A comprehensive review of the taxonomic diversity within the freshwater catfish genus Parauchenoglanis (Siluriformes, Auchenoglanididae)
- Authors: Sithole, Yonela
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/402992 , vital:69912
- Description: Thesis embargoed. To be released early 2026. , Thesis (PhD) -- Faculty of Science, Ichthyology & Fisheries Science, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Sithole, Yonela
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/402992 , vital:69912
- Description: Thesis embargoed. To be released early 2026. , Thesis (PhD) -- Faculty of Science, Ichthyology & Fisheries Science, 2023
- Full Text:
- Date Issued: 2023-10-13
A formative evaluation and critical analysis of an alcohol and pregnancy intervention in the Eastern Cape of South Africa
- Authors: Graham, Nicola Susan Jearey
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432541 , vital:72879 , DOI 10.21504/10962/432541
- Description: Some communities in South Africa have the highest documented rates of Foetal Alcohol Spectrum Disorders (FASD) in the world. Interventions to reduce alcohol consumption during pregnancy are crucial, but evaluations of such interventions are sparse. Formative evaluations are indicated to assist in the development of interventions. Harmful alcohol consumption during pregnancy is undergirded by a range of social injustices, including those imposed by colonisation and patriarchy; a feminist, decolonial approach to evaluations is, therefore, important. A research project, consisting of three arms, examined alcohol use during pregnancy in an under-resourced urban area of the Eastern Cape, and this research was one of those arms. An intervention was being rolled out in this area and I gathered a range of data from it. I engaged in a formative evaluation of it, and I reflect on the difficulties that I encountered in this endeavour. In the bulk of this thesis, I examine the power apparatuses and technologies that were used during the intervention to discursively position pregnant women. My analysis was guided by Foucauldian and post-Foucauldian theories, using Foucauldian Discourse Analysis and simplified Conversation Analysis (CA). Power apparatuses of coloniality, patriarchy, and pastoral power were used in the intervention to construct positions for pregnant women who drink alcohol as ignorant children, sinners, criminals, or “Mommies”. The foetus was constructed as a precious, vulnerable baby, while the person with FASD was constructed as the defiled Other, responsible for societal dissolution. The intervention used various disciplinary techniques to exhort women to follow their dictates. Women were generally compliant with being positioned as ignorant children, which absolved them from any blame for pre-natal drinking. However, some resistance was evident. I then introduce an ethics of care and justice, and I argue that pregnant/newly parenting women need to be positioned within such an ethics, which acknowledges both the universal resources that they require for reproductive freedoms, as well as their particular care needs. I highlight the few times when women were positioned in this way in the data, and I look at how the common positions could be altered or expanded to promote such an ethics. I conclude by arguing that alcohol use during pregnancy cannot be separated from the larger context of the cultural hegemony of alcohol use in some communities, and the social injustices that potentiate this use. I provide suggestions for country-wide policies and interventions, as well as specific FASD prevention programmes, and I argue that a feminist decolonising approach, within an ethics of care and justice, should guide interventions at all levels. , Thesis (PhD) -- Faculty of Humanities, Psychology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Graham, Nicola Susan Jearey
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432541 , vital:72879 , DOI 10.21504/10962/432541
- Description: Some communities in South Africa have the highest documented rates of Foetal Alcohol Spectrum Disorders (FASD) in the world. Interventions to reduce alcohol consumption during pregnancy are crucial, but evaluations of such interventions are sparse. Formative evaluations are indicated to assist in the development of interventions. Harmful alcohol consumption during pregnancy is undergirded by a range of social injustices, including those imposed by colonisation and patriarchy; a feminist, decolonial approach to evaluations is, therefore, important. A research project, consisting of three arms, examined alcohol use during pregnancy in an under-resourced urban area of the Eastern Cape, and this research was one of those arms. An intervention was being rolled out in this area and I gathered a range of data from it. I engaged in a formative evaluation of it, and I reflect on the difficulties that I encountered in this endeavour. In the bulk of this thesis, I examine the power apparatuses and technologies that were used during the intervention to discursively position pregnant women. My analysis was guided by Foucauldian and post-Foucauldian theories, using Foucauldian Discourse Analysis and simplified Conversation Analysis (CA). Power apparatuses of coloniality, patriarchy, and pastoral power were used in the intervention to construct positions for pregnant women who drink alcohol as ignorant children, sinners, criminals, or “Mommies”. The foetus was constructed as a precious, vulnerable baby, while the person with FASD was constructed as the defiled Other, responsible for societal dissolution. The intervention used various disciplinary techniques to exhort women to follow their dictates. Women were generally compliant with being positioned as ignorant children, which absolved them from any blame for pre-natal drinking. However, some resistance was evident. I then introduce an ethics of care and justice, and I argue that pregnant/newly parenting women need to be positioned within such an ethics, which acknowledges both the universal resources that they require for reproductive freedoms, as well as their particular care needs. I highlight the few times when women were positioned in this way in the data, and I look at how the common positions could be altered or expanded to promote such an ethics. I conclude by arguing that alcohol use during pregnancy cannot be separated from the larger context of the cultural hegemony of alcohol use in some communities, and the social injustices that potentiate this use. I provide suggestions for country-wide policies and interventions, as well as specific FASD prevention programmes, and I argue that a feminist decolonising approach, within an ethics of care and justice, should guide interventions at all levels. , Thesis (PhD) -- Faculty of Humanities, Psychology, 2023
- Full Text:
- Date Issued: 2023-10-13
A molecular investigation of stem-galling Tetramesa Walker (Hymenoptera: Eurytomidae) on African grasses: applications to biological control
- Van Steenderen, Clarke Julian Mignon
- Authors: Van Steenderen, Clarke Julian Mignon
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432565 , vital:72881 , DOI 10.21504/10962/432565
- Description: South Africa is a larger donor than receiver of alien grasses, where approximately 15% (_ 165 spp.) of the country's native grass species have become naturalised elsewhere. Many of these grasses have become serious invaders, causing significant damage to native species, habitat structure, and ecosystem functioning. Biological control is a sustainable and cost-effective method for the control of invasive weeds, but its application to invasive grasses has been approached with trepidation in the past due to the fears of a lack of host-specific herbivores that may cause non-target damage to agriculturally-important crops. The Tetramesa Walker genus (Hymenoptera: Eurytomidae) is one of three genera in the family that feed exclusively on grasses, and have a record of being host-specific to a particular species, or complex of closely-related congeners. There are over 200 described Tetramesa species, but this taxonomic effort has occurred almost exclusively in the Northern Hemisphere. Only about 2% of the described species are from Africa, with none from southern Africa despite the high diversity of grasses in the region. The low morphological variability between many Tetramesa groups has made identification difficult, where there may in fact be multiple undiscovered cryptic species. This thesis generated genetic sequence data (mitochondrial COI and nuclear 28S) that revealed at least eight native southern African Tetramesa taxa that are new to science, focusing particularly on the assemblages associated with Eragrostis curvula Nees (African lovegrass) and Sporobolus pyramidalis Beauv. and S. natalensis Steud. (giant rat's tail grass) which are alien invasive pests in Australia. Approximately 200 eurytomid wasps were collected and sequenced from 19 grass species across six South African provinces. Additionally, 27 grass species were sequenced using four gene regions (rps16-trnK, rps16, rpl32-trnL, and ITS), which were added to existing sequence data to build a dataset comprising over 700 sequences. Field host ranges and the use of host grass genetic proxies were important in making inferences about the host-specificity of eurytomid wasps of interest. Nine Tetramesa groups appeared to be host-specific to a single grass species, while six Tetramesa were associated with multiple species in a single grass genus. Since S. pyramidalis, S. natalensis, S. africanus, Hyparrhenia hirta, E. trichophora, and Andropogon gayanus are weeds elsewhere, there are at least six potential Tetramesa biological control agents that have been identified. A high diversity of Tetramesa on grasses within the Eragrostis genus was reported, with at least four taxa associated with E. curvula. It is currently uncertain whether these taxa represent different cryptic species or intraspecific populations that are the result of geographic sub-structuring. No-choice host-specificity testing using Tetramesa sp. 4 on E. curvula revealed that the wasp could complete its lifecycle on two non-target African grasses; namely E. plana and E. planiculmis. The wasp was also recorded on other Eragrostis species in the field (namely E. biflora and E. capensis). Using grass genetic sequences obtained in this study, it was found that there are four native Australian Eragrostis species that are more closely related to target E. curvula than to the non-target E. plana and E. planiculmis. This suggests that Tetramesa sp. 4 may not be suitably host-specific for use as a biological control agent. Further host-specificity testing on these native Australian species is required, however, before this insect is ruled out completely. The Tetramesa on S. pyramidalis (Tetramesa sp. 1), and the unidentified Sporobolus species presumed to be S. africanus, were suitably host-specific to be used as biological control agents. Since it was unclear whether some phylogenetic clades were true species or intraspecific populations, which is essential to understand when selecting agents for biological control, a new piece of software, SPEDE-sampler", was developed. It offers users of the Generalised Mixed Yule Coalescent (GMYC) species delimitation model a means of assessing the degree to which sampling effects such as data size and parameter choice can influence species diversity estimates. When applied to the Tetramesa data set, the software assisted in identifying which groups may contain cryptic species, uncovering that the COI marker is affected more by singletons than the 28S marker (i.e. species diversity tends to be overestimated), and confirming putative Tetramesa taxa that could be useful for biological control programmes going forward. This thesis has provided evidence that South Africa contains a diverse assemblage of Tetramesa and other eurytomids that are closely associated with their grass hosts, and that many of these taxa hold promise for grass biological control. This work has also highlighted the importance of integrative taxonomy in the discovery of novel taxa, and that biological control practitioners need to be aware of the caveats of each line of evidence used in the delimitation of putative species. , Thesis (PhD) -- Faculty of Science, Zoology and Entomology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Van Steenderen, Clarke Julian Mignon
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432565 , vital:72881 , DOI 10.21504/10962/432565
- Description: South Africa is a larger donor than receiver of alien grasses, where approximately 15% (_ 165 spp.) of the country's native grass species have become naturalised elsewhere. Many of these grasses have become serious invaders, causing significant damage to native species, habitat structure, and ecosystem functioning. Biological control is a sustainable and cost-effective method for the control of invasive weeds, but its application to invasive grasses has been approached with trepidation in the past due to the fears of a lack of host-specific herbivores that may cause non-target damage to agriculturally-important crops. The Tetramesa Walker genus (Hymenoptera: Eurytomidae) is one of three genera in the family that feed exclusively on grasses, and have a record of being host-specific to a particular species, or complex of closely-related congeners. There are over 200 described Tetramesa species, but this taxonomic effort has occurred almost exclusively in the Northern Hemisphere. Only about 2% of the described species are from Africa, with none from southern Africa despite the high diversity of grasses in the region. The low morphological variability between many Tetramesa groups has made identification difficult, where there may in fact be multiple undiscovered cryptic species. This thesis generated genetic sequence data (mitochondrial COI and nuclear 28S) that revealed at least eight native southern African Tetramesa taxa that are new to science, focusing particularly on the assemblages associated with Eragrostis curvula Nees (African lovegrass) and Sporobolus pyramidalis Beauv. and S. natalensis Steud. (giant rat's tail grass) which are alien invasive pests in Australia. Approximately 200 eurytomid wasps were collected and sequenced from 19 grass species across six South African provinces. Additionally, 27 grass species were sequenced using four gene regions (rps16-trnK, rps16, rpl32-trnL, and ITS), which were added to existing sequence data to build a dataset comprising over 700 sequences. Field host ranges and the use of host grass genetic proxies were important in making inferences about the host-specificity of eurytomid wasps of interest. Nine Tetramesa groups appeared to be host-specific to a single grass species, while six Tetramesa were associated with multiple species in a single grass genus. Since S. pyramidalis, S. natalensis, S. africanus, Hyparrhenia hirta, E. trichophora, and Andropogon gayanus are weeds elsewhere, there are at least six potential Tetramesa biological control agents that have been identified. A high diversity of Tetramesa on grasses within the Eragrostis genus was reported, with at least four taxa associated with E. curvula. It is currently uncertain whether these taxa represent different cryptic species or intraspecific populations that are the result of geographic sub-structuring. No-choice host-specificity testing using Tetramesa sp. 4 on E. curvula revealed that the wasp could complete its lifecycle on two non-target African grasses; namely E. plana and E. planiculmis. The wasp was also recorded on other Eragrostis species in the field (namely E. biflora and E. capensis). Using grass genetic sequences obtained in this study, it was found that there are four native Australian Eragrostis species that are more closely related to target E. curvula than to the non-target E. plana and E. planiculmis. This suggests that Tetramesa sp. 4 may not be suitably host-specific for use as a biological control agent. Further host-specificity testing on these native Australian species is required, however, before this insect is ruled out completely. The Tetramesa on S. pyramidalis (Tetramesa sp. 1), and the unidentified Sporobolus species presumed to be S. africanus, were suitably host-specific to be used as biological control agents. Since it was unclear whether some phylogenetic clades were true species or intraspecific populations, which is essential to understand when selecting agents for biological control, a new piece of software, SPEDE-sampler", was developed. It offers users of the Generalised Mixed Yule Coalescent (GMYC) species delimitation model a means of assessing the degree to which sampling effects such as data size and parameter choice can influence species diversity estimates. When applied to the Tetramesa data set, the software assisted in identifying which groups may contain cryptic species, uncovering that the COI marker is affected more by singletons than the 28S marker (i.e. species diversity tends to be overestimated), and confirming putative Tetramesa taxa that could be useful for biological control programmes going forward. This thesis has provided evidence that South Africa contains a diverse assemblage of Tetramesa and other eurytomids that are closely associated with their grass hosts, and that many of these taxa hold promise for grass biological control. This work has also highlighted the importance of integrative taxonomy in the discovery of novel taxa, and that biological control practitioners need to be aware of the caveats of each line of evidence used in the delimitation of putative species. , Thesis (PhD) -- Faculty of Science, Zoology and Entomology, 2023
