Potential running related injury contributors in South African long-distance runners
- Authors: Jäger, Chloë Rose Laubscher
- Date: 2022-04-06
- Subjects: Running injuries South Africa , Long-distance running South Africa , Running Physiological aspects , Running shoes , Biomechanics , Chi-square test , Fisher exact test
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/290943 , vital:56801
- Description: Running related injuries (RRIs) are a common problem among long-distance runners, with injury rates ranging from 19.4% to 79.3%. Many studies have been done, investigating possible contributors to RRIs however, very few studies have investigated RRIs in South African long-distance runners, a population which may differ from previously studied populations. The current study aimed to build a descriptive profile of South African long-distance runners, as well as to determine associated factors that may contribute to RRIs. In order to do this, a cross-sectional, retrospective study design was employed using a questionnaire which was mostly electronically distributed. The sample consisted of 378 long-distance runners from each province in South Africa (SA). Using the Chi-square analysis and Fisher exact tests, significant associations were established (p<0.05). The current study found that certain RRI variables were associated with specific aspects of the participants’ personal characteristics and demographics, training characteristics, running experience, footwear, and cross training activities. Footwear and training characteristics produced the largest number of significant RRI associations. The findings of the current study could assist future research on RRIs in South African long-distance runners, by informing researchers of potential areas where more in-depth research is needed. In the long term, researchers may be able to narrow down the main contributors to RRI, possibly decreasing RRI rates in the unique population of South African long-distance runners. , Thesis (MSc) -- Faculty of Science, Human Kinetics and Ergonomics, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Jäger, Chloë Rose Laubscher
- Date: 2022-04-06
- Subjects: Running injuries South Africa , Long-distance running South Africa , Running Physiological aspects , Running shoes , Biomechanics , Chi-square test , Fisher exact test
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/290943 , vital:56801
- Description: Running related injuries (RRIs) are a common problem among long-distance runners, with injury rates ranging from 19.4% to 79.3%. Many studies have been done, investigating possible contributors to RRIs however, very few studies have investigated RRIs in South African long-distance runners, a population which may differ from previously studied populations. The current study aimed to build a descriptive profile of South African long-distance runners, as well as to determine associated factors that may contribute to RRIs. In order to do this, a cross-sectional, retrospective study design was employed using a questionnaire which was mostly electronically distributed. The sample consisted of 378 long-distance runners from each province in South Africa (SA). Using the Chi-square analysis and Fisher exact tests, significant associations were established (p<0.05). The current study found that certain RRI variables were associated with specific aspects of the participants’ personal characteristics and demographics, training characteristics, running experience, footwear, and cross training activities. Footwear and training characteristics produced the largest number of significant RRI associations. The findings of the current study could assist future research on RRIs in South African long-distance runners, by informing researchers of potential areas where more in-depth research is needed. In the long term, researchers may be able to narrow down the main contributors to RRI, possibly decreasing RRI rates in the unique population of South African long-distance runners. , Thesis (MSc) -- Faculty of Science, Human Kinetics and Ergonomics, 2022
- Full Text:
- Date Issued: 2022-04-06
An analysis of crime trends at University of Fort Hare, Alice campus: Ten years (2008-2018) projection case studies
- Giyama, Mlungisi https://orcid.org/0000-0002-4024-9447
- Authors: Giyama, Mlungisi https://orcid.org/0000-0002-4024-9447
- Date: 2020
- Subjects: Criminal statistics , Victims of crimes surveys
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10353/28584 , vital:74447
- Description: This research has concerted on the trend of crimes committed at University Fort Hare over past ten years. The previous conducted researches show several forms of crimes committed at different higher learning institutions and some crime are even cited happening in South Africa. The problem is Incompetence of University of Fort Hare security guards, which are responsible to prevent the occurrence of crime at the Alice campus. The university have scarcity of programmes that intends to inform students and staff members on how to protect themselves when there is crime threat. University of Fort Hare has unlimited access by community members. The knowledge gap on crimes committed at higher leaning is unexplained psychological such as depression and stress experienced by perpetrators. Secondly, there is lack of studies focused on the discussion about importance of criminal background check of prospective students. The unavailability of electronics that scans dangerous weapons such as knife (okapi) result to crimes such as murder at University of Fort Hare. The problem of abusing alcohol and other drugs by students result to rapes when