Falcipain 2 and 3 as malarial drug targets: deciphering the effects of missense mutations and identification of allosteric modulators via computational approaches
- Authors: Okeke, Chiamaka Jessica
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432170 , vital:72848 , DOI 10.21504/10962/432170
- Description: Malaria, caused by an obligate unicellular protozoan parasite of the genus Plasmodium, is a disease of global health importance that remains a major cause of morbidity and mortality in developing countries. The World Health Organization (WHO) reported nearly 247 million malaria cases in 2021, causing 619,000 deaths, the vast majority ascribed to pregnant women and young children in sub-Saharan Africa. A critical component of malaria mitigation and elimination efforts worldwide is antimalarial drugs. However, resistance to available antimalarial drugs jeopardizes the treatment, prevention, and eradication of the disease. The recent emergence and spread of resistance to artemisinin (ART), the currently recommended first-line antimalarial drug, emphasizes the need to understand the resistance mechanism and apply this knowledge in developing new drugs that are effective against malaria. An insight into ART's mechanism of action indicates that ferrous iron (Fe2+) or heme, released when hemoglobin is degraded, cleaves the endoperoxide bridge. As a result, free radicals are formed, which alkylate many intracellular targets and result in plasmodial proteopathy. Aside from the existing evidence that mutations in the Kelch 13 protein propeller domain affect ART sensitivity and clearance rate by Plasmodium falciparum (Pf) parasites, recent investigations raise the possibility that additional target loci may be involved, and these include a nonsense (S69stop) and four missense variants (K255R, N257E, T343P, and D345G) in falcipain 2 (FP-2) protein. FP-2 and falcipain 3 (FP-3) are cysteine proteases responsible for hydrolyzing hemoglobin in the host erythrocytic cycle, a key virulence factor for malaria parasite growth and metabolism. Due to the obligatory nature of the hemoglobin degradation process, both proteases have become potential antimalarial drug targets attracting attention in recent years for the development of blood-stage antimalarial drugs. The alteration of the expression profile of FP-2 and FP-3 through gene manipulation approaches (knockout) or compound inhibition assays, respectively, induced parasites with swollen food vacuoles due to the accumulation of undegraded hemoglobin. Furthermore, missense mutations in FP-2 confer parasites with decreased ART sensitivity, probably due to altered enzyme efficiency and momentary decreased hemoglobin degradation. Hence, understanding how these mutations affect FP-2 (including those implicated in ART resistance) and FP-3 is imperative to finding potentially effective inhibitors. The first aim of this thesis is to characterize the effects of missense mutations on the partial zymogen complex and the catalytic domain of FP-2 and FP-3 using a range of computational approaches and tools such as homology modeling, molecular dynamics (MD) simulations, comparative essential dynamics, dynamic residue network (DRN) analysis, weighted residue contact map analysis, amongst others. The Pf genomic resource database (PlasmoDB) identified 41 missense mutations located in the partial zymogen and catalytic domains of FP-2 and FP-3. Using structure-based tools, six putative allosteric pockets were identified in FP-2 and FP-3. The effect of mutations on the whole protein, the central core, binding pocket residues and allosteric pockets was evaluated. The accurate 3D homology models of the WT and mutants were calculated. MD simulations were performed on the various systems as a quick starting point. MD simulations have provided a cornerstone for establishing numerous computational tools for describing changes arising from mutations, ligand binding, and environmental changes such as pH and temperature. Post-MD analysis was performed in two stages viz global and local analysis. Global analysis via radius of gyration (Rg) and comparative essential dynamic analysis revealed the conformational variability associated with all mutations. In the catalytic domain of FP-2, the presence of M245I mutation triggered the formation of a cryptic pocket via an exclusive mechanism involving the fusion of pockets 2 and 6. This striking observation was also detected in the partial zymogen complex of FP-2 and induced by A159V, M245I and E249A mutations. A similar observation was uncovered in the presence of A422T mutation in the catalytic domain of FP-3. Local DRN and contact map analyses identified conserved inter-residue interaction changes on important communication networks. This study brings a novel understanding of the effects of missense mutations in FP-2 and FP-3 and provides important insight which may help discover new anti-hemoglobinase drugs. The second aim is the identification of potential allosteric ligands against the WT and mutant systems of FP-2 and FP-3 using various computational tools. Of the six potential allosteric pockets identified in FP-2 and FP-3, pocket 1 was evaluated by SiteMap as the most druggable in both proteins. This pipeline was implemented to screen pocket 1 of FP-2 and FP-3 against 2089 repositionable compounds obtained from the DrugBank database. In order to ensure selectivity and specificity to the Plasmodium protein, the human homologs (Cat K and Cat L) were screened, and compounds binding to these proteins were exempted from further analysis. Subsequently, eight compounds (DB00128, DB00312, DB00766, DB00951, DB02893, DB03754, DB13972, and DB14159) were identified as potential allosteric hits for FP-2 and five (DB00853, DB00951, DB01613, DB04173 and DB09419) for FP-3. These compounds were subjected to MD simulation and post-MD trajectory analysis to ascertain their stability in their respective protein structures. The effects of the stable compounds on the WT and mutant systems of FP-2 and FP-3 were then evaluated using DRN analysis. Attention has recently been drawn towards identifying novel allosteric compounds targeting FP-2 and FP-3; hence this study explores the potential allosteric inhibitory mechanisms in the presence and absence of mutations in FP-2 and FP-3. Overall, the results presented in this thesis provide (i) an understanding of the role mutations in the partial zymogen complex play in the activation of the active enzyme, (ii) an insight into the possible allosteric mechanisms induced by mutations on the active enzymes, and (iii) a computational pipeline for the development of novel allosteric modulators for malaria inhibition studies. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Okeke, Chiamaka Jessica
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432170 , vital:72848 , DOI 10.21504/10962/432170
- Description: Malaria, caused by an obligate unicellular protozoan parasite of the genus Plasmodium, is a disease of global health importance that remains a major cause of morbidity and mortality in developing countries. The World Health Organization (WHO) reported nearly 247 million malaria cases in 2021, causing 619,000 deaths, the vast majority ascribed to pregnant women and young children in sub-Saharan Africa. A critical component of malaria mitigation and elimination efforts worldwide is antimalarial drugs. However, resistance to available antimalarial drugs jeopardizes the treatment, prevention, and eradication of the disease. The recent emergence and spread of resistance to artemisinin (ART), the currently recommended first-line antimalarial drug, emphasizes the need to understand the resistance mechanism and apply this knowledge in developing new drugs that are effective against malaria. An insight into ART's mechanism of action indicates that ferrous iron (Fe2+) or heme, released when hemoglobin is degraded, cleaves the endoperoxide bridge. As a result, free radicals are formed, which alkylate many intracellular targets and result in plasmodial proteopathy. Aside from the existing evidence that mutations in the Kelch 13 protein propeller domain affect ART sensitivity and clearance rate by Plasmodium falciparum (Pf) parasites, recent investigations raise the possibility that additional target loci may be involved, and these include a nonsense (S69stop) and four missense variants (K255R, N257E, T343P, and D345G) in falcipain 2 (FP-2) protein. FP-2 and falcipain 3 (FP-3) are cysteine proteases responsible for hydrolyzing hemoglobin in the host erythrocytic cycle, a key virulence factor for malaria parasite growth and metabolism. Due to the obligatory nature of the hemoglobin degradation process, both proteases have become potential antimalarial drug targets attracting attention in recent years for the development of blood-stage antimalarial drugs. The alteration of the expression profile of FP-2 and FP-3 through gene manipulation approaches (knockout) or compound inhibition assays, respectively, induced parasites with swollen food vacuoles due to the accumulation of undegraded hemoglobin. Furthermore, missense mutations in FP-2 confer parasites with decreased ART sensitivity, probably due to altered enzyme efficiency and momentary decreased hemoglobin degradation. Hence, understanding how these mutations affect FP-2 (including those implicated in ART resistance) and FP-3 is imperative to finding potentially effective inhibitors. The first aim of this thesis is to characterize the effects of missense mutations on the partial zymogen complex and the catalytic domain of FP-2 and FP-3 using a range of computational approaches and tools such as homology modeling, molecular dynamics (MD) simulations, comparative essential dynamics, dynamic residue network (DRN) analysis, weighted residue contact map analysis, amongst others. The Pf genomic resource database (PlasmoDB) identified 41 missense mutations located in the partial zymogen and catalytic domains of FP-2 and FP-3. Using structure-based tools, six putative allosteric pockets were identified in FP-2 and FP-3. The effect of mutations on the whole protein, the central core, binding pocket residues and allosteric pockets was evaluated. The accurate 3D homology models of the WT and mutants were calculated. MD simulations were performed on the various systems as a quick starting point. MD simulations have provided a cornerstone for establishing numerous computational tools for describing changes arising from mutations, ligand binding, and environmental changes such as pH and temperature. Post-MD analysis was performed in two stages viz global and local analysis. Global analysis via radius of gyration (Rg) and comparative essential dynamic analysis revealed the conformational variability associated with all mutations. In the catalytic domain of FP-2, the presence of M245I mutation triggered the formation of a cryptic pocket via an exclusive mechanism involving the fusion of pockets 2 and 6. This striking observation was also detected in the partial zymogen complex of FP-2 and induced by A159V, M245I and E249A mutations. A similar observation was uncovered in the presence of A422T mutation in the catalytic domain of FP-3. Local DRN and contact map analyses identified conserved inter-residue interaction changes on important communication networks. This study brings a novel understanding of the effects of missense mutations in FP-2 and FP-3 and provides important insight which may help discover new anti-hemoglobinase drugs. The second aim is the identification of potential allosteric ligands against the WT and mutant systems of FP-2 and FP-3 using various computational tools. Of the six potential allosteric pockets identified in FP-2 and FP-3, pocket 1 was evaluated by SiteMap as the most druggable in both proteins. This pipeline was implemented to screen pocket 1 of FP-2 and FP-3 against 2089 repositionable compounds obtained from the DrugBank database. In order to ensure selectivity and specificity to the Plasmodium protein, the human homologs (Cat K and Cat L) were screened, and compounds binding to these proteins were exempted from further analysis. Subsequently, eight compounds (DB00128, DB00312, DB00766, DB00951, DB02893, DB03754, DB13972, and DB14159) were identified as potential allosteric hits for FP-2 and five (DB00853, DB00951, DB01613, DB04173 and DB09419) for FP-3. These compounds were subjected to MD simulation and post-MD trajectory analysis to ascertain their stability in their respective protein structures. The effects of the stable compounds on the WT and mutant systems of FP-2 and FP-3 were then evaluated using DRN analysis. Attention has recently been drawn towards identifying novel allosteric compounds targeting FP-2 and FP-3; hence this study explores the potential allosteric inhibitory mechanisms in the presence and absence of mutations in FP-2 and FP-3. Overall, the results presented in this thesis provide (i) an understanding of the role mutations in the partial zymogen complex play in the activation of the active enzyme, (ii) an insight into the possible allosteric mechanisms induced by mutations on the active enzymes, and (iii) a computational pipeline for the development of novel allosteric modulators for malaria inhibition studies. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
Field facilitation in open and distance learning in resource-constrained environments: a case of Mzuzu University, Malawi
- Authors: Kalima, Robert Chagwamtsoka
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431554 , vital:72785 , DOI 10.21504/10962/431554
