Application of In Vitro Release Testing (IVRT) and a dermatopharmacokinetic approach (tape stripping) for the assessment of Metronidazole topical formulations
- Rath, Seeprarani Prabirkumar
- Authors: Rath, Seeprarani Prabirkumar
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164617 , vital:41148 , doi:10.21504/10962/164617
- Description: Thesis (PhD)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
- Authors: Rath, Seeprarani Prabirkumar
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164617 , vital:41148 , doi:10.21504/10962/164617
- Description: Thesis (PhD)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
Application of machine learning, molecular modelling and structural data mining against antiretroviral drug resistance in HIV-1
- Sheik Amamuddy, Olivier Serge André
- Authors: Sheik Amamuddy, Olivier Serge André
- Date: 2020
- Subjects: Machine learning , Molecules -- Models , Data mining , Neural networks (Computer science) , Antiretroviral agents , Protease inhibitors , Drug resistance , Multidrug resistance , Molecular dynamics , Renin-angiotensin system , HIV (Viruses) -- South Africa , HIV (Viruses) -- Social aspects -- South Africa , South African Natural Compounds Database
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/115964 , vital:34282
- Description: Millions are affected with the Human Immunodeficiency Virus (HIV) world wide, even though the death toll is on the decline. Antiretrovirals (ARVs), more specifically protease inhibitors have shown tremendous success since their introduction into therapy since the mid 1990’s by slowing down progression to the Acquired Immune Deficiency Syndrome (AIDS). However, Drug Resistance Mutations (DRMs) are constantly selected for due to viral adaptation, making drugs less effective over time. The current challenge is to manage the infection optimally with a limited set of drugs, with differing associated levels of toxicities in the face of a virus that (1) exists as a quasispecies, (2) may transmit acquired DRMs to drug-naive individuals and (3) that can manifest class-wide resistance due to similarities in design. The presence of latent reservoirs, unawareness of infection status, education and various socio-economic factors make the problem even more complex. Adequate timing and choice of drug prescription together with treatment adherence are very important as drug toxicities, drug failure and sub-optimal treatment regimens leave room for further development of drug resistance. While CD4 cell count and the determination of viral load from patients in resource-limited settings are very helpful to track how well a patient’s immune system is able to keep the virus in check, they can be lengthy in determining whether an ARV is effective. Phenosense assay kits answer this problem using viruses engineered to contain the patient sequences and evaluating their growth in the presence of different ARVs, but this can be expensive and too involved for routine checks. As a cheaper and faster alternative, genotypic assays provide similar information from HIV pol sequences obtained from blood samples, inferring ARV efficacy on the basis of drug resistance mutation patterns. However, these are inherently complex and the various methods of in silico prediction, such as Geno2pheno, REGA and Stanford HIVdb do not always agree in every case, even though this gap decreases as the list of resistance mutations is updated. A major gap in HIV treatment is that the information used for predicting drug resistance is mainly computed from data containing an overwhelming majority of B subtype HIV, when these only comprise about 12% of the worldwide HIV infections. In addition to growing evidence that drug resistance is subtype-related, it is intuitive to hypothesize that as subtyping is a phylogenetic classification, the more divergent a subtype is from the strains used in training prediction models, the less their resistance profiles would correlate. For the aforementioned reasons, we used a multi-faceted approach to attack the virus in multiple ways. This research aimed to (1) improve resistance prediction methods by focusing solely on the available subtype, (2) mine structural information pertaining to resistance in order to find any exploitable weak points and increase knowledge of the mechanistic processes of drug resistance in HIV protease. Finally, (3) we screen for protease inhibitors amongst a database of natural compounds [the South African natural compound database (SANCDB)] to find molecules or molecular properties usable to come up with improved inhibition against the drug target. In this work, structural information was mined using the Anisotropic Network Model, Dynamics Cross-Correlation, Perturbation Response Scanning, residue contact network analysis and the radius of gyration. These methods failed to give any resistance-associated patterns in terms of natural movement, internal correlated motions, residue perturbation response, relational behaviour and global compaction respectively. Applications of drug docking, homology-modelling and energy minimization for generating features suitable for machine-learning were not very promising, and rather suggest that the value of binding energies by themselves from Vina may not be very reliable quantitatively. All these failures lead to a refinement that resulted in a highly sensitive statistically-guided network construction and analysis, which leads to key findings in the early dynamics associated with resistance across all PI drugs. The latter experiment unravelled a conserved lateral expansion motion occurring at the flap elbows, and an associated contraction that drives the base of the dimerization domain towards the catalytic site’s floor in the case of drug resistance. Interestingly, we found that despite the conserved movement, bond angles were degenerate. Alongside, 16 Artificial Neural Network models were optimised for HIV proteases and reverse transcriptase inhibitors, with performances on par with Stanford HIVdb. Finally, we prioritised 9 compounds with potential protease inhibitory activity using virtual screening and molecular dynamics (MD) to additionally suggest a promising modification to one of the compounds. This yielded another molecule inhibiting equally well both opened and closed receptor target conformations, whereby each of the compounds had been selected against an array of multi-drug-resistant receptor variants. While a main hurdle was a lack of non-B subtype data, our findings, especially from the statistically-guided network analysis, may extrapolate to a certain extent to them as the level of conservation was very high within subtype B, despite all the present variations. This network construction method lays down a sensitive approach for analysing a pair of alternate phenotypes for which complex patterns prevail, given a sufficient number of experimental units. During the course of research a weighted contact mapping tool was developed to compare renin-angiotensinogen variants and packaged as part of the MD-TASK tool suite. Finally the functionality, compatibility and performance of the MODE-TASK tool were evaluated and confirmed for both Python2.7.x and Python3.x, for the analysis of normals modes from single protein structures and essential modes from MD trajectories. These techniques and tools collectively add onto the conventional means of MD analysis.
- Full Text:
- Date Issued: 2020
- Authors: Sheik Amamuddy, Olivier Serge André
- Date: 2020
- Subjects: Machine learning , Molecules -- Models , Data mining , Neural networks (Computer science) , Antiretroviral agents , Protease inhibitors , Drug resistance , Multidrug resistance , Molecular dynamics , Renin-angiotensin system , HIV (Viruses) -- South Africa , HIV (Viruses) -- Social aspects -- South Africa , South African Natural Compounds Database
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/115964 , vital:34282
- Description: Millions are affected with the Human Immunodeficiency Virus (HIV) world wide, even though the death toll is on the decline. Antiretrovirals (ARVs), more specifically protease inhibitors have shown tremendous success since their introduction into therapy since the mid 1990’s by slowing down progression to the Acquired Immune Deficiency Syndrome (AIDS). However, Drug Resistance Mutations (DRMs) are constantly selected for due to viral adaptation, making drugs less effective over time. The current challenge is to manage the infection optimally with a limited set of drugs, with differing associated levels of toxicities in the face of a virus that (1) exists as a quasispecies, (2) may transmit acquired DRMs to drug-naive individuals and (3) that can manifest class-wide resistance due to similarities in design. The presence of latent reservoirs, unawareness of infection status, education and various socio-economic factors make the problem even more complex. Adequate timing and choice of drug prescription together with treatment adherence are very important as drug toxicities, drug failure and sub-optimal treatment regimens leave room for further development of drug resistance. While CD4 cell count and the determination of viral load from patients in resource-limited settings are very helpful to track how well a patient’s immune system is able to keep the virus in check, they can be lengthy in determining whether an ARV is effective. Phenosense assay kits answer this problem using viruses engineered to contain the patient sequences and evaluating their growth in the presence of different ARVs, but this can be expensive and too involved for routine checks. As a cheaper and faster alternative, genotypic assays provide similar information from HIV pol sequences obtained from blood samples, inferring ARV efficacy on the basis of drug resistance mutation patterns. However, these are inherently complex and the various methods of in silico prediction, such as Geno2pheno, REGA and Stanford HIVdb do not always agree in every case, even though this gap decreases as the list of resistance mutations is updated. A major gap in HIV treatment is that the information used for predicting drug resistance is mainly computed from data containing an overwhelming majority of B subtype HIV, when these only comprise about 12% of the worldwide HIV infections. In addition to growing evidence that drug resistance is subtype-related, it is intuitive to hypothesize that as subtyping is a phylogenetic classification, the more divergent a subtype is from the strains used in training prediction models, the less their resistance profiles would correlate. For the aforementioned reasons, we used a multi-faceted approach to attack the virus in multiple ways. This research aimed to (1) improve resistance prediction methods by focusing solely on the available subtype, (2) mine structural information pertaining to resistance in order to find any exploitable weak points and increase knowledge of the mechanistic processes of drug resistance in HIV protease. Finally, (3) we screen for protease inhibitors amongst a database of natural compounds [the South African natural compound database (SANCDB)] to find molecules or molecular properties usable to come up with improved inhibition against the drug target. In this work, structural information was mined using the Anisotropic Network Model, Dynamics Cross-Correlation, Perturbation Response Scanning, residue contact network analysis and the radius of gyration. These methods failed to give any resistance-associated patterns in terms of natural movement, internal correlated motions, residue perturbation response, relational behaviour and global compaction respectively. Applications of drug docking, homology-modelling and energy minimization for generating features suitable for machine-learning were not very promising, and rather suggest that the value of binding energies by themselves from Vina may not be very reliable quantitatively. All these failures lead to a refinement that resulted in a highly sensitive statistically-guided network construction and analysis, which leads to key findings in the early dynamics associated with resistance across all PI drugs. The latter experiment unravelled a conserved lateral expansion motion occurring at the flap elbows, and an associated contraction that drives the base of the dimerization domain towards the catalytic site’s floor in the case of drug resistance. Interestingly, we found that despite the conserved movement, bond angles were degenerate. Alongside, 16 Artificial Neural Network models were optimised for HIV proteases and reverse transcriptase inhibitors, with performances on par with Stanford HIVdb. Finally, we prioritised 9 compounds with potential protease inhibitory activity using virtual screening and molecular dynamics (MD) to additionally suggest a promising modification to one of the compounds. This yielded another molecule inhibiting equally well both opened and closed receptor target conformations, whereby each of the compounds had been selected against an array of multi-drug-resistant receptor variants. While a main hurdle was a lack of non-B subtype data, our findings, especially from the statistically-guided network analysis, may extrapolate to a certain extent to them as the level of conservation was very high within subtype B, despite all the present variations. This network construction method lays down a sensitive approach for analysing a pair of alternate phenotypes for which complex patterns prevail, given a sufficient number of experimental units. During the course of research a weighted contact mapping tool was developed to compare renin-angiotensinogen variants and packaged as part of the MD-TASK tool suite. Finally the functionality, compatibility and performance of the MODE-TASK tool were evaluated and confirmed for both Python2.7.x and Python3.x, for the analysis of normals modes from single protein structures and essential modes from MD trajectories. These techniques and tools collectively add onto the conventional means of MD analysis.
- Full Text:
- Date Issued: 2020
Applied phylogeography : mapping the genetic resource of Honeybush across the Cape Floristic Region
- Authors: Galuszynski, Nicholas C
- Date: 2020
- Subjects: Phylogeography -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/46771 , vital:39655
- Description: Aim: Honeybush tea is a herbal infusion made from members of the Cape Floristic Region (CFR) endemic Cyclopia Vent. Consting of 21 extant species, six are anthropogenically redistributed across the CFR for Honeybush cultivation. However, with no information regarding the distribution and levels of genetic diversity among wild Honeybush populations, anthropogenic translocation of cultivated genotypes may risk disrupting natural genetic diversity patterns. In this thesis, an applied phylogeographic approach is used to provide baseline insights into the spatial structuring of Honeybush genetic diversity. Location: The Cape Floristic Region (CFR), located along the southern Cape of South Africa. Methods: Spatial structuring of evolutionary lineages within Cyclopia are explored at a genus level using data generated from the combination of Anchored Hybrid Enrichment library preparation and high through put sequencing. A High Resolution Melt analysis (HRM) toolkit is then developed to screen haplotype variation across three non-coding chloroplast loci. This HRM toolkit coupled with haplotype confirmation Sanger sequencing is then applied to describe the spatial structuring of genetic diversity in wild populations for two Honeybush species (C. intermedia and C. subternata) and to compare genetic diversity among wild and cultivated populations of three Honeybush species (C. intermedia, C. subternata, and C. longifolia). A reanalysis of published phylogeographic data focusing on CFR plant taxa is used to test if phylogeographic breaks occur across the boundaries among adjacent Centers of Endemism (CoEs). Finally, the low-copy nuclear data set generated via AHE and high throughput sequencing is summarized. Results: Phylogeographic structuring was detected at the inter- and intraspecific levels in Cyclopia. The genus level analysis revealed a strong phylogenetic split between western CFR and eastern CFR endemic species in the nuclear and chloroplast genomes. At the intraspecific level, HRM proved to be a high throughput and accurate tool for haplotype detection, revealing phylogeographic structuring of genetic diversity in C.intermediaand C.subternata. This genetic diversity and structuring was not detected in cultivated Honeybush populations, which appear to have originated from a small number of founding individuals and have experienced a genetic bottleneck. Spatial structuring of genetic lineages is common among CFR plant taxa and the reanalysis of existing data found a significant trend for phylogeographic breaks tooccuracrosstheboundariesamongadjacentCoEs. Finally, over200000baseswere sequenced across 445 low-copy nuclear loci for 14 Cyclopia species. Conclusions: This thesis provides important baseline information on the spatial distribution of wild Honeybush genetic diversity. Phylogeographic structuring is present in wild Honeybush populations. This however is not accounted for in cultivated populations, which may place wild genetic diversity at risk of being disrupted if geneflow among wild and cultivated populations occurs. The results from this thesis should therefore be used to develop precautionary guidelines for the anthropogenic redistribution of Honeybush genetic material for cultivation. Furthermore, the novel insights into regional patterns of phylogeohraphic structuring of plant populations should encourage more efficient and hypothesis driven sampling designs in future phylogeographic work in the CFR. The high throughput sequence data generated in this thesis should transform Cyclopia to a model organism for the study of molecular evolution in the CFR.
