A Comparison of Mitochondrial Heat Shock Protein 70 and Hsp70 Escort Protein 1 Orthologues from Trypanosoma brucei and Homo sapiens
- Authors: Hand, Francis Bryan
- Date: 2023-03-29
- Subjects: Trypanosoma brucei , Heat shock proteins , Molecular chaperones , Transport protein , AlphaFold , Mitochondrial heat shock protein
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/422281 , vital:71927
- Description: The causative agent of African trypanosomiasis, Trypanosoma brucei (T. brucei), has an expanded retinue of specialized heat shock proteins, which have been identified as crucial to the progression of the disease. These play a central role in disease progression and transmission through their involvement in cell-cycle pathways which bring about cell-cycle arrest and differentiation. Hsp70 proteins are essential for the maintenance of proteostasis in the cell. Mitochondrial Hsp70 (mtHsp70) is a highly conserved molecular chaperone required for both the translocation of nuclear encoded proteins across the two mitochondrial membranes and the subsequent folding of proteins in the matrix. The T. brucei genome encodes three copies of mtHsp70 which are 100% identical. MtHsp70 self-aggregates, a property unique to this isoform, and an Hsp70 escort protein (Hep1) is required to maintain the molecular chaperone in a soluble, functional state. This study aimed to compare the solubilizing interaction of Hep1 from T. brucei and Homo sapiens (H. sapien). The recently introduced Alphafold program was used to analyze the structures of mtHsp70 and Hep1 proteins and allowed observations of structures unavailable to other modelling techniques. The GVFEV motif found in the ATPase domain of mtHsp70s interacted with the linker region, resulting in aggregation, the Alphafold models produced indicated that the replacement of the lysine (K) residue within the KTFEV motif of DnaK (prokaryotic Hsp70) with Glycine (G), may abrogate bond formation between the motif and a region between lobe I and II of the ATPase domain. This may facilitate the aggregation reaction of mtHsp70 orthologues and provides a residue of interest for future studies. Both TbHep1 and HsHep1 reduced the thermal aggregation of TbmtHsp70 and mortalin (H. sapien mtHsp70) respectively, however, TbHep1 was ~ 15 % less effective than HsHep1 at higher concentrations (4 uM). TbHep1 itself appeared to be aggregation-prone when under conditions of thermal stress, Alphafold models suggest this may be due to an N-terminal α- helical structure not present in HsHep1. These results indicate that TbHep1 is functionally similar to HsHep1, however, the orthologue may operate in a unique manner which requires further investigation. , Thesis (MSc) -- Faculty of Science, Biotechnology Innovation Centre, 2023
- Full Text:
- Authors: Hand, Francis Bryan
- Date: 2023-03-29
- Subjects: Trypanosoma brucei , Heat shock proteins , Molecular chaperones , Transport protein , AlphaFold , Mitochondrial heat shock protein
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/422281 , vital:71927
- Description: The causative agent of African trypanosomiasis, Trypanosoma brucei (T. brucei), has an expanded retinue of specialized heat shock proteins, which have been identified as crucial to the progression of the disease. These play a central role in disease progression and transmission through their involvement in cell-cycle pathways which bring about cell-cycle arrest and differentiation. Hsp70 proteins are essential for the maintenance of proteostasis in the cell. Mitochondrial Hsp70 (mtHsp70) is a highly conserved molecular chaperone required for both the translocation of nuclear encoded proteins across the two mitochondrial membranes and the subsequent folding of proteins in the matrix. The T. brucei genome encodes three copies of mtHsp70 which are 100% identical. MtHsp70 self-aggregates, a property unique to this isoform, and an Hsp70 escort protein (Hep1) is required to maintain the molecular chaperone in a soluble, functional state. This study aimed to compare the solubilizing interaction of Hep1 from T. brucei and Homo sapiens (H. sapien). The recently introduced Alphafold program was used to analyze the structures of mtHsp70 and Hep1 proteins and allowed observations of structures unavailable to other modelling techniques. The GVFEV motif found in the ATPase domain of mtHsp70s interacted with the linker region, resulting in aggregation, the Alphafold models produced indicated that the replacement of the lysine (K) residue within the KTFEV motif of DnaK (prokaryotic Hsp70) with Glycine (G), may abrogate bond formation between the motif and a region between lobe I and II of the ATPase domain. This may facilitate the aggregation reaction of mtHsp70 orthologues and provides a residue of interest for future studies. Both TbHep1 and HsHep1 reduced the thermal aggregation of TbmtHsp70 and mortalin (H. sapien mtHsp70) respectively, however, TbHep1 was ~ 15 % less effective than HsHep1 at higher concentrations (4 uM). TbHep1 itself appeared to be aggregation-prone when under conditions of thermal stress, Alphafold models suggest this may be due to an N-terminal α- helical structure not present in HsHep1. These results indicate that TbHep1 is functionally similar to HsHep1, however, the orthologue may operate in a unique manner which requires further investigation. , Thesis (MSc) -- Faculty of Science, Biotechnology Innovation Centre, 2023