students are drunk or high. The study aims to evaluate the trend in crimes that occurred from July 2008 to August 2018 at the University of Fort Hare Alice Campus. The objective is to find out types of crimes that occur quarterly at the University of Fort Hare Alice Campus. To discover the perception of selected staff members and students about the safety on campus and to find strategies introduced by the university to address crimes that are committed at University of Fort Hare Alice campus. The study has adopted qualitative research method and exploratory research design. The questions to be asked include what types of crimes occur at University of Fort Hare Alice Campus and how is the perception of selected staff members and students about the safety on campus? The researcher found out that crimes occurring at the University of Fort Hare Alice Campus has changed to new forms of crimes such as murder, looting of shops, slaughtering cattle, deformation of character on social media, bribery for academic admission, arson of buildings, stealing of university property, rapes and sexual assaults meanwhile these crimes were not prominent before 2008. The researcher discovered that students are the ones mostly affected by crimes that happened at University of Fort Hare (UFH) Alice campus in 2015, 2016 and 2018 thereafter followed staff members. Most people who are victims of crimes at University of Fort Hare (UFH) Alice campus arrived between 2014 and 2016. The study indicates that fewer security officers and lack of security equipment such as communicating radios cause crimes at University of Fort Hare (UFH) Alice campus. Cases reported to the security office takes a long time to conclude. Dark parts at the campus are found to cause some of crimes at the University of Fort Hare Alice campus. The significant of conducting this study, will help University of Fort Hare develop better policies regarding crimes on campus. The researcher also wanted to support the consistency of trying to find out a solution for university crime. It is recommended that University of Fort Hare management needs to hire more guards to make sure that each residence and building has a guard. During events at Alice campus that includes people from outside, there must be police and event’s organisers need to present security plan when they are requesting university facilities to ensure the safeness of staff members and students. , Thesis (MSoc) -- Faculty of Social Sciences and Humanities, 2020
- Full Text:
- Date Issued: 2020
- Authors: Giyama, Mlungisi https://orcid.org/0000-0002-4024-9447
- Date: 2020
- Subjects: Criminal statistics , Victims of crimes surveys
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10353/28584 , vital:74447
- Description: This research has concerted on the trend of crimes committed at University Fort Hare over past ten years. The previous conducted researches show several forms of crimes committed at different higher learning institutions and some crime are even cited happening in South Africa. The problem is Incompetence of University of Fort Hare security guards, which are responsible to prevent the occurrence of crime at the Alice campus. The university have scarcity of programmes that intends to inform students and staff members on how to protect themselves when there is crime threat. University of Fort Hare has unlimited access by community members. The knowledge gap on crimes committed at higher leaning is unexplained psychological such as depression and stress experienced by perpetrators. Secondly, there is lack of studies focused on the discussion about importance of criminal background check of prospective students. The unavailability of electronics that scans dangerous weapons such as knife (okapi) result to crimes such as murder at University of Fort Hare. The problem of abusing alcohol and other drugs by students result to rapes when students are drunk or high. The study aims to evaluate the trend in crimes that occurred from July 2008 to August 2018 at the University of Fort Hare Alice Campus. The objective is to find out types of crimes that occur quarterly at the University of Fort Hare Alice Campus. To discover the perception of selected staff members and students about the safety on campus and to find strategies introduced by the university to address crimes that are committed at University of Fort Hare Alice campus. The study has adopted qualitative research method and exploratory research design. The questions to be asked include what types of crimes occur at University of Fort Hare Alice Campus and how is the perception of selected staff members and students about the safety on campus? The researcher found out that crimes occurring at the University of Fort Hare Alice Campus has changed to new forms of crimes such as murder, looting of shops, slaughtering cattle, deformation of character on social media, bribery for academic admission, arson of buildings, stealing of university property, rapes and sexual assaults meanwhile these crimes were not prominent before 2008. The researcher discovered that students are the ones mostly affected by crimes that happened at University of Fort Hare (UFH) Alice campus in 2015, 2016 and 2018 thereafter followed staff members. Most people who are victims of crimes at University of Fort Hare (UFH) Alice campus arrived between 2014 and 2016. The study indicates that fewer security officers and lack of security equipment such as communicating radios cause crimes at University of Fort Hare (UFH) Alice campus. Cases reported to the security office takes a long time to conclude. Dark parts at the campus are found to cause some of crimes at the University of Fort Hare Alice campus. The significant of conducting this study, will help University of Fort Hare develop better policies regarding crimes on campus. The researcher also wanted to support the consistency of trying to find out a solution for university crime. It is recommended that University of Fort Hare management needs to hire more guards to make sure that each residence and building has a guard. During events at Alice campus that includes people from outside, there must be police and event’s organisers need to present security plan when they are requesting university facilities to ensure the safeness of staff members and students. , Thesis (MSoc) -- Faculty of Social Sciences and Humanities, 2020