- Full Text:
- Date Issued: 2020
- Authors: Galuszynski, Nicholas C
- Date: 2020
- Subjects: Phylogeography -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/46771 , vital:39655
- Description: Aim: Honeybush tea is a herbal infusion made from members of the Cape Floristic Region (CFR) endemic Cyclopia Vent. Consting of 21 extant species, six are anthropogenically redistributed across the CFR for Honeybush cultivation. However, with no information regarding the distribution and levels of genetic diversity among wild Honeybush populations, anthropogenic translocation of cultivated genotypes may risk disrupting natural genetic diversity patterns. In this thesis, an applied phylogeographic approach is used to provide baseline insights into the spatial structuring of Honeybush genetic diversity. Location: The Cape Floristic Region (CFR), located along the southern Cape of South Africa. Methods: Spatial structuring of evolutionary lineages within Cyclopia are explored at a genus level using data generated from the combination of Anchored Hybrid Enrichment library preparation and high through put sequencing. A High Resolution Melt analysis (HRM) toolkit is then developed to screen haplotype variation across three non-coding chloroplast loci. This HRM toolkit coupled with haplotype confirmation Sanger sequencing is then applied to describe the spatial structuring of genetic diversity in wild populations for two Honeybush species (C. intermedia and C. subternata) and to compare genetic diversity among wild and cultivated populations of three Honeybush species (C. intermedia, C. subternata, and C. longifolia). A reanalysis of published phylogeographic data focusing on CFR plant taxa is used to test if phylogeographic breaks occur across the boundaries among adjacent Centers of Endemism (CoEs). Finally, the low-copy nuclear data set generated via AHE and high throughput sequencing is summarized. Results: Phylogeographic structuring was detected at the inter- and intraspecific levels in Cyclopia. The genus level analysis revealed a strong phylogenetic split between western CFR and eastern CFR endemic species in the nuclear and chloroplast genomes. At the intraspecific level, HRM proved to be a high throughput and accurate tool for haplotype detection, revealing phylogeographic structuring of genetic diversity in C.intermediaand C.subternata. This genetic diversity and structuring was not detected in cultivated Honeybush populations, which appear to have originated from a small number of founding individuals and have experienced a genetic bottleneck. Spatial structuring of genetic lineages is common among CFR plant taxa and the reanalysis of existing data found a significant trend for phylogeographic breaks tooccuracrosstheboundariesamongadjacentCoEs. Finally, over200000baseswere sequenced across 445 low-copy nuclear loci for 14 Cyclopia species. Conclusions: This thesis provides important baseline information on the spatial distribution of wild Honeybush genetic diversity. Phylogeographic structuring is present in wild Honeybush populations. This however is not accounted for in cultivated populations, which may place wild genetic diversity at risk of being disrupted if geneflow among wild and cultivated populations occurs. The results from this thesis should therefore be used to develop precautionary guidelines for the anthropogenic redistribution of Honeybush genetic material for cultivation. Furthermore, the novel insights into regional patterns of phylogeohraphic structuring of plant populations should encourage more efficient and hypothesis driven sampling designs in future phylogeographic work in the CFR. The high throughput sequence data generated in this thesis should transform Cyclopia to a model organism for the study of molecular evolution in the CFR.
- Full Text:
- Date Issued: 2020
Assessment of the microbial quality of various domestic rainwater harvesting systems and the suitability of a nano based treatment method
- Authors: Malema, Mokaba Shirley
- Date: 2020
- Language: English
- Type: thesis , text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/110218 , vital:33249 , https://dx.doi.org/10.21504/10962/110218
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Chemistry, 2020.
- Full Text: false
- Date Issued: 2020
- Authors: Malema, Mokaba Shirley
- Date: 2020
- Language: English
- Type: thesis , text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/110218 , vital:33249 , https://dx.doi.org/10.21504/10962/110218
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Chemistry, 2020.
- Full Text: false
- Date Issued: 2020
Attention-deficit/hyperactivity disorder (ADHD) in South Africa: diagnosis and treatment from childhood to adulthood
- Munasur-Naidoo, Ashmitha Premchand
- Authors: Munasur-Naidoo, Ashmitha Premchand
- Date: 2020
- Subjects: Attention-deficit hyperactivity disorder
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/46398 , vital:39603
- Description: Background: Historically Attention-Deficit/hyperactivity disorder (ADHD) was, considered to be a condition that affected mainly children. Over a period of time, there has been a greater understanding to recognize that this condition is also present in the adult population. Globally, treatment for adults has been established as is evident from the various guidelines available. In South Africa, however,healthcare is split into the public and private sectors, which results in differences in the extent of diagnosis and treatment for adults with ADHD.Aim: The primary aim of the study was to evaluate ADHD in South Africa from childhood to adulthood and to determine to what extent adults are being diagnosed and treated.Method: This study comprised of two facets, namely, a drug utilization review and a questionnaire survey. The first part comprised of a retrospective drug utilization study evaluating the consumption and cost of medication used in the treatment of ADHD. The questionnaire was undertaken using a survey methodology amongst selected healthcare professionals in South Africa involved in the diagnosis and treatment of adult ADHD. The data generated from this study together with available guidelines was assessed and a proposed framework for the treatment and diagnosis of adult ADHD was developed for use in the South African public healthcare sector. Results: Based on the registered medication available to treat ADHD, the consumption of methylphenidate and atomoxetine in the private healthcare sector using the Intercontinental Marketing Service database from 2013 to 2016was established. Despite the controversy regarding stimulant medication, methylphenidate was shown to be the medication of choice in South Africa. The consumption of methylphenidate (95.85%) was higher when compared to atomoxetine (4.15%) in 2013 and very slight changes were observed in 2016 were the consumption was 96.40% and 3.60%, respectively. Similarly, over a four-year period, the spend on ADHD medication increased in 2013 to 2016 by 62.63%. Furthermore, the market share for ADHD is dominated by extended-release methylphenidate tablets (59.53%). The questionnaire survey amongst selected healthcare professionals in South Africa involved in the diagnosis and treatment of adult ADHDhighlighted the tools used for diagnosis, pharmacological and non-pharmacological treatment options, which treatment has been found to be most successful, difference in treatment between genders, incorporation of supplementation into the management of patients, difficulties experienced by patients and which co-morbid conditions were also prevalent with ADHD. Based on the data collated in this study and an evaluation of the available guidelines, a framework for treatment of adult patients in the public healthcare sector has been proposed for South Africa at a provincial and national level. Conclusion: In South Africa treatment for ADHD is increasing in the private healthcare sector. The cost and consumption of methylphenidate and atomoxetine has risen over a short period. The treatment of adults in the private sector has also garnered interest, however, the public sector has not yet published guidelines enabling access to diagnosis and treatment for these adult patients. Given the chronic, costly, and debilitating nature of this condition more needs to be done to assist those affected by it. Further studies in this area of neuropsychiatry in South Africa is required to enable access to diagnosis and treatment in the public healthcare sector.
- Full Text:
- Date Issued: 2020
- Authors: Munasur-Naidoo, Ashmitha Premchand
- Date: 2020
- Subjects: Attention-deficit hyperactivity disorder
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/46398 , vital:39603
- Description: Background: Historically Attention-Deficit/hyperactivity disorder (ADHD) was, considered to be a condition that affected mainly children. Over a period of time, there has been a greater understanding to recognize that this condition is also present in the adult population. Globally, treatment for adults has been established as is evident from the various guidelines available. In South Africa, however,healthcare is split into the public and private sectors, which results in differences in the extent of diagnosis and treatment for adults with ADHD.Aim: The primary aim of the study was to evaluate ADHD in South Africa from childhood to adulthood and to determine to what extent adults are being diagnosed and treated.Method: This study comprised of two facets, namely, a drug utilization review and a questionnaire survey. The first part comprised of a retrospective drug utilization study evaluating the consumption and cost of medication used in the treatment of ADHD. The questionnaire was undertaken using a survey methodology amongst selected healthcare professionals in South Africa involved in the diagnosis and treatment of adult ADHD. The data generated from this study together with available guidelines was assessed and a proposed framework for the treatment and diagnosis of adult ADHD was developed for use in the South African public healthcare sector. Results: Based on the registered medication available to treat ADHD, the consumption of methylphenidate and atomoxetine in the private healthcare sector using the Intercontinental Marketing Service database from 2013 to 2016was established. Despite the controversy regarding stimulant medication, methylphenidate was shown to be the medication of choice in South Africa. The consumption of methylphenidate (95.85%) was higher when compared to atomoxetine (4.15%) in 2013 and very slight changes were observed in 2016 were the consumption was 96.40% and 3.60%, respectively. Similarly, over a four-year period, the spend on ADHD medication increased in 2013 to 2016 by 62.63%. Furthermore, the market share for ADHD is dominated by extended-release methylphenidate tablets (59.53%). The questionnaire survey amongst selected healthcare professionals in South Africa involved in the diagnosis and treatment of adult ADHDhighlighted the tools used for diagnosis, pharmacological and non-pharmacological treatment options, which treatment has been found to be most successful, difference in treatment between genders, incorporation of supplementation into the management of patients, difficulties experienced by patients and which co-morbid conditions were also prevalent with ADHD. Based on the data collated in this study and an evaluation of the available guidelines, a framework for treatment of adult patients in the public healthcare sector has been proposed for South Africa at a provincial and national level. Conclusion: In South Africa treatment for ADHD is increasing in the private healthcare sector. The cost and consumption of methylphenidate and atomoxetine has risen over a short period. The treatment of adults in the private sector has also garnered interest, however, the public sector has not yet published guidelines enabling access to diagnosis and treatment for these adult patients. Given the chronic, costly, and debilitating nature of this condition more needs to be done to assist those affected by it. Further studies in this area of neuropsychiatry in South Africa is required to enable access to diagnosis and treatment in the public healthcare sector.
- Full Text:
- Date Issued: 2020
Attentive amelioration: developing and evaluating an applied mindfulness programme for psychologists
- Authors: McGarvie, Susan
- Date: 2020
- Subjects: Attentive Amelioration Programme , Mindfulness (Psychology) , Psychotherapy -- Practice , Counseling -- Practice , Medical professionals -- Mental health
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/166186 , vital:41336
- Description: It is readily accepted that healthcare in many third world countries is in crisis, but interestingly, even in wealthy first world countries, many healthcare systems are stretched to their limits, as fewer people choose to follow a career in healthcare and more staff members struggle under the pressures of an overextended system (Krasner, et al., 2009). Ways to improve healthcare practitioner wellbeing is thus a relevant and widely investigated topic (McCann et al., 2013), which has, until recently, been aimed at reducing the negative symptoms associated with poor wellbeing, such as stress and burnout. More recently, there has been burgeoning interest in the effects and potential benefits of mindfulness practice to wellbeing, especially in developed English-speaking countries like the UK, Canada, USA, Australia, as well as in Europe. The aim of this study was to contribute to this body of literature by proposing a more personalised and person-centred means to support and improve wellbeing. It was guided by an overarching research question, about the benefits of a mindfulness-based wellness course for practicing psychologists. This study is a mixed-methods narrative inquiry which employs both Action Research (AR) and Programme Evaluation methods. It involved the design, implementation and evaluation of a mindful-wellness programme, subsequently named the Attentive Amelioration programme. Ten participants were purposively recruited and enrolled in the programme, which ran over eight weeks and included coaching and blended learning facilitation methods, including: an introductory workshop (with a pedagogical mix of lecture, group discussion, practical activities, learners manual and YouTube clips), individual and group coaching sessions, and an online learning programme. The findings suggest that psychologists do experience a great deal of stress and perceived levels of burnout are high, even if the scores on the pre- and post- intervention self-assessment scales do not entirely support this perception. This study found that participants were open to and engaged with mindfulness training and practice and sustained that practice for several months post-intervention. Finally, overall findings suggest that while the Attentive Amelioration programme was effective as a means to cultivate and develop mindfulness, self-compassion and overall wellbeing in the short-term, further investigation is required to determine the sustainability of the effects over the long-term. The findings of this study support the overall aims of the study in that it has found that the participating psychologists found the Attentive Amelioration programme to be beneficial, supportive and even therapeutic. By contributing to and supporting findings of existing research, that suggest that a mindfulness-based coaching programme would be beneficial to psychologist wellbeing and therapeutic proficiency, it serves to advocate for mindfulness as a means to improve and sustain psychologist wellbeing..
