Identification of novel SNPSTRs by 454 sequencing in Nguni and Sotho-Tswana populations
- Authors: Laurence, Jo-Anne Elizabeth
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/55885 , vital:26752
- Description: DNA profiling is currently performed by analysis of the electropherogram that results following the amplification of a panel of Short Tandem Repeat (STR) loci. A need has arisen, however, for the development of a typing method that generates results which are compatible and comparable with existing databases, but that have a higher discrimination power by supplying sequence data as well as repeat-number data. Recent studies that explore these alternative typing methodologies have revealed the existence of a number of STR variants. There is, however, little information about the exact nature and prevalence of these sub-alleles. There have also been limited population studies of the genetic profiles of sub-Saharan African populations, despite the fact that evidence suggests that there is greater genetic structure and genetic diversity in these populations. In this study, a processing protocol for the generation of 454 sequencing-ready amplicons of vWA, D2S441, D3S1358, D13S317, D21S11 and D7S820 loci was developed. This protocol was applied to buccal swabs collected from 144 individuals of the Nguni and Sotho-Tswana population groups. A total of 145 485 reads were obtained from the sequencing of these amplicons, of which 97 400 and 48 085 reads were obtained for the Nguni and Sotho-Tswana populations respectively. The proportional representation for each locus ranged from 8-20%, and the allele calls and observed frequencies of these alleles suggested a high degree of relatedness between population groups. The sequencing results, furthermore, enabled the identification of a number of previously undescribed STR variants and SNPSTRs; with allele 13´ for D13S317 representing a SNP that may be predictive of Nguni-ancestry. The results also demonstrated the usefulness of next generation sequencing for increasing the number of discernible alleles for STR profiling.
- Full Text:
- Authors: Laurence, Jo-Anne Elizabeth
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/55885 , vital:26752
- Description: DNA profiling is currently performed by analysis of the electropherogram that results following the amplification of a panel of Short Tandem Repeat (STR) loci. A need has arisen, however, for the development of a typing method that generates results which are compatible and comparable with existing databases, but that have a higher discrimination power by supplying sequence data as well as repeat-number data. Recent studies that explore these alternative typing methodologies have revealed the existence of a number of STR variants. There is, however, little information about the exact nature and prevalence of these sub-alleles. There have also been limited population studies of the genetic profiles of sub-Saharan African populations, despite the fact that evidence suggests that there is greater genetic structure and genetic diversity in these populations. In this study, a processing protocol for the generation of 454 sequencing-ready amplicons of vWA, D2S441, D3S1358, D13S317, D21S11 and D7S820 loci was developed. This protocol was applied to buccal swabs collected from 144 individuals of the Nguni and Sotho-Tswana population groups. A total of 145 485 reads were obtained from the sequencing of these amplicons, of which 97 400 and 48 085 reads were obtained for the Nguni and Sotho-Tswana populations respectively. The proportional representation for each locus ranged from 8-20%, and the allele calls and observed frequencies of these alleles suggested a high degree of relatedness between population groups. The sequencing results, furthermore, enabled the identification of a number of previously undescribed STR variants and SNPSTRs; with allele 13´ for D13S317 representing a SNP that may be predictive of Nguni-ancestry. The results also demonstrated the usefulness of next generation sequencing for increasing the number of discernible alleles for STR profiling.
- Full Text:
If I Stay Right Here
- Authors: Ngamlana, Chwayita
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193498 , vital:45337
- Description: My novella concerns the dynamics of a relationship between two girls. It shows the heterosexual‐like nature of the relationship rather than dwelling on the pressures on lesbians from society as a whole. At its core is the raw emotion and passion of the relationship, which is at the same time toxic, destructive and volatile because of their class differences and other insecurities. The work is influenced by the grit, openness, and innovation of several contemporary writers. , Thesis (MA) -- Faculty of Humanities, Institute for the Study of English in Africa, 2015
- Full Text:
- Authors: Ngamlana, Chwayita
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193498 , vital:45337
- Description: My novella concerns the dynamics of a relationship between two girls. It shows the heterosexual‐like nature of the relationship rather than dwelling on the pressures on lesbians from society as a whole. At its core is the raw emotion and passion of the relationship, which is at the same time toxic, destructive and volatile because of their class differences and other insecurities. The work is influenced by the grit, openness, and innovation of several contemporary writers. , Thesis (MA) -- Faculty of Humanities, Institute for the Study of English in Africa, 2015
- Full Text:
Invariant control systems and sub-Riemannian structures on lie groups: equivalence and isometries
- Authors: Biggs, Rory
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64815 , vital:28607
- Description: In this thesis we consider invariant optimal control problems and invariant sub-Riemannian structures on Lie groups. Primarily, we are concerned with the equivalence and classification of problems (resp. structures). In the first chapter, both the class of invariant optimal control problems and the class of invariant sub-Riemannian structures are organised as categories. The latter category is shown to be functorially equivalent to a subcategory of the former category. Via the Pontryagin Maximum Principle, we associate to each invariant optimal control problem (resp. invariant sub-Riemannian structure) a quadratic Hamilton-Poisson system on the associated Lie-Poisson space. These Hamiltonian systems are also organised as a category and hence the Pontryagin lift is realised as a contravariant functor. Basic properties of these categories are investigated. The rest of this thesis is concerned with the classification (and investigation) of certain subclasses of structures and systems. In the second chapter, the homogeneous positive semidefinite quadratic Hamilton-Poisson systems on three-dimensional Lie-Poisson spaces are classified up to compatibility with a linear isomorphism; a list of 23 normal forms is exhibited. In the third chapter, we classify the invariant sub-Riemannian structures in three dimensions and calculate the isometry group for each normal form. By comparing our results with known results, we show that most isometries (in three dimensions) are in fact the composition of a left translation and a Lie group isomorphism. In the fourth and last chapter of this thesis, we classify the sub-Riemannian and Riemannian structures on the (2n + 1)-dimensional Heisenberg groups. Furthermore, we find the isometry group and geodesics of each normal form.
- Full Text:
- Authors: Biggs, Rory
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64815 , vital:28607
- Description: In this thesis we consider invariant optimal control problems and invariant sub-Riemannian structures on Lie groups. Primarily, we are concerned with the equivalence and classification of problems (resp. structures). In the first chapter, both the class of invariant optimal control problems and the class of invariant sub-Riemannian structures are organised as categories. The latter category is shown to be functorially equivalent to a subcategory of the former category. Via the Pontryagin Maximum Principle, we associate to each invariant optimal control problem (resp. invariant sub-Riemannian structure) a quadratic Hamilton-Poisson system on the associated Lie-Poisson space. These Hamiltonian systems are also organised as a category and hence the Pontryagin lift is realised as a contravariant functor. Basic properties of these categories are investigated. The rest of this thesis is concerned with the classification (and investigation) of certain subclasses of structures and systems. In the second chapter, the homogeneous positive semidefinite quadratic Hamilton-Poisson systems on three-dimensional Lie-Poisson spaces are classified up to compatibility with a linear isomorphism; a list of 23 normal forms is exhibited. In the third chapter, we classify the invariant sub-Riemannian structures in three dimensions and calculate the isometry group for each normal form. By comparing our results with known results, we show that most isometries (in three dimensions) are in fact the composition of a left translation and a Lie group isomorphism. In the fourth and last chapter of this thesis, we classify the sub-Riemannian and Riemannian structures on the (2n + 1)-dimensional Heisenberg groups. Furthermore, we find the isometry group and geodesics of each normal form.
- Full Text:
Isolation and structure elucidation of halogenated metabolites from Portieria hornemannii and Portieria tripinnata
- Authors: Adam, Mohammed
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/64674 , vital:28591
- Description: The red marine algal genus, Portieria, is known to produce a number of potent cytotoxic compounds with anticancer potential. The most important anticancer lead produced by this genus is the compound halomon. Unfortunately, the lack of sufficient quantities of this compound hampered its further development. Two Portieria species, Portieria hornemannii and Portieria tripinnata, are found along the South African coastline. Recent studies, based on DNA analysis, suggest that Portieria hornemannii may in fact be divided into several cryptic species. The current project is part of a larger study designed to investigate the use of secondary metabolites to identify new marine algal species. In this study 1H NMR profiles of the organic extracts of selected Portieria spp were compared in order to identify new species. Selected compounds were then isolated and characterised as potential chemotaxonomic markers. Four halogenated monoterpenes were isolated from Portieria hornemannii. Two of these were new compounds 4-(3-bromo-4-chloro-4-methylpentyl)-3-chlorofuran-2(5H)-one, which were isomers of each other. The two known compounds had been previously isolated from Portieria hornemannii samples off the Madagascar coast. These compounds could prove to be useful as chemotaxonomic marker compounds, as they have never been isolated from any other species of marine algae. Three known halogenated monoterpenes were isolated from Portieria tripinnata. These compounds had been previously isolated from different species of marine algae and therefore, could not serve as chemotaxonomic marker compounds for this species of marine alga. Further work needs to be done on Portieria tripinnata, with regards to its chemistry, as it is a species of marine algae that has not been previously researched.
- Full Text:
- Authors: Adam, Mohammed
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/64674 , vital:28591
- Description: The red marine algal genus, Portieria, is known to produce a number of potent cytotoxic compounds with anticancer potential. The most important anticancer lead produced by this genus is the compound halomon. Unfortunately, the lack of sufficient quantities of this compound hampered its further development. Two Portieria species, Portieria hornemannii and Portieria tripinnata, are found along the South African coastline. Recent studies, based on DNA analysis, suggest that Portieria hornemannii may in fact be divided into several cryptic species. The current project is part of a larger study designed to investigate the use of secondary metabolites to identify new marine algal species. In this study 1H NMR profiles of the organic extracts of selected Portieria spp were compared in order to identify new species. Selected compounds were then isolated and characterised as potential chemotaxonomic markers. Four halogenated monoterpenes were isolated from Portieria hornemannii. Two of these were new compounds 4-(3-bromo-4-chloro-4-methylpentyl)-3-chlorofuran-2(5H)-one, which were isomers of each other. The two known compounds had been previously isolated from Portieria hornemannii samples off the Madagascar coast. These compounds could prove to be useful as chemotaxonomic marker compounds, as they have never been isolated from any other species of marine algae. Three known halogenated monoterpenes were isolated from Portieria tripinnata. These compounds had been previously isolated from different species of marine algae and therefore, could not serve as chemotaxonomic marker compounds for this species of marine alga. Further work needs to be done on Portieria tripinnata, with regards to its chemistry, as it is a species of marine algae that has not been previously researched.
- Full Text:
Love in a cold war
- Authors: Christenson, Anna
- Date: 2015
- Subjects: South African fiction (English) -- 21st century
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: vital:5988
- Description: A collection of short stories in two parts written in realist and fabulist styles. The first part looks at the post-war generation of baby boomers growing up in the American Midwest. The second half follows an American abroad and explores themes of disintegration, the shifting power balance in relationships and the terrible hole at the core of expatriate identity.
