Factors influencing the number of non-timber forest product species used at the individual, household and village levels in Vhembe, Limpopo Province, South Africa
- Authors: Mulaudzi, Takalani Rachel
- Date: 2023-03-29
- Subjects: Non-timber forest products South Africa Vhembe District Municipality , Household ecology , Principal components analysis , Detrended Correspondence Analysis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/422481 , vital:71946
- Description: Non-Timber Forest Products (NTFPs) are wild biological resources obtained from natural landscapes, agricultural systems, and rural and urban regions for a variety of uses. NTFPs contribute significantly to livelihoods and living standards by offering a variety of socioeconomic benefits such as food, health, income generation, and safety nets. These multiple benefits are provided by a wide diversity of plant, animal and fungal species in different settings. However, the precise number of NTFP species used depends on the scale of assessment, namely use by individuals, by households and by villages. Consequently, it is difficult to compare numbers of species used between studies because of the differing scales. As a result, the objective of this study was to determine the number of NTFP species used at three different scales and how each is correlated with appropriate scale-dependent contextual variables. This objective was met by sampling individuals and whole households in five villages in the Vhembe District in Limpopo Province, South Africa. Twenty households were randomly selected in each village, providing a total sample of 100 households and 179 individuals in those households. In each household, every adult member was interviewed individually about the NTFPs that they used or knew. The major questions covered the NTFP species used, the respondents' socioeconomic level, the NTFP species used previously, and if the number of NTFP species are changing in the landscape. Data were reported per individual as well as per household and per village. The household level was derived by adding the responses of all the adults in each household but excluding duplicates. The same approach was used at the village scale, namely, the data across the 20 households were pooled, and duplicates were omitted. Patterns of NTFP use were examined by type of NTFP, and analysis using standard statistical tests, along with a Principal Components Analysis and a multivariate Detrended Correspondence Analysis of the NTFP species composition across villages. A total of 275 species of NTFPs were mentioned across the entire sample, including 81 species of firewood, 48 species of edible insects, 43 species of wild vegetables, 40 species of edible fruits, 38 species of wood utensils, 28 species of medicinal plants, 23 species of thatch grass, 19 species of poles, 19 species of wood for carvings, nine species of reeds, eight species of mushroom, and eight species of fodder. Of these species, some species had more than one use. Approximately 90% of the species used by the respondents were native species. Wild vegetables (e.g., Corchorus olitorius, Amaranthus capensis, Bidens pilosa), firewood (e.g., Colophospermum mopane, Parinari curatellifolia, Combretum hereroense), wild fruit (e.g., Landolphia kirkii, Vangueria infausta), and edible insects (e.g., Imbrasia belina, Macrotermes michaelseni, Encosternum delegorguei) were the most often used NTFPs by communities in the Vhembe area. Most of the households relied on NTFPs for subsistence. At the scale of an individual, the mean number of NTFP species used was 26.8±12.6 across the five villages. When considering a household, the mean number was 36.1±10.7 species. When aggregated across the 20 households per village, the mean number per village was 105.2±34.1 species. The species accumulation curve showed that 20 households per village were reasonably representative for four of the five villages. The results from the principal component analysis (PCA) and correlation analysis revealed that age, education, and employment status were significantly associated with the number of species used by individuals, whereas gender showed no clear correlation. At the household scale, household size was positively related with the number of species used, but income level and income source were not. At the village scale, attributes such as proximity to a town, settlement type, vegetation type, and distance to a nearby savanna all had some influence on the number of NTFP species listed. Most of the respondents felt that the number of species used had increased over the last 10–15 years, although some stated the opposite. Increases were attributed by traditional councils bans, the establishment of protected areas, and restoration. Activities eroding the number of NTFP species were identified as clear felling for farming, climate change, and over-harvesting. This study suggests that communities must be made more aware of the overharvesting of NTFP species in the savanna to avoid biodiversity loss. , Thesis (MSc) -- Faculty of Science, Environmental Science, 2023
- Full Text:
- Authors: Mulaudzi, Takalani Rachel
- Date: 2023-03-29