- Full Text:
- Date Issued: 2020
Determination of speaker configuration for an immersive audio content creation system
- Authors: Lebusa, Motebang
- Date: 2020
- Subjects: Loudspeakers , Surround-sound systems , Algorithms , Coordinates
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/163375 , vital:41034
- Description: Various spatialisation algorithms require the knowledge of speaker locations to accurately localise sound in 3D environments. The rendering process uses speaker coordinates to feed into their algorithms so that they can render the immersive audio content as intended by an artist. The need to measure the loudspeaker coordinates becomes necessary, especially in environments where the speaker layouts change frequently. Manually measuring the coordinates, however, tends to be a laborious task that is prone to errors. This research provides an automated solution to the problem of speaker coordinates measurement. The solution system, SDIAS, is a client-server system that uses the capabilities provided by the Ethernet Audio Video Bridging standard to measure the 3D loudspeaker coordinates for immersive sound systems. SDIAS deploys commodity hardware and readily available software to implement the solution. A server sends a short tone to each speaker in the speaker configuration, at equal intervals. A microphone attached to a mobile device picks up these transmitted tones on the client side, from different locations. The transmission and reception times from both components of the system are used to measure the time of flight for each tone sent to a loudspeaker. These are then used to determine the 3D coordinates of each loudspeaker in the available layout. Tests were performed to determine the accuracy of the determination algorithm for SDIAS, and were compared to the manually measured coordinates. , Thesis (MSc) -- Faculty of Science, Computer Science, 2020
- Full Text:
- Date Issued: 2020
- Authors: Lebusa, Motebang
- Date: 2020
- Subjects: Loudspeakers , Surround-sound systems , Algorithms , Coordinates
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/163375 , vital:41034
- Description: Various spatialisation algorithms require the knowledge of speaker locations to accurately localise sound in 3D environments. The rendering process uses speaker coordinates to feed into their algorithms so that they can render the immersive audio content as intended by an artist. The need to measure the loudspeaker coordinates becomes necessary, especially in environments where the speaker layouts change frequently. Manually measuring the coordinates, however, tends to be a laborious task that is prone to errors. This research provides an automated solution to the problem of speaker coordinates measurement. The solution system, SDIAS, is a client-server system that uses the capabilities provided by the Ethernet Audio Video Bridging standard to measure the 3D loudspeaker coordinates for immersive sound systems. SDIAS deploys commodity hardware and readily available software to implement the solution. A server sends a short tone to each speaker in the speaker configuration, at equal intervals. A microphone attached to a mobile device picks up these transmitted tones on the client side, from different locations. The transmission and reception times from both components of the system are used to measure the time of flight for each tone sent to a loudspeaker. These are then used to determine the 3D coordinates of each loudspeaker in the available layout. Tests were performed to determine the accuracy of the determination algorithm for SDIAS, and were compared to the manually measured coordinates. , Thesis (MSc) -- Faculty of Science, Computer Science, 2020
- Full Text:
- Date Issued: 2020
Intersection of race, gender and class in the interventional life-writings of four selected South African authors
- Ndlovu, Siphatisiwe Patricia
- Authors: Ndlovu, Siphatisiwe Patricia
- Date: 2020
- Subjects: Post-apartheid era -- South Africa , Interventional writing , Fred Khumalo , Malaika wa Azania , Khaya Dlanga , Tumi Morake
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/11260/3414 , vital:43345