- Description: As part of the drive to enhance students’ learning experiences and success for students pursuing the B.Ed Science programme through distance education at Mzuzu University (Mzuni), the Open and Distance Learning (ODL) Steering Committee of Mzuni introduced the field facilitation strategy in 2014 to provide additional academic support to such students off campus. There have been questions, though, regarding the effectiveness of this strategy in terms of enhancement of student learning and success. This study, therefore, sought to examine the current field facilitation strategy in the B.Ed Science programme under the ODL mode of delivery, with a view to proposing improvements that would be made to the field facilitation strategy so that it enables enhanced learning and success in Science and Mathematics at Mzuni. Efforts to improve the current field facilitation strategy have been informed by an empirically based understanding of the shortfalls and strengths of the existing field facilitation strategy for ODL students in the B.Ed Science programme. To enhance students’ learning and success for ODL students in resource-constrained contexts such as Mzuni and similar contexts, the study adopted a qualitative case study design guided by tools from the second generation of the Cultural Historical Activity Theory. Qualitative data was obtained in two phases, a contextual profiling phase and a modified Change Laboratory Workshop phase. The modified Change Laboratory Workshops were conducted through the social media application ‘WhatsApp’ rather than in person as is usually done. Qualitative data in the contextual profiling phase was obtained from three categories of participants, namely, Science and Mathematics lecturers, Science and Mathematics field facilitators, and Science and Mathematics students. The contextual profiling phase included surveys, focus group interviews, individual interviews with lecturers at Mzuni and the field facilitators from the five satellite learning centres of Mzuni, and document analysis. The contextual profiling data acted as the mirror data for the next phase of data generation (Change Laboratory Workshop phase). The findings indicated that the support currently rendered by field facilitators to ODL Science and Mathematics students was inadequate and consisted of a shallow mode of instruction focusing on v traditional ways of teaching and learning. This meant that the field facilitators focused on lecturing as a pedagogical strategy for supporting the learning of Science and Mathematics. This was largely because the support offered to field facilitators by Mzuni was inadequate and did not empower them to generate their own strategies of conducting field facilitation innovatively and creatively, which would in turn empower the students to engage actively and reflectively in their own learning activities. This was due to structural, historical and cultural tensions that existed in the larger system (the university system). The implementation of the field facilitation strategy was challenged by such conflicts in the university structure which manifested themselves in the smaller activity system (the field facilitation activity system) which is the focus of this study. Thematically, such conflicts included students’ attributes, institutional policies, institutional pedagogy and the material and digital divide which Mzuni has not harnessed to support field facilitation. The study further established that institutional sensitivity to the conflicts raised above would result in an improved field facilitation strategy as the conflicts at the higher level (university level) have an impact on what happens in the smaller systems, for example the ODL in general and the field facilitation activity system in particular. The improved field facilitation strategy was supposed to recognise ODL students as students in transit from the traditional face-to-face learning context to the novel ODL learning context. As such, the transitional period of study from secondary school to university, particularly to year one, required an intensive field facilitation support strategy, and thus greater institutional support for both field facilitators and students for enhanced learning experiences and success that would eventually result in improved students’ retention and throughput. The findings of this study will therefore inform all those involved in ODL, particularly those in resource-constrained contexts, to be conscious when implementing ODL innovations. Serious consideration of the contexts in which the innovations are to be implemented is critical. , Thesis (PhD) -- Faculty of Education, Primary and Early Childhood Education, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Kalima, Robert Chagwamtsoka
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431554 , vital:72785 , DOI 10.21504/10962/431554
- Description: As part of the drive to enhance students’ learning experiences and success for students pursuing the B.Ed Science programme through distance education at Mzuzu University (Mzuni), the Open and Distance Learning (ODL) Steering Committee of Mzuni introduced the field facilitation strategy in 2014 to provide additional academic support to such students off campus. There have been questions, though, regarding the effectiveness of this strategy in terms of enhancement of student learning and success. This study, therefore, sought to examine the current field facilitation strategy in the B.Ed Science programme under the ODL mode of delivery, with a view to proposing improvements that would be made to the field facilitation strategy so that it enables enhanced learning and success in Science and Mathematics at Mzuni. Efforts to improve the current field facilitation strategy have been informed by an empirically based understanding of the shortfalls and strengths of the existing field facilitation strategy for ODL students in the B.Ed Science programme. To enhance students’ learning and success for ODL students in resource-constrained contexts such as Mzuni and similar contexts, the study adopted a qualitative case study design guided by tools from the second generation of the Cultural Historical Activity Theory. Qualitative data was obtained in two phases, a contextual profiling phase and a modified Change Laboratory Workshop phase. The modified Change Laboratory Workshops were conducted through the social media application ‘WhatsApp’ rather than in person as is usually done. Qualitative data in the contextual profiling phase was obtained from three categories of participants, namely, Science and Mathematics lecturers, Science and Mathematics field facilitators, and Science and Mathematics students. The contextual profiling phase included surveys, focus group interviews, individual interviews with lecturers at Mzuni and the field facilitators from the five satellite learning centres of Mzuni, and document analysis. The contextual profiling data acted as the mirror data for the next phase of data generation (Change Laboratory Workshop phase). The findings indicated that the support currently rendered by field facilitators to ODL Science and Mathematics students was inadequate and consisted of a shallow mode of instruction focusing on v traditional ways of teaching and learning. This meant that the field facilitators focused on lecturing as a pedagogical strategy for supporting the learning of Science and Mathematics. This was largely because the support offered to field facilitators by Mzuni was inadequate and did not empower them to generate their own strategies of conducting field facilitation innovatively and creatively, which would in turn empower the students to engage actively and reflectively in their own learning activities. This was due to structural, historical and cultural tensions that existed in the larger system (the university system). The implementation of the field facilitation strategy was challenged by such conflicts in the university structure which manifested themselves in the smaller activity system (the field facilitation activity system) which is the focus of this study. Thematically, such conflicts included students’ attributes, institutional policies, institutional pedagogy and the material and digital divide which Mzuni has not harnessed to support field facilitation. The study further established that institutional sensitivity to the conflicts raised above would result in an improved field facilitation strategy as the conflicts at the higher level (university level) have an impact on what happens in the smaller systems, for example the ODL in general and the field facilitation activity system in particular. The improved field facilitation strategy was supposed to recognise ODL students as students in transit from the traditional face-to-face learning context to the novel ODL learning context. As such, the transitional period of study from secondary school to university, particularly to year one, required an intensive field facilitation support strategy, and thus greater institutional support for both field facilitators and students for enhanced learning experiences and success that would eventually result in improved students’ retention and throughput. The findings of this study will therefore inform all those involved in ODL, particularly those in resource-constrained contexts, to be conscious when implementing ODL innovations. Serious consideration of the contexts in which the innovations are to be implemented is critical. , Thesis (PhD) -- Faculty of Education, Primary and Early Childhood Education, 2023
- Full Text:
- Date Issued: 2023-10-13
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:
- Date Issued: 2023-10-13
- 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:
- Date Issued: 2023-10-13
From more sustainable isocyanide-based multicomponent reactions to spiro-heterocyclic compound syntheses
- Authors: Salami, Sodeeq Aderotimi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432229 , vital:72853 , DOI 10.21504/10962/432229
- Description: The global pharmaceutical industry has undergone profound transformations in the past two decades in the search for new drugs. For this reason, most pharmaceutical companies made significant investments not only in the development of new drugs but new methodologies. Modern drug development is confronted with the challenge of developing chemical reactions that are highly capable of providing most of the elements of structural complexity and diversity with the fewest possible synthetic steps for the specific target with the most intriguing properties. The discovery of more sustainable, environmentally friendly reactions capable of forming multiple bonds in a single step has been a challenge in organic synthesis over the years. Many organic chemists have recently started focusing on creative ways of reducing environmental pollution. The use of hazardous solvents has been reduced or eliminated in research to limit harm to both people and the environment. The pursuit of this goal has drawn many organic chemists to the study of various sustainable synthetic techniques including catalysis, aqueous organic reactions and mechanochemistry. The scope of this thesis was to apply sustainable techniques to design multicomponent synthetic protocols for the Passerini reaction and further apply these new protocols to construct spiro-heterocyclic compounds, all based on green chemistry principles. There is a need to develop rapid, efficient, and versatile strategies for the synthesis of bioactive molecules via multicomponent reactions. This project tried to avoid some of the pitfalls of traditional approaches, such as toxicity, low yield, long reaction times, harsh conditions, experimental complexity, and limited functionalization scope. This was achieved by focussing on the use of isonitriles and isothiocyanates as key reactive intermediates, and making extensive use of aqueous reaction conditions, mechanochemistry and microwave activation. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Salami, Sodeeq Aderotimi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432229 , vital:72853 , DOI 10.21504/10962/432229
- Description: The global pharmaceutical industry has undergone profound transformations in the past two decades in the search for new drugs. For this reason, most pharmaceutical companies made significant investments not only in the development of new drugs but new methodologies. Modern drug development is confronted with the challenge of developing chemical reactions that are highly capable of providing most of the elements of structural complexity and diversity with the fewest possible synthetic steps for the specific target with the most intriguing properties. The discovery of more sustainable, environmentally friendly reactions capable of forming multiple bonds in a single step has been a challenge in organic synthesis over the years. Many organic chemists have recently started focusing on creative ways of reducing environmental pollution. The use of hazardous solvents has been reduced or eliminated in research to limit harm to both people and the environment. The pursuit of this goal has drawn many organic chemists to the study of various sustainable synthetic techniques including catalysis, aqueous organic reactions and mechanochemistry. The scope of this thesis was to apply sustainable techniques to design multicomponent synthetic protocols for the Passerini reaction and further apply these new protocols to construct spiro-heterocyclic compounds, all based on green chemistry principles. There is a need to develop rapid, efficient, and versatile strategies for the synthesis of bioactive molecules via multicomponent reactions. This project tried to avoid some of the pitfalls of traditional approaches, such as toxicity, low yield, long reaction times, harsh conditions, experimental complexity, and limited functionalization scope. This was achieved by focussing on the use of isonitriles and isothiocyanates as key reactive intermediates, and making extensive use of aqueous reaction conditions, mechanochemistry and microwave activation. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
