Growth and photosynthetic responses of Acacia (Vachellia) seedlings to atmospheric CO2 increased from glacial to current concentrations: underlying mechanisms and ecological implications
- Authors: Anderson, Bruce Maurice
- Date: 2020
- Subjects: Acacia vachellia , Acacia vachellia -- Growth , Acacia -- South Africa
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/138182 , vital:37604
- Description: The African Acacia species Vachellia karroo, V. robusta, V. nilotica, and V. tortilis are some of the most invasive species implicated in bush encroachment and woody thickening of historically open savannas in southern Africa. This is partially explained by historic increases in atmospheric CO2 concentrations, which are proposed to have promoted the growth and survivorship of C3 tree seedlings relative to C4 grasses. However, the uniformity of CO2 responsiveness and differences among Vachellia species remain largely undetermined. Here we investigate the growth and photosynthetic responses of four Vachellia species, all implicated in woody encroachment, but originating from distinct climatic niches. Exposing these species to a range of sub-ambient CO2 concentrations (12 – 40 Pa) showed that V. karroo, V. robusta, V. nilotica and V. tortilis all responded strongly and fairly consistently to increasing CO2 concentrations, acting as a ‘functional type’ despite being selected from different geographic regions and having different climatic niches. Combined average net CO2 assimilation rates increased by 130% despite significant, but low levels of down-regulation and decreased stomatal conductance. The increased photosynthetic rates stimulated growth and biomass production in all compartments, with no significant differences in interspecific above and below ground allocation. Growth rates and dry biomass increased by 50% and 186%, respectively, while leaf level water use efficiency (ratio of net CO2 assimilation rate to transpiration rate) increased by an average of 218%. When this was scaled to the whole plant level, this stimulation was decreased to 80%. The decrease was the result of the CO2 stimulated increase in canopy areas, which increased leaf area for water loss. The seedlings’ total number of spinescent physical defenses, as well as the average mass and spine mass fraction also increased with rising CO2. These thicker spines could act as better deterrents against vertebrate browsers. Spine density was unchanged, however, showing that the increased spine numbers were associated with larger seedlings at higher CO2 rather than an increase in the number of spines per stem length. The stimulatory effects of increasing CO2 concentrations since the last glacial maximum and resultant increases in seedling growth and biomass are likely to have had important consequences for the survival and establishment of Acacia seedlings. Tolerance of drought and disturbance has been related to seedling size, hence stimulating the growth rate could confer disturbance tolerance and this tolerance would develop more rapidly with increasing CO2 concentrations. Furthermore, increased nitrogen and water use efficiency have the potential to support seedling establishment in environments where these resources would otherwise be limited at lower atmospheric CO2 concentrations. Resulting in a larger proportion of CO2 fertilization responsive woody seedlings surviving the seedling size classes, and persisting within historically open savannas. Where interspecific differences occurred they are likely to have arisen from adaptation to specific climates where these species are native and selection would have been driven by factors such climate, resource availability, levels of disturbance and competitive interactions. V. karroo had the highest growth rates and strong CO2 driven increases in biomass accumulation, despite having the lowest inherent photosynthetic rates. V. karroo also had the lowest increase in water use efficiency and high transpiration rates could potentially increase access to soil nutrients through mass flow. This species had the highest mean spine mass and showed significant increases in spine mass fraction at elevated CO2 concentrations, which may be important for deterring herbivores. V. robusta’s distribution to the mesic east coast of Africa suggests that water is an important limitation to its distribution. Hence, the CO2 stimulated increase in water use efficiency at both leaf and whole canopy level allows speculation that this may be an important driver of this species’ range expansion, which might continue if increasing levels of CO2 continue to promote water use efficiency. V. nilotica occupies a broad range of habitats, inhabiting large areas of the subtropics both north and south of the equator, with the strongest climatic correlates being the precipitation of the wettest quarter followed by high temperature seasonality. In response to increasing CO2, V. nilotica showed overall strong increases in growth, water use efficiency, and physical defenses. These responses may explain why V. nilotica has been such a successful encroacher in a broad range of habitats where limitations are likely to include multiple climatic factors and disturbances. V. tortilis has the widest distribution of all the species studied, covering broad ranges of Africa and only being excluded from the wettest parts of the equator and driest parts of the deserts. In these experiments this species showed the lowest biomass responsiveness to CO2, but had especially large increases in water use efficiency at both the leaf and canopy level. This may have been an important driver for this species’ encroachment into the more arid parts of its distribution, however this link will need to be verified with further experimentation.
- Full Text:
- Date Issued: 2020
- Authors: Anderson, Bruce Maurice
- Date: 2020
- Subjects: Acacia vachellia , Acacia vachellia -- Growth , Acacia -- South Africa
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/138182 , vital:37604
- Description: The African Acacia species Vachellia karroo, V. robusta, V. nilotica, and V. tortilis are some of the most invasive species implicated in bush encroachment and woody thickening of historically open savannas in southern Africa. This is partially explained by historic increases in atmospheric CO2 concentrations, which are proposed to have promoted the growth and survivorship of C3 tree seedlings relative to C4 grasses. However, the uniformity of CO2 responsiveness and differences among Vachellia species remain largely undetermined. Here we investigate the growth and photosynthetic responses of four Vachellia species, all implicated in woody encroachment, but originating from distinct climatic niches. Exposing these species to a range of sub-ambient CO2 concentrations (12 – 40 Pa) showed that V. karroo, V. robusta, V. nilotica and V. tortilis all responded strongly and fairly consistently to increasing CO2 concentrations, acting as a ‘functional type’ despite being selected from different geographic regions and having different climatic niches. Combined average net CO2 assimilation rates increased by 130% despite significant, but low levels of down-regulation and decreased stomatal conductance. The increased photosynthetic rates stimulated growth and biomass production in all compartments, with no significant differences in interspecific above and below ground allocation. Growth rates and dry biomass increased by 50% and 186%, respectively, while leaf level water use efficiency (ratio of net CO2 assimilation rate to transpiration rate) increased by an average of 218%. When this was scaled to the whole plant level, this stimulation was decreased to 80%. The decrease was the result of the CO2 stimulated increase in canopy areas, which increased leaf area for water loss. The seedlings’ total number of spinescent physical defenses, as well as the average mass and spine mass fraction also increased with rising CO2. These thicker spines could act as better deterrents against vertebrate browsers. Spine density was unchanged, however, showing that the increased spine numbers were associated with larger seedlings at higher CO2 rather than an increase in the number of spines per stem length. The stimulatory effects of increasing CO2 concentrations since the last glacial maximum and resultant increases in seedling growth and biomass are likely to have had important consequences for the survival and establishment of Acacia seedlings. Tolerance of drought and disturbance has been related to seedling size, hence stimulating the growth rate could confer disturbance tolerance and this tolerance would develop more rapidly with increasing CO2 concentrations. Furthermore, increased nitrogen and water use efficiency have the potential to support seedling establishment in environments where these resources would otherwise be limited at lower atmospheric CO2 concentrations. Resulting in a larger proportion of CO2 fertilization responsive woody seedlings surviving the seedling size classes, and persisting within historically open savannas. Where interspecific differences occurred they are likely to have arisen from adaptation to specific climates where these species are native and selection would have been driven by factors such climate, resource availability, levels of disturbance and competitive interactions. V. karroo had the highest growth rates and strong CO2 driven increases in biomass accumulation, despite having the lowest inherent photosynthetic rates. V. karroo also had the lowest increase in water use efficiency and high transpiration rates could potentially increase access to soil nutrients through mass flow. This species had the highest mean spine mass and showed significant increases in spine mass fraction at elevated CO2 concentrations, which may be important for deterring herbivores. V. robusta’s distribution to the mesic east coast of Africa suggests that water is an important limitation to its distribution. Hence, the CO2 stimulated increase in water use efficiency at both leaf and whole canopy level allows speculation that this may be an important driver of this species’ range expansion, which might continue if increasing levels of CO2 continue to promote water use efficiency. V. nilotica occupies a broad range of habitats, inhabiting large areas of the subtropics both north and south of the equator, with the strongest climatic correlates being the precipitation of the wettest quarter followed by high temperature seasonality. In response to increasing CO2, V. nilotica showed overall strong increases in growth, water use efficiency, and physical defenses. These responses may explain why V. nilotica has been such a successful encroacher in a broad range of habitats where limitations are likely to include multiple climatic factors and disturbances. V. tortilis has the widest distribution of all the species studied, covering broad ranges of Africa and only being excluded from the wettest parts of the equator and driest parts of the deserts. In these experiments this species showed the lowest biomass responsiveness to CO2, but had especially large increases in water use efficiency at both the leaf and canopy level. This may have been an important driver for this species’ encroachment into the more arid parts of its distribution, however this link will need to be verified with further experimentation.
- Full Text:
- Date Issued: 2020
Towards a capability maturity model for a cyber range
- Authors: Aschmann, Michael Joseph
- Date: 2020
- Subjects: Computer software -- Development , Computer security
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163142 , vital:41013
- Description: This work describes research undertaken towards the development of a Capability Maturity Model (CMM) for Cyber Ranges (CRs) focused on cyber security. Global cyber security needs are on the rise, and the need for attribution within the cyber domain is of particular concern. This has prompted major efforts to enhance cyber capabilities within organisations to increase their total cyber resilience posture. These efforts include, but are not limited to, the testing of computational devices, networks, and applications, and cyber skills training focused on prevention, detection and cyber attack response. A cyber range allows for the testing of the computational environment. By developing cyber events within a confined virtual or sand-boxed cyber environment, a cyber range can prepare the next generation of cyber security specialists to handle a variety of potential cyber attacks. Cyber ranges have different purposes, each designed to fulfil a different computational testing and cyber training goal; consequently, cyber ranges can vary greatly in the level of variety, capability, maturity and complexity. As cyber ranges proliferate and become more and more valued as tools for cyber security, a method to classify or rate them becomes essential. Yet while a universal criteria for measuring cyber ranges in terms of their capability maturity levels becomes more critical, there are currently very limited resources for researchers aiming to perform this kind of work. For this reason, this work proposes and describes a CMM, designed to give organisations the ability to benchmark the capability maturity of a given cyber range. This research adopted a synthesised approach to the development of a CMM, grounded in prior research and focused on the production of a conceptual model that provides a useful level of abstraction. In order to achieve this goal, the core capability elements of a cyber range are defined with their relative importance, allowing for the development of a proposed classification cyber range levels. An analysis of data gathered during the course of an expert review, together with other research, further supported the development of the conceptual model. In the context of cyber range capability, classification will include the ability of the cyber range to perform its functions optimally with different core capability elements, focusing on the Measurement of Capability (MoC) with its elements, namely effect, performance and threat ability. Cyber range maturity can evolve over time and can be defined through the Measurement of Maturity (MoM) with its elements, namely people, processes, technology. The combination of these measurements utilising the CMM for a CR determines the capability maturity level of a CR. The primary outcome of this research is the proposed level-based CMM framework for a cyber range, developed using adopted and synthesised CMMs, the analysis of an expert review, and the mapping of the results.
- Full Text:
- Date Issued: 2020
- Authors: Aschmann, Michael Joseph
- Date: 2020
- Subjects: Computer software -- Development , Computer security
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163142 , vital:41013
- Description: This work describes research undertaken towards the development of a Capability Maturity Model (CMM) for Cyber Ranges (CRs) focused on cyber security. Global cyber security needs are on the rise, and the need for attribution within the cyber domain is of particular concern. This has prompted major efforts to enhance cyber capabilities within organisations to increase their total cyber resilience posture. These efforts include, but are not limited to, the testing of computational devices, networks, and applications, and cyber skills training focused on prevention, detection and cyber attack response. A cyber range allows for the testing of the computational environment. By developing cyber events within a confined virtual or sand-boxed cyber environment, a cyber range can prepare the next generation of cyber security specialists to handle a variety of potential cyber attacks. Cyber ranges have different purposes, each designed to fulfil a different computational testing and cyber training goal; consequently, cyber ranges can vary greatly in the level of variety, capability, maturity and complexity. As cyber ranges proliferate and become more and more valued as tools for cyber security, a method to classify or rate them becomes essential. Yet while a universal criteria for measuring cyber ranges in terms of their capability maturity levels becomes more critical, there are currently very limited resources for researchers aiming to perform this kind of work. For this reason, this work proposes and describes a CMM, designed to give organisations the ability to benchmark the capability maturity of a given cyber range. This research adopted a synthesised approach to the development of a CMM, grounded in prior research and focused on the production of a conceptual model that provides a useful level of abstraction. In order to achieve this goal, the core capability elements of a cyber range are defined with their relative importance, allowing for the development of a proposed classification cyber range levels. An analysis of data gathered during the course of an expert review, together with other research, further supported the development of the conceptual model. In the context of cyber range capability, classification will include the ability of the cyber range to perform its functions optimally with different core capability elements, focusing on the Measurement of Capability (MoC) with its elements, namely effect, performance and threat ability. Cyber range maturity can evolve over time and can be defined through the Measurement of Maturity (MoM) with its elements, namely people, processes, technology. The combination of these measurements utilising the CMM for a CR determines the capability maturity level of a CR. The primary outcome of this research is the proposed level-based CMM framework for a cyber range, developed using adopted and synthesised CMMs, the analysis of an expert review, and the mapping of the results.