- Full Text:
- Date Issued: 2020
Attentive amelioration: developing and evaluating an applied mindfulness programme for psychologists
- Authors: McGarvie, Susan
- Date: 2020
- Subjects: Attentive Amelioration Programme , Mindfulness (Psychology) , Psychotherapy -- Practice , Counseling -- Practice , Medical professionals -- Mental health
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/166186 , vital:41336
- Description: It is readily accepted that healthcare in many third world countries is in crisis, but interestingly, even in wealthy first world countries, many healthcare systems are stretched to their limits, as fewer people choose to follow a career in healthcare and more staff members struggle under the pressures of an overextended system (Krasner, et al., 2009). Ways to improve healthcare practitioner wellbeing is thus a relevant and widely investigated topic (McCann et al., 2013), which has, until recently, been aimed at reducing the negative symptoms associated with poor wellbeing, such as stress and burnout. More recently, there has been burgeoning interest in the effects and potential benefits of mindfulness practice to wellbeing, especially in developed English-speaking countries like the UK, Canada, USA, Australia, as well as in Europe. The aim of this study was to contribute to this body of literature by proposing a more personalised and person-centred means to support and improve wellbeing. It was guided by an overarching research question, about the benefits of a mindfulness-based wellness course for practicing psychologists. This study is a mixed-methods narrative inquiry which employs both Action Research (AR) and Programme Evaluation methods. It involved the design, implementation and evaluation of a mindful-wellness programme, subsequently named the Attentive Amelioration programme. Ten participants were purposively recruited and enrolled in the programme, which ran over eight weeks and included coaching and blended learning facilitation methods, including: an introductory workshop (with a pedagogical mix of lecture, group discussion, practical activities, learners manual and YouTube clips), individual and group coaching sessions, and an online learning programme. The findings suggest that psychologists do experience a great deal of stress and perceived levels of burnout are high, even if the scores on the pre- and post- intervention self-assessment scales do not entirely support this perception. This study found that participants were open to and engaged with mindfulness training and practice and sustained that practice for several months post-intervention. Finally, overall findings suggest that while the Attentive Amelioration programme was effective as a means to cultivate and develop mindfulness, self-compassion and overall wellbeing in the short-term, further investigation is required to determine the sustainability of the effects over the long-term. The findings of this study support the overall aims of the study in that it has found that the participating psychologists found the Attentive Amelioration programme to be beneficial, supportive and even therapeutic. By contributing to and supporting findings of existing research, that suggest that a mindfulness-based coaching programme would be beneficial to psychologist wellbeing and therapeutic proficiency, it serves to advocate for mindfulness as a means to improve and sustain psychologist wellbeing..
- Full Text:
- Date Issued: 2020
Barriers to, and enablers of urban tree planting in low-cost housing areas: lessons from participatory learning processes in South Africa
- Authors: Gwedla, Nanamhla
- Date: 2020
- Subjects: Urban ecology (Sociology) -- South Africa -- Eastern Cape , Tree planting -- South Africa -- Eastern Cape , Trees in cities -- South Africa -- Eastern Cape , Urban forestry -- Law and legislation -- South Africa -- Eastern Cape , Low-income housing -- South Africa -- Eastern Cape , Cultural Historical Activity Theory (CHAT)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/167065 , vital:41434
- Description: The recent pronouncement of low-cost housing areas as sustainable human settlements came with an expectation for their development in line with Sustainable Development Goal (SDG) 11. Unfortunately, the historical legacy and various socio-economic, socio-political, and socio-cultural dynamics characteristic of these areas have proven it challenging for them to conform to all requirements of urban sustainability, as evidenced in part by the virtual lack of greenspaces and urban trees. Through a three-tier inquiry of urban tree planting in low-cost housing areas using inductive and deductive mixed methods approaches, the aim of this research was to investigate the barriers to, and enablers of, tree planting in low-cost housing areas, and explore participatory learning opportunities to address the challenges and enhance the enablers. In the first segment, a participatory urban forest governance conceptual framing lens was used to situate the various actors in the development of the low-cost housing area urban forest and the dynamics of their involvement in that regard. Inquiry focused on an overview of tree planting across South Africa using key informant interviews, observations and document analysis. Secondly, distribution of trees, and barriers and enablers of tree planting in selected low-cost housing areas in the Eastern Cape province using household surveys, observations, key informant interviews and document analysis were investigated. Finally, drawing on interventionist methodology and adoption of Cultural-Historical Activity Theory (CHAT), the third segment tested scenarios of tree planting in three different small towns through focus group discussions and knowledge-sharing awareness events about trees and tree planting using an activity systems approach. Findings from the first segment ascertain the national Department of Environment, Forestry and Fisheries (DEFF) as the custodian of forestry, and by extension urban forestry in South Africa. Municipalities are tasked with implementing greening plans and strategies for public space planting, while private businesses collaborate with entities to contribute to tree-planting as part of their Corporate Social Responsibility (CSR). Civil society, including residents and Non-Governmental Organizations (NGOs) also contribute, especially for private space planting. However, there are currently very few initiatives implemented in low-cost housing areas. An assessment of ten tree planting initiatives revealed that the DEFF is the most common partner and stakeholder, and normally provides resources such as funding and trees. Most programs reported having undertaken community engagement before and during the tree planting. The general outcomes of these initiatives were centred on the survival rate of trees, job creation, and development of parks and gardens. Findings from the first part of the second segment, conducted in eight small-medium sized towns in the Eastern Cape, revealed a general lack of trees along streets of both the newly developed and old low-cost housing areas. In the private spaces, most households (52 %) reported having at least one tree in their yard, with households in the older suburbs (60 %) reporting more trees than the newer ones (44 %). Most of these trees (66 %) had been planted as opposed to natural regeneration. Previous participation in urban tree planting programs was low, but 75 % of residents expressed willingness to participate in the future. Municipal officials from these towns corroborated that they do not host tree planting events or initiatives, which was demonstrated by the limited incorporation of urban forestry and urban greening in municipal Integrated Development Plans (IDP). In the second part of the second segment, three groupings of barriers and enablers into biophysical, social, and resources revealed that the most mentioned barriers for the private space were resource barriers. The most prominent barriers were limited space in people’s yards, insufficient funds for tree purchases and associated resources, the lack of equipment, and damage to planted trees. Private space enablers of tree planting suggested include the availability of funds, allocation of space, and changes in attitudes towards trees. According to residents, the most prominent barriers to public space planting include the perceived incompetence of municipalities, limited space on the street, insufficient funds for tree planting programmes, damage to trees in public spaces, crime associated with street trees, and politics. Additionally, municipal officials reported that their efforts to plant trees were hindered by lack of communication and coordination between municipal departments. Residents suggested that enlisting the skills of residents for tree planting, engaging in education and awareness initiatives about trees and tree planting, and changing attitudes towards trees could enable tree planting. Municipal officials opined that education and awareness, revisions to and implementation of Environmental Management Plans, and inter-departmental collaborations and partnerships could improve the prospects for public space planting. Drawing on key findings from the second segment, an intervention to involve communities in tree planting using a case study approach in three towns ensued. Here an activity systems analysis of participatory tree planting initiatives was used. Findings revealed an array of multi-activity systems with multiple and partially overlapping objectives related to tree planting. Residents demonstrated that, with support, they can champion urban tree planting for their suburbs. However, contradictions and tensions within and between various activity systems emerged, creating opportunities for the expansive transformation of an activity that was previously not a priority. This study highlights the current distribution of power and resources in the governance system of the urban forest, ascertains the spatial heterogeneity of urban trees in areas of a similar socio-economic context, and provides lessons for best-practice in tree planting that involves multiple actors. It provides in-depth insights into what constrains tree planting, and highlights the importance of residents in the governance system of urban forests and how this can constrain or advance tree planting. Further research in participatory urban forest governance for a developing country, low-income context could utilize an expansive learning platform as this will provide first-hand experiences into learning what is not yet there, and provide communities with the opportunities to explore and devise localized solutions to the lack of trees in their residential areas.
- Full Text:
- Date Issued: 2020
- Authors: Gwedla, Nanamhla
- Date: 2020
- Subjects: Urban ecology (Sociology) -- South Africa -- Eastern Cape , Tree planting -- South Africa -- Eastern Cape , Trees in cities -- South Africa -- Eastern Cape , Urban forestry -- Law and legislation -- South Africa -- Eastern Cape , Low-income housing -- South Africa -- Eastern Cape , Cultural Historical Activity Theory (CHAT)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/167065 , vital:41434
- Description: The recent pronouncement of low-cost housing areas as sustainable human settlements came with an expectation for their development in line with Sustainable Development Goal (SDG) 11. Unfortunately, the historical legacy and various socio-economic, socio-political, and socio-cultural dynamics characteristic of these areas have proven it challenging for them to conform to all requirements of urban sustainability, as evidenced in part by the virtual lack of greenspaces and urban trees. Through a three-tier inquiry of urban tree planting in low-cost housing areas using inductive and deductive mixed methods approaches, the aim of this research was to investigate the barriers to, and enablers of, tree planting in low-cost housing areas, and explore participatory learning opportunities to address the challenges and enhance the enablers. In the first segment, a participatory urban forest governance conceptual framing lens was used to situate the various actors in the development of the low-cost housing area urban forest and the dynamics of their involvement in that regard. Inquiry focused on an overview of tree planting across South Africa using key informant interviews, observations and document analysis. Secondly, distribution of trees, and barriers and enablers of tree planting in selected low-cost housing areas in the Eastern Cape province using household surveys, observations, key informant interviews and document analysis were investigated. Finally, drawing on interventionist methodology and adoption of Cultural-Historical Activity Theory (CHAT), the third segment tested scenarios of tree planting in three different small towns through focus group discussions and knowledge-sharing awareness events about trees and tree planting using an activity systems approach. Findings from the first segment ascertain the national Department of Environment, Forestry and Fisheries (DEFF) as the custodian of forestry, and by extension urban forestry in South Africa. Municipalities are tasked with implementing greening plans and strategies for public space planting, while private businesses collaborate with entities to contribute to tree-planting as part of their Corporate Social Responsibility (CSR). Civil society, including residents and Non-Governmental Organizations (NGOs) also contribute, especially for private space planting. However, there are currently very few initiatives implemented in low-cost housing areas. An assessment of ten tree planting initiatives revealed that the DEFF is the most common partner and stakeholder, and normally provides resources such as funding and trees. Most programs reported having undertaken community engagement before and during the tree planting. The general outcomes of these initiatives were centred on the survival rate of trees, job creation, and development of parks and gardens. Findings from the first part of the second segment, conducted in eight small-medium sized towns in the Eastern Cape, revealed a general lack of trees along streets of both the newly developed and old low-cost housing areas. In the private spaces, most households (52 %) reported having at least one tree in their yard, with households in the older suburbs (60 %) reporting more trees than the newer ones (44 %). Most of these trees (66 %) had been planted as opposed to natural regeneration. Previous participation in urban tree planting programs was low, but 75 % of residents expressed willingness to participate in the future. Municipal officials from these towns corroborated that they do not host tree planting events or initiatives, which was demonstrated by the limited incorporation of urban forestry and urban greening in municipal Integrated Development Plans (IDP). In the second part of the second segment, three groupings of barriers and enablers into biophysical, social, and resources revealed that the most mentioned barriers for the private space were resource barriers. The most prominent barriers were limited space in people’s yards, insufficient funds for tree purchases and associated resources, the lack of equipment, and damage to planted trees. Private space enablers of tree planting suggested include the availability of funds, allocation of space, and changes in attitudes towards trees. According to residents, the most prominent barriers to public space planting include the perceived incompetence of municipalities, limited space on the street, insufficient funds for tree planting programmes, damage to trees in public spaces, crime associated with street trees, and politics. Additionally, municipal officials reported that their efforts to plant trees were hindered by lack of communication and coordination between municipal departments. Residents suggested that enlisting the skills of residents for tree planting, engaging in education and awareness initiatives about trees and tree planting, and changing attitudes towards trees could enable tree planting. Municipal officials opined that education and awareness, revisions to and implementation of Environmental Management Plans, and inter-departmental collaborations and partnerships could improve the prospects for public space planting. Drawing on key findings from the second segment, an intervention to involve communities in tree planting using a case study approach in three towns ensued. Here an activity systems analysis of participatory tree planting initiatives was used. Findings revealed an array of multi-activity systems with multiple and partially overlapping objectives related to tree planting. Residents demonstrated that, with support, they can champion urban tree planting for their suburbs. However, contradictions and tensions within and between various activity systems emerged, creating opportunities for the expansive transformation of an activity that was previously not a priority. This study highlights the current distribution of power and resources in the governance system of the urban forest, ascertains the spatial heterogeneity of urban trees in areas of a similar socio-economic context, and provides lessons for best-practice in tree planting that involves multiple actors. It provides in-depth insights into what constrains tree planting, and highlights the importance of residents in the governance system of urban forests and how this can constrain or advance tree planting. Further research in participatory urban forest governance for a developing country, low-income context could utilize an expansive learning platform as this will provide first-hand experiences into learning what is not yet there, and provide communities with the opportunities to explore and devise localized solutions to the lack of trees in their residential areas.