- Subjects: Non-timber forest products South Africa Vhembe District Municipality , Household ecology , Principal components analysis , Detrended Correspondence Analysis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/422481 , vital:71946
- Description: Non-Timber Forest Products (NTFPs) are wild biological resources obtained from natural landscapes, agricultural systems, and rural and urban regions for a variety of uses. NTFPs contribute significantly to livelihoods and living standards by offering a variety of socioeconomic benefits such as food, health, income generation, and safety nets. These multiple benefits are provided by a wide diversity of plant, animal and fungal species in different settings. However, the precise number of NTFP species used depends on the scale of assessment, namely use by individuals, by households and by villages. Consequently, it is difficult to compare numbers of species used between studies because of the differing scales. As a result, the objective of this study was to determine the number of NTFP species used at three different scales and how each is correlated with appropriate scale-dependent contextual variables. This objective was met by sampling individuals and whole households in five villages in the Vhembe District in Limpopo Province, South Africa. Twenty households were randomly selected in each village, providing a total sample of 100 households and 179 individuals in those households. In each household, every adult member was interviewed individually about the NTFPs that they used or knew. The major questions covered the NTFP species used, the respondents' socioeconomic level, the NTFP species used previously, and if the number of NTFP species are changing in the landscape. Data were reported per individual as well as per household and per village. The household level was derived by adding the responses of all the adults in each household but excluding duplicates. The same approach was used at the village scale, namely, the data across the 20 households were pooled, and duplicates were omitted. Patterns of NTFP use were examined by type of NTFP, and analysis using standard statistical tests, along with a Principal Components Analysis and a multivariate Detrended Correspondence Analysis of the NTFP species composition across villages. A total of 275 species of NTFPs were mentioned across the entire sample, including 81 species of firewood, 48 species of edible insects, 43 species of wild vegetables, 40 species of edible fruits, 38 species of wood utensils, 28 species of medicinal plants, 23 species of thatch grass, 19 species of poles, 19 species of wood for carvings, nine species of reeds, eight species of mushroom, and eight species of fodder. Of these species, some species had more than one use. Approximately 90% of the species used by the respondents were native species. Wild vegetables (e.g., Corchorus olitorius, Amaranthus capensis, Bidens pilosa), firewood (e.g., Colophospermum mopane, Parinari curatellifolia, Combretum hereroense), wild fruit (e.g., Landolphia kirkii, Vangueria infausta), and edible insects (e.g., Imbrasia belina, Macrotermes michaelseni, Encosternum delegorguei) were the most often used NTFPs by communities in the Vhembe area. Most of the households relied on NTFPs for subsistence. At the scale of an individual, the mean number of NTFP species used was 26.8±12.6 across the five villages. When considering a household, the mean number was 36.1±10.7 species. When aggregated across the 20 households per village, the mean number per village was 105.2±34.1 species. The species accumulation curve showed that 20 households per village were reasonably representative for four of the five villages. The results from the principal component analysis (PCA) and correlation analysis revealed that age, education, and employment status were significantly associated with the number of species used by individuals, whereas gender showed no clear correlation. At the household scale, household size was positively related with the number of species used, but income level and income source were not. At the village scale, attributes such as proximity to a town, settlement type, vegetation type, and distance to a nearby savanna all had some influence on the number of NTFP species listed. Most of the respondents felt that the number of species used had increased over the last 10–15 years, although some stated the opposite. Increases were attributed by traditional councils bans, the establishment of protected areas, and restoration. Activities eroding the number of NTFP species were identified as clear felling for farming, climate change, and over-harvesting. This study suggests that communities must be made more aware of the overharvesting of NTFP species in the savanna to avoid biodiversity loss. , Thesis (MSc) -- Faculty of Science, Environmental Science, 2023
- Full Text:
A systematic methodology to evaluating optimised machine learning based network intrusion detection systems
- Authors: Chindove, Hatitye Ethridge
- Date: 2022-10-14
- Subjects: Intrusion detection systems (Computer security) , Machine learning , Computer networks Security measures , Principal components analysis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362774 , vital:65361