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An in vitro investigation of novel quinolone derivatives on selected pharmacological targets for diabetes mellitus and associated complications
- Authors: Ayodele, Omobolanle Opeyemi
- Date: 2023-03-29
- Subjects: Diabetes , Hyperglycemia , Quinolone antibacterial agents , Cardiovascular system Diseases , Diabetes Alternative treatment , In vitro experiment
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/409813 , vital:70632
- Description: Diabetes mellitus (DM) is a group of endocrine and metabolic disorders characterised and identified by the presence of hyperglycaemia over a long period and, to an extent, accompanied by hyperlipidaemia. CVD has been reported to be the leading cause of mortality in patients with DM. Several antidiabetic agents are available for managing DM, but these agents are not for curative therapy and present with undesirable side effects. In addition, these agents become less effective as the patient's condition progresses to complete beta-cell failure. Therefore, developing newer antidiabetic agents with minimal undesirable side effects, prolonged efficacy and protection against the development of DM complications are necessary. This study was conducted to identify potential novel antidiabetic agents with cardiovascular-protective activity. The compounds of interest for the study were quinolone derivatives since quinolones have been reported to have an antihyperglycaemic effect. , Thesis (MSc) -- Faculty of Pharmacy, 2023
- Full Text:
- Authors: Ayodele, Omobolanle Opeyemi
- Date: 2023-03-29
- Subjects: Diabetes , Hyperglycemia , Quinolone antibacterial agents , Cardiovascular system Diseases , Diabetes Alternative treatment , In vitro experiment
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/409813 , vital:70632
- Description: Diabetes mellitus (DM) is a group of endocrine and metabolic disorders characterised and identified by the presence of hyperglycaemia over a long period and, to an extent, accompanied by hyperlipidaemia. CVD has been reported to be the leading cause of mortality in patients with DM. Several antidiabetic agents are available for managing DM, but these agents are not for curative therapy and present with undesirable side effects. In addition, these agents become less effective as the patient's condition progresses to complete beta-cell failure. Therefore, developing newer antidiabetic agents with minimal undesirable side effects, prolonged efficacy and protection against the development of DM complications are necessary. This study was conducted to identify potential novel antidiabetic agents with cardiovascular-protective activity. The compounds of interest for the study were quinolone derivatives since quinolones have been reported to have an antihyperglycaemic effect. , Thesis (MSc) -- Faculty of Pharmacy, 2023
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Source of introduced populations of Hemidactylus mabouia (Moreau de Jonnès, 1818) into the Eastern Cape Province and the potential spread to other South African regions
- Authors: Jeme, Alungile
- Date: 2023-03-29
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/422334 , vital:71933
- Description: Human movements globally have resulted in dispersal and introduction of terrestrial and marine organisms into areas outside of their native range. Species that have been introduced to new habitats can either be alien (not causing any harm to the new environment) or invasive alien species (destroying or competing with the indigenous species for resources). Investigating the source of these introductions is important as it provides baseline information about their biology and evolution. It also allows for better prevention measures for future invasions and for effective conservation strategies. In this study, I investigate the source of the introduced populations of tropical house geckos Hemidactylus mabouia in the Eastern Cape Province using two mitochondrial gene regions, ribosomal 16S and NADH dehydrogenase subunit 4 (ND4). We also look at the potential spread of these species using species distribution models (SDMs). The phylogeny showed that the introduced populations into the Eastern Cape were genetically similar to both H. mabouia lineages found in Central & Southern Africa. The phylogeny produced two clades from which the majority of the introduced samples were grouped in a clade with samples from Angola, DRC, and Mozambique, and only a few nested within the second clade with the South African native population. Haplotype networks from both genes also showed two clades, matching those found in the phylogeny. The introduced samples were associated with samples from Angola and those from South Africa (native) as these localities had a number of shared haplotypes. SDMs showed less evidence that these individuals could naturally move west down the coast as the probability of occurrence was below 0.4 from the Eastern Cape to the Western Cape. Our conclusion was that the introductions may be due to multiple avenues like species moving down the east coast or human translocation including trade routes. From this we can conclude that geckos are largely translocated through human movement as they are known for their opportunistic behaviours as they are commensal with humans. , Thesis (MSc) -- Faculty of Science, Zoology and Entomology, 2023
- Full Text:
- Authors: Jeme, Alungile
- Date: 2023-03-29