- Full Text:
- Authors: Christenson, Anna
- Date: 2015
- Subjects: South African fiction (English) -- 21st century
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: vital:5988
- Description: A collection of short stories in two parts written in realist and fabulist styles. The first part looks at the post-war generation of baby boomers growing up in the American Midwest. The second half follows an American abroad and explores themes of disintegration, the shifting power balance in relationships and the terrible hole at the core of expatriate identity.
- Full Text:
Modification and application of the decentralised wastewater treatment technology for greywater treatment to reduce water needs
- Authors: Ngqwala, Nosiphiwe Patience
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/193509 , vital:45338
- Description: Water is a scarce resource that is being acknowledged as a limiting factor to further social- economic growth and development. Demand for freshwater is increasing with corresponding increases in human population, industrial and agricultural activities. Alternative sources, such as greywater and rainwater are often polluted. Though greywater can be used for non-potable purposes, such as irrigation, it still requires some measures of treatment to improve its quality. To improve on greywater quality to facilitate its reuse, decentralised wastewater treatment technologies carry a great potential as complementary and alternative means of wastewater management particularly in peri-urban areas. Five research goals are addressed in this thesis: (i) to monitor the performance of Fly Ash Lime Filter Tower (FLFT) in the treatment of greywater; (ii) to modify the Fly Ash Lime Filter Tower in the treatment of greywater in order to reduce the pH of the greywater, and improved on the reduction of chemical oxygen demand (COD) and coliform counts; (iii) to investigate the potential of the reuse of greywater for irrigation; (iv) to undertake a techno analysis of the FLFT system for commercial use; and (v) to evaluate the use of hydrogen-sulphide (H2S) test kit to monitor faecal contamination of various water sources using a multidisciplinary approach. The modification of the FLFT indicated good treatment efficiency, reducing the concentrations of COD, chlorides, nitrates, ammonia and sulphate by 82.6%, 60.4%, 72.9%, 60.5%, and 53.9%, respectively; while the average pH was at 8.3. Greywater contains nutrients that are beneficial to the growth of most plants. Growth variables included biomass, stem height, number of leaves and number of vegetables harvested. Soil analysis showed no effects of the treated greywater on soil physico-chemical and microbial quality with bulk density 2.0g/cm3, average pH 7.4, total phosphorus 0.16mg/L 8, faecal coliform 0.3 CFU/100 ml. The tomatoes had high biomass and dry weight (150 g; 33g) than beetroot (35 g; 15 g). Crops irrigated with greywater significantly grew faster compared with those irrigated with tap water. The community approach highlighted the value of knowledge management in greywater reuse. It highlighted the importance of creating an institutional knowledge in water management using the H2S kit. The techno-economic analysis was used to evaluate key factors and the activities that are relevant to develop a sustainable FLFT in order to gain insights into the possibility of developing, and incorporating a business model framework to support decision making in value creation and value capturing during the research and the scaling up of the system. By this, a long term perspective to accomplish sustainable FLFT service businesses can be achieved. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2015
- Full Text:
- Authors: Ngqwala, Nosiphiwe Patience
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/193509 , vital:45338
- Description: Water is a scarce resource that is being acknowledged as a limiting factor to further social- economic growth and development. Demand for freshwater is increasing with corresponding increases in human population, industrial and agricultural activities. Alternative sources, such as greywater and rainwater are often polluted. Though greywater can be used for non-potable purposes, such as irrigation, it still requires some measures of treatment to improve its quality. To improve on greywater quality to facilitate its reuse, decentralised wastewater treatment technologies carry a great potential as complementary and alternative means of wastewater management particularly in peri-urban areas. Five research goals are addressed in this thesis: (i) to monitor the performance of Fly Ash Lime Filter Tower (FLFT) in the treatment of greywater; (ii) to modify the Fly Ash Lime Filter Tower in the treatment of greywater in order to reduce the pH of the greywater, and improved on the reduction of chemical oxygen demand (COD) and coliform counts; (iii) to investigate the potential of the reuse of greywater for irrigation; (iv) to undertake a techno analysis of the FLFT system for commercial use; and (v) to evaluate the use of hydrogen-sulphide (H2S) test kit to monitor faecal contamination of various water sources using a multidisciplinary approach. The modification of the FLFT indicated good treatment efficiency, reducing the concentrations of COD, chlorides, nitrates, ammonia and sulphate by 82.6%, 60.4%, 72.9%, 60.5%, and 53.9%, respectively; while the average pH was at 8.3. Greywater contains nutrients that are beneficial to the growth of most plants. Growth variables included biomass, stem height, number of leaves and number of vegetables harvested. Soil analysis showed no effects of the treated greywater on soil physico-chemical and microbial quality with bulk density 2.0g/cm3, average pH 7.4, total phosphorus 0.16mg/L 8, faecal coliform 0.3 CFU/100 ml. The tomatoes had high biomass and dry weight (150 g; 33g) than beetroot (35 g; 15 g). Crops irrigated with greywater significantly grew faster compared with those irrigated with tap water. The community approach highlighted the value of knowledge management in greywater reuse. It highlighted the importance of creating an institutional knowledge in water management using the H2S kit. The techno-economic analysis was used to evaluate key factors and the activities that are relevant to develop a sustainable FLFT in order to gain insights into the possibility of developing, and incorporating a business model framework to support decision making in value creation and value capturing during the research and the scaling up of the system. By this, a long term perspective to accomplish sustainable FLFT service businesses can be achieved. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2015
- Full Text:
Modification and application of the decentralised wastewater treatment technology for greywater treatment to reduce water needs
- Authors: Ngqwala, Nosiphiwe P
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/103714 , vital:32290
- Description: Expected release date-April 2017
- Full Text: false
- Authors: Ngqwala, Nosiphiwe P
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/103714 , vital:32290
- Description: Expected release date-April 2017
- Full Text: false
Spatio-temporal variation in the phytobenthos and phytoplankton community structure and composition of particulate matter along a river-estuary continuum assessed using microscopic and stable isotope analyses
- Authors: Dalu, Tatenda
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54416 , vital:26563
- Description: Phytoplankton and phytobenthos communities play an important role in lotic systems as primary producers providing essential biomolecules to higher trophic oganisms and are important indicators for environmental or ecological change. In this thesis, field studies (observational and experimental) along a river–estuary continuum were conducted to assess the spatio-temporal variation and development of phytobenthos and phytoplankton communities using a combination of stable isotope and community analyses in a temperate southern African system across four study periods: September (early spring) and November/December (late spring) 2012, and February (summer) and May/June (winter) 2013. Additionally, the sources and composition of the particulate organic matter were also analysed using stable isotope (δ15N and δ13C) analysis. The effects of substrate type and flood occurrence were assessed through experimental studies at an up- and downstream site of the river after a major flood event that occurred between October and November 2012. Common household tiles were used as artificial substrates to study the development/succession of phytobenthos communities after the flood disturbance. Distinct diatom communities were observed between upstream and downstream sites and at each site, community structure changed with time indicating succession. In addition to recording diatom characteristics on three natural substrates, namely; macrophytes, rocks and sediment, artificial substrates observations were also made on three different types of artificial substrates, namely; brick, brown clay and grey clay tiles. The natural (species richness 78) and artificial substrates (sp. richness 93) had different communities with the latter having greater species richness. Common phytobenthos taxa were not restricted to a single substrate but preference was generally high for the artificial substrates, especially brown tiles (mean sp. richness 47). Results of the redundancy analysis (RDA) analysis indicated that ammonium, conductivity, total dissolved solids, salinity, pH, oxygen reduction potential, phosphate and water depth were the major determinants of the phytobenthos composition at the two sites. The spatio–temporal variation of phytoplankton and phytobenthos communities and allochthonous organic matter along the river–estuary continuum was assessed at 8 sites using a combination of community and stable isotope analyses. A total of 178 species belonging to 78 genera were recorded with diatoms being predominant, accounting for 81.9 % of the total abundance. The total chl-a concentration along the river-estuary continuum increased from spring to a high in summer before decreasing to a low in winter. Periphyton communities were observed to be significantly different across sites (p < 0.05) in terms of species richness, abundances and isotopically The high periphytic δ15N values (range 7.9–15.2 ‰) recorded at the downstream sites compared to the pristine upstream sites (δ15N values range 4–7 ‰) suggest nutrient enrichment most likely derived from anthropogenic sources. Overall, our results reveal general patterns of periphyton communities and stable isotopes and provide improved information in the use of periphyton δ15N as an excellent indicator of anthropogenic nitrogen pollution. Ecologists are interested in the factors that control, and the variability in, the contributions of different sources to mixed organic materials traveling through lotic systems. We hypothesized that the source matter fuelling mixed organic pools in a river-estuary continuum varies over space and time, with the upper reaches of a system characterized by allochthonous-dominated material and autochthonous contributions becoming more important in the lower reaches. Samples of the mixed organic pools and allochthonous and autochthonous source materials were collected during the four study periods. The C:N ratios of suspended particulate matter (SPM) collected during summer and winter indicated that the lower reaches of the system had similar organic matter contributions from the freshwater and terrestrial sources. Stable isotope analysis in R revealed that the contributions of autochthonous organic matter were high in SPM along the entire continuum, and aquatic macrophytes were significant contributors to SPM specifically in the upper reaches. The terrestrial leaves made major contributions to the SPM in the middle regions of the system (i.e. downstream sites of the river, particularly in early and late spring). Bulk detritus had large allochthonous matter components in the lower reaches (estuary), and the contributions of aquatic macrophytes and benthic algae to bulk detritus were high (> 50 %) in the upper to middle reaches (river), but low (< 20 %) in the lower reaches (estuary). The current investigation represents the first attempt to assess the validity of the River Continuum Concept (RCC) in a southern African temperate river. The phytoplankton and phytobenthos communities, and chl-a concentration followed a trend similar to that proposed for the river continuum concept (RCC). The middle reaches based on the phytobenthos or phytoplankton communities and chl-a concentrations which were employed as proxies for primary production, were the most productive, while the upper reaches were the least primary productive. The evaluation of organic matter contributions to the SPM and detritus along the river–estuary continuum provided a baseline assessment of the nature and sources of potential food for consumers inhabiting different locations during different times of the year. Incorporating such spatio-temporal variations in SPM and detritus into food web studies will improve our understanding of the flow of carbon through aquatic systems.
