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:
- 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:
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:
- 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:
Analysing equity and ethical dimensions of water governance challenges in the lower section of the upper Vaal River catchment, Gauteng, South Africa
- Authors: Tavengwa, Noleen Shamiso
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424199 , vital:72132
- Description: Poor water governance practices have been identified as one of the root causes of water problems confronting the South African water sector. This is evident in the lower section of the Upper Vaal River Catchment, where ineffective implementation of the regulatory measures has resulted in multiple incidents of illegal discharge of effluent from municipal wastewater treatment works, industrial and mining activities. Pollution and deterioration of water quality is a major challenge in the catchment; the Vaal River is severely polluted beyond acceptable standards and impacts negatively on other water users who have legitimate rights to the water resources. Pollution not only affects human activities and use, but also has negative impacts on ecological health and functionality. Poor water governance practices raise ethical implications for the rights to water for both social and ecological components. Although many water governance challenges in South Africa have implications that border on values and ethics, the relationship between these concepts has hardly been explored. In order to contribute towards filling this gap, this study explores water governance challenges and their ethical implications, and then analyse the equity dimensions of key water challenges among institutional actors in the lower section of the Upper Vaal WMA, Gauteng. The study uses a qualitative research approach which involves several methods of data collection: document analysis, workshops, focus group discussions, key informant interviews and participant observation. The data collected were analysed using thematic analysis, and then applied an ethical framework to distil ethical implications of the identified water governance challenges. There are five water governance challenges that were identified, which are i) failure in the implementation of water legislation and regulations, ii) ineffective leadership and management, iii) cooperative governance and poor accountability, iv) decentralisation and ineffective participation, and v) finance, infrastructure, and technical capacity. The deterioration of water quality and pollution due to ineffective implementation of the regulatory system has ethical implications towards protection of the ecological system and sustainable management of the water resources for the present and future generation. Ineffective implementation of the regulatory measure also raises the issue of distributive equity between different water users and between current and future users. These implications are critical particularly when viewed from the perspective of systemic-relational ethical approach which posit that in social-ecological systems, all components ought to be treated with equal regards, and their inherent worth respected in order to maintain the unity of the SES. The idea of equal regards to the inherent worth of the component implies due respect, in ways that do not undermine the integrity of the entire system. The challenges identified in the system suggest that i) the right of the ecological system to water is undermined due to anthropogenic activities, which may in the long term undermine the functionality of the entire SES; ii) the right of the margined to access to water of the right quality is also undermined, and pollution costs is externalised. These are matters of ethics that thus deserved attention in policy and management considerations. The study analysed equity dimensions (distributive and procedural), targeting the key institutional water users (i.e., mines, industries, agriculture, municipalities, and the wastewater treatment works) in the lower section of the Upper Vaal River Catchment as equity candidates due to their activities that significantly impact the environment and the water resources. The cost of pollution caused by mining activities, industrial activities and the wastewater treatment works is externalised to other users who are not responsible for the pollution. In this regard study identified key drivers that raise concerns linked to distributive equity, which are ) pollution and water quality deterioration, ii) the legacies of mining activities, and iii) poor infrastructure maintenance, vandalism, and theft. Identifying these key drivers of distributive equity concerns is critical in ensuring that the water governance processes are designed in a way that stakeholders and actors reliant on water resources within the catchment have equitable and fair access without the effects of externalised costs from other actors. The identified water governance challenges in the catchment all borders on ethics, thus an ethical framework is crucial in tackling water related problems. The principles of ethics can be used as guidelines to decision-making process for the management and governance of water resources in South Africa. Therefore, implementing and incorporating principles of the systemic-relational ethics into policy making and water resources management will yield sustainable, efficient, and equitable use and management of water resources. , Thesis (MSc) -- Faculty of Science, Institute for Water Research, 2023
- Full Text:
- Authors: Tavengwa, Noleen Shamiso
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424199 , vital:72132
- Description: Poor water governance practices have been identified as one of the root causes of water problems confronting the South African water sector. This is evident in the lower section of the Upper Vaal River Catchment, where ineffective implementation of the regulatory measures has resulted in multiple incidents of illegal discharge of effluent from municipal wastewater treatment works, industrial and mining activities. Pollution and deterioration of water quality is a major challenge in the catchment; the Vaal River is severely polluted beyond acceptable standards and impacts negatively on other water users who have legitimate rights to the water resources. Pollution not only affects human activities and use, but also has negative impacts on ecological health and functionality. Poor water governance practices raise ethical implications for the rights to water for both social and ecological components. Although many water governance challenges in South Africa have implications that border on values and ethics, the relationship between these concepts has hardly been explored. In order to contribute towards filling this gap, this study explores water governance challenges and their ethical implications, and then analyse the equity dimensions of key water challenges among institutional actors in the lower section of the Upper Vaal WMA, Gauteng. The study uses a qualitative research approach which involves several methods of data collection: document analysis, workshops, focus group discussions, key informant interviews and participant observation. The data collected were analysed using thematic analysis, and then applied an ethical framework to distil ethical implications of the identified water governance challenges. There are five water governance challenges that were identified, which are i) failure in the implementation of water legislation and regulations, ii) ineffective leadership and management, iii) cooperative governance and poor accountability, iv) decentralisation and ineffective participation, and v) finance, infrastructure, and technical capacity. The deterioration of water quality and pollution due to ineffective implementation of the regulatory system has ethical implications towards protection of the ecological system and sustainable management of the water resources for the present and future generation. Ineffective implementation of the regulatory measure also raises the issue of distributive equity between different water users and between current and future users. These implications are critical particularly when viewed from the perspective of systemic-relational ethical approach which posit that in social-ecological systems, all components ought to be treated with equal regards, and their inherent worth respected in order to maintain the unity of the SES. The idea of equal regards to the inherent worth of the component implies due respect, in ways that do not undermine the integrity of the entire system. The challenges identified in the system suggest that i) the right of the ecological system to water is undermined due to anthropogenic activities, which may in the long term undermine the functionality of the entire SES; ii) the right of the margined to access to water of the right quality is also undermined, and pollution costs is externalised. These are matters of ethics that thus deserved attention in policy and management considerations. The study analysed equity dimensions (distributive and procedural), targeting the key institutional water users (i.e., mines, industries, agriculture, municipalities, and the wastewater treatment works) in the lower section of the Upper Vaal River Catchment as equity candidates due to their activities that significantly impact the environment and the water resources. The cost of pollution caused by mining activities, industrial activities and the wastewater treatment works is externalised to other users who are not responsible for the pollution. In this regard study identified key drivers that raise concerns linked to distributive equity, which are ) pollution and water quality deterioration, ii) the legacies of mining activities, and iii) poor infrastructure maintenance, vandalism, and theft. Identifying these key drivers of distributive equity concerns is critical in ensuring that the water governance processes are designed in a way that stakeholders and actors reliant on water resources within the catchment have equitable and fair access without the effects of externalised costs from other actors. The identified water governance challenges in the catchment all borders on ethics, thus an ethical framework is crucial in tackling water related problems. The principles of ethics can be used as guidelines to decision-making process for the management and governance of water resources in South Africa. Therefore, implementing and incorporating principles of the systemic-relational ethics into policy making and water resources management will yield sustainable, efficient, and equitable use and management of water resources. , Thesis (MSc) -- Faculty of Science, Institute for Water Research, 2023