- Full Text:
- Date Issued: 2020
Design, formulation and evalauation of liposomes co-loaded with human serum Albumin and Rifampicin
- Authors: Bapolisi, Alain Murhimalika
- Date: 2020
- Subjects: Liposomes , Serum albumin , Rifampin , Mycobacterium tuberculosis
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/161780 , vital:40670
- Description: Tuberculosis (TB) is a devastating infectious disease caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious agent. The high morbidity and mortality rates of TB are partly due to factors such as the lengthy regimen (of 6–24 months), the development of drug resistance, and the pathogen location within the macrophages. These, with poor physiochemical properties of existing drugs hamper the effectiveness of the treatment despite the existence of potent antibiotics such as Rifampicin (Rif). Hydrophobicity plagues many drugs, including Rif, which are then particularly affected due to inherently poor intracellular availability. Novel drug delivery approaches are therefore needed in order to optimize the cytotoxic potential of said antitubercular drugs. To improve the bioavailability of hydrophobic drugs, numerous delivery strategies have been developed. Amongst these, the coordination of cytotoxic drugs to therapeutic proteins have shown some success for improved efficacy in the management of illnesses including infectious diseases. Of therapeutic proteins, Human Serum Albumin (HSA) is an attractive drug carrier with interestingbenefits such as low immunogenicity, antioxidant properties and improving cellular uptake ofdrugs through HSA-specific binding sites which are expressed on most cells including macrophages, where M. tuberculosis often resides. Hence, combination of Rif to HSA (Rif-HSA)seems a promising approach for improved intracellular delivery of Rif. However, the in vivo stability of colloidal protein-based therapeutics is mostly challenging and an effective vehicle is needed to control the biological fate of such conjugates.Liposomes seem to be appropriate carriers for the Rif-HSA complex due to their reputable applicability for encapsulating diverse materials (i.e., hydrophobic and hydrophilic compounds or small and complex molecules) and preventing chemical and biological degradation of the cargo. Therefore, the main objective of this study was to simultaneously encapsulate Rif and HSA in liposomes, which, to the best of our knowledge, has not been done before. The dual liposomes (Rif-HSA-lip) were made by a modified “Reverse Phase Evaporation” method (REV), following a Design of Experiments (DOE) approach to determine which factors impact the formulation. In addition, liposomes were made from crude soybean lecithin (CSL), rather than expensive and highly purified lipids. The liposomes were fully characterised, and the encapsulation efficiency (î) was monitored using high-performance liquid chromatography (HPLC). The results were correlated with factors such as organic and aqueous phase composition, as well as the in vitro release profile of Rif. Transmission electron microscopy (TEM) results confirmed the formation of spherical dual liposomes nanoparticles of roughly 200 nm. Dynamic light scattering (DLS) and Zeta potential measurements showed a negative charge (<–45 mV) and with satisfactory polydispersity (PDI<0.5). HSA dramatically improved the aqueous solubility of Rif (from1.9 mg/ml in water to around 4.3 mg/ml in HSA 10% solution) mainly due to Rif-HSA hydrophobic interactions. This resulted in a good î of almost 60% for Rif, despite the presence of bulky HSA in the lipid bilayer. These details were confirmed using proton nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FTIR). Furthermore, energy dispersive X-ray (EDX) and DLS data suggested the presence of HSA poking out on the surface of liposomes, which is encouraging for potential targeted delivery in the future. The in vitro release studies also depicted a substantial improvement in the diffusion of Rif in dual liposomes versus free Rif, from 65% after 12 hours for free Rif to 95% after only 5 hours for Rif- HSA-lip. Finally, stability studies conducted over 30 days at room temperature, showed that the freeze-dried formulations of Rif-HSA-lip exhibited good shelf stability over liposomes with no HSA. This study represents an illustrative example of co-loading of antibiotics and proteins into liposomes, which could encourage further development of novel nanoparticulate tools for the effective management of both drug-susceptible and -resistant infectious diseases such as TB.
- Full Text:
- Date Issued: 2020
- Authors: Bapolisi, Alain Murhimalika
- Date: 2020
- Subjects: Liposomes , Serum albumin , Rifampin , Mycobacterium tuberculosis
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/161780 , vital:40670
- Description: Tuberculosis (TB) is a devastating infectious disease caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious agent. The high morbidity and mortality rates of TB are partly due to factors such as the lengthy regimen (of 6–24 months), the development of drug resistance, and the pathogen location within the macrophages. These, with poor physiochemical properties of existing drugs hamper the effectiveness of the treatment despite the existence of potent antibiotics such as Rifampicin (Rif). Hydrophobicity plagues many drugs, including Rif, which are then particularly affected due to inherently poor intracellular availability. Novel drug delivery approaches are therefore needed in order to optimize the cytotoxic potential of said antitubercular drugs. To improve the bioavailability of hydrophobic drugs, numerous delivery strategies have been developed. Amongst these, the coordination of cytotoxic drugs to therapeutic proteins have shown some success for improved efficacy in the management of illnesses including infectious diseases. Of therapeutic proteins, Human Serum Albumin (HSA) is an attractive drug carrier with interestingbenefits such as low immunogenicity, antioxidant properties and improving cellular uptake ofdrugs through HSA-specific binding sites which are expressed on most cells including macrophages, where M. tuberculosis often resides. Hence, combination of Rif to HSA (Rif-HSA)seems a promising approach for improved intracellular delivery of Rif. However, the in vivo stability of colloidal protein-based therapeutics is mostly challenging and an effective vehicle is needed to control the biological fate of such conjugates.Liposomes seem to be appropriate carriers for the Rif-HSA complex due to their reputable applicability for encapsulating diverse materials (i.e., hydrophobic and hydrophilic compounds or small and complex molecules) and preventing chemical and biological degradation of the cargo. Therefore, the main objective of this study was to simultaneously encapsulate Rif and HSA in liposomes, which, to the best of our knowledge, has not been done before. The dual liposomes (Rif-HSA-lip) were made by a modified “Reverse Phase Evaporation” method (REV), following a Design of Experiments (DOE) approach to determine which factors impact the formulation. In addition, liposomes were made from crude soybean lecithin (CSL), rather than expensive and highly purified lipids. The liposomes were fully characterised, and the encapsulation efficiency (î) was monitored using high-performance liquid chromatography (HPLC). The results were correlated with factors such as organic and aqueous phase composition, as well as the in vitro release profile of Rif. Transmission electron microscopy (TEM) results confirmed the formation of spherical dual liposomes nanoparticles of roughly 200 nm. Dynamic light scattering (DLS) and Zeta potential measurements showed a negative charge (<–45 mV) and with satisfactory polydispersity (PDI<0.5). HSA dramatically improved the aqueous solubility of Rif (from1.9 mg/ml in water to around 4.3 mg/ml in HSA 10% solution) mainly due to Rif-HSA hydrophobic interactions. This resulted in a good î of almost 60% for Rif, despite the presence of bulky HSA in the lipid bilayer. These details were confirmed using proton nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FTIR). Furthermore, energy dispersive X-ray (EDX) and DLS data suggested the presence of HSA poking out on the surface of liposomes, which is encouraging for potential targeted delivery in the future. The in vitro release studies also depicted a substantial improvement in the diffusion of Rif in dual liposomes versus free Rif, from 65% after 12 hours for free Rif to 95% after only 5 hours for Rif- HSA-lip. Finally, stability studies conducted over 30 days at room temperature, showed that the freeze-dried formulations of Rif-HSA-lip exhibited good shelf stability over liposomes with no HSA. This study represents an illustrative example of co-loading of antibiotics and proteins into liposomes, which could encourage further development of novel nanoparticulate tools for the effective management of both drug-susceptible and -resistant infectious diseases such as TB.
- Full Text:
- Date Issued: 2020
Design, formulation and evaluation of liposomes co-loaded with human serum albumin and rifampicin
- Authors: Bapolisi, Alain Murhimalika
- Date: 2020
- Subjects: Liposomes , Rifampin , Antitubercular agents , Serum albumin , Albumins , Tuberculosis -- Treatment
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163179 , vital:41016
- Description: Tuberculosis (TB) is a devastating infectious disease caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious agent. The high morbidity and mortality rates of TB are partly due to factors such as the lengthy regimen (of 6–24 months), the development of drug resistance, and the pathogen location within the macrophages. These, with poor physiochemical properties of existing drugs hamper the effectiveness of the treatment despite the existence of potent antibiotics such as Rifampicin (Rif). Hydrophobicity plagues many drugs, including Rif, which are then particularly affected due to inherently poor intracellular availability. Novel drug delivery approaches are therefore needed in order to optimize the cytotoxic potential of said antitubercular drugs. To improve the bioavailability of hydrophobic drugs, numerous delivery strategies have been developed. Amongst these, the coordination of cytotoxic drugs to therapeutic proteins have shown some success for improved efficacy in the management of illnesses including infectious diseases. Of therapeutic proteins, Human Serum Albumin (HSA) is an attractive drug carrier with interesting benefits such as low immunogenicity, antioxidant properties and improving cellular uptake of drugs through HSA-specific binding sites which are expressed on most cells including macrophages, where M. tuberculosis often resides. Hence, combination of Rif to HSA (Rif-HSA) seems a promising approach for improved intracellular delivery of Rif. However, the in vivo stability of colloidal protein-based therapeutics is mostly challenging and an effective vehicle is needed to control the biological fate of such conjugates. Liposomes seem to be appropriate carriers for the Rif-HSA complex due to their reputable applicability for encapsulating diverse materials (i.e., hydrophobic and hydrophilic compounds or small and complex molecules) and preventing chemical and biological degradation of the cargo. Therefore, the main objective of this study was to simultaneously encapsulate Rif and HSA in liposomes, which, to the best of our knowledge, has not been done before. The dual liposomes (Rif-HSA-lip) were made by a modified “Reverse Phase Evaporation” method (REV), following a Design of Experiments (DOE) approach to determine which factors impact the formulation. In addition, liposomes were made from crude soybean lecithin (CSL), rather than expensive and highly purified lipids. iv The liposomes were fully characterised, and the encapsulation efficiency (î) was monitored using high-performance liquid chromatography (HPLC). The results were correlated with factors such as organic and aqueous phase composition, as well as the in vitro release profile of Rif. Transmission electron microscopy (TEM) results confirmed the formation of spherical dual liposomes nanoparticles of roughly 200 nm. Dynamic light scattering (DLS) and Zeta potential measurements showed a negative charge (<–45 mV) and with satisfactory polydispersity (PDI<0.5). HSA dramatically improved the aqueous solubility of Rif (from1.9 mg/ml in water to around 4.3 mg/ml in HSA 10% solution) mainly due to Rif-HSA hydrophobic interactions. This resulted in a good î of almost 60% for Rif, despite the presence of bulky HSA in the lipid bilayer. These details were confirmed using proton nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FTIR). Furthermore, energy dispersive X-ray (EDX) and DLS data suggested the presence of HSA poking out on the surface of liposomes, which is encouraging for potential targeted delivery in the future. The in vitro release studies also depicted a substantial improvement in the diffusion of Rif in dual liposomes versus free Rif, from 65% after 12 hours for free Rif to 95% after only 5 hours for Rif- HSA-lip. Finally, stability studies conducted over 30 days at room temperature, showed that the freeze-dried formulations of Rif-HSA-lip exhibited good shelf stability over liposomes with no HSA. This study represents an illustrative example of co-loading of antibiotics and proteins into liposomes, which could encourage further development of novel nanoparticulate tools for the effective management of both drug-susceptible and -resistant infectious diseases such as TB.