Health communication for antimicrobial resistance and stewardship in the Makana Local Municipality, South Africa
- Authors: Sharma, Samridhi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431531 , vital:72783
- Description: Access restricted. Expected release date 2025. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Sharma, Samridhi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431531 , vital:72783
- Description: Access restricted. Expected release date 2025. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2023
- Full Text:
- Date Issued: 2023-10-13
HOP abundance affects nuclear pore components and the export of protein and RNA cargo
- Authors: Oladipo, Hannah Oluwakemi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432192 , vital:72850
- Description: Access restricted. Expected release date 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Oladipo, Hannah Oluwakemi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432192 , vital:72850
- Description: Access restricted. Expected release date 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
Identification of novel therapeutic agents targeting Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication
- Authors: Okpara, Michael Obinna
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432181 , vital:72849
- Description: Access restricted. Expected release date 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Okpara, Michael Obinna
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432181 , vital:72849
- Description: Access restricted. Expected release date 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
In silico characterization of missense mutations in infectious diseases: case studies of tuberculosis and COVID-19
- Authors: Barozi, Victor
- Date: 2023-10-13
- Subjects: Microbial mutation , COVID-19 (Disease) , Drug resistance in microorganisms , Antitubercular agents , Tuberculosis , Molecular dynamics , Single nucleotide polymorphisms
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431626 , vital:72791 , DOI 10.21504/10962/431626
- Description: One of the greatest challenges facing modern medicine and the global public health today is antimicrobial drug resistance (AMR). This “silent pandemic,” as coined by the world health organization (WHO), is steadily increasing with an estimated 4.95 million mortalities attributed to AMR in 2019, 1.27 million of which were directly linked to AMR. Some of the contributors to AMR include self-prescription, drug overuse, sub-optimal drug prescriptions by health workers, and inaccessibility to drugs, especially in remote areas, which leads to poor adherence. The situation is aggravated by the upsurge of new zoonotic infections like the coronavirus disease 2019, which present unique challenges and take the bulk of resources hence stunting the fight against AMR. Quite alarming still is our current antimicrobial arsenal, which hasn’t had any novel antimicrobial drug discovery/addition, of a new class, since the 1980s. This puts a burden on the existing broad-spectrum antimicrobial drugs which are already struggling against multi-drug resistant strains like multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Besides the search for new antimicrobial agents, the other avenue for addressing AMR is studying drug resistance mechanisms, especially single nucleotide polymorphisms (SNPs), that change drug target characteristics. With the advancement of computational power and data storage resources, computational approaches can be applied in mutational studies to provide insight into the drug resistance mechanisms with an aim to inform future drug design and development. Therefore, in the first part of this thesis, we employ integrative in silico approaches, including 3D structure modeling, molecular dynamic (MD) simulations, comparative essential dynamics (ED), and protein network analysis approaches i.e., dynamic residue network (DRN) analysis to decipher drug resistance mechanisms in tuberculosis (TB). This involved an investigation of the drug resistance mutations in the catalase-peroxidase (KatG) and pyrazinamidase (MtPncA) enzymes which are responsible for activation of TB first-line drugs; Isoniazid (INH) and Pyrazinamide (PZA), respectively. In the case of KatG, eleven high confidence (HC) KatG mutations associated with a high prevalence of phenotypic INH resistance were identified and their 3D structures modeled before subjecting them to MD simulations. Global analysis showed an unstable KatG structure and active site environment in the mutants compared to the wildtype. Active site dynamics in the mutants compromised cofactor (heme) interactions resulting in less bonds/interactions compared to the wildtype. Given the importance of the heme, reduced interactions affect enzyme function. Trajectory analysis also showed asymmetric protomer behavior both in the wildtype and mutant systems. DRN analysis identified the KatG dimerization domain and C-terminal domain as functionally important and influential in the enzyme function as per betweenness centrality and eigenvector centrality distribution. In the case of the MtPncA enzyme, our main focus was on understanding the MtPncA binding ability of Nicotinamide (an analogue of PZA) in comparison to PZA, especially in the presence of 82 resistance conferring MtPncA mutations. Like in KatG, the mutant structures were modeled and subjected to MD simulations and analysis. Interestingly, more MtPncA mutants favored NAM interactions compared to PZA i.e., 34 MtPncA mutants steadily coordinated NAM compared to 21 in the case of PZA. Trajectory and ligand interaction analysis showed how increased active site lid loop dynamics affect the NAM binding, especially in the systems with the active site mutations i.e., H51Y, W68R, C72R, L82R, K96N, L159N, and L159R. This led to fewer protein-ligand interactions and eventually ligand ejection. Network analysis further identified the protein core, metal binding site (MBS), and substrate binding site as the most important regions of the enzyme. Furthermore, the degree of centrality analysis showed how specific MtPncA mutations i.e., C14H, F17D, and T412P, interrupt intra-protein communication from the MtPncA core to the MBS, affecting enzyme activity. The analysis of KatG and MtPncA enzyme mutations not only identified the effects of mutations on enzyme behaviour and communication, but also established a framework of computational approaches that can be used for mutational studies in any protein. Besides AMR, the continued encroachment of wildlife habitats due to population growth has exposed humans to wildlife pathogens leading to zoonotic diseases, a recent example being coronavirus disease 2019 (COVID-19). In the second part of the thesis, the established computational approaches in Part 1, were employed to investigate the changes in inter-protein interactions and communication patterns between the severe acute respiratory coronavirus 2 (SARS-CoV-2) with the human host receptor protein (ACE2: angiotensin-converting enzyme 2) consequent to mutations in the SARS-CoV-2 receptor binding domain (RBD). Here, the focus was on RBD mutations of the Omicron sub-lineages. We identified four Omicron-sub lineages with RBD mutations i.e., BA.1, BA.2, BA.3 and BA.4. Each sub-lineage mutations were modeled into RBD structure in complex with the hACE2. MD analysis of the RBD-hACE2 complex highlighted how the RBD mutations change the conformational flexibility of both the RBD and hACE2 compared to the wildtype (WT). Furthermore, DRN analysis identified novel allosteric paths composed of residues with high betweenness and eigenvector centralities linking the RBD to the hACE2 in both the wildtype and mutant systems. Interestingly, these paths were modified with the progression of Omicron sub-lineages, highlighting how the virus evolution affects protein interaction. Lastly, the effect of mutations on S RBD and hACE2 interaction was investigated from the hACE2 perspective by focusing on mutations in the hACE2 protein. Here, naturally occurring hACE2 polymorphisms in African populations i.e., S19P, K26R, M82I, K341R, N546D, and D597Q, were identified and their effects on RBD-hACE2 interactions investigated in presence of the Omicron BA.4/5 RBD mutations. The hACE2 polymorphisms subtly affected the complex dynamics; however, RBD-hACE2 interaction analysis showed that hACE2 mutations effect the complex formation and interaction. Here, the K26R mutation favored RBD-hACE2 interactions, whereas S19P resulted in fewer inter-protein interactions than the reference system. The M82I mutation resulted in a higher RBD-hACE2 binding energy compared to the wildtype meaning that the mutation might not favor RBD binding to the hACE2. On the other hand, K341R had the most RBD-hACE2 interactions suggesting that it probably favors RBD binding to the hACE2. N546D and D597Q had diminutive differences to the reference system. Interestingly, the network of high betweenness centrality residues linking the two proteins, as seen in the previous paragraph, were maintained/modified in presence of hACE2 mutations. HACE2 mutations also changed the enzyme network patterns resulting in a concentration of high eigenvector centrality residues around the zinc-binding and active site region, ultimately influencing the enzyme functionality. Altogether, the thesis highlights fundamental structural and network changes consequent to mutations both in TB and COVID-19 proteins of interest using in silico approaches. These approaches not only provide a new context on impact of mutations in TB and COVID target proteins, but also presents a framework that be implemented in other protein mutation studies. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Barozi, Victor
- Date: 2023-10-13
- Subjects: Microbial mutation , COVID-19 (Disease) , Drug resistance in microorganisms , Antitubercular agents , Tuberculosis , Molecular dynamics , Single nucleotide polymorphisms
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431626 , vital:72791 , DOI 10.21504/10962/431626
- Description: One of the greatest challenges facing modern medicine and the global public health today is antimicrobial drug resistance (AMR). This “silent pandemic,” as coined by the world health organization (WHO), is steadily increasing with an estimated 4.95 million mortalities attributed to AMR in 2019, 1.27 million of which were directly linked to AMR. Some of the contributors to AMR include self-prescription, drug overuse, sub-optimal drug prescriptions by health workers, and inaccessibility to drugs, especially in remote areas, which leads to poor adherence. The situation is aggravated by the upsurge of new zoonotic infections like the coronavirus disease 2019, which present unique challenges and take the bulk of resources hence stunting the fight against AMR. Quite alarming still is our current antimicrobial arsenal, which hasn’t had any novel antimicrobial drug discovery/addition, of a new class, since the 1980s. This puts a burden on the existing broad-spectrum antimicrobial drugs which are already struggling against multi-drug resistant strains like multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Besides the search for new antimicrobial agents, the other avenue for addressing AMR is studying drug resistance mechanisms, especially single nucleotide polymorphisms (SNPs), that change drug target characteristics. With the advancement of computational power and data storage resources, computational approaches can be applied in mutational studies to provide insight into the drug resistance mechanisms with an aim to inform future drug design and development. Therefore, in the first part of this thesis, we employ integrative in silico approaches, including 3D structure modeling, molecular dynamic (MD) simulations, comparative essential dynamics (ED), and protein network analysis approaches i.e., dynamic residue network (DRN) analysis to decipher drug resistance mechanisms in tuberculosis (TB). This involved an investigation of the drug resistance mutations in the catalase-peroxidase (KatG) and pyrazinamidase (MtPncA) enzymes which are responsible for activation of TB first-line drugs; Isoniazid (INH) and Pyrazinamide (PZA), respectively. In the case of KatG, eleven high confidence (HC) KatG mutations associated with a high prevalence of phenotypic INH resistance were identified and their 3D structures modeled before subjecting them to MD simulations. Global analysis showed an unstable KatG structure and active site environment in the mutants compared to the wildtype. Active site dynamics in the mutants compromised cofactor (heme) interactions resulting in less bonds/interactions compared to the wildtype. Given the importance of the heme, reduced interactions affect enzyme function. Trajectory analysis also showed asymmetric protomer behavior both in the wildtype and mutant systems. DRN analysis identified the KatG dimerization domain and C-terminal domain as functionally important and influential in the enzyme function as per betweenness centrality and eigenvector centrality distribution. In the case of the MtPncA enzyme, our main focus was on understanding the MtPncA binding ability of Nicotinamide (an analogue of PZA) in comparison to PZA, especially in the presence of 82 resistance conferring MtPncA mutations. Like in KatG, the mutant structures were modeled and subjected to MD simulations and analysis. Interestingly, more MtPncA mutants favored NAM interactions compared to PZA i.e., 34 MtPncA mutants steadily coordinated NAM compared to 21 in the case of PZA. Trajectory and ligand interaction analysis showed how increased active site lid loop dynamics affect the NAM binding, especially in the systems with the active site mutations i.e., H51Y, W68R, C72R, L82R, K96N, L159N, and L159R. This led to fewer protein-ligand interactions and eventually