Cyclooxygenase-1 as an anti-stroke target: potential inhibitor identification and non-synonymous single nucleotide polymorphism analysis
- Authors: Muronzi, Tendai
- Date: 2020
- Subjects: Cerebrovascular disease , Cerebrovascular disease -- Treatment , Cerebrovascular disease -- Chemotherapy , Cyclooxygenases , High throughput screening (Drug development) , Drug development , Molecular dynamics , South African Natural Compounds Database , ZINC database
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/143404 , vital:38243
- Description: Stroke is the third leading cause of death worldwide, with 87% of cases being ischemic stroke. The two primary therapeutic strategies to reduce post-ischemic brain damage are cellular and vascular approaches. The vascular strategy aims to rapidly re-open obstructed blood vessels, while the cellular approach aims to interfere with the signalling pathways that facilitate neuron damage and death. Unfortunately, popular vascular treatments have adverse side effects, necessitating the need for alternative chemotherapeutics. In this study, cyclooxygenase-1 (COX-1), which plays a significant role in the post- ischemic neuroinflammation and neuronal death, was targeted for identification of novel drug compounds and to assess the effect of nsSNPs on its structure and function. In a drug discovery part, ligands from the South African Natural Compounds Database (SANCDB-https://sancdb.rubi.ru.ac.za/) and ZINC database (http://zinc15.docking.org/) were used for high-throughput virtual screening (HVTS) against COX-1. Additionally, five nsSNPs were being investigated to assess their impact on protein structure and function. Three of these SNPs were in the COX-1 dimer interface. Molecular docking and molecular dynamics simulations revealed asymmetric nature of the protein. Several ligands, peculiar to each monomer, exhibited favourable binding energies in the respective active sites. SNP analysis indicated effects on inter-monomer interactions and protein stability.
- Full Text:
- Date Issued: 2020
- Authors: Muronzi, Tendai
- Date: 2020
- Subjects: Cerebrovascular disease , Cerebrovascular disease -- Treatment , Cerebrovascular disease -- Chemotherapy , Cyclooxygenases , High throughput screening (Drug development) , Drug development , Molecular dynamics , South African Natural Compounds Database , ZINC database
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/143404 , vital:38243
- Description: Stroke is the third leading cause of death worldwide, with 87% of cases being ischemic stroke. The two primary therapeutic strategies to reduce post-ischemic brain damage are cellular and vascular approaches. The vascular strategy aims to rapidly re-open obstructed blood vessels, while the cellular approach aims to interfere with the signalling pathways that facilitate neuron damage and death. Unfortunately, popular vascular treatments have adverse side effects, necessitating the need for alternative chemotherapeutics. In this study, cyclooxygenase-1 (COX-1), which plays a significant role in the post- ischemic neuroinflammation and neuronal death, was targeted for identification of novel drug compounds and to assess the effect of nsSNPs on its structure and function. In a drug discovery part, ligands from the South African Natural Compounds Database (SANCDB-https://sancdb.rubi.ru.ac.za/) and ZINC database (http://zinc15.docking.org/) were used for high-throughput virtual screening (HVTS) against COX-1. Additionally, five nsSNPs were being investigated to assess their impact on protein structure and function. Three of these SNPs were in the COX-1 dimer interface. Molecular docking and molecular dynamics simulations revealed asymmetric nature of the protein. Several ligands, peculiar to each monomer, exhibited favourable binding energies in the respective active sites. SNP analysis indicated effects on inter-monomer interactions and protein stability.