- Full Text:
- Authors: Dalu, Tatenda
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54416 , vital:26563
- Description: Phytoplankton and phytobenthos communities play an important role in lotic systems as primary producers providing essential biomolecules to higher trophic oganisms and are important indicators for environmental or ecological change. In this thesis, field studies (observational and experimental) along a river–estuary continuum were conducted to assess the spatio-temporal variation and development of phytobenthos and phytoplankton communities using a combination of stable isotope and community analyses in a temperate southern African system across four study periods: September (early spring) and November/December (late spring) 2012, and February (summer) and May/June (winter) 2013. Additionally, the sources and composition of the particulate organic matter were also analysed using stable isotope (δ15N and δ13C) analysis. The effects of substrate type and flood occurrence were assessed through experimental studies at an up- and downstream site of the river after a major flood event that occurred between October and November 2012. Common household tiles were used as artificial substrates to study the development/succession of phytobenthos communities after the flood disturbance. Distinct diatom communities were observed between upstream and downstream sites and at each site, community structure changed with time indicating succession. In addition to recording diatom characteristics on three natural substrates, namely; macrophytes, rocks and sediment, artificial substrates observations were also made on three different types of artificial substrates, namely; brick, brown clay and grey clay tiles. The natural (species richness 78) and artificial substrates (sp. richness 93) had different communities with the latter having greater species richness. Common phytobenthos taxa were not restricted to a single substrate but preference was generally high for the artificial substrates, especially brown tiles (mean sp. richness 47). Results of the redundancy analysis (RDA) analysis indicated that ammonium, conductivity, total dissolved solids, salinity, pH, oxygen reduction potential, phosphate and water depth were the major determinants of the phytobenthos composition at the two sites. The spatio–temporal variation of phytoplankton and phytobenthos communities and allochthonous organic matter along the river–estuary continuum was assessed at 8 sites using a combination of community and stable isotope analyses. A total of 178 species belonging to 78 genera were recorded with diatoms being predominant, accounting for 81.9 % of the total abundance. The total chl-a concentration along the river-estuary continuum increased from spring to a high in summer before decreasing to a low in winter. Periphyton communities were observed to be significantly different across sites (p < 0.05) in terms of species richness, abundances and isotopically The high periphytic δ15N values (range 7.9–15.2 ‰) recorded at the downstream sites compared to the pristine upstream sites (δ15N values range 4–7 ‰) suggest nutrient enrichment most likely derived from anthropogenic sources. Overall, our results reveal general patterns of periphyton communities and stable isotopes and provide improved information in the use of periphyton δ15N as an excellent indicator of anthropogenic nitrogen pollution. Ecologists are interested in the factors that control, and the variability in, the contributions of different sources to mixed organic materials traveling through lotic systems. We hypothesized that the source matter fuelling mixed organic pools in a river-estuary continuum varies over space and time, with the upper reaches of a system characterized by allochthonous-dominated material and autochthonous contributions becoming more important in the lower reaches. Samples of the mixed organic pools and allochthonous and autochthonous source materials were collected during the four study periods. The C:N ratios of suspended particulate matter (SPM) collected during summer and winter indicated that the lower reaches of the system had similar organic matter contributions from the freshwater and terrestrial sources. Stable isotope analysis in R revealed that the contributions of autochthonous organic matter were high in SPM along the entire continuum, and aquatic macrophytes were significant contributors to SPM specifically in the upper reaches. The terrestrial leaves made major contributions to the SPM in the middle regions of the system (i.e. downstream sites of the river, particularly in early and late spring). Bulk detritus had large allochthonous matter components in the lower reaches (estuary), and the contributions of aquatic macrophytes and benthic algae to bulk detritus were high (> 50 %) in the upper to middle reaches (river), but low (< 20 %) in the lower reaches (estuary). The current investigation represents the first attempt to assess the validity of the River Continuum Concept (RCC) in a southern African temperate river. The phytoplankton and phytobenthos communities, and chl-a concentration followed a trend similar to that proposed for the river continuum concept (RCC). The middle reaches based on the phytobenthos or phytoplankton communities and chl-a concentrations which were employed as proxies for primary production, were the most productive, while the upper reaches were the least primary productive. The evaluation of organic matter contributions to the SPM and detritus along the river–estuary continuum provided a baseline assessment of the nature and sources of potential food for consumers inhabiting different locations during different times of the year. Incorporating such spatio-temporal variations in SPM and detritus into food web studies will improve our understanding of the flow of carbon through aquatic systems.
- Full Text:
Studies towards the development of novel antimalarial agents
- Authors: Adeyemi, Christiana Modupe
- Date: 2015
- Subjects: Antimalarials , Malaria , Drug resistance , Drug development , Enzyme inhibitors , Plasmodium
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/54645 , vital:26596
- Description: Considerable efforts have been made in the modification of existing antimalarial drugs, and the support of incentive programmes have led to a drastic decrease in malaria cases reported by WHO during the past 6 years. However, the development of drug resistance threatens the eradication of this deadly disease and has prompted research on the synthesis of novel antimalarial drugs. Our research has involved the design and synthesis of novel benzylated phosphonate esters as potential 1-deoxy-D-xylose-5-phosphate reductoisomerase (DXR) inhibitors. A series of amidoalkylphosphonate esters were obtained by reacting various 3-subsituted anilines and heterocyclic amines with chloroalkanoyl chlorides and reacting the resulting chloroalkanamides with triethyl phosphite using Michaelis-Arbuzov methodology. Benzylation of the phosphonate esters afforded a series of novel N-benzylated derivatives in good yields and these compounds were fully characterised by NMR and HRMS methods. Several approaches to the introduction of a benzyl group at the C-2 position of the phosphonate ester derivatives have been explored, leading unexpectedly to the isolation of unprecedented tetrahydrofuranyl derivatives. Studies towards the preparation of potential bi-functional PfDXR / HIV-1 RT inhibitors have also been initiated. Preliminary in silico docking studies of selected non-benzylated and benzylated phosphonated derivatives into the Pf-DXR active-site has provided useful insight into the binding potential of these ligands. Bioassays have revealed a very low toxicity for all the synthesised phosphonated compounds and a number of these ligands also exhibit a promising inhibitory activity against the Plasmodium parasite.
- Full Text:
- Authors: Adeyemi, Christiana Modupe
- Date: 2015
- Subjects: Antimalarials , Malaria , Drug resistance , Drug development , Enzyme inhibitors , Plasmodium
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/54645 , vital:26596
- Description: Considerable efforts have been made in the modification of existing antimalarial drugs, and the support of incentive programmes have led to a drastic decrease in malaria cases reported by WHO during the past 6 years. However, the development of drug resistance threatens the eradication of this deadly disease and has prompted research on the synthesis of novel antimalarial drugs. Our research has involved the design and synthesis of novel benzylated phosphonate esters as potential 1-deoxy-D-xylose-5-phosphate reductoisomerase (DXR) inhibitors. A series of amidoalkylphosphonate esters were obtained by reacting various 3-subsituted anilines and heterocyclic amines with chloroalkanoyl chlorides and reacting the resulting chloroalkanamides with triethyl phosphite using Michaelis-Arbuzov methodology. Benzylation of the phosphonate esters afforded a series of novel N-benzylated derivatives in good yields and these compounds were fully characterised by NMR and HRMS methods. Several approaches to the introduction of a benzyl group at the C-2 position of the phosphonate ester derivatives have been explored, leading unexpectedly to the isolation of unprecedented tetrahydrofuranyl derivatives. Studies towards the preparation of potential bi-functional PfDXR / HIV-1 RT inhibitors have also been initiated. Preliminary in silico docking studies of selected non-benzylated and benzylated phosphonated derivatives into the Pf-DXR active-site has provided useful insight into the binding potential of these ligands. Bioassays have revealed a very low toxicity for all the synthesised phosphonated compounds and a number of these ligands also exhibit a promising inhibitory activity against the Plasmodium parasite.
- Full Text:
Synthesis and biological evaluation of truncated sarganaphthoquinoic acid derivatives as Hsp90 inhibitors
- Authors: Chiwakata, Maynard T
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64708 , vital:28594
- Description: Hsp90 inhibition has been at the centre of attention in current research due to the possibility of “cracking down” on the entire process leading to the development of malignant cancers. Small underlying principles common in all types of cancers have been determined that govern the transformation of normal human cells into cancerous cells, with all relying on the ATPase activity of Hsp90 protein. Hsp90 protein is therefore an attractive drug target that if successfully inhibited can result in the remission of cancer tumours by one form of treatment. To date, no Hsp90 inhibitor has been sanctioned for cancer treatment as most are still in clinical development. Our research was therefore inspired by reports that indicated the potential of quinones / naphthoquinones to act as Hsp90 inhibitors. Preliminary results of a few selected marine natural product quinone systems i.e. sargaquinoic acid (SQA) (2.47) and lapachol (3.6) showed moderate cytotoxicity and weak interactions with the Hsp90 molecular chaperone, and evidence suggested C-terminal binding of these molecules. No correlation has been determined yet between cytotoxicity and Hsp90 inhibition, hence we aimed to develop natural product inspired molecules that exhibit both cytotoxic and Hsp90 inhibition properties. Due to limited amounts of the natural product that can be acquired from natural sources, synthetic analogues were opted for. Isolation of a few selected quinones was conducted to have material that could be used in biological assays. For structural modifications, a series of truncated naphthoquinone systems were prepared adopting the sarganaphthoquinoic acid (3.5) scaffold. The naphthoquinones were prepared via Diels-Alder reactions of relevant benzoquinones with myrcene, followed by aromatization reactions using MnO2. Various alkyl and aryl amines were then coupled to the C-2/3 position of the naphthoquinone using Michael’s addition reactions. Tricyclic naphthoquinones were also synthesized from reactions with hypotaurine and citral. Design of the analogues incorporated functionalities from known Hsp90 inhibitors e.g. geldanamycin (2.28) and its analogues. Preliminary results obtained showed that coupling of naphthoquinones with aryl-amines resulted in the most cytotoxic compounds (4.14-4.19) with IC50 values as low as 0.3 μM against Hs578T breast cancer carcinoma (triple negative). Most of the alkyl amines (4.20-4.25) had IC50 values greater than 50 μM except for 4.20 and 4.21 that showed IC50 values of 7.6 μM and 2.6 μM respectively. Tricyclic naphthoquinones (4.28-4.29) showed moderate cytotoxic activity of approximately 10 μM. Hsp90 inhibition was assessed by client protein degradation assays, of which SQA (2.47), showed the best Hsp90 inhibition properties, followed by compound 4.20. The most cytotoxic arylamino-naphthoquinone (4.16) and tricyclic naphthoquinones (4.28-4.29) showed only moderate inhibition. None of the compounds led to Hsp70 induction, suggesting possible binding to the C-terminus of Hsp90. Interactions at the binding site were assessed by molecular docking studies and saturation transfer difference (STD) NMR. Docking studies were conducted on the N-terminus of Hsp90 and better binding was observed for arylamino naphthoquinones (4.14-4.19) than for other series of compounds. Unfortunately, the co-crystal structure for the C-terminus of Hsp90 is unavailable, hence docking study comparisons on both domains could not be conducted. However, STD NMR offered a platform to assess binding interactions between the naphthoquinones and the N- or C-terminal domains of Hsp90. However no interactions were observed at both the N- and C- termini of Hsp90 due to either weak binding of ligands to the protein or poor water solubility of the ligands. From these preliminary results, naphthoquinones bind to Hsp90 protein but conclusive remarks to which terminal domain they bind to could not be made. The best candidate from amongst the series of naphthoquinones prepared that showed moderate cytotoxicity and promising Hsp90 inhibition was compound 4.20. We therefore succeeded in developing a new series of naphthoquinones that possess moderate cytotoxicity and show Hsp90 inhibition.
