To see the other types of publications on this topic, follow the link: Cell surface molecules][Morphogenesis.
Dissertations / Theses on the topic 'Cell surface molecules][Morphogenesis'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 38 dissertations / theses for your research on the topic 'Cell surface molecules][Morphogenesis.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Hinton, I. E. "The developmental biology of Drosophila cell surfaces." Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233464.
Full text
2
Kaplan, Elizabeth Danford. "Cell adhesion molecules in human hair follicle morphogenesis /." Thesis, Connect to this title online; UW restricted, 1996. http://hdl.handle.net/1773/5688.
Full text
3
Preston, Alexandra McEwan. "Interactions of immunoglobulin superfamily leukocyte cell surface molecules." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318630.
Full text
4
Snell, Daniel C. "Cell-surface molecules of developing chicken B cells." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326977.
Full text
5
Tasker, Lynn. "Cell surface molecules involved in the regulation of B cell activation." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261832.
Full text
6
Morris, L. "Expression of surface molecules on mouse foetal macrophages." Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235069.
Full text
7
Tennant, Ian. "Antibody-based strategies for identifying novel apoptotic-cell surface-associated molecules." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/29395.
Full textAbstract:
Defective clearance of apoptotic cells (ACs) is linked to autoimmune and inflammatory disease states such as systemic lupus erythematosus and cystic fibrosis. Relatively few markers exist for the ‘eat me’ signals displayed on the AC surface despite the great potential for such molecules as diagnostic or therapeutic reagents. In this work various antibody-based strategies were employed in an attempt to identify novel AC-specific epitopes. An initial strategy utilised a phage displayed antibody library containing a repertoire of ~108 antibody fragments encoded by human germline genes as an unbiased source of binding specificity. An alternative approach was based on the knowledge that receptors used by macrophages to recognise ACs also recognise pathogen-associated molecules. By looking for the ability of antibodies raised against pathogens to cross-react with ACs the hypothesis that cells undergoing apoptosis reveal molecular patterns that resemble those on pathogen related structures was tested. Screening of antibodies raised in vivo, that have previously been characterised as having specificity for pathogen-associated molecular patterns (PAMPs) revealed that some cross-react with cells undergoing apoptosis. One of these antibodies was found to bind an epitope found on the ubiquitously expressed ~40KDa precursor to Laminin-Binding-Protein (LBP/p40). These findings suggest that epitopes resembling PAMPs appear on the surface of mammalian cells as a result of apoptosis and that these epitopes can be found on endogenously expressed molecules which are normally excluded from the surface of viable cells. The ability of host receptors to cross-react with host and pathogen-associated epitopes in this way may lead to a greater understanding of the mechanisms of autoimmune reactions and allow design of approaches to stimulate the immune system for the treatment of cancer.
8
Bloom, Stuart. "Adhesion molecules in the gastrointestinal tract : a search for cell surface molecules upregulated in inflammatory bowel disease." Thesis, University of Oxford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239338.
Full text
9
McConnell, Michael James. "Cell-surface Tumoricidal Molecules and NF-kB in the Tumor-burdened Host." Thesis, Virginia Tech, 2002. http://hdl.handle.net/10919/9609.
Full textAbstract:
Tumor-distal immune suppression promotes tumor growth by preventing the recruitment of leukocytes to the tumor-proximal microenvironment. Tumor necrosis factor (TNF)-a is both secreted by and expressed on the cell-surface (mTNF-a) of macrophages. When stimulated with LPS, tumor-burdened host (TBH) macrophages secrete more TNF-a than normal host (NH) macrophages. In this study, I showed that mTNF-a is elevated both in freshly isolated and stimulated TBH macrophages. Additionally, I analyzed the expression of Fas and FasL on freshly isolated and LPS-stimulated macrophages and found no differences between TBH and NH macrophages. Fas and Fas ligand (FasL) cell-surface expression was analyzed on NH and TBH T-cells. While no difference was observed in freshly isolated cells, cell-surface expression of both proteins remained higher in TBH T-cells than NH T-cells after mitogenic stimulation. Fas and FasL analysis was also extended to the MethKDE fibrosarcoma and I found that these tumor cells express high levels of FasL. Because past observations show increased TNF-a mRNA expression in TBH macrophages relative to NH macrophages, I hypothesized that NF-kB activation may be increased as well. NF-kB is a transcription factor whose activation is required for TNF-a transcription. I observed increased NF-kB activation in both splenic and peritoneal TBH macrophages. Interestingly, electrophoretic mobility shift analysis (EMSA) suggests that different species of NF-kB were found in each distinct population of macrophages. Together, these data demonstrate that cell-surface tumoricidal molecules and NF-kB are dysregulated in the tumor-burdened host.Master of Science
10
Mitakidis, Nikolaos. "Structural studies of cell surface signalling molecules for neuronal guidance and connectivity." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:67a41765-afb6-4cbe-ae60-884773127b6c.
Full textAbstract:
Signal transduction is critical during the lifetime of a neuron as it navigates to reach its targets, forms functional synaptic connections and adjusts the molecular architecture of these connections in an activity-dependent manner. Understanding the molecular organisation of components required for neuronal signalling will provide novel biological insight and can contribute to the design of therapeutics for neurodevelopmental and neurodegenerative disorders. The focus of the thesis is on determining mechanistic molecular details of a number of distinct cell surface systems implicated in neuronal signalling. Crystallographic studies on the cell surface complex between Eph receptor A4 and ephrinA5 contributed to understanding how the modes of higher order arrangements of receptors involved in guidance affect signal transduction across the membrane. A set of structural and biophysical studies addressed the proteoglycan regulation of RPTPσ-TrkCtrans-synaptic interaction and contributed to deciphering the principles of the switch from axonal growth to synapse establishment and formation. A crystallographic and biochemical analysis of the neuronal C1q-like family, enabled mapping their interactions with potential synaptic partners, and guided functional studies aimed at elucidating their roles in the maintenance of synaptic integrity. Preliminary work on the neuronal Sigma-1 receptor chaperone laid the foundations for the structural determination of this receptor.
11
Cole, Louise. "Immunocytochemical studies of fungal cell surface molecules and the Vicia faba-Botrytis interaction." Thesis, Oxford Brookes University, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308926.
Full text
12
Dumon, Valerie Marie-Claude. "Cell surface molecules involved in the development and survival of cerebellar Purkinje cells." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267887.
Full text
13
Han, Y. "Towards retinal repair : analysis of photoreceptor precursor cells and their cell surface molecules." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1417170/.