- Full Text:
- Date Issued: 2020
- Authors: Bapolisi, Alain Murhimalika
- Date: 2020
- Subjects: Liposomes , Rifampin , Antitubercular agents , Serum albumin , Albumins , Tuberculosis -- Treatment
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163179 , vital:41016
- Description: Tuberculosis (TB) is a devastating infectious disease caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious agent. The high morbidity and mortality rates of TB are partly due to factors such as the lengthy regimen (of 6–24 months), the development of drug resistance, and the pathogen location within the macrophages. These, with poor physiochemical properties of existing drugs hamper the effectiveness of the treatment despite the existence of potent antibiotics such as Rifampicin (Rif). Hydrophobicity plagues many drugs, including Rif, which are then particularly affected due to inherently poor intracellular availability. Novel drug delivery approaches are therefore needed in order to optimize the cytotoxic potential of said antitubercular drugs. To improve the bioavailability of hydrophobic drugs, numerous delivery strategies have been developed. Amongst these, the coordination of cytotoxic drugs to therapeutic proteins have shown some success for improved efficacy in the management of illnesses including infectious diseases. Of therapeutic proteins, Human Serum Albumin (HSA) is an attractive drug carrier with interesting benefits such as low immunogenicity, antioxidant properties and improving cellular uptake of drugs through HSA-specific binding sites which are expressed on most cells including macrophages, where M. tuberculosis often resides. Hence, combination of Rif to HSA (Rif-HSA) seems a promising approach for improved intracellular delivery of Rif. However, the in vivo stability of colloidal protein-based therapeutics is mostly challenging and an effective vehicle is needed to control the biological fate of such conjugates. Liposomes seem to be appropriate carriers for the Rif-HSA complex due to their reputable applicability for encapsulating diverse materials (i.e., hydrophobic and hydrophilic compounds or small and complex molecules) and preventing chemical and biological degradation of the cargo. Therefore, the main objective of this study was to simultaneously encapsulate Rif and HSA in liposomes, which, to the best of our knowledge, has not been done before. The dual liposomes (Rif-HSA-lip) were made by a modified “Reverse Phase Evaporation” method (REV), following a Design of Experiments (DOE) approach to determine which factors impact the formulation. In addition, liposomes were made from crude soybean lecithin (CSL), rather than expensive and highly purified lipids. iv The liposomes were fully characterised, and the encapsulation efficiency (î) was monitored using high-performance liquid chromatography (HPLC). The results were correlated with factors such as organic and aqueous phase composition, as well as the in vitro release profile of Rif. Transmission electron microscopy (TEM) results confirmed the formation of spherical dual liposomes nanoparticles of roughly 200 nm. Dynamic light scattering (DLS) and Zeta potential measurements showed a negative charge (<–45 mV) and with satisfactory polydispersity (PDI<0.5). HSA dramatically improved the aqueous solubility of Rif (from1.9 mg/ml in water to around 4.3 mg/ml in HSA 10% solution) mainly due to Rif-HSA hydrophobic interactions. This resulted in a good î of almost 60% for Rif, despite the presence of bulky HSA in the lipid bilayer. These details were confirmed using proton nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FTIR). Furthermore, energy dispersive X-ray (EDX) and DLS data suggested the presence of HSA poking out on the surface of liposomes, which is encouraging for potential targeted delivery in the future. The in vitro release studies also depicted a substantial improvement in the diffusion of Rif in dual liposomes versus free Rif, from 65% after 12 hours for free Rif to 95% after only 5 hours for Rif- HSA-lip. Finally, stability studies conducted over 30 days at room temperature, showed that the freeze-dried formulations of Rif-HSA-lip exhibited good shelf stability over liposomes with no HSA. This study represents an illustrative example of co-loading of antibiotics and proteins into liposomes, which could encourage further development of novel nanoparticulate tools for the effective management of both drug-susceptible and -resistant infectious diseases such as TB.
- Full Text:
- Date Issued: 2020
Change of perspectives and behaviour regarding lifestyle, with emphasis on dietary habits, in a rural community
- Authors: Barnard, Mariska
- Date: 2020
- Subjects: Food habits
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/46384 , vital:39565
- Description: Background: The steady increase in deaths due to non-communicable diseases (NCDs) in South Africa is raising concern, as 63% of all deaths worldwide are attributed to NCDs and these diseases cause 36 million deaths each year, with 80 % of incidences occurring in low-and middle-income countries. In rural communities where income is increasing, the prevalence of NCDs are increasing as well. Due to the lack of NCD prevention and treatment in rural communities, it is expected that, if health promotion strategies are not implemented and socio-economic development in South Africa continues, there will soon be an uncontrollable NCD epidemic. It has been found that dietary risks affected people’s healthirrespective of their age, gender or residential sociodemographic development and that dietary improvement might prevent one in every five deaths worldwide.Aim:The aim of this study was to determine the factors that influence the perceptions and behaviour in a rural community with a low socio-economic status regarding dietary habits and to use the knowledge to formulate an effective dietary modification strategy.Designand methodology:For this study,action research with a quantitative and qualitative component was followed.The quantitative component focuses on measureable aspects, and the qualitative component focuses on meaning. Data was collected following the standard operating procedure for anthropometry, blood pressure and blood glucose. Further methods used were questionnaires, 24-hour dietary recalls and focus group discussions. Data were analysed using Microsoft Excel, FoodFinder3 and other calculations.Sample and setting:A convenience sample (n = 16) wasused and this study was undertaken on request of the non-governmental organization, Karoo Angels and included all participants who earn an income and who do not work for themselves, that were willing to participate and living in Rietbron and Vondeling, in the Sarah BaartmanDistrict in the Eastern Cape. Results:Weight changes took place, both the crafters in the mild thinness category gained weight, one gained 3.9 kg and the other 0.5 kg. The three crafters in the normal category did not have to gain or lose weight, but all three ofthem gained an average of 3.6 kg. For the group who had to lose weight, no statistically significant weight change took place from before the intervention (76.08 ±17.67 kg) to after the intervention (75.81 ± 17.81 kg, t(10) = 0.692, p = 0.505). The maximum weight lost ivwas 3.1 kg and the maximum weight gained was 3.2 kg. Changes took place regarding BMI, waist circumference, waist-to-hip ratio and neck circumference. Some positively changed their BMI status.After the implementation of the intervention, there was a slight decrease in frequency of alcohol consumption, but smoking and physical activity remained mostly the same. Hypertension was the most prevalent NCD and is linked to smoking and alcohol consumption which is prevalent in this study. Fruit and vegetable consumption is low, and a slight increase in consumption was evident. A maximum dietary diversityscore of seven and minimum of two, where the mean was 3.81was found. The crafters’ diet did not meet the DASH diet recommendation,the mean energy distribution is of all macronutrients differ with ±4% and none of the participants’ mean micronutrients intake met the recommendations of the DASH diet or RDA. Factors that prevent them from reaching their goals included low income, low availability of fruit, vegetables and transport and no storage for food.Conclusion:It is important to consider the individuals’ living conditions, resources, knowledge, motivation and social group. The environment and resources available have a significant impact on the lifestyle of the individuals. Directing efforts of behaviour change to increase dietary diversity as the main objective, might be a more efficient way to change behaviour.Recommendations:Future studies should consider doing this study over a longer time period. The involvement of a psychologist would also be beneficial to assist the process of behaviour change.
- Full Text:
- Date Issued: 2020
- Authors: Barnard, Mariska
- Date: 2020
- Subjects: Food habits
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/46384 , vital:39565
- Description: Background: The steady increase in deaths due to non-communicable diseases (NCDs) in South Africa is raising concern, as 63% of all deaths worldwide are attributed to NCDs and these diseases cause 36 million deaths each year, with 80 % of incidences occurring in low-and middle-income countries. In rural communities where income is increasing, the prevalence of NCDs are increasing as well. Due to the lack of NCD prevention and treatment in rural communities, it is expected that, if health promotion strategies are not implemented and socio-economic development in South Africa continues, there will soon be an uncontrollable NCD epidemic. It has been found that dietary risks affected people’s healthirrespective of their age, gender or residential sociodemographic development and that dietary improvement might prevent one in every five deaths worldwide.Aim:The aim of this study was to determine the factors that influence the perceptions and behaviour in a rural community with a low socio-economic status regarding dietary habits and to use the knowledge to formulate an effective dietary modification strategy.Designand methodology:For this study,action research with a quantitative and qualitative component was followed.The quantitative component focuses on measureable aspects, and the qualitative component focuses on meaning. Data was collected following the standard operating procedure for anthropometry, blood pressure and blood glucose. Further methods used were questionnaires, 24-hour dietary recalls and focus group discussions. Data were analysed using Microsoft Excel, FoodFinder3 and other calculations.Sample and setting:A convenience sample (n = 16) wasused and this study was undertaken on request of the non-governmental organization, Karoo Angels and included all participants who earn an income and who do not work for themselves, that were willing to participate and living in Rietbron and Vondeling, in the Sarah BaartmanDistrict in the Eastern Cape. Results:Weight changes took place, both the crafters in the mild thinness category gained weight, one gained 3.9 kg and the other 0.5 kg. The three crafters in the normal category did not have to gain or lose weight, but all three ofthem gained an average of 3.6 kg. For the group who had to lose weight, no statistically significant weight change took place from before the intervention (76.08 ±17.67 kg) to after the intervention (75.81 ± 17.81 kg, t(10) = 0.692, p = 0.505). The maximum weight lost ivwas 3.1 kg and the maximum weight gained was 3.2 kg. Changes took place regarding BMI, waist circumference, waist-to-hip ratio and neck circumference. Some positively changed their BMI status.After the implementation of the intervention, there was a slight decrease in frequency of alcohol consumption, but smoking and physical activity remained mostly the same. Hypertension was the most prevalent NCD and is linked to smoking and alcohol consumption which is prevalent in this study. Fruit and vegetable consumption is low, and a slight increase in consumption was evident. A maximum dietary diversityscore of seven and minimum of two, where the mean was 3.81was found. The crafters’ diet did not meet the DASH diet recommendation,the mean energy distribution is of all macronutrients differ with ±4% and none of the participants’ mean micronutrients intake met the recommendations of the DASH diet or RDA. Factors that prevent them from reaching their goals included low income, low availability of fruit, vegetables and transport and no storage for food.Conclusion:It is important to consider the individuals’ living conditions, resources, knowledge, motivation and social group. The environment and resources available have a significant impact on the lifestyle of the individuals. Directing efforts of behaviour change to increase dietary diversity as the main objective, might be a more efficient way to change behaviour.Recommendations:Future studies should consider doing this study over a longer time period. The involvement of a psychologist would also be beneficial to assist the process of behaviour change.
- Full Text:
- Date Issued: 2020
Understanding of the underlying resistance mechanism of the Kat-G protein against isoniazid in Mycobacterium tuberculosis using bioinformatics approaches
- Authors: Barozi, Victor
- Date: 2020
- Subjects: Mycobacterium tuberculosis , Isoniazid , Drug resistance in microorganisms , Proteins -- Microbiology
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/146592 , vital:38540
- Description: Tuberculosis (TB) is a multi-organ infection caused by rod-shaped acid-fast Mycobacterium tuberculosis. The World Health Organization (WHO) ranks TB among the top 10 fatal infections and the leading the cause of death from a single infection. In 2017, TB was responsible for an estimated 1.3 million deaths among both the HIV negative and positive populations worldwide (WHO, 2018). Approximately 23% (roughly 1.7 billion) of the world’s population is estimated to have latent TB with a high risk of reverting to active TB infection. In 2017, an estimated 558,000 people developed drug resistant TB worldwide with 82% of the cases being multi-drug resistant TB (WHO, 2018). South Africa is ranked among the 30 high TB burdened countries with a TB incidence of 322,000 cases in 2017 accounting for 3% of the world’s TB cases. TB is curable and is clinically managed through a combination of intensive and continuation phases of first-line drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide). Second-line drugs which include fluoroquinolones, injectable aminoglycoside and injectable polypeptides are used in cases of first line drug resistance. The third-line drugs include amoxicillin, clofazimine, linezolid and imipenem. These have variable but unproven efficacy to TB and are the last resort in cases of total drug resistance (Jilani et al., 2019). TB drug resistance to first-line drugs especially isoniazid in M. tuberculosis has been attributed to single nucleotide polymorphisms (SNPs) in the catalase peroxidase enzyme (katG), a protein important in the activation of the pro-drug isoniazid. The SNPs especially at position 315 of the katG enzyme are believed to reduce the sensitivity of the M. tuberculosis to isoniazid while still maintaining the enzyme’s catalytic activity - a mechanism not completely understood. KatG protein is important for protecting the bacteria from hydro peroxides and hydroxyl radicals present in an aerobic environment. This study focused on understanding the mechanism of isoniazid drug resistance in M. tuberculosis as a result of high confidence mutations in the katG through modelling the enzyme with its respective variants, performing MD simulations to explore the protein behaviour, calculating the dynamic residue network analysis (DRN) of the variants in respect to the wild type katG and finally performing alanine scanning. From the MD simulations, it was observed that the high confidence mutations i.e. S140R, S140N, G279D, G285D, S315T, S315I, S315R, S315N, G316D, S457I and G593D were not only reducing the backbone flexibility of the protein but also reducing the protein’s conformational variation and space. All the variant protein structures were observed to be more compact compared to the wild type. Residue fluctuation results indicated reduced residue flexibility across all variants in the loop region (position 26-110) responsible for katG dimerization. In addition, mutation S315T is believed to reduce the size of the active site access channel in the protein. From the DRN data, residues in the interface region between the N and C-terminal domains were observed to gain importance in the variants irrespective of the mutation location indicating an allosteric effect of the mutations on the interface region. Alanine scanning results established that residue Leucine at position 48 was not only important in the protein communication but also a destabilizing residue across all the variants. The study not only demonstrated change in the protein behaviour but also showed allosteric effect of the mutations in the katG protein.