- Full Text:
- Authors: Chiwakata, Maynard T
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64708 , vital:28594
- Description: Hsp90 inhibition has been at the centre of attention in current research due to the possibility of “cracking down” on the entire process leading to the development of malignant cancers. Small underlying principles common in all types of cancers have been determined that govern the transformation of normal human cells into cancerous cells, with all relying on the ATPase activity of Hsp90 protein. Hsp90 protein is therefore an attractive drug target that if successfully inhibited can result in the remission of cancer tumours by one form of treatment. To date, no Hsp90 inhibitor has been sanctioned for cancer treatment as most are still in clinical development. Our research was therefore inspired by reports that indicated the potential of quinones / naphthoquinones to act as Hsp90 inhibitors. Preliminary results of a few selected marine natural product quinone systems i.e. sargaquinoic acid (SQA) (2.47) and lapachol (3.6) showed moderate cytotoxicity and weak interactions with the Hsp90 molecular chaperone, and evidence suggested C-terminal binding of these molecules. No correlation has been determined yet between cytotoxicity and Hsp90 inhibition, hence we aimed to develop natural product inspired molecules that exhibit both cytotoxic and Hsp90 inhibition properties. Due to limited amounts of the natural product that can be acquired from natural sources, synthetic analogues were opted for. Isolation of a few selected quinones was conducted to have material that could be used in biological assays. For structural modifications, a series of truncated naphthoquinone systems were prepared adopting the sarganaphthoquinoic acid (3.5) scaffold. The naphthoquinones were prepared via Diels-Alder reactions of relevant benzoquinones with myrcene, followed by aromatization reactions using MnO2. Various alkyl and aryl amines were then coupled to the C-2/3 position of the naphthoquinone using Michael’s addition reactions. Tricyclic naphthoquinones were also synthesized from reactions with hypotaurine and citral. Design of the analogues incorporated functionalities from known Hsp90 inhibitors e.g. geldanamycin (2.28) and its analogues. Preliminary results obtained showed that coupling of naphthoquinones with aryl-amines resulted in the most cytotoxic compounds (4.14-4.19) with IC50 values as low as 0.3 μM against Hs578T breast cancer carcinoma (triple negative). Most of the alkyl amines (4.20-4.25) had IC50 values greater than 50 μM except for 4.20 and 4.21 that showed IC50 values of 7.6 μM and 2.6 μM respectively. Tricyclic naphthoquinones (4.28-4.29) showed moderate cytotoxic activity of approximately 10 μM. Hsp90 inhibition was assessed by client protein degradation assays, of which SQA (2.47), showed the best Hsp90 inhibition properties, followed by compound 4.20. The most cytotoxic arylamino-naphthoquinone (4.16) and tricyclic naphthoquinones (4.28-4.29) showed only moderate inhibition. None of the compounds led to Hsp70 induction, suggesting possible binding to the C-terminus of Hsp90. Interactions at the binding site were assessed by molecular docking studies and saturation transfer difference (STD) NMR. Docking studies were conducted on the N-terminus of Hsp90 and better binding was observed for arylamino naphthoquinones (4.14-4.19) than for other series of compounds. Unfortunately, the co-crystal structure for the C-terminus of Hsp90 is unavailable, hence docking study comparisons on both domains could not be conducted. However, STD NMR offered a platform to assess binding interactions between the naphthoquinones and the N- or C-terminal domains of Hsp90. However no interactions were observed at both the N- and C- termini of Hsp90 due to either weak binding of ligands to the protein or poor water solubility of the ligands. From these preliminary results, naphthoquinones bind to Hsp90 protein but conclusive remarks to which terminal domain they bind to could not be made. The best candidate from amongst the series of naphthoquinones prepared that showed moderate cytotoxicity and promising Hsp90 inhibition was compound 4.20. We therefore succeeded in developing a new series of naphthoquinones that possess moderate cytotoxicity and show Hsp90 inhibition.
- Full Text:
The design and evaluation of targeted patient-centred health information to improve knowledge and behavioural outcomes in tuberculosis patients with limited literacy
- Authors: Patel, Sonal
- Date: 2015
- Subjects: Tuberculosis Patients , Health literacy , Patient education , Communication in medicine , Picture-writing
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/194071 , vital:45420 , DOI 10.21504/10962/194071
- Description: South Africa carries a significant TB burden as evidenced in the 2013 statistics which report 450 000 new active TB cases and 890 000 TB-related mortalities. For successful treatment outcomes, 90% adherence is necessary, but many patients prematurely discontinue treatment due to poor knowledge and understanding of their complex TB medicines. Patient education is pivotal in improving knowledge, health literacy and behavioural outcomes such as health information seeking, self-efficacy and adherence. In the under-resourced South African healthcare system, time and capacity to adequately counsel patients are limited. The value of written medicine information (WMI) to supplement the verbal information provided by healthcare professionals (HCPs) has been widely investigated but minimal South African research is available. Current WMI distributed in South Africa is mainly generated by pharmaceutical manufacturers and is complex, incomprehensible and undesirable to patients. TB-related WMI focuses mainly on the disease, with little information relating to TB medicines and their use. The overall aim of this project was to improve patient knowledge about their TB medicines through the use of a simple illustrated patient information leaflet (PIL). Objectives to achieve this aim included: investigation of the medicine information seeking behaviour (MISB) of long term patients attending public health sector facilities; the development and validation of a medicine literacy test (MLT) to identify patients with limited health literacy requiring additional support and counselling; the development and evaluation of a patient-centred illustrated PIL for first-line TB treatment; the assessment of self-efficacy and adherence using modified versions of the HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES) and Morisky 8-item Medicine Adherence Scale (MMAS-8), respectively, and the investigation of the impact of the PIL on patient knowledge and these health-related behaviours. Six focus group discussions (FGDs) conducted in 34 isiXhosa-speaking patients with limited formal education taking long-term treatment explored themes related to information needs, information-seeking practices and awareness of and ability to utilize information sources. Codes were analysed and potential themes and subthemes were identified and refined. The findings of this study reflected a passive, disempowered patient due to both patient-related and systemic healthcare factors. Poor awareness of information sources, lack of health-related knowledge, stigma and lack of awareness of the importance of appropriate medicine-related knowledge contributed to a lack of information-seeking practice. Patients neither asked questions nor were encouraged to do so. All expressed an unmet need for information and a desire for receiving relevant, appropriate, written medicine-related information. Feedback from this phase of the study was used to inform the development of the targeted patientcentred PIL. A double-sided A4 PIL containing information about TB medicines was designed giving careful consideration to content, format and layout features. Twenty five pictograms were designed through a rigorous, iterative design process and were included in the PIL that was evaluated in a randomised control trial (RCT) conducted amongst 120 TB patients attending a high burden TB clinic in South Africa. Interviews were conducted in either isiXhosa or Afrikaans via a trained interpreter. Patients were randomly allocated to either a control (standard care) or an experimental group (standard care plus brief counselling using the PIL). Two interviews were conducted using a prepared questionnaire; one at baseline followed by a 4-week follow-up. Baseline data included demographics, medicine literacy test, health information sources, knowledge of TB medicines, self-reported adherence and self-efficacy. Data collected at the 4-week follow-up interview included TB knowledge, self-reported adherence, self-efficacy, opinion of TB medicine information and interpretation of pictograms. Data were analysed using t-test, correlations, chi-square and ANOVA tests at a 0.05 level of significance. The PIL was successful in improving patient knowledge of the disease, TB medicine-taking, side effects, drug-resistant TB and HIV and TB co-infection. At baseline, there was no significant difference in the overall mean percentage knowledge score between the control and experimental groups (p=0.074). At follow-up, the percentage knowledge score for the experimental group increased significantly from 59.0% to 84.6% (p<0.001) and showed a significantly higher score than the control group (p<0.001), displaying evidence of the impact of the PIL as a counselling tool on patient knowledge. The PIL generated a highly positive response in the experimental group who indicated that they had referred to the leaflet over the last month and that it had played an important role in improving their TB medicine-related knowledge. This was reflected in the experimental group knowledge score of greater than 80% for almost three quarters of the patients whereas only 14% in the control group achieved this score. Patients appreciated the inclusion of pictograms and strongly felt that they helped them to recall and understand the textual PIL content. The study found that patients want side effect information and, interestingly, did not perceive the presentation of side effects in pictorial form to constitute a risk factor for nonadherence. Use of the illustrated PIL (experimental group) resulted in a significant improvement in patient self-efficacy (p=0.002), but showed no effect on self-reported adherence (p=0.563). Neither self-efficacy nor adherence was influenced by gender, age or education. An education effect on knowledge was only observed in the control group at baseline. The newly developed MLT was shown to be a valid and reliable tool and a moderate, positive and significant correlation was noted between the MLT score and baseline TB medicine-related knowledge in both the control and experimental groups. As there is a paucity of studies investigating the influence of take-home written leaflets on TB medicine knowledge and on patient behaviour, this study represents a significant knowledge contribution. It is the first study to report the development and evaluation of a patient-centred PIL to address the dearth of available TB medicine information. The use of targeted user-friendly, illustrated information leaflets can be a valuable counselling aid to improve patient knowledge and self-efficacy, particularly among patients with limited literacy. However, careful consideration of the design and content, with input from the endusers at all stages of the process, will optimise its effectiveness. The proposed framework for the development and implementation of patient-centred health and medicines information in a developing country context presented in this thesis could be used as a theoretical basis for informing the development of effective information materials targeting other disease states. Local patients taking TB medicines identified nurses, WMI and media as their current sources of information but they expressed a strong desire to know more about their treatment. Targeted public health interventions that focus on medicine-taking information and behaviours and encourage patients to adopt a more active, questioning role in health consultations could improve health literacy and empower patients in their medicine-taking practices. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2015
- Full Text:
- Authors: Patel, Sonal
- Date: 2015
- Subjects: Tuberculosis Patients , Health literacy , Patient education , Communication in medicine , Picture-writing
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/194071 , vital:45420 , DOI 10.21504/10962/194071