Full textAbstract:
Photoreceptor cells are the sensory cells of the retina, responsible for detecting light and conducting the signals to secondary neurons. Because they cannot be regenerated, loss of photoreceptor cells leads to irreversible blindness. Cell transplantation with postmitotic photoreceptor precursor cells has been shown as a feasible approach to rescue vision in animal models, but the molecular properties of these transplantation-competent cells are not understood. The aims of this thesis are to 1) determine the properties of photoreceptor precursor cells by transcriptome and proteome analysis; 2) identify cell surface molecules that can be used to isolate these cells from cell mixtures and/or that are important for their migration and correct integration in development and in a transplantation context. Nrl/CrxGFP transgene-labelled photoreceptor precursor cells were separated from other retinal cells by flow cytometry and subjected to microarray and mass spectrometry analysis. Bioinformatics analysis showed that the photoreceptor precursor cells were enriched in expression of genes encoding cell projection proteins. Over 200 cell surface molecule candidates were identified and 32 genes encoding confirmed extracellular domains were expressed > 5-fold higher in photoreceptor precursors than other retinal cells. These included the stem cell marker Prom1 (CD133), which was specifically expressed in photoreceptor cells (particularly on their cilia) throughout development as well as on transplanted photoreceptors. Together with CD73 and CD24, it serves as a specific marker to isolate photoreceptor cells for transplantation. An axon guidance molecule Sema7a was shown to be highly expressed in photoreceptor cells. It co-labels with PlxnC1, rather than the expected receptor Itgb1, in developing retina, as well as transplanted migrating photoreceptor cells. Knockout of Sema7a resulted in retinal holes and abnormal photoreceptor synapse projection indicating a role of Sema7a in outer retina lamination. This study sets the foundation for future work on photoreceptor cell surface molecules in development and retinal repair.
14
Torun, Engin. "Electronic Properties Of Dye Molecules Adsorbed On Anatase-titania Surface For Solar Cell Applications." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/12610846/index.pdf.
Full textAbstract:
Wide band gap metal oxides have recently become one of the most investigated materials in
surface science. Among these metal oxides especially TiO2 attracts great interest, because of
its wide range applications, low cost, biocompatibility and ease of analysis by all experimental
techniques. The usage of TiO2 as a component in solar cell technology is one of the most
investigated applications of TiO2 . The wide band gap of TiO2 renders it inecient for isolated
use in solar cells. TiO2 surface are therefore coated with a dye in order to increase eciency.
This type of solar cells are called dye sensitized solar cells .
The eciency of dye sensitized solar cells is directly related with the absorbed light portion of
the entire solar spectrum by the dye molecule. Inspite of the early dyes, recent dye molcules,
which are called wider wavelength response dye molecules, can absorb a larger portion of
entire solar spectrum. Thus, the eciency of dye sensitized solar cells is increased by a
considerably amount.
In this thesis the electronic structure of organic rings, which are the fundamental components
of the dye molecules, adsorbed on anatase (001) surface is analyzed using density functionaltheory. The main goal is to obtain a trend in the electronic structure of the system as a function of increasing ring number. Electronic structure analysis is conducted through band structure
and density of states calculations. Results are presented and discussed in the framework of
dye sensitized solar cells theory.
15
Hedley, Susan Jennifer. "Investigation of pigmentation and immune-related cell surface molecules in cultured normal and vitiligo melanocytes." Thesis, University of Sheffield, 1999. http://etheses.whiterose.ac.uk/3483/.
Full textAbstract:
Vitiligo is an acquired idiopathic hypomelanotic disorder which has an unknown aetiology and ultimately affects melanocytes, primarily of the skin. Many patients with vitiligo suffer from psychological distress and therefore it is important to determine why melanocytes are destroyed. The aim of this study was to learn more about the basic cellular physiology of normal and vitiligo melanocytes. Morphology, proliferation and pigmentation in normal melanocytes were highly influenced by media additives, bovine pituitary extract (BPE), cholera toxin (CT), foetal calf serum (FCS) and phorbol 12-myristate 13 acetate (PMA). In the absence of these factors, extracellular matrix (ECM) proteins increased survival, proliferation and pigmentation of normal melanocytes, while ultraviolet irradiation (UVR) increased dendricity and pigmentation in the presence of these factors. Normal and vitiligo melanocytes were morphologically very similar and long-term cultured vitiligo melanocytes had proliferation which was not significantly different to that of normal melanocytes. Constitutive and cytokine-stimulated expression of intercellular adhesion molecule-1 (ICAM-1), major histocompatibility complex (MHC) class I and II were not different between normal and vitiligo melanocytes in vitro. The latter suggested that vitiligo melanocytes do not have an inherent defect in regulation of these adhesion molecules which could lead to their premature interaction with the immune system. a-melanocyte stimulating hormone (a-MSH) has a controversial pigmentary role in man. In normal melanocytes, only under a limited number of media conditions did melanocytes exhibit increased melanogenesis to a-MSH. However a-MSH was found to be particularly effective at opposing the actions of TNF-a-stimulated ICAM-1 expression in melanocytes. This finding supported an immunomodulatory role for a-MSH in normal melanocytes. Finally a surgical treatment using cultured epithelial autograis (CEA) was used to treat 3 patients with symmetrical (generalised) vitiligo, with mixed results. One patient showed good repigmentation, while the response was less promising in the other-two patients.
16
Selby, Anna Louise. "Identification of novel T-cell surface molecules that induce inflammatory cytokine production in human monocytes :." Thesis, St George's, University of London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423142.
Full text
17
Collie, Angela M. B. "The macrophage response to biomaterial topography : gene expression, integrin signaling, and surface adhesions /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/8115.
Full text
18
Bahra, Sukhvinder Singh. "Investigations into the mobility of cell-surface MHC molecules using an IgG-Oregon Green probe : a FRAP investigation." Thesis, University of Essex, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396061.
Full text
19
Maccormac, Luci Penelope. "The effect of cytomegalovirus infection of endothelial cells on cell surface molecules involved in leukocyte adhesion, migration and immune recognition." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300625.
Full text
20
Grunkemeier, John M. "Effect of adhesion proteins and surface chemistry on the procoagulant state of adherent platelets /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/8087.
Full text
21
Nguyen, Beth P. "Integrin alpha 6 beta 4 ligation to laminin 5 and phosphoinositide 3-OH kinase define differences in alpha 3 beta 1-laminin 5 and alpha 2 beta 1-collagen spreading : implications for epidermal wound repair /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/9286.
Full text
22
Tay, Chin Hun. "In Vivo Regulation of Murine Cytomegalovirus Infections: The Role of Cell Surface Molecules and Mechanisms of Control by Natural Killer Cells: A Dissertation." eScholarship@UMMS, 1997. https://escholarship.umassmed.edu/gsbs_diss/64.