- Full Text:
- Date Issued: 2020
- Authors: Barozi, Victor
- Date: 2020
- Subjects: Mycobacterium tuberculosis , Isoniazid , Drug resistance in microorganisms , Proteins -- Microbiology
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/146592 , vital:38540
- Description: Tuberculosis (TB) is a multi-organ infection caused by rod-shaped acid-fast Mycobacterium tuberculosis. The World Health Organization (WHO) ranks TB among the top 10 fatal infections and the leading the cause of death from a single infection. In 2017, TB was responsible for an estimated 1.3 million deaths among both the HIV negative and positive populations worldwide (WHO, 2018). Approximately 23% (roughly 1.7 billion) of the world’s population is estimated to have latent TB with a high risk of reverting to active TB infection. In 2017, an estimated 558,000 people developed drug resistant TB worldwide with 82% of the cases being multi-drug resistant TB (WHO, 2018). South Africa is ranked among the 30 high TB burdened countries with a TB incidence of 322,000 cases in 2017 accounting for 3% of the world’s TB cases. TB is curable and is clinically managed through a combination of intensive and continuation phases of first-line drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide). Second-line drugs which include fluoroquinolones, injectable aminoglycoside and injectable polypeptides are used in cases of first line drug resistance. The third-line drugs include amoxicillin, clofazimine, linezolid and imipenem. These have variable but unproven efficacy to TB and are the last resort in cases of total drug resistance (Jilani et al., 2019). TB drug resistance to first-line drugs especially isoniazid in M. tuberculosis has been attributed to single nucleotide polymorphisms (SNPs) in the catalase peroxidase enzyme (katG), a protein important in the activation of the pro-drug isoniazid. The SNPs especially at position 315 of the katG enzyme are believed to reduce the sensitivity of the M. tuberculosis to isoniazid while still maintaining the enzyme’s catalytic activity - a mechanism not completely understood. KatG protein is important for protecting the bacteria from hydro peroxides and hydroxyl radicals present in an aerobic environment. This study focused on understanding the mechanism of isoniazid drug resistance in M. tuberculosis as a result of high confidence mutations in the katG through modelling the enzyme with its respective variants, performing MD simulations to explore the protein behaviour, calculating the dynamic residue network analysis (DRN) of the variants in respect to the wild type katG and finally performing alanine scanning. From the MD simulations, it was observed that the high confidence mutations i.e. S140R, S140N, G279D, G285D, S315T, S315I, S315R, S315N, G316D, S457I and G593D were not only reducing the backbone flexibility of the protein but also reducing the protein’s conformational variation and space. All the variant protein structures were observed to be more compact compared to the wild type. Residue fluctuation results indicated reduced residue flexibility across all variants in the loop region (position 26-110) responsible for katG dimerization. In addition, mutation S315T is believed to reduce the size of the active site access channel in the protein. From the DRN data, residues in the interface region between the N and C-terminal domains were observed to gain importance in the variants irrespective of the mutation location indicating an allosteric effect of the mutations on the interface region. Alanine scanning results established that residue Leucine at position 48 was not only important in the protein communication but also a destabilizing residue across all the variants. The study not only demonstrated change in the protein behaviour but also showed allosteric effect of the mutations in the katG protein.
- Full Text:
- Date Issued: 2020
The effects of elevated atmospheric CO2 on the biological control of invasive aquatic weeds in South Africa
- Authors: Baso, Nompumelelo Catherine
- Date: 2020
- Subjects: Aquatic weeds -- Biological control -- South Africa , Plants -- Effect of atmospheric carbon dioxide on , Atmospheric carbon dioxide -- Environmental aspects
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/140772 , vital:37917
- Description: There has been a rapid increase in atmospheric CO2 concentration, from pre-industrial values of 280 ppm to more than 400 ppm currently, and this is expected to more than double by the end of the 21st century. Studies have shown that plants grown above 600 ppm tend to have an increased growth rate and invest more in carbon-based defences. This has important implications for the management of invasive alien plants, especially for the field of biological control which is mostly dependent on herbivorous insects. This is because insects reared on such plants have been shown to have reduced overall fitness. Nevertheless, most of the studies on potential changes in plant-insect interactions under elevated CO2 are based on agricultural systems, with only a limited number of these types of studies conducted on alien invasive weeds. However, climate change and invasive species are two of the most prevalent features of global environmental change. Therefore, this also warrants active research and experimental studies to better understand how these systems will be affected by future climates. Thus, the aim of this study was to investigate the effects of elevated atmospheric CO2 on the biological control of four invasive aquatic weeds (Azolla filiculoides, Salvinia molesta, Pistia stratiotes, and Myriophyllum aquaticum). These species are a threat to natural resources in South Africa but are currently under successful control by their biological control agents (Stenopelmus rufinasus, Cyrtobagous salviniae, Neohydronomus affinis, and Lysathia n. sp.). To achieve this, the selected plant species were grown in a three-factor experimental design in winter (CO2 X nutrients X herbivory), and another two-factorial design in summer (CO2 X herbivory). Atmospheric CO2 concentrations were set at ambient (400 ppm) or elevated (800 ppm), as per the predictions of the IPCC. As per my hypothesis, the results suggest that these species will become more challenging in future due to increased biomass production, asexual reproduction and a higher C: N ratio which is evident under high CO2 concentrations. Although the biological control agents were in some instances able to reduce this CO2 fertilisation effect, their efficacy was significantly reduced compared with the levels of control observed at ambient CO2. These results suggest that additional biological control agents and other management methods may be needed for continued control of these invasive macrophytes, both in South Africa and further afield where they are problematic.
- Full Text:
- Date Issued: 2020
- Authors: Baso, Nompumelelo Catherine
- Date: 2020
- Subjects: Aquatic weeds -- Biological control -- South Africa , Plants -- Effect of atmospheric carbon dioxide on , Atmospheric carbon dioxide -- Environmental aspects
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/140772 , vital:37917
- Description: There has been a rapid increase in atmospheric CO2 concentration, from pre-industrial values of 280 ppm to more than 400 ppm currently, and this is expected to more than double by the end of the 21st century. Studies have shown that plants grown above 600 ppm tend to have an increased growth rate and invest more in carbon-based defences. This has important implications for the management of invasive alien plants, especially for the field of biological control which is mostly dependent on herbivorous insects. This is because insects reared on such plants have been shown to have reduced overall fitness. Nevertheless, most of the studies on potential changes in plant-insect interactions under elevated CO2 are based on agricultural systems, with only a limited number of these types of studies conducted on alien invasive weeds. However, climate change and invasive species are two of the most prevalent features of global environmental change. Therefore, this also warrants active research and experimental studies to better understand how these systems will be affected by future climates. Thus, the aim of this study was to investigate the effects of elevated atmospheric CO2 on the biological control of four invasive aquatic weeds (Azolla filiculoides, Salvinia molesta, Pistia stratiotes, and Myriophyllum aquaticum). These species are a threat to natural resources in South Africa but are currently under successful control by their biological control agents (Stenopelmus rufinasus, Cyrtobagous salviniae, Neohydronomus affinis, and Lysathia n. sp.). To achieve this, the selected plant species were grown in a three-factor experimental design in winter (CO2 X nutrients X herbivory), and another two-factorial design in summer (CO2 X herbivory). Atmospheric CO2 concentrations were set at ambient (400 ppm) or elevated (800 ppm), as per the predictions of the IPCC. As per my hypothesis, the results suggest that these species will become more challenging in future due to increased biomass production, asexual reproduction and a higher C: N ratio which is evident under high CO2 concentrations. Although the biological control agents were in some instances able to reduce this CO2 fertilisation effect, their efficacy was significantly reduced compared with the levels of control observed at ambient CO2. These results suggest that additional biological control agents and other management methods may be needed for continued control of these invasive macrophytes, both in South Africa and further afield where they are problematic.
- Full Text:
- Date Issued: 2020
Identification of SANCDB compounds against G2019S and I2020T variants of leucine-rich repeat Kinase 2 (LRRK2) for the development of drugs against Parkinson’s Disease
- Authors: Baye, Bertha Cinthia
- Date: 2020
- Subjects: Antiparkinsonian agents , Parkinson's disease -- Treatment , Protein kinases , Parkinson's disease -- Chemotherapy , Molecules -- Models
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/138764 , vital:37671
- Description: Parkinson’s disease is a type of movement disorder that occurs when nerve cells in the brain stop producing dopamine. It is the second neurodegenerative disease affecting 1-2% of people above the ages of 65 years old. There is a worldwide prevalence of 7 to 10 million affected people of all cultures and race. Studies have shown that mutation that causes Parkinson’s disease result in increased kinase activity. The c.6055 G > A in exon 41 is the most prevalent LRRK2 variation which causes a substitution of glycine to serine in G2019S in the highly activated loop of its MAP kinase domain. The LRRK2 G2019S variant is the most common genetic determinant of Parkinson’s disease identified to date. This work focused on building accurate 3D models of the LRRK2 kinase domain, that were used for large-scale in silico docking against South African natural compounds from the South African Natural Compounds Database (SANCDB; https://sancdb.rubi.ru.ac.za/). Molecular docking was performed to identify compounds that formed interactions with the active site of the protein and had the lowest binding energy scores. Molecular dynamics simulations showed different movements of the protein-ligand complexes and behavioural difference of the wildtype and the variants, all three structures proved to be compact. Network analysis was done to study residue interactions, contact maps, dynamic cross correlations, average BC and average L were used to study the residue interactions and general residue contribution to the functioning of the protein..
- Full Text:
- Date Issued: 2020
- Authors: Baye, Bertha Cinthia
- Date: 2020
- Subjects: Antiparkinsonian agents , Parkinson's disease -- Treatment , Protein kinases , Parkinson's disease -- Chemotherapy , Molecules -- Models
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/138764 , vital:37671
- Description: Parkinson’s disease is a type of movement disorder that occurs when nerve cells in the brain stop producing dopamine. It is the second neurodegenerative disease affecting 1-2% of people above the ages of 65 years old. There is a worldwide prevalence of 7 to 10 million affected people of all cultures and race. Studies have shown that mutation that causes Parkinson’s disease result in increased kinase activity. The c.6055 G > A in exon 41 is the most prevalent LRRK2 variation which causes a substitution of glycine to serine in G2019S in the highly activated loop of its MAP kinase domain. The LRRK2 G2019S variant is the most common genetic determinant of Parkinson’s disease identified to date. This work focused on building accurate 3D models of the LRRK2 kinase domain, that were used for large-scale in silico docking against South African natural compounds from the South African Natural Compounds Database (SANCDB; https://sancdb.rubi.ru.ac.za/). Molecular docking was performed to identify compounds that formed interactions with the active site of the protein and had the lowest binding energy scores. Molecular dynamics simulations showed different movements of the protein-ligand complexes and behavioural difference of the wildtype and the variants, all three structures proved to be compact. Network analysis was done to study residue interactions, contact maps, dynamic cross correlations, average BC and average L were used to study the residue interactions and general residue contribution to the functioning of the protein..