- Full Text:
- Date Issued: 2020
Between nationalism and transnationalism: entanglements of history, individual narrative, and memory in diaspora spaces in selected transnational fiction
- Authors: Bosman, Sean James
- Date: 2020
- Subjects: Literature and transnationalism , Gurnah, Abdulrazak, 1948- , Gurnah, Abdulrazak, 1948- -- By the sea , Gurnah, Abdulrazak, 1948- -- Gravel heart , Nguyen, Viet Thanh, 1971- , Nguyen, Viet Thanh, 1971- -- The sympathizer , Nguyen, Viet Thanh, 1971- -- The refugees , Urrea, Luis Alberto , Urrea, Luis Alberto -- The house of broken angels , Urrea, Luis Alberto -- The water museum
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/140932 , vital:37930
- Description: This thesis offers close readings and a comparative analysis of selected works by Abdulrazak Gurnah, Viet Thanh Nguyen, and Luis Alberto Urrea. The selected primary texts used are Gurnah’s By the Sea (2000) and Gravel Heart (2017), Nguyen’s The Sympathizer (2015) and The Refugees (2017), and Urrea’s The Water Museum (2015) and The House of Broken Angels (2018). Analyses are informed by a conceptual framework that draws on critical works by Avtar Brah, J. U. Jacobs, Sarah Nuttall, Homi K. Bhabha, Judith Butler, Stuart Hall, Paul Ricoeur, Viet Thanh Nguyen, and Christopher B. Patterson. These theories are deployed to analyse how the selected works engage with the entanglements of history, individual narratives, and memory in the diaspora spaces they articulate. The thesis argues that the selected works indicate an emerging subgenre within the broader category of transnational literature. This subgenre rejects disempowering interpolations of transnational identities. Instead, it prioritises ethical forms of memory. These acknowledge that transnational subjects share at least partial accountability for the precarity they experience in diaspora spaces. The selected literature limns how this may be accomplished by rejecting the label of victim. In so doing, the selected literature also suggests that the elevation of transnationals to full ethical agency would enable them to exercise power in their diaspora spaces. All three authorial projects studied here also give rise to uncomfortable juxtapositions that suggest a mounting fear that, as nationalisms become more pronounced in the UK and the USA, transnationals may have to re-experience conditions from which they have already fled. The thesis concludes by identifying four additional areas of confluence amongst the selected literature worthy of future study.
- Full Text:
- Date Issued: 2020
- Authors: Bosman, Sean James
- Date: 2020
- Subjects: Literature and transnationalism , Gurnah, Abdulrazak, 1948- , Gurnah, Abdulrazak, 1948- -- By the sea , Gurnah, Abdulrazak, 1948- -- Gravel heart , Nguyen, Viet Thanh, 1971- , Nguyen, Viet Thanh, 1971- -- The sympathizer , Nguyen, Viet Thanh, 1971- -- The refugees , Urrea, Luis Alberto , Urrea, Luis Alberto -- The house of broken angels , Urrea, Luis Alberto -- The water museum
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/140932 , vital:37930
- Description: This thesis offers close readings and a comparative analysis of selected works by Abdulrazak Gurnah, Viet Thanh Nguyen, and Luis Alberto Urrea. The selected primary texts used are Gurnah’s By the Sea (2000) and Gravel Heart (2017), Nguyen’s The Sympathizer (2015) and The Refugees (2017), and Urrea’s The Water Museum (2015) and The House of Broken Angels (2018). Analyses are informed by a conceptual framework that draws on critical works by Avtar Brah, J. U. Jacobs, Sarah Nuttall, Homi K. Bhabha, Judith Butler, Stuart Hall, Paul Ricoeur, Viet Thanh Nguyen, and Christopher B. Patterson. These theories are deployed to analyse how the selected works engage with the entanglements of history, individual narratives, and memory in the diaspora spaces they articulate. The thesis argues that the selected works indicate an emerging subgenre within the broader category of transnational literature. This subgenre rejects disempowering interpolations of transnational identities. Instead, it prioritises ethical forms of memory. These acknowledge that transnational subjects share at least partial accountability for the precarity they experience in diaspora spaces. The selected literature limns how this may be accomplished by rejecting the label of victim. In so doing, the selected literature also suggests that the elevation of transnationals to full ethical agency would enable them to exercise power in their diaspora spaces. All three authorial projects studied here also give rise to uncomfortable juxtapositions that suggest a mounting fear that, as nationalisms become more pronounced in the UK and the USA, transnationals may have to re-experience conditions from which they have already fled. The thesis concludes by identifying four additional areas of confluence amongst the selected literature worthy of future study.
- Full Text:
- Date Issued: 2020
Biodiversity conservation and rural livelihoods across four nature reserves in the Eastern Cape Province, South Africa: Striving towards a balance between livelihoods and conservation
- Authors: Angwenyi, Daniel
- Date: 2020
- Subjects: National parks and reserves -- South Africa -- Eastern Cape , Nature conservation -- South Africa -- Eastern Cape , Biodiversity conservation -- South Africa -- Eastern Cape , Rural population -- South Africa -- Eastern Cape , Sustainable development -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/138551 , vital:37649
- Description: The realisation that biodiversity is being lost at alarming rates, and that intact ecosystems are essential for ecological functioning and sustenance of human life, has led to biodiversity taking centre stage in national and international agencies’ environmental talks agendas. Protected areas are viable option to stem biodiversity loss. However, the establishment of protected areas might have negative impacts on communities living adjacent to them, leading to poor relations and frequent conflicts between these communities and the managers of protected areas. The Eastern Cape Province has twenty-one nature reserves and three national parks. Since the province is rural, the assumption was likelihood that households in the province depended on natural resources, specifically non-timber forest products for their day-to-day needs. Therefore, it was hypothesised that conserving natural resources, was likely to negatively impact on the livelihoods of most households adjacent to these areas, which in turn would influence their perceptions towards these resources and eventually the effectiveness of conservation efforts. This study aimed at examining the relationship between biodiversity conservation and rural livelihoods in the Eastern Cape Province, South Africa, focusing on four nature reserves – Tsolwana, Hluleka, Mkambati and Great Fish River. The objectives of the study were to: I I. Compare the vegetation productivity inside and outside, as well as land cover change in four nature reserves, as an indicator of conservation effectiveness. II II. Evaluate the relationship between biodiversity conservation and livelihoods in four nature reserves. III III. Evaluate how people’s expectations of nature reserves and perceptions towards nature reserve influence their support of conservation activities. Four hundred semi-structured questionnaires were administered to household heads of communities living at various distances from the four nature reserves, using a gradient design (based on distance). The motive of using distance was to assess whether livelihood status varied with distance from the nature reserves, since data on livelihood before the reserves’ establishment could not be obtained. Through a questionnaire survey, data on demographic information, livelihood assets, livelihood activities, livelihood strategies, livelihood trends, and impacts of the reserves on local communities were gathered. Focus group interviews were also conducted to complement the household surveys. A chi-square test was used to test if there was a relationship between distance from the reserves’ boundaries and local communities’ state of livelihoods. NVivo was used to analyse qualitative data Themes substantiated using literature. The study finds that the reserves did not have any impact on livelihood assets because most households in the study area did not directly depend on the resources found in the reserves. These households depended mostly on government grants and remittances from relatives working in other areas in the country. The reserves, however, supplied some goods and services to local communities, including meat, jobs, water, building materials, security from wild animals, education, skills development, and recreation. There were also a number of negative impacts associated with the reserves including resource use restrictions, harassment by reserves management, killing of domestic animals, and attacks on humans by wild animals escaping from the reserve. The majority (60%) of locals had substantive knowledge of the reserves’ role because of this awareness, 79% were supportive of reserves. However, there were mixed views by locals on the best way to manage these reserves. The most dominant view was that natural resources should be preserved for future generations, while meeting the current generation’s livelihood needs. Other lesser views included that the reserves’ management should involve locals in the management structures, either as active members or through consultation. Similarly, there were people feeling that the reserve is an obstacle to their livelihoods and should be closed and the land returned to the rightful owners. The vegetation productivity was better inside as compared to the outside the reserves. This activity also improved in the sixteen (16) years under assessment. This imply that the ecological functionality of the reserves is better than the surrounding areas and is improving with time. The research recommended that local communities could be an asset in conservation since most of them were in favour of the reserves. This, however, will need reserve managers to form workable partnerships with these communities, where the rights and responsibilities for both parties are defined. Besides these partnerships, lease agreements between local communities and reserves management to enhance benefits to the communities could encourage local communities to take pride in the natural resources within the reserves. This will ultimately becoming stewards to these resources. Development of tourism infrastructure such as curio shops and convenience stores to enhance livelihood opportunities could also help. For the local communities to be well represented it is important that the committees representing them in the various reserve matters be expanded and democratically elected. Where necessary, community awareness programmes on the importance of the reserves and the roles of local communities should be implemented.
