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: Uncatalogued
- 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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- Date Issued: 2023-03-29
The relationship between authentic leadership, psychological capital, psychological climate, team commitment and the intention to quit in a South African manufacturing organisation
- Authors: Munyaka, Sharon Audley
- Date: 2012
- Subjects: Leadership -- South Africa , Organizational commitment -- South Africa , Work environment -- South Africa , Employees -- Resignation -- South Africa , Tire industry workers -- South Africa
- Language: English
- Type: Thesis , Doctoral , DCom
- Identifier: vital:9418 , http://hdl.handle.net/10948/d1021088
- Description: Grounded in the positive psychology paradigm the recently recognised core construct of psychological capital was focussed in a South African study. A non-experimental, correlational study (n=204) examined the relationship between authentic leadership, psychological capital, psychological climate, team commitment and intention to quit. The present study was exploratory in nature and the pattern of relationships being investigated had not been previously tested in a South African context. A self-administered composite questionnaire consisting of five psychological scales were distributed to employees in the junior to senior management level at a global tyre manufacturing organisation based in Port Elizabeth, South Africa. The five scales were the Authentic Leadership Questionnaire by Walumbwa, Psychological Capital Questionnaire by Luthans, Psychological Climate by Koys and DeCotiis, Team Commitment by Bennett and the Intention to Quit Scale by Cohen. All the measures applied on the South African sample were developed outside South Africa and model equivalence had to be established. The content and structure of the measures were investigated through confirmatory factor analysis and exploratory factor analysis. With the exception of the Cohen scale of intention to quit, all other measures changed their factorial structures to suit the present data. The propositions in the study were tested through descriptive statistics, t-tests, ANOVA, post hoc tests, Cohen’s d, Pearson product-moment correlation and multiple regressions. Structural equation models were built to test the relationships between the scales and sub scales of authentic leadership, psychological capital, psychological climate, team commitment and intention to quit. Results of the analyses carried out, show significantly strong relationships between the variables. Of note is the marked relationship between authentic leadership and psychological climate. Most of the propositions were accepted in light of the relationships that emerged. The proposition indicating structural equation models was rejected because none of the models built in the study successfully produced an adequate fit on the data. Contributions of the study were in terms of the portability of the measurement instruments applied in the study as well as the relationships that emerged. Re-validation of the measures is required to enable clarity on how the variables in the study are interpreted across cultural contexts. Directions for future research include extending the study to other samples and other cultures. Measuring social desirability of the instruments could possibly provide clarity on how the different samples respond to the measures. Studies that compare the reading ability as well as the ability to comprehend the items in the measures would provide valuable information.
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- Date Issued: 2012