ligand ejection. Network analysis further identified the protein core, metal binding site (MBS), and substrate binding site as the most important regions of the enzyme. Furthermore, the degree of centrality analysis showed how specific MtPncA mutations i.e., C14H, F17D, and T412P, interrupt intra-protein communication from the MtPncA core to the MBS, affecting enzyme activity. The analysis of KatG and MtPncA enzyme mutations not only identified the effects of mutations on enzyme behaviour and communication, but also established a framework of computational approaches that can be used for mutational studies in any protein. Besides AMR, the continued encroachment of wildlife habitats due to population growth has exposed humans to wildlife pathogens leading to zoonotic diseases, a recent example being coronavirus disease 2019 (COVID-19). In the second part of the thesis, the established computational approaches in Part 1, were employed to investigate the changes in inter-protein interactions and communication patterns between the severe acute respiratory coronavirus 2 (SARS-CoV-2) with the human host receptor protein (ACE2: angiotensin-converting enzyme 2) consequent to mutations in the SARS-CoV-2 receptor binding domain (RBD). Here, the focus was on RBD mutations of the Omicron sub-lineages. We identified four Omicron-sub lineages with RBD mutations i.e., BA.1, BA.2, BA.3 and BA.4. Each sub-lineage mutations were modeled into RBD structure in complex with the hACE2. MD analysis of the RBD-hACE2 complex highlighted how the RBD mutations change the conformational flexibility of both the RBD and hACE2 compared to the wildtype (WT). Furthermore, DRN analysis identified novel allosteric paths composed of residues with high betweenness and eigenvector centralities linking the RBD to the hACE2 in both the wildtype and mutant systems. Interestingly, these paths were modified with the progression of Omicron sub-lineages, highlighting how the virus evolution affects protein interaction. Lastly, the effect of mutations on S RBD and hACE2 interaction was investigated from the hACE2 perspective by focusing on mutations in the hACE2 protein. Here, naturally occurring hACE2 polymorphisms in African populations i.e., S19P, K26R, M82I, K341R, N546D, and D597Q, were identified and their effects on RBD-hACE2 interactions investigated in presence of the Omicron BA.4/5 RBD mutations. The hACE2 polymorphisms subtly affected the complex dynamics; however, RBD-hACE2 interaction analysis showed that hACE2 mutations effect the complex formation and interaction. Here, the K26R mutation favored RBD-hACE2 interactions, whereas S19P resulted in fewer inter-protein interactions than the reference system. The M82I mutation resulted in a higher RBD-hACE2 binding energy compared to the wildtype meaning that the mutation might not favor RBD binding to the hACE2. On the other hand, K341R had the most RBD-hACE2 interactions suggesting that it probably favors RBD binding to the hACE2. N546D and D597Q had diminutive differences to the reference system. Interestingly, the network of high betweenness centrality residues linking the two proteins, as seen in the previous paragraph, were maintained/modified in presence of hACE2 mutations. HACE2 mutations also changed the enzyme network patterns resulting in a concentration of high eigenvector centrality residues around the zinc-binding and active site region, ultimately influencing the enzyme functionality. Altogether, the thesis highlights fundamental structural and network changes consequent to mutations both in TB and COVID-19 proteins of interest using in silico approaches. These approaches not only provide a new context on impact of mutations in TB and COVID target proteins, but also presents a framework that be implemented in other protein mutation studies. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
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:
- Date Issued: 2023-10-13
- 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:
- Date Issued: 2023-10-13
Jazz pedagogical strategies: an A/R/Tographic investigation into the implementation of the South African jazz CAPS syllabus
- Authors: Rungan, Natalie
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432488 , vital:72875 , DOI 10.21504/10962/432488
- Description: The Jazz stream of the Curriculum and Assessment Policy Statement Further Education and Training music curriculum was introduced in South Africa in 2012 (DBE, 2011a). Despite the intentions of the government to promote diversity, social transformation, and inclusion, subject music is still weighted towards Western Art Music, perpetuating past biases of a Eurocentric model for music education. This study, which uses a mixed-method approach, seeks to create strategies to advance Jazz education in South Africa through an a/r/tographic analysis of the author’s Jazz pedagogical methods at Durban High School in KwaZulu Natal, South Africa. Key approaches include curriculum theory, currere, a/r/tography, among others. After reviewing Jazz pedagogy in the U.S.A. and South Africa as a starting point, using Pinar’s (1994) method of currere, the author demonstrates how past personal music educational processes have led to present Jazz pedagogical methods. Six original compositions were written that outline the influences that infused these methods and added to the creative output related to this research. Interviews were conducted with key stakeholders in the Jazz community to gain perspective about the current state of Jazz education, and with students to provide insight into their reactions to the Jazz stream of CAPS. This presents new information about the curriculum from a learners’ perspective. Ethical clearance for research with children was sought and received (Appendix A). Findings show that the ability of learners to recognise the value in, and identity relating to, their African culture through Jazz points to a pivotal departure from previous Eurocentric music education models. However, despite South Africa being positioned as one of the only countries offering Jazz as a subject choice to high school learners, the selection of Jazz in the subject of Music remains underutilised. This study concludes that for Jazz education to advance in South African high schools, there needs to be intentional engagement with Jazz professionals at the high school level. , Thesis (PhD) -- Faculty of Humanities, Music and Musicology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Rungan, Natalie
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432488 , vital:72875 , DOI 10.21504/10962/432488
- Description: The Jazz stream of the Curriculum and Assessment Policy Statement Further Education and Training music curriculum was introduced in South Africa in 2012 (DBE, 2011a). Despite the intentions of the government to promote diversity, social transformation, and inclusion, subject music is still weighted towards Western Art Music, perpetuating past biases of a Eurocentric model for music education. This study, which uses a mixed-method approach, seeks to create strategies to advance Jazz education in South Africa through an a/r/tographic analysis of the author’s Jazz pedagogical methods at Durban High School in KwaZulu Natal, South Africa. Key approaches include curriculum theory, currere, a/r/tography, among others. After reviewing Jazz pedagogy in the U.S.A. and South Africa as a starting point, using Pinar’s (1994) method of currere, the author demonstrates how past personal music educational processes have led to present Jazz pedagogical methods. Six original compositions were written that outline the influences that infused these methods and added to the creative output related to this research. Interviews were conducted with key stakeholders in the Jazz community to gain perspective about the current state of Jazz education, and with students to provide insight into their reactions to the Jazz stream of CAPS. This presents new information about the curriculum from a learners’ perspective. Ethical clearance for research with children was sought and received (Appendix A). Findings show that the ability of learners to recognise the value in, and identity relating to, their African culture through Jazz points to a pivotal departure from previous Eurocentric music education models. However, despite South Africa being positioned as one of the only countries offering Jazz as a subject choice to high school learners, the selection of Jazz in the subject of Music remains underutilised. This study concludes that for Jazz education to advance in South African high schools, there needs to be intentional engagement with Jazz professionals at the high school level. , Thesis (PhD) -- Faculty of Humanities, Music and Musicology, 2023
- Full Text:
- Date Issued: 2023-10-13
Kenyan comedy: transmogrifying stereotypes and fashioning a ‘Kenyanness’ of aesthetic escapism
- Authors: Lumasia, Patrick Chesi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432477 , vital:72874 , DOI 10.21504/10962/432477
- Description: Despite the proliferation of stereotypes in Kenyan comedy, little research exists to show the two intersect to shape a peculiar notion of ‘Kenyanness’. Indeed, Kenyan comedy, besides reproducing and playing on the quotidian and the historical, is heavily invested with ethnic and gender stereotypes that reflect the Kenyan milieu as it intersects with the global. This comedy is oftentimes seen by some critics as detrimental to Kenyan society because it supposedly shapes and reinforces ethnic and/or gender relations in the country. However, this study contends that Kenyan comedy is open to multiple interpretations and meaning contestations that are not necessarily clear to the comedians and audiences due to the asymmetry that abounds between the production and consumption ends of the comedy’s spectrum. The comedy is therefore ambivalent. This research seeks to demonstrate that Kenyan comedy—as a form of entertainment and critique of society—does not seek to fix and reify Kenyan identities. Instead, the comedy frees these identities from the presumed vice-hold, constricting world of stereotypes by disrupting the linearity of the stereotypes, thereby unsettling the hierarchical structure of hegemonic ideology embedded in them through postmodern humour: a form of humour amenable to postmodern sensibilities. To this end, the comedy offers Kenyans momentary escape into a comedic utopia, through which, they address pertinent issues affecting their nationhood, even as they endeavor to fashion a ‘Kenyanness’ of aesthetic escapism that is celebratory of the country’s rich socio-cultural diversity. The study employs Jörg Schweinitz’s (2011) stereotype theory and the postpositivist realist theory of identity in its study of stand-up, scripted episodic and topical comedy as transposed on to YouTube. Specifically, the thesis considers: the Churchill Show (2012 – 2022) that aired on NTV; 2012–2022; The Real Househelps of Kawangware (2014–2021) on KTN/NTV; Auntie Boss (2016–2021) on NTV; The Wicked Edition and The Trending Trend Talkers (2014–). , Thesis (PhD) -- Faculty of Humanities, Literary Studies in English, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Lumasia, Patrick Chesi
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432477 , vital:72874 , DOI 10.21504/10962/432477
- Description: Despite the proliferation of stereotypes in Kenyan comedy, little research exists to show the two intersect to shape a peculiar notion of ‘Kenyanness’. Indeed, Kenyan comedy, besides reproducing and playing on the quotidian and the historical, is heavily invested with ethnic and gender stereotypes that reflect the Kenyan milieu as it intersects with the global. This comedy is oftentimes seen by some critics as detrimental to Kenyan society because it supposedly shapes and reinforces ethnic and/or gender relations in the country. However, this study contends that Kenyan comedy is open to multiple interpretations and meaning contestations that are not necessarily clear to the comedians and audiences due to the asymmetry that abounds between the production and consumption ends of the comedy’s spectrum. The comedy is therefore ambivalent. This research seeks to demonstrate that Kenyan comedy—as a form of entertainment and critique of society—does not seek to fix and reify Kenyan identities. Instead, the comedy frees these identities from the presumed vice-hold, constricting world of stereotypes by disrupting the linearity of the stereotypes, thereby unsettling the hierarchical structure of hegemonic ideology embedded in them through postmodern humour: a form of humour amenable to postmodern sensibilities. To this end, the comedy offers Kenyans momentary escape into a comedic utopia, through which, they address pertinent issues affecting their nationhood, even as they endeavor to fashion a ‘Kenyanness’ of aesthetic escapism that is celebratory of the country’s rich socio-cultural diversity. The study employs Jörg Schweinitz’s (2011) stereotype theory and the postpositivist realist theory of identity in its study of stand-up, scripted episodic and topical comedy as transposed on to YouTube. Specifically, the thesis considers: the Churchill Show (2012 – 2022) that aired on NTV; 2012–2022; The Real Househelps of Kawangware (2014–2021) on KTN/NTV; Auntie Boss (2016–2021) on NTV; The Wicked Edition and The Trending Trend Talkers (2014–). , Thesis (PhD) -- Faculty of Humanities, Literary Studies in English, 2023
- Full Text:
- Date Issued: 2023-10-13
Learning to make a difference: Small-scale women farmers in social learning spaces for climate action
- Authors: Chanyau, Ludwig
- Date: 2023-10-13
- Subjects: Social learning South Africa Amathole District Municipality , Value creation , Environmental education South Africa Amathole District Municipality , Climatic changes Study and teaching South Africa Amathole District Municipality , Communities of practice , Crops and climate South Africa Amathole District Municipality , Women farmers South Africa Amathole District Municipality , Farms, Small South Africa , Agricultural ecology South Africa
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/402944 , vital:69908 , DOI 10.21504/10962/402944
- Description: How do women farmers in Africa learn about climate change? What is quality climate change learning for farmers? How do farmers interface new knowledge with their long-held and trusted traditional knowledge? How do we evaluate learning at farm level and beyond? Using Okoli’s theory mining review, I untangled a tripartite knot of social learning literature to find Social Learning Theory (SLT) suitable for a study to explore my practical and scholarly curiosity as reflected in the above questions. Wenger’s theory of Social Learning emerged as the most appropriate for my research. The second phase of my study explored the climate change learning and practice terrain for small-scale women farmers, analysing the connection between learning, practice, and the resultant value in two case study areas, municipalities in the Amathole District of the Eastern Cape Province of South Africa. In addition to a paper on SLT mining review that unravels and chooses between the strands of social learning, the two case studies resulted in three articles that responded to the study’s objectives and the research questions. The thesis is introduced and synthesised through five 'book-end' chapters, as well as through these four articles. What were my findings? In the first case study, in the drought-stricken Raymond Mhlaba Municipality, I gathered the data through individual semi-structured interviews with farmers, extension officers and representatives of the involved organisations. I also conducted a group interview with farmers and analysed documents to supplement interview data. I analysed the data using concepts of Communities of Practice (CoP) and SLT to map out the learning and practice landscape. I discovered a constellation of CoPs interconnected by the shared drive for adaptive water management. The constellation is made up of tertiary institutions, government departments, non-governmental organisations and farmers of varying experiences and competencies, with women emerging as the more proactive gender, and state-led extension services being willing but overstretched and under-resourced. SLT effectively traced the apparent fragmented learning within and outside the CoPs and the sudden and extensive shifts in the CoP boundaries, especially in the context of COVID-19 pandemic lockdowns and the increased adoption of digital learning platforms. Despite the richness and diversity brought by the emergent new learning networks that involve participants in the province and further afield, the adoption of digital learning platforms worsened the existing generational digital divide among farmers. iii In the second case study, in the water scarce Buffalo City Metropolitan Municipality, I adopted the Value Creation Framework (VCF) to conduct an ethnographic evaluation that used semi-structured interviews, participant observation and document analysis of the learning experiences of women farmers in a social movement on agroecology. I found that the farmer-centred learning approach of the movement has created value for the farmers involved, evidenced by the adoption of agroecology by over 2700 members (including new urban farmers who are occupying open spaces typically used as dumpsites). The learning approach has facilitated expansive learning, enhanced resource mobilisation, new collaborations, partnerships, and seed sharing networks. Additionally, it necessitated context-appropriate and transformative changes to intersectional justice issues associated with historical inequalities in access to land and water and gender discrimination, leading to improved practices, new access to markets and improved quality yields. These are examples of immediate, potential, applied, realised, orienting, enabling and transformative as well as strategic value, as defined by the VCF. In reflecting on how women farmers learn in these social learning spaces I elucidate the learning impact pathways and local contextual influences in shifting CoP boundaries, domains, and practices during the climate crisis as it intersects with other compounding factors. I generated insights that could be useful for stakeholders in the agricultural (extension) sector to build better pathways for emancipatory and empowering expansive social learning in contexts characterised by resource constraints, but also by strong women-led agency. Such learning could make a difference and cushion small-scale farming from collapse especially in times of unprecedented changes. The agroecology movement and associated communities of practice explored in this study create transformative social learning spaces that are able to respond to climate change, and hence a model that state-led extension might want to adopt in other resource-constrained contexts. , Thesis (PhD) -- Faculty of Education, Education, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Chanyau, Ludwig
- Date: 2023-10-13
- Subjects: Social learning South Africa Amathole District Municipality , Value creation , Environmental education South Africa Amathole District Municipality , Climatic changes Study and teaching South Africa Amathole District Municipality , Communities of practice , Crops and climate South Africa Amathole District Municipality , Women farmers South Africa Amathole District Municipality , Farms, Small South Africa , Agricultural ecology South Africa
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/402944 , vital:69908 , DOI 10.21504/10962/402944
- Description: How do women farmers in Africa learn about climate change? What is quality climate change learning for farmers? How do farmers interface new knowledge with their long-held and trusted traditional knowledge? How do we evaluate learning at farm level and beyond? Using Okoli’s theory mining review, I untangled a tripartite knot of social learning literature to find Social Learning Theory (SLT) suitable for a study to explore my practical and scholarly curiosity as reflected in the above questions. Wenger’s theory of Social Learning emerged as the most appropriate for my research. The second phase of my study explored the climate change learning and practice terrain for small-scale women farmers, analysing the connection between learning, practice, and the resultant value in two case study areas, municipalities in the Amathole District of the Eastern Cape Province of South Africa. In addition to a paper on SLT mining review that unravels and chooses between the strands of social learning, the two case studies resulted in three articles that responded to the study’s objectives and the research questions. The thesis is introduced and synthesised through five 'book-end' chapters, as well as through these four articles. What were my findings? In the first case study, in the drought-stricken Raymond Mhlaba Municipality, I gathered the data through individual semi-structured interviews with farmers, extension officers and representatives of the involved organisations. I also conducted a group interview with farmers and analysed documents to supplement interview data. I analysed the data using concepts of Communities of Practice (CoP) and SLT to map out the learning and practice landscape. I discovered a constellation of CoPs interconnected by the shared drive for adaptive water management. The constellation is made up of tertiary institutions, government departments, non-governmental organisations and farmers of varying experiences and competencies, with women emerging as the more proactive gender, and state-led extension services being willing but overstretched and under-resourced. SLT effectively traced the apparent fragmented learning within and outside the CoPs and the sudden and extensive shifts in the CoP boundaries, especially in the context of COVID-19 pandemic lockdowns and the increased adoption of digital learning platforms. Despite the richness and diversity brought by the emergent new learning networks that involve participants in the province and further afield, the adoption of digital learning platforms worsened the existing generational digital divide among farmers. iii In the second case study, in the water scarce Buffalo City Metropolitan Municipality, I adopted the Value Creation Framework (VCF) to conduct an ethnographic evaluation that used semi-structured interviews, participant observation and document analysis of the learning experiences of women farmers in a social movement on agroecology. I found that the farmer-centred learning approach of the movement has created value for the farmers involved, evidenced by the adoption of agroecology by over 2700 members (including new urban farmers who are occupying open spaces typically used as dumpsites). The learning approach has facilitated expansive learning, enhanced resource mobilisation, new collaborations, partnerships, and seed sharing networks. Additionally, it necessitated context-appropriate and transformative changes to intersectional justice issues associated with historical inequalities in access to land and water and gender discrimination, leading to improved practices, new access to markets and improved quality yields. These are examples of immediate, potential, applied, realised, orienting, enabling and transformative as well as strategic value, as defined by the VCF. In reflecting on how women farmers learn in these social learning spaces I elucidate the learning impact pathways and local contextual influences in shifting CoP boundaries, domains, and practices during the climate crisis as it intersects with other compounding factors. I generated insights that could be useful for stakeholders in the agricultural (extension) sector to build better pathways for emancipatory and empowering expansive social learning in contexts characterised by resource constraints, but also by strong women-led agency. Such learning could make a difference and cushion small-scale farming from collapse especially in times of unprecedented changes. The agroecology movement and associated communities of practice explored in this study create transformative social learning spaces that are able to respond to climate change, and hence a model that state-led extension might want to adopt in other resource-constrained contexts. , Thesis (PhD) -- Faculty of Education, Education, 2023
- Full Text:
- Date Issued: 2023-10-13
Leverage points for meaningful participatory governance: lessons from the Tsitsa River catchment, South Africa
- Authors: Fry, Anthony St Leger
- Date: 2023-10-13
- Subjects: Watershed management South Africa Eastern Cape Citizen participation , Political participation South Africa , Twelve leverage points , Transdisciplinarity , Socio-ecological system
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431714 , vital:72798 , DOI 10.21504/10962/431714
- Description: South Africa underwent the renowned transition into a representative multiracial democracy in 1994. While there has been notable progress in many developmental aspects of South African society, many inherited dilemmas persist, and myriad novel ones are emerging. In land and water governance, the nascent institutions do not reflect the visions laid out in the pioneering and substantive legislation, policies, and guidelines generated in the post-1994 period. Unaddressed dilemmas include widespread failures in local water governance, persistent inequality of access to land and water, poor or non-existent service delivery in rural areas, underdeveloped institutions for integrated and inclusive water resource management, and pernicious divisions between institutions. Overcoming these challenges, which are embedded in complex social-ecological systems across South Africa, will require the collaborative effort of diverse actors from different levels and sectors of society. So how do we foster meaningful participation in ways that are not tyrannical, tokenistic, or manipulative? How do we build local institutions that make sense in the broader political system and in the lives of rural residents? How do we support institutions that meaningfully include diverse voices and enable tangible development outcomes? This thesis explores these questions as part of the Tsitsa Project, a transdisciplinary landscape management project working in the Tsitsa River Catchment (TsRC) in the rural parts of the Eastern Cape province of South Africa. Based on the valuable water resources, severe ecosystem degradation, overlapping traditional and democratic governance systems, and impoverished population, the TsRC is a worthwhile candidate for in-depth study paired with innovative efforts towards systemic development. The single place-based case study approach drew on systems thinking within an evolving transdisciplinary methodology. Qualitative data were collected through extended fieldwork and analysed through an adaptive and iterative approach. Governance mapping elucidated the multiple levels of governance, and a systemic analysis explored meaningful participation at the local level through causal diagramming and observation-based narratives. From the findings, a synthetic analysis identified high leverage points to enable participatory governance interventions to have more sustained impacts. Governance manifestations in the TsRC generally align with existing descriptions of the fractures and associated dilemmas across South Africa, with the added complexities of being a rural landscape in which democratic and traditional governance systems overlap and interact. Local participatory institutions need to endure the broader instability and dysfunction. Interventions must, therefore, be oriented towards trust building and shared understanding while using more practical interventions that provide tangible outcomes, enable in-practice capacity development, and support platforms for all actors to experience and practice meaningful participation together. This thesis aims to unearth the lessons that one small rural catchment might hold for the governance of complex, contested land and for water governance contexts more broadly. , Thesis (PhD) -- Faculty of Science, Institute for Water Research, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Fry, Anthony St Leger