- Full Text:
- Date Issued: 2023-10-13
African population prevalent genetic variations of dihydropyrimidine dehydrogenase as the 5-flourouracil cancer drug metabolizing enzyme: computational approaches towards pharmacogenomics studies
- Authors: Tendwa, Maureen Bilinga
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432263 , vital:72856 , DOI 10.21504/10962/432270
- Description: In an era of newly emerging cases of non-communicable diseases such as cancer, research is vital for both the medical and economic well-being of humanity. Pharmacogenomics has laidthegroundworkfor the identification of potential genes in cancer progression and treatment outcome investigations. Researchers are increasingly discovering heterogeneity in the efficacy and toxicity responses of drugmetabolizing enzymes (DMEs) in diverse patient populations receiving anti-cancer therapy. DMEs comprise of Phase I (Cytochrome P450s) and Phase II (glutathione-S-transferases (GSTs), UDP-glucuronosyltransferases (UGTs), and dihydropyrimidine dehydrogenases (DPD)enzymes. The main cause of disparity in DME treatment outcomes is genetic variation,which causes missense mutations leading to structural and kinetic properties of the enzyme. These modifications have a deleterious impact on the pharmacodynamics and pharmacokinetics of drugs through multiple mechanisms. Presently, most cancer medicines are manufacturedin developed countries based on the genetic background of non-African subpopulations. Thus, these drugs may not be optimally effective or can cause adverse side effects. Even though heterogeneity in toxicity and efficacy of these drugs has been observed in African descent, the basis of this population variance remains partially understood. For instance,a deficiencyof DPD, the first-rate limiting metabolizing enzyme in the pyrimidinepathway, causes severe toxicity when exposed to 5-fluorouracil (5-FU) chemotherapy. However, minimum studies have been conducted to unravel itsmolecular mechanismwhich may unravel the observed drug treatment outcomes.The aim of this pharmacogenomics study was to determine the underlying mechanism by which DPD missense mutations, which are associated with an African ancestry subpopulation, provoke dysfunctional 5-FU metabolism, resulting in drug toxicity. This knowledge will be critical in designing drug modulators to aid in the restoration of DPD function, a hallmark of precision medicine. Therefore, in the first part of the research we identified and reviewed the general role of Phase I and Phase II cancer drug metabolizing enzymes. We then used World Health Organization (WHO) essential medicine and drug.com to authenticate the usage of 5-FU as an anti-cancer treatment agent. The 3D structure and chemical structure of the agent was then downloaded from the Drug bank. Subsequently, Human Mutation Analysis - Variant Analysis PORtal (HUMA) and Mendelian Inheritance in Man (OMIM) were used to obtain data on DPD non-synonymous genetic variants. Additionally, the aggregate information of DPD missense mutations and their relation to human health were extracted from ClinVar and Pharmacogenomics Knowledge Base (PharmKGB). This information, along with additional data from single nucleotide polymorphisms (dbSNP), 1000 Genomes Project and Exome Sequencing Project (ESP MAF) considering variants classified based on their minor allele frequency (MAF) of 0.001, as well as research articles, consolidated information on missense mutations associated with African subpopulations. Finally, the wild type (WT) and detected mutation sequences were obtained from the Universal Protein Resources database (UniProt). However, because the 3D structure of human DPD was missing, the dimeric wild type (WT) human 3-dimensional (3D) structure was modeled via MODELLER using the pig’s structure as a template. PRIMO, HHpred, and the Protein Data Bank (PDB) were all used to locate the suitable template. As a result, six clinical (C29R, M166V, Y186C, S534N, I543V, and D949V) and thirteen non-clinical (S201R, K259E, D342N, D432N, S492L, R592Q, A664S, G674D, A721T, V732G, T768K, R886C, and L993R) mutations were discovered. Using AMBER tools, we then determined accurate force field parameters for each monomer of DPD protein's Fe2+ centers. Following the creation of each mutation model structure in Discovery Studio, the resulting AMBER force field parameters were inferred. For each model structure, a drug free (inactive/open-conformation) and drug bound (active/closed-conformation) model structure was created (WT and mutations). The model structures were validated using the consensus of three validation programs, namely ERRAT, PROCHECK, and ProSA. Similarly, the impact on structural functionalities was predicted by consensus from Variant Analysis Porta (VAPOR) web server, which include three support vector machines (SVM)-based tools; PhD-SNP, MUpro, and I-Mutation. After protonation in the H++ web server, the six clinical and thirteen non-clinical (six active site and seven non-active site) mutations identified were then exposed to 600 ns molecular dynamic (MD) simulation. The non-clinical data was divided into two categories to better understand the impact of the mutation based on its position in the protein: six catalytic-domain (R592Q, A664S, G674D, A721T, V732G, and T768K) and seven remote (S201R, K259E, D342N, D432N, S492L, R886C, and L993R) missense mutations. The post-MD analysis was done using the typical existing computational global investigations [RMSD, all versus all RMSD, RMSF, RG, hydrogen bonds (H-bonds) and dynamic cross correlation (DCC)]. In addition, we used in silico tools newly developed within the Research Unit in Bioinformatics (RUBI) group, such as comparative essential dynamics (ED)-principal component analysis and dynamic residue network (DRN) multi-metric [betweenness centrality (BC), closeness centrality (CC), degree of centrality (DC), eigen-centrality (EC) and Katz centrality (KC)] analysis algorithms. From the analysis, it was observed that the loop regions of the mutation proteins had increased loop flexibility, particularly around the catalytic loop, which could account for the enhanced asymmetric behavior of the mutation’s monomers compared to the WT. Notably, the A664S mutant showed relatively lower fluctuations, deviating from the observed heightened flexibility in other mutants. A general decrease in hydrogen bonds was observed in the 5-FU binding environment of the mutations compared to the WT. In particular, 5-FU contact analysis of the WT versus the mutation revealed a reduction in contact between core 5-FU binding residues and catalytic residues Cys671 and Ser670, which form hydrogen bonds that initiate DPD catalytic action. Additionally, BC was used to quantify the importance of a protein residue based on how often it acted as a bridge along the shortest paths between other residues. It reflected the potential control or influence a residue may have over communication between different parts of a protein structure. DC assesses the number of connections or interactions a residue had with other residues in the protein, indicating its overall connectivity within the structure. In both drug free and drug bound state, DPD data from the active site hubs' BC and DC revealed a dimeric asymmetric communication pathway per monomer involving a cluster of newly introduced hubs ensemble along the oxidoreduction conduit from NADPH to 5-FU. The two BC communication pathways were located more on the interior of the oxidoreduction conduit, while the two DC communication pathways were located on the exterior. In both cases, one pathway dominated the other. Partially lost function reported in mutation systems could be credited to the compensation communication response to the catalytic site via the least compromised routes. Similar patterns were observed in allosteric communication pathways to the active site induced by remote mutations. Mutations may have destabilized the active-loop and 5-FU binding environment, resulting in a compensatory mechanism seen by the addition of new hubs to the communication network. Surprisingly, EC hubs in the WT were found within the catalytic site domain, indicating that the region is important in 5-FU metabolism. EC measured the importance of a residue by considering both its own degree of connectivity and the degrees of connectivity with its neighboring residues, highlighting its significance in information flow and communication. Herein, EC hubs in mutant systems were found to lose this importance, with active site domain mutations suffering the most. This could explain why non-clinical catalytic domain mutations R592Q, A664S, and G674D, as well as clinical catalytic domain mutations S534N and I543V, experienced drug exit in one of their monomers during simulation. In contrast, there was no 5-FU exit in the non-clinical remote domain. Additionally, aside from the active site, KC hubs were also found around the cofactors, indicating that these components were equally important in DPD overall function. KC combines the concepts of both degree centrality and eigen-centrality, it incorporated both direct and indirect interactions to evaluate the importance of a residue, assigning higher centrality to residues that have connections to other highly central residues. Hence, providing a more comprehensive measure of influence within the protein network. More importantly, CC is known to measure how efficiently a residue can interact with other residues in the protein, considering the shortest path lengths. It indicates the proximity of a residue to others, suggesting its potential for information transfer or functional integration. CC revealed that the majority of persistent hubs were found within the protein-cores known as cold-spots. Overall, this study highlighted the communication pathways triggered by active site domain mutations, as well as the allosteric communication pathways triggered by each remote mutation in both drug free and drug bound states of the DPD enzyme. Both clinical and non-clinical mutations revealed each protein's adaptive compensation mechanism, which results in partial function loss. In each case, the communication network of the different monomers changed from inactive to activated DPD protein. Cold-spot areas were discovered to contain key persistent residues involved in protein function and stability. These areas have been proposed as potential targets for new or repurposed pharmacological modulators that can restore enzyme function. In the pursuit of precision medicine, it also lays the groundwork for detecting and explaining the molecular mechanisms of other drug metabolizing enzymes related to the African-descent subpopulation. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Tendwa, Maureen Bilinga
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432263 , vital:72856 , DOI 10.21504/10962/432270
- Description: In an era of newly emerging cases of non-communicable diseases such as cancer, research is vital for both the medical and economic well-being of humanity. Pharmacogenomics has laidthegroundworkfor the identification of potential genes in cancer progression and treatment outcome investigations. Researchers are increasingly discovering heterogeneity in the efficacy and toxicity responses of drugmetabolizing enzymes (DMEs) in diverse patient populations receiving anti-cancer therapy. DMEs comprise of Phase I (Cytochrome P450s) and Phase II (glutathione-S-transferases (GSTs), UDP-glucuronosyltransferases (UGTs), and dihydropyrimidine dehydrogenases (DPD)enzymes. The main cause of disparity in DME treatment outcomes is genetic variation,which causes missense mutations leading to structural and kinetic properties of the enzyme. These modifications have a deleterious impact on the pharmacodynamics and pharmacokinetics of drugs through multiple mechanisms. Presently, most cancer medicines are manufacturedin developed countries based on the genetic background of non-African subpopulations. Thus, these drugs may not be optimally effective or can cause adverse side effects. Even though heterogeneity in toxicity and efficacy of these drugs has been observed in African descent, the basis of this population variance remains partially understood. For instance,a deficiencyof DPD, the first-rate limiting metabolizing enzyme in the pyrimidinepathway, causes severe toxicity when exposed to 5-fluorouracil (5-FU) chemotherapy. However, minimum studies have been conducted to unravel itsmolecular mechanismwhich may unravel the observed drug treatment outcomes.The aim of this pharmacogenomics study was to determine the underlying mechanism by which DPD missense mutations, which are associated with an African ancestry subpopulation, provoke dysfunctional 5-FU metabolism, resulting in drug toxicity. This knowledge will be critical in designing drug modulators to aid in the restoration of DPD function, a hallmark of precision medicine. Therefore, in the first part of the research we identified and reviewed the general role of Phase I and Phase II cancer drug metabolizing enzymes. We then used World Health Organization (WHO) essential medicine and drug.com to authenticate the usage of 5-FU as an anti-cancer treatment agent. The 3D structure and chemical structure of the agent was then downloaded from the Drug bank. Subsequently, Human Mutation Analysis - Variant Analysis PORtal (HUMA) and Mendelian Inheritance in Man (OMIM) were used to obtain data on DPD non-synonymous genetic variants. Additionally, the aggregate information of DPD missense mutations and their relation to human health were extracted from ClinVar and Pharmacogenomics Knowledge Base (PharmKGB). This information, along with additional data from single nucleotide polymorphisms (dbSNP), 1000 Genomes Project and Exome Sequencing Project (ESP MAF) considering variants classified based on their minor allele frequency (MAF) of 0.001, as well as research articles, consolidated information on missense mutations associated with African subpopulations. Finally, the wild type (WT) and detected mutation sequences were obtained from the Universal Protein Resources database (UniProt). However, because the 3D structure of human DPD was missing, the dimeric wild type (WT) human 3-dimensional (3D) structure was modeled via MODELLER using the pig’s structure as a template. PRIMO, HHpred, and the Protein Data Bank (PDB) were all used to locate the suitable template. As a result, six clinical (C29R, M166V, Y186C, S534N, I543V, and D949V) and thirteen non-clinical (S201R, K259E, D342N, D432N, S492L, R592Q, A664S, G674D, A721T, V732G, T768K, R886C, and L993R) mutations were discovered. Using AMBER tools, we then determined accurate force field parameters for each monomer of DPD protein's Fe2+ centers. Following the creation of each mutation model structure in Discovery Studio, the resulting AMBER force field parameters were inferred. For each model structure, a drug free (inactive/open-conformation) and drug bound (active/closed-conformation) model structure was created (WT and mutations). The model structures were validated using the consensus of three validation programs, namely ERRAT, PROCHECK, and ProSA. Similarly, the impact on structural functionalities was predicted by consensus from Variant Analysis Porta (VAPOR) web server, which include three support vector machines (SVM)-based tools; PhD-SNP, MUpro, and I-Mutation. After protonation in the H++ web server, the six clinical and thirteen non-clinical (six active site and seven non-active site) mutations identified were then exposed to 600 ns molecular dynamic (MD) simulation. The non-clinical data was divided into two categories to better understand the impact of the mutation based on its position in the protein: six catalytic-domain (R592Q, A664S, G674D, A721T, V732G, and T768K) and seven remote (S201R, K259E, D342N, D432N, S492L, R886C, and L993R) missense mutations. The post-MD analysis was done using the typical existing computational global investigations [RMSD, all versus all RMSD, RMSF, RG, hydrogen bonds (H-bonds) and dynamic cross correlation (DCC)]. In addition, we used in silico tools newly developed within the Research Unit in Bioinformatics (RUBI) group, such as comparative essential dynamics (ED)-principal component analysis and dynamic residue network (DRN) multi-metric [betweenness centrality (BC), closeness centrality (CC), degree of centrality (DC), eigen-centrality (EC) and Katz centrality (KC)] analysis algorithms. From the analysis, it was observed that the loop