- Full Text:
- Date Issued: 2020
- Authors: Angwenyi, Daniel
- Date: 2020
- Subjects: National parks and reserves -- South Africa -- Eastern Cape , Nature conservation -- South Africa -- Eastern Cape , Biodiversity conservation -- South Africa -- Eastern Cape , Rural population -- South Africa -- Eastern Cape , Sustainable development -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/138551 , vital:37649
- Description: The realisation that biodiversity is being lost at alarming rates, and that intact ecosystems are essential for ecological functioning and sustenance of human life, has led to biodiversity taking centre stage in national and international agencies’ environmental talks agendas. Protected areas are viable option to stem biodiversity loss. However, the establishment of protected areas might have negative impacts on communities living adjacent to them, leading to poor relations and frequent conflicts between these communities and the managers of protected areas. The Eastern Cape Province has twenty-one nature reserves and three national parks. Since the province is rural, the assumption was likelihood that households in the province depended on natural resources, specifically non-timber forest products for their day-to-day needs. Therefore, it was hypothesised that conserving natural resources, was likely to negatively impact on the livelihoods of most households adjacent to these areas, which in turn would influence their perceptions towards these resources and eventually the effectiveness of conservation efforts. This study aimed at examining the relationship between biodiversity conservation and rural livelihoods in the Eastern Cape Province, South Africa, focusing on four nature reserves – Tsolwana, Hluleka, Mkambati and Great Fish River. The objectives of the study were to: I I. Compare the vegetation productivity inside and outside, as well as land cover change in four nature reserves, as an indicator of conservation effectiveness. II II. Evaluate the relationship between biodiversity conservation and livelihoods in four nature reserves. III III. Evaluate how people’s expectations of nature reserves and perceptions towards nature reserve influence their support of conservation activities. Four hundred semi-structured questionnaires were administered to household heads of communities living at various distances from the four nature reserves, using a gradient design (based on distance). The motive of using distance was to assess whether livelihood status varied with distance from the nature reserves, since data on livelihood before the reserves’ establishment could not be obtained. Through a questionnaire survey, data on demographic information, livelihood assets, livelihood activities, livelihood strategies, livelihood trends, and impacts of the reserves on local communities were gathered. Focus group interviews were also conducted to complement the household surveys. A chi-square test was used to test if there was a relationship between distance from the reserves’ boundaries and local communities’ state of livelihoods. NVivo was used to analyse qualitative data Themes substantiated using literature. The study finds that the reserves did not have any impact on livelihood assets because most households in the study area did not directly depend on the resources found in the reserves. These households depended mostly on government grants and remittances from relatives working in other areas in the country. The reserves, however, supplied some goods and services to local communities, including meat, jobs, water, building materials, security from wild animals, education, skills development, and recreation. There were also a number of negative impacts associated with the reserves including resource use restrictions, harassment by reserves management, killing of domestic animals, and attacks on humans by wild animals escaping from the reserve. The majority (60%) of locals had substantive knowledge of the reserves’ role because of this awareness, 79% were supportive of reserves. However, there were mixed views by locals on the best way to manage these reserves. The most dominant view was that natural resources should be preserved for future generations, while meeting the current generation’s livelihood needs. Other lesser views included that the reserves’ management should involve locals in the management structures, either as active members or through consultation. Similarly, there were people feeling that the reserve is an obstacle to their livelihoods and should be closed and the land returned to the rightful owners. The vegetation productivity was better inside as compared to the outside the reserves. This activity also improved in the sixteen (16) years under assessment. This imply that the ecological functionality of the reserves is better than the surrounding areas and is improving with time. The research recommended that local communities could be an asset in conservation since most of them were in favour of the reserves. This, however, will need reserve managers to form workable partnerships with these communities, where the rights and responsibilities for both parties are defined. Besides these partnerships, lease agreements between local communities and reserves management to enhance benefits to the communities could encourage local communities to take pride in the natural resources within the reserves. This will ultimately becoming stewards to these resources. Development of tourism infrastructure such as curio shops and convenience stores to enhance livelihood opportunities could also help. For the local communities to be well represented it is important that the committees representing them in the various reserve matters be expanded and democratically elected. Where necessary, community awareness programmes on the importance of the reserves and the roles of local communities should be implemented.
- Full Text:
- Date Issued: 2020
Biogeographic patterns of endolithic cyanobacteria and their negative impacts on mussels along the South African coast
- Authors: Ndhlovu, Aldwin
- Date: 2020
- Subjects: Cyanobacteria -- South Africa , Cyanobacteria -- Geographical distribution , Prokaryotes -- South Africa , Mexilhao mussel -- South Africa , Mytilus galloprovincialis -- South Africa , Coastal biology -- South Africa , Coastal ecology -- South Africa , Mussels -- Geographical distribution , Mussels -- Predators of , Mussels -- Mortality -- South Africa , Mussels -- Ecology -- South Africa , Mussels -- Growth -- South Africa , Mussels -- Fertility -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/144656 , vital:38367
- Description: Endolithic cyanobacterial species occur in a wide range of environments including cold and hot deserts as well as marine systems where they attack biological material such as corals and the shells of molluscs including limpets, mussels and abalone. Endoliths live as parasites in mussel shells, where they erode and extract calcium carbonate leading to shell weakening, creating fracture holes that lead to shell collapse and death, but they also have positive effects when they lead to discolouration of mussel shells hence giving them the ability to reduce stressful heat gain during periods of extreme heat stress. Mussels are ecological engineers on which the abundance and diversity of associated species assemblages depend. Understanding how endolithic cyanobacteria affect mussels will not only help in predicting future patterns of mussel abundances, but also future patterns of the infauna that depend on them. Firstly, I identified endolithic species infesting mussels and assessed the prevalence of endolithic parasitism in two intertidal mussel species in South Africa, the native Perna perna and the invasive Mytilus galloprovincialis. Large-scale surveys of endolithic infestation of mussels were conducted along 2500 km of the South African coast, covering three biogeographic regions: the subtropical east coast, dominated by P. perna, the warm temperate south coast where the indigenous species coexists with M. galloprovincialis, and the cool temperate west coast which is dominated by M. galloprovincialis. The prevalence of endolithic infestation was higher in the cool temperate bioregion than in the warm temperate and subtropical bioregions which did not differ and for P. perna endolithic species assemblages revealed clear groupings by bioregion. Results for endolithic induced mortality followed the same trend, with no significant difference between the two mussel species where they coexist and these results attribute biogeography of endoliths to environmental factors rather than host identity. Secondly, I assessed energy budgets of infested and clean mussels, to evaluate the energetic cost of infestation. This involved measuring energy acquisition, expenditure, calculating scope for growth and lethal temperatures (LT50s). The results revealed that endolithic cyanobacteria have a negative effect on scope for growth due to increased metabolic rates for infested mussels, with no effect of endoliths on the rates or efficiency of energy acquisition through filtration and no effect on lethal temperatures. The effects of infestation were then examined in more detail through a qualitative and quantitative analysis of mussel gonads and byssal attachment strength to the substratum. Endolithic infestation was found to affect reproduction by affecting the size (mass) of gonads, but not the density of eggs within them. Attachment strength was affected by endolithic infestation with very infested mussels requiring much less force to detach them from the substratum compared to mussels with low or no infestation. These results show that endolithic infestation affects mussel fitness by directly affecting attachment strength and by reducing their reproductive output. Thirdly, endolithic succession within mussel shells was examined by assessing endolithic species composition in different regions of the shell and as a function of time. The results on the spatial distribution of endolith species within a shell supported those for temporal succession in shells deployed in the field. Endolithic species that were early colonists of clean shells were similar to those that were found in the distal edge, the new and growing region of the shell and species that arrived late in succession were similar to endolithic species found near the umbo, the oldest region of the shell. Overall, the study shows that endolithic cyanobacteria show the effects of biogeography on species distribution and clear patterns of succession within mussel shells. Cyanobacteria affect mussels negatively; they lead to low scope for growth and hence low growth rates, low reproductive output and reduced attachment strength for infested mussels. This, in turn is expected to have indirect consequences for other species that rely on mussels as ecological engineers for their survival.
- Full Text:
- Date Issued: 2020
- Authors: Ndhlovu, Aldwin
- Date: 2020
- Subjects: Cyanobacteria -- South Africa , Cyanobacteria -- Geographical distribution , Prokaryotes -- South Africa , Mexilhao mussel -- South Africa , Mytilus galloprovincialis -- South Africa , Coastal biology -- South Africa , Coastal ecology -- South Africa , Mussels -- Geographical distribution , Mussels -- Predators of , Mussels -- Mortality -- South Africa , Mussels -- Ecology -- South Africa , Mussels -- Growth -- South Africa , Mussels -- Fertility -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/144656 , vital:38367
- Description: Endolithic cyanobacterial species occur in a wide range of environments including cold and hot deserts as well as marine systems where they attack biological material such as corals and the shells of molluscs including limpets, mussels and abalone. Endoliths live as parasites in mussel shells, where they erode and extract calcium carbonate leading to shell weakening, creating fracture holes that lead to shell collapse and death, but they also have positive effects when they lead to discolouration of mussel shells hence giving them the ability to reduce stressful heat gain during periods of extreme heat stress. Mussels are ecological engineers on which the abundance and diversity of associated species assemblages depend. Understanding how endolithic cyanobacteria affect mussels will not only help in predicting future patterns of mussel abundances, but also future patterns of the infauna that depend on them. Firstly, I identified endolithic species infesting mussels and assessed the prevalence of endolithic parasitism in two intertidal mussel species in South Africa, the native Perna perna and the invasive Mytilus galloprovincialis. Large-scale surveys of endolithic infestation of mussels were conducted along 2500 km of the South African coast, covering three biogeographic regions: the subtropical east coast, dominated by P. perna, the warm temperate south coast where the indigenous species coexists with M. galloprovincialis, and the cool temperate west coast which is dominated by M. galloprovincialis. The prevalence of endolithic infestation was higher in the cool temperate bioregion than in the warm temperate and subtropical bioregions which did not differ and for P. perna endolithic species assemblages revealed clear groupings by bioregion. Results for endolithic induced mortality followed the same trend, with no significant difference between the two mussel species where they coexist and these results attribute biogeography of endoliths to environmental factors rather than host identity. Secondly, I assessed energy budgets of infested and clean mussels, to evaluate the energetic cost of infestation. This involved measuring energy acquisition, expenditure, calculating scope for growth and lethal temperatures (LT50s). The results revealed that endolithic cyanobacteria have a negative effect on scope for growth due to increased metabolic rates for infested mussels, with no effect of endoliths on the rates or efficiency of energy acquisition through filtration and no effect on lethal temperatures. The effects of infestation were then examined in more detail through a qualitative and quantitative analysis of mussel gonads and byssal attachment strength to the substratum. Endolithic infestation was found to affect reproduction by affecting the size (mass) of gonads, but not the density of eggs within them. Attachment strength was affected by endolithic infestation with very infested mussels requiring much less force to detach them from the substratum compared to mussels with low or no infestation. These results show that endolithic infestation affects mussel fitness by directly affecting attachment strength and by reducing their reproductive output. Thirdly, endolithic succession within mussel shells was examined by assessing endolithic species composition in different regions of the shell and as a function of time. The results on the spatial distribution of endolith species within a shell supported those for temporal succession in shells deployed in the field. Endolithic species that were early colonists of clean shells were similar to those that were found in the distal edge, the new and growing region of the shell and species that arrived late in succession were similar to endolithic species found near the umbo, the oldest region of the shell. Overall, the study shows that endolithic cyanobacteria show the effects of biogeography on species distribution and clear patterns of succession within mussel shells. Cyanobacteria affect mussels negatively; they lead to low scope for growth and hence low growth rates, low reproductive output and reduced attachment strength for infested mussels. This, in turn is expected to have indirect consequences for other species that rely on mussels as ecological engineers for their survival.
- Full Text:
- Date Issued: 2020
Bioinformatic analysis of Aminoacyl tRNA Synthetases as potential antimalarial drug targets
- Authors: Nyamai, Dorothy Wavinya
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164579 , vital:41142 , doi:10.21504/10962/164579
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Nyamai, Dorothy Wavinya
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164579 , vital:41142 , doi:10.21504/10962/164579
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
BODIPY dyes for use in nonlinear optics and optical sensing
- Authors: Kubheka, Gugu Patience
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163352 , vital:41032 , doi:10.21504/10962/163352
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Department of Chemistry, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Kubheka, Gugu Patience
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163352 , vital:41032 , doi:10.21504/10962/163352
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Department of Chemistry, 2020.
- Full Text:
- Date Issued: 2020
Carnivore intra-guild competition in Selati Game Reserve, Limpopo Province, South Africa
- Authors: Comley, Jessica
- Date: 2020
- Subjects: Hyenas -- Behavior -- South Africa , Hyenas -- South Africa , Hyenas -- Ecology -- South Africa , Top predators -- South Africa , Top predators -- Ecology -- South Africa , Animal communities -- South Africa , Animal behavior -- South Africa , Mutualism (Biology) -- South Africa , Coexistence of species -- South Africa , Game farms -- South Africa , Selati Game Reserve (South Africa)
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/115558 , vital:34163
- Description: Carnivore intra-guild interactions can be important drivers of carnivore community composition and ecosystem functioning. Large carnivores are particularly important since they occupy the highest trophic levels and can exert extensive influences on subordinate carnivores and prey species. Given Africa’s rapidly expanding human population, enclosed reserves such as those found in South Africa, may become increasingly important for carnivore conservation. A major concern, however, is that the interactions and co-existence of multiple carnivores in these systems is poorly understood. Additionally, the majority of reserves in South Africa are small ( 400km²), potentially increasing the likelihood of competition. My research aimed to provide insight into the interactions and co-existence of a multi-carnivore community within a small, enclosed reserve in South Africa (Selati Game Reserve). I tackled this task by using a combination of field techniques including camera trap surveys, ungulate transect surveys, aerial count surveys, location data collected from collared large carnivores and scat and kill site analyses. I found that carnivore-carnivore interactions, and their associated impacts, varied within the carnivore guild and that co-existence may be due to trade-offs between various risks (i.e. interference and exploitative competition) and benefits (i.e. resources such as food and space). My findings also revealed that large carnivores, such as lions (Panthera leo), spotted hyaenas (Crocuta crocuta) and leopards (Panthera pardus) do not have homogenous effects and that site-specific research on multiple-carnivores is integral for conserving biodiversity and ecosystem dynamics. Lions were the dominant large carnivore (in terms of intra-guild predation, space use and resource use) despite being outnumbered seven to one by spotted hyaenas. Leopard occupancy was negatively influenced by lions and leopard diet overlapped almost completely (91%) with spotted hyaenas, suggesting increased kleptoparasitism of leopard kills by spotted hyaenas. While my study provides valuable insight into the complexity of carnivore intra-guild competition in a small, enclosed reserve it also highlights major research gaps and emphasises the need for ecosystem-based research throughout southern Africa to fully understand how multiple sympatric carnivores co-exist in these systems.