- Full Text:
- Date Issued: 2020
Synthesis and characterization of MXS (M = Mo & V) and carbon supported MXS nanocomposites as Pt-free counter electrodes for electrode for DSSC application
- Authors: Bede, Asanda
- Date: 2020
- Subjects: Voltammetry
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/18599 , vital:42612
- Description: It has been reported that the morphology, crystalline phase composition and electrochemical properties of counter electrode materials such MxS (Mo, V) and carbon supported MxS (Mo, V) composite nanomaterials was of considerable importance because it governs the efficiency of many photon assisted chemical and physical reactions in dye sensitized solar cells (DSSCs). The efficiency of DSSCs with composite counter electrode materials is reliant on the stability of the photochemistry reactions which can be optimized by appropriate doping levels of the composite materials. Moreover, the microstructure such as surface area, distribution of the MxS (Mo, V) and carbon supported MxS (Mo, V) composite nanomaterials, and the stability of the electrostatic bonds between the MxS (Mo, V) with the carbon support also play a significant role in the performance of the DSSCs. This work evaluates the effect of different mole ratios of the MxS (Mo, V) and carbon supported MxS (Mo, V) composite nanomaterials on the morphological, structural and electrochemical properties of the composite materials. MoS2 nanoflakes nanostructures have been synthesized by hydrothermal technique using sodium orthovanadate (Na2MoO4) as precursor. In this work Carbon supported MoS2 NFs have been prepared by physically/chemically mixing different mole ratios of MoS2 NFs with multi-walled carbon nanotubes (MWCNTs) and polyvinylidene in N-methyl-2-pyrrolidinone. The morphological, structural and electrochemical properties of the composite counter electrode materials have been investigated using SEM, XRD FTIR, TEM, RS and CV. SEM analysis has revealed the presence of large MoS2 nanoflakes (NFs) as synthesized. SEM analysis has also revealed significant change in the surface morphology of carbon supported MoS2 composite nanostructures with the change in the mole ratio of the MoS2 NFs and carbon support multi-walled carbon nanotubes. Structural analysis through HRTEM analysis revealed a d-spacing of 0.65 nm with a corresponding (002) lattice plane belonging to a trigonal crystalline phase of MoS2. Also, HRTEM analysis has revealed d-spacing of 0.291 nm corresponding to 002 plane of MWCNTs. Raman spectroscopy has revealed Characteristic Raman vibration frequencies and symmetries at 264.6 cm-1(Eg), 354.2 cm-1 (Ag ) belonging trigonal phase of MoS2 (1T-MoS2). FTIR analysis has revealed a narrow peak at 457.6 cm-1 due Mo-S vibration bond. This observation confirms the success of synthesis of MoS2 nanostructures. Cyclic voltammetry (CV), charge-discharge (CD) and electrochemical impedance spectroscopy (EIS) measurements have revealed that the ratio 6:3:1 have shown to be optimum ratio due to its large reduction rate compared to pristine MoS2 NFs and other carbon supported MoS2 NFs. Calculated Rreduction for the carbon supported MoS2 NFs is the order 3:6:1>1:8:1>6:3:1>8:1:1 indicating the trend of ratio 3:6:1 appeared to have higher reduction rate than the rest of the material and it had far less ΔEpp than the rest of other ratios. All CV curves for both pristine MoS2 NFs and carbon supported MoS2 NFs confirmed a distinct Faradic characteristic. The VS2 nanosheets (NSs) and carbon supported VS2 NSs were also effectively synthesized via hydrothermal method. The SEM micrographs for VS2 NSs and carbon supported VS2 NSs samples reveals level increased. Furthermore, SEM-EDX analysis have confirmed the presence of V and S as well as C and O on carbon supported VS2 nanocomposites, and it clearly shown a gradually blending as the ratios increases. The structural studies through XRD analysis have revealed peaks at 2θ angles of 15.4◦, 28.2◦, 34.2◦, 36.2◦, 43.3◦,48.3◦, 54.4◦, 57.7◦ and 66.2◦ which correspond to the lattice planes (001), (002), (100), (011), (102), (003), (110), (103) and (201) belonging to hexagonal VS2 (H-VS2) crystalline phase as per JCPDS card 36-1139. The HRTEM have revealed that the VS2 NSs have an edge to edge length of ~ 0.294 – 1.248 µm. Also, HRTEM micrographs of VS2 NSs have revealed interplanar d spacing of 0.571 nm belonging to the (001) lattice plane of hexagonal VS2 (H-VS2) structure. FTIR analysis have shown a peak at 558 cm-1 attributed to V-S which is evident that sulfur has bonded with the metal (V) and is in agreement with EDS. CV, CD and EIS measurements have shown that the ratio 1:8:1 is more superior to VS2 NSs and other carbon supported VS2 NSs. Based on Rreduction for the carbon supported nanosheets VS2 nanosheets are ordered as 1:8:1>3:6:1>6:3:1>8:1:1. Carbon supported VS2 NSs of the mole ratio 1:8:1 showed a small resistance of 0.32 Ω. This is further evidence that the carbon supported VS2 NSs of the mole ratio 1:8:1 in addition to revealing excellent catalytic behaviour is also more chemically stable and has good conductivity properties._________
- Full Text:
- Date Issued: 2020
- Authors: Bede, Asanda
- Date: 2020
- Subjects: Voltammetry
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/18599 , vital:42612
- Description: It has been reported that the morphology, crystalline phase composition and electrochemical properties of counter electrode materials such MxS (Mo, V) and carbon supported MxS (Mo, V) composite nanomaterials was of considerable importance because it governs the efficiency of many photon assisted chemical and physical reactions in dye sensitized solar cells (DSSCs). The efficiency of DSSCs with composite counter electrode materials is reliant on the stability of the photochemistry reactions which can be optimized by appropriate doping levels of the composite materials. Moreover, the microstructure such as surface area, distribution of the MxS (Mo, V) and carbon supported MxS (Mo, V) composite nanomaterials, and the stability of the electrostatic bonds between the MxS (Mo, V) with the carbon support also play a significant role in the performance of the DSSCs. This work evaluates the effect of different mole ratios of the MxS (Mo, V) and carbon supported MxS (Mo, V) composite nanomaterials on the morphological, structural and electrochemical properties of the composite materials. MoS2 nanoflakes nanostructures have been synthesized by hydrothermal technique using sodium orthovanadate (Na2MoO4) as precursor. In this work Carbon supported MoS2 NFs have been prepared by physically/chemically mixing different mole ratios of MoS2 NFs with multi-walled carbon nanotubes (MWCNTs) and polyvinylidene in N-methyl-2-pyrrolidinone. The morphological, structural and electrochemical properties of the composite counter electrode materials have been investigated using SEM, XRD FTIR, TEM, RS and CV. SEM analysis has revealed the presence of large MoS2 nanoflakes (NFs) as synthesized. SEM analysis has also revealed significant change in the surface morphology of carbon supported MoS2 composite nanostructures with the change in the mole ratio of the MoS2 NFs and carbon support multi-walled carbon nanotubes. Structural analysis through HRTEM analysis revealed a d-spacing of 0.65 nm with a corresponding (002) lattice plane belonging to a trigonal crystalline phase of MoS2. Also, HRTEM analysis has revealed d-spacing of 0.291 nm corresponding to 002 plane of MWCNTs. Raman spectroscopy has revealed Characteristic Raman vibration frequencies and symmetries at 264.6 cm-1(Eg), 354.2 cm-1 (Ag ) belonging trigonal phase of MoS2 (1T-MoS2). FTIR analysis has revealed a narrow peak at 457.6 cm-1 due Mo-S vibration bond. This observation confirms the success of synthesis of MoS2 nanostructures. Cyclic voltammetry (CV), charge-discharge (CD) and electrochemical impedance spectroscopy (EIS) measurements have revealed that the ratio 6:3:1 have shown to be optimum ratio due to its large reduction rate compared to pristine MoS2 NFs and other carbon supported MoS2 NFs. Calculated Rreduction for the carbon supported MoS2 NFs is the order 3:6:1>1:8:1>6:3:1>8:1:1 indicating the trend of ratio 3:6:1 appeared to have higher reduction rate than the rest of the material and it had far less ΔEpp than the rest of other ratios. All CV curves for both pristine MoS2 NFs and carbon supported MoS2 NFs confirmed a distinct Faradic characteristic. The VS2 nanosheets (NSs) and carbon supported VS2 NSs were also effectively synthesized via hydrothermal method. The SEM micrographs for VS2 NSs and carbon supported VS2 NSs samples reveals level increased. Furthermore, SEM-EDX analysis have confirmed the presence of V and S as well as C and O on carbon supported VS2 nanocomposites, and it clearly shown a gradually blending as the ratios increases. The structural studies through XRD analysis have revealed peaks at 2θ angles of 15.4◦, 28.2◦, 34.2◦, 36.2◦, 43.3◦,48.3◦, 54.4◦, 57.7◦ and 66.2◦ which correspond to the lattice planes (001), (002), (100), (011), (102), (003), (110), (103) and (201) belonging to hexagonal VS2 (H-VS2) crystalline phase as per JCPDS card 36-1139. The HRTEM have revealed that the VS2 NSs have an edge to edge length of ~ 0.294 – 1.248 µm. Also, HRTEM micrographs of VS2 NSs have revealed interplanar d spacing of 0.571 nm belonging to the (001) lattice plane of hexagonal VS2 (H-VS2) structure. FTIR analysis have shown a peak at 558 cm-1 attributed to V-S which is evident that sulfur has bonded with the metal (V) and is in agreement with EDS. CV, CD and EIS measurements have shown that the ratio 1:8:1 is more superior to VS2 NSs and other carbon supported VS2 NSs. Based on Rreduction for the carbon supported nanosheets VS2 nanosheets are ordered as 1:8:1>3:6:1>6:3:1>8:1:1. Carbon supported VS2 NSs of the mole ratio 1:8:1 showed a small resistance of 0.32 Ω. This is further evidence that the carbon supported VS2 NSs of the mole ratio 1:8:1 in addition to revealing excellent catalytic behaviour is also more chemically stable and has good conductivity properties._________
- Full Text:
- Date Issued: 2020
The workload of flight attendants during short-haul flight operations: a system analysis
- Authors: Bennett, Chloe Kayla
- Date: 2020
- Subjects: Flight attendants -- Health and hygiene , Employees -- South Africa -- Workload
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/123431 , vital:35437
- Description: Background and aim: Flight attendants forms a significant part in 24-hour aviation industry. Flight attendant fatigue is a significant problem in the aviation industry as it continues to jeopardize the ability to fulfil important safety and security roles which is critical in performance duty of a flight attendant. However, little attention has been accomplished to the workload, working conditions and fatigue of flight attendants crew in transport aircraft. In addition, there is currently less research that have also embraced the problematic of smaller regional/commercial operation (short-haul flight operations) inducing fatigue among short-haul flight attendants as the nature of this operation are often characterised with high productivity expectations in a demanding environment with high time pressures resulting in high workloads and fatigue. Thus, flight attendant fatigue and workload is a worldwide challenge in this operational environment and less attention has been given to the determining factors. Therefore, the aim of the study was to determine the workload factors contributing to flight attendant fatigue during short-haul flight operations. Methods (System analysis): To achieve the research aim, the work system analysis, based on the Smith and Carayon-Sainfort model was chosen as the main research approach which was conducted in two ways; based on existing literature and secondly based on expert interviews. This method provided a systemic aspect to understand the whole work system of flight attendants work during short-haul operations in order to identify all the contributing factors to flight attendant fatigue and workload. Results: The literature analysis and the data from the expert interviews highlighted significant findings to flight attendant fatigue and workload. The reasons for flight attendant fatigue operating short-haul flights can be found at organizational, task, individual, environmental levels and tools and technologies and due to the interaction of the factors. The main factors of flight attendants’ fatigue are thought primarily as a function of scheduling due to irregular, mixed schedules with early starts and late finishes, extended duty days (long working hours), as well as high workload, due to the short turnaround flights, the number of sectors flown in a single duty period and duty length and high jobs demands. In addition, flight duty and rest regulations, confined work space in the cabin, vibrations, noise and lighting, sleeping in an unfamiliar environment, family responsibilities all add to additional stress placed on the body which can influence workload and sleep and consequently influencing fatigue. Conclusion: Overall the study determined that flight attendant fatigue is a significant problem in modern industry of short-haul operations. Using this systematic approach (work system analysis based on the framework of the work system model developed by Smith and Carayon-Sainfort (1989) allowed for an accurate representation of the complexity of flight attendant work environment in short-haul aviation industries, thus contributed to an increased understanding of fatigue and risk factors that span the entire work system and aid in identifying the patterns in combination of work system variables that are associated with increased risk to flight attendant fatigue. Overall flight attendant fatigue is a product of interactions with the short-haul environment. It can have a negative impact on safety, performance and well-being. Therefore, it needs to be managed and dealt with in the near future.
- Full Text:
- Date Issued: 2020
- Authors: Bennett, Chloe Kayla
- Date: 2020
- Subjects: Flight attendants -- Health and hygiene , Employees -- South Africa -- Workload
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/123431 , vital:35437
- Description: Background and aim: Flight attendants forms a significant part in 24-hour aviation industry. Flight attendant fatigue is a significant problem in the aviation industry as it continues to jeopardize the ability to fulfil important safety and security roles which is critical in performance duty of a flight attendant. However, little attention has been accomplished to the workload, working conditions and fatigue of flight attendants crew in transport aircraft. In addition, there is currently less research that have also embraced the problematic of smaller regional/commercial operation (short-haul flight operations) inducing fatigue among short-haul flight attendants as the nature of this operation are often characterised with high productivity expectations in a demanding environment with high time pressures resulting in high workloads and fatigue. Thus, flight attendant fatigue and workload is a worldwide challenge in this operational environment and less attention has been given to the determining factors. Therefore, the aim of the study was to determine the workload factors contributing to flight attendant fatigue during short-haul flight operations. Methods (System analysis): To achieve the research aim, the work system analysis, based on the Smith and Carayon-Sainfort model was chosen as the main research approach which was conducted in two ways; based on existing literature and secondly based on expert interviews. This method provided a systemic aspect to understand the whole work system of flight attendants work during short-haul operations in order to identify all the contributing factors to flight attendant fatigue and workload. Results: The literature analysis and the data from the expert interviews highlighted significant findings to flight attendant fatigue and workload. The reasons for flight attendant fatigue operating short-haul flights can be found at organizational, task, individual, environmental levels and tools and technologies and due to the interaction of the factors. The main factors of flight attendants’ fatigue are thought primarily as a function of scheduling due to irregular, mixed schedules with early starts and late finishes, extended duty days (long working hours), as well as high workload, due to the short turnaround flights, the number of sectors flown in a single duty period and duty length and high jobs demands. In addition, flight duty and rest regulations, confined work space in the cabin, vibrations, noise and lighting, sleeping in an unfamiliar environment, family responsibilities all add to additional stress placed on the body which can influence workload and sleep and consequently influencing fatigue. Conclusion: Overall the study determined that flight attendant fatigue is a significant problem in modern industry of short-haul operations. Using this systematic approach (work system analysis based on the framework of the work system model developed by Smith and Carayon-Sainfort (1989) allowed for an accurate representation of the complexity of flight attendant work environment in short-haul aviation industries, thus contributed to an increased understanding of fatigue and risk factors that span the entire work system and aid in identifying the patterns in combination of work system variables that are associated with increased risk to flight attendant fatigue. Overall flight attendant fatigue is a product of interactions with the short-haul environment. It can have a negative impact on safety, performance and well-being. Therefore, it needs to be managed and dealt with in the near future.
- Full Text:
- Date Issued: 2020
System analysis of fatigue in pilots and co-pilots executing short-hall flight operations
- Authors: Bennett, Cleo Taylor
- Date: 2020
- Subjects: Air pilots -- Health and hygiene , Fatigue , Work environment -- Psychological aspects , Work environment -- Physiological aspects
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/146622 , vital:38543
- Description: Background: This study was conducted as part of Denel’s South African Regional Aircraft (SARA) development project. Regional aircraft have a maximum flight time of 60 minutes. Hence, the study focuses on matters pertaining to the short-haul flight context. Pilot fatigue has been recognised as a safety concern in the aviation industry. It impacts on pilot performance across the board, not least in the short-haul context. However, the specific factors that lead to pilot fatigue in short-haul operations have not been well researched. Research Aim: To identify and examine the factors which influence pilot/co-pilot fatigue in short-haul aviation contexts. Method: Fatigue is multifaceted, and has multiple definitions and descriptions. It is acknowledged as a complex phenomenon, the development of which is dynamically influenced by various factors. Thus, a systems approach based on the work system model by Smith and Carayon-Sainfort (1989) was adopted for this study. A systems analysis was conducted in two parts: 1) a literature analysis, and 2) expert interviews. Results: Both the literature analysis and the interviews indicated that pilot fatigue in short-haul flight operations represent composite system outcomes influenced by various factors. The factors identified were structured (systematised) into categories, namely organizational factors, task-related factors, environmental factors, factors linked to technology and tools, and non-work-related factors specific to the individual pilot. An example of a task-related factor would be the performance by pilots of multiple take-offs and landings; organizational factors include work time arrangements and duty scheduling (e.g. unpredictable schedule, early starts/late finishes, number of flight sectors in a shift, extended working hours, numerous consecutive work days, standby duties, flight, duty and rest limitations (regulations and guidelines); and short turnaround periods); environmental factors might include the small pressurised cockpit environment, movement restriction, very low humidity, low air pressure, vibrations, high noise levels, low light intensity light, and inclement weather); there are many examples of how tools and technology utilized by pilots might affect their fatigue levels; and finally, pilot-specific non-work-related factors would include things like the pilot’s age, health (lifestyle), family stress, work experience and sleep environment. All of these factors were identified during the literature analysis and have a significant bearing on how fatigue could present in short-haul pilots/co-pilots. Other important fatigue-related factors revealed during the expert interviews included, organizational culture, time management, health implications of fatigue, and management of fatigue. Conclusions: Pilot fatigue is a complex and multi-factorial physiological condition. There are many interacting components which contribute to pilot fatigue in short-haul operations. These should be viewed from an integrated perspective and holistic, systems-based approaches should be taken to manage these issues, particularly in the context of short-haul operations. This would optimize pilot performance and well-being and, most importantly, improve the safety of the work environment to enhance overall operation safety. Limitations: The study does not quantify the contributions made to pilot fatigue by the various factors explored. Therefore, care needs to be taken when designing and implementing interventions based on this research.
- Full Text:
- Date Issued: 2020
- Authors: Bennett, Cleo Taylor
- Date: 2020
- Subjects: Air pilots -- Health and hygiene , Fatigue , Work environment -- Psychological aspects , Work environment -- Physiological aspects
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/146622 , vital:38543
- Description: Background: This study was conducted as part of Denel’s South African Regional Aircraft (SARA) development project. Regional aircraft have a maximum flight time of 60 minutes. Hence, the study focuses on matters pertaining to the short-haul flight context. Pilot fatigue has been recognised as a safety concern in the aviation industry. It impacts on pilot performance across the board, not least in the short-haul context. However, the specific factors that lead to pilot fatigue in short-haul operations have not been well researched. Research Aim: To identify and examine the factors which influence pilot/co-pilot fatigue in short-haul aviation contexts. Method: Fatigue is multifaceted, and has multiple definitions and descriptions. It is acknowledged as a complex phenomenon, the development of which is dynamically influenced by various factors. Thus, a systems approach based on the work system model by Smith and Carayon-Sainfort (1989) was adopted for this study. A systems analysis was conducted in two parts: 1) a literature analysis, and 2) expert interviews. Results: Both the literature analysis and the interviews indicated that pilot fatigue in short-haul flight operations represent composite system outcomes influenced by various factors. The factors identified were structured (systematised) into categories, namely organizational factors, task-related factors, environmental factors, factors linked to technology and tools, and non-work-related factors specific to the individual pilot. An example of a task-related factor would be the performance by pilots of multiple take-offs and landings; organizational factors include work time arrangements and duty scheduling (e.g. unpredictable schedule, early starts/late finishes, number of flight sectors in a shift, extended working hours, numerous consecutive work days, standby duties, flight, duty and rest limitations (regulations and guidelines); and short turnaround periods); environmental factors might include the small pressurised cockpit environment, movement restriction, very low humidity, low air pressure, vibrations, high noise levels, low light intensity light, and inclement weather); there are many examples of how tools and technology utilized by pilots might affect their fatigue levels; and finally, pilot-specific non-work-related factors would include things like the pilot’s age, health (lifestyle), family stress, work experience and sleep environment. All of these factors were identified during the literature analysis and have a significant bearing on how fatigue could present in short-haul pilots/co-pilots. Other important fatigue-related factors revealed during the expert interviews included, organizational culture, time management, health implications of fatigue, and management of fatigue. Conclusions: Pilot fatigue is a complex and multi-factorial physiological condition. There are many interacting components which contribute to pilot fatigue in short-haul operations. These should be viewed from an integrated perspective and holistic, systems-based approaches should be taken to manage these issues, particularly in the context of short-haul operations. This would optimize pilot performance and well-being and, most importantly, improve the safety of the work environment to enhance overall operation safety. Limitations: The study does not quantify the contributions made to pilot fatigue by the various factors explored. Therefore, care needs to be taken when designing and implementing interventions based on this research.
- Full Text:
- Date Issued: 2020
A stunting profile of children under the age of five visiting Bhisho hospital clinic, part of the umbrella project: a profile of stunting in children under the age of five in food insecure villages in Mqanduli, Ngqushwa and Bhisho hospital, Eastern Cape, South Africa
- Authors: Beyleveld, Janine
- Date: 2020
- Subjects: Children -- growth
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/50201 , vital:42066
- Description: Introduction and Background: Stunting is the most prevalent form of childhood malnutrition where about 149 million children under the age of five can be classified as stunted globally. South Africa has one of the highest stunting rates in the world at 27%, causing devastating effects on economic productivity as well as on an individual’s nutritional status. The presence of stunted growth in children is a strong indicator of chronic undernutrition and highlights injustices experienced within communities. Aims and Objectives: The aim of this study is to develop a stunning profile of children under the age of five, visiting BhishoHospital’s gateway clinic in the Eastern Cape, South Africa. The objectives were to determine the prevalence of stunting of the children visiting Bhisho Hospital’s clinic and to identify the drivers of stunting in the area. Methodology: A quantitative study with a descriptive, cross-sectional design was used. The study population included all children under the age of five visiting Bhisho Hospital’s clinic. Data was collected by means of an interview-administered questionnaire. Results: The prevalence of stunting in the area was 47.5%. A significant association was found between the participants' main form of sanitation and stunting category in the group of infants younger than six months (p = 0.007) and the group older than six months(p = 0.040). Discussion: The prevalence of stunting in the area was far higher than the national average of 27%, although the majority of the sample had a normal weight. The use of non-flush toilets was found to be a risk factor for childhood stunting. Recommendation: Financial and political investment in child health needs to be placed as a top priority in South Africa to reduce stunting rates.
- Full Text:
- Date Issued: 2020
- Authors: Beyleveld, Janine
- Date: 2020
- Subjects: Children -- growth
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/50201 , vital:42066
- Description: Introduction and Background: Stunting is the most prevalent form of childhood malnutrition where about 149 million children under the age of five can be classified as stunted globally. South Africa has one of the highest stunting rates in the world at 27%, causing devastating effects on economic productivity as well as on an individual’s nutritional status. The presence of stunted growth in children is a strong indicator of chronic undernutrition and highlights injustices experienced within communities. Aims and Objectives: The aim of this study is to develop a stunning profile of children under the age of five, visiting BhishoHospital’s gateway clinic in the Eastern Cape, South Africa. The objectives were to determine the prevalence of stunting of the children visiting Bhisho Hospital’s clinic and to identify the drivers of stunting in the area. Methodology: A quantitative study with a descriptive, cross-sectional design was used. The study population included all children under the age of five visiting Bhisho Hospital’s clinic. Data was collected by means of an interview-administered questionnaire. Results: The prevalence of stunting in the area was 47.5%. A significant association was found between the participants' main form of sanitation and stunting category in the group of infants younger than six months (p = 0.007) and the group older than six months(p = 0.040). Discussion: The prevalence of stunting in the area was far higher than the national average of 27%, although the majority of the sample had a normal weight. The use of non-flush toilets was found to be a risk factor for childhood stunting. Recommendation: Financial and political investment in child health needs to be placed as a top priority in South Africa to reduce stunting rates.
- Full Text:
- Date Issued: 2020
Impacts of cattle grazing pressure on vegetation and soil characteristics in an arid grassland of South Africa
- Authors: Botha, Gert Stephanus
- Date: 2020
- Subjects: Grazing -- Environmental aspects -- South Africa , Cattle -- Feeding and feeds -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/${Handle} , vital:39749
- Description: Natural rangelands are often degraded due to the implementation of incorrect grazing systems. One potential solution is the use of short duration, high intensity grazing. The impacts of this grazing system on, inter alia, vegetation and soil properties have not yet been comprehensively tested within the arid rangelands of South Africa. This study aimed to determine the impacts of grazing intensity on vegetation composition, forage quantity and quality, and soil compaction, soil water infiltration rates and soil chemical properties in an arid grassland in South Africa. The following three grazing treatments were compared: no grazing (NG), low intensity grazing (LIG) and high intensity grazing (HIG). A total of 18 plots (six replicates per treatment) were grazed with Bonsmara cattle. Each plot, 4 ha in size, was surveyed pre-grazing, directly after grazing, and again three, six and 12 months post-grazing. The results indicated that different grazing intensities did not affect grass diversity and the veld condition a year after grazing. Phytomass was influenced by grazing intensity, with no grazing having the highest phytomass throughout the study period. Soil compaction differed among seasons but not among treatments, with summer surveys recording the lowest soil compaction rates. The soil water infiltration rates did not differ between the three different treatments, indicating that grazing intensity did not affect infiltration rates. However, grazing did seem to improve soil nutrient levels when compared to NG. The grazed treatments had higher NH4+, K+, and organic carbon than the NG treatment. Nevertheless, there was no significant difference in nutrients levels when comparing the LIG system to the HIG system. When comparing the soil nutrients levels within a treatment over time, only the HIG treatment showed an increase in soil nutrient levels (Mg2+) over time, whereas the LIG and NG treatments showed no changed throughout the study period. Generally, the study results indicated that in the short term there was no advantage to using higher grazing intensity, although the presence of grazing (as opposed to no grazing) is advantageous to arid grassland functioning.