regions of the mutation proteins had increased loop flexibility, particularly around the catalytic loop, which could account for the enhanced asymmetric behavior of the mutation’s monomers compared to the WT. Notably, the A664S mutant showed relatively lower fluctuations, deviating from the observed heightened flexibility in other mutants. A general decrease in hydrogen bonds was observed in the 5-FU binding environment of the mutations compared to the WT. In particular, 5-FU contact analysis of the WT versus the mutation revealed a reduction in contact between core 5-FU binding residues and catalytic residues Cys671 and Ser670, which form hydrogen bonds that initiate DPD catalytic action. Additionally, BC was used to quantify the importance of a protein residue based on how often it acted as a bridge along the shortest paths between other residues. It reflected the potential control or influence a residue may have over communication between different parts of a protein structure. DC assesses the number of connections or interactions a residue had with other residues in the protein, indicating its overall connectivity within the structure. In both drug free and drug bound state, DPD data from the active site hubs' BC and DC revealed a dimeric asymmetric communication pathway per monomer involving a cluster of newly introduced hubs ensemble along the oxidoreduction conduit from NADPH to 5-FU. The two BC communication pathways were located more on the interior of the oxidoreduction conduit, while the two DC communication pathways were located on the exterior. In both cases, one pathway dominated the other. Partially lost function reported in mutation systems could be credited to the compensation communication response to the catalytic site via the least compromised routes. Similar patterns were observed in allosteric communication pathways to the active site induced by remote mutations. Mutations may have destabilized the active-loop and 5-FU binding environment, resulting in a compensatory mechanism seen by the addition of new hubs to the communication network. Surprisingly, EC hubs in the WT were found within the catalytic site domain, indicating that the region is important in 5-FU metabolism. EC measured the importance of a residue by considering both its own degree of connectivity and the degrees of connectivity with its neighboring residues, highlighting its significance in information flow and communication. Herein, EC hubs in mutant systems were found to lose this importance, with active site domain mutations suffering the most. This could explain why non-clinical catalytic domain mutations R592Q, A664S, and G674D, as well as clinical catalytic domain mutations S534N and I543V, experienced drug exit in one of their monomers during simulation. In contrast, there was no 5-FU exit in the non-clinical remote domain. Additionally, aside from the active site, KC hubs were also found around the cofactors, indicating that these components were equally important in DPD overall function. KC combines the concepts of both degree centrality and eigen-centrality, it incorporated both direct and indirect interactions to evaluate the importance of a residue, assigning higher centrality to residues that have connections to other highly central residues. Hence, providing a more comprehensive measure of influence within the protein network. More importantly, CC is known to measure how efficiently a residue can interact with other residues in the protein, considering the shortest path lengths. It indicates the proximity of a residue to others, suggesting its potential for information transfer or functional integration. CC revealed that the majority of persistent hubs were found within the protein-cores known as cold-spots. Overall, this study highlighted the communication pathways triggered by active site domain mutations, as well as the allosteric communication pathways triggered by each remote mutation in both drug free and drug bound states of the DPD enzyme. Both clinical and non-clinical mutations revealed each protein's adaptive compensation mechanism, which results in partial function loss. In each case, the communication network of the different monomers changed from inactive to activated DPD protein. Cold-spot areas were discovered to contain key persistent residues involved in protein function and stability. These areas have been proposed as potential targets for new or repurposed pharmacological modulators that can restore enzyme function. In the pursuit of precision medicine, it also lays the groundwork for detecting and explaining the molecular mechanisms of other drug metabolizing enzymes related to the African-descent subpopulation. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
An analysis of power relations, affiliation and individuation in selected coup, secession, and inaugural speeches of Nigerian leaders, 1960-2015
- Authors: Unegbu, Osondu Chukwuemeka
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432399 , vital:72867 , DOI 10.21504/10962/432399
- Description: This study examines the positioning of Zimbabwe and the United Kingdom (UK) in the language of news articles about diplomatic relations between the two countries published in two prominent Zimbabwean newspapers, The Herald and The Standard, between 2016 and 2020, using Systemic Functional Linguistics (SFL) and Legitimation Code Theory (LCT). Zimbabwe's present diplomatic discourses are a product of its colonial and post-independence history. This thesis places The Herald and The Standard within the larger context of the Zimbabwean media landscape as a state-owned and a privately owned newspaper, respectively. It contends that the two newspapers influence the positioning of Zimbabwe and the United Kingdom in public spheres where readers engage with the news concerning diplomatic ties. The research begins with a corpus-based examination of 42 news articles published between 2016 and 2020 in The Herald and The Standard. The investigation identified several angles through which Zimbabwe and the UK are positioned in the coverage. Zimbabwe is positioned through reference to its reform agenda, intentions for free and fair elections, and its diplomatic re-engagement drive. The UK is positioned as a source of development funding and new trade agreements, while improved diplomatic relations and the removal of restrictive measures against Zimbabwe are anticipated. Fine-grained analysis was conducted on four articles, two from each newspaper, selected to reflect the trends found in the corpus analysis. The fine-grained analyses showed how linguistic resources contributed to the positioning of the UK and Zimbabwe. Complementary analyses of these articles were conducted using LCT and SFL to describe how readers' knowledge of diplomatic relations is built using language in The Herald and The Standard. The study used the concepts of constellations and cosmologies from LCT to demonstrate how diplomatic knowledge is built in these news articles. In the articles, the constellations are related to policies such as Zimbabwe's reform agenda, people (diplomats and government officials) and moral judgments. Both newspapers contain both positive and negative positioning of Zimbabwe and the UK. However, The Standard is generally critical of removing the UK's sanctions on Zimbabwe and of the Zimbabwean government's reform agenda. Meanwhile, The Herald justifies Zimbabwe's Fast-track Land Reform Programme as resulting from Britain's refusal to fund a land redistribution programme as per the 1979 Lancaster House Agreement. The use of SFL's Appraisal framework helps to examine the linguistic resources used by The Herald and The Standard to describe the positioning of the two countries in relation to each other. Lexical strings help to establish diplomatic positioning in the news articles. These couple with Appraisal to accomplish individuation and affiliation. Affect and Judgement resources revealed the decisions taken by the UK to solve the conflict by encouraging the implementation of a reform agenda by Zimbabwe. Negative evaluation is consistently used to disalign with sanctions. The emerging patterns in the data show that diplomats representing the UK affiliate with Zimbabwe's stated economic and political reforms, and the government of Zimbabwe affiliates with the new trade agreement between Zimbabwe and the UK. At the same time, the UK diplomats individuate away from human rights abuses and the Fast-track Land Reform Programme. Affiliation strengthens confidence in diplomatic ties between Zimbabwe and the UK because the emphasis is placed on restoring them despite the conditions attached. The Herald and The Standard position Zimbabwe as a reformed country ready to implement policies to improve citizens' lives and as a country violating human rights and the rule of law. They position the UK as asserting power over Zimbabwe, willing to resolve the crisis through its foreign policy, and credited for assisting Zimbabwe. This strengthens re-engagement in diplomatic relations and commercial trade between the UK and Zimbabwe. In light of these findings, Zimbabweans are encouraged to cultivate an awareness that enables them to reflect on the challenges associated with diplomatic discourses and the implications for critically analysing the re-engagement initiative. They can promote re-engagement by being cognisant of specific values portrayed in The Herald and The Standard and challenging these values in the light of policy transformation to revive the relations between the two countries. The re-engagement process requires a transformation in Zimbabwe's modus operandi to improve the country's positioning in the diplomatic relations between it and the UK. , Thesis (PhD) -- Faculty of Humanities, Linguistics and Applied Language Studies, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Unegbu, Osondu Chukwuemeka
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432399 , vital:72867 , DOI 10.21504/10962/432399
- Description: This study examines the positioning of Zimbabwe and the United Kingdom (UK) in the language of news articles about diplomatic relations between the two countries published in two prominent Zimbabwean newspapers, The Herald and The Standard, between 2016 and 2020, using Systemic Functional Linguistics (SFL) and Legitimation Code Theory (LCT). Zimbabwe's present diplomatic discourses are a product of its colonial and post-independence history. This thesis places The Herald and The Standard within the larger context of the Zimbabwean media landscape as a state-owned and a privately owned newspaper, respectively. It contends that the two newspapers influence the positioning of Zimbabwe and the United Kingdom in public spheres where readers engage with the news concerning diplomatic ties. The research begins with a corpus-based examination of 42 news articles published between 2016 and 2020 in The Herald and The Standard. The investigation identified several angles through which Zimbabwe and the UK are positioned in the coverage. Zimbabwe is positioned through reference to its reform agenda, intentions for free and fair elections, and its diplomatic re-engagement drive. The UK is positioned as a source of development funding and new trade agreements, while improved diplomatic relations and the removal of restrictive measures against Zimbabwe are anticipated. Fine-grained analysis was conducted on four articles, two from each newspaper, selected to reflect the trends found in the corpus analysis. The fine-grained analyses showed how linguistic resources contributed to the positioning of the UK and Zimbabwe. Complementary analyses of these articles were conducted using LCT and SFL to describe how readers' knowledge of diplomatic relations is built using language in The Herald and The Standard. The study used the concepts of constellations and cosmologies from LCT to demonstrate how diplomatic knowledge is built in these news articles. In the articles, the constellations are related to policies such as Zimbabwe's reform agenda, people (diplomats and government officials) and moral judgments. Both newspapers contain both positive and negative positioning of Zimbabwe and the UK. However, The Standard is generally critical of removing the UK's sanctions on Zimbabwe and of the Zimbabwean government's reform agenda. Meanwhile, The Herald justifies Zimbabwe's Fast-track Land Reform Programme as resulting from Britain's refusal to fund a land redistribution programme as per the 1979 Lancaster House Agreement. The use of SFL's Appraisal framework helps to examine the linguistic resources used by The Herald and The Standard to describe the positioning of the two countries in relation to each other. Lexical strings help to establish diplomatic positioning in the news articles. These couple with Appraisal to accomplish individuation and affiliation. Affect and Judgement resources revealed the decisions taken by the UK to solve the conflict by encouraging the implementation of a reform agenda by Zimbabwe. Negative evaluation is consistently used to disalign with sanctions. The emerging patterns in the data show that diplomats representing the UK affiliate with Zimbabwe's stated economic and political reforms, and the government of Zimbabwe affiliates with the new trade agreement between Zimbabwe and the UK. At the same time, the UK diplomats individuate away from human rights abuses and the Fast-track Land Reform Programme. Affiliation strengthens confidence in diplomatic ties between Zimbabwe and the UK because the emphasis is placed on restoring them despite the conditions attached. The Herald and The Standard position Zimbabwe as a reformed country ready to implement policies to improve citizens' lives and as a country violating human rights and the rule of law. They position the UK as asserting power over Zimbabwe, willing to resolve the crisis through its foreign policy, and credited for assisting Zimbabwe. This strengthens re-engagement in diplomatic relations and commercial trade between the UK and Zimbabwe. In light of these findings, Zimbabweans are encouraged to cultivate an awareness that enables them to reflect on the challenges associated with diplomatic discourses and the implications for critically analysing the re-engagement initiative. They can promote re-engagement by being cognisant of specific values portrayed in The Herald and The Standard and challenging these values in the light of policy transformation to revive the relations between the two countries. The re-engagement process requires a transformation in Zimbabwe's modus operandi to improve the country's positioning in the diplomatic relations between it and the UK. , Thesis (PhD) -- Faculty of Humanities, Linguistics and Applied Language Studies, 2023
- Full Text:
- Date Issued: 2023-10-13
Analysis of the role and regulation of HOP1a and HOP1b splice variants in cancer biology
- Authors: Schwarz, Kelly
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432240 , vital:72854
- Description: Restricted access. Expected lease date in 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Schwarz, Kelly
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432240 , vital:72854
- Description: Restricted access. Expected lease date in 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
Arbuscular mycorrhizal fungi associated with maize in South Africa, under conventional and conservation agricultural cultivation
- Maússe Sitoe, Sílvia Natal David
- Authors: Maússe Sitoe, Sílvia Natal David
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431846 , vital:72808
- Description: Access restricted. Expected release date in 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Maússe Sitoe, Sílvia Natal David
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431846 , vital:72808
- Description: Access restricted. Expected release date in 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
Arbuscular mycorrhizal fungi associated with wheat under conventional and conservation agricultural cultivation
- Authors: Dube, Makasithembe
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431688 , vital:72796
- Description: Access restricted. Expected release date in 2024. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Dube, Makasithembe
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431688 , vital:72796
- Description: Access restricted. Expected release date in 2024. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
Asymmetrical zinc(II) phthalocyanines conjugated to nanomaterials for degradation of organic pollutants and inactivation of Staphylococcus aureus bacteria
- Authors: Mgidlana, Sithi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431859 , vital:72809 , DOI 10.21504/10962/431860