- Description: South Africa carries a significant TB burden as evidenced in the 2013 statistics which report 450 000 new active TB cases and 890 000 TB-related mortalities. For successful treatment outcomes, 90% adherence is necessary, but many patients prematurely discontinue treatment due to poor knowledge and understanding of their complex TB medicines. Patient education is pivotal in improving knowledge, health literacy and behavioural outcomes such as health information seeking, self-efficacy and adherence. In the under-resourced South African healthcare system, time and capacity to adequately counsel patients are limited. The value of written medicine information (WMI) to supplement the verbal information provided by healthcare professionals (HCPs) has been widely investigated but minimal South African research is available. Current WMI distributed in South Africa is mainly generated by pharmaceutical manufacturers and is complex, incomprehensible and undesirable to patients. TB-related WMI focuses mainly on the disease, with little information relating to TB medicines and their use. The overall aim of this project was to improve patient knowledge about their TB medicines through the use of a simple illustrated patient information leaflet (PIL). Objectives to achieve this aim included: investigation of the medicine information seeking behaviour (MISB) of long term patients attending public health sector facilities; the development and validation of a medicine literacy test (MLT) to identify patients with limited health literacy requiring additional support and counselling; the development and evaluation of a patient-centred illustrated PIL for first-line TB treatment; the assessment of self-efficacy and adherence using modified versions of the HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES) and Morisky 8-item Medicine Adherence Scale (MMAS-8), respectively, and the investigation of the impact of the PIL on patient knowledge and these health-related behaviours. Six focus group discussions (FGDs) conducted in 34 isiXhosa-speaking patients with limited formal education taking long-term treatment explored themes related to information needs, information-seeking practices and awareness of and ability to utilize information sources. Codes were analysed and potential themes and subthemes were identified and refined. The findings of this study reflected a passive, disempowered patient due to both patient-related and systemic healthcare factors. Poor awareness of information sources, lack of health-related knowledge, stigma and lack of awareness of the importance of appropriate medicine-related knowledge contributed to a lack of information-seeking practice. Patients neither asked questions nor were encouraged to do so. All expressed an unmet need for information and a desire for receiving relevant, appropriate, written medicine-related information. Feedback from this phase of the study was used to inform the development of the targeted patientcentred PIL. A double-sided A4 PIL containing information about TB medicines was designed giving careful consideration to content, format and layout features. Twenty five pictograms were designed through a rigorous, iterative design process and were included in the PIL that was evaluated in a randomised control trial (RCT) conducted amongst 120 TB patients attending a high burden TB clinic in South Africa. Interviews were conducted in either isiXhosa or Afrikaans via a trained interpreter. Patients were randomly allocated to either a control (standard care) or an experimental group (standard care plus brief counselling using the PIL). Two interviews were conducted using a prepared questionnaire; one at baseline followed by a 4-week follow-up. Baseline data included demographics, medicine literacy test, health information sources, knowledge of TB medicines, self-reported adherence and self-efficacy. Data collected at the 4-week follow-up interview included TB knowledge, self-reported adherence, self-efficacy, opinion of TB medicine information and interpretation of pictograms. Data were analysed using t-test, correlations, chi-square and ANOVA tests at a 0.05 level of significance. The PIL was successful in improving patient knowledge of the disease, TB medicine-taking, side effects, drug-resistant TB and HIV and TB co-infection. At baseline, there was no significant difference in the overall mean percentage knowledge score between the control and experimental groups (p=0.074). At follow-up, the percentage knowledge score for the experimental group increased significantly from 59.0% to 84.6% (p<0.001) and showed a significantly higher score than the control group (p<0.001), displaying evidence of the impact of the PIL as a counselling tool on patient knowledge. The PIL generated a highly positive response in the experimental group who indicated that they had referred to the leaflet over the last month and that it had played an important role in improving their TB medicine-related knowledge. This was reflected in the experimental group knowledge score of greater than 80% for almost three quarters of the patients whereas only 14% in the control group achieved this score. Patients appreciated the inclusion of pictograms and strongly felt that they helped them to recall and understand the textual PIL content. The study found that patients want side effect information and, interestingly, did not perceive the presentation of side effects in pictorial form to constitute a risk factor for nonadherence. Use of the illustrated PIL (experimental group) resulted in a significant improvement in patient self-efficacy (p=0.002), but showed no effect on self-reported adherence (p=0.563). Neither self-efficacy nor adherence was influenced by gender, age or education. An education effect on knowledge was only observed in the control group at baseline. The newly developed MLT was shown to be a valid and reliable tool and a moderate, positive and significant correlation was noted between the MLT score and baseline TB medicine-related knowledge in both the control and experimental groups. As there is a paucity of studies investigating the influence of take-home written leaflets on TB medicine knowledge and on patient behaviour, this study represents a significant knowledge contribution. It is the first study to report the development and evaluation of a patient-centred PIL to address the dearth of available TB medicine information. The use of targeted user-friendly, illustrated information leaflets can be a valuable counselling aid to improve patient knowledge and self-efficacy, particularly among patients with limited literacy. However, careful consideration of the design and content, with input from the endusers at all stages of the process, will optimise its effectiveness. The proposed framework for the development and implementation of patient-centred health and medicines information in a developing country context presented in this thesis could be used as a theoretical basis for informing the development of effective information materials targeting other disease states. Local patients taking TB medicines identified nurses, WMI and media as their current sources of information but they expressed a strong desire to know more about their treatment. Targeted public health interventions that focus on medicine-taking information and behaviours and encourage patients to adopt a more active, questioning role in health consultations could improve health literacy and empower patients in their medicine-taking practices. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2015
- Full Text:
The development of biological tools to aid in the genetic investigation of the black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros mitochondrial genomes
- Authors: Parsons, Michelle
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/56059 , vital:26769
- Description: The black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros are found in South Africa. A decline in the populations of these species has resulted due to human activities such as habitat fragmentation and poaching. This has contributed to the loss of genetic diversity amongst the black and white rhinoceros. Conservation and anti-poaching efforts are needed to help maintain genetic diversity. These efforts could be improved through the development of non-invasive techniques to examine DNA from threatened animals. The aim of this research was to develop a molecular technique which would allow for the identification of the black and white rhinoceros and to develop a molecular technique which would allow for intraspecies genetic variation to be examined. DNA extractions were performed on matched faecal and tissue samples that were collected from two regions in South Africa. Polymerase chain reaction (PCR) primer sets were designed to investigate several regions of the rhinoceros mitochondrial genome. PCR optimisation was completed for the target regions. Sequencing was conducted on all final PCR products. The cytochrome c oxidase subunit 1 (COIi) gene allowed for the rhinoceros family to be identified. This region was digested with the HindIII restriction enzyme, which allowed for the specific identification of either the black or white rhinoceros. A subsequent region of the cytochrome c oxidase subunit 1 (COIii) as well as the D-loop, hypervariable regions (HV1 and HV2), cytochrome b (cytb) and 16s rRNA regions were investigated. These regions displayed potential for establishing geographic origin for black rhinoceros samples, whereas the D-loop and HV2 show potential for the white rhinoceros. The white rhinoceros displayed sequence variation in the HV2 and cytb region, while variation was observed in the COIi and HV1 for the black rhinoceros. All investigated target regions allowed for the rhinoceros family to be identified. The COI (COIi and COIii), HV2 and cytb regions allowed for the subspecies of rhinoceros to be identified, however the D-loop was not able to identify the white rhinoceros species. The 16s rRNA and HV1 regions allowed for the correct subspecies of rhinoceros to be identified, however as the primers were only compatible for the black rhinoceros therefore a subsequent investigation is required for the white rhinoceros. The establishment of this novel PCR based technique to identify white and black rhinoceros will allow for efficient species identification in wildlife forensic cases. A biological method was established to study intraspecies variation for the white and black rhinoceros; however the investigated target regions did not yield sufficient genetic variation. The core techniques developed in this study will be valuable for future studies that wish to investigate genetic variation in mammal species.
- Full Text:
- Authors: Parsons, Michelle
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/56059 , vital:26769
- Description: The black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros are found in South Africa. A decline in the populations of these species has resulted due to human activities such as habitat fragmentation and poaching. This has contributed to the loss of genetic diversity amongst the black and white rhinoceros. Conservation and anti-poaching efforts are needed to help maintain genetic diversity. These efforts could be improved through the development of non-invasive techniques to examine DNA from threatened animals. The aim of this research was to develop a molecular technique which would allow for the identification of the black and white rhinoceros and to develop a molecular technique which would allow for intraspecies genetic variation to be examined. DNA extractions were performed on matched faecal and tissue samples that were collected from two regions in South Africa. Polymerase chain reaction (PCR) primer sets were designed to investigate several regions of the rhinoceros mitochondrial genome. PCR optimisation was completed for the target regions. Sequencing was conducted on all final PCR products. The cytochrome c oxidase subunit 1 (COIi) gene allowed for the rhinoceros family to be identified. This region was digested with the HindIII restriction enzyme, which allowed for the specific identification of either the black or white rhinoceros. A subsequent region of the cytochrome c oxidase subunit 1 (COIii) as well as the D-loop, hypervariable regions (HV1 and HV2), cytochrome b (cytb) and 16s rRNA regions were investigated. These regions displayed potential for establishing geographic origin for black rhinoceros samples, whereas the D-loop and HV2 show potential for the white rhinoceros. The white rhinoceros displayed sequence variation in the HV2 and cytb region, while variation was observed in the COIi and HV1 for the black rhinoceros. All investigated target regions allowed for the rhinoceros family to be identified. The COI (COIi and COIii), HV2 and cytb regions allowed for the subspecies of rhinoceros to be identified, however the D-loop was not able to identify the white rhinoceros species. The 16s rRNA and HV1 regions allowed for the correct subspecies of rhinoceros to be identified, however as the primers were only compatible for the black rhinoceros therefore a subsequent investigation is required for the white rhinoceros. The establishment of this novel PCR based technique to identify white and black rhinoceros will allow for efficient species identification in wildlife forensic cases. A biological method was established to study intraspecies variation for the white and black rhinoceros; however the investigated target regions did not yield sufficient genetic variation. The core techniques developed in this study will be valuable for future studies that wish to investigate genetic variation in mammal species.