- Date: 2023-10-13
- Subjects: Watershed management South Africa Eastern Cape Citizen participation , Political participation South Africa , Twelve leverage points , Transdisciplinarity , Socio-ecological system
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431714 , vital:72798 , DOI 10.21504/10962/431714
- Description: South Africa underwent the renowned transition into a representative multiracial democracy in 1994. While there has been notable progress in many developmental aspects of South African society, many inherited dilemmas persist, and myriad novel ones are emerging. In land and water governance, the nascent institutions do not reflect the visions laid out in the pioneering and substantive legislation, policies, and guidelines generated in the post-1994 period. Unaddressed dilemmas include widespread failures in local water governance, persistent inequality of access to land and water, poor or non-existent service delivery in rural areas, underdeveloped institutions for integrated and inclusive water resource management, and pernicious divisions between institutions. Overcoming these challenges, which are embedded in complex social-ecological systems across South Africa, will require the collaborative effort of diverse actors from different levels and sectors of society. So how do we foster meaningful participation in ways that are not tyrannical, tokenistic, or manipulative? How do we build local institutions that make sense in the broader political system and in the lives of rural residents? How do we support institutions that meaningfully include diverse voices and enable tangible development outcomes? This thesis explores these questions as part of the Tsitsa Project, a transdisciplinary landscape management project working in the Tsitsa River Catchment (TsRC) in the rural parts of the Eastern Cape province of South Africa. Based on the valuable water resources, severe ecosystem degradation, overlapping traditional and democratic governance systems, and impoverished population, the TsRC is a worthwhile candidate for in-depth study paired with innovative efforts towards systemic development. The single place-based case study approach drew on systems thinking within an evolving transdisciplinary methodology. Qualitative data were collected through extended fieldwork and analysed through an adaptive and iterative approach. Governance mapping elucidated the multiple levels of governance, and a systemic analysis explored meaningful participation at the local level through causal diagramming and observation-based narratives. From the findings, a synthetic analysis identified high leverage points to enable participatory governance interventions to have more sustained impacts. Governance manifestations in the TsRC generally align with existing descriptions of the fractures and associated dilemmas across South Africa, with the added complexities of being a rural landscape in which democratic and traditional governance systems overlap and interact. Local participatory institutions need to endure the broader instability and dysfunction. Interventions must, therefore, be oriented towards trust building and shared understanding while using more practical interventions that provide tangible outcomes, enable in-practice capacity development, and support platforms for all actors to experience and practice meaningful participation together. This thesis aims to unearth the lessons that one small rural catchment might hold for the governance of complex, contested land and for water governance contexts more broadly. , Thesis (PhD) -- Faculty of Science, Institute for Water Research, 2023
- Full Text:
- Date Issued: 2023-10-13
Lifting the veil on the "Untouchable": a study of Muslims living with HIV in Durban, South Africa
- Authors: Shaik, Shabnam
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432518 , vital:72877 , DOI 10.21504/10962/432519
- Description: HIV and AIDS has been prominently studied, by both biomedical and social scientists, since the 1980s. Despite the extensive research that has emerged globally, Muslims have largely been absent in much of the discourse on HIV and AIDS. While the disease is said to be under control in many parts of the world, hidden populations pose a risk to increase in prevalence. Muslims living with HIV are one such hidden population and are only recently gaining representation in studies on HIV and AIDS. Quantitative studies reflect a sharp increase in HIV prevalence in countries with significant Muslim populations, however, more in-depth qualitative studies are needed to garner an understanding of the nature of the disease among Muslims. Muslims have a long history in South Africa, beginning with indentured slavery in Natal (now KwaZulu-Natal) in 1860. There are no specific HIV and AIDS prevention campaigns directed at Muslims in Durban, KwaZulu-Natal, South Africa. Muslims in Durban do not regard HIV is a significant concern for them due to religious doctrine, which they believe if followed will keep them safe from infection. My findings suggest that there is cause for concern over the spread of HIV and AIDS amongst Muslims in Durban. The hidden nature of the disease in the Muslim community has created challenges to curbing the spread of the disease due to the concealment of its presence and the marginalisation of Muslims living with HIV and AIDS. This study conceptualises the HIV and AIDS lived experience amongst Muslims in Durban, South Africa, and uncovers the social and cultural context of the disease. The qualitative study used life histories with ten Muslims living with HIV and semi-structured and unstructured interviews with ten caregivers, five health care professionals and two religious leaders to gain a detailed understanding of the lived experiences of Muslims in Durban. Through the lenses of Purity and Danger, Stigma and Spoilt Identity, and Social Death, this study found that religion [Islam] and its strong moral code influences understandings and perceptions of HIV and AIDS which, in turn affects diagnosis, treatment, care, social identity, and the social well-being of Muslims living with HIV who face stigma, discrimination, shame, and ostracisation from their own community. This study highlights the gaps in the literature on Muslims living with HIV and by providing insight into the lives of participants, the study draws attention to the plight of Muslims living with HIV and AIDS (MLWHIV) and encourages more qualitative studies to be conducted so that a multifaceted understanding of Muslims living with HIV can be created. , Thesis (PhD) -- Faculty of Humanities, Anthropology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Shaik, Shabnam
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432518 , vital:72877 , DOI 10.21504/10962/432519
- Description: HIV and AIDS has been prominently studied, by both biomedical and social scientists, since the 1980s. Despite the extensive research that has emerged globally, Muslims have largely been absent in much of the discourse on HIV and AIDS. While the disease is said to be under control in many parts of the world, hidden populations pose a risk to increase in prevalence. Muslims living with HIV are one such hidden population and are only recently gaining representation in studies on HIV and AIDS. Quantitative studies reflect a sharp increase in HIV prevalence in countries with significant Muslim populations, however, more in-depth qualitative studies are needed to garner an understanding of the nature of the disease among Muslims. Muslims have a long history in South Africa, beginning with indentured slavery in Natal (now KwaZulu-Natal) in 1860. There are no specific HIV and AIDS prevention campaigns directed at Muslims in Durban, KwaZulu-Natal, South Africa. Muslims in Durban do not regard HIV is a significant concern for them due to religious doctrine, which they believe if followed will keep them safe from infection. My findings suggest that there is cause for concern over the spread of HIV and AIDS amongst Muslims in Durban. The hidden nature of the disease in the Muslim community has created challenges to curbing the spread of the disease due to the concealment of its presence and the marginalisation of Muslims living with HIV and AIDS. This study conceptualises the HIV and AIDS lived experience amongst Muslims in Durban, South Africa, and uncovers the social and cultural context of the disease. The qualitative study used life histories with ten Muslims living with HIV and semi-structured and unstructured interviews with ten caregivers, five health care professionals and two religious leaders to gain a detailed understanding of the lived experiences of Muslims in Durban. Through the lenses of Purity and Danger, Stigma and Spoilt Identity, and Social Death, this study found that religion [Islam] and its strong moral code influences understandings and perceptions of HIV and AIDS which, in turn affects diagnosis, treatment, care, social identity, and the social well-being of Muslims living with HIV who face stigma, discrimination, shame, and ostracisation from their own community. This study highlights the gaps in the literature on Muslims living with HIV and by providing insight into the lives of participants, the study draws attention to the plight of Muslims living with HIV and AIDS (MLWHIV) and encourages more qualitative studies to be conducted so that a multifaceted understanding of Muslims living with HIV can be created. , Thesis (PhD) -- Faculty of Humanities, Anthropology, 2023
- Full Text:
- Date Issued: 2023-10-13
Liposomal formulations of metallophthalocyanines-nanoparticle conjugates for hypoxic photodynamic therapy and photoelectrocatalysis
- Authors: Nwahara, Nnamdi Ugochinyere
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432159 , vital:72847 , DOI 10.21504/10962/432159
- Description: This thesis investigates new strategies to enhance the efficacy of photodynamic therapy (PDT) under hypoxic conditions using in-vitro cancer cell models. Phthalocyanines are chosen as viable photosensitizer complexes owing to the favourable absorption properties. To this end, this thesis reports on the synthesis and photophysicochemical properties of various zinc and silicon phthalocyanines (Pcs). To afford better photophysicochemical properties, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. All the studied Pcs showed relatively high triplet and singlet oxygen quantum yields corresponding to their low fluorescence quantum yields. The various mechanisms for hypoxic response include (i) Type I PDT, (ii) PDT coupled with oxygen-independent therapy and (iii) in-situ oxygen generation using catalase-mimicking nanoparticles which serve to supplement in-vitro oxygen concentrations using MPcs or MPc-NPs conjugates. The mechanisms were assessed using electrochemical, computational techniques and catalase mimicking experiments. The as-synthesised Pcs or Pc-NPs were subjected to liposomal loading before PDT studies which led to enhanced biocompatibility and aqueous dispersity. The in-vitro dark cytotoxicity tests and photodynamic therapy activities of the fabricated Pc-liposomes and Pc-NPs-liposomes on either Henrietta Lacks (HeLa) or Michigan Cancer Foundation-7 (MCF-7) breast cancer cells are presented herein. This work further showed that folic acid (FA) functionalization of liposomes could be exploited for active drug delivery and herein led to an almost 3-fold increase in drug uptake vs non-FA functionalised liposomes in accordance with folate receptor (FR) expression levels between HeLa and MCF-7 cells. The in-vitro dark cytotoxicity and photodynamic therapy of selected Pc complexes and conjugates were accessed using MCF-7 and HeLa cell lines. The various mechanisms; (i) Type I PDT, (ii) PDT coupled with oxygen -independent therapy and (iii) in-situ oxygen generation using catalase-mimicking nanoparticles were shown to adequately compensate for the otherwise attenuation of PDT activity under hypoxia. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Nwahara, Nnamdi Ugochinyere
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432159 , vital:72847 , DOI 10.21504/10962/432159