- Full Text:
- Date Issued: 2020
- Authors: Comley, Jessica
- Date: 2020
- Subjects: Hyenas -- Behavior -- South Africa , Hyenas -- South Africa , Hyenas -- Ecology -- South Africa , Top predators -- South Africa , Top predators -- Ecology -- South Africa , Animal communities -- South Africa , Animal behavior -- South Africa , Mutualism (Biology) -- South Africa , Coexistence of species -- South Africa , Game farms -- South Africa , Selati Game Reserve (South Africa)
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/115558 , vital:34163
- Description: Carnivore intra-guild interactions can be important drivers of carnivore community composition and ecosystem functioning. Large carnivores are particularly important since they occupy the highest trophic levels and can exert extensive influences on subordinate carnivores and prey species. Given Africa’s rapidly expanding human population, enclosed reserves such as those found in South Africa, may become increasingly important for carnivore conservation. A major concern, however, is that the interactions and co-existence of multiple carnivores in these systems is poorly understood. Additionally, the majority of reserves in South Africa are small ( 400km²), potentially increasing the likelihood of competition. My research aimed to provide insight into the interactions and co-existence of a multi-carnivore community within a small, enclosed reserve in South Africa (Selati Game Reserve). I tackled this task by using a combination of field techniques including camera trap surveys, ungulate transect surveys, aerial count surveys, location data collected from collared large carnivores and scat and kill site analyses. I found that carnivore-carnivore interactions, and their associated impacts, varied within the carnivore guild and that co-existence may be due to trade-offs between various risks (i.e. interference and exploitative competition) and benefits (i.e. resources such as food and space). My findings also revealed that large carnivores, such as lions (Panthera leo), spotted hyaenas (Crocuta crocuta) and leopards (Panthera pardus) do not have homogenous effects and that site-specific research on multiple-carnivores is integral for conserving biodiversity and ecosystem dynamics. Lions were the dominant large carnivore (in terms of intra-guild predation, space use and resource use) despite being outnumbered seven to one by spotted hyaenas. Leopard occupancy was negatively influenced by lions and leopard diet overlapped almost completely (91%) with spotted hyaenas, suggesting increased kleptoparasitism of leopard kills by spotted hyaenas. While my study provides valuable insight into the complexity of carnivore intra-guild competition in a small, enclosed reserve it also highlights major research gaps and emphasises the need for ecosystem-based research throughout southern Africa to fully understand how multiple sympatric carnivores co-exist in these systems.
- Full Text:
- Date Issued: 2020
Child marriage as a hindrance to the realisation of child rights in Zimbabwe: consolidated approaches towards eradication
- Authors: Ndhlovu, Ntandokayise
- Date: 2020
- Subjects: Teenage marriage Children's rights
- Language: English
- Type: Thesis , Doctoral , LLD
- Identifier: http://hdl.handle.net/10353/18359 , vital:42256
- Description: Child marriage is defined as any marriage where one of the spouses is younger than 18 years old. A number of deep, complex, interrelated and interlinked factors are responsible for the practice in Zimbabwe and elsewhere. These include the weak enforcement of existing laws, legal contradictions, slow alignment of laws to the Constitution and international child rights, entrenched harmful religious and cultural practices, and acute poverty. It was at the fulcrum of this dissertation thus to examine the unfair limitations caused by child marriage, on the realisation and enjoyment of child rights in Zimbabwe. The United Nations International Children’s Emergency Fund reported an estimated 31 percent prevalence of the scourge in the country. These percentages translate to millions of children, and the numbers could be on the rise. Child marriage has intense consequences for the realisation and enjoyment of rights by many children in Zimbabwe. Of note, child marriage ends childhoods. It impairs the children’s right to education, minimises their economic opportunities and fair chances in life, and increases their vulnerability to domestic violence, marital rape and sexually transmitted diseases. The grave ramifications of child marriage, in terms of the realisation of child rights have led to a number of international, regional and national efforts to curb this scourge. However, owing to an array of multifaceted and complex causes, the practice remains highly prevalent in Zimbabwe. After decades of side-lining, child rights in Zimbabwe, have finally gained constitutional protection under the 2013 Constitution. While the comprehensive protection of child rights as justiciable rights is an acceptable standard, a plethora of practices such as child marriage are a practical and real threat to the realisation of these rights. Therefore, it is incumbent upon Zimbabwe to ensure that child rights as stipulated in the Constitution are respected, promoted, protected and fulfilled. The elimination of child marriage is a daunting yet possible task. Through desktop based qualitative research, this dissertation ascertained the main drivers of the practice in the country, and its impact on the realisation of fundamental child rights in Zimbabwe. The study further explored the contribution, as well as the insufficiencies of International and African Human Rights systems, to the protection of children from child marriage. It also assesses the prospects and challenges of the existing domestic (legislative and constitutional norms) in protecting child rights in the Southern African country. The impetus behind this iii examination is to recommend a comprehensive and holistic effort to curb child marriage and suggest a consolidated legal and non-legal approach to end it
- Full Text:
- Date Issued: 2020
- Authors: Ndhlovu, Ntandokayise
- Date: 2020
- Subjects: Teenage marriage Children's rights
- Language: English
- Type: Thesis , Doctoral , LLD
- Identifier: http://hdl.handle.net/10353/18359 , vital:42256
- Description: Child marriage is defined as any marriage where one of the spouses is younger than 18 years old. A number of deep, complex, interrelated and interlinked factors are responsible for the practice in Zimbabwe and elsewhere. These include the weak enforcement of existing laws, legal contradictions, slow alignment of laws to the Constitution and international child rights, entrenched harmful religious and cultural practices, and acute poverty. It was at the fulcrum of this dissertation thus to examine the unfair limitations caused by child marriage, on the realisation and enjoyment of child rights in Zimbabwe. The United Nations International Children’s Emergency Fund reported an estimated 31 percent prevalence of the scourge in the country. These percentages translate to millions of children, and the numbers could be on the rise. Child marriage has intense consequences for the realisation and enjoyment of rights by many children in Zimbabwe. Of note, child marriage ends childhoods. It impairs the children’s right to education, minimises their economic opportunities and fair chances in life, and increases their vulnerability to domestic violence, marital rape and sexually transmitted diseases. The grave ramifications of child marriage, in terms of the realisation of child rights have led to a number of international, regional and national efforts to curb this scourge. However, owing to an array of multifaceted and complex causes, the practice remains highly prevalent in Zimbabwe. After decades of side-lining, child rights in Zimbabwe, have finally gained constitutional protection under the 2013 Constitution. While the comprehensive protection of child rights as justiciable rights is an acceptable standard, a plethora of practices such as child marriage are a practical and real threat to the realisation of these rights. Therefore, it is incumbent upon Zimbabwe to ensure that child rights as stipulated in the Constitution are respected, promoted, protected and fulfilled. The elimination of child marriage is a daunting yet possible task. Through desktop based qualitative research, this dissertation ascertained the main drivers of the practice in the country, and its impact on the realisation of fundamental child rights in Zimbabwe. The study further explored the contribution, as well as the insufficiencies of International and African Human Rights systems, to the protection of children from child marriage. It also assesses the prospects and challenges of the existing domestic (legislative and constitutional norms) in protecting child rights in the Southern African country. The impetus behind this iii examination is to recommend a comprehensive and holistic effort to curb child marriage and suggest a consolidated legal and non-legal approach to end it
- Full Text:
- Date Issued: 2020
CO2-induced woody thickening depends strongly on interacting abiotic and biotic factors
- Authors: Raubenheimer, Sarah Lynn
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164646 , vital:41151 , doi:10.21504/10962/164646
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Botany, 2020
- Full Text:
- Date Issued: 2020
- Authors: Raubenheimer, Sarah Lynn
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164646 , vital:41151 , doi:10.21504/10962/164646
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Botany, 2020
- Full Text:
- Date Issued: 2020
Commercial maritime higher education needs in South Africa
- Authors: Allison, Lee-Ann
- Date: 2020
- Subjects: Marine resources
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/47496 , vital:40117
- Description: Seaborne cargo trade accounts for over 80% of the physical volume of global trade. Maritime transport thus fulfills an integral function in the economy of the world. South Africa generates approximately 3.5% of the world’s seaborne trade by value and 1.61% by tonnage, but the business of shipping all that cargo is undertaken by foreign firms. Operation Phakisa, the Comprehensive Maritime Transport Policy, and the South African Maritime Road Map, in pursuance of the National Development Plan, aim to revive the commercial maritime sector. In order to meet the demand for the skills and innovative abilities sought at executive and managerial levels in the commercial maritime sector, higher education in the knowledge of maritime business is increasingly becoming a prerequisite. Investment in higher education of quality and relevance in the maritime field would contribute to achieving the goals of the government for harnessing the potential of South Africa’s blue economy. The literature is researched in order to establish an authoritative view that the knowledge and the inspiration for entrepreneurial activity in the maritime sector can be imparted through higher education; and for example, that a viable shipping sector can contribute to the growth of a country’s economy. The South African maritime sector is then described. The commercial maritime higher education available at universities and other institutions of higher learning in South Africa, as well as in other African countries and elsewhere in the world, is examined, in order to be able to identify the degree and diploma courses available. Maritime courses imply not only the content of the educational material, but also the method whereby the knowledge is instilled in learners, and which extends well beyond the classroom. A survey, by way of the personal interviews of leaders in maritime business, maritime government affairs, and academics teaching maritime topics, is then undertaken to ascertain their views on the education required to promote the maritime sector in South Africa, using the list of subjects available for study worldwide, to assist their choice. The literature research and the interview survey by design also enable the secondary aims of the study to be achieved. Those aims include determining how awareness of the maritime domain could be raised and how co-operation between academia, business, and government, known as the triple helix could be organized, to promote the growth of the maritime sector. The results of the survey are analyzed and tabulated, in order to illustrate the extent of the agreement between those interviewed and the conclusions reached. These conclusions establish: (i) that the commercial maritime education currently available in South Africa, is inadequate to meet the aim of the government to the sector; (ii) that a post-graduate degree iv in the specified maritime studies incorporating a period of internship, and following on the first degree in business subjects, is required; (iii) that a triple helix of co-operation between academia, business, and the government is essential to grow the commercial maritime sector in which South African entrepreneurs educated in such business will have the advantage; (iv) that greater awareness of the maritime domain is essential in South Africa if entrepreneurship in maritime business is to be cultivated; and (v)that such awareness can be cultivated in various ways; but it should start by including more maritime topics in the current school curricula.
- Full Text:
- Date Issued: 2020
- Authors: Allison, Lee-Ann
- Date: 2020
- Subjects: Marine resources
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/47496 , vital:40117
- Description: Seaborne cargo trade accounts for over 80% of the physical volume of global trade. Maritime transport thus fulfills an integral function in the economy of the world. South Africa generates approximately 3.5% of the world’s seaborne trade by value and 1.61% by tonnage, but the business of shipping all that cargo is undertaken by foreign firms. Operation Phakisa, the Comprehensive Maritime Transport Policy, and the South African Maritime Road Map, in pursuance of the National Development Plan, aim to revive the commercial maritime sector. In order to meet the demand for the skills and innovative abilities sought at executive and managerial levels in the commercial maritime sector, higher education in the knowledge of maritime business is increasingly becoming a prerequisite. Investment in higher education of quality and relevance in the maritime field would contribute to achieving the goals of the government for harnessing the potential of South Africa’s blue economy. The literature is researched in order to establish an authoritative view that the knowledge and the inspiration for entrepreneurial activity in the maritime sector can be imparted through higher education; and for example, that a viable shipping sector can contribute to the growth of a country’s economy. The South African maritime sector is then described. The commercial maritime higher education available at universities and other institutions of higher learning in South Africa, as well as in other African countries and elsewhere in the world, is examined, in order to be able to identify the degree and diploma courses available. Maritime courses imply not only the content of the educational material, but also the method whereby the knowledge is instilled in learners, and which extends well beyond the classroom. A survey, by way of the personal interviews of leaders in maritime business, maritime government affairs, and academics teaching maritime topics, is then undertaken to ascertain their views on the education required to promote the maritime sector in South Africa, using the list of subjects available for study worldwide, to assist their choice. The literature research and the interview survey by design also enable the secondary aims of the study to be achieved. Those aims include determining how awareness of the maritime domain could be raised and how co-operation between academia, business, and government, known as the triple helix could be organized, to promote the growth of the maritime sector. The results of the survey are analyzed and tabulated, in order to illustrate the extent of the agreement between those interviewed and the conclusions reached. These conclusions establish: (i) that the commercial maritime education currently available in South Africa, is inadequate to meet the aim of the government to the sector; (ii) that a post-graduate degree iv in the specified maritime studies incorporating a period of internship, and following on the first degree in business subjects, is required; (iii) that a triple helix of co-operation between academia, business, and the government is essential to grow the commercial maritime sector in which South African entrepreneurs educated in such business will have the advantage; (iv) that greater awareness of the maritime domain is essential in South Africa if entrepreneurship in maritime business is to be cultivated; and (v)that such awareness can be cultivated in various ways; but it should start by including more maritime topics in the current school curricula.