- Description: A network intrusion detection system (NIDS) is essential for mitigating computer network attacks in various scenarios. However, the increasing complexity of computer networks and attacks makes classifying unseen or novel network traffic challenging. Supervised machine learning techniques (ML) used in a NIDS can be affected by different scenarios. Thus, dataset recency, size, and applicability are essential factors when selecting and tuning a machine learning classifier. This thesis explores developing and optimising several supervised ML algorithms with relatively new datasets constructed to depict real-world scenarios. The methodology includes empirical analyses of systematic ML-based NIDS for a near real-world network system to improve intrusion detection. The thesis is experimental heavy for model assessment. Data preparation methods are explored, followed by feature engineering techniques. The model evaluation process involves three experiments testing against a validation, un-trained, and retrained set. They compare several traditional machine learning and deep learning classifiers to identify the best NIDS model. Results show that the focus on feature scaling, feature selection methods and ML algo- rithm hyper-parameter tuning per model is an essential optimisation component. Distance based ML algorithm performed much better with quantile transformation whilst the tree based algorithms performed better without scaling. Permutation importance performs as a feature selection method compared to feature extraction using Principal Component Analysis (PCA) when applied against all ML algorithms explored. Random forests, Sup- port Vector Machines and recurrent neural networks consistently achieved the best results with high macro f1-score results of 90% 81% and 73% for the CICIDS 2017 dataset; and 72% 68% and 73% against the CICIDS 2018 dataset. , Thesis (MSc) -- Faculty of Science, Computer Science, 2022
- Full Text:
- Authors: Chindove, Hatitye Ethridge
- Date: 2022-10-14
- Subjects: Intrusion detection systems (Computer security) , Machine learning , Computer networks Security measures , Principal components analysis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362774 , vital:65361
- Description: A network intrusion detection system (NIDS) is essential for mitigating computer network attacks in various scenarios. However, the increasing complexity of computer networks and attacks makes classifying unseen or novel network traffic challenging. Supervised machine learning techniques (ML) used in a NIDS can be affected by different scenarios. Thus, dataset recency, size, and applicability are essential factors when selecting and tuning a machine learning classifier. This thesis explores developing and optimising several supervised ML algorithms with relatively new datasets constructed to depict real-world scenarios. The methodology includes empirical analyses of systematic ML-based NIDS for a near real-world network system to improve intrusion detection. The thesis is experimental heavy for model assessment. Data preparation methods are explored, followed by feature engineering techniques. The model evaluation process involves three experiments testing against a validation, un-trained, and retrained set. They compare several traditional machine learning and deep learning classifiers to identify the best NIDS model. Results show that the focus on feature scaling, feature selection methods and ML algo- rithm hyper-parameter tuning per model is an essential optimisation component. Distance based ML algorithm performed much better with quantile transformation whilst the tree based algorithms performed better without scaling. Permutation importance performs as a feature selection method compared to feature extraction using Principal Component Analysis (PCA) when applied against all ML algorithms explored. Random forests, Sup- port Vector Machines and recurrent neural networks consistently achieved the best results with high macro f1-score results of 90% 81% and 73% for the CICIDS 2017 dataset; and 72% 68% and 73% against the CICIDS 2018 dataset. , Thesis (MSc) -- Faculty of Science, Computer Science, 2022
- Full Text:
Rural households’ perceptions of an invasive alien species rosa rubiginosa l. (rosehip) and the role it plays in rural livelihoods in Lesotho
- Authors: Makhorole, Thato Violet
- Date: 2022-10-14
- Subjects: Rose hips Lesotho , Invasive plants Lesotho , Rural poor Lesotho , Probit model , Principal components analysis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/403069 , vital:69919