- Full Text:
- Date Issued: 2020
Reporting drought: framing an anthropogenic natural disaster in the South African mainstream publication, City Press, over three years (2015-2018)
- Authors: Matyobeni, Thandiwe
- Date: 2020
- Subjects: City Press , City Press -- Criticism, Textual , Droughts -- South Africa , Mass media and the environment -- South Africa , Climatic changes in mass media -- South Africa , Press -- South Africa
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/143179 , vital:38208
- Description: This study interrogates how the ongoing anthropogenic drought, declared a disaster in five South African provinces in 2015, has been represented by mainstream news media. The news media enables public participation which is vital to climate action and the regulation of harmful neoliberal practices that fuel climate change and are thus necessary to provide information about climate change and to support political interventions. Despite the gravity of the drought crisis, there is a severe lack of public opinion about it and the complex weather patterns to which it is attributed. This study thus investigates how the drought has been framed by mainstream news media in South Africa, confining itself to a single title, the City Press. To analyse representations of drought in the City Press, this study adopts a Foucauldian approach to discourse which considers representations as meaning constructed through language. The knowledge perpetuated in news texts is thus frequently perceived as the ‘truth’ about the drought. This knowledge is imbued with power as those in positions of authority determine what is articulated as truth. Through various institutional practices, journalists limit what is said about the drought, framing it in particular ways and privileging particular voices. What the public learns about the drought (and in turn, climate change) is thus limited by the norms and routines of the journalistic regime and the corporate nature of ownership. Notably, the City Press operates within the neoliberal economic order to which climate change is attributed. This study is located within the Cultural Studies and Journalism Studies paradigms and is further informed by a qualitative methodology and two methods of textual analysis, that is, thematic analysis and Critical Discourse Analysis. The sampling process produced a database of 26 news texts published by the City Press between the years 2015 to 2018. Five texts were purposively selected for an in-depth analysis based on a broad thematic analysis as reasonably representative of the discourses that recur. Although the City Press positions itself as a critical purveyor of political information, only three themes recur in the texts. These themes position drought in relation to the agricultural economy and urban infrastructure; foreground the voices of corporate entities; while the climate science behind weather patterns is inadequately interpreted. Any discussion of climate change and alternatives to mainstream economic practices is almost entirely omitted.
- Full Text:
- Date Issued: 2020
- Authors: Matyobeni, Thandiwe
- Date: 2020
- Subjects: City Press , City Press -- Criticism, Textual , Droughts -- South Africa , Mass media and the environment -- South Africa , Climatic changes in mass media -- South Africa , Press -- South Africa
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/143179 , vital:38208
- Description: This study interrogates how the ongoing anthropogenic drought, declared a disaster in five South African provinces in 2015, has been represented by mainstream news media. The news media enables public participation which is vital to climate action and the regulation of harmful neoliberal practices that fuel climate change and are thus necessary to provide information about climate change and to support political interventions. Despite the gravity of the drought crisis, there is a severe lack of public opinion about it and the complex weather patterns to which it is attributed. This study thus investigates how the drought has been framed by mainstream news media in South Africa, confining itself to a single title, the City Press. To analyse representations of drought in the City Press, this study adopts a Foucauldian approach to discourse which considers representations as meaning constructed through language. The knowledge perpetuated in news texts is thus frequently perceived as the ‘truth’ about the drought. This knowledge is imbued with power as those in positions of authority determine what is articulated as truth. Through various institutional practices, journalists limit what is said about the drought, framing it in particular ways and privileging particular voices. What the public learns about the drought (and in turn, climate change) is thus limited by the norms and routines of the journalistic regime and the corporate nature of ownership. Notably, the City Press operates within the neoliberal economic order to which climate change is attributed. This study is located within the Cultural Studies and Journalism Studies paradigms and is further informed by a qualitative methodology and two methods of textual analysis, that is, thematic analysis and Critical Discourse Analysis. The sampling process produced a database of 26 news texts published by the City Press between the years 2015 to 2018. Five texts were purposively selected for an in-depth analysis based on a broad thematic analysis as reasonably representative of the discourses that recur. Although the City Press positions itself as a critical purveyor of political information, only three themes recur in the texts. These themes position drought in relation to the agricultural economy and urban infrastructure; foreground the voices of corporate entities; while the climate science behind weather patterns is inadequately interpreted. Any discussion of climate change and alternatives to mainstream economic practices is almost entirely omitted.