- Full Text:
- Date Issued: 2020
Commercial maritime higher education needs in South Africa
- Authors: Allison, Lee-Anne
- Date: 2020
- Subjects: Education, Higher -- Curricula , Education, Higher -- Research Merchant marine Shipping -- Economic aspects
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/50350 , vital:42111
- Description: Seaborne cargo trade accounts for over 80% of the physical volume of global trade. Maritime transport thus fulfils an integral function in the economy of the world. South Africa generates approximately 3.5% of the world’s seaborne trade by value and 1.61% by tonnage; but the business of shipping all that cargo is undertaken by foreign firms. Operation Phakisa, the Comprehensive Maritime Transport Policy and the South African Maritime Road Map, in pursuance of the National Development Plan, aim to revive the commercial maritime sector. In order to meet the demand for the skills and innovative abilities sought at executive and managerial levels in the commercial maritime sector, higher education in the knowledge of maritime business is increasingly becoming a prerequisite. Investment in higher education of quality and relevance in the maritime field would contribute to achieving the goals of the government for harnessing the potential of South Africa’s blue economy. The literature is researched in order to establish an authoritative view that the knowledge and the inspiration for entrepreneurial activity in the maritime sector can be imparted through higher education; and for example, that a viable shipping sector can contribute to the growth of a country’s economy. The South African maritime sector is then described. The commercial maritime higher education available at universities and other institutions of higher learning in South Africa, as well as in other African countries and elsewhere in the world, is examined, in order to be able to identify the degree and diploma courses available. Maritime courses imply not only the content of the educational material, but also the method whereby the knowledge is instilled in learners, and which extends well beyond the classroom. A survey, by way of the personal interviews of leaders in maritime business, maritime government affairs, and academics teaching maritime topics, is then undertaken to ascertain their views on the education required to promote the maritime sector in South Africa, using the list of subjects available for study worldwide, to assist their choice. The literature research and the interview survey by design also enable the secondary aims of the study to be achieved. Those aims include determining how awareness of the maritime domain could be raised and how co-operation between academia, business and government, known as the triple helix could be organised, to promote the growth of the maritime sector. The results of the survey are analysed and tabulated, in order to illustrate the extent of the agreement between those interviewed and the conclusions reached. These conclusions establish: that the commercial maritime education currently available in South Africa, is inadequate to meet the aim of the government to the sector; that a post-graduate degree in the specified maritime studies incorporating a period of internship, and following on a first degree in business subjects, is required; that a triple helix of co-operation between academia, business and the government is essential to grow the commercial maritime sector in which South African entrepreneurs educated in such business will have the advantage; that greater awareness of the maritime domain is essential in South Africa if entrepreneurship in maritime business is to be cultivated; and that such awareness can be cultivated in various ways; but it should start by including more maritime topics in the current school curricula.
- Full Text:
- Date Issued: 2020
- Authors: Allison, Lee-Anne
- Date: 2020
- Subjects: Education, Higher -- Curricula , Education, Higher -- Research Merchant marine Shipping -- Economic aspects
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/50350 , vital:42111
- Description: Seaborne cargo trade accounts for over 80% of the physical volume of global trade. Maritime transport thus fulfils an integral function in the economy of the world. South Africa generates approximately 3.5% of the world’s seaborne trade by value and 1.61% by tonnage; but the business of shipping all that cargo is undertaken by foreign firms. Operation Phakisa, the Comprehensive Maritime Transport Policy and the South African Maritime Road Map, in pursuance of the National Development Plan, aim to revive the commercial maritime sector. In order to meet the demand for the skills and innovative abilities sought at executive and managerial levels in the commercial maritime sector, higher education in the knowledge of maritime business is increasingly becoming a prerequisite. Investment in higher education of quality and relevance in the maritime field would contribute to achieving the goals of the government for harnessing the potential of South Africa’s blue economy. The literature is researched in order to establish an authoritative view that the knowledge and the inspiration for entrepreneurial activity in the maritime sector can be imparted through higher education; and for example, that a viable shipping sector can contribute to the growth of a country’s economy. The South African maritime sector is then described. The commercial maritime higher education available at universities and other institutions of higher learning in South Africa, as well as in other African countries and elsewhere in the world, is examined, in order to be able to identify the degree and diploma courses available. Maritime courses imply not only the content of the educational material, but also the method whereby the knowledge is instilled in learners, and which extends well beyond the classroom. A survey, by way of the personal interviews of leaders in maritime business, maritime government affairs, and academics teaching maritime topics, is then undertaken to ascertain their views on the education required to promote the maritime sector in South Africa, using the list of subjects available for study worldwide, to assist their choice. The literature research and the interview survey by design also enable the secondary aims of the study to be achieved. Those aims include determining how awareness of the maritime domain could be raised and how co-operation between academia, business and government, known as the triple helix could be organised, to promote the growth of the maritime sector. The results of the survey are analysed and tabulated, in order to illustrate the extent of the agreement between those interviewed and the conclusions reached. These conclusions establish: that the commercial maritime education currently available in South Africa, is inadequate to meet the aim of the government to the sector; that a post-graduate degree in the specified maritime studies incorporating a period of internship, and following on a first degree in business subjects, is required; that a triple helix of co-operation between academia, business and the government is essential to grow the commercial maritime sector in which South African entrepreneurs educated in such business will have the advantage; that greater awareness of the maritime domain is essential in South Africa if entrepreneurship in maritime business is to be cultivated; and that such awareness can be cultivated in various ways; but it should start by including more maritime topics in the current school curricula.
- Full Text:
- Date Issued: 2020
Comparative analysis of the known Hop1b and the novel Hop1a isoforms of the Hop gene
- Authors: Makhubu, Portia
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164311 , vital:41108 , doi:10.21504/10962/164311
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Makhubu, Portia
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164311 , vital:41108 , doi:10.21504/10962/164311
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Comprehensive characterization of the antidiabetic potential of selected plants and macrofungi from Africa using an in vitro target-directed screening platform and cellomics
- Authors: Pringle, Nadine Alex
- Date: 2020
- Subjects: Hypoglycemic agents
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/46750 , vital:39653
- Description: Several synthetic antidiabetic drugs have been developed to date, however, most are accompanied by adverse side-effects while remaining expensive and largely inaccessible to the vast majority of those who need it. To provide enough scientific evidence to support the inclusion of more affordable African antidiabetic medicinal plants and macrofungi into healthcare programs, this study sought out to develop a comprehensive in vitro antidiabetic target-directed screening platform incorporating high content screening and analysis/ cellomics. To test the success of this model, the potential antidiabetic mechanisms of five plants (Aspalathus linearis, Brachylaena discolor, Carpobrotus deliciosus, Sutherlandia frutescens and Tarchonanthus camphoratus) and two macrofungal species (Ganoderma lucidum and Hericium erinaceus) were explored. The screening model consisted of approximately 22 assays exploring the antidiabetic effects of selected aqueous and ethanolic extracts in five well-characterised antidiabetic targets: the intestine, liver, skeletal muscle, adipose tissue/ obesity and pancreatic β-cells. These targets were further categorised and scored under three mechanistic classes/ therapeutic targets (postprandial hyperglycaemia; insulin resistance and inflammation; pancreatic β-cell function) to elucidate their potential mechanisms of action and select appropriate animal models for future studies. Almost any normal or diabetic rodent model would be suitable to explore the antidiabetic potential of extracts such as A. linearis, B. discolor ethanol, C. deliciosus ethanol or T. camphoratus which obtained high cumulative scores under postprandial hyperglycaemia while high fat diet and genetic models of obesity appear more suited towards extracts such as H. erinaceus aqueous that obtained their highest cumulative score under insulin resistance. In general, a combination of rodent models ranging from non-obese models to models of obesity and β-cell destruction presenting symptoms from all three mechanistic classes should be considered due to the pleiotropic nature of the tested extracts, however, establishing appropriate experimental designs is crucial. To demonstrate the versatility of the screening platform and emphasise the importance of in vitro screening pertaining to diabetic complications, a more detailed biochemical investigation into the potential therapeutic benefits of A. linearis in the treatment of diabetic wounds was conducted. Several properties supporting the therapeutic potential of rooibos were highlighted with the green and fermented extracts presenting distinctly different characteristics. The pro-inflammatory nature of fermented rooibos may have therapeutic value for wounds characterised with a delayed initial inflammatory phase, such as early diabetic wounds while the green extract appears more suited to wounds burdened with excessive inflammation as it attenuated COX-2 levels and effectively protected fibroblasts against oxidative stress. To date, this appears to be the most comprehensive antidiabetic screening platform in existence and consequently provides the only feasible solution that will enable natural product antidiabetic research to progress to the point where natural products can be commercialised and incorporated into meaningful healthcare programs. Future research should be focussed towards further expanding this model by incorporating additional targets, more sophisticated cell culturing techniques, multiplexed high content screening assays and carrying out combination treatments that explore the antidiabetic effects of two or more crude extracts to establish whether they are capable of acting in a synergistic manner.
- Full Text:
- Date Issued: 2020
- Authors: Pringle, Nadine Alex
- Date: 2020
- Subjects: Hypoglycemic agents
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/46750 , vital:39653
- Description: Several synthetic antidiabetic drugs have been developed to date, however, most are accompanied by adverse side-effects while remaining expensive and largely inaccessible to the vast majority of those who need it. To provide enough scientific evidence to support the inclusion of more affordable African antidiabetic medicinal plants and macrofungi into healthcare programs, this study sought out to develop a comprehensive in vitro antidiabetic target-directed screening platform incorporating high content screening and analysis/ cellomics. To test the success of this model, the potential antidiabetic mechanisms of five plants (Aspalathus linearis, Brachylaena discolor, Carpobrotus deliciosus, Sutherlandia frutescens and Tarchonanthus camphoratus) and two macrofungal species (Ganoderma lucidum and Hericium erinaceus) were explored. The screening model consisted of approximately 22 assays exploring the antidiabetic effects of selected aqueous and ethanolic extracts in five well-characterised antidiabetic targets: the intestine, liver, skeletal muscle, adipose tissue/ obesity and pancreatic β-cells. These targets were further categorised and scored under three mechanistic classes/ therapeutic targets (postprandial hyperglycaemia; insulin resistance and inflammation; pancreatic β-cell function) to elucidate their potential mechanisms of action and select appropriate animal models for future studies. Almost any normal or diabetic rodent model would be suitable to explore the antidiabetic potential of extracts such as A. linearis, B. discolor ethanol, C. deliciosus ethanol or T. camphoratus which obtained high cumulative scores under postprandial hyperglycaemia while high fat diet and genetic models of obesity appear more suited towards extracts such as H. erinaceus aqueous that obtained their highest cumulative score under insulin resistance. In general, a combination of rodent models ranging from non-obese models to models of obesity and β-cell destruction presenting symptoms from all three mechanistic classes should be considered due to the pleiotropic nature of the tested extracts, however, establishing appropriate experimental designs is crucial. To demonstrate the versatility of the screening platform and emphasise the importance of in vitro screening pertaining to diabetic complications, a more detailed biochemical investigation into the potential therapeutic benefits of A. linearis in the treatment of diabetic wounds was conducted. Several properties supporting the therapeutic potential of rooibos were highlighted with the green and fermented extracts presenting distinctly different characteristics. The pro-inflammatory nature of fermented rooibos may have therapeutic value for wounds characterised with a delayed initial inflammatory phase, such as early diabetic wounds while the green extract appears more suited to wounds burdened with excessive inflammation as it attenuated COX-2 levels and effectively protected fibroblasts against oxidative stress. To date, this appears to be the most comprehensive antidiabetic screening platform in existence and consequently provides the only feasible solution that will enable natural product antidiabetic research to progress to the point where natural products can be commercialised and incorporated into meaningful healthcare programs. Future research should be focussed towards further expanding this model by incorporating additional targets, more sophisticated cell culturing techniques, multiplexed high content screening assays and carrying out combination treatments that explore the antidiabetic effects of two or more crude extracts to establish whether they are capable of acting in a synergistic manner.