- Description: This thesis investigates new strategies to enhance the efficacy of photodynamic therapy (PDT) under hypoxic conditions using in-vitro cancer cell models. Phthalocyanines are chosen as viable photosensitizer complexes owing to the favourable absorption properties. To this end, this thesis reports on the synthesis and photophysicochemical properties of various zinc and silicon phthalocyanines (Pcs). To afford better photophysicochemical properties, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. All the studied Pcs showed relatively high triplet and singlet oxygen quantum yields corresponding to their low fluorescence quantum yields. The various mechanisms for hypoxic response include (i) Type I PDT, (ii) PDT coupled with oxygen-independent therapy and (iii) in-situ oxygen generation using catalase-mimicking nanoparticles which serve to supplement in-vitro oxygen concentrations using MPcs or MPc-NPs conjugates. The mechanisms were assessed using electrochemical, computational techniques and catalase mimicking experiments. The as-synthesised Pcs or Pc-NPs were subjected to liposomal loading before PDT studies which led to enhanced biocompatibility and aqueous dispersity. The in-vitro dark cytotoxicity tests and photodynamic therapy activities of the fabricated Pc-liposomes and Pc-NPs-liposomes on either Henrietta Lacks (HeLa) or Michigan Cancer Foundation-7 (MCF-7) breast cancer cells are presented herein. This work further showed that folic acid (FA) functionalization of liposomes could be exploited for active drug delivery and herein led to an almost 3-fold increase in drug uptake vs non-FA functionalised liposomes in accordance with folate receptor (FR) expression levels between HeLa and MCF-7 cells. The in-vitro dark cytotoxicity and photodynamic therapy of selected Pc complexes and conjugates were accessed using MCF-7 and HeLa cell lines. The various mechanisms; (i) Type I PDT, (ii) PDT coupled with oxygen -independent therapy and (iii) in-situ oxygen generation using catalase-mimicking nanoparticles were shown to adequately compensate for the otherwise attenuation of PDT activity under hypoxia. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
Mechanisms conditioning the implementation of an integrated quality assurance and enhancement approach at a South African University of Technology
- Authors: Mabote, Ntele Emily
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431576 , vital:72787 , DOI 10.21504/10962/431576
- Description: Literature related to quality in higher education argues that achieving an integrated approach which balances improvement and accountability in a single quality assurance (QA) system, is not easy. In response to the literature, I decided to conduct a realist study to identify mechanisms that can enable or constrain the implementation of an integrated approach in a single quality assurance system at the Tshwane University of Technology (TUT). The scope of my study was limited to teaching and learning as one of the University’s core functions. An integrated approach encouraged a deliberate focus and attention on transformative learning and teaching. The main research question, “what mechanisms enable or constrain the implementation of an integrated approach to quality assurance and enhancement at the Tshwane University of Technology,” underpinned this study. I used Bhaskar’s critical realist philosophy as an underlabourer for the study and Archer’s social realism as an analytical framework to enable me to seek answers to the research questions. The study took the form of a case study at TUT. Data was generated through document analysis and thirty-five semi-structured interviews with agents from across the various levels and campuses of TUT. In keeping with a social realist study, I used Archer’s concept of analytical dualism to analyse structure, culture, and agency separately, and their interplay. My findings indicated that compliance and accountability are related cultural mechanisms and were dominant in the University’s cultural system. This signalled a strong emphasis on quality assurance (QA) rather than quality enhancement (QE). In addition, the findings showed that the University has established sufficient structural and agential enablements to assure the quality of learning and teaching. However, there is a need to integrate transformative cultural mechanisms into the University’s QA system. Furthermore, there were limited structural, cultural, and agential enablements to encourage enhancement. In this regard, I recommended mechanisms that should be in place for an integrated QA and QE approach to be successful at TUT. My main argument is that an institutional context that encourages structural, cultural, and agential QA and QE mechanisms to work in tandem can enable an integrated QA and QE approach. , Thesis (PhD) -- Faculty of Education, Centre for Higher Education Research, Teaching and Learning, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Mabote, Ntele Emily
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431576 , vital:72787 , DOI 10.21504/10962/431576
- Description: Literature related to quality in higher education argues that achieving an integrated approach which balances improvement and accountability in a single quality assurance (QA) system, is not easy. In response to the literature, I decided to conduct a realist study to identify mechanisms that can enable or constrain the implementation of an integrated approach in a single quality assurance system at the Tshwane University of Technology (TUT). The scope of my study was limited to teaching and learning as one of the University’s core functions. An integrated approach encouraged a deliberate focus and attention on transformative learning and teaching. The main research question, “what mechanisms enable or constrain the implementation of an integrated approach to quality assurance and enhancement at the Tshwane University of Technology,” underpinned this study. I used Bhaskar’s critical realist philosophy as an underlabourer for the study and Archer’s social realism as an analytical framework to enable me to seek answers to the research questions. The study took the form of a case study at TUT. Data was generated through document analysis and thirty-five semi-structured interviews with agents from across the various levels and campuses of TUT. In keeping with a social realist study, I used Archer’s concept of analytical dualism to analyse structure, culture, and agency separately, and their interplay. My findings indicated that compliance and accountability are related cultural mechanisms and were dominant in the University’s cultural system. This signalled a strong emphasis on quality assurance (QA) rather than quality enhancement (QE). In addition, the findings showed that the University has established sufficient structural and agential enablements to assure the quality of learning and teaching. However, there is a need to integrate transformative cultural mechanisms into the University’s QA system. Furthermore, there were limited structural, cultural, and agential enablements to encourage enhancement. In this regard, I recommended mechanisms that should be in place for an integrated QA and QE approach to be successful at TUT. My main argument is that an institutional context that encourages structural, cultural, and agential QA and QE mechanisms to work in tandem can enable an integrated QA and QE approach. , Thesis (PhD) -- Faculty of Education, Centre for Higher Education Research, Teaching and Learning, 2023
- Full Text:
- Date Issued: 2023-10-13
Mega-churches and the neo-Pentecostalisation of South Africa’s black middle class
- Authors: Ngoma, Amuzweni Lerato
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432422 , vital:72869 , DOI 10.21504/10962/432422
- Description: This thesis argues that the presence and expansion of South African neo-Pentecostal Charismatic Churches (neo-PCCs) and mega-churches holds significant political economy consequences. Methodologically, the thesis is anchored on digital and in-person ethnography, life history and in-depth interviews. The central argument of this thesis is that neo-PCCs and mega-churches are holding spaces for societal change. The symbolic capital of neo-PCCs and mega-churches and the neo-Pentecostalised habitus, which is co-produced by middle-classes acts as a conduit that facilitates social transitions of political and economic orders. Indeed, religion emerges as a transition mechanism as Durkheim argued for France. It has helped South African social groups to extricate themselves from racist discourses, foster non-racialism and build empowered, somewhat deracialised modern middle-class discourses and tastes. White and Black middle classes have co-produced neo-Pentecostal habiti in the post-apartheid era, that have first, built dispositions for neoliberal capital democracy from apartheid capitalism, second as a middle classing and elite making mechanism and field, third as a stabilising, consolidating and upward strategy of social reproduction. In this way, neo-PCCs and the Black middle class have significantly affected the post-apartheid social formation by producing dispositions that uphold financialised neoliberal capitalism. Significantly, accumulated cultural capital is an indispensable resource in initiating and building post-apartheid institutions. As in the neo-PCC field, it has been pastors, prophets and bishops that have demonstrated the capability to accumulate, transubstantiate and maintain cultural capital that has made their churches comparatively durable social institutions. In a political economy context of state-capture and corruption, a post-GFC-and-COVID-19 milieu characterised by the absence of economic growth, rising unemployment, business closure and ever-increasing interest rates that affect indebted middle-class households and the poor alike, the mega-churches studied herein and their neo-Pentecostalised Black middle class adherents expressed an intense dislike for South African politicians across party lines, and especially the poor performance of the African National Congress-dominated state. So that it is possible that mega-churches and their leaders will outlive many new political parties and independents in the same way that they have outlived post-1994 political parties such as the New National Party, Agang South Africa and the Independent Democrats. Much like the buffer Black middle class that was promoted by the apartheid state as a project of reforming apartheid in the 1970s, whose political activism was pragramatically disengaged, this will likely continue, unless if, generally the post-apartheid Black middle classes shift their sociality from in-ward looking-enclaved social anxiety. , Thesis (PhD) -- Faculty of Humanities, Sociology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Ngoma, Amuzweni Lerato
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432422 , vital:72869 , DOI 10.21504/10962/432422
- Description: This thesis argues that the presence and expansion of South African neo-Pentecostal Charismatic Churches (neo-PCCs) and mega-churches holds significant political economy consequences. Methodologically, the thesis is anchored on digital and in-person ethnography, life history and in-depth interviews. The central argument of this thesis is that neo-PCCs and mega-churches are holding spaces for societal change. The symbolic capital of neo-PCCs and mega-churches and the neo-Pentecostalised habitus, which is co-produced by middle-classes acts as a conduit that facilitates social transitions of political and economic orders. Indeed, religion emerges as a transition mechanism as Durkheim argued for France. It has helped South African social groups to extricate themselves from racist discourses, foster non-racialism and build empowered, somewhat deracialised modern middle-class discourses and tastes. White and Black middle classes have co-produced neo-Pentecostal habiti in the post-apartheid era, that have first, built dispositions for neoliberal capital democracy from apartheid capitalism, second as a middle classing and elite making mechanism and field, third as a stabilising, consolidating and upward strategy of social reproduction. In this way, neo-PCCs and the Black middle class have significantly affected the post-apartheid social formation by producing dispositions that uphold financialised neoliberal capitalism. Significantly, accumulated cultural capital is an indispensable resource in initiating and building post-apartheid institutions. As in the neo-PCC field, it has been pastors, prophets and bishops that have demonstrated the capability to accumulate, transubstantiate and maintain cultural capital that has made their churches comparatively durable social institutions. In a political economy context of state-capture and corruption, a post-GFC-and-COVID-19 milieu characterised by the absence of economic growth, rising unemployment, business closure and ever-increasing interest rates that affect indebted middle-class households and the poor alike, the mega-churches studied herein and their neo-Pentecostalised Black middle class adherents expressed an intense dislike for South African politicians across party lines, and especially the poor performance of the African National Congress-dominated state. So that it is possible that mega-churches and their leaders will outlive many new political parties and independents in the same way that they have outlived post-1994 political parties such as the New National Party, Agang South Africa and the Independent Democrats. Much like the buffer Black middle class that was promoted by the apartheid state as a project of reforming apartheid in the 1970s, whose political activism was pragramatically disengaged, this will likely continue, unless if, generally the post-apartheid Black middle classes shift their sociality from in-ward looking-enclaved social anxiety. , Thesis (PhD) -- Faculty of Humanities, Sociology, 2023
- Full Text:
- Date Issued: 2023-10-13
Movement ecology of a West African sciaenid fish, Argyrosomus coronus, in southern Angola
- Authors: Parkinson, Matthew Cameron
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432203 , vital:72851 , DOI 10.21504/10962/432203