- Description: The interventional life writings of second generation life writers (young, black, middleclass South Africans) in post-apartheid South Africa have not attracted much academic debate in spite of the burgeoning of such writings recently. The intersection of race, class and gender in post-apartheid South Africa remains a problem and a rich site of research, hence this research’s reading of four selected life writings by young, black, middle-class South Africans living in post-apartheid South Africa: Fred Khumalo’s Touch My Blood: The Early Years (2006), Malaika Wa Azania’s Memoires of a Born Free: Reflections on the Rainbow Nation (2014), Khaya Dlanga’s To Quote Myself (2015) and Tumi Morake’s And Then Mama Said… Words That Set My Life Alight (2018). Using the intersectional approach, the study explores the lives narrated by second generation South Africans, in a manner similar to the grand narratives because of their historical and social context. The study focalises life/self-writers who have experienced post-apartheid trauma of being racialized, gendered and classed in a democratic country. This is a shift from the staple analysis of lives of political struggle against apartheid, narrated by historical legends such as Nelson Mandela. The study then, by focusing on ‘small voices’ closes a critical gap created by over-attention paid to grand narratives in South African life writing. Self-narrations by young, black, middle-class South Africans emerge not only as a way of narrating history but also as a means of making history. Through the deployment of the intersectional approach (the interconnectedness of inequalities) to analyse the systems of oppression associated with democratic South Africa, the four selected interventional life writers reveal how their experiences and identities are an outcome of constantly renegotiating power relations. , Thesis (MA) -- Faculty of Humanities, Social Sciences and Law, 2020
- Full Text:
- Date Issued: 2020
- Authors: Ndlovu, Siphatisiwe Patricia
- Date: 2020
- Subjects: Post-apartheid era -- South Africa , Interventional writing , Fred Khumalo , Malaika wa Azania , Khaya Dlanga , Tumi Morake
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/11260/3414 , vital:43345
- Description: The interventional life writings of second generation life writers (young, black, middleclass South Africans) in post-apartheid South Africa have not attracted much academic debate in spite of the burgeoning of such writings recently. The intersection of race, class and gender in post-apartheid South Africa remains a problem and a rich site of research, hence this research’s reading of four selected life writings by young, black, middle-class South Africans living in post-apartheid South Africa: Fred Khumalo’s Touch My Blood: The Early Years (2006), Malaika Wa Azania’s Memoires of a Born Free: Reflections on the Rainbow Nation (2014), Khaya Dlanga’s To Quote Myself (2015) and Tumi Morake’s And Then Mama Said… Words That Set My Life Alight (2018). Using the intersectional approach, the study explores the lives narrated by second generation South Africans, in a manner similar to the grand narratives because of their historical and social context. The study focalises life/self-writers who have experienced post-apartheid trauma of being racialized, gendered and classed in a democratic country. This is a shift from the staple analysis of lives of political struggle against apartheid, narrated by historical legends such as Nelson Mandela. The study then, by focusing on ‘small voices’ closes a critical gap created by over-attention paid to grand narratives in South African life writing. Self-narrations by young, black, middle-class South Africans emerge not only as a way of narrating history but also as a means of making history. Through the deployment of the intersectional approach (the interconnectedness of inequalities) to analyse the systems of oppression associated with democratic South Africa, the four selected interventional life writers reveal how their experiences and identities are an outcome of constantly renegotiating power relations. , Thesis (MA) -- Faculty of Humanities, Social Sciences and Law, 2020
- Full Text:
- Date Issued: 2020
Investigating cannabinoids and endocannabinoid receptors as drug targets for pain and inflammation
- Authors: Marwarwa, Sinobomi Zamachi
- Date: 2020
- Subjects: Cannabinoids , Cannabinoids Receptors , Inflammation Alternative treatment , Pain Alternative treatment , Drug targeting
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/164468 , vital:41121
- Description: Cannabinoids and the endocannabinoid system have been studied in the past decades but have yet to be fully understood. An insight into interactions that occur between cannabinoid compounds and their receptors is important for understanding the cannabinoids and the endocannabinoid system. Cannabinoids are natural products found in some cannabis plants, and they have similar effects to endocannabinoids, which are chemicals in the body that are involved many aspects of health from appetite, memory, and movement to pain, inflammation and response to cancer. Cannabinoids have a high impact on the treatment of pain and inflammation, they show different antinociceptive mechanisms to existing drugs like opioids, also, they have antimigraine properties better than those achieved by aspirin. The CB1 and CB2 human receptors have been the most studied cannabinoid receptors. In this project, we used a combination of mass-spectrometry to generate plausible chemical fragments and computational techniques to assess the binding of these fragments to these two main CB receptors. CB1 was adapted from the protein data bank (PBD), file 5U09 and the CB2 model was predicted using the hierarchical protocol I-TASSER, starting from the amino acid sequence in UniProt (P34972 CNR2_HUMAN). The proposed active site for CB1 was reported in a publication accompanying the 5U09 PDB model, which was originally generated with a pre-existing ligand in the active site. However, CB2 had to be built from a homology model and the active site determined using a combination of I-TASSER, Maestro, and CASTp the more favourable binding energies were determined by CASTp, leading to the use of the CASTp coordinates as default for docking in the CB2 human receptor. The molecular docking of cannabinoids THC, CBD, CBDV, CBG and CBN on both the CB1 and CB2 proteins was