Full textAbstract:
The overall aim of this thesis was to determine how natural killer (NK) cells regulate virus infections in vivo. Anti-viral mechanisms by which NK cells control murine cytomegalovirus (MCMV) infection in the spleens and livers of adult C57BL/6 mice were first studied, revealing different mechanisms of control in different organs. Three days post-infection, MCMV titers in the spleens of perforin-deficient (perforin 0/0) mice were higher than in wild type controls, but no elevation of liver titers was found in perforin 0/0 mice. NK cell depletion in MCMV-infected perforin 0/0 mice resulted only in an increase in liver viral titers but not in spleen titers. Depletion of IFN-γ in adult C57BL/6 mice by injections with mAbs to IFN-γ resulted in an increase in viral titers in the liver but not in the spleen. Analyses using IFN-γ-receptor-deficient (IFN-γR0/0) mice, rendered chimeric with C57BL/6 bone marrow cells, indicated that even though the donor spleen cells could respond to IFN-γ, the depletion of NK cells in a recipient environment where the host cells could not respond to IFN-γ caused an increase in MCMV titers in the spleens but had little effect in the liver. IFN-γ has the ability to induce a variety of cells to produce nitric oxide (NO), and administrating the nitric oxide synthase (NOS) inhibitor Nω-monomethyl-L-arginine (L-NMA) into MCMV-infected adult C57BL/6 mice resulted in MCMV titer increases in the liver but not in the spleen. These data indicate that in adult C57BL/6 mice, there is a dichotomy in the mechanisms utilized by NK cells in the regulation of MCMV in different organs. In the spleen NK cells exert their effects in a perforin-dependent manner, suggesting a cytotoxic mechanism, whereas in the liver the production of IFN-γ by NK cells may be a predominant mechanism in the regulation of MCMV synthesis. These results may explain why the Cmv-1r (Cmv-1-resistant) locus, which maps closely to genes regulating NK cell cytotoxic function, confers an NK cell-dependent resistance to MCMV infection in the spleen but not in the liver.
The ability of adoptively transferred cells to protect suckling mice from MCMV was another model used to study the mechanisms utilized by NK cells in the regulation of MCMV. Adoptive transfers of 129, C57BL/6 and perforin 0/0 spleen cells or lymphokine-activated killer (LAK) cells into 4 - 6 day old MCMV-infected C57BL/6 suckling mice significantly lowered the splenic MCMV titers in these mice compared to the infected controls. Adoptive transfers of C57BL/6 spleen cells into MCMV-infected 129 suckling mice also decreased the amount of MCMV in the 129 suckling mice, but C57BL/6 spleen cells could not regulate MCMV synthesis when adoptively transferred into 129/IFN-γR0/0 suckling mice. These results suggest that, in the suckling mouse model, the regulation of MCMV by the adoptively transferred NK cells is via an IFN-γ-dependent, perforin-independent, Cmv-1-independent mechanism.
The Cmv-1 gene locus resides within the NK gene complex, in close proximity to the Ly49 NK cell receptor family. Analyses were carried out to determine if any of the 4 known Ly49 NK cell receptors (Ly49A, C, D and G2) played a role in the control of MCMV synthesis by NK cells. Studies comparing the expression of the different Ly49 NK cell subsets in the spleen and the peritoneal cavity revealed that there were differences in the distribution of the Ly49 receptors on NK1.1+ cells. Three days post-MCMV infection, the percentage of NK1.1+- Ly49+ NK cells in the spleen and the peritoneal cavity were different than in naive controls. Within the splenic NK1.1+ population, increases in NK1.1+ -Ly49A+ and NK1.1+-Ly49G2+ cells but decreases in NK1.1+-Ly49C+ and NK1.1+-Ly49D+ cells were observed. These changes in the spleen were accompanied by a concomitant decrease in NK1.1+ - Ly49A+ cells and increases in NK1.1+-Ly49C+, NK1.1+-Ly49D+ and NK1.1+-Ly49G2+ cells within the NK1.1+ population in the peritoneal cavity. These data suggest that 3 days post-MCMV infection, there may be movement of NK cells between the different organs. The role of Ly49 NK cell receptors in the regulation of MCMV was tested using adult C57BL/6 mice depleted of single or multiple Ly49 NK cell subsets. These in vivo depletions did not affect the ability of the residual NK cells to regulate MCMV synthesis. LAK cells sorted into the different Ly49 NK cell subsets and adoptively transferred into C57BL/6 suckling mice lowered the splenic MCMV titers in these mice. Together, these results indicate that even though there is a redistribution of the Ly49 NK cell subsets during MCMV infection, the presence or absence of anyone of the 4 tested Ly49 NK cell receptors does not affect the regulation of MCMV by NK cells. However, there remain a possibility that one of the undefined Ly49 receptors or an untested NK cell receptor may be important in the control ofMCMV.
Most of the cloned NK cell receptors have been shown to bind to MHC class I molecules, and MHC class I antigens have been implicated as modulators of target cell sensitivity to NK cell-mediated lysis. The regulation of virus infections and the fate of NK cells and their natural targets was examined in β2-microglobulin-deficient mice [β2m (-/-)], which have defective MHC class I expression. Infections with either the NK cell-sensitive MCMV or the NK cell-resistant lymphocytic choriomeningitis virus (LCMV) significantly augmented NK cell activity in either C57BL/6 or β2m (-/-) mice. Depletion of NK cells in vivo with antiserum to asialo GM1 markedly enhanced the synthesis of MCMV but had no effect on the synthesis of LCMV in either strain of mouse. Adoptively transferred β2m (-/-) spleen cells lowered splenic MCMV titers in C57BL/6 suckling mice, not unlike adoptively transferred C57BL/6 spleen cells. Analysis of naturally NK cell-sensitive thymocyte targets from these virus-infected β2m (-/-) mice revealed no cell surface expression of class I MHC detectable by conformation-dependent or -independent antibodies, but the virus infections enhanced class I expression on thymocytes from C57BL/6 mice. The sensitivity of C57BL/6 thymocytes to NK cell-mediated lysis was markedly reduced after in vivo poly inosinic:cytidylic (poly I:C) treatment or viral infection; in contrast, the sensitivity of the β2m (-/-) thymocytes was significantly less affected by poly I:C or viral infection. These data indicate that the normal expression of MHC class I antigens on NK cells or their targets is not required for the anti-viral functions of NK cells against an NK-sensitive virus (MCMV) nor do they protect an NK-resistant virus (LCMV) from the anti-viral activity of NK cells.
Together, the data presented in this thesis help to further our understanding of the mechanisms utilized by NK cells in the control ofMCMV in both adult and suckling mice, and also help clarify the roles played by Ly49 NK cell receptors and MHC class I molecules in the regulation of MCMV.
23
Hu, Jian. "L'etude de la regulation de l'activation de clones de lymphocytes t humains helpers et cytotoxiques par les molecules cd2." Paris 7, 1988. http://www.theses.fr/1988PA077078.
Full text
24
Davì, Valeria. "Dynamique de la paroi cellulaire dans la régulation de la morphogenèse et de la croissance cellulaire." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS295/document.
Full textAbstract:
Les cellules dans la nature se développent dans un large éventail de formes, suivant divers modèles de croissance. Malgré l'importance de ces processus fondamentaux, la façon dont les cellules régulent leur croissance et leur morphogenèse est encore mal comprise. Dans cette thèse, j'ai exploré ces aspects, avec une approche principalement biomécanique, en concentrant mes investigations sur des cellules à paroi à croissance de pointe et en exploitant en particulier la levure fissipare Schyzosaccharomyces pombe. J'ai d'abord développé de nouvelles méthodes pour mesurer les paramètres mécaniques clés de la paroi cellulaire in vivo et à grande échelle, ce qui a permis les premières observations de la dynamique des parois cellulaires. Ceci a révélé que la paroi cellulaire est plus souple et très variable au niveau des pôles de croissance, et presque stable et plus rigide dans les sites non cultivés. Au cours de l'allongement, il existe une interaction entre la mécanique des parois et la croissance cellulaire, dont le contrôle actif permet l'expansion cellulaire tout en préservant l'intégrité des cellules. De plus, j'ai observé qu'il existe une forte corrélation entre la mécanique des parois cellulaires et la morphologie cellulaire, et des perturbations des propriétés de la paroi affectent directement l'établissement et la maintenance de la forme. Ensemble, mes résultats montrent que la régulation de la paroi est fondamentale dans la détermination de la dynamique cellulaire dans les cellules à parois épaissies. Globalement, cela suggère que l'observation dynamique de la mécanique de surface cellulaire est essentielle pour une compréhension complète des processus multifactoriels et complexes comme la croissance et la morphogenèseCells in nature develop in a wide range of forms, following diverse growth patterns. Despite the importance of these fundamental processes, how cells regulate their growth and morphogenesis is still poorly understood. In this thesis, I explored these processes, focusing my investigations on tip growing walled cells and in particular, by exploiting the fission yeast Schyzosaccharomyces pombe, adopting a mainly biomechanical approach. To this aim, I first developed novel methods to measure key cell wall mechanical parameters in vivo and in large scale, which allowed the very first observations of cell wall dynamics. This revealed that the cell wall is softer and highly variable at growing poles, and almost stable and stiffer at non-growing sites. During elongation, there is an interplay between wall mechanics and cell growth, whose active control allows cell expansion while preserving cell integrity. In addition, I observed that there is a strong correlation between cell wall mechanics and cell morphology, and ectopic perturbations of wall properties directly affect shape establishment and maintenance. Together my results show that the regulation of wall mechanics is fundamental in the determination of cell dynamics in tip growing walled cells. Moreover, this suggests that dynamic observation of cell surface mechanics is crucial for a complete understanding of multifactorial and complex processes as growth and morphogenesis
25
Höglund, Pär J. "Identification, Characterization and Evolution of Membrane-bound Proteins /." Uppsala : Acta Universitatis Upsaliensis Acta Universitatis Upsaliensis, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9329.
Full text
26
Brckalo, Tamara. "Functional characterization of the CD300e leukocyte receptor." Doctoral thesis, Universitat Pompeu Fabra, 2011. http://hdl.handle.net/10803/7238.
Full textAbstract:
The focus of this work was to functionally characterize the CD300e receptor expressed in human monocytes and myeloid dendritic cells and investigate the implications that receptor engagement has on their biology. We provide evidence formally supporting that CD300e functions as an activating receptor capable of regulating the innate immune response by triggering various pro- inflammatory functions including intracellular calcium mobilization, superoxide anion production, pro-inflammatory cytokine release and up-regulation of co-stimulatory molecules in myeloid cells. We also report that ligation of CD300e on the surface of monocytes results in their differentiation to functional MΦ2-like macrophages by an autocrine mechanism that involves M-CSF and its receptor (CD115).L'objectiu d'aquest treball ha estat caracteritzar funcionalment el receptor CD300e expressat en monòcits i cèl·lules dendrítiques mieloides humanes, així com investigar les implicacions que l'activació d'aquest receptor pot tenir en la seva biologia. Demostrem formalment que el receptor CD300e funciona com un receptor activador capaç de regular la resposta immune innata activant diverses funcions proinflamatòries, incloent la mobilització de calci intracel·lular, la producció d'anió superòxid, la secreció de citocines proinflamatòries i la inducció de molècules coestimuladores en cèl·lules mieloides. També descrivim que l'activació del receptor CD300e a la superfície dels monòcits provoca la seva diferenciació cap a macròfags funcionals del tipus MΦ2 gràcies a un mecanisme autocrí que funciona a través del M-CSF i el seu receptor (CD115).
27
Lu, Biao. "Evaluation of physico-chemical properties of biorefinery-derived amphiphilic molecules and their effects on multi-scale biological models." Thesis, Compiègne, 2015. http://www.theses.fr/2015COMP2218/document.
Full textAbstract:
Aujourd'hui, un grand nombre de nouvelles molécules peuvent être synthétisées à partir de la biomasse. Les tensioactifs dérivés de sucre sont notamment considérés comme une alternative aux tensioactifs fossiles en raison de leur biodégradabilité et de leur biocompatibilité. Cependant, les études associant la caractérisation physico-chimique et les propriétés biologiques de ce type de tensio-actifs sont limitées. Il est ainsi difficile de prédire les propriétés d'un tensioactif à partir de sa structure chimique. L'établissement d'une méthodologie permettant de relier la structure des surfactants à leurs propriétés apparait pertinent. Dans ce travail, quatre surfactants dérivés de sucre ayant chacun une chaîne C8 liée à une tête glucose ou maltose par un groupe amide ont été caractérisés par leurs propriétés tensio-actives dans différentes solutions (eau et milieu biologique). Leurs interactions avec des protéines ont également été analysées. Concernant l'évaluation des propriétés biologiques, des tests de cytotoxicité/irritation ont été effectués sur trois modèles in-vitro : 1) modèle cellulaire 20 (cellules L929 cultivées en monocouche), Il) modèle cellulaire 30 (cellules L929 cultivées dans un gel de collagène), Ill) épiderme humain reconstitué. Les résultats indiquent que les quatre surfactants synthétisés présentent de bonnes propriétés tensio-actives et trois d'entre eux sont moins cytotoxiques que des tensioactifs de référence. Plusieurs hypothèses permettant de relier la structure chimique des molécules à leurs propriétés physico-chimiques et biologiques ont été proposées. Des travaux futurs permettront d'enrichir la base de données sur les relations structure-propriétés des tensioactifs issus de la biomasse, et de l'utiliser pour synthétiser des surfactants présentant des propriétés adaptées aux applications envisagéesNowadays, a wide variety of new molecules can derive from biomass. Among them, the family of sugar-based surfactants, which are considered as alternatives to fossil-based surfactants, due to their relatively high biodegradability and biocompatibility, exhibit interesting properties both in terms of their self-assembly and their ability to induce biological responses. In the study, for the purpose to analyse these properties, different methodologies have been established. In this work, physico-chemistry and cellular biology methodologies are associated to analyse the properties of pre-selected molecules characterized by gradua) structure modifications. Firstly, we have screened synthesized sugar-based surfactants according to their solubility and their ability to reduce surface tension of water. Four pre-selected molecules, with a C8 chain linked to a glucose or maltose head through an amide functional group, either under the form of carbamoyl (carbohydrate scaffold bearing the carbonyl) or alkylcarboxamide (the alkyl chain bearing the carbonyl), were then dissolved in water/ cell culture media for surface tension measurements. Their behaviors in solutions were characterized by Krafft points, Critical Micellar Concentrations or self-assembling properties through different methods. To evaluate the cytotoxic/ irritant effects of these molecules on cells and tissues, 3 in-vitro models were established: I) 2D cell culture mode! (L929 cell monolayer) II) 3D ce!! culture mode! (L929 cells embedded in collagen gel) and III) Reconstituted human epidermis (differentiated human keratinocytes). Corresponding experiments were carried out on these models with increasing complexity. Results show that the synthesized sugar-based surfactants, GlulamideC8, Glu6amideC8, Glu6amideC8' and MallamideC8 can reduce the surface tension of water solution to the came level as standard surfactants (Tween 20 and Hecameg). In the meantime, GlulamideC8, Glu6amideC8' and MallamideC8 present Iess cytotoxicity effects on L929 cells both in the monolayer model and the 3D mode! than Tween 20 and Hecameg. All synthesized and standard surfactants (GlulamideC8, Glu6amideC8, Gu6amideC8', MallamideC8, Tween 20 and Hecameg) have no significant cytotoxic/ irritant effects on reconstituted human epidermis at 1000 ig/mL after 48 h of topical application. Discussions have been made according to the results of experiments to establish possible structures/ physico-chemical properties - cytotoxicity relationships of these surfactants
28
Cordier, Baptiste. "Compréhension des processus cellulaires associés à l' enveloppe de Bacillus subtilis : GluP, une protéase intramembranaire impliquée dans la dégradation des protéines membranaires & CmmB, un cofacteur de la synthèse de la paroi bactérienne." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM4006.
Full textAbstract:
L'enveloppe cellulaire bactérienne joue plus qu'un rôle de barrière d'échange. Elle est au coeur des processus cellulaires essentiels comme la morphogenèse et la division. Cette structure abrite environ un quart des protéines codées par le génome. Le but de mon travail a été de mieux comprendre le rôle de deux protéines membranaires dans la construction et la dynamique de l'enveloppe chez Bacillus subtilis. GluP est une protéase intramembranaire rhomboïde. Ces protéases clivent des segments transmembranaires dans la membrane afin de moduler l'activité de diverses protéines. Elles participent à de nombreux processus cellulaires chez les eucaryotes. Cependant, les fonctions biologiques des rhomboïdes procaryotes sont pour l'heure presque totalement inconnues. Nos résultats suggèrent que GluP participe au contrôle qualité des protéines membranaires à la manière des pseudo-rhomboïdes associées au système ERAD eucaryote. Elle forme un complexe avec FtsH, une protéase majeure du contrôle qualité des protéines. Ce complexe est impliqué dans la dégradation d'un substrat de rhomboïde. Le rôle de GluP serait de permettre la dislocation du segment transmembranaire et faciliter la prise en charge du substrat par FtsH. Le second projet auquel j'ai participé a consisté à comprendre le rôle de la protéine CmmB dans la morphogenèse. Son absence conduit à une morphologie cellulaire élargie. CmmB semble faire partie de la machinerie de synthèse du peptidoglycane au cours de l'élongation de la paroi. Elle serait nécessaire au bon fonctionnement d'une ou de plusieurs penicillin-binding proteins (PBPs). En particulier, nous proposons que CmmB est un cofacteur de la transpeptidase PBP2aThe bacterial cell envelope is an obligatory barrier. It is a fundamental component in essential cellular processes such as morphogenesis and cell division. It hosts about a quarter of the proteins encoded in the genome. My work was aimed at understanding the function of two membrane proteins in the building and the dynamics of the cell envelope in the model bacterium Bacillus subtilis.GluP is a rhomboid intramembrane protease. Usually, rhomboids cleave transmembrane segments within the membrane to modulate protein functions. In eukaryotes, they participate in many cellular processes and their dysfunction lead to several pathologies. However, prokaryotic rhomboid functions remain almost totally unknown. Our results suggest that GluP is involved in bacterial membrane protein quality control, in a process akin to pseudo-rhomboid dependent endoplasmic reticulum associated protein degradation in eukaryotes. GluP forms a complex with FtsH, a major protease in protein quality control. That complex is not involved in the cleavage of a membrane substrate but in its degradation. We propose that GluP is required for the dislocation of the transmembrane segment, thus facilitating full-length substrate degradation by FtsH in the cytoplasm. My thesis second objective was to understand the role of the CmmB protein in morphogenesis. The absence of CmmB leads to slightly enlarged cells. CmmB seems to belong to the peptidoglycan synthesis machinery for cell-wall elongation. Our data support the idea that it is required for the proper activity of one or several penicillin-binding proteins (PBPs). In particular, we propose that CmmB is a cofactor of the PBP2a transpeptidase
29
Shi, Lei. "Molecular Mechanisms of Neurite Complexity in the Drosophila Brain: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/474.
Full textAbstract:
Development of functional neural circuits involves a series of complicated steps, including neurogenesis and neuronal morphogenesis. To understand the molecular mechasnims of neurite complexity, especially neurite branching/arborization, the Drosophila brain, especially MBNs (mushroom body neurons) and PNs (projection neurons) in olfactory circuitry, was used in this dissertation work as the model system to study how two molecules, Dscam and Kr-h1 affect neurite complexity in the Drosophilabrain.
For the Drosophila Dscam, through alternative splicing it could encode up to 152,064 distinct immunoglobulin/fibronectin type cell adhesion molecules. Each Dscam isoform is derived from one of the 19,008 ectodomain variants connected with one of the two alternative transmembrane segments and one of the four possible endodomain portions. Recent studies revealed that Dscam was widely required for neurite branching/arborizaiton. However, due to the technical difficulty, the functional roles of Dscam transmembrane variants and ectodomain variants remain unclear. In this thesis work, a microRNA based RNA interference was used to knock down distinct subsets of Dscam isoform. First, loss of Dscam[TM1] versus Dscam[TM2], two distinct Dscam transmembrane variants, disrupted the dendritic versus axonal morphogenesis, respectively. Furthermore, structural analysis suggested that the juxtamembrane portion of transmembrane segment was required for the Dscam protein targeting in dendrites/axons and this differential protein targeting might account for the functional distinction between Dscam[TM1] and Dscam[TM2]. Second, to further address the functional significance of having two Dscam transmembrane variants in axons versus dendrites, the possibility that there might be different usage of Dscam repertoire between axons and dendrites that lead to different levels of morphological complexity between axons and dendrites in the same neuron was examined. To this end, end-in targeting approaches were used to exchange Dscam populations between axons and dendrites. Though the genetic data suggested that Dscam populations were exchanged between axons and dendrites, the phenotypic analysis in various neuronal types revealed that depending on the neuronal types, exchange of Dscam populations between axons and dendrites might primarily affect either axonal or dendritic morphology, suggesting that different usage of Dscam population between axons and dendrites might regulate complex patterns of neurite morphology. Finally, the functions of Dscam exon 4 variants had been addressed in different model neurons in the Drosophilabrain. First, 12 Dscam exon 4 variants were divided into three groups based on their phylogenetic distance. Then, three miRNA constructs were engineered to knock down one group at a time. The genetic data suggested that different Dscam exon 4 variants are differentially required in different neurons to support their proper neuronal morphogenesis. In summary, this part of my thesis work identified and characterized previously unrecognized functions of all these distinct Dscam variants and provided novel insights into how diverse Dscam isoforms regulate the different aspects of neuronal morphogenesis.
In the honey bee brain, Kr-h1 is upregulated during the behavioral shift from nursing to foraging when there is increased neurite branching in the brain. To directly examine the hypothesis that altered Kr-h1 expression might regulate morphological complexity of neurites, this research work involved the MARCM (mosaic analysis with a repressible cell marker) and TARGET (temporal and regional gene expression targeting) techniques to analyze the roles of Kr-h1 in Drosophila neuronal morphogenesis. Interestingly, increased expression of Kr-h1 blocked the axon branching and further disrupted the lobe formation in the mushroom body whereas the loss-of-Kr-h1 did not show any apparent neuronal morphogenetic defects. In addition, it was observed that Kr-h1 was expressed when MB (mushroom body) did not undergo active morphogenesis, suggesting its potential anti-morphogenetic activity. Indeed, loss of Kr-h1 (Kruppel homolog 1) enhanced the neuronal morphogenesis that was otherwise delayed due to the defective TGF-beta signaling. Furthermore, Kr-h1 expression was closely linked to ecdysone dependent signaling: Kr-h1 was first regulated by usp (ultraspiracle), which dimerized with various ecdysone receptors and then Kr-h1 expression was essential for proper ecdysone patterning in the larval CNS (central nervous system). Together, though Kr-h1could potentially regulate the neurite complexity, it seems primarily involved in the coordinating ecdysone signaling.
In conclusion, the powerful genetic toolkit available in the Drosophila has allowed the investigation in the molecular mechanisms of neuronal morphogenesis and understanding of these mechanisms will enhance our understanding of how the complex nervous system is wired to perform the delicate behaviors.
30
Ek, Moira. "Bacterial Display of a Tau-Binding Affibody Construct:Towards Affinity Maturation." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-278580.
Full textAbstract:
Aggregation of microtubule-associated protein tau is involved in the pathology of several neurodegenerative diseases, including Alzheimer’s disease. The affibody TP4 has been shown to inhibit this aggregation process, and its target-binding positions were previously grafted onto a dimeric affibody scaffold, creating the sequestrin seqTP4. This project constitutes a part of the affinity maturation process of seqTP4, using two different bacterial display methods. An error-prone PCR library was first expressed on Staphylococcus carnosus cells for selection of variants with improved tau-binding properties, resulting in a library of 1.4×107 transformants. Flow cytometric tests indicated difficulties in the setup due to nonspecific interactions, and whereas several different approaches to alleviate the problems were investigated, two cell sorting attempts were ultimately unsuccessful. Subcloning of seqTP4 and the library to an Escherichia coli surface display vector resulted in functional surface expression of seqTP4 on E. coli JK321 and BL21 cells, and a BL21 library size of 1.6×109 transformants. An initial flow cytometric test of this library indicates the presence of improved tau-binding variants, paving the way for future cell sorting.Aggregering av mikrotubuli-associerat protein tau är involverad i patologin av flera neurodegenerativa sjukdomar, däribland Alzheimers sjukdom. Affibodymolekylen TP4 har visat sig inhibera denna aggregeringsprocess, och överföring av dess målbindande positioner till ett dimeriskt affibodyprotein har tidigare gett upphov till seqTP4, en så kallad sequestrin. Detta projekt utgör ett led i processen att affinitetsmaturera seqTP4, med hjälp av två olika metoder för presentation av proteiner på ytan av bakterieceller. Ett error-prone PCR-bibliotek uttrycktes först på ytan av Staphylococcus carnosus-celler för selektion av varianter med ökad affinitet för tau, vilket resulterade i ett bibliotek av 1.4×107 transformanter. Flödescytometriska tester tydde på svårigheter i detta upplägg på grund av ospecifika interaktioner, och emedan flera olika angreppssätt för att förmildra dessa problem undersöktes, misslyckades slutligen två cellsorteringsförsök. Omkloning av seqTP4 och biblioteket till en vektor för ytpresentation på Escherichia coli resulterade i funktionellt ytuttryck av seqTP4 på E. coli JK321- och BL21-celler, och ett BL21-bibliotek bestående av 1.6×109 transformanter. Ett första flödescytometriskt test av detta bibliotek tyder på närvaron av varianter med förbättrad förmåga att binda tau, och vägen ligger nu relativt öppen för cellsortering.
31
Shaw, Yen-Hao, and 邵彥豪. "Investigation of cell surface molecules essential for CTGF stimulation on monocytes." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/97444698316225620580.
Full textAbstract:
碩士臺北醫學大學
醫學科學研究所
98
Connective Tissue Growth Factor (CTGF), is one member of secretory protein CCN family that mediates the interaction of cell surface and extracellular matrix (ECM). Among the many function of CTGF are angiogenesis, adhesion, osteogenesis, tissue repair, fibrosis, proliferation, migration, and differentiation, CTGF is also a pathogenic factor in variety of fibrotic disorders. In our previous study, CTGF has been found to induce IL-8 secretion on human CD14+ monocytes. However, the signal transduction pathway of CTGF and the specific receptor recognized by CTGF on human monocytes are still poorly understood. In this study, we investigated the interaction between surface fibronectin, heparin, heparan sulfate and CTGF, found heparin sulfate proteoglycans involved in CTGF function. To further identify the receptor of CTGF, we used antagonist of integrin ??2 to define whether integrin ??2 is the specific receptor for CTGF. Then we utilized TrkA inhibitor K-252a to identify whether TrkA participate in the IL-8 secretion pathway induced by CTGF. Finally we used lactoferrin competed with CTGF binding to LRP1 to clarifying whether LRP1 is the receptor for CTGF. Furthermore, we utilized additional endocytosis inhibitor Phenylarsine Oxide and endosome inhibitor NH4Cl to identify whether IL-8 induction through endocytosis. Data suggested that on human CD14+ monocytes, CTGF might bind to LRP1 and TrkA then internalized into cells by endocytosis, combined with endosome then activated MAP Kinase p38, ERK and JNK eventually increased IL-8 secretion.