- Full Text:
The diets of co-occuring anurans in a small South African river: assessments using stomach contents, stable isotope ratios and fatty acid profiles
- Authors: Sikutshwa, Likho
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/54405 , vital:26562
- Description: During their life cycle amphibians change their habitat and feeding, and are important consumers in both terrestrial and aquatic habitats. The trophic ecology of anurans has been studied intensively using gut content analysis, but very little work has been done using biochemical techniques such as stable isotope and fatty acid analyses. These biochemical techniques produce data that allow for additional inferences about the trophic ecology of anurans, as they reveal what the organisms assimilated over time rather than what was recently ingested. The investigation of the feeding ecology and trophic interactions of anurans using gut content analyses together with stable isotope and fatty acid analyses will help us to better understand their ecological roles. The objective of this thesis was to assess the feeding ecology of four anurans (Amietia angolensis, Amietophyrnus rangeri, Strongylopus grayii and Xenopus laevis) in a temperate river using a combination of gut content, stable isotope and fatty acid analyses. Frogs, tadpoles and potential food sources were sampled in two sites (upstream and downstream) in the Kowie River, Eastern Cape Province, South Africa. Gut content analyses identified 147 prey items belonging to 12 prey orders in the stomachs of the sampled specimens. In both A. angolensis and S. grayii the most important prey category was Coleoptera, followed by Hemiptera, Diptera and Hymenoptera at both sites. Aquatic prey items (aquatic hemipterans, chirinomids and blackflies) were the most important food sources for X. laevis (Alimentary Index (IAi) = 6.4; 5.2; 4.2). In Am. rangeri, Hymenoptera was the most important prey category (IAi = 8.3). The trophic niche overlap between A. angolensis and S. grayii was biologically significant (> 0.6), and in the remaining species there was no significant trophic niche overlap. Amietia angolensis showed a larger trophic niche (Levin’s measure; B = 7.7 and Bst = 0.84 downstream, and upstream B = 7.6 (Bst = 0.82) compared to the other species. The gut content analyses showed that frogs feed on a variety of prey items that constitutes food sources from both aquatic and terrestrial habitats. Stable isotopes indicated that aquatic derived sources contributed significantly more towards the diets of X. laevis, A. angolensis tadpoles and S. grayii tadpoles compared with the other anurans, whereas aquatic and terrestrial derived food sources contributed equally to the diets of A. angolensis and S. grayii. Increased trophic positions in A. angolensis and S. grayii occurred throughout their development. The four different species had similar fatty acid profiles in the upstream region, and fairly similar δ13C values, suggesting that they probably consumed similar food. Fatty acid profiles of anurans in the downstream region showed distinct separations among the species. Tadpoles had high levels of diatom-associated fatty acids (20:5ω3; A. angolensis tadpole – 8.4 %, S. grayii tadpole – 9.4 % upstream and downstream; 9.1 and 6.1 % total fatty acids (TFA), respectively). All four species had substantial contributions from bacterial fatty acids, and large proportions of saturated fatty acids (30.6 - 50.0 %) including those with 14 and 18 carbons, indicating that bacterial and detritus food sources played an important role in their diets. The fatty acid profiles revealed high proportions of polyunsaturated fatty acids (PUFAs) and essential fatty acids (EFAs) in all species, indicating a good quality of food and that the quality of food consumed was similar among species. The results demonstrated the usefulness of a combination of traditional techniques (gut content techniques) and biochemical techniques (stable isotopes and fatty acid analysis) for assessing consumption and assimilation. The amphibian assemblages examined derived much of their energy from terrestrial and aquatic sources. This information will allow more precise and comprehensive assessments of trophic interactions in freshwater habitats, along with aiding in future amphibian conservation and management efforts.
- Full Text:
- Authors: Sikutshwa, Likho
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/54405 , vital:26562
- Description: During their life cycle amphibians change their habitat and feeding, and are important consumers in both terrestrial and aquatic habitats. The trophic ecology of anurans has been studied intensively using gut content analysis, but very little work has been done using biochemical techniques such as stable isotope and fatty acid analyses. These biochemical techniques produce data that allow for additional inferences about the trophic ecology of anurans, as they reveal what the organisms assimilated over time rather than what was recently ingested. The investigation of the feeding ecology and trophic interactions of anurans using gut content analyses together with stable isotope and fatty acid analyses will help us to better understand their ecological roles. The objective of this thesis was to assess the feeding ecology of four anurans (Amietia angolensis, Amietophyrnus rangeri, Strongylopus grayii and Xenopus laevis) in a temperate river using a combination of gut content, stable isotope and fatty acid analyses. Frogs, tadpoles and potential food sources were sampled in two sites (upstream and downstream) in the Kowie River, Eastern Cape Province, South Africa. Gut content analyses identified 147 prey items belonging to 12 prey orders in the stomachs of the sampled specimens. In both A. angolensis and S. grayii the most important prey category was Coleoptera, followed by Hemiptera, Diptera and Hymenoptera at both sites. Aquatic prey items (aquatic hemipterans, chirinomids and blackflies) were the most important food sources for X. laevis (Alimentary Index (IAi) = 6.4; 5.2; 4.2). In Am. rangeri, Hymenoptera was the most important prey category (IAi = 8.3). The trophic niche overlap between A. angolensis and S. grayii was biologically significant (> 0.6), and in the remaining species there was no significant trophic niche overlap. Amietia angolensis showed a larger trophic niche (Levin’s measure; B = 7.7 and Bst = 0.84 downstream, and upstream B = 7.6 (Bst = 0.82) compared to the other species. The gut content analyses showed that frogs feed on a variety of prey items that constitutes food sources from both aquatic and terrestrial habitats. Stable isotopes indicated that aquatic derived sources contributed significantly more towards the diets of X. laevis, A. angolensis tadpoles and S. grayii tadpoles compared with the other anurans, whereas aquatic and terrestrial derived food sources contributed equally to the diets of A. angolensis and S. grayii. Increased trophic positions in A. angolensis and S. grayii occurred throughout their development. The four different species had similar fatty acid profiles in the upstream region, and fairly similar δ13C values, suggesting that they probably consumed similar food. Fatty acid profiles of anurans in the downstream region showed distinct separations among the species. Tadpoles had high levels of diatom-associated fatty acids (20:5ω3; A. angolensis tadpole – 8.4 %, S. grayii tadpole – 9.4 % upstream and downstream; 9.1 and 6.1 % total fatty acids (TFA), respectively). All four species had substantial contributions from bacterial fatty acids, and large proportions of saturated fatty acids (30.6 - 50.0 %) including those with 14 and 18 carbons, indicating that bacterial and detritus food sources played an important role in their diets. The fatty acid profiles revealed high proportions of polyunsaturated fatty acids (PUFAs) and essential fatty acids (EFAs) in all species, indicating a good quality of food and that the quality of food consumed was similar among species. The results demonstrated the usefulness of a combination of traditional techniques (gut content techniques) and biochemical techniques (stable isotopes and fatty acid analysis) for assessing consumption and assimilation. The amphibian assemblages examined derived much of their energy from terrestrial and aquatic sources. This information will allow more precise and comprehensive assessments of trophic interactions in freshwater habitats, along with aiding in future amphibian conservation and management efforts.
- Full Text:
The economics of institutions, institutional governance and efficiency: the case of water distribution in Lower Sundays River Valley
- Authors: Madigele, Patricia Kefilwe
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10962/54777 , vital:26611
- Description: The institutional dynamics, policies and legislation that were prevalent during the apartheid era have left imprints that are difficult to ignore as they still dictate the interaction between different elements in the water sector to date. During the apartheid era, the formulation of policies was informed by racial segregation, resulting in a socio-economic pattern that dictated the distribution and access of resources for the people of different races in the country. Post-apartheid, the National Water Act has established the basis for management of water resources on a catchment basis (for equity, efficiency and sustainability), and the Water Services Act aims to ensure everybody has access to basic water supply and sanitation services. Regardless of the improvements in water supply to the rural sector made by the South African government, many of the current patterns of water use are still characterised by inequality, inefficiency, and inadequacy. The poor remain marginalised, and emerging farmers and poor rural communities have limited access to water resources while water continues to be used inefficiently by some farmers in the agricultural sector with few incentives to improve its water use efficiency. Despite the existence of the thriving citrus industry in the area, around 60% of people in the Sundays River Valley Municipality (SRVM) live below the poverty datum line. The inequality between the municipal populace and the commercial citrus industry is noticeable and the inequitable water redistribution is prevalent in the Lower Sundays River Valley (LSRV). The problem of disrupted water supply is prevalent in the catchment. However, there is also currently no physical shortage of water in the catchment. Therefore, the currently experienced problems with water supply in the LSRV are consequence of a lack of effective institutions and infrastructure, not of physical water scarcity. It is argued in this paper that there is a notable lack of understanding about the design of institutions for water management in developing countries. The vast majority of research on water management and access is premised on neoclassical economics ideas related to water markets and pricing among others. The neoclassical economics approach, however, does not adequately define the role of institutions in shaping the direction of water access and supply. This study uses new institutional economics (NIE) arguments to define the institutional arrangements and dynamics defining the water sector in South Africa, using the Lower Sunday River Water Users Association (LSR-WUA) as the case study. It aims at analysing the institutional governance and performance of the using equity, efficiency and effectiveness as key indicators. The various research methods employed in this study include; interpretive and post-positivist paradigms, quantitative and qualitative research, the case study research method and in-depth key informant interviews. It is concluded that that the current and future decisions made by the LSR-WUA are not entirely independent of those made in the past under Sundays River Irrigation Board (SRIB). The thesis argues that such factors as old effective networks, vested interests of commercial farmers, sunk costs towards the building of canals, among other factors, may have influenced the dependence of the LSR-WUA on the SRIB’s set path. It is further concluded that the absence of contractual agreement between the LRS-WUA which acts as the bulk water supplier, and the SRVM which acts as both the water services authority (WSA) and the water service provider (WSP) creates an institutional arrangement deficiency. Such an institutional arrangement vacuum can lead to a failure of the water institutions in the catchment to provide water resources effectively. The study further argues that because the post-apartheid National Water Policy of South Africa is largely influenced by neoclassical economics foundations, the desired results in the water sector, such as equitable distribution of water resources, have not yet been fulfilled completely.
- Full Text:
- Authors: Madigele, Patricia Kefilwe
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10962/54777 , vital:26611
- Description: The institutional dynamics, policies and legislation that were prevalent during the apartheid era have left imprints that are difficult to ignore as they still dictate the interaction between different elements in the water sector to date. During the apartheid era, the formulation of policies was informed by racial segregation, resulting in a socio-economic pattern that dictated the distribution and access of resources for the people of different races in the country. Post-apartheid, the National Water Act has established the basis for management of water resources on a catchment basis (for equity, efficiency and sustainability), and the Water Services Act aims to ensure everybody has access to basic water supply and sanitation services. Regardless of the improvements in water supply to the rural sector made by the South African government, many of the current patterns of water use are still characterised by inequality, inefficiency, and inadequacy. The poor remain marginalised, and emerging farmers and poor rural communities have limited access to water resources while water continues to be used inefficiently by some farmers in the agricultural sector with few incentives to improve its water use efficiency. Despite the existence of the thriving citrus industry in the area, around 60% of people in the Sundays River Valley Municipality (SRVM) live below the poverty datum line. The inequality between the municipal populace and the commercial citrus industry is noticeable and the inequitable water redistribution is prevalent in the Lower Sundays River Valley (LSRV). The problem of disrupted water supply is prevalent in the catchment. However, there is also currently no physical shortage of water in the catchment. Therefore, the currently experienced problems with water supply in the LSRV are consequence of a lack of effective institutions and infrastructure, not of physical water scarcity. It is argued in this paper that there is a notable lack of understanding about the design of institutions for water management in developing countries. The vast majority of research on water management and access is premised on neoclassical economics ideas related to water markets and pricing among others. The neoclassical economics approach, however, does not adequately define the role of institutions in shaping the direction of water access and supply. This study uses new institutional economics (NIE) arguments to define the institutional arrangements and dynamics defining the water sector in South Africa, using the Lower Sunday River Water Users Association (LSR-WUA) as the case study. It aims at analysing the institutional governance and performance of the using equity, efficiency and effectiveness as key indicators. The various research methods employed in this study include; interpretive and post-positivist paradigms, quantitative and qualitative research, the case study research method and in-depth key informant interviews. It is concluded that that the current and future decisions made by the LSR-WUA are not entirely independent of those made in the past under Sundays River Irrigation Board (SRIB). The thesis argues that such factors as old effective networks, vested interests of commercial farmers, sunk costs towards the building of canals, among other factors, may have influenced the dependence of the LSR-WUA on the SRIB’s set path. It is further concluded that the absence of contractual agreement between the LRS-WUA which acts as the bulk water supplier, and the SRVM which acts as both the water services authority (WSA) and the water service provider (WSP) creates an institutional arrangement deficiency. Such an institutional arrangement vacuum can lead to a failure of the water institutions in the catchment to provide water resources effectively. The study further argues that because the post-apartheid National Water Policy of South Africa is largely influenced by neoclassical economics foundations, the desired results in the water sector, such as equitable distribution of water resources, have not yet been fulfilled completely.