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Application of in vitro release testing (IVRT) to assess “sameness”/differences of topical clotrimazole formulations
- Wellington, Hannah Margaret Mary
- Authors: Wellington, Hannah Margaret Mary
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/419599 , vital:71658
- Description: Embargoed. Possible release date early 2025 pending publications. , Thesis (MSC Pharm) -- Faculty of Pharmacy, 2023
- Full Text:
- Authors: Wellington, Hannah Margaret Mary
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/419599 , vital:71658
- Description: Embargoed. Possible release date early 2025 pending publications. , Thesis (MSC Pharm) -- Faculty of Pharmacy, 2023
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Comparison of the metabolic physiology of exploited and unexploited populations of red roman (Chrysoblephus laticeps) along the south coast of South Africa
- Authors: Nabani, Xolani Prince
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424358 , vital:72146
- Description: Anthropogenic-induced climate change and exploitation pose threat to many marine fishes on which a vast majority of people around the world depend. Rapid changes in sea surface temperature have a direct impact on the physiology of ectothermic organisms such as fish, potentially resulting in changes to population distribution, abundance, and demographics. In the face of climate change, the impacts of increasing temperature variability on fish populations may be exacerbated by exploitation. Understanding how the resilience of exploited populations is affected by climate change is critical to predict how fishes will respond in the future. This study aimed to augment our knowledge on the impact of exploitation and thermal variability on fishes by comparing the thermal physiology of an exploited and unexploited population of the resident, reef-dwelling, Chrysoblephus laticeps. Twenty live fish were collected from the exploited, Cape St Francis and 18 fish from the unexploited, Goukamma Marine Protected Area and transported to the laboratory. The metabolic performance, in terms of standard metabolic rate (SMR), maximum metabolic rate (MMR) and aerobic scope (AS) of individual C. laticeps were estimated repeatedly at 10 ℃, 16 °C and 21 °C. Linear mixed effects models were used to examine the relationship between temperature, population, and metabolic rate and a ‘cvequality’ test analysis was used to compare the variance structure of the metabolic rate regression model for each population. Overall, the findings of this study show that Chrysoblephus laticeps from the unexploited population maintains a significantly higher aerobic scope (AS) across all temperature treatments (10, 16 and 21 ℃) when compared with those from the exploited population. In addition, the maximum metabolic rate (MMR) of individuals from the unexploited population was significantly higher than that of individuals from the exploited population, but there was no evidence to suggest that variability was significantly different between the populations. On the other hand, the individuals from an exploited population had a significantly higher standard metabolic rate (SMR) at high temperatures of 21 ℃, while the unexploited population had a low SMR at these high temperatures, but a high SMR at 10 ℃. Despite these differences there was no significant variation in the SMR between the two populations. The findings of this study confirm previous work on different exploited and unexploited populations of C. laticeps and together these findings suggest that hook and line exploitation lead to reduced physiological phenotypic diversity and reduced physiological performance in exploited fish populations. These findings emphasise the importance of incorporating the iii physiological information to develop viable fisheries management tools in the context of climate change. This study also highlights the effectiveness of MPAs in conserving highperformance physiological phenotypes to maintain phenotypic diversity in fish populations. Future research should aim to evaluate the efficacy of existing MPAs in preserving the physiological diversity of important hook and line fisheries species, while fisheries managers should consider augmenting their approaches through the incorporation of well-designed MPA’s to promote physiological diversity. This will be critical to advance the development of sustainable management practices, not only in a South African context but globally, where oceanic and coastal environmental conditions are expected to rapidly change in the future. , Thesis (MSc) -- Faculty of Science, Ichthyology and Fisheries Science, 2023
- Full Text:
- Authors: Nabani, Xolani Prince
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424358 , vital:72146
- Description: Anthropogenic-induced climate change and exploitation pose threat to many marine fishes on which a vast majority of people around the world depend. Rapid changes in sea surface temperature have a direct impact on the physiology of ectothermic organisms such as fish, potentially resulting in changes to population distribution, abundance, and demographics. In the face of climate change, the impacts of increasing temperature variability on fish populations may be exacerbated by exploitation. Understanding how the resilience of exploited populations is affected by climate change is critical to predict how fishes will respond in the future. This study aimed to augment our knowledge on the impact of exploitation and thermal variability on fishes by comparing the thermal physiology of an exploited and unexploited population of the resident, reef-dwelling, Chrysoblephus laticeps. Twenty live fish were collected from the exploited, Cape St Francis and 18 fish from the unexploited, Goukamma Marine Protected Area and transported to the laboratory. The metabolic performance, in terms of standard metabolic rate (SMR), maximum metabolic rate (MMR) and aerobic scope (AS) of individual C. laticeps were estimated repeatedly at 10 ℃, 16 °C and 21 °C. Linear mixed effects models were used to examine the relationship between temperature, population, and metabolic rate and a ‘cvequality’ test analysis was used to compare the variance structure of the metabolic rate regression model for each population. Overall, the findings of this study show that Chrysoblephus laticeps from the unexploited population maintains a significantly higher aerobic scope (AS) across all temperature treatments (10, 16 and 21 ℃) when compared with those from the exploited population. In addition, the maximum metabolic rate (MMR) of individuals from the unexploited population was significantly higher than that of individuals from the exploited population, but there was no evidence to suggest that variability was significantly different between the populations. On the other hand, the individuals from an exploited population had a significantly higher standard metabolic rate (SMR) at high temperatures of 21 ℃, while the unexploited population had a low SMR at these high temperatures, but a high SMR at 10 ℃. Despite these differences there was no significant variation in the SMR between the two populations. The findings of this study confirm previous work on different exploited and unexploited populations of C. laticeps and together these findings suggest that hook and line exploitation lead to reduced physiological phenotypic diversity and reduced physiological performance in exploited fish populations. These findings emphasise the importance of incorporating the iii physiological information to develop viable fisheries management tools in the context of climate change. This study also highlights the effectiveness of MPAs in conserving highperformance physiological phenotypes to maintain phenotypic diversity in fish populations. Future research should aim to evaluate the efficacy of existing MPAs in preserving the physiological diversity of important hook and line fisheries species, while fisheries managers should consider augmenting their approaches through the incorporation of well-designed MPA’s to promote physiological diversity. This will be critical to advance the development of sustainable management practices, not only in a South African context but globally, where oceanic and coastal environmental conditions are expected to rapidly change in the future. , Thesis (MSc) -- Faculty of Science, Ichthyology and Fisheries Science, 2023
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COVID19 and accountability in South Africa: legislation, ethics and disaster risk management
- Authors: Chapman, Emma Deidre
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/419565 , vital:71655
- Description: Embargoed. Possible release in 2026 pending publication. , Thesis (MSC Pharm) -- Faculty of Pharmacy, 2023
- Full Text:
- Authors: Chapman, Emma Deidre
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/419565 , vital:71655
- Description: Embargoed. Possible release in 2026 pending publication. , Thesis (MSC Pharm) -- Faculty of Pharmacy, 2023
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Enhancement of the electrocatalytic activity of phthalocyanines through the reduction in symmetry and conjugation to detonation nanodiamonds
- Authors: Ncwane, Lunathi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424541 , vital:72162
- Description: This thesis reports on the synthesis of novel phthalocynines tetrakis[(benzo[d]thiazol-2ylthio)phthalocyaninato]cobalt(II)chloride (complex 1) and tris(2-(ethylthio)benzo[d]thiazole)2-(phthalocyanine-9-ylthio)propionate cobalt(II) chloride (complex 2). The complexes are combined with DNDs via different techniques such as π-π stacking, covalent linkage and sequential modification on glassy carbon electrode. The synthesized MPcs and conjugates were characterized using UV-visible, mass, Fourier transform infrared, and Raman spectroscopies as well as transmission electron microscopy and dynamic light scattering. Combining MPcs with DNDs sought to improve electrooxidation of hydrazine. The electrochemical studies were conducted using cyclic voltammetry, chronocoloumetry, electrochemical impedance spectroscopy and chronoamperometry. Hydrazine was utilized as an analyte of interest, due to its mutagenic and carcinogenic effects. Glassy carbon electrodes (GCE) were modified using drop and dry method. The conjugation via covalent linkage proved to be the best way of enhancing electrocatalytic properties. Since it performed better in terms of limit of detection (0.33 μM), even though catalytic rate and sensitivity are not the highest. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Authors: Ncwane, Lunathi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424541 , vital:72162