- Description: Despite the vast research on the negative impacts of invasive alien species on the environment, these species remain part of the rural communities due to their numerous livelihood uses. Thus, more research is required, focusing mainly on the impacts of invasive alien species on the livelihoods of rural communities. This study investigated the community perceptions of rosehip (Rosa rubiginosa) and its contribution to rural communities as an invasive alien species. Four community councils, Pitseng, Matlameng, Limamarela and Mphorosane in the Leribe District Lesotho, were assessed. The study followed the pragmatism paradigm. The contribution of rosehip to rural livelihoods was analysed by comparing income from rosehip with other income sources. The study used simple random sampling and snowball sampling to select a representative of 160 respondents. The primary data was collected using semi-structured questionnaires. Moreover, SPSS and Stata statistical package programs were used for statistical analyses. The results showed that rosehip's livelihood benefits, its negative impacts, the length of time it has been available in the area, and its abundance highly influence the social, economic and environmental perception of rural communities. Furthermore, the study revealed that although the income from rosehip is extremely low and available for only three months of the year, the income plays an important part to the poorer households who have no other income sources. The study found that the main reason for engagement in rosehip harvesting despite its challenging nature was unemployment. The study also revealed that rosehip is part of the risk-reducing strategy or income diversification. Some households used it to complement other sources of income, such as agricultural production. Rosehip trade, if well-controlled, has the potential to alleviate rural poverty by creating job opportunities, providing a source of household income, and acting as a safety net in the face of shocks such as limited job opportunities and food shortages. In conclusion, households’ perceptions of rosehip have proven that rosehip is a valuable resource that provides a supplementary income that contributes towards alleviating poverty in Lesotho’s rural communities. The study recommends the private sector to establish and manages small agro-processing industries focusing on products used daily. The study also encourages environmental education and indigenous knowledge among community members, which would include knowledge and recognition of invasive alien species and their potential benefits and threats. , Thesis (MEcon) -- Faculty of Commerce, Economics and Economic History, 2022
- Full Text:
- Authors: Makhorole, Thato Violet
- Date: 2022-10-14
- Subjects: Rose hips Lesotho , Invasive plants Lesotho , Rural poor Lesotho , Probit model , Principal components analysis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/403069 , vital:69919
- Description: Despite the vast research on the negative impacts of invasive alien species on the environment, these species remain part of the rural communities due to their numerous livelihood uses. Thus, more research is required, focusing mainly on the impacts of invasive alien species on the livelihoods of rural communities. This study investigated the community perceptions of rosehip (Rosa rubiginosa) and its contribution to rural communities as an invasive alien species. Four community councils, Pitseng, Matlameng, Limamarela and Mphorosane in the Leribe District Lesotho, were assessed. The study followed the pragmatism paradigm. The contribution of rosehip to rural livelihoods was analysed by comparing income from rosehip with other income sources. The study used simple random sampling and snowball sampling to select a representative of 160 respondents. The primary data was collected using semi-structured questionnaires. Moreover, SPSS and Stata statistical package programs were used for statistical analyses. The results showed that rosehip's livelihood benefits, its negative impacts, the length of time it has been available in the area, and its abundance highly influence the social, economic and environmental perception of rural communities. Furthermore, the study revealed that although the income from rosehip is extremely low and available for only three months of the year, the income plays an important part to the poorer households who have no other income sources. The study found that the main reason for engagement in rosehip harvesting despite its challenging nature was unemployment. The study also revealed that rosehip is part of the risk-reducing strategy or income diversification. Some households used it to complement other sources of income, such as agricultural production. Rosehip trade, if well-controlled, has the potential to alleviate rural poverty by creating job opportunities, providing a source of household income, and acting as a safety net in the face of shocks such as limited job opportunities and food shortages. In conclusion, households’ perceptions of rosehip have proven that rosehip is a valuable resource that provides a supplementary income that contributes towards alleviating poverty in Lesotho’s rural communities. The study recommends the private sector to establish and manages small agro-processing industries focusing on products used daily. The study also encourages environmental education and indigenous knowledge among community members, which would include knowledge and recognition of invasive alien species and their potential benefits and threats. , Thesis (MEcon) -- Faculty of Commerce, Economics and Economic History, 2022
- Full Text:
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:
- 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:
Targeting allosteric sites of Escherichia coli heat shock protein 70 for antibiotic development