- Full Text:
The effect of extracellular Hsp90β and TGF-β1 on colon cancer biology
- Authors: Perks, Tamarin
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/55896 , vital:26753
- Description: The TGF-β signaling pathway is known to be one of the most commonly mutated pathways in human cancers, while Hsp90 is a bone fide drug target that is involved in regulating the conformation and activity of many oncoproteins. The role of intracellular Hsp90 in cancer has thus far been established and there is a growing link between extracellular Hsp90 and cancer metastasis, as well as the role of TGF-β in metastasis. This study aimed to analyse the interaction between Hsp90 (both intracellular and extracellular) and the TGF-β machinery in cancer cells, as well as to determine the effect of these proteins on cellular responses on the biology of cancer cells. This was achieved by studying the expression of Hsp90; TGF-βRII and TGF-β1 in cancer cell lines of various origins using flow cytometry, ELISA, and western blot analysis. The genetically paired SW480 and SW620 colon cancer cell lines, derived from a primary tumour and lymph node metastasis, respectively, were selected for further study due to differences in expression levels and activation of the TGF-β1 pathway. SW480 cells expressed double the level of TGF-βRII compared to SW620 cells, while SW620 expressed two times more extracellular TGF-β1 than SW480 cells. A direct interaction between TGF-β1 and Hsp90β was determined in vitro, and confirmed in vivo in SW620 cells. Growth, adhesion and migration were analysed in SW480 and SW620 cells. SW480 cells adhered significantly faster than SW620 cells, while SW620 cells had a greater rate of migration. Inhibiting the TGF-β pathway, specifically TGF-βRI, using SB 431542, as well as inhibiting Hsp90 with novobiocin, caused an increase in migration in SW480 cells. Only the addition of TGF-β1 in combination with Hsp90 as well as SB 431542 caused an increase in migration in SW620 cells. The canonical TGF-β1/TGF-βRI/TGF-βRII pathway may be constitutively active in SW620 cells and the inhibition of TGF-βRI may suggest an alternate pathway or receptor in both SW480 and SW620 cells.
- Full Text:
- Authors: Perks, Tamarin
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/55896 , vital:26753
- Description: The TGF-β signaling pathway is known to be one of the most commonly mutated pathways in human cancers, while Hsp90 is a bone fide drug target that is involved in regulating the conformation and activity of many oncoproteins. The role of intracellular Hsp90 in cancer has thus far been established and there is a growing link between extracellular Hsp90 and cancer metastasis, as well as the role of TGF-β in metastasis. This study aimed to analyse the interaction between Hsp90 (both intracellular and extracellular) and the TGF-β machinery in cancer cells, as well as to determine the effect of these proteins on cellular responses on the biology of cancer cells. This was achieved by studying the expression of Hsp90; TGF-βRII and TGF-β1 in cancer cell lines of various origins using flow cytometry, ELISA, and western blot analysis. The genetically paired SW480 and SW620 colon cancer cell lines, derived from a primary tumour and lymph node metastasis, respectively, were selected for further study due to differences in expression levels and activation of the TGF-β1 pathway. SW480 cells expressed double the level of TGF-βRII compared to SW620 cells, while SW620 expressed two times more extracellular TGF-β1 than SW480 cells. A direct interaction between TGF-β1 and Hsp90β was determined in vitro, and confirmed in vivo in SW620 cells. Growth, adhesion and migration were analysed in SW480 and SW620 cells. SW480 cells adhered significantly faster than SW620 cells, while SW620 cells had a greater rate of migration. Inhibiting the TGF-β pathway, specifically TGF-βRI, using SB 431542, as well as inhibiting Hsp90 with novobiocin, caused an increase in migration in SW480 cells. Only the addition of TGF-β1 in combination with Hsp90 as well as SB 431542 caused an increase in migration in SW620 cells. The canonical TGF-β1/TGF-βRI/TGF-βRII pathway may be constitutively active in SW620 cells and the inhibition of TGF-βRI may suggest an alternate pathway or receptor in both SW480 and SW620 cells.
- Full Text:
The isolation, characterisation and chemotaxonomic significance of secondary metabolites from selected South African Laurencia spp. Rhodophyta
- Authors: Fakee, Jameel
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64696 , vital:28593
- Description: Bioprospection of marine organisms as a potential source for lead drugs is becoming increasingly popular. The secondary metabolome of these organisms consists of structurally diverse molecules possessing unprecedented carbon skeletons, the biosynthesis of which occurs via complex metabolomic pathways driven by specialist enzymes. This structural novelty is highly influential on the favourable bioactivity these compounds display. A prominent example of such a compound is trabectedin marketed as Yondelis®. Registered for the treatment of soft tissue sarcomas, this marine drug was developed from extracts of the tunicate Ecteinascidia turbinata. South Africa is renowned for possessing a highly diverse marine biota including several endemic species of marine red algae belonging to the Laurencia sensu stricto genus, which falls within the Laurencia complex. Despite having a good reputation for fascinating secondary metabolites, the taxonomy of Laurencia natural products is proving challenging for reasons including the presence of cryptic species, as well as individual species displaying morphological variability. The aim of this study was thus to isolate secondary metabolites from various South African Laurencia spp. and subsequently assess their chemotaxonomic significance by analysis of a parallel plastid rbcL phylogeny study of Laurencia spp. This study reports the first phycochemical investigation into Laurencia natalensis Kylin, Laurencia cf. corymbosa J.Agardh, Laurencia complanata (Suhr) Kützing, Laurencia sodwaniensis Francis, Bolton, Mattio and Anderson submitted, Laurencia multiclavata Francis, Bolton, Mattio and Anderson submitted, and a South African specimen of Laurenciella marilzae Gil-Rodríguez, Sentíes, Díaz-Larrea, Cassano and M.T. Fujii (basionym: Laurencia marilzae) originally described from Spain. Additionally, the chemical profiles of previously explored species Laurencia flexuosa Kützing and Laurencia glomerata Kützing were re-investigated. The organic extracts of the above species afforded 31 compounds belonging to a wide array of structural classes including halo-chamigranes, linear C15 acetogenins, indole alkaloids, cuparanes and cyclic bromo-ethers. A new tri-cyclic keto-cuparane (4.4) was isolated from L.cf. corymbosa alongside the new cuparanes 4.1 and 4.7. Algoane (5.9), a unique marker compound isolated from L. natalensis, was previously only reported from a sea-hare. Such marker compounds which are exclusive to an individual algal species increase the ease of their subsequent identification. The feasibility of chemotaxonomy as an additional tool to classify Laurencia spp. Was established as broad predictions of a specimen’s phylogeny, based on representatives of its secondary metabolome, proved viable. The study specimens were shown to possess similar chemical profiles to their sister species e.g. L. complanata, L. sodwaniensis and L. multiclavata produced similar metabolites to their sister species as inferred by an rbcL phylogeny tree. Finally, a 1H NMR profiling study on the crude organic extracts of various Laurencia spp. generated distinctive, reproducible spectra, exposing the value of NMR spectroscopy as a rudimentary species discernment tool.
- Full Text:
- Authors: Fakee, Jameel
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64696 , vital:28593
- Description: Bioprospection of marine organisms as a potential source for lead drugs is becoming increasingly popular. The secondary metabolome of these organisms consists of structurally diverse molecules possessing unprecedented carbon skeletons, the biosynthesis of which occurs via complex metabolomic pathways driven by specialist enzymes. This structural novelty is highly influential on the favourable bioactivity these compounds display. A prominent example of such a compound is trabectedin marketed as Yondelis®. Registered for the treatment of soft tissue sarcomas, this marine drug was developed from extracts of the tunicate Ecteinascidia turbinata. South Africa is renowned for possessing a highly diverse marine biota including several endemic species of marine red algae belonging to the Laurencia sensu stricto genus, which falls within the Laurencia complex. Despite having a good reputation for fascinating secondary metabolites, the taxonomy of Laurencia natural products is proving challenging for reasons including the presence of cryptic species, as well as individual species displaying morphological variability. The aim of this study was thus to isolate secondary metabolites from various South African Laurencia spp. and subsequently assess their chemotaxonomic significance by analysis of a parallel plastid rbcL phylogeny study of Laurencia spp. This study reports the first phycochemical investigation into Laurencia natalensis Kylin, Laurencia cf. corymbosa J.Agardh, Laurencia complanata (Suhr) Kützing, Laurencia sodwaniensis Francis, Bolton, Mattio and Anderson submitted, Laurencia multiclavata Francis, Bolton, Mattio and Anderson submitted, and a South African specimen of Laurenciella marilzae Gil-Rodríguez, Sentíes, Díaz-Larrea, Cassano and M.T. Fujii (basionym: Laurencia marilzae) originally described from Spain. Additionally, the chemical profiles of previously explored species Laurencia flexuosa Kützing and Laurencia glomerata Kützing were re-investigated. The organic extracts of the above species afforded 31 compounds belonging to a wide array of structural classes including halo-chamigranes, linear C15 acetogenins, indole alkaloids, cuparanes and cyclic bromo-ethers. A new tri-cyclic keto-cuparane (4.4) was isolated from L.cf. corymbosa alongside the new cuparanes 4.1 and 4.7. Algoane (5.9), a unique marker compound isolated from L. natalensis, was previously only reported from a sea-hare. Such marker compounds which are exclusive to an individual algal species increase the ease of their subsequent identification. The feasibility of chemotaxonomy as an additional tool to classify Laurencia spp. Was established as broad predictions of a specimen’s phylogeny, based on representatives of its secondary metabolome, proved viable. The study specimens were shown to possess similar chemical profiles to their sister species e.g. L. complanata, L. sodwaniensis and L. multiclavata produced similar metabolites to their sister species as inferred by an rbcL phylogeny tree. Finally, a 1H NMR profiling study on the crude organic extracts of various Laurencia spp. generated distinctive, reproducible spectra, exposing the value of NMR spectroscopy as a rudimentary species discernment tool.