performed to identify the amino acids that interact with these compounds at their active sites. This would provide a guide to a future fragment-based drug discovery (FBDD) synthesis project. The docking in this work showed adequate accuracy with binding energies between -8.23 kcal/mol and -9.97 kcal/mol for CB1 and between -6.78 kcal/mol and -7.74 kcal/mol for CB2. An observation made was that binding energies of the CB1 human receptor docking were higher than those of the CB2 human receptor, which could support the widely held belief that CB1 is more important in cannabinoid interactions. The cannabinoids were then subjected to collision-induced dissociation to produce fragment structures predicted in chapter 2. These hypothetical fragments were docked in the CB1 and CB2 human receptor, the general trend again being the binding energies for the CB1 receptor was again around 10% higher than those of the CB2 receptor. As expected, larger fragments tended to have better binding, with the fragment proposed from m/z 259 with binding energies -9.62 kcal/mol in CB1 and -6.26 kcal/mol. Those fragments with significant lipophilic side chains or some aromatic moiety also showed good binding or around -6.00 kcal/mol, similar to the intact cannabinoids. In our case, this fragment was proposed from m/z 223 with binding energies -7.71 kcal/mol in CB1 and -6.5 kcal/mol in CB2. The results from the fragment dockings were favourable in that they have binding affinities lower than -6.0 kcal/mol which is good enough for the structures to be leads in the creation of fragment libraries. The docking was performed with Autodock 1.5.6 and data visualization with a discovery studio. , Thesis (MSc) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
- Authors: Marwarwa, Sinobomi Zamachi
- Date: 2020
- Subjects: Cannabinoids , Cannabinoids Receptors , Inflammation Alternative treatment , Pain Alternative treatment , Drug targeting
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/164468 , vital:41121
- Description: Cannabinoids and the endocannabinoid system have been studied in the past decades but have yet to be fully understood. An insight into interactions that occur between cannabinoid compounds and their receptors is important for understanding the cannabinoids and the endocannabinoid system. Cannabinoids are natural products found in some cannabis plants, and they have similar effects to endocannabinoids, which are chemicals in the body that are involved many aspects of health from appetite, memory, and movement to pain, inflammation and response to cancer. Cannabinoids have a high impact on the treatment of pain and inflammation, they show different antinociceptive mechanisms to existing drugs like opioids, also, they have antimigraine properties better than those achieved by aspirin. The CB1 and CB2 human receptors have been the most studied cannabinoid receptors. In this project, we used a combination of mass-spectrometry to generate plausible chemical fragments and computational techniques to assess the binding of these fragments to these two main CB receptors. CB1 was adapted from the protein data bank (PBD), file 5U09 and the CB2 model was predicted using the hierarchical protocol I-TASSER, starting from the amino acid sequence in UniProt (P34972 CNR2_HUMAN). The proposed active site for CB1 was reported in a publication accompanying the 5U09 PDB model, which was originally generated with a pre-existing ligand in the active site. However, CB2 had to be built from a homology model and the active site determined using a combination of I-TASSER, Maestro, and CASTp the more favourable binding energies were determined by CASTp, leading to the use of the CASTp coordinates as default for docking in the CB2 human receptor. The molecular docking of cannabinoids THC, CBD, CBDV, CBG and CBN on both the CB1 and CB2 proteins was performed to identify the amino acids that interact with these compounds at their active sites. This would provide a guide to a future fragment-based drug discovery (FBDD) synthesis project. The docking in this work showed adequate accuracy with binding energies between -8.23 kcal/mol and -9.97 kcal/mol for CB1 and between -6.78 kcal/mol and -7.74 kcal/mol for CB2. An observation made was that binding energies of the CB1 human receptor docking were higher than those of the CB2 human receptor, which could support the widely held belief that CB1 is more important in cannabinoid interactions. The cannabinoids were then subjected to collision-induced dissociation to produce fragment structures predicted in chapter 2. These hypothetical fragments were docked in the CB1 and CB2 human receptor, the general trend again being the binding energies for the CB1 receptor was again around 10% higher than those of the CB2 receptor. As expected, larger fragments tended to have better binding, with the fragment proposed from m/z 259 with binding energies -9.62 kcal/mol in CB1 and -6.26 kcal/mol. Those fragments with significant lipophilic side chains or some aromatic moiety also showed good binding or around -6.00 kcal/mol, similar to the intact cannabinoids. In our case, this fragment was proposed from m/z 223 with binding energies -7.71 kcal/mol in CB1 and -6.5 kcal/mol in CB2. The results from the fragment dockings were favourable in that they have binding affinities lower than -6.0 kcal/mol which is good enough for the structures to be leads in the creation of fragment libraries. The docking was performed with Autodock 1.5.6 and data visualization with a discovery studio. , Thesis (MSc) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
Synthesis and in vitro biological evaluation of 2,3-substituted quinoline derivatives