- Description: This thesis reports on the synthesis of novel phthalocynines tetrakis[(benzo[d]thiazol-2ylthio)phthalocyaninato]cobalt(II)chloride (complex 1) and tris(2-(ethylthio)benzo[d]thiazole)2-(phthalocyanine-9-ylthio)propionate cobalt(II) chloride (complex 2). The complexes are combined with DNDs via different techniques such as π-π stacking, covalent linkage and sequential modification on glassy carbon electrode. The synthesized MPcs and conjugates were characterized using UV-visible, mass, Fourier transform infrared, and Raman spectroscopies as well as transmission electron microscopy and dynamic light scattering. Combining MPcs with DNDs sought to improve electrooxidation of hydrazine. The electrochemical studies were conducted using cyclic voltammetry, chronocoloumetry, electrochemical impedance spectroscopy and chronoamperometry. Hydrazine was utilized as an analyte of interest, due to its mutagenic and carcinogenic effects. Glassy carbon electrodes (GCE) were modified using drop and dry method. The conjugation via covalent linkage proved to be the best way of enhancing electrocatalytic properties. Since it performed better in terms of limit of detection (0.33 μM), even though catalytic rate and sensitivity are not the highest. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
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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:
- 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
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Enteric microbial responses to host hyperthermia in southern African insectivorous bats: a test of thermal co-adaptation
- Authors: Hunter, Amy Alison
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424391 , vital:72149
- Description: Embargoed. Expected release date 2025. , Thesis (MSc) -- Faculty of Science, Zoology and Entomology, 2023
- Full Text:
- Authors: Hunter, Amy Alison
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424391 , vital:72149
- Description: Embargoed. Expected release date 2025. , Thesis (MSc) -- Faculty of Science, Zoology and Entomology, 2023
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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:
- 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:
From euphoria to disenchantment: the intangible in Black post-apartheid South African fiction
- Authors: Kenqu, Amanda Yoliswa
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432466 , vital:72873
- Description: Access restricted. Exptected release date 2025. , Thesis (PhD) -- Faculty of Humanities, Literary Studies in English, 2023
- Full Text:
- Authors: Kenqu, Amanda Yoliswa
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432466 , vital:72873
- Description: Access restricted. Exptected release date 2025. , Thesis (PhD) -- Faculty of Humanities, Literary Studies in English, 2023
- Full Text:
Identification of novel Arf1 GTPase inhibitors for cancer target validation
- Authors: Mqwathi, Nomxolisi Vuyokasi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424666 , vital:72173
- Description: The key regulators of both anterograde and retrograde vesicular traffic, adenosine diphosphate-ribosylation factors (Arfs), also coordinate various signalling pathways and regulate cellular processes required for cell survival and function. In addition to its role in mediating secretory trafficking in the Golgi apparatus, the involvement of Arf1 in signalling pathways that contribute to the formation and progression of cancer has become apparent, and the overexpression and deregulation of Arf1 activity has been associated with cancer cell invasion, proliferation and metastasis. As with other small GTPases, Arf1 must cycle back and forth between an inactive (GDP-bound) and active (GTP-bound) conformation to carry out its function. However, the cycle of Arf1 inactivation and activation is controlled by Arf GTPase activating proteins (Arf-GAPs) that stimulate Arf1 to hydrolyse the bound GTP to GDP and Arf guanine nucleotide exchange factors (Arf-GEFs) that facilitate GDP for GTP exchange on Arf1, respectively. The identification of Arf1 inhibitors that indirectly disrupt Arf1 function by blocking its interaction with Arf-GAPs or Arf-GEFs has generated interest in their use as possible anti-cancer agents. The suppression of Arf1 activation (by targeting Arf-GEFs) has been investigated as a potential cancer therapeutic target and resulted in inhibitor compounds that have micromolar-range activity against cancer cells and targets and promising results in mouse models, but experience problems with bioavailability when used in vivo. This motivates the search for novel Arf1 inhibitors for validation purposes to question whether Arf1 is a viable target for cancer therapy. The purpose of the study was to employ a recently developed colourimetric screening assay to identify inhibitors of Arf1 activation (Arf-GEF inhibitors) and deactivation (Arf-GAP inhibitors), with a focus on evaluating the potential of Arf1 deactivation as an entirely novel anti-cancer target. The proteins required for the assay (Arf1, Arf-GEF and -GAP domains and a reporter protein, GST-GGA3) were expressed in E. coli. and purified using affinity chromatography. The assay could detect the activation of Arf1 by the catalytic Sec7 domain of the three Arf-GEFs chosen for this study, but reproducibility was compromised by the occasional spontaneous activation of Arf1 in the absence of the Arf-GEFs. By contrast, the assay could reproducibly detect Arf1 deactivation by an Arf-GAP domain (Arf-GAP1GAP) and was subsequently used to screen a library of α-helix mimetics. Thirteen hit compounds with IC50 values ranging from 0.53 to 20.95 μM were found to inhibit Arf-GAP1GAP-mediated stimulation of GTP hydrolysis by Arf1-GTP in this assay format, however, they did not effectively suppress the proliferation of three tested cell lines (HeLa, MCF-7 and MCF-12A). Interestingly, the results obtained from fluorescence microscopy studies suggested that the compounds disrupt Golgi structure and Arf1 localisation, presumably by keeping Arf1 in its active conformation by blocking Arf-GAP1 function. This suggests that the compounds affect Arf1 function in cells, and may be used to explore the feasibility of targeting Arf1 deactivation for anti-cancer purposes in a wider range of cell lines and experiments. It has been reported that Arf-GAP1 inhibition is associated with the suppression of cell migration, and the potential of the compounds as metastasis inhibitors may also be explored. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Authors: Mqwathi, Nomxolisi Vuyokasi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424666 , vital:72173
- Description: The key regulators of both anterograde and retrograde vesicular traffic, adenosine diphosphate-ribosylation factors (Arfs), also coordinate various signalling pathways and regulate cellular processes required for cell survival and function. In addition to its role in mediating secretory trafficking in the Golgi apparatus, the involvement of Arf1 in signalling pathways that contribute to the formation and progression of cancer has become apparent, and the overexpression and deregulation of Arf1 activity has been associated with cancer cell invasion, proliferation and metastasis. As with other small GTPases, Arf1 must cycle back and forth between an inactive (GDP-bound) and active (GTP-bound) conformation to carry out its function. However, the cycle of Arf1 inactivation and activation is controlled by Arf GTPase activating proteins (Arf-GAPs) that stimulate Arf1 to hydrolyse the bound GTP to GDP and Arf guanine nucleotide exchange factors (Arf-GEFs) that facilitate GDP for GTP exchange on Arf1, respectively. The identification of Arf1 inhibitors that indirectly disrupt Arf1 function by blocking its interaction with Arf-GAPs or Arf-GEFs has generated interest in their use as possible anti-cancer agents. The suppression of Arf1 activation (by targeting Arf-GEFs) has been investigated as a potential cancer therapeutic target and resulted in inhibitor compounds that have micromolar-range activity against cancer cells and targets and promising results in mouse models, but experience problems with bioavailability when used in vivo. This motivates the search for novel Arf1 inhibitors for validation purposes to question whether Arf1 is a viable target for cancer therapy. The purpose of the study was to employ a recently developed colourimetric screening assay to identify inhibitors of Arf1 activation (Arf-GEF inhibitors) and deactivation (Arf-GAP inhibitors), with a focus on evaluating the potential of Arf1 deactivation as an entirely novel anti-cancer target. The proteins required for the assay (Arf1, Arf-GEF and -GAP domains and a reporter protein, GST-GGA3) were expressed in E. coli. and purified using affinity chromatography. The assay could detect the activation of Arf1 by the catalytic Sec7 domain of the three Arf-GEFs chosen for this study, but reproducibility was compromised by the occasional spontaneous activation of Arf1 in the absence of the Arf-GEFs. By contrast, the assay could reproducibly detect Arf1 deactivation by an Arf-GAP domain (Arf-GAP1GAP) and was subsequently used to screen a library of α-helix mimetics. Thirteen hit compounds with IC50 values ranging from 0.53 to 20.95 μM were found to inhibit Arf-GAP1GAP-mediated stimulation of GTP hydrolysis by Arf1-GTP in this assay format, however, they did not effectively suppress the proliferation of three tested cell lines (HeLa, MCF-7 and MCF-12A). Interestingly, the results obtained from fluorescence microscopy studies suggested that the compounds disrupt Golgi structure and Arf1 localisation, presumably by keeping Arf1 in its active conformation by blocking Arf-GAP1 function. This suggests that the compounds affect Arf1 function in cells, and may be used to explore the feasibility of targeting Arf1 deactivation for anti-cancer purposes in a wider range of cell lines and experiments. It has been reported that Arf-GAP1 inhibition is associated with the suppression of cell migration, and the potential of the compounds as metastasis inhibitors may also be explored. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
In-silico investigation of the effects of genetic mutations on the structural dynamics of thiopurine s-methyltransferase and their implications on the metabolism of 6-mercaptopurine
- Authors: Mwaniki, Rehema Mukami