- Full Text:
- Date Issued: 2020
- Authors: Botha, Gert Stephanus
- Date: 2020
- Subjects: Grazing -- Environmental aspects -- South Africa , Cattle -- Feeding and feeds -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/${Handle} , vital:39749
- Description: Natural rangelands are often degraded due to the implementation of incorrect grazing systems. One potential solution is the use of short duration, high intensity grazing. The impacts of this grazing system on, inter alia, vegetation and soil properties have not yet been comprehensively tested within the arid rangelands of South Africa. This study aimed to determine the impacts of grazing intensity on vegetation composition, forage quantity and quality, and soil compaction, soil water infiltration rates and soil chemical properties in an arid grassland in South Africa. The following three grazing treatments were compared: no grazing (NG), low intensity grazing (LIG) and high intensity grazing (HIG). A total of 18 plots (six replicates per treatment) were grazed with Bonsmara cattle. Each plot, 4 ha in size, was surveyed pre-grazing, directly after grazing, and again three, six and 12 months post-grazing. The results indicated that different grazing intensities did not affect grass diversity and the veld condition a year after grazing. Phytomass was influenced by grazing intensity, with no grazing having the highest phytomass throughout the study period. Soil compaction differed among seasons but not among treatments, with summer surveys recording the lowest soil compaction rates. The soil water infiltration rates did not differ between the three different treatments, indicating that grazing intensity did not affect infiltration rates. However, grazing did seem to improve soil nutrient levels when compared to NG. The grazed treatments had higher NH4+, K+, and organic carbon than the NG treatment. Nevertheless, there was no significant difference in nutrients levels when comparing the LIG system to the HIG system. When comparing the soil nutrients levels within a treatment over time, only the HIG treatment showed an increase in soil nutrient levels (Mg2+) over time, whereas the LIG and NG treatments showed no changed throughout the study period. Generally, the study results indicated that in the short term there was no advantage to using higher grazing intensity, although the presence of grazing (as opposed to no grazing) is advantageous to arid grassland functioning.
- Full Text:
- Date Issued: 2020
An explorative study of Makana local football association coaches characteristics, experiences and needs
- Authors: Callow, Gavin
- Date: 2020
- Subjects: Makana Local Football Association (South Africa) , Football -- Coaching -- South Africa , Football coaches -- South Africa
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/138785 , vital:37672
- Description: Introduction: Sports participation has been associated with a number of benefits to young athletes, outside of purely physical health. One of the key components of a successful sports talent identification and development program is effective coaching. A foundation of effective coaching is the coach’s knowledge which can be developed through formal, non-formal and informal means of education. The majority of coach education literature has however focused on coaches from developed countries. Limited studies have looked at the educational experiences and needs of South African coaches, particularly football coaches. The purpose of the current investigation is to establish Local Football Association (LFA) coaches’ perceptions of their educational backgrounds and what knowledge they deem important to be effective coaches. Method: A mixed methods approach was used in which (n=25) Makana LFA coaches answered a questionnaire with the aim of identifying their educational histories and what their current educational needs were. A semi-structured interview was also implemented in which some of the respondents (n=4) were asked more in-depth questions around the same topics, to create a more complete coaching profile. Results: The questionnaire responses highlighted that only 8% of the coaches possess a formal coaching qualification and all of the coaches work on a volunteer basis. Previous experience as a player is the chief source of knowledge for Makana LFA coaches. Not having enough available time is the main perceived barrier for 56% of participants to seeking out further educational opportunities. Fundamentals of coaching was selected by 56% of the coaches as a key subject they want to learn more about. Findings from the interview demonstrate that participants coach multiple teams and often have to rely on senior players to take up assistant coach positions, as well as managing their time effectively to work with all their teams. Informal education is the main source of information for the coaches which includes asking for advice, reading coaching manuals or having a mentor. The coaches value all 3 forms of education, however non-formal workshops are favoured. This is due to all of the coaches already having some form of informal learning experience and formal learning opportunities being too costly to pursue. A combination of lectures, practical sessions and group discussions is desired as a delivery method of coaching knowledge. Discussion: The level of coaching qualifications in the LFA is low, this may have significant implications for talent identification and development in the Sarah Baartman region. All the coaches are volunteer coaches, who primarily rely on informal means of coaching education. ‘Time’ was indicated to be a major barrier, to coaches seeking out educational opportunities. Coaches indicated that they would benefit from a coaching program if it took into consideration their needs, such as wanting to learn more about interpersonal and intrapersonal awareness. Conclusion: If local coaching programs are to be effective, they must reflect the educational needs of their community.
- Full Text:
- Date Issued: 2020
- Authors: Callow, Gavin
- Date: 2020
- Subjects: Makana Local Football Association (South Africa) , Football -- Coaching -- South Africa , Football coaches -- South Africa
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/138785 , vital:37672
- Description: Introduction: Sports participation has been associated with a number of benefits to young athletes, outside of purely physical health. One of the key components of a successful sports talent identification and development program is effective coaching. A foundation of effective coaching is the coach’s knowledge which can be developed through formal, non-formal and informal means of education. The majority of coach education literature has however focused on coaches from developed countries. Limited studies have looked at the educational experiences and needs of South African coaches, particularly football coaches. The purpose of the current investigation is to establish Local Football Association (LFA) coaches’ perceptions of their educational backgrounds and what knowledge they deem important to be effective coaches. Method: A mixed methods approach was used in which (n=25) Makana LFA coaches answered a questionnaire with the aim of identifying their educational histories and what their current educational needs were. A semi-structured interview was also implemented in which some of the respondents (n=4) were asked more in-depth questions around the same topics, to create a more complete coaching profile. Results: The questionnaire responses highlighted that only 8% of the coaches possess a formal coaching qualification and all of the coaches work on a volunteer basis. Previous experience as a player is the chief source of knowledge for Makana LFA coaches. Not having enough available time is the main perceived barrier for 56% of participants to seeking out further educational opportunities. Fundamentals of coaching was selected by 56% of the coaches as a key subject they want to learn more about. Findings from the interview demonstrate that participants coach multiple teams and often have to rely on senior players to take up assistant coach positions, as well as managing their time effectively to work with all their teams. Informal education is the main source of information for the coaches which includes asking for advice, reading coaching manuals or having a mentor. The coaches value all 3 forms of education, however non-formal workshops are favoured. This is due to all of the coaches already having some form of informal learning experience and formal learning opportunities being too costly to pursue. A combination of lectures, practical sessions and group discussions is desired as a delivery method of coaching knowledge. Discussion: The level of coaching qualifications in the LFA is low, this may have significant implications for talent identification and development in the Sarah Baartman region. All the coaches are volunteer coaches, who primarily rely on informal means of coaching education. ‘Time’ was indicated to be a major barrier, to coaches seeking out educational opportunities. Coaches indicated that they would benefit from a coaching program if it took into consideration their needs, such as wanting to learn more about interpersonal and intrapersonal awareness. Conclusion: If local coaching programs are to be effective, they must reflect the educational needs of their community.
- Full Text:
- Date Issued: 2020
Underutilisation of information communication and technology in the building construction industry case study: Department of Public Works in the Amathole district in the Eastern Cape
- Authors: Camngca, Vuyokazi Precious
- Date: 2020
- Subjects: Construction industry -- Information technology , Construction industry -- Data processing Information technology Communication and technology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/50632 , vital:42280
- Description: This study investigated the causes and effects of the underutilisation of Information Communication Technology (ICT) in the building section of the Amathole Region. The construction industry’s daily processes demand both heavy usages of data and data communication between project participants to meet client requirements. This industry is characterised by inaccurate and untimely communications that often result in costly delays and extensions of the project timeframe. ICT is a potential solution to this problem. The objectives of the study are, therefore, to determine why the above, a technically skilled occupational government institution in the Eastern Cape, does not employ ICT efficiently and optimally during this time of the looming global fourth industrial revolution. The literature review detailed the causes of and impact level of ICT’s utilisation and its potential benefits. For data collection, the researcher held unstructured interviews with a Chief Quantity Surveyor, Chief Architect, Engineer, Building Inspectors, and a Quantity Surveyor who dealt directly with construction projects. The key findings revealed that a lack of understanding of existing and newly available ICT software and hardware technology existed amongst certain senior officials within the building technology. The previously alluded, combined with the fear of the inability to learn and apply such new technology, has led to a culture of resistance to change from these more senior officials to utilise applications such as AutoCAD. The above-mentioned resistance, has also triggered the prevention of access to and lack of ICT resources, training, and inadequate funding, thereby eventually resulting in the underutilisation of ICT within the whole building section. This change also adversely affects all officials, especially the junior officials who have graduated using the most recent ICT technology during their studies. The researcher deduced, from the above findings, that adequate change management and continuous development, combined with the allocation of proper resources, would be necessary for all staff members. It was also determined that investments had to be made in the ICT equipment through the provision of a sufficient budget in the building section at AR.
- Full Text:
- Date Issued: 2020
- Authors: Camngca, Vuyokazi Precious
- Date: 2020
- Subjects: Construction industry -- Information technology , Construction industry -- Data processing Information technology Communication and technology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/50632 , vital:42280
- Description: This study investigated the causes and effects of the underutilisation of Information Communication Technology (ICT) in the building section of the Amathole Region. The construction industry’s daily processes demand both heavy usages of data and data communication between project participants to meet client requirements. This industry is characterised by inaccurate and untimely communications that often result in costly delays and extensions of the project timeframe. ICT is a potential solution to this problem. The objectives of the study are, therefore, to determine why the above, a technically skilled occupational government institution in the Eastern Cape, does not employ ICT efficiently and optimally during this time of the looming global fourth industrial revolution. The literature review detailed the causes of and impact level of ICT’s utilisation and its potential benefits. For data collection, the researcher held unstructured interviews with a Chief Quantity Surveyor, Chief Architect, Engineer, Building Inspectors, and a Quantity Surveyor who dealt directly with construction projects. The key findings revealed that a lack of understanding of existing and newly available ICT software and hardware technology existed amongst certain senior officials within the building technology. The previously alluded, combined with the fear of the inability to learn and apply such new technology, has led to a culture of resistance to change from these more senior officials to utilise applications such as AutoCAD. The above-mentioned resistance, has also triggered the prevention of access to and lack of ICT resources, training, and inadequate funding, thereby eventually resulting in the underutilisation of ICT within the whole building section. This change also adversely affects all officials, especially the junior officials who have graduated using the most recent ICT technology during their studies. The researcher deduced, from the above findings, that adequate change management and continuous development, combined with the allocation of proper resources, would be necessary for all staff members. It was also determined that investments had to be made in the ICT equipment through the provision of a sufficient budget in the building section at AR.