- Authors: Okeke, Chiamaka Jessica
- Date: 2019
- Subjects: Heat shock proteins , Escherichia coli , Allosteric proteins , Antibiotics , Molecular chaperones , Ligands (Biochemistry) , Molecular dynamics , Principal components analysis , South African Natural Compounds Database
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/115998 , vital:34287
- Description: Hsp70s are members of the heat shock proteins family with a molecular weight of 70-kDa and are the most abundant group in bacterial and eukaryotic systems, hence the most extensively studied ones. These proteins are molecular chaperones that play a significant role in protein homeostasis by facilitating appropriate folding of proteins, preventing proteins from aggregating and misfolding. They are also involved in translocation of proteins into subcellular compartments and protection of cells against stress. Stress caused by environmental or biological factors affects the functionality of the cell. In response to these stressful conditions, up-regulation of Hsp70s ensures that the cells are protected by balancing out unfolded proteins giving them ample time to repair denatured proteins. Hsp70s is connected to numerous illnesses such as autoimmune and neurodegenerative diseases, bacterial infection, cancer, malaria, and obesity. The multi-functional nature of Hsp70s predisposes them as promising therapeutic targets. Hsp70s play vital roles in various cell developments, and survival pathways, therefore targeting this protein will provide a new avenue towards the discovery of active therapeutic agents for the treatment of a wide range of diseases. Allosteric sites of these proteins in its multi-conformational states have not been explored for inhibitory properties hence the aim of this study. This study aims at identifying allosteric sites that inhibit the ATPase and substrate binding activities using computational approaches. Using E. coli as a model organism, molecular docking for high throughput virtual screening was carried out using 623 compounds from the South African Natural Compounds Database (SANCDB; https://sancdb.rubi.ru.ac.za/) against identified allosteric sites. Ligands with the highest binding affinity (good binders) interacting with critical allosteric residues that are druggable were identified. Molecular dynamics (MD) simulation was also performed on the identified hits to assess for protein-inhibitor complex stability. Finally, principal component analysis (PCA) was performed to understand the structural dynamics of the ligand-free and ligand-bound structures during MD simulation.
- Full Text:
- Authors: Okeke, Chiamaka Jessica
- Date: 2019
- Subjects: Heat shock proteins , Escherichia coli , Allosteric proteins , Antibiotics , Molecular chaperones , Ligands (Biochemistry) , Molecular dynamics , Principal components analysis , South African Natural Compounds Database
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/115998 , vital:34287
- Description: Hsp70s are members of the heat shock proteins family with a molecular weight of 70-kDa and are the most abundant group in bacterial and eukaryotic systems, hence the most extensively studied ones. These proteins are molecular chaperones that play a significant role in protein homeostasis by facilitating appropriate folding of proteins, preventing proteins from aggregating and misfolding. They are also involved in translocation of proteins into subcellular compartments and protection of cells against stress. Stress caused by environmental or biological factors affects the functionality of the cell. In response to these stressful conditions, up-regulation of Hsp70s ensures that the cells are protected by balancing out unfolded proteins giving them ample time to repair denatured proteins. Hsp70s is connected to numerous illnesses such as autoimmune and neurodegenerative diseases, bacterial infection, cancer, malaria, and obesity. The multi-functional nature of Hsp70s predisposes them as promising therapeutic targets. Hsp70s play vital roles in various cell developments, and survival pathways, therefore targeting this protein will provide a new avenue towards the discovery of active therapeutic agents for the treatment of a wide range of diseases. Allosteric sites of these proteins in its multi-conformational states have not been explored for inhibitory properties hence the aim of this study. This study aims at identifying allosteric sites that inhibit the ATPase and substrate binding activities using computational approaches. Using E. coli as a model organism, molecular docking for high throughput virtual screening was carried out using 623 compounds from the South African Natural Compounds Database (SANCDB; https://sancdb.rubi.ru.ac.za/) against identified allosteric sites. Ligands with the highest binding affinity (good binders) interacting with critical allosteric residues that are druggable were identified. Molecular dynamics (MD) simulation was also performed on the identified hits to assess for protein-inhibitor complex stability. Finally, principal component analysis (PCA) was performed to understand the structural dynamics of the ligand-free and ligand-bound structures during MD simulation.