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/432553 , vital:72880
- Description: Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds such as 6-mercaptopurine (6MP), 6-thioguanine (6TG) and azathioprine (AZA) which is first converted to 6MP through reduction by glutathione S- transferases (GST). The compounds, generally referred to as thiopurines, are immunosuppressants used to treat childhood acute lymphoblastic leukemia (ALL), autoimmune disorders and transplant rejection. Thiopurines are prodrugs which require metabolic activation to give thioguanine nucleotides that exert their cytotoxic effects by incorporation into DNA or inhibiting purine synthesis. The methylation reaction by TPMT utilizing S-adenosylmethionine (SAM) as the methyl donor prevents their conversion to these toxic compounds. The catalytic activity of TPMT in metabolising these compounds has been associated with occurrence of genetic variations. The variations that result to missense mutations cause amino-acid changes and in turn alter the polypeptide sequence of the protein. This could alter functionality and structural dynamics of the enzyme. This study sought to understand the underlying mechanism by which 7 specially selected mutations impede metabolic activity of the enzyme on 6-MP using in silico techniques. VAPOR and PredictSNP were used to predict the effects of single nucleotide polymorphisms (SNPs) on the stability and function of the enzyme. Of the 7 mutations, only H227Q was predicted to be functionally benign while the rest (L49S, L69V, A80P, R163H, R163C and R163P) were predicted to be deleterious or associated with disease. All the SNPs were predicted to destabilize the enzyme. Molecular dynamics (MD) simulations were preformed to mimic the behaviour of the apo, holo and drug-bound WT and mutant enzymes in vivo. This was followed by post-MD analysis to identify changes in the local and global motions of the protein in the presence of mutations and changes in intra-protein communication networks through contact map and centrality metrics calculations. RMSD and Rg analyses were performed to assess changes in global motions and compactness of the enzyme in the apo, holo and drug-bound states and in the presence of mutations. These revealed that binding of the ligand had a stabilizing effect on the WT enzyme evident from more steady trends from the analyses across trajectories in the holo and drug-bound enzymes compared to the apoenzyme. The occurrence of mutations had an effect on the global motions and compactness of the enzyme across the trajectories. Most mutations resulted in destabilized systems and less compact structures shown by unsteady RMSD and Rg across trajectories respectively. The drugbound systems appeared to be more stable in most of the systems meaning that the binding of 6MP stabilized the enzyme regardless of the presence of a mutation. RMSF analysis recorded local changes in residue flexibility due to the presence of mutations in all the systems. All the drug-bound mutant systems lost flexibility on the αAhelix which caps the active site. This could have an effect on drug binding and result to defective drug metabolism. The A80P mutation resulted to a more rigid structure from both global and local motions compared to the WT enzyme which could be associated with its nearly loss of function in vivo and in vitro. Dynamic cross correlation calculations were performed to assess how the atoms moved together. Correlated, anti-correlated and areas of no correlations were recorded in all the systems and in similar places when compared to each other. This meant that occurrence of mutations had no effect on how the atoms moved together. Contact map analysis showed that occurrence of mutations caused changes in interactions around the positions where the mutations occurred, which could have an effect on protein structural dynamics. The A80P substitution which occurred on the surface away from the binding site was identified as an allosteric mutation that resulted to changes in the catalytic site. Contact maps for the drug-cofactor complex in the mutant systems in comparison with the WT protein revealed changes that could suggest reorientation of the drug at the catalytic site. This could be an implication to altered drug metabolism. Eigenvector centrality (EC) and betweenness centrality (BC) for the most equilibrated portions of the trajectories were calculated for all the studied systems to identify residues connected to the most important residues and those that were spanned the most in shortest paths connecting other residues. Areas that scored highest in these metrics where mostly found in regions surrounding the catalytic site. Top 5% centrality hubs calculations showed loss of major hubs due to mutations with gaining of new ones. This means that mutations affected communication networks within the protein. The gained hubs were in areas close-by the lost ones which could have been an attempt of the protein to accommodate the mutations. Persistent top 5% BC hubs were identified at positions 90 and 151 while one persistent top 5% EC hub was identified at position 70. This positions play important roles in shaping the catalytic site and are in direct contact with the ligands. It was concluded that in silico techniques and analysis applied in this study revealed possible mechanisms in which genetic variations affected the structural dynamics of TMPT enzyme an affecte 6MP metabolism. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Authors: Mwaniki, Rehema Mukami
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/432553 , vital:72880
- Description: Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds such as 6-mercaptopurine (6MP), 6-thioguanine (6TG) and azathioprine (AZA) which is first converted to 6MP through reduction by glutathione S- transferases (GST). The compounds, generally referred to as thiopurines, are immunosuppressants used to treat childhood acute lymphoblastic leukemia (ALL), autoimmune disorders and transplant rejection. Thiopurines are prodrugs which require metabolic activation to give thioguanine nucleotides that exert their cytotoxic effects by incorporation into DNA or inhibiting purine synthesis. The methylation reaction by TPMT utilizing S-adenosylmethionine (SAM) as the methyl donor prevents their conversion to these toxic compounds. The catalytic activity of TPMT in metabolising these compounds has been associated with occurrence of genetic variations. The variations that result to missense mutations cause amino-acid changes and in turn alter the polypeptide sequence of the protein. This could alter functionality and structural dynamics of the enzyme. This study sought to understand the underlying mechanism by which 7 specially selected mutations impede metabolic activity of the enzyme on 6-MP using in silico techniques. VAPOR and PredictSNP were used to predict the effects of single nucleotide polymorphisms (SNPs) on the stability and function of the enzyme. Of the 7 mutations, only H227Q was predicted to be functionally benign while the rest (L49S, L69V, A80P, R163H, R163C and R163P) were predicted to be deleterious or associated with disease. All the SNPs were predicted to destabilize the enzyme. Molecular dynamics (MD) simulations were preformed to mimic the behaviour of the apo, holo and drug-bound WT and mutant enzymes in vivo. This was followed by post-MD analysis to identify changes in the local and global motions of the protein in the presence of mutations and changes in intra-protein communication networks through contact map and centrality metrics calculations. RMSD and Rg analyses were performed to assess changes in global motions and compactness of the enzyme in the apo, holo and drug-bound states and in the presence of mutations. These revealed that binding of the ligand had a stabilizing effect on the WT enzyme evident from more steady trends from the analyses across trajectories in the holo and drug-bound enzymes compared to the apoenzyme. The occurrence of mutations had an effect on the global motions and compactness of the enzyme across the trajectories. Most mutations resulted in destabilized systems and less compact structures shown by unsteady RMSD and Rg across trajectories respectively. The drugbound systems appeared to be more stable in most of the systems meaning that the binding of 6MP stabilized the enzyme regardless of the presence of a mutation. RMSF analysis recorded local changes in residue flexibility due to the presence of mutations in all the systems. All the drug-bound mutant systems lost flexibility on the αAhelix which caps the active site. This could have an effect on drug binding and result to defective drug metabolism. The A80P mutation resulted to a more rigid structure from both global and local motions compared to the WT enzyme which could be associated with its nearly loss of function in vivo and in vitro. Dynamic cross correlation calculations were performed to assess how the atoms moved together. Correlated, anti-correlated and areas of no correlations were recorded in all the systems and in similar places when compared to each other. This meant that occurrence of mutations had no effect on how the atoms moved together. Contact map analysis showed that occurrence of mutations caused changes in interactions around the positions where the mutations occurred, which could have an effect on protein structural dynamics. The A80P substitution which occurred on the surface away from the binding site was identified as an allosteric mutation that resulted to changes in the catalytic site. Contact maps for the drug-cofactor complex in the mutant systems in comparison with the WT protein revealed changes that could suggest reorientation of the drug at the catalytic site. This could be an implication to altered drug metabolism. Eigenvector centrality (EC) and betweenness centrality (BC) for the most equilibrated portions of the trajectories were calculated for all the studied systems to identify residues connected to the most important residues and those that were spanned the most in shortest paths connecting other residues. Areas that scored highest in these metrics where mostly found in regions surrounding the catalytic site. Top 5% centrality hubs calculations showed loss of major hubs due to mutations with gaining of new ones. This means that mutations affected communication networks within the protein. The gained hubs were in areas close-by the lost ones which could have been an attempt of the protein to accommodate the mutations. Persistent top 5% BC hubs were identified at positions 90 and 151 while one persistent top 5% EC hub was identified at position 70. This positions play important roles in shaping the catalytic site and are in direct contact with the ligands. It was concluded that in silico techniques and analysis applied in this study revealed possible mechanisms in which genetic variations affected the structural dynamics of TMPT enzyme an affecte 6MP metabolism. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