- Full Text:
- Date Issued: 2020
An ergonomics approach to understanding perceived barriers to the provision of high-quality healthcare: a Sarah Baartman District clinics case study
- Authors: Card, Jason
- Date: 2020
- Subjects: Medical care -- South Africa -- Eastern Cape , Public health -- South Africa -- Eastern Cape
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/170536 , vital:41933
- Description: Background:The complex nature of healthcare systemsoftenresultsinthe emergence of context-specific barriers that limit the ability for healthcare stakeholders to ensure safe and effective care delivery. In low-to middle-income (LMIC) countries, such as South Africa (SA), limited financial, material and human resources coupled withpoor infrastructure and poor public health determinants, includingpoverty andpoor education, affectthe ability to maintain andimprove on quality care outcomes.Understanding what different stakeholders perceive as barriers, and if these barriers are understood at different levels, is therefore important when attempting to mitigate the risk for unsafe or inefficient care delivery. Human Factors and Ergonomics (HFE) adoptssystems and participatory approaches for the exploration, analysis, and design of socio-technical systems to optimize both human wellbeing and system performance.The barriers to safe and effective healthcare delivery, from an HFE perspective, are not known in the South African context, particularly in parts of the Eastern Cape Province. Elucidatingthesebarriers, even if self-reported,may guidefuture efforts aimed at mitigating risks.The purpose of this study, therefore,wasto explore and highlight the perceived systemic barriers to local and national healthcare delivery, within the Sarah Baartman District in the Eastern Cape Province of South Africa.Methods: Ashort discussion aimed at introducing HFE and components of the Work Systems Model, followed by a survey that captured participant demographics, job characteristics, the perceived national and local systemic barriers, and proposed solutions, was administered withhealthcare stakeholders from 14 primary healthcare facilities and 1 department office within the Sarah Baartman District.Participants (n=120) included management, pharmacy, administration, maintenance, community-and home-based care and nursing staff.Data from the surveys were thematically analysed and categorised according to components of the work system model (Carayon, 2009) and respective workgroup.Results: The findings revealed many overlapping,systemic barriersthat includedshortages of staff, poor management and leadership, a lack of equipmentand basic necessities, poor infrastructure, patient complexity,and high workloads. The results further indicate that the way in which the reported barriers affect worksystem interactionsand performance are unique to different workgroups. Stakeholders iiproposedthat,among others, the absorption of contract workers, the provision of training and adequate human and medical resources and the maintenance of facilities may mitigate the barriers and improve healthcare delivery.Conclusion: The findings highlight a myriad of perceived systemic barriers perceived in the Sarah Baartman district, some of which were fundamental for the effective function of any healthcare system. These barriers may have wide-spread implications for stakeholders at all levels, ultimately affecting the performance, satisfaction and safety and the quality of care. It is especially important to consider these barriers in light of the COVID-19 epidemic, which emerged throughout this study and the major threat it presents to South African healthcare systems. Future research should aim to explore how these barriers interact to contribute to processes and outcomes, as well as explore the perceptions at provincial and national levels in order to better identify areas and strategies for improvement.
- Full Text:
- Date Issued: 2020
- Authors: Card, Jason
- Date: 2020
- Subjects: Medical care -- South Africa -- Eastern Cape , Public health -- South Africa -- Eastern Cape
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/170536 , vital:41933
- Description: Background:The complex nature of healthcare systemsoftenresultsinthe emergence of context-specific barriers that limit the ability for healthcare stakeholders to ensure safe and effective care delivery. In low-to middle-income (LMIC) countries, such as South Africa (SA), limited financial, material and human resources coupled withpoor infrastructure and poor public health determinants, includingpoverty andpoor education, affectthe ability to maintain andimprove on quality care outcomes.Understanding what different stakeholders perceive as barriers, and if these barriers are understood at different levels, is therefore important when attempting to mitigate the risk for unsafe or inefficient care delivery. Human Factors and Ergonomics (HFE) adoptssystems and participatory approaches for the exploration, analysis, and design of socio-technical systems to optimize both human wellbeing and system performance.The barriers to safe and effective healthcare delivery, from an HFE perspective, are not known in the South African context, particularly in parts of the Eastern Cape Province. Elucidatingthesebarriers, even if self-reported,may guidefuture efforts aimed at mitigating risks.The purpose of this study, therefore,wasto explore and highlight the perceived systemic barriers to local and national healthcare delivery, within the Sarah Baartman District in the Eastern Cape Province of South Africa.Methods: Ashort discussion aimed at introducing HFE and components of the Work Systems Model, followed by a survey that captured participant demographics, job characteristics, the perceived national and local systemic barriers, and proposed solutions, was administered withhealthcare stakeholders from 14 primary healthcare facilities and 1 department office within the Sarah Baartman District.Participants (n=120) included management, pharmacy, administration, maintenance, community-and home-based care and nursing staff.Data from the surveys were thematically analysed and categorised according to components of the work system model (Carayon, 2009) and respective workgroup.Results: The findings revealed many overlapping,systemic barriersthat includedshortages of staff, poor management and leadership, a lack of equipmentand basic necessities, poor infrastructure, patient complexity,and high workloads. The results further indicate that the way in which the reported barriers affect worksystem interactionsand performance are unique to different workgroups. Stakeholders iiproposedthat,among others, the absorption of contract workers, the provision of training and adequate human and medical resources and the maintenance of facilities may mitigate the barriers and improve healthcare delivery.Conclusion: The findings highlight a myriad of perceived systemic barriers perceived in the Sarah Baartman district, some of which were fundamental for the effective function of any healthcare system. These barriers may have wide-spread implications for stakeholders at all levels, ultimately affecting the performance, satisfaction and safety and the quality of care. It is especially important to consider these barriers in light of the COVID-19 epidemic, which emerged throughout this study and the major threat it presents to South African healthcare systems. Future research should aim to explore how these barriers interact to contribute to processes and outcomes, as well as explore the perceptions at provincial and national levels in order to better identify areas and strategies for improvement.
- Full Text:
- Date Issued: 2020
Molecular simulations of potential agents and targets of Alzheimer’s disease
- Authors: Carlisle, Tanya
- Date: 2020
- Subjects: Alzheimer's disease -- Treatment , Alzheimer's disease -- Molecular aspects , Amyloid beta-protein precurs , Amyloid beta-protein
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/140025 , vital:37825
- Description: The World Alzheimer Report statedin 2016 that approximately 46.8 million people were living with dementia and this figure is expected to triple by 2050. Alzheimer’s Disease was discovered to be a precursor to dementia in 1976 and since then efforts to understand Alzheimer’s have been prioritized. To date, there are very few effective forms of treatment for Alzheimer’s, many are known to offer only mild calming of the symptoms and have side effects such as diarrhea, nausea, loss of appetite and sleep disturbances. This has been due to lack of understanding on how Alzheimer’s is caused. With the two main hallmarks of the disease now being more understood it has opened the doorway into the discovery of new treatments for this disease. This study focuses on the hallmark involving the aggregation of the β-amyloid protein to form plaques surrounding the neurons of the brain. Copper, Zinc and Iron have also been found in high concentrations in and surrounding these plaques. This study focused on the screening of the South African Natural Compound database (SANCDB) to discover hits that have potential destabilizing action against the Beta-amyloid aggregate. If one of these compounds could prove to have destabilizing action on the aggregate it could open the doorway to new potential forms of treatment. Over 700 SANCDB compounds were docked, and the top hits were taken to molecular dynamics to further study the interactions of the compounds and the aggregate. However, the hits identified had strong binding to the aggregate causing it to become stable instead of the desired effect of destabilizing the structure. This information, however, does not rule out the possibility of these compounds preventing the formation of the aggregates. Further, interactions of copper with β-amyloid and copper were determined by solubilizing the aggregate and introducing copper ions in a dynamics simulation. Possible interactions between copper and the methionine residues were visualised.
- Full Text:
- Date Issued: 2020
- Authors: Carlisle, Tanya
- Date: 2020
- Subjects: Alzheimer's disease -- Treatment , Alzheimer's disease -- Molecular aspects , Amyloid beta-protein precurs , Amyloid beta-protein
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/140025 , vital:37825
- Description: The World Alzheimer Report statedin 2016 that approximately 46.8 million people were living with dementia and this figure is expected to triple by 2050. Alzheimer’s Disease was discovered to be a precursor to dementia in 1976 and since then efforts to understand Alzheimer’s have been prioritized. To date, there are very few effective forms of treatment for Alzheimer’s, many are known to offer only mild calming of the symptoms and have side effects such as diarrhea, nausea, loss of appetite and sleep disturbances. This has been due to lack of understanding on how Alzheimer’s is caused. With the two main hallmarks of the disease now being more understood it has opened the doorway into the discovery of new treatments for this disease. This study focuses on the hallmark involving the aggregation of the β-amyloid protein to form plaques surrounding the neurons of the brain. Copper, Zinc and Iron have also been found in high concentrations in and surrounding these plaques. This study focused on the screening of the South African Natural Compound database (SANCDB) to discover hits that have potential destabilizing action against the Beta-amyloid aggregate. If one of these compounds could prove to have destabilizing action on the aggregate it could open the doorway to new potential forms of treatment. Over 700 SANCDB compounds were docked, and the top hits were taken to molecular dynamics to further study the interactions of the compounds and the aggregate. However, the hits identified had strong binding to the aggregate causing it to become stable instead of the desired effect of destabilizing the structure. This information, however, does not rule out the possibility of these compounds preventing the formation of the aggregates. Further, interactions of copper with β-amyloid and copper were determined by solubilizing the aggregate and introducing copper ions in a dynamics simulation. Possible interactions between copper and the methionine residues were visualised.
- Full Text:
- Date Issued: 2020
Analysis of bacterial Mur amide ligase enzymes for the identification of inhibitory compounds by in silico methods
- Chamboko, Chiratidzo Respina
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Mur amide ligases , Ligases , Ligand binding (Biochemistry) , Antibacterial agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163430 , vital:41036
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
- Date Issued: 2020
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Mur amide ligases , Ligases , Ligand binding (Biochemistry) , Antibacterial agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163430 , vital:41036
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
- Date Issued: 2020
Analysis of bacterial Mur amide ligase enzymes for the identification of inhibitory compounds by in silico methods
- Chamboko, Chiratidzo Respina
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Pathogenic microorganisms -- Analysis , Drug resistance in microorganisms , Microorganisms -- Effect of drugs on , Antibiotics -- Effectiveness , Pathogenic bacteria , Drug tolerance , Enzymes -- Analysis , Peptide antibiotics
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/161911 , vital:40690
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
- Date Issued: 2020
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Pathogenic microorganisms -- Analysis , Drug resistance in microorganisms , Microorganisms -- Effect of drugs on , Antibiotics -- Effectiveness , Pathogenic bacteria , Drug tolerance , Enzymes -- Analysis , Peptide antibiotics
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/161911 , vital:40690
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
- Date Issued: 2020
A 150 MHz all sky survey with the Precision Array to Probe the Epoch of Reionization
- Authors: Chege, James Kariuki
- Date: 2020
- Subjects: Epoch of reionization -- Research , Astronomy -- Observations , Radio interferometers
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/117733 , vital:34556
- Description: The Precision Array to Probe the Epoch of Reionization (PAPER) was built to measure the redshifted 21 cm line of hydrogen from cosmic reionization. Such low frequency observations promise to be the best means of understanding the cosmic dawn; when the first galaxies in the universe formed, and also the Epoch of Reionization; when the intergalactic medium changed from neutral to ionized. The major challenges to these observations is the presence of astrophysical foregrounds that are much brighter than the cosmological signal. Here, I present an all-sky survey at 150 MHz obtained from the analysis of 300 hours of PAPER observations. Particular focus is given to the calibration and imaging techniques that need to deal with the wide field of view of a non-tracking instrument. The survey covers ~ 7000 square degrees of the southern sky. From a sky area of 4400 square degrees out of the total survey area, I extract a catalogue of sources brighter than 4 Jy whose accuracy was tested against the published GLEAM catalogue, leading to a fractional difference rms better than 20%. The catalogue provides an all-sky accurate model of the extragalactic foreground to be used for the calibration of future Epoch of Reionization observations and to be subtracted from the PAPER observations themselves in order to mitigate the foreground contamination.
- Full Text:
- Date Issued: 2020
- Authors: Chege, James Kariuki
- Date: 2020
- Subjects: Epoch of reionization -- Research , Astronomy -- Observations , Radio interferometers
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/117733 , vital:34556
- Description: The Precision Array to Probe the Epoch of Reionization (PAPER) was built to measure the redshifted 21 cm line of hydrogen from cosmic reionization. Such low frequency observations promise to be the best means of understanding the cosmic dawn; when the first galaxies in the universe formed, and also the Epoch of Reionization; when the intergalactic medium changed from neutral to ionized. The major challenges to these observations is the presence of astrophysical foregrounds that are much brighter than the cosmological signal. Here, I present an all-sky survey at 150 MHz obtained from the analysis of 300 hours of PAPER observations. Particular focus is given to the calibration and imaging techniques that need to deal with the wide field of view of a non-tracking instrument. The survey covers ~ 7000 square degrees of the southern sky. From a sky area of 4400 square degrees out of the total survey area, I extract a catalogue of sources brighter than 4 Jy whose accuracy was tested against the published GLEAM catalogue, leading to a fractional difference rms better than 20%. The catalogue provides an all-sky accurate model of the extragalactic foreground to be used for the calibration of future Epoch of Reionization observations and to be subtracted from the PAPER observations themselves in order to mitigate the foreground contamination.
- Full Text:
- Date Issued: 2020