- Bokosi, Fostino Raphael Bentry
- Authors: Bokosi, Fostino Raphael Bentry
- Date: 2020
- Subjects: Quinoline , Malaria Chemotherapy , Tuberculosis Chemotherapy , African trypanosomiasis Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/163193 , vital:41017
- Description: The urgent need for new systemic pharmacological entities prompted us to report a library of 2,3-substituted quinoline derivatives. Considering the ubiquity of quinoline-containing compounds in pharmacologically active small molecules, synthesized 2,3-substituted quinoline derivatives were in vitro biologically evaluated for their potential antitubercular, antimalarial and antitrypanosomal activities. Quinoline scaffold was achieved by the Vilsmeier-Haack methodology, affording synthetically useful chloro and formyl substituents on C-2 and C-3 respectively. These two substituents acted as handles in expanding the chemical space around the quinoline ring. Target compounds were synthesized in six to seven steps, employing conventional synthetic organic protocols adapted from various literature. The final compounds were accessed in moderate to good yields. The structural identity of each compound was confirmed by common spectroscopic techniques. Aryl quinoline carboxamide derivatives 3.113 – 3.126 were isolated as rotamers, hence, Variable-Temperature Nuclear Magnetic Resonance (VT-NMR) was employed in resolving 1H splitting. At elevated temperature (~328 K); N-methylene carbons were not visible on 13C NMR due to signal line broadening effects. The presence of these nuclei in such cases was, however, supported by 2-dimensional NMR and high-resolution MS data. Most of the compounds achieved in this study displayed promising antimalarial activity against chloroquine-sensitive 3D7 strain of Plasmodium falciparum compared to antitrypanosomal activity against Trypanosoma brucei brucei 427 strain. In particular, compounds 3.80 and 3.108 showed superior activity against chloroquine-sensitive 3D7 P. falciparum strain with IC50 values < 1 μM. More importantly, most of the compounds were non-toxic as determined by HeLa cells, indicating their selectivity towards the parasites. Exploring the space provided on the quinoline scaffold revealed that methoxy incorporation on C-2 is very critical in enhancing antimalarial activity of this class of quinoline compounds. The preliminary SAR of compounds 3.57 – 3.72 showed that compounds containing the 3-cinnamate exhibited enhanced antimalarial activity compared to 2 and 4-cinnamates. Finally, benzamide compounds 3.113 − 3.126 showed poor activity against Mycobacterium tuberculosis H37Rv strain with only compounds 3.113, 3.117 – 3.120 and 3.126 showing appreciable MIC90 values in the range of 40 – 85 μM. , Thesis (MSc) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
- Authors: Bokosi, Fostino Raphael Bentry
- Date: 2020
- Subjects: Quinoline , Malaria Chemotherapy , Tuberculosis Chemotherapy , African trypanosomiasis Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/163193 , vital:41017
- Description: The urgent need for new systemic pharmacological entities prompted us to report a library of 2,3-substituted quinoline derivatives. Considering the ubiquity of quinoline-containing compounds in pharmacologically active small molecules, synthesized 2,3-substituted quinoline derivatives were in vitro biologically evaluated for their potential antitubercular, antimalarial and antitrypanosomal activities. Quinoline scaffold was achieved by the Vilsmeier-Haack methodology, affording synthetically useful chloro and formyl substituents on C-2 and C-3 respectively. These two substituents acted as handles in expanding the chemical space around the quinoline ring. Target compounds were synthesized in six to seven steps, employing conventional synthetic organic protocols adapted from various literature. The final compounds were accessed in moderate to good yields. The structural identity of each compound was confirmed by common spectroscopic techniques. Aryl quinoline carboxamide derivatives 3.113 – 3.126 were isolated as rotamers, hence, Variable-Temperature Nuclear Magnetic Resonance (VT-NMR) was employed in resolving 1H splitting. At elevated temperature (~328 K); N-methylene carbons were not visible on 13C NMR due to signal line broadening effects. The presence of these nuclei in such cases was, however, supported by 2-dimensional NMR and high-resolution MS data. Most of the compounds achieved in this study displayed promising antimalarial activity against chloroquine-sensitive 3D7 strain of Plasmodium falciparum compared to antitrypanosomal activity against Trypanosoma brucei brucei 427 strain. In particular, compounds 3.80 and 3.108 showed superior activity against chloroquine-sensitive 3D7 P. falciparum strain with IC50 values < 1 μM. More importantly, most of the compounds were non-toxic as determined by HeLa cells, indicating their selectivity towards the parasites. Exploring the space provided on the quinoline scaffold revealed that methoxy incorporation on C-2 is very critical in enhancing antimalarial activity of this class of quinoline compounds. The preliminary SAR of compounds 3.57 – 3.72 showed that compounds containing the 3-cinnamate exhibited enhanced antimalarial activity compared to 2 and 4-cinnamates. Finally, benzamide compounds 3.113 − 3.126 showed poor activity against Mycobacterium tuberculosis H37Rv strain with only compounds 3.113, 3.117 – 3.120 and 3.126 showing appreciable MIC90 values in the range of 40 – 85 μM. , Thesis (MSc) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