International students’ experiences of othering in tertiary education in South Africa: an exploratory study
- Authors: Lobakeng, Tsholofelo
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424986 , vital:72199
- Description: Despite rising cases of xenophobia in South Africa, international students remain committed to enrolling in its universities. Surprisingly, there is limited research looking into xenophobia in tertiary institutions. Therefore, the present study aimed to contribute to the scarcity of knowledge on the experiences of international students in South Africa. Thus, the study explored experiences of Othering among international students in tertiary education in South Africa and how they make sense of these experiences. Purposive and snowballing sampling techniques were employed to recruit international students (N=5) from Botswana, China, Zambia, and Zimbabwe. Data was collected through semi-structured, face-to-face online interviews. Participants reported experiencing a variety of non-violent forms of Othering, such as feeling excluded due to the intentional use of local languages in both classroom and social settings; being rejected by local students who refused to work with them; and being accused of stealing opportunities from local students. At an institutional level, participants reported systemic Othering rooted in unsupportive policies and practices that led to a negative and oppressive environment. The findings support previous research studies that purport the Othering of international students in higher education in South Africa mainly manifests through non-violent and covert forms. Moreover, participants attributed Othering of immigrants to racism, a perceived lack of exposure to diversity among locals, perceived lack of compassion for immigrants, and the tendency to scapegoat immigrants for the lack of employment opportunities in the country. The findings underscore the intricate nature of Othering and the need for further research to gain a greater understanding of this complex phenomenon. Furthermore, the findings highlight the importance of implementing effective strategies of inclusion and integration of international students at these institutions of higher learning. , Thesis (MA) -- Faculty of Humanities, Psychology, 2023
- Full Text:
- Authors: Lobakeng, Tsholofelo
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424986 , vital:72199
- Description: Despite rising cases of xenophobia in South Africa, international students remain committed to enrolling in its universities. Surprisingly, there is limited research looking into xenophobia in tertiary institutions. Therefore, the present study aimed to contribute to the scarcity of knowledge on the experiences of international students in South Africa. Thus, the study explored experiences of Othering among international students in tertiary education in South Africa and how they make sense of these experiences. Purposive and snowballing sampling techniques were employed to recruit international students (N=5) from Botswana, China, Zambia, and Zimbabwe. Data was collected through semi-structured, face-to-face online interviews. Participants reported experiencing a variety of non-violent forms of Othering, such as feeling excluded due to the intentional use of local languages in both classroom and social settings; being rejected by local students who refused to work with them; and being accused of stealing opportunities from local students. At an institutional level, participants reported systemic Othering rooted in unsupportive policies and practices that led to a negative and oppressive environment. The findings support previous research studies that purport the Othering of international students in higher education in South Africa mainly manifests through non-violent and covert forms. Moreover, participants attributed Othering of immigrants to racism, a perceived lack of exposure to diversity among locals, perceived lack of compassion for immigrants, and the tendency to scapegoat immigrants for the lack of employment opportunities in the country. The findings underscore the intricate nature of Othering and the need for further research to gain a greater understanding of this complex phenomenon. Furthermore, the findings highlight the importance of implementing effective strategies of inclusion and integration of international students at these institutions of higher learning. , Thesis (MA) -- Faculty of Humanities, Psychology, 2023
- Full Text:
Investigation into methods of recovering campylobacter spp. from river water samples
- Authors: Ngoni, Nandipha
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424177 , vital:72130
- Description: Campylobacter species are slender, gram-negative, rod-shaped, spiral- or curved-shaped with single or pairs of flagella. They are the leading cause of diarrheal disease globally, consumption of and contact with water contaminated by faeces is a major risk factor for transmission of these organisms to humans. Rivers used for recreation and domestic and agricultural activities represent all the risk factors for Campylobacter spp. pollution and human exposure. Campylobacter spp. However, effective methods to recover Campylobacter spp. from river water samples are lacking, indicating the need for the development of more efficient methods of detection and isolation of these organisms from environmental water samples. Campylobacter detection in a water sample is critical to ascertain potential risks to humans. The aim of this study was to determine a suitable method for the detection of Campylobacter spp. from river water samples and the objectives were to (i) to evaluate the performance of different methods used for the recovery of Campylobacter spp. from environmental water samples based on Campylobacter colony count and PCR identification results, (ii) isolate and enumerate Campylobacter cells from river water samples, and (iii) identify Campylobacter spp. in river water samples. The Bloukrans River was chosen for this study because it is suspected to be contaminated by faecal inputs from nearby informal settlements without adequate sanitation, as well as untreated/insufficiently treated effluents from nearby wastewater treatment plants. First, the physicochemical quality of the river water and the presence of faecal contamination were assessed to confirm suitability for Campylobacter spp. survival and presence. Then different approaches to sample, concentrate and recover Campylobacter spp. from river water samples were assessed. The different methods assessed were (i) direct enrichment of water samples without prior concentration, (ii) prior concentration of water samples by centrifugation followed by membrane filtration of supernatant, and after that, pooling the residue and pellet together for enrichment, (iii) sampling by the Moore Swab technique. For all three methods, enrichment in Bolton broth supplemented with Bolton antibiotics was conducted. This was followed by plating on modified cefoperazone charcoal deoxycholate agar (mCCDA) and incubation under a microaerophilic atmosphere at 42°C for 48 h. Colony morphology, Gram staining and polymerase chain reaction (PCR) were used to identify and characterize the microorganisms. The growth of blue colonies on the mFc agar surface confirmed presence and faecal pollution of the Bloukrans River. The physicochemical properties, based on the range of pH measured at different sites of the river (between acidic 3.45 to 6.42 and alkaline 7.2 to 8.74) indicate that Campylobacter spp. can thrive in the river. Based on the results from enumeration and sequencing of colonies recovered by each method, it was discovered that the most suitable method to recover Campylobacter spp. from river water samples is by prior centrifugation (14,000 × g for 30 minutes) followed by membrane filtration of the supernatant, and subsequent pooling of the residue and pellet. The pooled residue and pellet might have increased Campylobacter spp. concentrations aiding more growth during the enrichment of Campylobacter spp. from the river water samples. Results from enumerating Campylobacter spp. cells from river water samples indicate that Campylobacter spp. are present in Bloukrans River. The sequence obtained from the PCR product indicates that the species found were Campylobacter jejuni (96% homology as evaluated by BLAST). This study provided a procedure effective for obtaining a satisfactory quantitative recovery of Campylobacter spp. from environmental waters, a critical need for quantitative microbial risk assessment studies. , Thesis (MSc) -- Faculty of Science, Institute for Water Research, 2023
- Full Text:
- Authors: Ngoni, Nandipha
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424177 , vital:72130