- Full Text:
- Date Issued: 2020
Towards realising the benefits of citizen participation in environmental monitoring: a case study in an Eastern Cape natural resource management programme
- Authors: Mtati, Nosiseko
- Date: 2020
- Subjects: Tsitsa Project , Rural development projects -- South Africa -- Eastern Cape , Environmental monitoring -- South Africa -- Tsitsa River , Environmental monitoring -- Citizen participation -- South Africa -- Tsitsa River , Water supply, Agricultural -- South Africa -- Tsitsa River , Environmental education -- South Africa
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/167562 , vital:41492
- Description: The Tsitsa Project focusses on land use management and rural livelihoods in the Tsitsa River catchment in the Eastern Cape Province of South Africa. It is funded by the Department of Environmental Affairs and the environmental monitoring initiative is implemented by Rhodes University, where I am employed as the catchment coordinator. This study explores the environmental monitoring initiative within the bigger Tsitsa Project. Community members in the catchment monitor sediment transportation in the Tsitsa River and its tributaries, which originally became of interest because it is proposed that a dam (Ntabelanga Dam) be established here. This study aims to understand citizen environmental monitoring in the Tsitsa Project; what the project managers regarded as benefits; and how the monitors themselves perceived benefits of participating as monitors. A realist approach was followed, in order to understand the connections between the context and the mechanisms in the project, and how these combined to result in the outcomes observed. Realist research emphasises the importance of context in shaping outcomes such as the achieved benefits of citizen monitoring. Data was collected using a case study method, where each individual monitor and their particular context, was regarded as a case. Semistructured interviews were conducted with 17 monitors and five Tsitsa Project staff; this was supported by field notes and the reviewing of project documents including field reports. The realist analysis looked at the context of the monitors in general and the mechanisms applied by the project in recruiting, training and managing the monitors. A second layer of mechanisms was identified as those responses from the monitors to what the project was introducing to them. Outcomes were both positive and negative, including how long monitors remained in the initiative, what benefits they derived from the process, and what potential benefits they did not achieve. This included lost opportunities to provide recognition for skills and experience gained. Recommendations are made regarding the recruitment, training and management of monitors, to optimise benefits for the monitors, the host institution and the initiative’s staff. The study is significant because of its particular yet representative characteristics and it will assist both the Tsitsa Project, which aims to expand its citizen environmental monitoring initiative, as well as wider Natural Resource Management Programmes in South Africa. It is also hoped that it will contribute to the literature on environmental monitoring as a little researched form of citizen science globally.
- Full Text:
- Date Issued: 2020
- Authors: Mtati, Nosiseko
- Date: 2020
- Subjects: Tsitsa Project , Rural development projects -- South Africa -- Eastern Cape , Environmental monitoring -- South Africa -- Tsitsa River , Environmental monitoring -- Citizen participation -- South Africa -- Tsitsa River , Water supply, Agricultural -- South Africa -- Tsitsa River , Environmental education -- South Africa
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/167562 , vital:41492
- Description: The Tsitsa Project focusses on land use management and rural livelihoods in the Tsitsa River catchment in the Eastern Cape Province of South Africa. It is funded by the Department of Environmental Affairs and the environmental monitoring initiative is implemented by Rhodes University, where I am employed as the catchment coordinator. This study explores the environmental monitoring initiative within the bigger Tsitsa Project. Community members in the catchment monitor sediment transportation in the Tsitsa River and its tributaries, which originally became of interest because it is proposed that a dam (Ntabelanga Dam) be established here. This study aims to understand citizen environmental monitoring in the Tsitsa Project; what the project managers regarded as benefits; and how the monitors themselves perceived benefits of participating as monitors. A realist approach was followed, in order to understand the connections between the context and the mechanisms in the project, and how these combined to result in the outcomes observed. Realist research emphasises the importance of context in shaping outcomes such as the achieved benefits of citizen monitoring. Data was collected using a case study method, where each individual monitor and their particular context, was regarded as a case. Semistructured interviews were conducted with 17 monitors and five Tsitsa Project staff; this was supported by field notes and the reviewing of project documents including field reports. The realist analysis looked at the context of the monitors in general and the mechanisms applied by the project in recruiting, training and managing the monitors. A second layer of mechanisms was identified as those responses from the monitors to what the project was introducing to them. Outcomes were both positive and negative, including how long monitors remained in the initiative, what benefits they derived from the process, and what potential benefits they did not achieve. This included lost opportunities to provide recognition for skills and experience gained. Recommendations are made regarding the recruitment, training and management of monitors, to optimise benefits for the monitors, the host institution and the initiative’s staff. The study is significant because of its particular yet representative characteristics and it will assist both the Tsitsa Project, which aims to expand its citizen environmental monitoring initiative, as well as wider Natural Resource Management Programmes in South Africa. It is also hoped that it will contribute to the literature on environmental monitoring as a little researched form of citizen science globally.
- Full Text:
- Date Issued: 2020
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