The novobiocin-induced turnover of fibronectin via low density lipoprotein receptor-related protein 1 alters matrix morphology with physiological consequences on cell growth and migration
- Authors: Boёl, Natasha Marie-Eraine
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/114778 , vital:34034 , 10.21504/10962/114778
- Description: Fibronectin (FN), an extracellular matrix protein, is secreted as a soluble dimer which is assembled into an insoluble extracellular matrix. The dynamics of FN matrix assembly and degradation play a large role in cell migration and invasion thereby contributing to the metastatic potential of cancer cells. Previous studies have shown the direct binding of Heat Shock Protein 90 kDa (Hsp90) and FN in vitro, and that inhibition of Hsp90 with novobiocin (NOV) caused internalisation of the FN matrix. Low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitous receptor known to bind both Hsp90 and FN. Using an LRP1 expressing Hs578T breast cancer cell line and an isogenic mouse embryonic fibroblast (MEF) model system of differential LRP1 expression we demonstrate that LRP1 is involved in turnover of FN in response to C-terminal Hsp90 inhibition. The first objective of this study was to identify the mechanism of NOV-induced LRP1-mediated FN turnover. Our data show that NOV-mediated FN turnover via LRP1 did not require the activity of matrix metalloproteinases (MMPs), which play an important role in processing and degradation of the extracellular matrix and FN. In addition, the levels of the main FN receptor responsible for its extracellular assembly, β1-integrin, did not change in response to NOV. LRP1 is known to undergo regulated intramembrane proteolysis (RIP) which generates smaller fragments that may translocate to the nucleus and modulate gene transcription. Using inhibitors of LRP1 cleavage and nuclear fractionation we determined that LRP1 processing was not required for the NOV-induced FN response suggesting that a mechanism unrelated to LRP1 RIP is involved. A possible mechanism may be in altered Hsp90-LRP1 cell signalling as we observed disruption of the FN-Hsp90-LRP1 complex at the cell surface in NOV treated cells. How this affects downstream eHsp90-LRP1 signalling is still to be determined but may be related to a significant increase in phospho-AKT and loss of phospho-ERK upon NOV-treatment; two key signalling proteins involved in FN matrix regulation and which are downstream of LRP1 signalling. The second objective of this study was to determine the physiological consequences associated with FN turnover in response to NOV treatment. Using migration assays we demonstrated that levels of insoluble matrix-associated FN and FN concentration are not solely responsible for migratory capacity of cells on decellularized extracellular matrices, but rather that structural composition and integrity of the matrix plays a bigger role. Using confocal and scanning electron microscopy, we identified NOV treated matrices to be flatter, less mature and contain thicker, rope-like FN fibrils to which cells adhered better but were generally less proliferative. Comparatively, cells adhered less to the more mature and 3-dimensional untreated matrices but exhibited increased spreading and cell growth, which may in part be due to the thinner fibrils and web-like matrix. In summary, this study substantiates the role of LRP1 in NOV-mediated FN turnover, and provides new insights into the possible mechanisms of the Hsp90-LRP1 mediated loss of FN matrix. This is the first study to demonstrate some of the functional consequences related to FN turnover by NOV at the ECM level. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text: false
- Date Issued: 2020
- Authors: Boёl, Natasha Marie-Eraine
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/114778 , vital:34034 , 10.21504/10962/114778
- Description: Fibronectin (FN), an extracellular matrix protein, is secreted as a soluble dimer which is assembled into an insoluble extracellular matrix. The dynamics of FN matrix assembly and degradation play a large role in cell migration and invasion thereby contributing to the metastatic potential of cancer cells. Previous studies have shown the direct binding of Heat Shock Protein 90 kDa (Hsp90) and FN in vitro, and that inhibition of Hsp90 with novobiocin (NOV) caused internalisation of the FN matrix. Low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitous receptor known to bind both Hsp90 and FN. Using an LRP1 expressing Hs578T breast cancer cell line and an isogenic mouse embryonic fibroblast (MEF) model system of differential LRP1 expression we demonstrate that LRP1 is involved in turnover of FN in response to C-terminal Hsp90 inhibition. The first objective of this study was to identify the mechanism of NOV-induced LRP1-mediated FN turnover. Our data show that NOV-mediated FN turnover via LRP1 did not require the activity of matrix metalloproteinases (MMPs), which play an important role in processing and degradation of the extracellular matrix and FN. In addition, the levels of the main FN receptor responsible for its extracellular assembly, β1-integrin, did not change in response to NOV. LRP1 is known to undergo regulated intramembrane proteolysis (RIP) which generates smaller fragments that may translocate to the nucleus and modulate gene transcription. Using inhibitors of LRP1 cleavage and nuclear fractionation we determined that LRP1 processing was not required for the NOV-induced FN response suggesting that a mechanism unrelated to LRP1 RIP is involved. A possible mechanism may be in altered Hsp90-LRP1 cell signalling as we observed disruption of the FN-Hsp90-LRP1 complex at the cell surface in NOV treated