- Full Text:
- Date Issued: 2020
Computer aided approaches against Human African Trypanosomiasis
- Authors: Kimuda, Magambo Phillip
- Date: 2020
- Subjects: African trypanosomiasis , African trypanosomiasis -- Chemotherapy , Genomics , Macrophage migration inhibitory factor , Trypanosoma brucei , Pteridines , Tetrahydrofolate dehydrogenase , Adenylic acid , Molecular dynamics , Principal components analysis , Bioinformatics , Single nucleotide polymorphisms , Single Nucleotide Variants , Candidate Gene Association Study (CGAS)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/142542 , vital:38089
- Description: The thesis presented here is divided into two parts under a common theme that is the use of computer based tools, genomics, and in vitro experiments to develop innovative ways of tackling Human African Trypanosomiasis (HAT). Part I of this thesis focused on the human host genetic determinants while Part II focused on the discovery of novel chemotherapeutics against the parasite. Part I is further sub-divided into two parts: The first involves a Candidate Gene Association Study (CGAS) on an African population to identify genetic determinants associated with disease and/or susceptibility to HAT. The second involves studying the effects of missense Single Nucleotide Variants (SNVs) on protein structure, dynamics, and function using Macrophage Migration Inhibitory Factor (MIF) as a case study. Part II is also sub-divided into two parts: The first involves a computer based rational drug discovery of potential inhibitors against the Trypanosoma the folate pathway; particularly by targeting Trypanosoma brucei Pteridine Reductase (TbPTR1) which is an enzyme used by trypanosomes to overcome T. brucei Dihydrofolate Reductase (TbDHFR) inhibition. Lastly the derivation of CHARMM force-field parameters that can be used to accurately model the geometry and dynamics of the T. brucei Phosphodiesterase B1 enzyme (TbrPDEB1) bimetallic active site center. The derived parameters were then used in MD simulations to characterise protein-ligand residue interactions that are important in TbrPDEB1 inhibition with the goal of targeting the cyclic Adenosine Monophosphate (cAMP) signalling pathway. In the CGAS we were unable to detect any genetic associations in the Ugandan cohort analysed that passed correction for multiple testing in spite of the study being sufficiently powered. Additionally, our study found no association of the Apo lipoprotein 1 (APOL1) G2 allele association with protection against acute HAT that has been previously reported. Future investigations for example, Genome Wide Association Studies using larger samples sizes (>3000 cases and controls) are required. Macrophage migration inhibitory factor (MIF) is a cytokine that is important in both innate and adaptive immunity that has been shown to play a role in T. brucei pathogenicity using murine models. A total of 27 missense SNVs were modelled using homology modelling to create MIF protein mutants that were investigated using in silico effect prediction tools, molecular dynamics (MD), Principal Component Analysis (PCA), and Dynamic Residue Network (DRN) analysis. Our results demonstrate that mutations P2Q, I5M, P16Q, L23F, T24S, T31I, Y37H, H41P, M48V, P44L, G52C, S54R, I65M, I68T, S75F, N106S, and T113S caused significant conformational changes. Further, DRN analysis showed that residues P2, T31, Y37, G52, I65, I68, S75, N106, and T113S are part of a similar local residue interaction network with functional significance. These results show how polymorphisms such as missense SNVs can affect protein conformation, dynamics, and function. Trypanosomes are auxotrophic for folates and pterins but require them for survival. They scavenge them from their hosts. PTR1 is a multifunctional enzyme that is unique to trypanosomatids that reduces both pterins and folates. In the presence of DHFR inhibitors, PTR1 is over-expressed thus providing an escape from the effects of DHFR inhibition. Both TbPTR1 and TbDHFR are pharmacologically and genetically validated drug targets. In this study 5742 compounds were screened using molecular docking, and 13 promising binding modes were further analysed using MD simulations. The trajectories were analysed using RMSD, Rg, RMSF, PCA, Essential Dynamics Analysis (EDA), Molecular Mechanics Poisson–Boltzmann surface area (MM-PBSA) binding free energy calculations, and DRN analysis. The computational screening approach allowed us to identify five of the compounds, named RUBi004, RUBi007, RUBi014, RUBi016 and RUBi018 that exhibited antitrypanosomal growth activities against trypanosomes in culture with IC50 values of 12.5 ± 4.8 μM, 32.4 ± 4.2 μM, 5.9 ± 1.4 μM, 28.2 ± 3.3 μM, and 9.7 ± 2.1 μM, respectively. Further when used in combination with WR99210 a known TbDHFR inhibitor RUBi004, RUBi007, RUBi014 and RUBi018 showed antagonism while RUBi016 showed an additive effect. These results indicate that the four compounds might be competing with TbDHFR while RUBi016 might be more specific for TbPTR1. These compounds provide scaffolds that can be further optimised to improve their potency and specificity. Lastly, using a systematic approach we derived CHARMM force-field parameters to accurately describe the TbrPDEB1 bi-metal catalytic center. For dynamics, we employed mixed bonded and non-bonded approach. We optimised the structure using a two-layer QM/MM ONIOM (B3LYP/6-31(g): UFF). The TbrPDEB1 bi-metallic center bonds, angles, and dihedrals were parameterized by fitting the energy profiles from Potential Energy Surface (PES) scans to the CHARMM potential energy function. The parameters were validated by means of MD simulations and analysed using RMSD, Rg, RMSF, hydrogen bonding, bond/angle/dihedral evaluations, EDA, PCA, and DRN analysis. The force-field parameters were able to accurately reproduce the geometry and dynamics of the TbrPDEB1 bi-metal catalytic center during MD simulations. Molecular docking was used to identify 6 potential hits, that inhibited trypanosome growth in vitro. The derived force-field parameters were used to simulate the 6 protein-ligand complexes with the aim of elucidating crucial protein-ligand residue interactions. Using the most potent ligand RUBi022 that had an IC50 of 14.96 μM we were able to identify key residue interactions that can be of use in in silico prediction of potential TbrPDEB1 inhibitors. Overall we demonstrate how bioinformatics tools can complement current disease eradication strategies. Future work will focus on identifying variants identified in Genome Wide Association Studies and partnering with wet labs to carry out further enzyme-ligand activity relationship studies, structure determination or characterisation of appropriate protein-ligand complexes by crystallography, and site specific mutation studies
- Full Text:
- Date Issued: 2020
- Authors: Kimuda, Magambo Phillip
- Date: 2020
- Subjects: African trypanosomiasis , African trypanosomiasis -- Chemotherapy , Genomics , Macrophage migration inhibitory factor , Trypanosoma brucei , Pteridines , Tetrahydrofolate dehydrogenase , Adenylic acid , Molecular dynamics , Principal components analysis , Bioinformatics , Single nucleotide polymorphisms , Single Nucleotide Variants , Candidate Gene Association Study (CGAS)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/142542 , vital:38089
- Description: The thesis presented here is divided into two parts under a common theme that is the use of computer based tools, genomics, and in vitro experiments to develop innovative ways of tackling Human African Trypanosomiasis (HAT). Part I of this thesis focused on the human host genetic determinants while Part II focused on the discovery of novel chemotherapeutics against the parasite. Part I is further sub-divided into two parts: The first involves a Candidate Gene Association Study (CGAS) on an African population to identify genetic determinants associated with disease and/or susceptibility to HAT. The second involves studying the effects of missense Single Nucleotide Variants (SNVs) on protein structure, dynamics, and function using Macrophage Migration Inhibitory Factor (MIF) as a case study. Part II is also sub-divided into two parts: The first involves a computer based rational drug discovery of potential inhibitors against the Trypanosoma the folate pathway; particularly by targeting Trypanosoma brucei Pteridine Reductase (TbPTR1) which is an enzyme used by trypanosomes to overcome T. brucei Dihydrofolate Reductase (TbDHFR) inhibition. Lastly the derivation of CHARMM force-field parameters that can be used to accurately model the geometry and dynamics of the T. brucei Phosphodiesterase B1 enzyme (TbrPDEB1) bimetallic active site center. The derived parameters were then used in MD simulations to characterise protein-ligand residue interactions that are important in TbrPDEB1 inhibition with the goal of targeting the cyclic Adenosine Monophosphate (cAMP) signalling pathway. In the CGAS we were unable to detect any genetic associations in the Ugandan cohort analysed that passed correction for multiple testing in spite of the study being sufficiently powered. Additionally, our study found no association of the Apo lipoprotein 1 (APOL1) G2 allele association with protection against acute HAT that has been previously reported. Future investigations for example, Genome Wide Association Studies using larger samples sizes (>3000 cases and controls) are required. Macrophage migration inhibitory factor (MIF) is a cytokine that is important in both innate and adaptive immunity that has been shown to play a role in T. brucei pathogenicity using murine models. A total of 27 missense SNVs were modelled using homology modelling to create MIF protein mutants that were investigated using in silico effect prediction tools, molecular dynamics (MD), Principal Component Analysis (PCA), and Dynamic Residue Network (DRN) analysis. Our results demonstrate that mutations P2Q, I5M, P16Q, L23F, T24S, T31I, Y37H, H41P, M48V, P44L, G52C, S54R, I65M, I68T, S75F, N106S, and T113S caused significant conformational changes. Further, DRN analysis showed that residues P2, T31, Y37, G52, I65, I68, S75, N106, and T113S are part of a similar local residue interaction network with functional significance. These results show how polymorphisms such as missense SNVs can affect protein conformation, dynamics, and function. Trypanosomes are auxotrophic for folates and pterins but require them for survival. They scavenge them from their hosts. PTR1 is a multifunctional enzyme that is unique to trypanosomatids that reduces both pterins and folates. In the presence of DHFR inhibitors, PTR1 is over-expressed thus providing an escape from the effects of DHFR inhibition. Both TbPTR1 and TbDHFR are pharmacologically and genetically validated drug targets. In this study 5742 compounds were screened using molecular docking, and 13 promising binding modes were further analysed using MD simulations. The trajectories were analysed using RMSD, Rg, RMSF, PCA, Essential Dynamics Analysis (EDA), Molecular Mechanics Poisson–Boltzmann surface area (MM-PBSA) binding free energy calculations, and DRN analysis. The computational screening approach allowed us to identify five of the compounds, named RUBi004, RUBi007, RUBi014, RUBi016 and RUBi018 that exhibited antitrypanosomal growth activities against trypanosomes in culture with IC50 values of 12.5 ± 4.8 μM, 32.4 ± 4.2 μM, 5.9 ± 1.4 μM, 28.2 ± 3.3 μM, and 9.7 ± 2.1 μM, respectively. Further when used in combination with WR99210 a known TbDHFR inhibitor RUBi004, RUBi007, RUBi014 and RUBi018 showed antagonism while RUBi016 showed an additive effect. These results indicate that the four compounds might be competing with TbDHFR while RUBi016 might be more specific for TbPTR1. These compounds provide scaffolds that can be further optimised to improve their potency and specificity. Lastly, using a systematic approach we derived CHARMM force-field parameters to accurately describe the TbrPDEB1 bi-metal catalytic center. For dynamics, we employed mixed bonded and non-bonded approach. We optimised the structure using a two-layer QM/MM ONIOM (B3LYP/6-31(g): UFF). The TbrPDEB1 bi-metallic center bonds, angles, and dihedrals were parameterized by fitting the energy profiles from Potential Energy Surface (PES) scans to the CHARMM potential energy function. The parameters were validated by means of MD simulations and analysed using RMSD, Rg, RMSF, hydrogen bonding, bond/angle/dihedral evaluations, EDA, PCA, and DRN analysis. The force-field parameters were able to accurately reproduce the geometry and dynamics of the TbrPDEB1 bi-metal catalytic center during MD simulations. Molecular docking was used to identify 6 potential hits, that inhibited trypanosome growth in vitro. The derived force-field parameters were used to simulate the 6 protein-ligand complexes with the aim of elucidating crucial protein-ligand residue interactions. Using the most potent ligand RUBi022 that had an IC50 of 14.96 μM we were able to identify key residue interactions that can be of use in in silico prediction of potential TbrPDEB1 inhibitors. Overall we demonstrate how bioinformatics tools can complement current disease eradication strategies. Future work will focus on identifying variants identified in Genome Wide Association Studies and partnering with wet labs to carry out further enzyme-ligand activity relationship studies, structure determination or characterisation of appropriate protein-ligand complexes by crystallography, and site specific mutation studies
- Full Text:
- Date Issued: 2020