- Description: Campylobacter species are slender, gram-negative, rod-shaped, spiral- or curved-shaped with single or pairs of flagella. They are the leading cause of diarrheal disease globally, consumption of and contact with water contaminated by faeces is a major risk factor for transmission of these organisms to humans. Rivers used for recreation and domestic and agricultural activities represent all the risk factors for Campylobacter spp. pollution and human exposure. Campylobacter spp. However, effective methods to recover Campylobacter spp. from river water samples are lacking, indicating the need for the development of more efficient methods of detection and isolation of these organisms from environmental water samples. Campylobacter detection in a water sample is critical to ascertain potential risks to humans. The aim of this study was to determine a suitable method for the detection of Campylobacter spp. from river water samples and the objectives were to (i) to evaluate the performance of different methods used for the recovery of Campylobacter spp. from environmental water samples based on Campylobacter colony count and PCR identification results, (ii) isolate and enumerate Campylobacter cells from river water samples, and (iii) identify Campylobacter spp. in river water samples. The Bloukrans River was chosen for this study because it is suspected to be contaminated by faecal inputs from nearby informal settlements without adequate sanitation, as well as untreated/insufficiently treated effluents from nearby wastewater treatment plants. First, the physicochemical quality of the river water and the presence of faecal contamination were assessed to confirm suitability for Campylobacter spp. survival and presence. Then different approaches to sample, concentrate and recover Campylobacter spp. from river water samples were assessed. The different methods assessed were (i) direct enrichment of water samples without prior concentration, (ii) prior concentration of water samples by centrifugation followed by membrane filtration of supernatant, and after that, pooling the residue and pellet together for enrichment, (iii) sampling by the Moore Swab technique. For all three methods, enrichment in Bolton broth supplemented with Bolton antibiotics was conducted. This was followed by plating on modified cefoperazone charcoal deoxycholate agar (mCCDA) and incubation under a microaerophilic atmosphere at 42°C for 48 h. Colony morphology, Gram staining and polymerase chain reaction (PCR) were used to identify and characterize the microorganisms. The growth of blue colonies on the mFc agar surface confirmed presence and faecal pollution of the Bloukrans River. The physicochemical properties, based on the range of pH measured at different sites of the river (between acidic 3.45 to 6.42 and alkaline 7.2 to 8.74) indicate that Campylobacter spp. can thrive in the river. Based on the results from enumeration and sequencing of colonies recovered by each method, it was discovered that the most suitable method to recover Campylobacter spp. from river water samples is by prior centrifugation (14,000 × g for 30 minutes) followed by membrane filtration of the supernatant, and subsequent pooling of the residue and pellet. The pooled residue and pellet might have increased Campylobacter spp. concentrations aiding more growth during the enrichment of Campylobacter spp. from the river water samples. Results from enumerating Campylobacter spp. cells from river water samples indicate that Campylobacter spp. are present in Bloukrans River. The sequence obtained from the PCR product indicates that the species found were Campylobacter jejuni (96% homology as evaluated by BLAST). This study provided a procedure effective for obtaining a satisfactory quantitative recovery of Campylobacter spp. from environmental waters, a critical need for quantitative microbial risk assessment studies. , Thesis (MSc) -- Faculty of Science, Institute for Water Research, 2023
- Full Text:
InVisible freedom fighter: a critical analysis of portrayals of women in archival photographs, independence monuments and contemporary art in Zambia (Northern Rhodesia) and Zimbabwe (Southern Rhodesia)
- Authors: Kalichini, Gladys Melina
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432433 , vital:72870 , DOI 10.21504/10962/432433
- Description: This doctoral dissertation in art history develops a notion of invisibility by critically analysing processes in which narratives about women are either concealed or uncovered in visual portrayals relating to the independence of Zambia (former Northern Rhodesia) and Zimbabwe (previously Southern Rhodesia). This study concentrates on three main visual categories that include archival photographs, national monuments, and visual art. It critically engages with concepts of memory and history through a framework of gender. The concept of invisibility developed in this thesis articulates a dynamic process in which independence narratives evolve over time, sometimes revealing memories associated with women and at other times rendering women invisible. National liberation in many African states is dominantly accredited to the political parties that were in power at the time of independence. In Zambia, the United National Independence Party (UNIP) is acknowledged for spearheading efforts to overthrow the colonial administration, while in Zimbabwe it is the Zimbabwe African National Union – Patriotic Front (ZANU – PF). Both political parties were headed by men, and the majority of their memberships was also comprised of men; as such, the dominant narratives largely illuminate the stories of men associated with these political parties. The overarching argument of this doctoral dissertation is that there is a gender bias inherent in dominant independence struggles narratives that are communicated through cultural heritage sites such as monuments and archives. In this study, art and art making inform theory as the methodological approach takes the direction in which selected artworks and visual materials are employed as a starting point of considering concepts that relate to the visibilities of stories about women. This approach cogitates the function of art, visual culture, and art history in the production of knowledges that foster in-depth understandings of concepts that explain social phenomena such as historical erasure. This doctoral dissertation in art history is divided into two parts, A and B, that conceptually complement each other. In section A which comprises of chapters one and two, the study develops an alternative visual archive that surveys the involvements of six specific women in the attainment of national independence in their respective countries, and critically analyses the Freedom Statue in Zambia and the National Heroes Acre in Zimbabwe as monuments dedicated to commemorating the independence struggle in the two countries. In Chapters three to five which form the second section of this dissertation, the emphasis of the discussion is on how selected visual artworks of three selected artists disrupt, counter or engage with dominant historical accounts that either exclude or marginalise narratives about women. The three artists include myself, Gladys Kalichini, and Zimbabwean born artists Kudzanai Chiurai and Gresham Tapiwa Nyaude. This thesis offers a culturally rich conversation about visual representations of social, political and cultural roles women performed in the colonial times in Northern and Southern Rhodesia and gives insight into the evolution of the luminosity of contemporary performances of women’s social collectives in Zambia and Zimbabwe. , Thesis (PhD) -- Faculty of Humanities, Fine Art, 2023
- Full Text:
- Authors: Kalichini, Gladys Melina
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432433 , vital:72870 , DOI 10.21504/10962/432433
- Description: This doctoral dissertation in art history develops a notion of invisibility by critically analysing processes in which narratives about women are either concealed or uncovered in visual portrayals relating to the independence of Zambia (former Northern Rhodesia) and Zimbabwe (previously Southern Rhodesia). This study concentrates on three main visual categories that include archival photographs, national monuments, and visual art. It critically engages with concepts of memory and history through a framework of gender. The concept of invisibility developed in this thesis articulates a dynamic process in which independence narratives evolve over time, sometimes revealing memories associated with women and at other times rendering women invisible. National liberation in many African states is dominantly accredited to the political parties that were in power at the time of independence. In Zambia, the United National Independence Party (UNIP) is acknowledged for spearheading efforts to overthrow the colonial administration, while in Zimbabwe it is the Zimbabwe African National Union – Patriotic Front (ZANU – PF). Both political parties were headed by men, and the majority of their memberships was also comprised of men; as such, the dominant narratives largely illuminate the stories of men associated with these political parties. The overarching argument of this doctoral dissertation is that there is a gender bias inherent in dominant independence struggles narratives that are communicated through cultural heritage sites such as monuments and archives. In this study, art and art making inform theory as the methodological approach takes the direction in which selected artworks and visual materials are employed as a starting point of considering concepts that relate to the visibilities of stories about women. This approach cogitates the function of art, visual culture, and art history in the production of knowledges that foster in-depth understandings of concepts that explain social phenomena such as historical erasure. This doctoral dissertation in art history is divided into two parts, A and B, that conceptually complement each other. In section A which comprises of chapters one and two, the study develops an alternative visual archive that surveys the involvements of six specific women in the attainment of national independence in their respective countries, and critically analyses the Freedom Statue in Zambia and the National Heroes Acre in Zimbabwe as monuments dedicated to commemorating the independence struggle in the two countries. In Chapters three to five which form the second section of this dissertation, the emphasis of the discussion is on how selected visual artworks of three selected artists disrupt, counter or engage with dominant historical accounts that either exclude or marginalise narratives about women. The three artists include myself, Gladys Kalichini, and Zimbabwean born artists Kudzanai Chiurai and Gresham Tapiwa Nyaude. This thesis offers a culturally rich conversation about visual representations of social, political and cultural roles women performed in the colonial times in Northern and Southern Rhodesia and gives insight into the evolution of the luminosity of contemporary performances of women’s social collectives in Zambia and Zimbabwe. , Thesis (PhD) -- Faculty of Humanities, Fine Art, 2023
- Full Text:
Phylogeography of two small owl species in South Africa: population genetics and phenotypic variation in the African Barred Owlet (Glaucidium capense) and the African Scops Owl (Otus senegalensis)
- Authors: Balmer, Jonathan Peter
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424369 , vital:72147
- Description: Embargoed. Expected release date in 2025. , Thesis (MSc) -- Faculty of Science, Zoology and Entomology, 2023
- Full Text:
- Authors: Balmer, Jonathan Peter
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424369 , vital:72147
- Description: Embargoed. Expected release date in 2025. , Thesis (MSc) -- Faculty of Science, Zoology and Entomology, 2023
- Full Text:
Playing it back: audible traces in contemporary African art
- Authors: Panchia, Bhavisha Laximi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432455 , vital:72872
- Description: Access restricted. Exptected release date 2025. , Thesis (PhD) -- Faculty of Humanities, Fine Art, 2023
- Full Text:
- Authors: Panchia, Bhavisha Laximi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432455 , vital:72872
- Description: Access restricted. Exptected release date 2025. , Thesis (PhD) -- Faculty of Humanities, Fine Art, 2023
- Full Text:
Porphyrinoid dyes for photodynamic anticancer and antimicrobial therapy treatments
- Authors: Soy, Rodah Cheruto
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432252 , vital:72855 , DOI 10.21504/10962/432252
- Description: The search for alternative therapies and non-toxic photosensitizer drugs that can efficiently generate cytotoxic reactive oxygen species for biomedical applications, such as in alternative photodynamic therapy (PDT) for cancer treatment and photodynamic antimicrobial chemotherapy (PACT) for drug-resistant bacteria treatment is on the rise. Nevertheless, the lack of photosensitizer dyes that absorb light strongly within the therapeutic window (620−850 nm) that can locally target the tumor and bacterial cells and generate singlet oxygen efficiently are some of the main challenges in PDT and PACT treatment. This study sought to address the challenges that impede PDT and PACT from realizing their full potential by synthesizing a series of meso-aryltetrapyrrolic photosensitizer dyes that absorb light within the therapeutic window. These include meso-tetraarylporphyrin (Por), A3-type meso-triarylcorrole (Cor), meso-tetraarylchlorin (Chl), and N-confused meso-tetraarylporphyrin (NCP) dyes with 4-thiomethylphenyl (1), thien-3-yl (2), thien-2-yl (3), 5-bromo-thien-2-yl (4), 4-methoxyphenyl (5), 3-methoxyphenyl (6), 4-hydroxyphenyl (7) and 4-hydroxy-3-methoxyphenyl (8) meso-aryl rings. Por, Cor, Chl and NCP dyes and and their Ga(III), P(V), In(III) and/or Sn(IV) complexes with 1-8, 1-4, 5-8 and 5 meso-aryl rings were studied, along with two A2B-type Ga(III) meso-triarylcorroles with pentafluorophenyl rings at the A2 positions and 3,6-di-t-butyl-9H-carbazole (9) or N-butyl-4-carbazole (10) rings at the B position that were prepared in the laboratory of Prof. Xu Liang of Jiangsu University in the People’s Republic of China. The carbazole nitrogen of 10-GaCor was quaternized at Rhodes University with ethyl iodide to form a cationic species (10-GaCor-Q) for PDT and PACT activity studies. The structures of the synthesized dyes were confirmed using UV-visible absorption and 1H NMR spectroscopy, and MALDI-TOF-mass spectrometry. 1-4-InPor In(III) porphyrins, 1-4-PVCor, 1-4-GaCor A3 PV and GaIII corrole dyes were also conjugated to gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) via sulfur-gold and sulfur-silver affinities. The successful conjugation of the dyes onto the nanoparticles to form dye-AuNP or dye-AgNP nanoassemblies was confirmed using transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectroscopy, X-ray powered diffraction (XRD), and (X-ray photon spectroscopy) XPS. The photophysicochemical, photostability, and lipophilicity properties of the dyes and their PDT and PACT activities were investigated, and the structure-property relationships were analyzed. This was accomplished by analyzing the changes in the properties of the dyes due to the meso-aryl substituents, central ions, molecular symmetry, and heavy atom effects. Time-dependent-density functional theory (TD-DFT) calculations were also used to further probe the electronic and optical spectroscopic properties of the dyes. The analysis of the photophysicochemical, photostability, and lipophilicity data for the synthesized dyes demonstrated that there are inherent structure-property relationships for the dyes studied. The TD-DFT calculations also assisted in rationalizing the observed optical spectroscopic data for the dyes. The introduction of different meso-aryl substituents resulted in minor absorption spectral changes on the parent structures of the dyes due to their inductive and mesomeric effects, while the insertion of Ga(III), In(III), and Sn(IV) electropositive metal centers resulted in marked red shifts of the B bands due to favorable interactions with the porphyrin or porphyrinoid ligand core. The lower symmetries of the corrole, chlorin, and N-confused porphyrin dyes resulted in enhanced absorption properties within the therapeutic window relative to porphyrins. The heavy atom effect from the Ga(III), In(III), and Sn(IV) central ions, the meso-aryl groups, and the external heavy atom effect from the AuNPs and AgNPs significantly reduced the fluorescence quantum yield values of the dyes resulting in high singlet oxygen quantum yields. The dye complexes also exhibited properly balanced lipophilic properties and high photostabilities. The P(V) ion of the A3 PV corrole dyes reduced the aggregation effects, enhanced cellular uptake, and lowered the lipophilicity values relative to the A3 GaIII corrole dyes. The porphyrin and porphyrinoid complexes studied exhibited relatively low in vitro dark cytotoxicity toward MCF-7 cancer cells, which is enhanced for AuNP nanoconjugates of 1-InPor, 1-3-PVCor, and 1-3-GaCor. The dyes also have low in vitro dark cytotoxicity toward planktonic and biofilm cells of S. aureus and E. coli. The complexes also exhibited favorable PDT and PACT activities toward MCF-7 cancer cells, and planktonic and biofilm S. aureus and E. coli bacteria due to their high singlet oxygen quantum yields. AuNP and AgNP nanoconjugates of 1-4-InPor, 1-4-PVCor, and 1-4-GaCor exhibited enhanced PDT and PACT activities due to the favorable synergistic effects of nanoparticles. The PDT and PACT activities of A3 PV corrole dyes and the nanoconjugates of 1-4-PVCor are slightly higher than those of A3-type GaIII corroles and their nanoconjugates due to decreased aggregation effects and enhanced PS drug uptake. The cationic 10-GaCor-Q species also exhibit favorable PDT and PACT activities in contrast to the neutral 9-10-GaCor dyes due to enhanced PS drug penetration into the tumor or bacteria cells. The complexes also exhibited high Log10 reduction values for planktonic S. aureus suggesting that the dyes are highly efficient PS dyes. The activities of the complexes toward planktonic E. coli bacteria are moderate except for 10-GaCor-Q, 2-4-PVCor-AgNPs, and 5-8-SnChl chlorins exhibiting relatively favorable activity with > 3 Log10 CFU.mL−1 values. The dyes also exhibit moderate activities toward the S. aureus and E. coli biofilm cells, which are lower than for the planktonic cells, as shown by their lower Log10 reduction values. The data demonstrate that the low symmetry corrole, chlorin, and N-confused porphyrin complexes that absorb light strongly within the therapeutic window have significantly enhanced PDT and PACT activities relative to their porphyrin analogs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Authors: Soy, Rodah Cheruto
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432252 , vital:72855 , DOI 10.21504/10962/432252
- Description: The search for alternative therapies and non-toxic photosensitizer drugs that can efficiently generate cytotoxic reactive oxygen species for biomedical applications, such as in alternative photodynamic therapy (PDT) for cancer treatment and photodynamic antimicrobial chemotherapy (PACT) for drug-resistant bacteria treatment is on the rise. Nevertheless, the lack of photosensitizer dyes that absorb light strongly within the therapeutic window (620−850 nm) that can locally target the tumor and bacterial cells and generate singlet oxygen efficiently are some of the main challenges in PDT and PACT treatment. This study sought to address the challenges that impede PDT and PACT from realizing their full potential by synthesizing a series of meso-aryltetrapyrrolic photosensitizer dyes that absorb light within the therapeutic window. These include meso-tetraarylporphyrin (Por), A3-type meso-triarylcorrole (Cor), meso-tetraarylchlorin (Chl), and N-confused meso-tetraarylporphyrin (NCP) dyes with 4-thiomethylphenyl (1), thien-3-yl (2), thien-2-yl (3), 5-bromo-thien-2-yl (4), 4-methoxyphenyl (5), 3-methoxyphenyl (6), 4-hydroxyphenyl (7) and 4-hydroxy-3-methoxyphenyl (8) meso-aryl rings. Por, Cor, Chl and NCP dyes and and their Ga(III), P(V), In(III) and/or Sn(IV) complexes with 1-8, 1-4, 5-8 and 5 meso-aryl rings were studied, along with two A2B-type Ga(III) meso-triarylcorroles with pentafluorophenyl rings at the A2 positions and 3,6-di-t-butyl-9H-carbazole (9) or N-butyl-4-carbazole (10) rings at the B position that were prepared in the laboratory of Prof. Xu Liang of Jiangsu University in the People’s Republic of China. The carbazole nitrogen of 10-GaCor was quaternized at Rhodes University with ethyl iodide to form a cationic species (10-GaCor-Q) for PDT and PACT activity studies. The structures of the synthesized dyes were confirmed using UV-visible absorption and 1H NMR spectroscopy, and MALDI-TOF-mass spectrometry. 1-4-InPor In(III) porphyrins, 1-4-PVCor, 1-4-GaCor A3 PV and GaIII corrole dyes were also conjugated to gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) via sulfur-gold and sulfur-silver affinities. The successful conjugation of the dyes onto the nanoparticles to form dye-AuNP or dye-AgNP nanoassemblies was confirmed using transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectroscopy, X-ray powered diffraction (XRD), and (X-ray photon spectroscopy) XPS. The photophysicochemical, photostability, and lipophilicity properties of the dyes and their PDT and PACT activities were investigated, and the structure-property relationships were analyzed. This was accomplished by analyzing the changes in the properties of the dyes due to the meso-aryl substituents, central ions, molecular symmetry, and heavy atom effects. Time-dependent-density functional theory (TD-DFT) calculations were also used to further probe the electronic and optical spectroscopic properties of the dyes. The analysis of the photophysicochemical, photostability, and lipophilicity data for the synthesized dyes demonstrated that there are inherent structure-property relationships for the dyes studied. The TD-DFT calculations also assisted in rationalizing the observed optical spectroscopic data for the dyes. The introduction of different meso-aryl substituents resulted in minor absorption spectral changes on the parent structures of the dyes due to their inductive and mesomeric effects, while the insertion of Ga(III), In(III), and Sn(IV) electropositive metal centers resulted in marked red shifts of the B bands due to favorable interactions with the porphyrin or porphyrinoid ligand core. The lower symmetries of the corrole, chlorin, and N-confused porphyrin dyes resulted in enhanced absorption properties within the therapeutic window relative to porphyrins. The heavy atom effect from the Ga(III), In(III), and