolium spp. with Rhizobium leguminosarum bv. trifolii. PhD thesis, Murdoch University, 2008. https://researchrepository.murdoch.edu.au/id/eprint/1699/.
Full textYates, Ronald. "Symbiotic Interactions of Geographically Diverse Annual and Perennial Trifolium spp. with Rhizobium leguminosarum bv. trifolii." Yates, Ronald (2008) Symbiotic Interactions of Geographically Diverse Annual and Perennial Trifolium spp. with Rhizobium leguminosarum bv. trifolii. PhD thesis, Murdoch University, 2008. http://researchrepository.murdoch.edu.au/1699/.
Full textMohale, Matsie Agnes. "Interactions of diverse students in a South African university residence : the case of Tuks Village." Diss., University of Pretoria, 2013. http://hdl.handle.net/2263/57494.
Full textDissertation (MEd)--University of Pretoria, 2013.
tm2016
Humanities Education
MEd
Unrestricted
Mishra, M. "Interactions between diverse proteinase inhibitors from Capsicum annuum and insects pests : biochemical & molecular approach." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2012. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/2130.
Full textRahaman, Habibur. "Diverse Interactions of Some Significant Compounds Prevailing in Different Solvent Systems with the Manifestation of Solvation Consequence by Physicochemical Investigations." Thesis, University of North Bengal, 2019. http://ir.nbu.ac.in/handle/123456789/2814.
Full textChoudhury, Subhankar. "Physicochemical study of diverse interactions of ionic liquids and biologically active solutes prevailing in liquid environments." Thesis, University of North Bengal, 2016. http://ir.nbu.ac.in/handle/123456789/2763.
Full textKretov, Dmitry. "Mechanisms of YB-1/nucleic acids interaction and its implication in diverse cellular processes." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLE017.
Full textYB-1 is a member of the cold-shock protein superfamily. It binds to both RNA and DNA. Correlations between high level of YB-1, elevated expression of P-glycoprotein MDR1 and poor patient prognosis were made for several types of cancer. The role of YB-1 in cancerogenesis can be accounted by several mechanisms: i) activation of transcription; ii) participation in DNA repair; iii) regulation of translation. The first two proposals imply a nuclear localization for YB-1, despite the fact that it appears mainly in the cytoplasm under physiological conditions and the mechanisms for its nuclear accumulation remain unclear. In this work we attempted to identify the mechanisms that trigger the nuclear translocation of YB-1. It appeared that this depends on the level of mRNA in the cytoplasm and thus on active transcription, rather than on the presence of nuclear DNA damages. In contrast to its function in the nucleus, the role of YB-1 in the regulation of translation was clearly established. YB-1 may therefore orchestrate a translation bias in order to promote cancer progression independently of its putative functions in the nucleus. Here we demonstrated, using atomic force microscopy and biochemical methods, that YB-1 binds mRNA in a highly cooperative manner and this has direct consequences on mRNA selection and following translational modulation. Beyond this research, we took advantage of our knowledge of the biology of YB-1 to develop a new method to detect protein-protein interactions in cellular context, using YB-1 as model protein. Besides the fact that we confirmed ability of YB-1 to make oligomers in the presence of mRNA, we also highlighted its potential interaction with Lin28, using this method
Talmadge, Rosemary A. "Campus diversity and perspective-changing| Students describe the impact of their interactions with diverse peers and viewpoints." Thesis, Fielding Graduate University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3614922.
Full textPreparing students to become effective citizens in an increasingly interdependent world is one of today's most critical challenges. Effective global citizens need to be able to do more than imagine themselves in another's position, a common definition of perspective-taking. To bridge current divides of culture, religion, and nationality, they also must be willing to deeply question and sometimes revise their own prior beliefs and assumptions.
This study explored how interactions with diversity at a highly diverse and international community college impact students' capacity for perspective-changing. Through a hermeneutic inquiry, it brought community college students' voices into the scholarly conversation about the impact of campus diversity. Eighteen students from 11 countries participated in semi-structured interviews, discussing their pre-college experiences with diversity, their own definitions of diversity, critical incidents in their interactions with diversity, and the impacts of those interactions.
Several strands of scholarship informed this research. The first was the literature on perspective-taking particularly Piaget's original work as it was extended by Robert Selman and Jack Martin and his colleagues. Other core contributions included Jack Mezirow's theory of perspective transformation, Robert Kegan's work on self-authorship, and recent research on campus diversity conducted by educational researchers including Patricia Gurin, Sylvia Hurtado, Rona Halualani, and Victor Saenz.
Findings suggest that pre-college experiences shaped students' interactions with peers and the benefits they accrued. Almost all benefited from their interactions with diversity, but they benefited differentially. Work and family demands, limited English speaking ability, lack of prior experience with diversity, and deeply engrained cultural norms sometimes hindered their ability to engage with diverse peers and perspectives.
The analysis indicates that interactions with peers led to a range of outcomes including learning about and becoming more open to diversity, being able to engage with diversity, questioning and revising prior beliefs, and changing behaviors. A key finding was that engaging with diverse viewpoints did not occur informally, only in structured settings and almost always with the support of faculty or staff. Findings pointed to a need for more opportunities for engaging with diverse viewpoints, more targeted approaches, specific professional development for faculty and staff, and more research on community college campuses.
Wheeler, Sassy Cenita. "Novice Special Education Teachers' Experiences with Students with Disabilities from Culturally and Linguistically Diverse Backgrounds: The Effects of Perceptions on Interactions." ScholarWorks@UNO, 2007. http://scholarworks.uno.edu/td/580.
Full textScott, Brown Alison Sarah. "Interactions of thrips and their control agents on host plants within a glasshouse containing a diverse collection of plant species." Thesis, Birkbeck (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398082.
Full textDas, Koyeli. "Physicochemical investigation of assorted interactions of some imperative compounds with the manifestation of solvation effects prevalent in diverse solvent systems." Thesis, University of North Bengal, 2018. http://ir.nbu.ac.in/handle/123456789/2684.
Full textFouquier, D´Hérouel Aymeric. "On diverse biophysical aspects of genetics : from the action of regulators to the characterization of transcripts." Doctoral thesis, KTH, Beräkningsbiologi, CB, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-31490.
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Altfeld, Laura F. "Herbivore Abundance in Simple and Diverse Habitats: The Direct and Indirect Effects of Plant Diversity and Habitat Structure." [Tampa, Fla.] : University of South Florida, 2003. http://purl.fcla.edu/fcla/etd/SFE0000062.
Full textJarsch, Iris Katharina [Verfasser], and Thomas [Akademischer Betreuer] Ott. "Remorin proteins in Arabidopsis thaliana : markers for diverse embrane micro-domains with roles in plant-microbe interactions / Iris Jarsch. Betreuer: Thomas Ott." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2014. http://d-nb.info/1072038250/34.
Full textYasmin, Ananya. "Investigation of Host Guest Inclusion Complexations and Diverse Interactions of Some Industrially and Biologically Potent Molecules in Assorted Phases by Physicochemical Methodologies." Thesis, University of North Bengal, 2019. http://ir.nbu.ac.in/handle/123456789/2854.
Full textMatsuda, Sachiko. "The role of the global co-activator CREB-binding protein in transcription : a study of competitive interactions of diverse nuclear proteins with CBP." Thesis, University of Leicester, 2006. http://hdl.handle.net/2381/29713.
Full textJouan, Romain. "The fitness landscape of the soil bacteria Caballeronia insecticola and Sinorhizobium meliloti in diverse natural and synthetic environments." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASB076.
Full textSoil bacteria are adapted to survive in their abiotic soil environment as well as to cope with different organisms, including other bacteria, fungi, plants and insects with which they share that environment. With the objective to contribute to the understanding of these adaptations and to answer the question if adaptations are overlapping or unique for each of these lifestyles, I used the transposon-sequencing (Tn-seq) approach to identify essential and conditionally fitness genes in two well-studied soil bacteria, Caballeronia insecticola and Sinorhizobium meliloti. The experimental strategy consisted in the use of Tn-seq screens performed in the natural, in situ environments of the microbes combined with multiple in vitro experiments in synthetic environments. The selection of these in vitro conditions was informed by available transcriptome analyses, physiological studies, genetics, genomics and biochemical analyses as well as the in situ Tn-seq experiments themselves. The selected in vitro conditions were a variety of stressors (e.g. antimicrobial peptides or AMPs) or nutritional (e.g. a panel of carbon, nitrogen and sulphur sources) and physiological (e.g. motility and chemotaxis) conditions that the microbes encounter in their natural environments. These simplified synthetic conditions decompose the complexity of natural conditions in single components and facilitate thereby the interpretation of the in situ Tn-seq screens.C. insecticola is a versatile bacterium establishing specific interactions with insects, plants, fungi and other bacteria. I analyzed four different lifestyles of C. insecticola with the Tn-seq approach: soil, the rhizosphere of soybean plants, the gut symbiotic organ of the insect Riptortus pedestris and the surface of the hyphae of Cunninghamella fungi. For bacteria-bacteria interactions, I focused on the competition of the rhizobium strain S. meliloti with the toxin producing strain Rhizobium sp. Pop5 because this interaction is well characterized and based on the production of the AMP phazolicin by the strain Pop5.In total, 34 screens in C. insecticola and 4 screens in S. meliloti were performed and analysed, resulting in the discovery of phenotypes for 1162 C. insecticola genes and 264 S. meliloti genes. In C. insecticola, the essential genome, i.e. the set of genes that cannot be removed and that are therefore indispensable to support bacterial life, was precisely defined. I found that it is constituted of 498 genes, including the genes encoding the expected cellular functions, like transcription, translation, energy production, cell envelope biosynthesis and cell cycle, but also less expected genes like those involved in the specific modification of the lipid A moiety of lipopolysaccharide with 4-amino-4-deoxy-L arabinose groups. Results of the different Tn-seq screens were verified by independent experiments, using insertion or deletion mutants of C. insecticola and S. meliloti in selected genes and characterization of the phenotype of these mutants in the relevant environmental and in vitro conditions. In total, 23 mutants in C. insecticola and 8 mutants in S. meliloti were phenotyped. In each case, the phenotyping of these mutants confirmed the Tn-seq data, illustrating the robustness and potential of the method.Among the crucial bacterial functions in all natural environments, in both C. insecticola and S. meliloti, is the bacterial envelope, suggesting that it constitutes a shield, fending of environmental stresses, in particular AMPs frequently produced by other organisms. Bacterial motility and chemotaxis in C. insecticola are particularly important in the interaction with insects but also in the soil, when bacteria hitchhike on fungal hyphae. Finally, each environment imposes specific metabolic constraints on the bacteria. Together, this work highlighted both generalist and environment-specific adaptations in soil bacteria
Leiva, Torres Luis Alberto. "Diverse Contributions to Implicit Human-Computer Interaction." Doctoral thesis, Universitat Politècnica de València, 2012. http://hdl.handle.net/10251/17803.
Full textLeiva Torres, LA. (2012). Diverse Contributions to Implicit Human-Computer Interaction [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/17803
Palancia
Young, Nancy Diane. "Peer interaction and learning in compositionally diverse residence halls." College Park, Md.: University of Maryland, 2007. http://hdl.handle.net/1903/7759.
Full textThesis research directed by: Dept. of Education Policy, Planning, and Administration. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
GERSCHWILER, SOPHIE. "Etude des interactions entre polyoxometallates et divers materiaux d'electrode." Paris 11, 1998. http://www.theses.fr/1998PA112098.
Full textLettéron, Philippe. "Rôle des métabolites réactifs dans diverses hépatites et interactions médicamenteuses." Paris 11, 1989. http://www.theses.fr/1989PA114839.
Full textHegedus, Katalin. "Dialogue journal writing : meaningful written interaction in language and culturally diverse classrooms." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/29929.
Full textEducation, Faculty of
Language and Literacy Education (LLED), Department of
Graduate
Bigarre, Laurent. "Diversite des geminivirus et interactions avec leurs hotes." Paris 11, 1999. http://www.theses.fr/1999PA112380.
Full textPolyakova, Evgenia I. "A general theory for evaluating joint data interaction when combining diverse data sources /." May be available electronically:, 2008. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
Full textWong, Sato Akira Armando. "Diverse adaptations to increase pollination success in zoophilous plants." Kyoto University, 2018. http://hdl.handle.net/2433/232377.
Full text0048
新制・課程博士
博士(人間・環境学)
甲第21176号
人博第848号
新制||人||203(附属図書館)
29||人博||848(吉田南総合図書館)
京都大学大学院人間・環境学研究科相関環境学専攻
(主査)教授 加藤 眞, 教授 市岡 孝朗, 教授 瀬戸口 浩彰
学位規則第4条第1項該当
Vickers, Caroline H. "Interactional accommodation and the construction of social roles among culturally diverse undergraduates." Diss., The University of Arizona, 2004. http://hdl.handle.net/10150/290133.
Full textParadis, Geneviève. "Transport de protéines thérapeutiques à travers diverses barrières biologiques à l'aide d'un ligand peptidique." Sherbrooke : Université de Sherbrooke, 2004.
Find full textOng, Saro. "Divers aspects des collisions photon-photon : corrections radiatives, et corrélations azimutales." Paris 6, 1988. http://www.theses.fr/1988PA066450.
Full textGrevet, Catherine. "Being nice on the internet: Designing for the coexistence of diverse opinions online." Diss., Georgia Institute of Technology, 2016. http://hdl.handle.net/1853/55002.
Full textBost, Pierre. "Decoding cellular communications and interactions between immune cells by using single-cell approaches." Electronic Thesis or Diss., Sorbonne université, 2020. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2020SORUS020.pdf.
Full textCellular communications are essential to the proper functioning of multi-cellular organisms, particularly in order to adapt to a constantly changing environment. The cells of the immune system are no exception to this rule, but the interactions between immune cells remain little known and complicated to study. The recent emergence of 'single cell' sequencing technologies represents a unique opportunity to study these communications. In this thesis, different experimental and analytical approaches have been developed to study these communications on a single cell scale. These strategies were then applied to different disease contexts, including COVID-19, Alzheimer's disease or immunisation with inactivated pathogens, and identified previously unknown or poorly understood cellular communication pathways. However, the effectiveness of these approaches is limited by the lack of information on cell location and further work integrating such data will be essential to go further in the dissection of immune cell communications
Casadevall, Dario. "Skunkworks Finder: A Design Study into the Diverse Ecosystem of Creativity and Innovation Spaces." Thesis, Ludwig-Maximilians-Universitat München, 2018. https://eprints.qut.edu.au/122139/1/Masterthesis_DarioCasadevall%20Kopie.pdf.
Full textKoran, L. "Aphasia in a linguistically diverse population : resources for turn construction and interactional adaptations of Malaysian adults." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1468881/.
Full textDe, Poorter Cédric. "Mécanismes d'activation et interactions fonctionnelles hétérologues des récepteurs aux chimiokines." Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209589.
Full textLes chimiokines sont de petites protéines qui régulent la migration des cellules immunitaires. Elles exercent leur action en se liant à des récepteurs appartenant à la famille des récepteurs couplés aux protéines G (RCPG) dont la fonction est intimement liée à la régulation des cellules immunitaires. Notre laboratoire étudie depuis plusieurs années les relations reliant la structure et la fonction des récepteurs aux chimiokines. Ces dernières années, un nouveau concept est venu révolutionner le mode de fonctionnement des RCPGs. En effet, des travaux ont montré que la plupart des RCPGs sont capables de former des dimères. Le but de cette thèse de doctorat est d’étudier de manière systématique la dimérisation des récepteurs aux chimiokines et d’analyser les conséquences fonctionnelles de la dimérisation.
Dimérisation des récepteurs humains aux chimiokines et conséquences fonctionnelles
En utilisant une technique biophysique basée sur un transfert d’énergie de luminescence (BRET) nous avons montré au cours de ce travail de thèse que les récepteurs CCR1, CCR2, CCR5, CCR7 et CXCR4 sont capables de former des homodimères et des hétérodimères. De plus, une dimérisation entre ChemR23, dont le ligand naturel, la chémérine, est structurellement différent des chimiokines, et les récepteurs CCR7 et CXCR4, a également été identifiée.
D’un point de vue fonctionnel, des expériences réalisées au laboratoire dans le cadre d’un autre travail de thèse ont identifié une forme de compétition croisée entre CCR2, CCR5 et CXCR4 où la liaison de ligands (agonistes ou antagonistes) spécifiques de l'un des deux récepteurs inhibe la liaison des ligands spécifiques de l’autre. Ces effets ont été démontrés sur des cellules recombinantes mais aussi sur des cellules immunes et dans un modèle in vivo. (El-Asmar, 2005; Springael, 2006; Sohy, 2007; Sohy, 2009). Au cours de ce travail, nous nous sommes dans un premier temps focalisés sur les
hétéromères de ChemR23 avec CXCR4 et CCR7 et nous avons ensuite étudié plus en profondeur les hétéromères de CCR7. Concernant la dimérisation de ChemR23 avec les récepteurs aux chimiokines CCR7 et CXCR4, nous avons pu mettre en évidence une coopérativité négative de liaison entre les agonistes des récepteurs comme cela avait pu être démontré pour CCR2/CCR5/CXCR4. Par contre, nous n’avons observé aucun effet de compétition hétérologue ou d’inhibition fonctionnelle croisée de l’AMD3100 sur ChemR23 quand il est coexprimé avec CXCR4. De manière additionnelle, nous avons pu observer cette compétition croisée sur des cellules dendritiques murines immatures, démontrant l’existence des effets de l’hétérodimérisation lorsque les récepteurs sont exprimés à un niveau physiologique. Lors de l’étude approfondie des hétéromères de CCR7, nous avons montré que les conséquences fonctionnelles de l’hétérodimérisation de CCR7 sont différentes suivant le récepteur avec lequel il interagit. Pour l’hétérodimère CCR7/CCR2, nous avons identifié une forme de compétition croisée, où la liaison de ligands spécifiques de l'un des deux récepteurs inhibe la liaison des ligands spécifiques de l’autre, rejoignant les effets mis en évidence pour les hétéromères CCR2/CCR5/CXCR4. Ensuite, nous avons montré pour l’hétérodimère CCR7/CCR5 que les ligands de CCR7 sont capables d’inhiber la liaison des ligands spécifiques sur CCR5 mais que l’inverse n’est pas vrai. Enfin, pour l’hétérodimère CCR7/CXCR4, nous n’avons pas pu mettre en évidence d’inhibition croisée, que ce soit dans un sens ou dans l’autre. D’autre part, un effet inhibiteur de CCR7 a également été identifié pour les hétéromères CCR7/CCR5 et CCR7/CXCR4. Nous avons pu montrer que l’expression de CCR7 exerce un effet négatif sur la réponse fonctionnelle de certains récepteurs hétérologues comme CCR5 et CXCR4 mais pas CCR2 ou ChemR23.
L’ensemble de ces données permet de mieux comprendre les interactions entre récepteurs et pourrait mener à l’identification de nouvelles cibles pour les programmes de recherche de molécules thérapeutiques, qui, jusqu’à présent, ciblaient presque exclusivement un seul et unique récepteur.
Etude du mécanisme d’activation du récepteur CCR5 et étude de la relation entre activité constitutive et dimérisation.
De nombreux travaux ont été menés ces dernières années afin de mieux comprendre les mécanismes moléculaires à la base de l’activation des récepteurs couplés aux protéines G (RCPG). Il apparaît que les RCPGs peuvent se trouver dans plusieurs états conformationnels, dont certains sont favorisés par la présence d’agonistes ou d’antagonistes, ou encore d’anticorps reconnaissant des épitopes conformationnels. Certaines mutations peuvent également induire la stabilisation de certaines conformations, actives ou inactives. Pour les RCPGs appartenant à la famille de la rhodopsine, il en a résulté un modèle selon lequel les récepteurs sont maintenus dans une conformation inactive par un ensemble d’interactions ioniques impliquant l’arginine (R3.50) d’un motif DRY conservé, présent à l’extrémité cytosolique du troisième segment transmembranaire. Les interactions responsables de ce qu’on appelle le « DRY-lock » feraient intervenir notamment l’aspartate (D3.49) adjacent de l’arginine et un aspartate ou glutamate (D/E6.30) localisé au sein de l’hélice 6. Selon ce modèle, la liaison d’un agoniste, ainsi que certaines mutations, favoriseraient la rupture de ces interactions ioniques, et une conformation permettant aux récepteurs de se coupler plus efficacement aux protéines G. Des résultats du laboratoire indiquent cependant que ce modèle ne serait pas transposable complètement au récepteur CCR5.
CCR5 possède intrinsèquement une activité constitutive en absence d'agoniste. Cette activité peut être mise en évidence par l'action d'un des antagonistes de CCR5, le TAK-779, qui s'est révélé posséder une activité de type agoniste inverse. D'autre part, CCR5 possède au sein de l'hélice 6 une arginine en position 6.30 et non pas un glutamate ou un aspartate. Une arginine à cette position ne peut donc contribuer au maintien d’une conformation inactive par interaction avec R3.50 .Dans le but de tester le modèle de « DRY-lock » sur CCR5 et de mieux comprendre les interactions moléculaires impliquées dans l’activation du récepteur, plusieurs récepteurs mutants ont été construits au laboratoire. Tout d’abord, l’arginine 3.50 du motif DRY a été mutée en Asn (R3.50N) afin de rompre les interactions ioniques de ce résidu. L’aspartate 3.49 a été muté en Asn (D3.49N) ou en Val (D3.49V), afin de neutraliser une des interactions du « DRY-lock » (Lagane, 2005). L’arginine 6.30 a été mutée d’une part en Asp (R6.30D) ou en Glu (R6.30E), afin de rétablir une possibilité d’interaction avec R3.50, d’autre part en Ala (R6.30A) et en Gln (R6.30Q) afin de mieux cerner le rôle de la charge de l’arginine. Afin de tester l’hypothèse d’interaction entre le résidu 6.30 et le résidu 2.40, l’aspartate 2 .40 a été mutée en Ala (D2.40A) ou en Arg (D2.40R) et des récepteurs présentant les deux mutations ont également construits (D2.40A/R6.30A et D2.40R/R6.30D). L’ensemble des résultats obtenus par l’analyse de ces mutants a permis de montrer que la nature des interactions entre l’extrémité cytosolique des hélices 3 et 6 influence l’activité du récepteur CCR5 (Springael, 2007). Une interaction forte conduit à une forme de récepteur inactif alors qu’une interaction faible s’accompagne d’une augmentation d’activité constitutive. Cette propriété de CCR5 serait donc partagée avec d’autres récepteurs appartenant à la famille de la rhodopsine. Cependant les interactions inter-hélice stabilisant ces conformations seraient différentes pour CCR5. D’autre part, l’étude de la position 2.40 laisse supposer l'importance du résidu aspartate 2.40 dans le maintien d'une conformation permettant l'activité constitutive du récepteur. Nous avons également testé s’il existait une corrélation entre activité constitutive et capacité du récepteur CCR5 à former des dimères, mais les résultats ne nous ont pas permis de mettre en évidence une quelconque relation entre activité et dimérisation.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished
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Full textAcanthamoeba spp. are ubiquitous phagocytic protists in soil and water. Giant viruses, including mimiviruses, marseillevirus or pandoraviruses, are among Acanthamoeba-resistant microorganisms. They have a sympatric lifestyle with other microorganisms within amoebae, and many lateral sequence transfers have been described that involved Acanthamoeba castellanii. In addition, some Acanthamoeba species appear to have different levels of susceptibility to giant viruses.The objective of this work was to explore for the first time the gene repertoire of the genomes of 14 different species of Acanthamoeba, as well as that of the two species Vermamoeba vermiformis CDC-19 and Willaertia magna c2c maky, and to study the genetic relationship of these amoebae with giant viruses.This work provided important genetic information for several species of amoebae with different susceptibility to giant viral infection. An additional work aimed to discuss the defense strategies observed or predicted for giant viruses and their hosts. The search for sequence homologies in other giant viruses genomes revealed the presence of several sequences suspected to be involved in defense mechanisms. However, no significant evidence of integration of known genomes or virophages sequences has been identified in all available genomes of Acanthamoeba species.Finally, we have designed three PCR primer systems targeting a conserved gene that encodes an alanine-tRNA ligase, for an effective and specific identification of Acanthamoeba. This work opens up several potential leads for future work on the interactions between amoebae and giant viruses
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Full textClay minerals which can be found in granular materials strongly influence the rheological properties of fresh concrete. Due to the recent technical evolution of concrete, the understanding of the effect of clays in such systems takes on a significant industrial interest. This study was divided into two part, the first one dealing with the adsorption mechanisms of two polymers onto clay surfaces: a superplasticizer (PCP) and a polycation (F25). IR and SAXS-WAXS analysis together with adsorption measurment revealed that superplasticizer are adsorbed by clays and that the used of polycation inhibites clays-PCP interactions. The adsorption process of F25 onto clays by cationic exchange explains the preferential adsorption of cationic compounds rather than PCP and the restructuration of clay particles at the nano and micronic scale during the adsorption. In a second part, the rheological study of granular suspensions revealed a strong effect of clay particles on the flow behaviors of such systems. The rheological study of pure clay suspensions allowed the modelisation of the effect of clays on granular suspensions using excluded volume. In this case, the anistropic features of clays particles characterized by various technics (TEM, SAXS-WAXS) explains water retention properties of such nanometric minerals
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