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An analysis of the long run comovements between financial system development and mining production in South Africa
- Authors: Ajagbe, Stephen Mayowa
- Date: 2011
- Subjects: Economic development -- South Africa , Econometric models , Mineral industries -- Economic aspects -- South Africa , South Africa -- Economic conditions , South Africa -- Economic policy , Principal components analysis , Cointegration , Stock exchanges -- South Africa , Banks and banking -- South Africa , Foreign exchange rates
- Language: English
- Type: Thesis , Masters , MCom
- Identifier: vital:955 , http://hdl.handle.net/10962/d1002689 , Economic development -- South Africa , Econometric models , Mineral industries -- Economic aspects -- South Africa , South Africa -- Economic conditions , South Africa -- Economic policy , Principal components analysis , Cointegration , Stock exchanges -- South Africa , Banks and banking -- South Africa , Foreign exchange rates
- Description: This study examines the nature of the relationship which exists between mining sector production and development of the financial systems in South Africa. This is particularly important in that the mining sector is considered to be one of the major contributors to the country’s overall economic growth. South Africa is also considered to have a very well developed financial system, to the point where the dominance of one over the other is difficult to identify. Therefore offering insight into the nature of this relationship will assist policy makers in identifying the most effective policies in order to ensure that the developments within the financial systems impact appropriately on the mining sector, and ultimately on the economy. In addition to using the conventional proxies of financial system development, this study utilises the principal component analysis (PCA) to construct an index for the entire financial system. The multivariate cointegration approach as proposed by Johansen (1988) and Johansen and Juselius (1990) was then used to estimate the relationship between the development of the financial systems and the mining sector production for the period 1988-2008. The study reveals mixed results for different measures of financial system development. Those involving the banking system show that a negative relationship exists between total mining production and total credit extended to the private sector, while liquid liabilities has a positive relationship. Similarly, with the stock market system, mixed results are also obtained which reveal a negative relationship between total mining production and stock market capitalisation, while a positive relationship is found with secondary market turnover. Of all the financial system variables, only that of stock market capitalisation was found to be significant. The result with the financial development index reveals that a significant negative relationship exists between financial system development and total mining sector production. Results on the other variables controlled in the estimation show that positive and significant relationships exist between total mining production and both nominal exchange rate and political stability respectively. Increased mining production therefore takes place in periods of appreciating exchange rates, and similarly in the post-apartheid era. On the other hand, negative relationships were found for both trade openness and inflation control variables. The impulse response and variance decomposition analyses showed that total mining production explains the largest amount of shocks within itself. Overall, the study reveals that the mining sector might not have benefited much from the development in the South African financial system.
- Full Text:
- Authors: Ajagbe, Stephen Mayowa
- Date: 2011
- Subjects: Economic development -- South Africa , Econometric models , Mineral industries -- Economic aspects -- South Africa , South Africa -- Economic conditions , South Africa -- Economic policy , Principal components analysis , Cointegration , Stock exchanges -- South Africa , Banks and banking -- South Africa , Foreign exchange rates
- Language: English
- Type: Thesis , Masters , MCom
- Identifier: vital:955 , http://hdl.handle.net/10962/d1002689 , Economic development -- South Africa , Econometric models , Mineral industries -- Economic aspects -- South Africa , South Africa -- Economic conditions , South Africa -- Economic policy , Principal components analysis , Cointegration , Stock exchanges -- South Africa , Banks and banking -- South Africa , Foreign exchange rates
- Description: This study examines the nature of the relationship which exists between mining sector production and development of the financial systems in South Africa. This is particularly important in that the mining sector is considered to be one of the major contributors to the country’s overall economic growth. South Africa is also considered to have a very well developed financial system, to the point where the dominance of one over the other is difficult to identify. Therefore offering insight into the nature of this relationship will assist policy makers in identifying the most effective policies in order to ensure that the developments within the financial systems impact appropriately on the mining sector, and ultimately on the economy. In addition to using the conventional proxies of financial system development, this study utilises the principal component analysis (PCA) to construct an index for the entire financial system. The multivariate cointegration approach as proposed by Johansen (1988) and Johansen and Juselius (1990) was then used to estimate the relationship between the development of the financial systems and the mining sector production for the period 1988-2008. The study reveals mixed results for different measures of financial system development. Those involving the banking system show that a negative relationship exists between total mining production and total credit extended to the private sector, while liquid liabilities has a positive relationship. Similarly, with the stock market system, mixed results are also obtained which reveal a negative relationship between total mining production and stock market capitalisation, while a positive relationship is found with secondary market turnover. Of all the financial system variables, only that of stock market capitalisation was found to be significant. The result with the financial development index reveals that a significant negative relationship exists between financial system development and total mining sector production. Results on the other variables controlled in the estimation show that positive and significant relationships exist between total mining production and both nominal exchange rate and political stability respectively. Increased mining production therefore takes place in periods of appreciating exchange rates, and similarly in the post-apartheid era. On the other hand, negative relationships were found for both trade openness and inflation control variables. The impulse response and variance decomposition analyses showed that total mining production explains the largest amount of shocks within itself. Overall, the study reveals that the mining sector might not have benefited much from the development in the South African financial system.
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Integration between the South African and international bond markets : implications for portfolio diversification
- Authors: Rabana, Phomolo
- Date: 2009
- Subjects: Bond market , Bond market -- South Africa , Principal components analysis , International finance , Foreign exchange rates -- South Africa , Investments -- South Africa
- Language: English
- Type: Thesis , Masters , MCom
- Identifier: vital:947 , http://hdl.handle.net/10962/d1002681 , Bond market , Bond market -- South Africa , Principal components analysis , International finance , Foreign exchange rates -- South Africa , Investments -- South Africa
- Description: International bond market linkages are examined using monthly bond yield data and total return indices on government bonds with ten years to maturity. The bond yield data covers a nineteen-year period from January 1990 to July 2008, while the bond total return index data covers a nine-year period from August 2000 to July 2008. The international bond markets included in the study are Australia, Canada, Germany, Japan, the United Kingdom, and the United States. The examination of international bond market linkages across these markets has important implications for the formulation of effective portfolio diversification strategies. The empirical analysis is carried out in three phases: the preliminary analysis, the principal component analysis (PCA), and the cointegration analysis. For each analysis and for each set of data the full sample period is first analysed and subsequently a five-year rolling window approach is implemented. Accordingly, this makes it possible to capture the time-varying nature of international bond market linkages. The preliminary analysis examines the bond market trends over the sample period, provides descriptive statistics, and reports the correlation coefficients between the selected bond markets. The PCA investigates the interrelationships among the bond markets according to their common sources of movement and identifies which markets tend to move together. The cointegration analysis is carried out using the Johansen cointegration procedure and investigates whether there is long-run comovement between South Africa and the selected bond markets. Where cointegration is found, Vector Error-Correction Models (VECMs) are estimated in order to examine the long-run equilibrium relationships in addition to their short-run adjustments over time. The empirical analysis results were robust, and overall integration between SA and the selected major bond markets remained weak and sporadic. In addition, the results showed that even after accounting for exchange rate differentials, international bond market diversification remained beneficial for a South African investor; and since international bond market linkages remained weak with no observable trend, international bond market diversification will remain beneficial for some time to come for a South African investor.