Sn(IV) central ions, the meso-aryl groups, and the external heavy atom effect from the AuNPs and AgNPs significantly reduced the fluorescence quantum yield values of the dyes resulting in high singlet oxygen quantum yields. The dye complexes also exhibited properly balanced lipophilic properties and high photostabilities. The P(V) ion of the A3 PV corrole dyes reduced the aggregation effects, enhanced cellular uptake, and lowered the lipophilicity values relative to the A3 GaIII corrole dyes. The porphyrin and porphyrinoid complexes studied exhibited relatively low in vitro dark cytotoxicity toward MCF-7 cancer cells, which is enhanced for AuNP nanoconjugates of 1-InPor, 1-3-PVCor, and 1-3-GaCor. The dyes also have low in vitro dark cytotoxicity toward planktonic and biofilm cells of S. aureus and E. coli. The complexes also exhibited favorable PDT and PACT activities toward MCF-7 cancer cells, and planktonic and biofilm S. aureus and E. coli bacteria due to their high singlet oxygen quantum yields. AuNP and AgNP nanoconjugates of 1-4-InPor, 1-4-PVCor, and 1-4-GaCor exhibited enhanced PDT and PACT activities due to the favorable synergistic effects of nanoparticles. The PDT and PACT activities of A3 PV corrole dyes and the nanoconjugates of 1-4-PVCor are slightly higher than those of A3-type GaIII corroles and their nanoconjugates due to decreased aggregation effects and enhanced PS drug uptake. The cationic 10-GaCor-Q species also exhibit favorable PDT and PACT activities in contrast to the neutral 9-10-GaCor dyes due to enhanced PS drug penetration into the tumor or bacteria cells. The complexes also exhibited high Log10 reduction values for planktonic S. aureus suggesting that the dyes are highly efficient PS dyes. The activities of the complexes toward planktonic E. coli bacteria are moderate except for 10-GaCor-Q, 2-4-PVCor-AgNPs, and 5-8-SnChl chlorins exhibiting relatively favorable activity with > 3 Log10 CFU.mL−1 values. The dyes also exhibit moderate activities toward the S. aureus and E. coli biofilm cells, which are lower than for the planktonic cells, as shown by their lower Log10 reduction values. The data demonstrate that the low symmetry corrole, chlorin, and N-confused porphyrin complexes that absorb light strongly within the therapeutic window have significantly enhanced PDT and PACT activities relative to their porphyrin analogs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
Relating vegetation distribution to cycles of erosion and deposition in the Kromme River wetlands
- Authors: Jarvis, Samuel Cameron
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424582 , vital:72166
- Description: The role of geomorphic disturbance has been increasingly recognized as fundamental in the creation and functioning of wetlands. This is true of the Kromme River wetland which has been formed through repeated cycles of erosion and deposition. However, the response – and influence – of wetland plants to these sorts of disturbance has not been investigated. This study sought to fill this knowledge gap by classifying vegetation communities over a range of hydrological and geomorphic disturbance regimes that have happened over the last few decades, and relating those vegetation communities to environmental factors. The study identified seven vegetation communities based on their species composition and abundance, which were related to geomorphic disturbance events. A conceptual model that accounts for vegetation distribution in the Kromme wetland was developed. Soil saturation was the most important factor explaining vegetation community distribution, which, in turn, is influenced by cycles of erosion and deposition. Following an erosional event on the valley floor, Prionium serratum dominated wetland is converted to a number of other vegetation communities. On the floodplain surface adjacent to the eroded gully, the Prionium serratum dominated wetland is transformed over time to Cynodon dactylon and Sporobolus fimbriatus communities. Prionium serratum clumps immediately adjacent to the recently incised gullies are able to persist, having sufficient access to water. Within the newly formed gullies, Juncus lomatophyllus colonizes the gully beds flooded to a shallow depth, Miscanthus capensis colonizes the gully bars and Setaria incrassata colonizes the exposed gully banks. Localised depositional features close to the thalweg in the gully are colonized by Prionium serratum seedlings and vegetative propagules. These plants represent the regenerating phase of Prionium serratum wetland, which also colonizes depositional floodouts downstream of the newly-formed gully. The Stenotaphrum secundatum community dominates drier, more elevated areas of the floodout. Over time, as the gully fills, Prionium serratum expands beyond the gully onto the valley floor, to replace the floodplain communities Cynodon dactylon and Sporobolus fimbriatus. Over time, Prionium serratum is thought to colonize the valley floor as the gully fills, stabilising it and promoting diffuse flow. Many restoration efforts in damaged palmiet wetlands have been focused on the preservation of intact palmiet communities upstream of erosional headcuts, with limited understanding of vegetation dynamics associated with the cut-and-fill cycles that naturally occur in these wetlands. Understanding the regeneration of Prionium serratum following erosional events is thus important for wetland restoration, as it should focus more attention on promoting palmiet restoration on depositional floodouts downstream of eroded gullies. A secondary aim of this study was to explore the possibility of mapping palmiet communities in Kromme River wetland using remote sensing techniques. Using a combination of ground-truthed data from this and previous studies in the Kromme River wetland, together with raster layers derived from a LiDAR survey, an overlay analysis was developed to effectively map the distribution of the Prionium serratum dominated community. The overlay was created using a machine learning library in RStudios known as Rpart. The results found that the model were 91% effective in classifying the distribution of the Prionium serratum community. A secondary finding was that the inclusion of a Relative Elevation Model in the overlay analysis allowed for the identification of Prionium serratum communities vulnerable to degradation following previous geomorphic disturbance events and those Prionium serratum communities that are likely to persist following a geomorphic disturbance event. , Thesis (MSc) -- Faculty of Science, Geography, 2023
- Full Text:
- Authors: Jarvis, Samuel Cameron
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424582 , vital:72166
- Description: The role of geomorphic disturbance has been increasingly recognized as fundamental in the creation and functioning of wetlands. This is true of the Kromme River wetland which has been formed through repeated cycles of erosion and deposition. However, the response – and influence – of wetland plants to these sorts of disturbance has not been investigated. This study sought to fill this knowledge gap by classifying vegetation communities over a range of hydrological and geomorphic disturbance regimes that have happened over the last few decades, and relating those vegetation communities to environmental factors. The study identified seven vegetation communities based on their species composition and abundance, which were related to geomorphic disturbance events. A conceptual model that accounts for vegetation distribution in the Kromme wetland was developed. Soil saturation was the most important factor explaining vegetation community distribution, which, in turn, is influenced by cycles of erosion and deposition. Following an erosional event on the valley floor, Prionium serratum dominated wetland is converted to a number of other vegetation communities. On the floodplain surface adjacent to the eroded gully, the Prionium serratum dominated wetland is transformed over time to Cynodon dactylon and Sporobolus fimbriatus communities. Prionium serratum clumps immediately adjacent to the recently incised gullies are able to persist, having sufficient access to water. Within the newly formed gullies, Juncus lomatophyllus colonizes the gully beds flooded to a shallow depth, Miscanthus capensis colonizes the gully bars and Setaria incrassata colonizes the exposed gully banks. Localised depositional features close to the thalweg in the gully are colonized by Prionium serratum seedlings and vegetative propagules. These plants represent the regenerating phase of Prionium serratum wetland, which also colonizes depositional floodouts downstream of the newly-formed gully. The Stenotaphrum secundatum community dominates drier, more elevated areas of the floodout. Over time, as the gully fills, Prionium serratum expands beyond the gully onto the valley floor, to replace the floodplain communities Cynodon dactylon and Sporobolus fimbriatus. Over time, Prionium serratum is thought to colonize the valley floor as the gully fills, stabilising it and promoting diffuse flow. Many restoration efforts in damaged palmiet wetlands have been focused on the preservation of intact palmiet communities upstream of erosional headcuts, with limited understanding of vegetation dynamics associated with the cut-and-fill cycles that naturally occur in these wetlands. Understanding the regeneration of Prionium serratum following erosional events is thus important for wetland restoration, as it should focus more attention on promoting palmiet restoration on depositional floodouts downstream of eroded gullies. A secondary aim of this study was to explore the possibility of mapping palmiet communities in Kromme River wetland using remote sensing techniques. Using a combination of ground-truthed data from this and previous studies in the Kromme River wetland, together with raster layers derived from a LiDAR survey, an overlay analysis was developed to effectively map the distribution of the Prionium serratum dominated community. The overlay was created using a machine learning library in RStudios known as Rpart. The results found that the model were 91% effective in classifying the distribution of the Prionium serratum community. A secondary finding was that the inclusion of a Relative Elevation Model in the overlay analysis allowed for the identification of Prionium serratum communities vulnerable to degradation following previous geomorphic disturbance events and those Prionium serratum communities that are likely to persist following a geomorphic disturbance event. , Thesis (MSc) -- Faculty of Science, Geography, 2023
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