- Description: Argyrosomus coronus is a large sciaenid species with a primary distribution between Cape Frio, in Namibia, and Luanda, in Angola, where it exists as a panmictic stock. Early juveniles (< 300 mm TL) occur on muddy offshore substrata (50–80 m deep) and at one year of age they recruit into the inshore zone. Adults are thought to predominantly occur inshore. Spawning occurs in the species during late spring. The species is heavily targeted by the recreational, subsistence, artisanal and commercial fisheries as juveniles through to adults and there are signs of population decline with declines in catch per unit effort (CPUE) and maximum size. A basic understanding of their movement ecology has emerged from previous studies, based on conventional tagging (mark-recapture) and CPUE monitoring from a shore-based recreational fishery. Juveniles were thought to be resident, with larger fish undertaking long distance migration southward in the austral summer and returning during the austral winter. In addition to the fishery-related threats faced by the species, the southern Angolan region has been identified to be an ocean warming hotspot, and this has been linked to a southward distribution shift and the recent hybridisation of A. coronus with its congener A. inodorus, in Namibia. This study aims to expand the knowledge of the movement ecology of A. coronus and to interrogate our current understanding of the movement patterns of the species using passive acoustic telemetry. Passive acoustic receivers were deployed at three study sites, Flamingo, where all tagging occurred, which lies ~ 200 km north of the Angolan border with Namibia, is a relatively exposed stretch of coastline; Tombua Bay, which lies 30 km south of Flamingo, is a small, sheltered natural embayment; and Baia dos Tigres, which lies 100 km south of Tombua Bay, is a sheltered lagoon in the lee of an island ~ 10 km from the mainland. Tagging occurred in two batches, one year apart. In the first batch, sub-adults (n = 3) and adults (n = 17) were tagged and monitored for two years. In the second batch, juveniles (n = 7) and sub-adults (n = 3) were tagged and monitored for one year. The first objective of this thesis (Chapter 3) was to examine the spatio-temporal dynamics of A. coronus at a regional-level (across study sites, to investigate the prevalence of the longshore migration), and at a local-level (within a study site), and to categorise the movement behaviour of juveniles, sub-adults and adults. Traditional seasons were not used in this thesis, as the study region alternates between ‘warm’ periods (up to ~ 26 °C mean daily water temperature), when Angola Current water covers the area, and ‘cold’ periods (down to ~ 15 °C mean daily water temperature), when Benguela Current water covers the area. A high degree of residency of tagged fish to the Flamingo study site, where tagging was conducted, was found, with juveniles and sub-adults never being detected outside of the Flamingo study site. Five adults (29 %) were detected haphazardly for between one and 36 days at Tombua Bay, following which they were typically detected again at the Flamingo study site. No fish were ever detected at the southernmost site, Baia dos Tigres, suggesting that none migrated to Namibia. Within the Flamingo study site, adults were found to group at the inshore mid-region of the study site during ‘cold’ periods, dispersing again during ‘warm’ periods, when there was a concomitant offshore shift in their area use. This explained the absence of the species from catches in the shore-based recreational fishery during ‘warm’ periods. These results challenge previous migration hypotheses for the species. Therefore, longshore return migrations which were evident from previously conducted conventional tagging, are probably not the norm for the species, but likely occur at a low frequency. The species exhibited a high degree of residency to their tagging site, despite the drastic seasonal changes in water temperatures and station-keeping was the dominant behaviour across all life stages. The constrained area-use noted in this study, relative to the known distribution of the species, suggests that A. coronus exists as a metapopulation, consisting of a network of subpopulations interconnected by gene flow that is most likely facilitated during their pelagic egg and larval phase. The second objective of this thesis was to examine the group formation observed at the Flamingo study site during ‘cold’ periods (Chapter 4). While this grouping of individuals was found to be correlated with water temperature, it was unlikely to be a causal relationship, as the water temperature was not dissimilar to adjacent areas. The area where individuals were concentrated is known to frequently attract large shoals of their dominant prey, Sardinella aurita. While the timing of this group formation aligns with a pre-spawning period, no studies have assessed the existence of local spawning. A. coronus were, however, likely utilising an abundant prey source, during the important pre-spawning period, in order to build up energy reserves. Group formation is a common feature of sciaenids, but literature on the subject is restricted to spawning congregations. Fish are not only more vulnerable to capture during these periods but may also be disturbed during these potentially important social periods. The third objective of this thesis was to investigate the presence of sociality in the species (Chapter 5). Evidence for sociality during and outside the seasonal group formation was explored using network analyses. There was evidence for sociality, with several groups, characterized by co-locations among individuals, identified. While these groups were fluid through time, there was evidence of persistent sociality, with two individuals in particular being consistently co-located over the entire study period. Due to the persistent nature of sociality, group foraging is suggested as an explanation for this, with anecdotal evidence of coordinated hunting supporting this. Acoustic telemetry vastly improved the knowledge of the movement ecology of A. coronus. Despite their panmictic population genetic structure, they were found to be largely resident, likely occurring as a metapopulation across their distribution, with egg and larval dispersal likely the primary mechanism for maintaining panmixia. Evidence for sociality was also found, which was previously unexplored in the species. The persistent nature of social groupings throughout the year, suggests that it may be linked with group foraging and is supported by anecdotal evidence of coordinated hunting by the species. While this study highlights the value of acoustic telemetry in studying movement ecology, it also shows the importance of drawing on multiple methods to fully understand a species’ spatial ecology, including mark-recapture, population genetics, and fishery catch and effort data. , Thesis (PhD) -- Faculty of Science, Ichthyology and Fisheries Science, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Parkinson, Matthew Cameron
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432203 , vital:72851 , DOI 10.21504/10962/432203
- Description: Argyrosomus coronus is a large sciaenid species with a primary distribution between Cape Frio, in Namibia, and Luanda, in Angola, where it exists as a panmictic stock. Early juveniles (< 300 mm TL) occur on muddy offshore substrata (50–80 m deep) and at one year of age they recruit into the inshore zone. Adults are thought to predominantly occur inshore. Spawning occurs in the species during late spring. The species is heavily targeted by the recreational, subsistence, artisanal and commercial fisheries as juveniles through to adults and there are signs of population decline with declines in catch per unit effort (CPUE) and maximum size. A basic understanding of their movement ecology has emerged from previous studies, based on conventional tagging (mark-recapture) and CPUE monitoring from a shore-based recreational fishery. Juveniles were thought to be resident, with larger fish undertaking long distance migration southward in the austral summer and returning during the austral winter. In addition to the fishery-related threats faced by the species, the southern Angolan region has been identified to be an ocean warming hotspot, and this has been linked to a southward distribution shift and the recent hybridisation of A. coronus with its congener A. inodorus, in Namibia. This study aims to expand the knowledge of the movement ecology of A. coronus and to interrogate our current understanding of the movement patterns of the species using passive acoustic telemetry. Passive acoustic receivers were deployed at three study sites, Flamingo, where all tagging occurred, which lies ~ 200 km north of the Angolan border with Namibia, is a relatively exposed stretch of coastline; Tombua Bay, which lies 30 km south of Flamingo, is a small, sheltered natural embayment; and Baia dos Tigres, which lies 100 km south of Tombua Bay, is a sheltered lagoon in the lee of an island ~ 10 km from the mainland. Tagging occurred in two batches, one year apart. In the first batch, sub-adults (n = 3) and adults (n = 17) were tagged and monitored for two years. In the second batch, juveniles (n = 7) and sub-adults (n = 3) were tagged and monitored for one year. The first objective of this thesis (Chapter 3) was to examine the spatio-temporal dynamics of A. coronus at a regional-level (across study sites, to investigate the prevalence of the longshore migration), and at a local-level (within a study site), and to categorise the movement behaviour of juveniles, sub-adults and adults. Traditional seasons were not used in this thesis, as the study region alternates between ‘warm’ periods (up to ~ 26 °C mean daily water temperature), when Angola Current water covers the area, and ‘cold’ periods (down to ~ 15 °C mean daily water temperature), when Benguela Current water covers the area. A high degree of residency of tagged fish to the Flamingo study site, where tagging was conducted, was found, with juveniles and sub-adults never being detected outside of the Flamingo study site. Five adults (29 %) were detected haphazardly for between one and 36 days at Tombua Bay, following which they were typically detected again at the Flamingo study site. No fish were ever detected at the southernmost site, Baia dos Tigres, suggesting that none migrated to Namibia. Within the Flamingo study site, adults were found to group at the inshore mid-region of the study site during ‘cold’ periods, dispersing again during ‘warm’ periods, when there was a concomitant offshore shift in their area use. This explained the absence of the species from catches in the shore-based recreational fishery during ‘warm’ periods. These results challenge previous migration hypotheses for the species. Therefore, longshore return migrations which were evident from previously conducted conventional tagging, are probably not the norm for the species, but likely occur at a low frequency. The species exhibited a high degree of residency to their tagging site, despite the drastic seasonal changes in water temperatures and station-keeping was the dominant behaviour across all life stages. The constrained area-use noted in this study, relative to the known distribution of the species, suggests that A. coronus exists as a metapopulation, consisting of a network of subpopulations interconnected by gene flow that is most likely facilitated during their pelagic egg and larval phase. The second objective of this thesis was to examine the group formation observed at the Flamingo study site during ‘cold’ periods (Chapter 4). While this grouping of individuals was found to be correlated with water temperature, it was unlikely to be a causal relationship, as the water temperature was not dissimilar to adjacent areas. The area where individuals were concentrated is known to frequently attract large shoals of their dominant prey, Sardinella aurita. While the timing of this group formation aligns with a pre-spawning period, no studies have assessed the existence of local spawning. A. coronus were, however, likely utilising an abundant prey source, during the important pre-spawning period, in order to build up energy reserves. Group formation is a common feature of sciaenids, but literature on the subject is restricted to spawning congregations. Fish are not only more vulnerable to capture during these periods but may also be disturbed during these potentially important social periods. The third objective of this thesis was to investigate the presence of sociality in the species (Chapter 5). Evidence for sociality during and outside the seasonal group formation was explored using network analyses. There was evidence for sociality, with several groups, characterized by co-locations among individuals, identified. While these groups were fluid through time, there was evidence of persistent sociality, with two individuals in particular being consistently co-located over the entire study period. Due to the persistent nature of sociality, group foraging is suggested as an explanation for this, with anecdotal evidence of coordinated hunting supporting this. Acoustic telemetry vastly improved the knowledge of the movement ecology of A. coronus. Despite their panmictic population genetic structure, they were found to be largely resident, likely occurring as a metapopulation across their distribution, with egg and larval dispersal likely the primary mechanism for maintaining panmixia. Evidence for sociality was also found, which was previously unexplored in the species. The persistent nature of social groupings throughout the year, suggests that it may be linked with group foraging and is supported by anecdotal evidence of coordinated hunting by the species. While this study highlights the value of acoustic telemetry in studying movement ecology, it also shows the importance of drawing on multiple methods to fully understand a species’ spatial ecology, including mark-recapture, population genetics, and fishery catch and effort data. , Thesis (PhD) -- Faculty of Science, Ichthyology and Fisheries Science, 2023
- Full Text:
- Date Issued: 2023-10-13
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:
- Date Issued: 2023-10-13
- 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:
- Date Issued: 2023-10-13
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:
- Date Issued: 2023-10-13
- 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:
- Date Issued: 2023-10-13