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- Authors: Rabana, Phomolo
- Date: 2009
- Subjects: Bond market , Bond market -- South Africa , Principal components analysis , International finance , Foreign exchange rates -- South Africa , Investments -- South Africa
- Language: English
- Type: Thesis , Masters , MCom
- Identifier: vital:947 , http://hdl.handle.net/10962/d1002681 , Bond market , Bond market -- South Africa , Principal components analysis , International finance , Foreign exchange rates -- South Africa , Investments -- South Africa
- Description: International bond market linkages are examined using monthly bond yield data and total return indices on government bonds with ten years to maturity. The bond yield data covers a nineteen-year period from January 1990 to July 2008, while the bond total return index data covers a nine-year period from August 2000 to July 2008. The international bond markets included in the study are Australia, Canada, Germany, Japan, the United Kingdom, and the United States. The examination of international bond market linkages across these markets has important implications for the formulation of effective portfolio diversification strategies. The empirical analysis is carried out in three phases: the preliminary analysis, the principal component analysis (PCA), and the cointegration analysis. For each analysis and for each set of data the full sample period is first analysed and subsequently a five-year rolling window approach is implemented. Accordingly, this makes it possible to capture the time-varying nature of international bond market linkages. The preliminary analysis examines the bond market trends over the sample period, provides descriptive statistics, and reports the correlation coefficients between the selected bond markets. The PCA investigates the interrelationships among the bond markets according to their common sources of movement and identifies which markets tend to move together. The cointegration analysis is carried out using the Johansen cointegration procedure and investigates whether there is long-run comovement between South Africa and the selected bond markets. Where cointegration is found, Vector Error-Correction Models (VECMs) are estimated in order to examine the long-run equilibrium relationships in addition to their short-run adjustments over time. The empirical analysis results were robust, and overall integration between SA and the selected major bond markets remained weak and sporadic. In addition, the results showed that even after accounting for exchange rate differentials, international bond market diversification remained beneficial for a South African investor; and since international bond market linkages remained weak with no observable trend, international bond market diversification will remain beneficial for some time to come for a South African investor.
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DRUBIS : a distributed face-identification experimentation framework - design, implementation and performance issues
- Authors: Ndlangisa, Mboneli
- Date: 2004
- Subjects: Principal components analysis , Human face recognition (Computer science) , Image processing , Biometric identification
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4704 , http://hdl.handle.net/10962/d1015768
- Description: We report on the design, implementation and performance issues of the DRUBIS (Distributed Rhodes University Biometric Identification System) experimentation framework. The Principal Component Analysis (PCA) face-recognition approach is used as a case study. DRUBIS is a flexible experimentation framework, distributed over a number of modules that are easily pluggable and swappable, allowing for the easy construction of prototype systems. Web services are the logical means of distributing DRUBIS components and a number of prototype applications have been implemented from this framework. Different popular PCA face-recognition related experiments were used to evaluate our experimentation framework. We extract recognition performance measures from these experiments. In particular, we use the framework for a more indepth study of the suitability of the DFFS (Difference From Face Space) metric as a means for image classification in the area of race and gender determination.
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- Authors: Ndlangisa, Mboneli
- Date: 2004
- Subjects: Principal components analysis , Human face recognition (Computer science) , Image processing , Biometric identification
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4704 , http://hdl.handle.net/10962/d1015768
- Description: We report on the design, implementation and performance issues of the DRUBIS (Distributed Rhodes University Biometric Identification System) experimentation framework. The Principal Component Analysis (PCA) face-recognition approach is used as a case study. DRUBIS is a flexible experimentation framework, distributed over a number of modules that are easily pluggable and swappable, allowing for the easy construction of prototype systems. Web services are the logical means of distributing DRUBIS components and a number of prototype applications have been implemented from this framework. Different popular PCA face-recognition related experiments were used to evaluate our experimentation framework. We extract recognition performance measures from these experiments. In particular, we use the framework for a more indepth study of the suitability of the DFFS (Difference From Face Space) metric as a means for image classification in the area of race and gender determination.
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