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/422334 , vital:71933
- Description: Human movements globally have resulted in dispersal and introduction of terrestrial and marine organisms into areas outside of their native range. Species that have been introduced to new habitats can either be alien (not causing any harm to the new environment) or invasive alien species (destroying or competing with the indigenous species for resources). Investigating the source of these introductions is important as it provides baseline information about their biology and evolution. It also allows for better prevention measures for future invasions and for effective conservation strategies. In this study, I investigate the source of the introduced populations of tropical house geckos Hemidactylus mabouia in the Eastern Cape Province using two mitochondrial gene regions, ribosomal 16S and NADH dehydrogenase subunit 4 (ND4). We also look at the potential spread of these species using species distribution models (SDMs). The phylogeny showed that the introduced populations into the Eastern Cape were genetically similar to both H. mabouia lineages found in Central & Southern Africa. The phylogeny produced two clades from which the majority of the introduced samples were grouped in a clade with samples from Angola, DRC, and Mozambique, and only a few nested within the second clade with the South African native population. Haplotype networks from both genes also showed two clades, matching those found in the phylogeny. The introduced samples were associated with samples from Angola and those from South Africa (native) as these localities had a number of shared haplotypes. SDMs showed less evidence that these individuals could naturally move west down the coast as the probability of occurrence was below 0.4 from the Eastern Cape to the Western Cape. Our conclusion was that the introductions may be due to multiple avenues like species moving down the east coast or human translocation including trade routes. From this we can conclude that geckos are largely translocated through human movement as they are known for their opportunistic behaviours as they are commensal with humans. , Thesis (MSc) -- Faculty of Science, Zoology and Entomology, 2023
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The proprietary consequences of foreign marriages for the purposes of estate planning and succession in South Africa
- Authors: Thorne, Aimee Liza
- Date: 2023-03-29
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/420725 , vital:71773
- Description: This thesis is intended to provide clarity regarding the proprietary consequences of foreign marriages in the context of estate planning and succession in South Africa. It includes an exploration into the impact of specific legislation on foreign marriages, the implications of matrimonial property regimes on a deceased estate in South Africa, private international law principles affecting matrimonial property and succession claims, the scope of antenuptial contracts and postnuptial contracts as existing remedies for foreign remedies, and the harmonisation of succession and matrimonial property law in the European Union (EU). It furthermore suggests potential reforms for the overhaul of the lex domicilii matrimonii principle and associated issues arising therefrom. Various specific issues discussed include the waiver of accrual claims, maintenance claims by surviving spouses of a foreign marriage, choice-of-law rules for matrimonial property rights and succession rights, the registration of a domestic or foreign antenuptial contract for foreign marriages, the formal validity and proper law of antenuptial contracts, the operation of the immutability principle on a domestic and international level, and the common-law approach to the recognition of postnuptial contracts and spousal donations. , Thesis (LLM) -- Faculty of Law, Law, 2023
- Full Text:
- Authors: Thorne, Aimee Liza
- Date: 2023-03-29
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/420725 , vital:71773
- Description: This thesis is intended to provide clarity regarding the proprietary consequences of foreign marriages in the context of estate planning and succession in South Africa. It includes an exploration into the impact of specific legislation on foreign marriages, the implications of matrimonial property regimes on a deceased estate in South Africa, private international law principles affecting matrimonial property and succession claims, the scope of antenuptial contracts and postnuptial contracts as existing remedies for foreign remedies, and the harmonisation of succession and matrimonial property law in the European Union (EU). It furthermore suggests potential reforms for the overhaul of the lex domicilii matrimonii principle and associated issues arising therefrom. Various specific issues discussed include the waiver of accrual claims, maintenance claims by surviving spouses of a foreign marriage, choice-of-law rules for matrimonial property rights and succession rights, the registration of a domestic or foreign antenuptial contract for foreign marriages, the formal validity and proper law of antenuptial contracts, the operation of the immutability principle on a domestic and international level, and the common-law approach to the recognition of postnuptial contracts and spousal donations. , Thesis (LLM) -- Faculty of Law, Law, 2023
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