cells. How this affects downstream eHsp90-LRP1 signalling is still to be determined but may be related to a significant increase in phospho-AKT and loss of phospho-ERK upon NOV-treatment; two key signalling proteins involved in FN matrix regulation and which are downstream of LRP1 signalling. The second objective of this study was to determine the physiological consequences associated with FN turnover in response to NOV treatment. Using migration assays we demonstrated that levels of insoluble matrix-associated FN and FN concentration are not solely responsible for migratory capacity of cells on decellularized extracellular matrices, but rather that structural composition and integrity of the matrix plays a bigger role. Using confocal and scanning electron microscopy, we identified NOV treated matrices to be flatter, less mature and contain thicker, rope-like FN fibrils to which cells adhered better but were generally less proliferative. Comparatively, cells adhered less to the more mature and 3-dimensional untreated matrices but exhibited increased spreading and cell growth, which may in part be due to the thinner fibrils and web-like matrix. In summary, this study substantiates the role of LRP1 in NOV-mediated FN turnover, and provides new insights into the possible mechanisms of the Hsp90-LRP1 mediated loss of FN matrix. This is the first study to demonstrate some of the functional consequences related to FN turnover by NOV at the ECM level. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text: false
- Date Issued: 2020
Understanding the livelihoods of Zimbabwean informal traders in South Africa: the case of Makhanda
- Musiyandaka, Tariro Henrietta
- Authors: Musiyandaka, Tariro Henrietta
- Date: 2020
- Subjects: Informal sector (Economics) South Africa Makhanda , Foreign workers, Zimbabwean South Africa Makhanda Economic conditions , Foreign workers, Zimbabwean South Africa Makhanda Social conditions , Street vendors South Africa Makhanda
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/164535 , vital:41127
- Description: Increasingly, Zimbabweans are migrating from their country for both economic and political reasons, with South Africa being the primary destination. In seeking employment in South Africa, Zimbabweans face numerous initial problems, including the high unemployment rate in the country alongside restrictions on their employment in the formal economy. In this context, Zimbabweans often turn to work in the informal economy, including as informal traders. This thesis seeks to understand the lives and livelihoods of Zimbabwean informal traders in Makhanda in the Eastern Cape Province of South Africa. Drawing upon the Sustainable Livelihoods Approach, and in the light of existing literature on Zimbabweans more broadly in South Africa, the thesis examines the livelihoods of a purposeful sampled grouping of six informal traders from Zimbabwe in Makhanda. It discusses their reasons for leaving Zimbabwe, their journey from Zimbabwe to Makhanda, relationships amongst themselves and their ongoing relationships with family back home, as well as their hopes and plans for the future. It also examines more specifically their livelihood activities, the daily challenges they face in pursuing their livelihoods and concerns about their livelihood status in South Africa. Despite the many deep-rooted systemic obstacles confronting these Zimbabwean informal traders, the thesis concludes that they demonstrate significant micro-level ingenuity in pursuing their livelihoods in South Africa. , Thesis (MA) -- Faculty of Faculty of Humanities, Sociology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Musiyandaka, Tariro Henrietta
- Date: 2020
- Subjects: Informal sector (Economics) South Africa Makhanda , Foreign workers, Zimbabwean South Africa Makhanda Economic conditions , Foreign workers, Zimbabwean South Africa Makhanda Social conditions , Street vendors South Africa Makhanda
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/164535 , vital:41127
- Description: Increasingly, Zimbabweans are migrating from their country for both economic and political reasons, with South Africa being the primary destination. In seeking employment in South Africa, Zimbabweans face numerous initial problems, including the high unemployment rate in the country alongside restrictions on their employment in the formal economy. In this context, Zimbabweans often turn to work in the informal economy, including as informal traders. This thesis seeks to understand the lives and livelihoods of Zimbabwean informal traders in Makhanda in the Eastern Cape Province of South Africa. Drawing upon the Sustainable Livelihoods Approach, and in the light of existing literature on Zimbabweans more broadly in South Africa, the thesis examines the livelihoods of a purposeful sampled grouping of six informal traders from Zimbabwe in Makhanda. It discusses their reasons for leaving Zimbabwe, their journey from Zimbabwe to Makhanda, relationships amongst themselves and their ongoing relationships with family back home, as well as their hopes and plans for the future. It also examines more specifically their livelihood activities, the daily challenges they face in pursuing their livelihoods and concerns about their livelihood status in South Africa. Despite the many deep-rooted systemic obstacles confronting these Zimbabwean informal traders, the thesis concludes that they demonstrate significant micro-level ingenuity in pursuing their livelihoods in South Africa. , Thesis (MA) -- Faculty of Faculty of Humanities, Sociology, 2020
- Full Text:
- Date Issued: 2020
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