32
Zhang, Liang. "Effects of Different Surface Expression of the CD40 Co-stimulatory Molecules on Dendritic Cell Functions." 2010. http://hdl.handle.net/1993/3982.
Full textAbstract:
Dendritic cell is one of the professional antigen presenting cells, and it bridges innate immunity and adaptive immunity. To fully activate naïve T cells, it requires DC to provide at least two signals, the interaction between T cell receptor and the MHC class II molecule loaded with antigen processed by DC, and the co-stimulatory signals provided by the co-stimulatory molecules expressed on DC. The identification of more and more co-stimulatory molecules expressed on DC and the studies on their functions highlight the importance of co-stimulatory molecules on the regulation of DC functions. We here hypothesized that different expression levels of co-stimulatory molecules expressed on DC is pivotal of directing DC function towards immunity, tolerance and polarization of Th1/Th2 immune response. Using CD40 as the model molecule to study the effect of its expression levels on DC functions, we found that no/low expression level of CD40 on DC induced antigen-specific immunological tolerance was due to the induction of CD4+CD25+Foxp3+ regulatory T cells, while the polarization of Th2 immune response induced by DC with medium expression level of CD40 was partially due to the impaired IL-12 production by DC during CD40 crosslinking. Our findings that different levels of co-stimulatory molecules have different regulations on DC functions has the significance in DC based immunotherapy for GVHD as well as the Th1 diseases.
33
Prasanna, S. Jyothi. "Roles Of Interferon-Modulated Genes In Cell Surface Expression Of Major Histocompatibility Complex Encoded Class I Molecules And Cell Survival In The Hepatoma Cell Line, H6." Thesis, 2005. http://etd.iisc.ernet.in/handle/2005/1367.
Full text
34
Chang, Ling-Ju, and 張齡如. "The Alteration of Tumor Cell Induced Angiogenesis and its Surface Adhesion Molecules Expression Caused by Hypoxia and their Effects." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/88049465327829035979.
Full textAbstract:
碩士國立臺灣大學
藥理學研究所
94
Previous studies have shown that angiogenesis is required for growth and metastasis of solid tumors. Many growth factors including vascular endothelial growth factors (VEGFs), basic fibroblast growth factor (bFGF), tumor necrosis factor-α (TNF-α) and epidermal growth factor (EGF) are potent angiogenesis inducers through stimulating the proliferation and migration of capillary endothelial cells. In many solid tumors, expression of these factors correlates with high vascularity, lymph node metastasis, and poor clinical prognosis. Tumor cells exposed to hypoxia have been shown to up-regulate the expression of VEGF. The purpose of the present study was to investigate whether hypoxia-induced upregulation of soluble mediators that are released into tumor cell conditioned medium (CM) can result in an induction of angiogenesis. The tumors studied were Neuro-2A neuroblastoma from strain A albino mice and B16F10 melanoma from C57BL/6J mice. A significant increase in cell proliferation was seen at 48 hr when HUVEC were cultured with the CM from hypoxic tumor cells as compared with normoxic counterpart. This increased proliferation was abrogated by preincubation of neutralizing VEGF antibodies with CM from hypoxic B16F10 cells. However, for Neuro-2A cells cultured under hypoxic and normoxic conditions, the increase of HUVEC proliferation was inhibited by adding neutralizing VEGF antibodies to both CMs. We also detected that hypoxia enhanced VEGF release from B16F10 cells. Therefore, we suggest that the increased production of VEGF induced by hypoxia stimulates endothelial cell proliferation. The effects of hypoxia on integrin expression and adhesion to extracellular matrix (ECM) proteins were investigated. Exposure of B16F10 cells to hypoxia caused a significant upregulation of β1 integrin and an associated increase in cell adhesion to fibronectin, but intriguingly, a decrease in adhesion to collagen type I. Through flow cytometric analysis, we did not find any prominent upregulation of αv and β3 integrin expression on B16F10 cell surface under hypoxic condition. However, we found an increase in cell adhesion to vitronectin. On the other hand, we did not find any significant alteration of integrin expression of Neuro-2A cells under hypoxic condition. Using microarray analysis, we also extensively observed the effect of hypoxia on the gene expression level of B16f10 cells and use this tool to confirm the above results. These results demonstrate that hypoxia may alter adhesion properties of B16F10 cells to ECM proteins through the interaction of β1–associated integrin(s). However, the identity of the specific integrin and its mechanism of regulating B16F10 cell adhesion to ECM or other behaviors related to tumor progression still need to be investigated.
35
Lin, Yu-Chieh, and 林玉潔. "Study of homocysteine on expression of cell surface molecules and pro-inflammatory cytokines as well as relevant signal pathway in human U937 monocytic cell lines." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/00379902897562085912.
Full textAbstract:
碩士高雄醫學大學
醫學檢驗生物技術學研究所
97
It has been reported that atherosclerosis is the main cause of death in the cardiovascular disease. Hyperhomocysteinemia (HHcy) is an independent risk factor of atherosclerosis and is caused by the deficiency of folate and/or vitamin B12, which are essential cofactors in the remethylation of homocysteine to methionine. Monocyte adhesion to and recruitment by endothelial cells are key progresses of atherogenesis. Nowadays, literatures point out that the interaction of activated α4 surface molecules (such as VLA4) and/or β2 surface molecules ( such as CD11/CD18 ) of monocyte with vascular cell adhesion molecule-1 (VCAM-1) and/or intercellular adhesion molecule-1 (ICAM-1) of endothelial cell is required for progress of atherosclerosis. That promotes monocytes’ adhesion to endothelial cell tightly and caused endothelial cell injured. The present study was designed to investigate the effect of homocysteine on the α4 surface molecules (such as VLA4) and β2 surface molecules (such as CD11/CD18) expressions of human monocytic cell. In 1993, Ross proposed that inflammatory cytokines secretions by either leukocyte or blood vessel cell were associated with the progress of atherosclerosis. Moreover, reports indicated that homocysteine could affect atherosclerosis progress by regulation of immunity. However, the exact mechanism or signal pathway is still unclear. In this study, we also explore the effect of homocysteine on inflammatory cytokine IL-1β and TNF-α expression as well as their downstream transcription factors. Results showed proliferation of human monocytic cell line (U937) was suppressed by the treatment of high concentration of homocysteine ( 2, 4, 8 mM ), whereas inflammatory cytokine TNF-α mRNA expression was increased resulting in prompting adhesion molecules of endothelial cell activated and recruitment of more immune cells to participate in inflammation. In addition, expression of surface molecules CD11b was enhanced which could aggravate inflammation response and cause endothelial cell damage. Besides, addition of vitamin B12 could effectively reverse the increase of TNF-α and CD11b, thus decrease endothelial cell’s damage. Furthermore, homocysteine regulated transcription factor c-fos expression to influence cell’s growth, differentiation, and apoptosis, and which was not via TNF-α mediated signal pathway. It would be worthwhile to further explore the pathway of homocystein on human monocytic cell.