- Description: This thesis reports on the syntheses and characterization of asymmetrical phthalocyanines (Pcs) with different ring substituents (tert-butyl, ester, diimide, trimethoxy, acetophenone, heptanoylphenoxy, perfluorophenoxy, dimethoxy, propanoic acid, acetic acid, carboxylic acid, aminophenoxy, acrylic acid). Several nanoparticles including metal tungstate, capped with glutathione and 1-mercaptohexanol are prepared and characterized using analytical techniques. The synthesized Pcs are covalently linked to various nanoparticles (NPs) through ester and amide bonds to form Pc-NP conjugates, in order to improve their catalytic properties. The Pcs and their conjugates are characterized using different analytical techniques. The photophysics and photochemistry of the MPcs and conjugates are studied. The conjugates T). The complexes and the conjugates with nanomaterials are evaluated for singlet oxygen-generating ability. Conjugates generate higher singlet oxygen in comparison to Pc complexes alone. The photocatalytic activity of the conjugates of ZnPc complexes with NiWO4, Ag2WO4, Bi2WO6, CoWO4, and Ag-Fe3O4-based nanoparticles is evaluated based on photodegradation of methylene blue, tetracycline, and dibenzothiophene. The photocatalytic efficiencies of the synthesized phthalocyanine complexes increased in the presence of nanoparticles. This work also reports on the photodynamic antimicrobial chemotherapy activity of these materials against Staphylococcus aureus (S. aureus) bacteria in DMSO. The results indicated that silver-based nanoconjugates exhibit high antimicrobial activity with high log reductions compared to NiWO4, CoWO4, and Ag-Fe3O4-based materials. The z-scan technique is employed to experimentally test the nonlinear optical response of complexes and nanoconjugates in solution. The nonlinear absorption coefficient, third-order optical susceptibility and optical limiting threshold of the materials are obtained from the Z-scan aperture data. The nonlinear absorption parameters improved in the presence of semiconductor quantum dots, with 1-ethanoic-CdTe/ZnSeS/ZnO giving the best results due to the presence of electron-donating substituents. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Mgidlana, Sithi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431859 , vital:72809 , DOI 10.21504/10962/431860
- Description: This thesis reports on the syntheses and characterization of asymmetrical phthalocyanines (Pcs) with different ring substituents (tert-butyl, ester, diimide, trimethoxy, acetophenone, heptanoylphenoxy, perfluorophenoxy, dimethoxy, propanoic acid, acetic acid, carboxylic acid, aminophenoxy, acrylic acid). Several nanoparticles including metal tungstate, capped with glutathione and 1-mercaptohexanol are prepared and characterized using analytical techniques. The synthesized Pcs are covalently linked to various nanoparticles (NPs) through ester and amide bonds to form Pc-NP conjugates, in order to improve their catalytic properties. The Pcs and their conjugates are characterized using different analytical techniques. The photophysics and photochemistry of the MPcs and conjugates are studied. The conjugates T). The complexes and the conjugates with nanomaterials are evaluated for singlet oxygen-generating ability. Conjugates generate higher singlet oxygen in comparison to Pc complexes alone. The photocatalytic activity of the conjugates of ZnPc complexes with NiWO4, Ag2WO4, Bi2WO6, CoWO4, and Ag-Fe3O4-based nanoparticles is evaluated based on photodegradation of methylene blue, tetracycline, and dibenzothiophene. The photocatalytic efficiencies of the synthesized phthalocyanine complexes increased in the presence of nanoparticles. This work also reports on the photodynamic antimicrobial chemotherapy activity of these materials against Staphylococcus aureus (S. aureus) bacteria in DMSO. The results indicated that silver-based nanoconjugates exhibit high antimicrobial activity with high log reductions compared to NiWO4, CoWO4, and Ag-Fe3O4-based materials. The z-scan technique is employed to experimentally test the nonlinear optical response of complexes and nanoconjugates in solution. The nonlinear absorption coefficient, third-order optical susceptibility and optical limiting threshold of the materials are obtained from the Z-scan aperture data. The nonlinear absorption parameters improved in the presence of semiconductor quantum dots, with 1-ethanoic-CdTe/ZnSeS/ZnO giving the best results due to the presence of electron-donating substituents. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
Beyond mastery: jazz, gender and power in postapartheid South Africa
- Authors: Williams, Ulagh
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432505 , vital:72876 , DOI 10.21504/10962/432512
- Description: This dissertation studies the musical lives of seven South African women who have built highprofile national and international careers as jazz musicians. Empirically it records self-reported experiences and actions that they have identified as relevant to their success within a notoriously patriarchal field. Drawing on feminist research methods and Interpretative Phenomenological Analysis the dissertation strives to develop an empathic yet critical epistemological framework attuned to the complexities of their lived experiences as women and as jazz musicians. Theoretically it investigates the power relations at play in the myriad ways they negotiate or have been impelled to negotiate gender and patriarchy as musicians. Chapter one draws attention to the ubiquity of patriarchy in South African and international jazz culture, and highlights the research participants’ numerous successes to date as performers, educators, composers, and bandleaders. Chapter two positions this study in relation to cognate work in South African jazz studies, international feminist jazz studies and feminist phenomenology. Chapters three to five successively consider the participants’ early enculturation as musical and gendered subjects, their agentic responses to structures of patriarchy and/or race as emerging and established professionals, and the ways these experiences have found expression in some of their musical utterances as performers and composers. Fusing art and activism, the participants challenge and transcend masculinist discourses of mastery that still dominate South African jazz as a field of production and aesthetic practice. , Thesis (PhD) -- Faculty of Humanities, Music and Musicology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Williams, Ulagh
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432505 , vital:72876 , DOI 10.21504/10962/432512
- Description: This dissertation studies the musical lives of seven South African women who have built highprofile national and international careers as jazz musicians. Empirically it records self-reported experiences and actions that they have identified as relevant to their success within a notoriously patriarchal field. Drawing on feminist research methods and Interpretative Phenomenological Analysis the dissertation strives to develop an empathic yet critical epistemological framework attuned to the complexities of their lived experiences as women and as jazz musicians. Theoretically it investigates the power relations at play in the myriad ways they negotiate or have been impelled to negotiate gender and patriarchy as musicians. Chapter one draws attention to the ubiquity of patriarchy in South African and international jazz culture, and highlights the research participants’ numerous successes to date as performers, educators, composers, and bandleaders. Chapter two positions this study in relation to cognate work in South African jazz studies, international feminist jazz studies and feminist phenomenology. Chapters three to five successively consider the participants’ early enculturation as musical and gendered subjects, their agentic responses to structures of patriarchy and/or race as emerging and established professionals, and the ways these experiences have found expression in some of their musical utterances as performers and composers. Fusing art and activism, the participants challenge and transcend masculinist discourses of mastery that still dominate South African jazz as a field of production and aesthetic practice. , Thesis (PhD) -- Faculty of Humanities, Music and Musicology, 2023
- Full Text:
- Date Issued: 2023-10-13
Computational studies in human African trypanosomiasis
- Authors: Muronzi, Tendai
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431883 , vital:72812 , DOI 10.21504/10962/431885
- Description: Human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) caused by two subspecies of the parasite, namely Trypanosoma brucei (Tb) gambiense (g-HAT) and rhodesiense (r-HAT). HAT is endemic in sub-Saharan countries, where the parasite transmission vectors, tsetse flies, breed. An estimated 70 million people remain at risk of contracting the disease, where the infection is classified as acute or chronic for g-HAT and r-HAT, respectively, with both forms ending in fatal meningoencephalitis when left untreated. Both g-HAT and r-HAT are responsible for widespread fatal epidemics throughout sub-Saharan African history, resulting from the complex molecular interplay between trypanosomes and humans through unique, innate immunity evasion mechanisms. Of interest, the Tbr subspecies expresses a serum resistance-associated protein (SRA), which binds to human serum lytic factor, apolipoprotein L1 (ApoL1), nullifying any trypanocidal activity. In response, ApoL1 (G1 and G2) variants found in humans of sub-Saharan African lineage have been cited for conferring resistance to the r-HAT infection in an interaction that is not fully elucidated In the event of successful infection, current HAT chemotherapeutics are plagued with complexity of administration, poor efficacy, toxicity, and potential drug resistance, highlighting a need for improved approaches. The parasite folate pathway provides a strategic target for alternative anti-trypanosomal drug development as trypanosomatids are folate auxotrophs, requiring host folate for growth and survival. Validated drug targets pteridine reductase (TbPTR1) and dihydrofolate reductase (TbDHFR) are essential for salvaging cofactors folate and folate biopterin crucial to parasite survival, making them viable targets for anti-folate investigation. The overall aims of this thesis were to a) provide insights into the molecular and dynamic basis of the SRA and ApoL1 interplay in HAT infection and b) identify safer and more efficient anti-folate anti-trypanosomal drug alternatives through in silico approaches. To achieve our first aim, in silico structure prediction was applied to generate 3D models of ApoL1 C-terminal variants G0, G1, G1G/M, G2 and G1G2, and four SRA variants retrieved from the NCBI database. The SRA and ApoL1 structures were inspected dynamically to identify the effect of the variants through molecular dynamics (MD) simulations. Dynamic residue network (DRN) analysis of MD trajectories was fundamental in identifying residues playing a vital role in the intramolecular communication of both proteins in the presence of mutations. Protein-protein docking was then applied to calculate plausible SRA-ApoL1 C-terminal wild-type complex structures to further elucidate the nature of SRA-mediated infection. Through MD simulations, twelve SRA-ApoL1 dimeric structures were narrowed down from five to two energetically sound complexes. The two feasible SRA-ApoL1 complexes (1 and 2) exhibited favourable communication observed through DRN analysis, including the retaining key communication residues identified in prior monomer DRN calculations. ApoL1 C-terminal variants were additionally incorporated into SRA-ApoL1 complexes 1 and 2 for further complex dynamics analysis This investigation into the nature of SRA-ApoL1 binding resulted in five primary outcomes: 1) highlighting the intramolecular effects ApoL1 variants have on the stability of the protein, 2) the identification of crucial SRA and ApoL1 communication residues in both monomeric or dimeric form, 3) the isolation of feasible SRA-ApoL1 complexes determined through global and local structural analyses 4) identification of residues crucial to the complex formation and maintenance of SRA-ApoL1, overlapping with those identified in (1), and 5) the minimal dissociative role of the G1 mutations in the complex, but compounding effect of the G2 deletion mutation. Computational modelling and drug repurposing were employed to achieve the thesis's second aim as they drastically cut down the costs involved in drug discovery and provide a more time-efficient screening method through numerous drug candidates. Using high throughput virtual screening, a subset of 2089 approved DrugBank compounds were screened against TbPTR1. The outputs were filtered to 24 viable compounds in 54 binding poses using binding energy and molecular interactions. Through subsequent MD simulations of 200ns, thirteen potential hit compounds were identified. The resultant hit compounds were subjected to further blind docking against TbDHFR and molecular dynamics to identify compounds with the potential for dual inhibition. The filtered subset was also tested in in vitro single concentration and dose-response bioassays to assess inhibitory properties against Trypanosoma brucei, complementing in silico findings. Post-molecular dynamics, four compounds exhibited high stabilities and molecular interactions with both TbPTR1 and TbDHFR, with two presenting favourable results in the in vitro assays. Three compounds additionally shared common structural moieties. In all, the in silico repurposing highlighted drugs characterised by favourable interactions and stabilities in TbPTR1, thus providing (1) a framework for further studies investigating anti-folate HAT compounds and (2) modulatory scaffolds based on identified moieties that can be used for the design of safe anti-folate trypanosomal drugs. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Muronzi, Tendai
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431883 , vital:72812 , DOI 10.21504/10962/431885
- Description: Human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) caused by two subspecies of the parasite, namely Trypanosoma brucei (Tb) gambiense (g-HAT) and rhodesiense (r-HAT). HAT is endemic in sub-Saharan countries, where the parasite transmission vectors, tsetse flies, breed. An estimated 70 million people remain at risk of contracting the disease, where the infection is classified as acute or chronic for g-HAT and r-HAT, respectively, with both forms ending in fatal meningoencephalitis when left untreated. Both g-HAT and r-HAT are responsible for widespread fatal epidemics throughout sub-Saharan African history, resulting from the complex molecular interplay between trypanosomes and humans through unique, innate immunity evasion mechanisms. Of interest, the Tbr subspecies expresses a serum resistance-associated protein (SRA), which binds to human serum lytic factor, apolipoprotein L1 (ApoL1), nullifying any trypanocidal activity. In response, ApoL1 (G1 and G2) variants found in humans of sub-Saharan African lineage have been cited for conferring resistance to the r-HAT infection in an interaction that is not fully elucidated In the event of successful infection, current HAT chemotherapeutics are plagued with complexity of administration, poor efficacy, toxicity, and potential drug resistance, highlighting a need for improved approaches. The parasite folate pathway provides a strategic target for alternative anti-trypanosomal drug development as trypanosomatids are folate auxotrophs, requiring host folate for growth and survival. Validated drug targets pteridine reductase (TbPTR1) and dihydrofolate reductase (TbDHFR) are essential for salvaging cofactors folate and folate biopterin crucial to parasite survival, making them viable targets for anti-folate investigation. The overall aims of this thesis were to a) provide insights into the molecular and dynamic basis of the SRA and ApoL1 interplay in HAT infection and b) identify safer and more efficient anti-folate anti-trypanosomal drug alternatives through in silico approaches. To achieve our first aim, in silico structure prediction was applied to generate 3D models of ApoL1 C-terminal variants G0, G1, G1G/M, G2 and G1G2, and four SRA variants retrieved from the NCBI database. The SRA and ApoL1 structures were inspected dynamically to identify the effect of the variants through molecular dynamics (MD) simulations. Dynamic residue network (DRN) analysis of MD trajectories was fundamental in identifying residues playing a vital role in the intramolecular communication of both proteins in the presence of mutations. Protein-protein docking was then applied to calculate plausible SRA-ApoL1 C-terminal wild-type complex structures to further elucidate the nature of SRA-mediated infection. Through MD simulations, twelve SRA-ApoL1 dimeric structures were narrowed down from five to two energetically sound complexes. The two feasible SRA-ApoL1 complexes (1 and 2) exhibited favourable communication observed through DRN analysis, including the retaining key communication residues identified in prior monomer DRN calculations. ApoL1 C-terminal variants were additionally incorporated into SRA-ApoL1 complexes 1 and 2 for further complex dynamics analysis This investigation into the nature of SRA-ApoL1 binding resulted in five primary outcomes: 1) highlighting the intramolecular effects ApoL1 variants have on the stability of the protein, 2) the identification of crucial SRA and ApoL1 communication residues in both monomeric or dimeric form, 3) the isolation of feasible SRA-ApoL1 complexes determined through global and local structural analyses 4) identification of residues crucial to the complex formation and maintenance of SRA-ApoL1, overlapping with those identified in (1), and 5) the minimal dissociative role of the G1 mutations in the complex, but compounding effect of the G2 deletion mutation. Computational modelling and drug repurposing were employed to achieve the thesis's second aim as they drastically cut down the costs involved in drug discovery and provide a more time-efficient screening method through numerous drug candidates. Using high throughput virtual screening, a subset of 2089 approved DrugBank compounds were screened against TbPTR1. The outputs were filtered to 24 viable compounds in 54 binding poses using binding energy and molecular interactions. Through subsequent MD simulations of 200ns, thirteen potential hit compounds were identified. The resultant hit compounds were subjected to further blind docking against TbDHFR and molecular dynamics to identify compounds with the potential for dual inhibition. The filtered subset was also tested in in vitro single concentration and dose-response bioassays to assess inhibitory properties against Trypanosoma brucei, complementing in silico findings. Post-molecular dynamics, four compounds exhibited high stabilities and molecular interactions with both TbPTR1 and TbDHFR, with two presenting favourable results in the in vitro assays. Three compounds additionally shared common structural moieties. In all, the in silico repurposing highlighted drugs characterised by favourable interactions and stabilities in TbPTR1, thus providing (1) a framework for further studies investigating anti-folate HAT compounds and (2) modulatory scaffolds based on identified moieties that can be used for the design of safe anti-folate trypanosomal drugs. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