- Full Text:
The reform of world order?: BRICS in an Interpolar world
- Authors: Phyllis, Yvonne
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193520 , vital:45339
- Description: International relations has recently seen new developments which are unpredictable and in their infant stage. The causes of these developments are plentiful, the consequences stemming from waning unipolarity to the emergence of new fora creating their own spaces. Whatever the case, international relations is not as it was in the period just after the Cold War. As a result, the terms of global governance established after 1990 have come under serious scrutiny. This transition has the makings of a new world order, an interpolar world order. This study asserts that we no longer live in a unipolar world, nor do we live in a world which can only be described as multipolar. It makes the argument that although multipolarity is a crucial element of the world, it only offers a partial description of today’s order. The study asserts that it is interpolarity which is closest in accounting for today’s world. Not only does it describe the world as multipolar, it also describes it as interdependent. To this end, the study provides a detailed account of what is meant by an interpolar world order and how differently it explains international events. It also provides an account of factors which can develop in an interpolar world. One of these includes allowing room for emerging powers to create their own spaces in efforts of avoiding co-option while continuing to realise the importance of operating within a context of continuity. This means that emerging countries create their own spaces but they also realise the importance of working with already established regimes such as the G20. BRICS (Brazil, Russia, India, China and South Africa) is used as a case study to indicate one of the new developments afforded by an interpolar order-the emergence of new fora. The study asserts that although BRICS is rife with internal dissimilarities, it has indicated some degree of political will in one aspect; that is; advocating for the reform of the terms of global governance, advocating for more representative forms of global governance. The study thus explores factors of a world whose contours are gradually changing but which are unpredictable and in flux. , Thesis (MA) -- Faculty of Humanities, Political and International Studies, 2015
- Full Text:
- Authors: Phyllis, Yvonne
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193520 , vital:45339
- Description: International relations has recently seen new developments which are unpredictable and in their infant stage. The causes of these developments are plentiful, the consequences stemming from waning unipolarity to the emergence of new fora creating their own spaces. Whatever the case, international relations is not as it was in the period just after the Cold War. As a result, the terms of global governance established after 1990 have come under serious scrutiny. This transition has the makings of a new world order, an interpolar world order. This study asserts that we no longer live in a unipolar world, nor do we live in a world which can only be described as multipolar. It makes the argument that although multipolarity is a crucial element of the world, it only offers a partial description of today’s order. The study asserts that it is interpolarity which is closest in accounting for today’s world. Not only does it describe the world as multipolar, it also describes it as interdependent. To this end, the study provides a detailed account of what is meant by an interpolar world order and how differently it explains international events. It also provides an account of factors which can develop in an interpolar world. One of these includes allowing room for emerging powers to create their own spaces in efforts of avoiding co-option while continuing to realise the importance of operating within a context of continuity. This means that emerging countries create their own spaces but they also realise the importance of working with already established regimes such as the G20. BRICS (Brazil, Russia, India, China and South Africa) is used as a case study to indicate one of the new developments afforded by an interpolar order-the emergence of new fora. The study asserts that although BRICS is rife with internal dissimilarities, it has indicated some degree of political will in one aspect; that is; advocating for the reform of the terms of global governance, advocating for more representative forms of global governance. The study thus explores factors of a world whose contours are gradually changing but which are unpredictable and in flux. , Thesis (MA) -- Faculty of Humanities, Political and International Studies, 2015
- Full Text:
The role of leadership style and organisational structure in organisational effectiveness: a case study
- Authors: Messaris, Annette
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10962/54452 , vital:26566
- Description: This research explores the role leadership style and organisational structure play in organisational effectiveness. Organisational effectiveness is one of the more complex terms to define although essential to understand in order for an organisation to grow and develop. A small to medium wine sales and distribution organisation, its leadership style and organisational structure were chosen as a focus of this case study. Organisational effectiveness in this study is understood by the terms growth and development using the Greiner Theory of Evolution and Revolution (1983). The literature explores the role of leadership style in organisational effectiveness by exploring various theories and focusing on The Full Range Leadership Model by Bass and Avolio (1994). In order to analyse the role of organisational structure in organisational effectiveness, the different forms of organisational structure and the role they have on the organisation’s ability to grow and develop are explored. The primary purpose of this study is to investigate the role leadership style and organisational structure play in organisational effectiveness. A qualitative content analysis paradigm was used with a Case Study method. The data was gathered using structured interviews conducted on all 39 permanent staff members, day to day observation and the Multifactor Leadership Questionnaire (MLQ). The MLQ is used as a supporting tool to verify the leadership findings in the interviews. The data was analysed using NVivo10 and STATISTICA to gain insight into the leadership style and organisational structure of the organisation. The findings reflected that certain themes were repeatedly mentioned in the interviews and the definition of organisational effectiveness: structured leadership, more active leadership, lack of communication, staff motivation, staff training and development and organisational culture. As regards organisational structure, the following themes arose: The need for regular meetings, increased team work and more structured job descriptions. Through the analysis of all the components, leadership style and organisational structure were identified as having a significant role in organisational effectiveness which will be further analysed in this study.
- Full Text:
- Authors: Messaris, Annette
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10962/54452 , vital:26566
- Description: This research explores the role leadership style and organisational structure play in organisational effectiveness. Organisational effectiveness is one of the more complex terms to define although essential to understand in order for an organisation to grow and develop. A small to medium wine sales and distribution organisation, its leadership style and organisational structure were chosen as a focus of this case study. Organisational effectiveness in this study is understood by the terms growth and development using the Greiner Theory of Evolution and Revolution (1983). The literature explores the role of leadership style in organisational effectiveness by exploring various theories and focusing on The Full Range Leadership Model by Bass and Avolio (1994). In order to analyse the role of organisational structure in organisational effectiveness, the different forms of organisational structure and the role they have on the organisation’s ability to grow and develop are explored. The primary purpose of this study is to investigate the role leadership style and organisational structure play in organisational effectiveness. A qualitative content analysis paradigm was used with a Case Study method. The data was gathered using structured interviews conducted on all 39 permanent staff members, day to day observation and the Multifactor Leadership Questionnaire (MLQ). The MLQ is used as a supporting tool to verify the leadership findings in the interviews. The data was analysed using NVivo10 and STATISTICA to gain insight into the leadership style and organisational structure of the organisation. The findings reflected that certain themes were repeatedly mentioned in the interviews and the definition of organisational effectiveness: structured leadership, more active leadership, lack of communication, staff motivation, staff training and development and organisational culture. As regards organisational structure, the following themes arose: The need for regular meetings, increased team work and more structured job descriptions. Through the analysis of all the components, leadership style and organisational structure were identified as having a significant role in organisational effectiveness which will be further analysed in this study.
- Full Text:
The role of Stress Inducible Protein 1 (STI1) in the regulation of actin dynamics
- Authors: Beckley, Samantha Joy
- Date: 2015
- Subjects: Heat shock proteins , Molecular chaperones , Actin , Microfilament proteins , Cell migration , Adenosine triphosphatase , Metastasis
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193941 , vital:45409
- Description: Stress-inducible protein 1 (STI1) otherwise known as Hop (Hsp70/Hsp90 organising protein) is a highly conserved abundant co-chaperone of the Hsp70 and Hsp90 chaperones. STI1 acts as an adapter protein, where it regulates the transfer of protein substrates from Hsp70 to Hsp90 during the assembly of a number of chaperone-client protein complexes. The role of STI1 associating independently with non-chaperone proteins has become increasingly prominent. Recent data from colocalisation and co-sedimentation analyses in our laboratory suggested a direct interaction between STI1 and the cytoskeletal protein, actin. However, there was a lack of information on the motifs which mediated this interaction, as well as the exact role of STI1 in the regulation of cytoskeletal dynamics. Two putative actin binding motifs, DAYKKK (within the TPR2A domain) and a polyproline region (after the DP1 domain), were identified in mammalian STI1. Our data from in vitro interaction studies including surface plasmon resonance and high speed co-sedimentation assays suggested that both TPR1 and TPR2AB were required for the STI1-actin interaction, and peptides corresponding to either the DAYKKK or the polyproline motif, alone or in combination, could not block the STI1-actin interaction. Full length mSTI1 was shown to have ATPase activity and when combined with actin an increase in ATPase activity was seen. Ex vivo studies using STI1 knockdown shRNA HEK293T cells and non-targeting control shRNA HEK293T cells showed a change of F-actin morphology as well as reduction in levels of actin-binding proteins profilin, cofilin and tubulin in the STI1 knockdown cells. These data extend our understanding of the role of STI1 in regulating actin dynamics and may have implications for cell migration. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2015
- Full Text:
- Authors: Beckley, Samantha Joy
- Date: 2015
- Subjects: Heat shock proteins , Molecular chaperones , Actin , Microfilament proteins , Cell migration , Adenosine triphosphatase , Metastasis
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193941 , vital:45409
- Description: Stress-inducible protein 1 (STI1) otherwise known as Hop (Hsp70/Hsp90 organising protein) is a highly conserved abundant co-chaperone of the Hsp70 and Hsp90 chaperones. STI1 acts as an adapter protein, where it regulates the transfer of protein substrates from Hsp70 to Hsp90 during the assembly of a number of chaperone-client protein complexes. The role of STI1 associating independently with non-chaperone proteins has become increasingly prominent. Recent data from colocalisation and co-sedimentation analyses in our laboratory suggested a direct interaction between STI1 and the cytoskeletal protein, actin. However, there was a lack of information on the motifs which mediated this interaction, as well as the exact role of STI1 in the regulation of cytoskeletal dynamics. Two putative actin binding motifs, DAYKKK (within the TPR2A domain) and a polyproline region (after the DP1 domain), were identified in mammalian STI1. Our data from in vitro interaction studies including surface plasmon resonance and high speed co-sedimentation assays suggested that both TPR1 and TPR2AB were required for the STI1-actin interaction, and peptides corresponding to either the DAYKKK or the polyproline motif, alone or in combination, could not block the STI1-actin interaction. Full length mSTI1 was shown to have ATPase activity and when combined with actin an increase in ATPase activity was seen. Ex vivo studies using STI1 knockdown shRNA HEK293T cells and non-targeting control shRNA HEK293T cells showed a change of F-actin morphology as well as reduction in levels of actin-binding proteins profilin, cofilin and tubulin in the STI1 knockdown cells. These data extend our understanding of the role of STI1 in regulating actin dynamics and may have implications for cell migration. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2015
- Full Text:
Thermal physiology and behavioural ecology of the white shark, carcharodon carcharias
- Authors: Gennari, Enrico
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64002 , vital:28522
- Description: Expected release date-May 2019
- Full Text:
- Authors: Gennari, Enrico
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64002 , vital:28522
- Description: Expected release date-May 2019
- Full Text: