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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Interactions Drosophiles-guêpes endoparasitoïdes : rôle des vésicules extracellulaires du venin de Leptopilina boulardi dans le transport de facteurs de virulence et la spécificité d’hôte / Drosophila-endoparasitoid wasp interaction : role of extracellular vesicles of Leptopilina boulardi venom in the transport of virulence factors and host specificity

Wan, Bin 21 December 2017 (has links)
Le développement larvaire de Leptopilina boulardi (guêpe endoparasitoïde) a lieu dans la larve de Drosophile hôte, principalement D. melanogaster. La réponse immunitaire de l’hôte est l’encapsulement, formation d’une capsule mélanisée formée de couches d’hémocytes spécialisés, les lamellocytes, autour de l’œuf du parasitoïde. Le succès de L. boulardi repose sur l’injection de venin qui bloque l’action des lamellocytes. Ce venin, contient des composants protéiques et des vésicules originales baptisées vénosomes. J’ai montré que deux facteurs de virulence (VFs), LbGAP et LbGAP2, s’intègrent aux vénosomes lors de leur assemblage qui semble se faire de façon extracellulaire dans le canal reliant la glande à venin au réservoir. La microinjection de vénosomes purifiés comme celle du venin inhibe l’encapsulement. Les vénosomes marqués par fluorescence et les VFs co-immunolocalisent dans les lamellocytes de l’hôte après injection, leur internalisation passe par une endocytose flotilline/raft-domaine dépendante. Le taux d’internalisation diffère fortement entre les espèces hôtes de Drosophile testées (D. melanogaster>D. simulans>D. yakuba>D. suzukii) et il est corrélé au taux de réussite parasitaire, suggérant l’existence d’un récepteur spécifique sur les lamellocytes de D. melanogaster. Grâce à la souche mutante HopTum-l qui produit des lamellocytes constitutivement, j’ai séparé ces cellules et entrepris l’analyse protéomique de leur membrane pour identifier des récepteurs candidats. Mes résultats démontrent que les vénosomes sont des véhicules de transport interespèces impliqués dans la virulence parasitaire et qu’ils représentent un nouveau niveau de spécificité d’hôte. / Endoparasitoid wasps, such as Leptopilina boulardi (Figitidae), develop inside Drosophila host larvae, mainly D. melanogaster. Egg oviposition normally results in a capsule formation by specialized haemocytes, the lamellocytes, associated with a melanization reaction. The parasitic success of L. boulardi relies on injection with the egg of venom that blocks the action of lamellocytes. This venom, synthesized at the level of a specialized gland and stored in a reservoir, contains protein components and original vesicles (venosomes). I have shown that two described virulence factors, LbGAP and LbGAP2 (VFs), are embedded in venosomes during their assembly which seems to occur extracellularly in the duct connecting the venom gland to the reservoir. Microinjection of purified venosomes protects the egg from encapsulation like venom injection. Fluorescently labelled venosomes and VFs co-immunolocalize in lamellocytes after injection and their internalization involves a flotillin/raft-domain-dependent endocytosis. The venosomes internalization rate differs significantly between the Drosophila host species tested (D. melanogaster>D. simulans>D. yakuba>D. suzukii) and is correlated with the parasite success rate, suggesting the existence of specific receptor on lamellocytes of D. melanogaster. Using the HopTum-1 mutant that constitutively produces lamellocytes, I have purified these cells and performed proteomic analysis of their membrane to identify candidate receptors. My results demonstrate that venosomes are interspecies transport vehicles involved in parasite virulence that represent a new level of host specificity.
42

Role of the tumor microenvironment on mechanosensitive TRPV4 channels and tumor angiogenesis

Guarino, Brianna D. 04 August 2021 (has links)
No description available.
43

The impact of the syndecan-PDZ interactome on endosomal trafficking and extracellular vesicle composition / L'impact de l'interaction syndecan-PDZ sur le trafic endosomal et la composition des vésicules extracellulaires

Castro Cruz, Monica del Carmen 19 July 2018 (has links)
Les syndécans forment une famille de quatre protéines transmembranaires qui sont substituées par l'héparane sulfate. Grâce à ces chaînes glucidiques extracellulaires, les syndécans contrôlent la signalisation d'une pléthore de facteurs de croissance et de molécules d'adhésion. Une autre caractéristique remarquable des syndécans est la conservation de leur domaine intracellulaire au cours de l'évolution. Ce domaine contient un motif C-terminal qui peut induire une interaction avec les protéines dites «PDZ». Les interactions PDZ sont promiscues et les protéines PDZ contrôlent divers aspects de la signalisation cellulaire et de la communication cellule-cellule. Quatre interactions syndecan-PDZ ont été décrites à ce jour et toutes ces interactions ont des effets drastiques sur le comportement des cellules. En particulier, il a été documenté que l'interaction syndécan-synténine a un impact sur le trafic intracellulaire de molécules de signalisation liant l’héparan sulfate. De plus, les syndécans et la synténine coopèrent dans le contrôle la biogenèse des exosomes, organites extracellulaires fonctionnant comme des médiateurs importants de la communication cellule-cellule (y compris dans différentes maladies systémiques comme le cancer). Le protéome humain compte 150 protéines PDZ qui contiennent 266 domaines PDZ. Dans ce travail, nous avons mis à jour la complexité de l'interactome syndecan-PDZ et testé son impact sur le trafic membranaire et sur la composition des vésicules extracellulaires. Notre travail ouvre la voie à une meilleure compréhension des réseaux moléculaires contrôlant la communication cellule-cellule en physio-pathologie. / Syndecans form a family of four transmembrane proteins that are substituted with heparan sulfate. By virtue of these extracellular carbohydrate chains, syndecans control the signaling of a plethora of growth factors and adhesion molecules. Another remarkable feature of syndecans is the conservation of their intracellular domain through evolution. This domain contains a C-terminal motif that can mediate interaction with PDZ proteins. PDZ interactions are promiscuous and PDZ proteins control various aspects of cell signaling and cell-cell communication. Four syndecan-PDZ interactions have been described so far and all these interactions have broad effects on cell behavior. In particular, it was documented that syndecan-syntenin interaction has impact on the intracellular trafficking of heparan sulfate cargo. Moreover syndecan-syntenin controls the biogenesis of exosomes, extracellular organelles emerging as important mediators of cell-cell communication in health and diseases. The human proteome contains 150 PDZ proteins and 266 PDZ domains. Here we started addressing the complexity of the syndecan-PDZ interactome and tested for its impact on membrane trafficking and on the composition of extracellular vesicles. Our work paves the way for a better understanding of the molecular mechanisms and networks controlling cell-cell communication in health and disease.
44

Characterization of the Immune Stimulated Release of Extracellular Vesicles from Murine Cells

Norrie, Andrew 31 March 2021 (has links)
Introduction: Viruses, extracellular vesicles (EVs) and endogenous retroviruses (ERVs) are types of sub-micron particles which are known to be released from a vast range of cell types, across many species. There are many medically relevant sub-micron particles which can enter healthy cells and enable the intercellular delivery of functional host-derived and foreign products, through their enclosed lipid layers. While multiple particle subsets have been identified, many of the properties, behaviors and biochemical functions have not been fully described and have yet to be characterized. Materials and Methods: CD4⁺ naïve T-cells were isolated from female C57BL6/N mice and stimulated with varying concentrations of PMA/I. In addition to concentration, the length of PMA/I activation was assessed. Supernatants and cells were harvested, filtered, and stained to be subsequently analyzed by Nanoscale Flow Cytometry, Nanoparticle Tracking Analysis and Flow Cytometry. Particle populations were quantified and sorted by size, by NTA. Labelling dye CFSE was used in conjunction with fluorescently conjugated CD81 and CD9 antibodies to separate EVs, including exosomes, from background signal. Naïve T-cell purity, viability and levels of activation were assessed by flow cytometry using CD3, CD4 and CD62L antibodies and viability staining. Results: Increasing PMA concentration led to a global increase in particles by T-cells and a specific increase in smaller particle production and were demonstrated to be significant by Welch’s T-test, when compared to non-activated and DMSO controls (p<0.0001). In addition to concentration, activation length also correlated with increases in total particle counts and a specific increase in the secretion of smaller particles in comparison to non-activated and DMSO controls (p<0.0001). Labelling techniques by NFC revealed an increased presence of CFSE-CD81 positive and CFSE-CD9 positive particles secreted by T-cells, treated for 24 hours, compared to the 0- and 12-hour timepoints. Conclusion: This work demonstrates preliminary steps and outlines methods to begin assessing discrete particle populations and subsets secreted by murine naïve T-cells. Being able to identify patterns of particle secretions by naïve T-cells, especially under immune-stimulated conditions, may be the solution to uncovering the necessary information on EV physiology, that is required to understand the roles EVs play in pathology and how these conserved pathways may lead conditions to become exacerbated. This knowledge is essential to uncovering the roles EVs play in pathophysiology, and in the development of novel rapid diagnostic tests, to screen for cancers, infections, autoimmune disorders, and numerous other pathological conditions.
45

Mesenchymal Stromal Cells to Treat Lung and Brain Injury in Neonatal Models of Chronic Lung Disease

Lithopoulos, Marissa Athena 13 May 2021 (has links)
No description available.
46

EFFECTS OF EXERCISE AND OBESITY ON SKELETAL MUSCLE DAMAGE AND REPAIR

Brian P Sullivan (11205489) 30 July 2021 (has links)
<p>Obesity is associated with an increase in low grade systemic inflammation. Skeletal muscle of individuals with obesity undergo numerous biochemical and morphological alterations including an increase in ectopic lipid accumulation in skeletal muscle and increased macrophage infiltration. Increased intermuscular adipose tissue and macrophages contribute to skeletal muscle inflammation and insulin resistance by secreting elevated proinflammatory cytokines and lipids. This also contributes to reduction in skeletal muscle quality, increasing the susceptibility of muscle to damage and impairing the regenerative response to muscle. Exercise training can reduce inflammation and improve skeletal muscle quality. Importantly reductions in inflammation occur without change in adiposity. Peroxisome proliferator activated receptor g coactivator 1-a (PGC-1a) exerts protective effects on skeletal muscle against damaging insults and may improve muscle regeneration.</p><p> The primary aim of my dissertation was to determine the mechanisms that lead to deficits in skeletal muscle integrity and regeneration in persons with obesity. In Chapter 1, an introduction to the various physiological, pathological, and clinical topics is provided. In Chapter 2, we investigated how exercise training and obesity independently alter skeletal muscle extracellular vesicle (EV) miRNA (miR) content. We found that obesity alters EV miR content indicative of altered anabolic signaling, while exercise training altered EV miR content in a manner indicative of reduced inflammation. In Chapter 3, we report that overexpression of PGC-1a reduces cardiotoxin induced damage of primary human myotubes but limits the ability of undifferentiated cells to reenter the cell cycle and produce progeny that could aid in the restoration of myotubes. In Chapter 4, we demonstrate that exposure to an obesogenic environment increases cardiotoxin induced damage of primary human myotubes from obese donors. In this study we also found that the restoration of myotube fusion index was reduced in lean and obese subjects when incubated with obesogenic media. In Chapter 5 is a review and summary of the outcomes described in Chapters 2-4, a discussion of the limitations of these experiments, and a discussion of future directions.</p>
47

Implementation of highly sensitive small extracellular vesicle (sEV) quantification method in the identification of novel sEV production modulators and the evaluation of sEV pharmacokinetics / 高感度定量法を利用した細胞外小胞の産生モジュレーターの探索と体内動態解析

Yamamoto, Aki 24 September 2021 (has links)
京都大学 / 新制・課程博士 / 博士(薬学) / 甲第23473号 / 薬博第849号 / 新制||薬||242(附属図書館) / 京都大学大学院薬学研究科薬学専攻 / (主査)教授 髙倉 喜信, 教授 山下 富義, 教授 小野 正博 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM
48

INVESTIGATION OF NOVEL THERAPIES AND DELIVERY SYSTEMS FOR TREATMENT OF HEPATOCELLULAR CARCINOMA

Badawi, Mohamed A. January 2017 (has links)
No description available.
49

Characterization of Histone H1 and Extracellular Vesicles by Mass Spectrometry

Harshman, Sean William January 2013 (has links)
No description available.
50

Investigating the Architecture and Vesicle Tethering Function of the Yeast Exocyst Complex: A Dissertation

Heider, Margaret R. 28 January 2016 (has links)
The exocyst is an evolutionarily conserved, hetero-octameric protein complex proposed to serve as a multi-subunit tethering complex for exocytosis, although it remains poorly understood at the molecular level. The classification of the exocyst as a multisubunit tethering complex (MTC) stems from its known interacting partners, polarized localization at the plasma membrane, and structural homology to other putative MTCs. The presence of 8 subunits begs the questions: why are so many subunits required for vesicle tethering and what are the contributions of each of these subunits to the overall structure of the complex? Additionally, are subunit or subcomplex dynamics a required feature of exocyst function? We purified endogenous exocyst complexes from Saccharomyces cerevisiae, and showed that the purified complexes are stable and consist of all eight subunits with equal stoichiometry. This conclusion contrasts starkly with current models suggesting that the yeast exocyst tethers vesicles by transient assembly of subcomplexes at sites of exocytosis. Using a combination of biochemical and auxininduced degradation experiments in yeast, we mapped the subunit connectivity, identified two stable four-subunit modules within the octamer, and demonstrated that several known exocyst binding partners are not necessary for exocyst assembly and stability. Furthermore, we visualized the structure of the yeast complex using negative stain electron microscopy; our results indicate that exocyst exists predominantly as an octameric complex in yeast with a stably assembled, elongated structure. This is the first complete structure of a CATCHR family MTC and it differs greatly from the EM structures available for the partial COG and Dsl1 complexes. Future work will be necessary to determine whether exocyst conformational changes are a required feature of vesicle tethering and how such changes are regulated. These architectural insights are now informing the design of the first in vitro functional assay for the exocyst complex. We developed methodology for attaching fluorescently-labeled exocyst complexes to glass slides and monitoring the capture of purified, endogenous secretory vesicles by single molecule TIRF microscopy. By this approach, we can monitor tethering events in real time and determine the required factors and kinetics of exocytic vesicle tethering.

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