Design of an LMS-mediated tutorial to support deep and effective engagement in the process of learning mathematics
- Authors: Kigundu, Stephen
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431565 , vital:72786 , DOI 10.21504/10962/431565
- Description: Many institutions of Higher Learning have adopted a variety of Learning Management Systems (LMS) as platforms for e-learning implementation. However, the design and nature of LMS technologies present challenges to the design of LMS-based activities that engage students in learning to do mathematics. There are no clear guidelines or strategies for designing LMS-based activities that engage students in complex mathematical processes. Hence, using technologies in mathematics education often replicates instructivist positions and practices. Conversely, using constructivist principles, modes of mathematical engagement, and e-learning tools to mediate learning provides an integrated framework to transform the use of an LMS as a platform for e-learning implementation and promote deep engagement in mathematical learning. The objective of this study was to explore mechanisms that could be useful for conceiving activities to support the learning of Mathematics using an LMS-mediated tutorial. The design, redesign and evaluation of the e-tutorial are reported upon. In preparation for the study, an LMS-based tutorial was designed and developed to be used as a test-bed to investigate how these e-learning tools could support learning to do mathematics. A Trigonometry module, consisting of course content in the form of resources and tasks to help the students to explore, practice and apply right triangle concepts, was used to investigate and derive design strategies. A mixed method research approach with a reflexive self-study research design was used. A group of first-year university student volunteers studying mathematics in the mechanical engineering department were used to test the tutorial. The students were asked to do a series of tasks using the e-learning environment during the Mathematics tutorial period. Data was collected using in-class observations, interviews, screen capture videos, student-written responses, and system-generated data. All students were encouraged to complete a learning journal detailing their experiences during the tutorial using an LMS-based tool. The students were given no training, but a tutor (researcher) was available to answer any questions they may have had. Contradiction analysis was used to evaluate the data, compare purpose and practice and judge whether the activity or tool was fitted for the intended purpose. Findings were in the form of transformations of the e-tutorial system as it was developed. Among the most noteworthy contributory modifications were changing from 1) “read first, then do” to “do first, read when necessary”, 2) “work on the computer” to “work on paper then capture on the computer”, 3) “physically separated work with computer-enabled social contact”, to "individual computer work in face-to-face social settings.” 4) “single-level of resource provision” to “multi-level, demand-driven resource provision” and 5) “self-regulated” learning process regulation to “computer-assisted” learning process regulation. The discussion of these findings indicated that to enable students’ deep and effective engagement in the process of learning fundamental trigonometry within an LMS-mediated tutorial, one needs to design the system with some activities that can create a demand for knowledge, encourage rough work and face-to-face social interaction, supported by multi-level, demand-driven resources, and computer-assisted learning-process regulation. Contributions to research by this study were in the form of 1) Design Principles for LMS-mediated tutorials, 2) Principles for an e-tutorial development methodology, and 3) The LMS-mediated tutorial system. , Thesis (PhD) -- Faculty of Education, Primary and Early Childhood Education, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Kigundu, Stephen
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431565 , vital:72786 , DOI 10.21504/10962/431565
- Description: Many institutions of Higher Learning have adopted a variety of Learning Management Systems (LMS) as platforms for e-learning implementation. However, the design and nature of LMS technologies present challenges to the design of LMS-based activities that engage students in learning to do mathematics. There are no clear guidelines or strategies for designing LMS-based activities that engage students in complex mathematical processes. Hence, using technologies in mathematics education often replicates instructivist positions and practices. Conversely, using constructivist principles, modes of mathematical engagement, and e-learning tools to mediate learning provides an integrated framework to transform the use of an LMS as a platform for e-learning implementation and promote deep engagement in mathematical learning. The objective of this study was to explore mechanisms that could be useful for conceiving activities to support the learning of Mathematics using an LMS-mediated tutorial. The design, redesign and evaluation of the e-tutorial are reported upon. In preparation for the study, an LMS-based tutorial was designed and developed to be used as a test-bed to investigate how these e-learning tools could support learning to do mathematics. A Trigonometry module, consisting of course content in the form of resources and tasks to help the students to explore, practice and apply right triangle concepts, was used to investigate and derive design strategies. A mixed method research approach with a reflexive self-study research design was used. A group of first-year university student volunteers studying mathematics in the mechanical engineering department were used to test the tutorial. The students were asked to do a series of tasks using the e-learning environment during the Mathematics tutorial period. Data was collected using in-class observations, interviews, screen capture videos, student-written responses, and system-generated data. All students were encouraged to complete a learning journal detailing their experiences during the tutorial using an LMS-based tool. The students were given no training, but a tutor (researcher) was available to answer any questions they may have had. Contradiction analysis was used to evaluate the data, compare purpose and practice and judge whether the activity or tool was fitted for the intended purpose. Findings were in the form of transformations of the e-tutorial system as it was developed. Among the most noteworthy contributory modifications were changing from 1) “read first, then do” to “do first, read when necessary”, 2) “work on the computer” to “work on paper then capture on the computer”, 3) “physically separated work with computer-enabled social contact”, to "individual computer work in face-to-face social settings.” 4) “single-level of resource provision” to “multi-level, demand-driven resource provision” and 5) “self-regulated” learning process regulation to “computer-assisted” learning process regulation. The discussion of these findings indicated that to enable students’ deep and effective engagement in the process of learning fundamental trigonometry within an LMS-mediated tutorial, one needs to design the system with some activities that can create a demand for knowledge, encourage rough work and face-to-face social interaction, supported by multi-level, demand-driven resources, and computer-assisted learning-process regulation. Contributions to research by this study were in the form of 1) Design Principles for LMS-mediated tutorials, 2) Principles for an e-tutorial development methodology, and 3) The LMS-mediated tutorial system. , Thesis (PhD) -- Faculty of Education, Primary and Early Childhood Education, 2023
- Full Text:
- Date Issued: 2023-10-13
Developing and exploring a career education programme for disadvantaged FET-phase learners in the northern areas of Gqeberha: a developmental-contextual approach
- Human, Antoinette Charlotte Lucy
- Authors: Human, Antoinette Charlotte Lucy
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432333 , vital:72862 , DOI 10.21504/10962/432333
- Description: Career development theory and assessments in South Africa have often been unscientifically applied to traditionally disadvantaged individuals, with little consideration of the diverse contexts of indigenous groups in the country. Assessment measures were not suited to the needs of learners from resource-constrained environments, nor could learners from these communities access these due to the associated financial costs. Recent research developments (using more holistic approaches) suggest that career counselling in South Africa should move towards better contextualized approaches to understanding and informing career development. Follow-up research projects show the value of such approaches with youth. Postmodern career development theories and models recognise that career counselling and development should focus on supporting individuals in constructing their careers from their own experiences within their environments, particularly for learners from disadvantaged communities whose career decisions and career development are inextricably influenced by their environments. The present study therefore employed the Developmental-Contextual Framework (DCF) to explore the perspectives of FET-phase Life Orientation (LO) educators on the LO curriculum (LO CAPS) for careers and career choices; as well as contextual factors influencing the career development of disadvantaged learners in public schools. The overall aim of the study was to co-construct and explore a customised career education programme, alongside LO educators, and determine whether FET-phase learners from disadvantaged public schools could benefit from such a programme. The DCF emphasises the dynamic relationship between an individual and the environment and the influences thereof on career development. The study draws from previous South African studies with disadvantaged learners and students that acknowledged the applicability of the DCF in the design of career programmes. This framework acknowledges the embeddedness of the individual in their proximal and distal environments and the role of these environments in the career decisionmaking of learners. The study was conducted in disadvantaged secondary schools in the Northern Areas of Gqeberha in the Eastern Cape, with LO educators in the FET-phase and the LO subject advisor at District level. At the initial interview stage the sample consisted of 9 participants and reduced to 6 participants in the focus group stage. The study underlined the impact of various contextual factors on career decision-making and the inclusion of these in career education programmes, particularly when working with learners from disadvantaged environments. Furthermore, the study illustrated that the career education of FET-phase learners in public high schools is lacking in many ways and that LO educators are not adequately trained to teach careers topics and therefore lack skills to support learners with their career development needs. The lack of, as well as poor and outdated career resources, impact negatively on the career education of learners in many public schools. Underpinned by Action Research, over a series of seven focus group meetings, an applicable and relevant programme of career-related activities based on the DCF was planned and evaluated by educators. The cumulative data were thematically analysed and the study revealed that the customised programme could potentially address the career development needs of learners from disadvantaged public schools, if educators are adequately trained to apply it. Recommendations are made for further piloting and implementation. , Thesis (PhD) -- Faculty of Humanities, Psychology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Human, Antoinette Charlotte Lucy
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432333 , vital:72862 , DOI 10.21504/10962/432333
- Description: Career development theory and assessments in South Africa have often been unscientifically applied to traditionally disadvantaged individuals, with little consideration of the diverse contexts of indigenous groups in the country. Assessment measures were not suited to the needs of learners from resource-constrained environments, nor could learners from these communities access these due to the associated financial costs. Recent research developments (using more holistic approaches) suggest that career counselling in South Africa should move towards better contextualized approaches to understanding and informing career development. Follow-up research projects show the value of such approaches with youth. Postmodern career development theories and models recognise that career counselling and development should focus on supporting individuals in constructing their careers from their own experiences within their environments, particularly for learners from disadvantaged communities whose career decisions and career development are inextricably influenced by their environments. The present study therefore employed the Developmental-Contextual Framework (DCF) to explore the perspectives of FET-phase Life Orientation (LO) educators on the LO curriculum (LO CAPS) for careers and career choices; as well as contextual factors influencing the career development of disadvantaged learners in public schools. The overall aim of the study was to co-construct and explore a customised career education programme, alongside LO educators, and determine whether FET-phase learners from disadvantaged public schools could benefit from such a programme. The DCF emphasises the dynamic relationship between an individual and the environment and the influences thereof on career development. The study draws from previous South African studies with disadvantaged learners and students that acknowledged the applicability of the DCF in the design of career programmes. This framework acknowledges the embeddedness of the individual in their proximal and distal environments and the role of these environments in the career decisionmaking of learners. The study was conducted in disadvantaged secondary schools in the Northern Areas of Gqeberha in the Eastern Cape, with LO educators in the FET-phase and the LO subject advisor at District level. At the initial interview stage the sample consisted of 9 participants and reduced to 6 participants in the focus group stage. The study underlined the impact of various contextual factors on career decision-making and the inclusion of these in career education programmes, particularly when working with learners from disadvantaged environments. Furthermore, the study illustrated that the career education of FET-phase learners in public high schools is lacking in many ways and that LO educators are not adequately trained to teach careers topics and therefore lack skills to support learners with their career development needs. The lack of, as well as poor and outdated career resources, impact negatively on the career education of learners in many public schools. Underpinned by Action Research, over a series of seven focus group meetings, an applicable and relevant programme of career-related activities based on the DCF was planned and evaluated by educators. The cumulative data were thematically analysed and the study revealed that the customised programme could potentially address the career development needs of learners from disadvantaged public schools, if educators are adequately trained to apply it. Recommendations are made for further piloting and implementation. , Thesis (PhD) -- Faculty of Humanities, Psychology, 2023
- Full Text:
- Date Issued: 2023-10-13
Disaster risk management issues in WASH in South Africa: an examination of selected challenges and development of possible solutions
- Authors: Madikizela, Phindile
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431520 , vital:72782
- Description: Access restricted. Expected release date 2025. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Madikizela, Phindile
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431520 , vital:72782
- Description: Access restricted. Expected release date 2025. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2023
- Full Text:
- Date Issued: 2023-10-13
Discovery and classification of compact radio sources in the MeerKAT Galactic Centre data
- Authors: Rammala, Isabella Dineo
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432218 , vital:72852
- Description: Access restricted. Expected release date in 2025. , Thesis (PhD) -- Faculty of Science, Physics and Electronics, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Rammala, Isabella Dineo
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432218 , vital:72852
- Description: Access restricted. Expected release date in 2025. , Thesis (PhD) -- Faculty of Science, Physics and Electronics, 2023
- Full Text:
- Date Issued: 2023-10-13
Enhancing the electrocatalytic activity of phthalocyanines through finding the ideal combination of substituents in push-pull phthalocyanine-based systems
- Nkhahle, Reitumetse Precious
- Authors: Nkhahle, Reitumetse Precious
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432578 , vital:72882 , DOI 10.21504/10962/432578
- Description: Phthalocyanines (Pcs) are a class of synthetic pigments with a similar structure to porphyrins. The work presented in this thesis is centred around these electron-rich macrocycles and their use in electrocatalysis. This body of work provides a more rigorous analysis on asymmetric Pcs, focusing on finding the “ideal” combination of substituents in the synthesis of A3B-type Pcs and how these asymmetric structures compare with their symmetric counterparts (A4) in the electrocatalysis of hydrazine and nitrite. The choice in substituents in the syntheses of the Pcs was such that there is both electron-donating and electron-withdrawing groups to induce a push-pull effect. In the studies involving the electrocatalysis of hydrazine, asymmetric cobalt Pcs (CoPcs) possessing alkyl groups as the primary substituents, with variations in the acid-containing group, along with their symmetric counterparts, probes with potential for further improvement were identified. Using voltammetric and amperometric techniques, the analyte-electrode kinetics, mechanism in which the electrochemical reaction proceeds along with the limits of detection (LoD) were determined. In the general sense, the pentadecylphenoxy-derived CoPcs performed better than those containing the tert-butyl substituent as the dominant substituent with the asymmetric CoPcs producing more favourable results than their symmetric analogues. With respect to the probes designed for nitrite, a multi-dimensional approach was undertaken in that acetaminophen was chosen as the primary substituent whilst multiple changes in the asymmetric component were made. In addition to varying the carboxylic acid-containing substituent, alkyne- and amine-based substituents were also explored in which the alkyne-containing Pc was anchored onto the electrode surface through click chemistry while the amine-bearing Pc was covalently linked (and π-stacked) to nitrogen-doped graphene quantum dots (NGQDs). Another component that was altered was the central metal where CoPcs were compared to manganese Pcs (MnPcs). The most desirable peak oxidation potential for nitrite was observed in the MnPcs as it was the lowest with adsorption sometimes being a better suited method of electrode modification relative to clicking. The inclusion of NGQDs was found to be beneficial when combined with the symmetric CoPc whilst in the presence of an asymmetric Pc complex, less desirable results were observed. Overall, there were variations in the results with the symmetric CoPc sometimes being better than some of the asymmetric CoPcs demonstrating that a blanket-approach in terms of synthesizing and applying asymmetric Pcs is not always viable. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Nkhahle, Reitumetse Precious
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432578 , vital:72882 , DOI 10.21504/10962/432578
- Description: Phthalocyanines (Pcs) are a class of synthetic pigments with a similar structure to porphyrins. The work presented in this thesis is centred around these electron-rich macrocycles and their use in electrocatalysis. This body of work provides a more rigorous analysis on asymmetric Pcs, focusing on finding the “ideal” combination of substituents in the synthesis of A3B-type Pcs and how these asymmetric structures compare with their symmetric counterparts (A4) in the electrocatalysis of hydrazine and nitrite. The choice in substituents in the syntheses of the Pcs was such that there is both electron-donating and electron-withdrawing groups to induce a push-pull effect. In the studies involving the electrocatalysis of hydrazine, asymmetric cobalt Pcs (CoPcs) possessing alkyl groups as the primary substituents, with variations in the acid-containing group, along with their symmetric counterparts, probes with potential for further improvement were identified. Using voltammetric and amperometric techniques, the analyte-electrode kinetics, mechanism in which the electrochemical reaction proceeds along with the limits of detection (LoD) were determined. In the general sense, the pentadecylphenoxy-derived CoPcs performed better than those containing the tert-butyl substituent as the dominant substituent with the asymmetric CoPcs producing more favourable results than their symmetric analogues. With respect to the probes designed for nitrite, a multi-dimensional approach was undertaken in that acetaminophen was chosen as the primary substituent whilst multiple changes in the asymmetric component were made. In addition to varying the carboxylic acid-containing substituent, alkyne- and amine-based substituents were also explored in which the alkyne-containing Pc was anchored onto the electrode surface through click chemistry while the amine-bearing Pc was covalently linked (and π-stacked) to nitrogen-doped graphene quantum dots (NGQDs). Another component that was altered was the central metal where CoPcs were compared to manganese Pcs (MnPcs). The most desirable peak oxidation potential for nitrite was observed in the MnPcs as it was the lowest with adsorption sometimes being a better suited method of electrode modification relative to clicking. The inclusion of NGQDs was found to be beneficial when combined with the symmetric CoPc whilst in the presence of an asymmetric Pc complex, less desirable results were observed. Overall, there were variations in the results with the symmetric CoPc sometimes being better than some of the asymmetric CoPcs demonstrating that a blanket-approach in terms of synthesizing and applying asymmetric Pcs is not always viable. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
Exploring the drivers of co-occurring multiple non-native fish assemblages within an invaded and flow-modified African river system
- Authors: Mpopetsi, Pule Peter
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431871 , vital:72810 , DOI 10.21504/10962/431871
- Description: Globally, there is growing concern on the negative impacts of species invasions and habitat disturbance because these have been shown to have the potential to disrupt native community structure and function. In some instances, these two stressors can occur in concert, such as in river systems associated with inter-basin water transfer (IBWT) schemes. The Great Fish River in the Eastern Cape, South Africa, is an example of a system affected by both habitat modification and multiple fish invasions largely because of an IBWT scheme. The opening of the Orange-Fish IBWT, which transfers water from the Orange River to the Great Fish River, modified the latter’s natural flow regime from irregular seasonal to perennial. In addition, the IBWT facilitated translocations of five fish species from the Gariep Dam (Orange River system) into the Great Fish River system. Proliferation of these non-native fish species, along with that of other fish species introduced for angling and biological control, raise questions on the mechanisms facilitating their existence within this highly modified river system. This thesis explored mechanisms associated with co-occurrences of these multiple non-native fishes within the Great Fish River. A comparison of historical and contemporary records on the ichthyofauna of the Great Fish River revealed that, of the 11 non-native fishes reported in this system, seven have established successfully, three have failed to establish and the status of one was uncertain. The Orange-Fish IBWT and angling were the main vectors of these invasions, accounting for 36% and 46%, respectively. The study also found that most established non-native fish species were large sized, had high longevity and wide habitat tolerance. Trait-based approaches were employed to investigate the role of functional diversity of non-native and native fishes in relation to their composition, distribution and environmental relationships. Although considerable interspecific variation in body morphology-related functional traits among species were observed, there was no clear distinction in these traits between native and non-native fish assemblages on a trait-ordination space. Furthermore, there were weak species-trait-environment relationships, suggesting that environmental filtering was less plausible in explaining the occurrence patterns of these fishes. Stable isotope-based trophic relationships were evaluated in three invaded sections: the upper (UGFR) mainstem sections of the Great Fish River; and lower (LGFR) mainstem sections of the Great Fish River; and its tributary, the Koonap River. It was observed that native and non-native fish assemblages exhibited variation in isotopic diversity typified by low isotopic diversity overlaps in UGFR and Koonap River, whereas the LGFR was characterised by high isotopic diversity overlap. Within the invaded sections, non-native fishes were found to have isotopic niches characterised by variable isotopic niche sizes and were more isotopically dissimilar with propensity towards trophic differentiation within the UGFR and Koonap River but were mostly characterised by high isotope niche overlaps in the LGFR. Overall, these results provided evidence of trophic niche differentiation as a probable mechanism associated with the co-occurrences of the non-native fishes. However, mechanisms facilitating these co-occurrences within the invaded sections appears to be complex, context-specific and, in some cases, unclear. Lastly, machine learning techniques, boosted (BRT) and multivariate (MRT) regression trees, revealed that the flow-disturbed habitats were invaded by multiple non-native species, whereas the non-disturbed headwaters remained invasion free. In addition, non-native species were predicted to co-occur with native species within the mainstem and large tributary sections of the Great Fish River system. Thus, the IBWT-disturbed mainstem sections were predicted to be more prone to multiple invasions compared to undisturbed headwater tributaries. , Tlhaselo ka mefuta ya diphoofolo-tsa-matswantle (non-native species), ha mmoho le phetolo/tsenyehelo ya bodulo ba diphoofolo-tsa-lehae (native species), di nkuwa ele tse pedi tsa tse kgolo ka ho fetisisa hara ditshoso tse kgahlanong le paballo kapa tshireletso ya diphoofolo-tsa-lehae tse phelang dinokeng kapa metsing. Maemong a mang, dikgatello tsena tse pedi dika etsahala ka nako e le nngwe, jwalo ka dinokeng tseo di amanang le maano a ho fetisa/tsamaisa metsi pakeng tsa dinoka tse fapa-fapaneng (IBWT). Enngwe ya dinoka tse jwalo, ke noka e bitswang ka Great Fish River, e fumanehang Kapa-Botjabela (Eastern Cape) ka hara naha ya Afrika Borwa (South Africa). Noka ena ya Great Fish River e angwa ke tshenyehelo ya bodulo ba ditlhapi-tsa-lehae, ha mmoho le tlhaselo ya tsona ka ditlhapi-tsa-matswantle. Tsena di etsahala hahololo ka lebaka la morero kapa leano la phepelo ya metsi le bitswang Orange-Fish IBWT, leo lona le ileng la fetola phallo ya tlhaho ya metsi a Great Fish River. Ho feta moo, leano lena la phephelo yametsi, Orange-Fish IBWT, le entse hore ho be bonolo ho fetisetswa ha mefuta e mehlano ya ditlhapi-tsa-matswantle ho tloha letamong le bitswang Gariep Dam, hoya kena ka hara noka ya Great Fish River. Ditla morao tsa tsena tsohle, ebile ho ata ha mefuta e mengata ya ditlhapi-tsa-matswantle ka hara noka ya Great Fish River. Ho ata hona ha ditlapi-tsa-matswantle ka hara noka ena ya Great Fish River, ho hlahisa dipotso mabapi le mekgwa e bebofatsang ho phela ha ditlhapi tsena tsa matswantle ka hara noka ena; hore ana ebe diphela jwang ka hara noka ya Great Fish River? Ka hona, sepheo le merero wa thuto ena ke ho phuputsa mekgwa e bebofatsang ho phela ha mefuta ena e fapaneng ya ditlhapi-tsa-matswantle ka hara noka ya Great Fish River. Dipheto tsa diphuputso di hlalosa hore, ha jwale, ka hara noka ena ya Great Fish River, hona le ditlhapi-tsa-matswantle tse leshome le motso o mong (11). Bosupa (7) ba tsona di phela ka katleho, ha tse tharo di hlolehile ho theha (3), mme e le nngwe (1) boemo ba teng ha bo hlake. Hare lekola hore ke efeng mekgwa e amanang le ho ata ha ditlhapi-tsa-matswantle ka hara Great Fish River, re fumana hore leano la phephelo ya metsi la Orange-Fish IBWT ka 36%, ha mmoho le boithapollo ba ho tshwasa ditlhapi (angling) ka 46%, ene ele tsona tsela tsa ho kena ha ditlhapi-tsa-matswantle ka hara Great Fish River, tse ka sehlohong. Re fumantsha hape hore katleho ya ditlhapi-tsa-matswantle e amahangwa le hore di boholo bo bokae, le hore diphela nako e ka kang. Mohlala, ditlhapi tse kgolo tse phelang nako etelele ka tlhaho ya tsona, di amahangwa le katleho ya ho theha ka hara noka ena. Ha tseo tse phelang nako e kgutshwanyane tsona disa amahangwe leho atleha ka hara noka ena. Tse ding tsa dipheto di hlalosa hore, ditlhapi-tsa-lehae le ditlhapi-tsa-matswantle, ka karolelano, hadi fapane haholo ka dibopeho tsa mmele, dihlopa tsena tse pedi diya tshwana. Re fumantsha hape hore dihlopa tsena tse pedi tsa ditlapi dija mefuta e fapaneng ya dijo. Eleng engwe ya dintho tse netefatsang katleho ya ditlhapi-tsa-matswantle ka hara noka ena ya Great fish river. Hona keka lebaka la hore, dihlopa tsena tse pedi hadi bakisane dijo, empa di phela ka mefuta e fapaneng ya dijo. Hare phethela, re fumantsha hore mefuta e fapafapaneng ya ditlhapi-tsa-matswantle e fumaneha feela ka hara madulo a amahangwang le phethoho ya phallo ya metsi (flow alteration), madulo asa amahangwang le phetoho ya phallo ya metsi ona ane a hloka ditlhapi-tsa-matswantle. Sena se bolela hore phetolo ya phallo ya metsi ya Great Fish River, ka lebaka la Orange-Fish IBWT, e fokoditse matla a noka ena ho lwantsha tlhaselo ya ditlhapi-tsa-matswantle. Ka hona, ho bobebe hore ditlhapi-tsa-matswantle di thehe ka katleho ka hara noka ena. Tsena tsohle keka baka la phetolo ya phallo ya metsi a Great Fish River e bakilweng ke leano la phephelo ya metsi la Orange-Fish IBWT. , Thesis (PhD) -- Faculty of Science, Faculty of Science, Ichthyology and Fisheries Science, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Mpopetsi, Pule Peter
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431871 , vital:72810 , DOI 10.21504/10962/431871
- Description: Globally, there is growing concern on the negative impacts of species invasions and habitat disturbance because these have been shown to have the potential to disrupt native community structure and function. In some instances, these two stressors can occur in concert, such as in river systems associated with inter-basin water transfer (IBWT) schemes. The Great Fish River in the Eastern Cape, South Africa, is an example of a system affected by both habitat modification and multiple fish invasions largely because of an IBWT scheme. The opening of the Orange-Fish IBWT, which transfers water from the Orange River to the Great Fish River, modified the latter’s natural flow regime from irregular seasonal to perennial. In addition, the IBWT facilitated translocations of five fish species from the Gariep Dam (Orange River system) into the Great Fish River system. Proliferation of these non-native fish species, along with that of other fish species introduced for angling and biological control, raise questions on the mechanisms facilitating their existence within this highly modified river system. This thesis explored mechanisms associated with co-occurrences of these multiple non-native fishes within the Great Fish River. A comparison of historical and contemporary records on the ichthyofauna of the Great Fish River revealed that, of the 11 non-native fishes reported in this system, seven have established successfully, three have failed to establish and the status of one was uncertain. The Orange-Fish IBWT and angling were the main vectors of these invasions, accounting for 36% and 46%, respectively. The study also found that most established non-native fish species were large sized, had high longevity and wide habitat tolerance. Trait-based approaches were employed to investigate the role of functional diversity of non-native and native fishes in relation to their composition, distribution and environmental relationships. Although considerable interspecific variation in body morphology-related functional traits among species were observed, there was no clear distinction in these traits between native and non-native fish assemblages on a trait-ordination space. Furthermore, there were weak species-trait-environment relationships, suggesting that environmental filtering was less plausible in explaining the occurrence patterns of these fishes. Stable isotope-based trophic relationships were evaluated in three invaded sections: the upper (UGFR) mainstem sections of the Great Fish River; and lower (LGFR) mainstem sections of the Great Fish River; and its tributary, the Koonap River. It was observed that native and non-native fish assemblages exhibited variation in isotopic diversity typified by low isotopic diversity overlaps in UGFR and Koonap River, whereas the LGFR was characterised by high isotopic diversity overlap. Within the invaded sections, non-native fishes were found to have isotopic niches characterised by variable isotopic niche sizes and were more isotopically dissimilar with propensity towards trophic differentiation within the UGFR and Koonap River but were mostly characterised by high isotope niche overlaps in the LGFR. Overall, these results provided evidence of trophic niche differentiation as a probable mechanism associated with the co-occurrences of the non-native fishes. However, mechanisms facilitating these co-occurrences within the invaded sections appears to be complex, context-specific and, in some cases, unclear. Lastly, machine learning techniques, boosted (BRT) and multivariate (MRT) regression trees, revealed that the flow-disturbed habitats were invaded by multiple non-native species, whereas the non-disturbed headwaters remained invasion free. In addition, non-native species were predicted to co-occur with native species within the mainstem and large tributary sections of the Great Fish River system. Thus, the IBWT-disturbed mainstem sections were predicted to be more prone to multiple invasions compared to undisturbed headwater tributaries. , Tlhaselo ka mefuta ya diphoofolo-tsa-matswantle (non-native species), ha mmoho le phetolo/tsenyehelo ya bodulo ba diphoofolo-tsa-lehae (native species), di nkuwa ele tse pedi tsa tse kgolo ka ho fetisisa hara ditshoso tse kgahlanong le paballo kapa tshireletso ya diphoofolo-tsa-lehae tse phelang dinokeng kapa metsing. Maemong a mang, dikgatello tsena tse pedi dika etsahala ka nako e le nngwe, jwalo ka dinokeng tseo di amanang le maano a ho fetisa/tsamaisa metsi pakeng tsa dinoka tse fapa-fapaneng (IBWT). Enngwe ya dinoka tse jwalo, ke noka e bitswang ka Great Fish River, e fumanehang Kapa-Botjabela (Eastern Cape) ka hara naha ya Afrika Borwa (South Africa). Noka ena ya Great Fish River e angwa ke tshenyehelo ya bodulo ba ditlhapi-tsa-lehae, ha mmoho le tlhaselo ya tsona ka ditlhapi-tsa-matswantle. Tsena di etsahala hahololo ka lebaka la morero kapa leano la phepelo ya metsi le bitswang Orange-Fish IBWT, leo lona le ileng la fetola phallo ya tlhaho ya metsi a Great Fish River. Ho feta moo, leano lena la phephelo yametsi, Orange-Fish IBWT, le entse hore ho be bonolo ho fetisetswa ha mefuta e mehlano ya ditlhapi-tsa-matswantle ho tloha letamong le bitswang Gariep Dam, hoya kena ka hara noka ya Great Fish River. Ditla morao tsa tsena tsohle, ebile ho ata ha mefuta e mengata ya ditlhapi-tsa-matswantle ka hara noka ya Great Fish River. Ho ata hona ha ditlapi-tsa-matswantle ka hara noka ena ya Great Fish River, ho hlahisa dipotso mabapi le mekgwa e bebofatsang ho phela ha ditlhapi tsena tsa matswantle ka hara noka ena; hore ana ebe diphela jwang ka hara noka ya Great Fish River? Ka hona, sepheo le merero wa thuto ena ke ho phuputsa mekgwa e bebofatsang ho phela ha mefuta ena e fapaneng ya ditlhapi-tsa-matswantle ka hara noka ya Great Fish River. Dipheto tsa diphuputso di hlalosa hore, ha jwale, ka hara noka ena ya Great Fish River, hona le ditlhapi-tsa-matswantle tse leshome le motso o mong (11). Bosupa (7) ba tsona di phela ka katleho, ha tse tharo di hlolehile ho theha (3), mme e le nngwe (1) boemo ba teng ha bo hlake. Hare lekola hore ke efeng mekgwa e amanang le ho ata ha ditlhapi-tsa-matswantle ka hara Great Fish River, re fumana hore leano la phephelo ya metsi la Orange-Fish IBWT ka 36%, ha mmoho le boithapollo ba ho tshwasa ditlhapi (angling) ka 46%, ene ele tsona tsela tsa ho kena ha ditlhapi-tsa-matswantle ka hara Great Fish River, tse ka sehlohong. Re fumantsha hape hore katleho ya ditlhapi-tsa-matswantle e amahangwa le hore di boholo bo bokae, le hore diphela nako e ka kang. Mohlala, ditlhapi tse kgolo tse phelang nako etelele ka tlhaho ya tsona, di amahangwa le katleho ya ho theha ka hara noka ena. Ha tseo tse phelang nako e kgutshwanyane tsona disa amahangwe leho atleha ka hara noka ena. Tse ding tsa dipheto di hlalosa hore, ditlhapi-tsa-lehae le ditlhapi-tsa-matswantle, ka karolelano, hadi fapane haholo ka dibopeho tsa mmele, dihlopa tsena tse pedi diya tshwana. Re fumantsha hape hore dihlopa tsena tse pedi tsa ditlapi dija mefuta e fapaneng ya dijo. Eleng engwe ya dintho tse netefatsang katleho ya ditlhapi-tsa-matswantle ka hara noka ena ya Great fish river. Hona keka lebaka la hore, dihlopa tsena tse pedi hadi bakisane dijo, empa di phela ka mefuta e fapaneng ya dijo. Hare phethela, re fumantsha hore mefuta e fapafapaneng ya ditlhapi-tsa-matswantle e fumaneha feela ka hara madulo a amahangwang le phethoho ya phallo ya metsi (flow alteration), madulo asa amahangwang le phetoho ya phallo ya metsi ona ane a hloka ditlhapi-tsa-matswantle. Sena se bolela hore phetolo ya phallo ya metsi ya Great Fish River, ka lebaka la Orange-Fish IBWT, e fokoditse matla a noka ena ho lwantsha tlhaselo ya ditlhapi-tsa-matswantle. Ka hona, ho bobebe hore ditlhapi-tsa-matswantle di thehe ka katleho ka hara noka ena. Tsena tsohle keka baka la phetolo ya phallo ya metsi a Great Fish River e bakilweng ke leano la phephelo ya metsi la Orange-Fish IBWT. , Thesis (PhD) -- Faculty of Science, Faculty of Science, Ichthyology and Fisheries Science, 2023
- Full Text:
- Date Issued: 2023-10-13
Exploring the interplay between foundation phase learners’ home and school literacy practices
- Authors: Magxala, Xoliswa Patience
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431587 , vital:72788 , DOI 10.21504/10962/431587
- Description: The thesis looked at Foundation Phase children’s early home literacy practices and examined how these literacy practices are adopted at school in Libode, Eastern Cape Province, South Africa, a rural area. The purpose of the study was to determine how early literacy practices at home are adopted in classrooms. The study aimed to determine the relationship between home and school literacy. To understand the literacy practices used at home and school by four Foundation Phase children and four Foundation Phase teachers, an interpretive ethnographic study design was used. Participants who spoke isiXhosa as their first language participated in data collection using structured observations, video and audio recordings, field notes, and unstructured interviews. The study’s framework, the Cultural Historical Activity Theory, was used as a tool to collect, examine, and interpret data through its various components. Themes were identified, arranged, and categorized. The findings revealed children from low socioeconomic backgrounds have rich literacy practices. Teachers do not acknowledge or recognize the contributions that these children’s cultural backgrounds make. The study recommends that schools start acknowledging the advantages that children’s environments have for them. It also suggests that teachers build on the knowledge that children bring from home, as this will have an impact on how they behave in class because students bring their family’s literacy habits, which serve as the foundation for their academic literacy habits, to school. , Thesis (PhD) -- Faculty of Education, Institute for the Study of Englishes in Africa, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Magxala, Xoliswa Patience
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431587 , vital:72788 , DOI 10.21504/10962/431587
- Description: The thesis looked at Foundation Phase children’s early home literacy practices and examined how these literacy practices are adopted at school in Libode, Eastern Cape Province, South Africa, a rural area. The purpose of the study was to determine how early literacy practices at home are adopted in classrooms. The study aimed to determine the relationship between home and school literacy. To understand the literacy practices used at home and school by four Foundation Phase children and four Foundation Phase teachers, an interpretive ethnographic study design was used. Participants who spoke isiXhosa as their first language participated in data collection using structured observations, video and audio recordings, field notes, and unstructured interviews. The study’s framework, the Cultural Historical Activity Theory, was used as a tool to collect, examine, and interpret data through its various components. Themes were identified, arranged, and categorized. The findings revealed children from low socioeconomic backgrounds have rich literacy practices. Teachers do not acknowledge or recognize the contributions that these children’s cultural backgrounds make. The study recommends that schools start acknowledging the advantages that children’s environments have for them. It also suggests that teachers build on the knowledge that children bring from home, as this will have an impact on how they behave in class because students bring their family’s literacy habits, which serve as the foundation for their academic literacy habits, to school. , Thesis (PhD) -- Faculty of Education, Institute for the Study of Englishes in Africa, 2023
- Full Text:
- Date Issued: 2023-10-13
Falcipain 2 and 3 as malarial drug targets: deciphering the effects of missense mutations and identification of allosteric modulators via computational approaches
- Authors: Okeke, Chiamaka Jessica
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432170 , vital:72848 , DOI 10.21504/10962/432170
- Description: Malaria, caused by an obligate unicellular protozoan parasite of the genus Plasmodium, is a disease of global health importance that remains a major cause of morbidity and mortality in developing countries. The World Health Organization (WHO) reported nearly 247 million malaria cases in 2021, causing 619,000 deaths, the vast majority ascribed to pregnant women and young children in sub-Saharan Africa. A critical component of malaria mitigation and elimination efforts worldwide is antimalarial drugs. However, resistance to available antimalarial drugs jeopardizes the treatment, prevention, and eradication of the disease. The recent emergence and spread of resistance to artemisinin (ART), the currently recommended first-line antimalarial drug, emphasizes the need to understand the resistance mechanism and apply this knowledge in developing new drugs that are effective against malaria. An insight into ART's mechanism of action indicates that ferrous iron (Fe2+) or heme, released when hemoglobin is degraded, cleaves the endoperoxide bridge. As a result, free radicals are formed, which alkylate many intracellular targets and result in plasmodial proteopathy. Aside from the existing evidence that mutations in the Kelch 13 protein propeller domain affect ART sensitivity and clearance rate by Plasmodium falciparum (Pf) parasites, recent investigations raise the possibility that additional target loci may be involved, and these include a nonsense (S69stop) and four missense variants (K255R, N257E, T343P, and D345G) in falcipain 2 (FP-2) protein. FP-2 and falcipain 3 (FP-3) are cysteine proteases responsible for hydrolyzing hemoglobin in the host erythrocytic cycle, a key virulence factor for malaria parasite growth and metabolism. Due to the obligatory nature of the hemoglobin degradation process, both proteases have become potential antimalarial drug targets attracting attention in recent years for the development of blood-stage antimalarial drugs. The alteration of the expression profile of FP-2 and FP-3 through gene manipulation approaches (knockout) or compound inhibition assays, respectively, induced parasites with swollen food vacuoles due to the accumulation of undegraded hemoglobin. Furthermore, missense mutations in FP-2 confer parasites with decreased ART sensitivity, probably due to altered enzyme efficiency and momentary decreased hemoglobin degradation. Hence, understanding how these mutations affect FP-2 (including those implicated in ART resistance) and FP-3 is imperative to finding potentially effective inhibitors. The first aim of this thesis is to characterize the effects of missense mutations on the partial zymogen complex and the catalytic domain of FP-2 and FP-3 using a range of computational approaches and tools such as homology modeling, molecular dynamics (MD) simulations, comparative essential dynamics, dynamic residue network (DRN) analysis, weighted residue contact map analysis, amongst others. The Pf genomic resource database (PlasmoDB) identified 41 missense mutations located in the partial zymogen and catalytic domains of FP-2 and FP-3. Using structure-based tools, six putative allosteric pockets were identified in FP-2 and FP-3. The effect of mutations on the whole protein, the central core, binding pocket residues and allosteric pockets was evaluated. The accurate 3D homology models of the WT and mutants were calculated. MD simulations were performed on the various systems as a quick starting point. MD simulations have provided a cornerstone for establishing numerous computational tools for describing changes arising from mutations, ligand binding, and environmental changes such as pH and temperature. Post-MD analysis was performed in two stages viz global and local analysis. Global analysis via radius of gyration (Rg) and comparative essential dynamic analysis revealed the conformational variability associated with all mutations. In the catalytic domain of FP-2, the presence of M245I mutation triggered the formation of a cryptic pocket via an exclusive mechanism involving the fusion of pockets 2 and 6. This striking observation was also detected in the partial zymogen complex of FP-2 and induced by A159V, M245I and E249A mutations. A similar observation was uncovered in the presence of A422T mutation in the catalytic domain of FP-3. Local DRN and contact map analyses identified conserved inter-residue interaction changes on important communication networks. This study brings a novel understanding of the effects of missense mutations in FP-2 and FP-3 and provides important insight which may help discover new anti-hemoglobinase drugs. The second aim is the identification of potential allosteric ligands against the WT and mutant systems of FP-2 and FP-3 using various computational tools. Of the six potential allosteric pockets identified in FP-2 and FP-3, pocket 1 was evaluated by SiteMap as the most druggable in both proteins. This pipeline was implemented to screen pocket 1 of FP-2 and FP-3 against 2089 repositionable compounds obtained from the DrugBank database. In order to ensure selectivity and specificity to the Plasmodium protein, the human homologs (Cat K and Cat L) were screened, and compounds binding to these proteins were exempted from further analysis. Subsequently, eight compounds (DB00128, DB00312, DB00766, DB00951, DB02893, DB03754, DB13972, and DB14159) were identified as potential allosteric hits for FP-2 and five (DB00853, DB00951, DB01613, DB04173 and DB09419) for FP-3. These compounds were subjected to MD simulation and post-MD trajectory analysis to ascertain their stability in their respective protein structures. The effects of the stable compounds on the WT and mutant systems of FP-2 and FP-3 were then evaluated using DRN analysis. Attention has recently been drawn towards identifying novel allosteric compounds targeting FP-2 and FP-3; hence this study explores the potential allosteric inhibitory mechanisms in the presence and absence of mutations in FP-2 and FP-3. Overall, the results presented in this thesis provide (i) an understanding of the role mutations in the partial zymogen complex play in the activation of the active enzyme, (ii) an insight into the possible allosteric mechanisms induced by mutations on the active enzymes, and (iii) a computational pipeline for the development of novel allosteric modulators for malaria inhibition studies. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Okeke, Chiamaka Jessica
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432170 , vital:72848 , DOI 10.21504/10962/432170
- Description: Malaria, caused by an obligate unicellular protozoan parasite of the genus Plasmodium, is a disease of global health importance that remains a major cause of morbidity and mortality in developing countries. The World Health Organization (WHO) reported nearly 247 million malaria cases in 2021, causing 619,000 deaths, the vast majority ascribed to pregnant women and young children in sub-Saharan Africa. A critical component of malaria mitigation and elimination efforts worldwide is antimalarial drugs. However, resistance to available antimalarial drugs jeopardizes the treatment, prevention, and eradication of the disease. The recent emergence and spread of resistance to artemisinin (ART), the currently recommended first-line antimalarial drug, emphasizes the need to understand the resistance mechanism and apply this knowledge in developing new drugs that are effective against malaria. An insight into ART's mechanism of action indicates that ferrous iron (Fe2+) or heme, released when hemoglobin is degraded, cleaves the endoperoxide bridge. As a result, free radicals are formed, which alkylate many intracellular targets and result in plasmodial proteopathy. Aside from the existing evidence that mutations in the Kelch 13 protein propeller domain affect ART sensitivity and clearance rate by Plasmodium falciparum (Pf) parasites, recent investigations raise the possibility that additional target loci may be involved, and these include a nonsense (S69stop) and four missense variants (K255R, N257E, T343P, and D345G) in falcipain 2 (FP-2) protein. FP-2 and falcipain 3 (FP-3) are cysteine proteases responsible for hydrolyzing hemoglobin in the host erythrocytic cycle, a key virulence factor for malaria parasite growth and metabolism. Due to the obligatory nature of the hemoglobin degradation process, both proteases have become potential antimalarial drug targets attracting attention in recent years for the development of blood-stage antimalarial drugs. The alteration of the expression profile of FP-2 and FP-3 through gene manipulation approaches (knockout) or compound inhibition assays, respectively, induced parasites with swollen food vacuoles due to the accumulation of undegraded hemoglobin. Furthermore, missense mutations in FP-2 confer parasites with decreased ART sensitivity, probably due to altered enzyme efficiency and momentary decreased hemoglobin degradation. Hence, understanding how these mutations affect FP-2 (including those implicated in ART resistance) and FP-3 is imperative to finding potentially effective inhibitors. The first aim of this thesis is to characterize the effects of missense mutations on the partial zymogen complex and the catalytic domain of FP-2 and FP-3 using a range of computational approaches and tools such as homology modeling, molecular dynamics (MD) simulations, comparative essential dynamics, dynamic residue network (DRN) analysis, weighted residue contact map analysis, amongst others. The Pf genomic resource database (PlasmoDB) identified 41 missense mutations located in the partial zymogen and catalytic domains of FP-2 and FP-3. Using structure-based tools, six putative allosteric pockets were identified in FP-2 and FP-3. The effect of mutations on the whole protein, the central core, binding pocket residues and allosteric pockets was evaluated. The accurate 3D homology models of the WT and mutants were calculated. MD simulations were performed on the various systems as a quick starting point. MD simulations have provided a cornerstone for establishing numerous computational tools for describing changes arising from mutations, ligand binding, and environmental changes such as pH and temperature. Post-MD analysis was performed in two stages viz global and local analysis. Global analysis via radius of gyration (Rg) and comparative essential dynamic analysis revealed the conformational variability associated with all mutations. In the catalytic domain of FP-2, the presence of M245I mutation triggered the formation of a cryptic pocket via an exclusive mechanism involving the fusion of pockets 2 and 6. This striking observation was also detected in the partial zymogen complex of FP-2 and induced by A159V, M245I and E249A mutations. A similar observation was uncovered in the presence of A422T mutation in the catalytic domain of FP-3. Local DRN and contact map analyses identified conserved inter-residue interaction changes on important communication networks. This study brings a novel understanding of the effects of missense mutations in FP-2 and FP-3 and provides important insight which may help discover new anti-hemoglobinase drugs. The second aim is the identification of potential allosteric ligands against the WT and mutant systems of FP-2 and FP-3 using various computational tools. Of the six potential allosteric pockets identified in FP-2 and FP-3, pocket 1 was evaluated by SiteMap as the most druggable in both proteins. This pipeline was implemented to screen pocket 1 of FP-2 and FP-3 against 2089 repositionable compounds obtained from the DrugBank database. In order to ensure selectivity and specificity to the Plasmodium protein, the human homologs (Cat K and Cat L) were screened, and compounds binding to these proteins were exempted from further analysis. Subsequently, eight compounds (DB00128, DB00312, DB00766, DB00951, DB02893, DB03754, DB13972, and DB14159) were identified as potential allosteric hits for FP-2 and five (DB00853, DB00951, DB01613, DB04173 and DB09419) for FP-3. These compounds were subjected to MD simulation and post-MD trajectory analysis to ascertain their stability in their respective protein structures. The effects of the stable compounds on the WT and mutant systems of FP-2 and FP-3 were then evaluated using DRN analysis. Attention has recently been drawn towards identifying novel allosteric compounds targeting FP-2 and FP-3; hence this study explores the potential allosteric inhibitory mechanisms in the presence and absence of mutations in FP-2 and FP-3. Overall, the results presented in this thesis provide (i) an understanding of the role mutations in the partial zymogen complex play in the activation of the active enzyme, (ii) an insight into the possible allosteric mechanisms induced by mutations on the active enzymes, and (iii) a computational pipeline for the development of novel allosteric modulators for malaria inhibition studies. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
Field facilitation in open and distance learning in resource-constrained environments: a case of Mzuzu University, Malawi
- Authors: Kalima, Robert Chagwamtsoka
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431554 , vital:72785 , DOI 10.21504/10962/431554
- Description: As part of the drive to enhance students’ learning experiences and success for students pursuing the B.Ed Science programme through distance education at Mzuzu University (Mzuni), the Open and Distance Learning (ODL) Steering Committee of Mzuni introduced the field facilitation strategy in 2014 to provide additional academic support to such students off campus. There have been questions, though, regarding the effectiveness of this strategy in terms of enhancement of student learning and success. This study, therefore, sought to examine the current field facilitation strategy in the B.Ed Science programme under the ODL mode of delivery, with a view to proposing improvements that would be made to the field facilitation strategy so that it enables enhanced learning and success in Science and Mathematics at Mzuni. Efforts to improve the current field facilitation strategy have been informed by an empirically based understanding of the shortfalls and strengths of the existing field facilitation strategy for ODL students in the B.Ed Science programme. To enhance students’ learning and success for ODL students in resource-constrained contexts such as Mzuni and similar contexts, the study adopted a qualitative case study design guided by tools from the second generation of the Cultural Historical Activity Theory. Qualitative data was obtained in two phases, a contextual profiling phase and a modified Change Laboratory Workshop phase. The modified Change Laboratory Workshops were conducted through the social media application ‘WhatsApp’ rather than in person as is usually done. Qualitative data in the contextual profiling phase was obtained from three categories of participants, namely, Science and Mathematics lecturers, Science and Mathematics field facilitators, and Science and Mathematics students. The contextual profiling phase included surveys, focus group interviews, individual interviews with lecturers at Mzuni and the field facilitators from the five satellite learning centres of Mzuni, and document analysis. The contextual profiling data acted as the mirror data for the next phase of data generation (Change Laboratory Workshop phase). The findings indicated that the support currently rendered by field facilitators to ODL Science and Mathematics students was inadequate and consisted of a shallow mode of instruction focusing on v traditional ways of teaching and learning. This meant that the field facilitators focused on lecturing as a pedagogical strategy for supporting the learning of Science and Mathematics. This was largely because the support offered to field facilitators by Mzuni was inadequate and did not empower them to generate their own strategies of conducting field facilitation innovatively and creatively, which would in turn empower the students to engage actively and reflectively in their own learning activities. This was due to structural, historical and cultural tensions that existed in the larger system (the university system). The implementation of the field facilitation strategy was challenged by such conflicts in the university structure which manifested themselves in the smaller activity system (the field facilitation activity system) which is the focus of this study. Thematically, such conflicts included students’ attributes, institutional policies, institutional pedagogy and the material and digital divide which Mzuni has not harnessed to support field facilitation. The study further established that institutional sensitivity to the conflicts raised above would result in an improved field facilitation strategy as the conflicts at the higher level (university level) have an impact on what happens in the smaller systems, for example the ODL in general and the field facilitation activity system in particular. The improved field facilitation strategy was supposed to recognise ODL students as students in transit from the traditional face-to-face learning context to the novel ODL learning context. As such, the transitional period of study from secondary school to university, particularly to year one, required an intensive field facilitation support strategy, and thus greater institutional support for both field facilitators and students for enhanced learning experiences and success that would eventually result in improved students’ retention and throughput. The findings of this study will therefore inform all those involved in ODL, particularly those in resource-constrained contexts, to be conscious when implementing ODL innovations. Serious consideration of the contexts in which the innovations are to be implemented is critical. , Thesis (PhD) -- Faculty of Education, Primary and Early Childhood Education, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Kalima, Robert Chagwamtsoka
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431554 , vital:72785 , DOI 10.21504/10962/431554
- Description: As part of the drive to enhance students’ learning experiences and success for students pursuing the B.Ed Science programme through distance education at Mzuzu University (Mzuni), the Open and Distance Learning (ODL) Steering Committee of Mzuni introduced the field facilitation strategy in 2014 to provide additional academic support to such students off campus. There have been questions, though, regarding the effectiveness of this strategy in terms of enhancement of student learning and success. This study, therefore, sought to examine the current field facilitation strategy in the B.Ed Science programme under the ODL mode of delivery, with a view to proposing improvements that would be made to the field facilitation strategy so that it enables enhanced learning and success in Science and Mathematics at Mzuni. Efforts to improve the current field facilitation strategy have been informed by an empirically based understanding of the shortfalls and strengths of the existing field facilitation strategy for ODL students in the B.Ed Science programme. To enhance students’ learning and success for ODL students in resource-constrained contexts such as Mzuni and similar contexts, the study adopted a qualitative case study design guided by tools from the second generation of the Cultural Historical Activity Theory. Qualitative data was obtained in two phases, a contextual profiling phase and a modified Change Laboratory Workshop phase. The modified Change Laboratory Workshops were conducted through the social media application ‘WhatsApp’ rather than in person as is usually done. Qualitative data in the contextual profiling phase was obtained from three categories of participants, namely, Science and Mathematics lecturers, Science and Mathematics field facilitators, and Science and Mathematics students. The contextual profiling phase included surveys, focus group interviews, individual interviews with lecturers at Mzuni and the field facilitators from the five satellite learning centres of Mzuni, and document analysis. The contextual profiling data acted as the mirror data for the next phase of data generation (Change Laboratory Workshop phase). The findings indicated that the support currently rendered by field facilitators to ODL Science and Mathematics students was inadequate and consisted of a shallow mode of instruction focusing on v traditional ways of teaching and learning. This meant that the field facilitators focused on lecturing as a pedagogical strategy for supporting the learning of Science and Mathematics. This was largely because the support offered to field facilitators by Mzuni was inadequate and did not empower them to generate their own strategies of conducting field facilitation innovatively and creatively, which would in turn empower the students to engage actively and reflectively in their own learning activities. This was due to structural, historical and cultural tensions that existed in the larger system (the university system). The implementation of the field facilitation strategy was challenged by such conflicts in the university structure which manifested themselves in the smaller activity system (the field facilitation activity system) which is the focus of this study. Thematically, such conflicts included students’ attributes, institutional policies, institutional pedagogy and the material and digital divide which Mzuni has not harnessed to support field facilitation. The study further established that institutional sensitivity to the conflicts raised above would result in an improved field facilitation strategy as the conflicts at the higher level (university level) have an impact on what happens in the smaller systems, for example the ODL in general and the field facilitation activity system in particular. The improved field facilitation strategy was supposed to recognise ODL students as students in transit from the traditional face-to-face learning context to the novel ODL learning context. As such, the transitional period of study from secondary school to university, particularly to year one, required an intensive field facilitation support strategy, and thus greater institutional support for both field facilitators and students for enhanced learning experiences and success that would eventually result in improved students’ retention and throughput. The findings of this study will therefore inform all those involved in ODL, particularly those in resource-constrained contexts, to be conscious when implementing ODL innovations. Serious consideration of the contexts in which the innovations are to be implemented is critical. , Thesis (PhD) -- Faculty of Education, Primary and Early Childhood Education, 2023
- Full Text:
- Date Issued: 2023-10-13