36
Hong, Claire. "Mapping the distribution of cell surface molecules by chromophore localization in the transmission electron microscope via low electron energy loss imaging." 2004. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=95157&T=F.
Full text
37
Loveless, Bianca C. "Studies on the expression of the major cell surface molecules of insect forms of Trypanosoma congolense, a major parasite of cattle in Africa." Thesis, 2010. http://hdl.handle.net/1828/3192.
Full textAbstract:
African trypanosomes are protozoan parasites that cause African trypanosomiasis, diseases that affect humans and their livestock. Not only has trypanosomiasis had an overwhelming effect on the development of tropical Africa in the past, but it also constitutes one of the most significant present economic problems of the continent. Trypanosomes alternate between a mammalian host and a tsetse vector using a complex life cycle. In the mammalian host the trypanosomes live as bloodstream forms (BSFs) that are so proficient at antigenic variation, and thus host immune system evasion, that no suitable vaccine candidates have yet been identified. In contrast, the lifecycle stages that exist in the tsetse vector do not undergo antigenic variation. This potentially makes the vector-occupying trypanosomes much better targets for control if strategies can be devised to disrupt their lifecycle in the vector or to interfere with their transmission to mammalian hosts.
The primary impediment to developing strategies for disruption of trypanosome life cycles in tsetse is a lack of understanding of the molecular basis of trypanosome-tsetse interactions. Although several major surface molecules have been identified on insect form trypanosomes, these have not been well studied due to a lack of appropriate antibody probes and to the difficulty in obtaining sufficient quantities of the different parasite life cycle stages required for such molecular studies.
My thesis research was focused on developing and using monoclonal antibody probes for analysis of expression of major surface molecules of Trypanosoma congolense, a serious pathogen of cattle in Africa. I used this species of trypanosome since in addition to being a socioeconomically important parasite, all four of its major life cycle stages can be grown in vitro in amounts sufficient for immunochemical analysis. I successfully derived and characterized monoclonal antibodies that were useful for detecting the three major surface proteins of T. congolense insect forms: glutamic acid/alanine rich protein (GARP), the T. congolense heptapeptide repeat protein (TcHRP) and congolense epimastogote specific protein (CESP). Selected monoclonal antibody probes were then employed for expression analysis of these molecules throughout the parasite life cycle using in vitro grown trypanosomes and parasites taken directly from infected tsetse. In addition, I determined the peptide epitopes for two of my GARP-specific monoclonal antibodies and in collaboration with Dr. Martin Boulanger and Jeremy Mason was able to localize the epitopes on a high resolution three-dimensional structure obtained by X-ray crystallography. This allowed us to derive a model that describes the orientation of GARP in the trypanosome surface membrane and explains the possible structure-function relationships involved in replacement of the bloodstream form variant surface glycoprotein (VSG) by GARP as trypanosomes differentiate in the tsetse vector after a bloodmeal.
38
Fares, Iman. "Expanding and defining human hematopoietic stem and progenitor cells ex vivo using small molecules." Thèse, 2016. http://hdl.handle.net/1866/18360.
Full textAbstract:
Human hematopoietic stem cells (HSCs) are defined by their capacity to self-renew and to differentiate into all blood lineages during an adult lifetime. Based on these unique properties, HSCs are used in transplantation procedures to treat various hematological diseases. However, the low number of HSCs in a graft limits the use of this treatment. To overcome this restrain, different approaches were established to expand HSCs ex vivo; yet, the absence of a reliable surface maker that correlates with HSC activity in culture made the assessment labor-intensive and time-consuming. Using a library of small molecules, we were able to identify pyrimidoindole derivative named UM171 as an agonist for HSC self-renewal. UM171 promotes ex vivo expansion of hematopoietic and stem cell progenitors (HSPC) independently of AhR suppression- a pathway reported by Boitano et al. to have the greatest effect in HSC expansion. Unlike AhR suppression that targets a hematopoietic population with limited proliferative potential, UM171 targets the long-term HSCs. Transcriptome analysis showed that UM171 reduces the levels of transcripts associated with lineage differentiation and induces the expression of genes encoding for membrane proteins, one of the best differentially expressed being the endothelial protein c receptor (EPCR). Cell sorting and transplantation experiments of EPCR expressing cells showed a high correlation with HSC activity. We demonstrated EPCR as a first reliable marker to enrich for HSC in culture and that it is required for HSPC function in vivo. These findings provide a valuable tool for clinical and research applications to optimize further HSPC expansion protocols and understand the molecular machinery that governs the HSC self-renewal.Le terme de cellules souches hématopoïétiques (CSH) désigne une population rare de cellules capables de générer l’ensemble des lignages hématopoïétiques. Cette définition implique une capacité d’auto-renouvèlement, ainsi qu'un potentiel de prolifération et de différenciation important. La greffe de cellules souches hématopoïétiques est aujourd'hui une modalité thérapeutique pour le traitement de diverses maladies hématologiques et représente pour de nombreux patients un traitement de dernier recours. Malheureusement, le nombre limité de ces cellules dans une unité de sang de cordon est à l’origine du faible taux de réussite des greffes de sang de cordon chez l'adulte. Plusieurs stratégies sont actuellement mises en place pour permettre la multiplication de ces CSH ex vivo. Cependant, Il n’y a jusqu’à ce jour aucun critère ou marqueur phénotypique fiable permettant spécifiquement d'identifier ou d'isoler ces CSH amplifiées, et leur caractérisation reste un défi majeur pour les chercheurs. Dans le laboratoire, nous avons effectué un criblage à haut débit afin de tester le potentiel d’un grand nombre de molécules chimiques à multiplier des cellules souches dérivées de sang de cordon ombilical et nous avons ainsi identifié la molécule UM171, un dérivé pyrimido-indole, qui permet de multiplier par 10 le nombre de CSH et par 100 leur descendance. Nous avons démontré qu' UM171 permet de multiplier les CSH sans affecter la voie de signalisation de la protéine AhR, récemment impliquée dans l'auto-renouvèlement des CSH. L'analyse du transcriptome des CSH exposées à la molécule UM171 a permis d'identifier le récepteur endothélial à la protéine C (EPCR), comme marqueur de surface permettant de prédire le nombre et l'activité des CSH en culture et par conséquent de les isoler et de mieux les caractériser. En combinant des techniques de cytométrie de flux et d'ARN interférents avec des expériences de transplantation à long terme dans des souris immuno-déficientes, nous avons pu démontrer qu' EPCR peut être considéré non seulement comme un premier marqueur fiable pour enrichir les CSH en culture mais aussi qu'il est nécessaire pour la fonction de ces CSH in vivo. Les résultats de ces travaux représentent une avancée majeure pour accélérer les recherches et les applications cliniques sur l'expansion des CSH ex vivo et permettra de comprendre les mécanismes moléculaires qui régissent l'auto-renouvèlement des CSH.