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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

Molecular biology of the voltage-gated sodium channel

Haque, Sharmeen January 2007 (has links)
No description available.
42

On the hydrodynamic properties of IgG1 glycoforms in comparison with pure protein and pure carbohydrate assemblies

Morou Besong, David Tabot January 2013 (has links)
Biological macromolecules are routinely exposed to various stresses during production, processing, transport and storage. Inadvertently, this may ultimately result in protein inactivation, denaturation and aggregation. The objective of the present study was to investigate the stability or instability which can occur fo llowing routine bio-processing of phannaceutical and other protein preparations with different levels of glycosylation, in addition to two polysaccharide samples of significant importance to the food industry. Using hydrodynamic techniques, the effects of physico-chemical factors on the stability of macromolecules, including three phannaceutical fannulations (monoclonal antibodies), was investigated via accelerated degradation or structural modifications. Besides glycosylation, the influence of various other parameters such as concentration, pH, storage temperature and structural modifications were examined. Deglycosylation of antibodies resulted in changes in intrinsic molecular properties such as sedimentation velocity and intrinsic viscosity with overall impact on stability. Both the maxi- and mini-ferritins follow a similar dissociation/reassembly pathway, the knowledge of which may be helpful in the engineering of similar molecules with applications in the pharmaceutical and medical fields. In-vitro mutagenesis in POR causes changes in structural flexibility and correlates to major differences in the formation of stabilized ternary complexes suggesting conformational changes, which is relevant to its structure and catalytic activity. Finally, characterisation of two polysaccharide gum samples showed significant differences in tenns of polydispersity, solution viscosity and molecular weight distribution compared to the protein and glycoprotein samples above. Intrinsic viscosity estimates differed from those of similar molecules with potential for industrial applications. Hydrodynamics techniques are invaluable for structural characterisation of macromolecular solutions.
43

Mathematical Modelling of Voltage-Gated Ion Channels

Ren, Yilei January 2010 (has links)
No description available.
44

Modelling of lipid raft formation in cell membranes

Fischer, Thorsten January 2010 (has links)
No description available.
45

Molecular basis for gelatinisation characteristics of cereal starches

Qi, Xin January 2002 (has links)
No description available.
46

Interactions between sponges and marine bacteria as a route to the discovery of novel bioactive compounds

Ismail, Noraznawati January 2006 (has links)
The bacterial community architecture associated with four species of sponges, Halichondria panicea, Suberites domuncula, S. carnosus and Pachymatismajohnstonia 'was investigated using culture-dependent and culture-independent strategies. Marine '/ agar was found to be the best of several media used for cultivation of culturable bacteria : associated with sponges. Molecular methods, including denaturing gradient gel ,electrophoresis (DGGE), 16S rDNA cloning and sequence analysis suggested a : bacterial community different from that identified using culture-dependent methods. DGGE can provide a profile of the whole community of the sponge and facilitate screening of large-scale samples. 90% ofthe bacteria associated with these four sponges were sponge species-specific. S. carnosus was also transferred to an aquarium to study kinetic changes of sponge-associ~tedbacterial communities. DGGE analysis showed 'the consistent presence of some particular bands suggesting the continued presence of species of symbiotic bacteria. Four Bacillus species (B. licheniformis SC-43, B. subtilis SD-8, B. pumilus HP-48 and B. cereus HP-22) isolated from the sponges exhibited antagonistic activity against isolates of Gram-positive bacteria obtained from the same .sponges. All strains tested were active against Micrococcus luteus, strain HP-5!6 isolated from H. panicea. This suggests that HP-5!6 can be used in the laboratory as a sensitive indicator of activity. A comparison of several media found Nutrient Agar! Broth containing glycerol and iron (NGF) to be the best medium tested for antimicrobial , compound production. B. licheniformis (SC-43), B. subtilis (SD-8), and Pantoea sp., SC-AF, in the presence of glycerol and ferric ion, could produce antimicrobial '. compounds when grown within ,biofilms; however, the corresponding shaken flask cultures could not. This effect could be related to oxidative stress defence responses. Pantoea sp., SC-AF produced several antimicrobial compounds active against M luteus, HP-5!6 which were different from previously reported Pantocin antimicrobials. In addition, Pantoea sp., SC-AF produced 'jelly-like' extracellular polysaccharide (EPS) ' on NGF and on the nylon membrane in Air-membrane surface bioreactor (AMS) cultures, along with the production of antimicrobial compounds. Only fructose and cellobiose after acid lysis of EPS of Pantoea sp., SC-AF have been identified. In addition, my study confirmed that sponges accommodate large amounts of uncultured bacteria, whose metabolic capability cannot be explored without cultivation. New cultivation strategies should be investigated and biofilm-based culture techniques incorporated in the future search for novel antibiotics.
47

The role of membrane lipids in Weibel Palade body formation

Houston, Karen Grace January 2009 (has links)
The Weibel Palade body (WPB) is the major regulated secretory organelle of endothelial cells. The WPB is used here as a model system to investigate the formation and acquisition of membrane identity of regulated secretory organelles. Heterologous expression of von Willebrand (VWF), the main secretory cargo of WPBs, in cells lacking endogenous VWF, is able to induce the formation of structures that are not only morphologically indistinguishable from WPBs but also recruit the appropriate membrane components resulting in the correct membrane identity. The question arises as to how VWF acts within the lumen of the secretory pathway to do this. The working hypothesis is that VWF drives the formation of WPB and the acquisition of membrane identity by direct interaction with specific lipids on the lumenal face of the lipid bilayer. This thesis describes attempts to test this hypothesis both directly, by looking for putative interactions of VWF with membrane lipids and indirectly, by studying the role of glycosphingolipids in WPB formation. To look for direct interaction of VWF with membrane lipids, attempts were made to produce recombinant, enzymatically tagged VWF probes and develop an overlay assay. Glycoarrays were also probed with VWF to identify potential glycan binding partners. VWF was found to bind to a class of fucosylated glycans on the array. In order to look for the influence of glycosphingolipids on WPB formation two distinct approaches were taken The effect of drug-mediated inhibition of membrane glycosphingolipid synthesis on WPB formation in cultured human endothelial cells was investigated. Inhibition of glucosylceramide synthesis, and hence complex glycosphingolipids, by N-butyldeoxygalactonojirimycin had no apparent effect on VWF trafficking. Trafficking of heterologously expressed VWF was studied in two epithelial cell lines, known to have distinct glycosphingolipid compositions. The two cell lines were shown to differ in VWF trafficking both morphologically and biochemically. VWF was also shown to be differentially glycosylated between the two cell lines, suggesting a link between VWF glycosylation and trafficking.
48

The interferon alpha receptor utilises T-cell receptor-associated proteins for signalling

Stevens, C. N. January 2009 (has links)
The interferon alpha receptor (IFNAR) and T-cell receptor (TCR) are expressed upon the T-cell surface. The dimeric Class I interferon receptor is a cytokine receptor that recognises interferons such as IFNα. Interferons (IFNs) are pluripotent, antiviral cytokines that causes antiproliferative effects, primarily through Jak/STAT signalling. The T-cell receptor is an antigenic receptor that recognises antigenically-derived peptides in the context of the MHC complex located on an antigen presenting cell, resulting in a cellular proliferation. Although both receptors elicit opposing cellular outcomes, both the TCR and IFNAR activate the ERK MAPK signalling pathway, albeit with a different time course. Furthermore, studies have shown that the IFNAR and TCR utilise an overlapping subset of proteins for this pathway to occur such as CD45, Lck and Zap70. In this study evidence is presented to show that two further TCR-associated proteins are phosphorylated in response to the IFNAR; the 95kDa guanosine nucleotide exchange factor, Vav, and the 76kDa adaptor protein Slp76. This proceeds in a similar manner to that observed at the TCR. Furthermore, the absence of either protein impairs IFNAR-induced ERK MAPK signalling. The similarities between TCR and IFNAR signalling led to questioning of whether crosstalk occurs between the two receptors. To address this possibility a TCRβ deficient cell line, which lacks functional TCR expression, was utilised. It was demonstrated that the absence of the TCR completely abrogates the ERK MAPK response emanating from the IFNAR yet Jak/STAT signalling is unaffected. These results highlight for the first time an intimate connection between the TCR and IFNAR.
49

Molecular cloning and characterisation of GABA-B receptors from Xenopus laevis

James, Robert January 2008 (has links)
Gamma-amino butyric acid (GABA) is the principal inhibitory neurotransmitter in the adult central nervous system (CNS) and signals via ionotropic GABAA receptors and metabotropic GABAB receptors. GABAB receptors are obligate heterodimers comprised of GABAB(i) and GABAB(2) subunits, members of the Family 3 G-protein coupled receptors (GPCRs). GABABL is an orphan Family 3 GPCR of unknown function, most closely related to GABAB receptors. To investigate the functions of these genes during vertebrate development, Xenopus laevis GABAB(1), GABAB(2) and GABABL cDNAs were isolated, and their spatiotemporal expression patterns during embryogenesis analysed by RT-PCR and in situ hybridization. Maternal GABAB(2) transcripts were detected by RT-PCR in blastulae, whereas GABAB(1) and GABABL transcripts were not detected until gastrulation and neurulation respectively. In situ hybridization revealed that GABAB(i} and GABAB{2) transcripts were co-expressed in most brain regions, although areas of unique GABAB(i} expression also existed, and GABABL transcripts were located primarily in the brain and otic vesicle of the tailbud embryo. Co-expression of GABAB(1) and GABAB(2) transcripts suggests a role for metabotropic GABA receptor signalling in the developing brain of Xenopus embryos. However, overexpression of GABAB(1) and GABAB(2) transcripts together or in isolation, during embryonic development did not generate a distinct morphological phenotype. In contrast, embryos overexpressing GABABL during embryonic development exhibited a significant body truncation phenotype. Animal cap assays indicated that GABABL overexpression interferes with mesodermal convergent extension, whilst RT-PCR shows that the expression of mesoderm-specific markers is not affected, demonstrating morphogenetic but not biochemical activity of GABABL. Whilst the temporal expression pattern of GABABL does not support an endogenous role in the regulation of convergent extension in Xenopus , these experiments demonstrate that GABABL is a functional protein that acts in a manner reminiscent of a GPCR by disrupting intracellular signalling cascades.
50

Alpha-2-delta subunits of voltage-gated calcium channels

Hendrich, Janek K. January 2008 (has links)
The calcium channel alpha-2-delta (0,28) subunit is an auxiliary subunit associated with voltage-dependent calcium channels. It is implicated in the trafficking and functional expression of the calcium channel complex. This study expands the functional role of the VWA domain and the RRR motif of the 0:26 subunit, and the interaction between this subunit and the anti-epileptic drug, gabapentin The VWA domain is normally found in integrins, where it mediates binding to extracellular proteins. A mutation in the 0:28-2 subunit VWA domain (uMIDAS) did not produce the increase in current amplitude elicited by the wildtype (WT) 0:28-2 control. Co-immunoprecipitation studies using tsA-201 cells (stably expressing OC28-2 containing a mid-HA tag) co-cultured with cerebellar granule cells identified potential proteins from the cerebellar cultures that co-immunoprecipitate with the 0:28-2 protein. This suggests that protein from cerebellar cultures may bind the 0:28-2 subunit. Secondly, an RRR motif found in 0128-I subunit has been implicated as important for binding of the anticonvulsant drug gabapentin (Wang et al., 1999). The electrophysiological properties of the RRA mutant OC28 proteins were examined, and found not to enhance current amplitude to the full extent seen by WT 0:28-1 and 0:28-2 coexpression. Binding studies using both membrane and lipid raft of tsA-201 cells expressing 0:28-1 confirmed a lack of 3H-gabapentin in the R217A mutant condition. Chronic exposure of tsA-201 cells expressing Cav2.1, p4, 0:28-2 or Cav2.2, pib, 0:28-1 to gabapentin resulted in a reduction in size of the resultant currents. The inhibitory action of gabapentin was prevented by pre-incubation of cells with the system-L amino-acid transport inhibitor, suggesting gabapentin acts intracellularly after uptake via this transport mechanism. The inhibitory effects of gabapentin exposure were not replicated using co-expression of 0:28-3, or the non gabapentin-binding mutant 0128-I R217A or a28-2 R282A proteins. This indicated the inhibitory effect was mediated through gabapentin-binding calcium channel a28 subunits.

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