List of Titles

Quick View

Financial technology and bank risk-taking behavior: a case of selected South African banks

- Magula, Zizipho

Authors: Magula, Zizipho
Date: 2022-04-06
Subjects: Uncatalogued
Language: English
Type: Master's theses , text
Identifier: http://hdl.handle.net/10962/234206 , vital:50172
Description: In this study, our analysis contributes to the emerging literature investigating if the introduction of FinTech enhances or diminishes the effect of the bank risk determinants in the South African banking sector and establish if FinTech can be a channel that affects bank risk-taking behaviour in South Africa. Using data collected from Thomson Reuters and the South African Reserve Bank covering the top ten South African banks based on the availability of data on all variables, we provide detailed evidence on the effects of FinTech on risk-taking behaviour of banks and the effects of FinTech on bank determinants such as Non-performing loans (NPL). Still, scant empirical research has investigated whether FinTech start-ups cause banks to increase their risk- taking behaviour to remain relevant, competitive and maintain their market share. From an economic perspective, it is crucial to close the research gap to understand better how FinTechs reshape the banking sector, the financial sector, and the economy by analyzing the effects of FinTech on bank characteristics. The study shows that banks' risk-taking behaviour is increased when the FinTech financial planning platform is introduced in the selected banks. Secondly, the effects of NPLs are enhanced through the following, which in turn affects the bank risk: 1. Credit dummy variable when the money market dummy variable is introduced in banks. 2. The interaction of NPL and the transfer dummy variable when the FinTech credit segment is introduced in banks. 3. Money market dummy variable and NPL interaction when the credit and transfer segment is introduced in banks. The findings of this study add to the advancement of bank and FinTech literature and provide new opportunities for future research, particularly in the South African context. Finance specialists may be interested in the changes that FinTechs make in the financial sector, while economists may investigate the implications for the overall economy or required policy reforms. , Thesis (MCom) -- Faculty of Commerce, Economics and Economic History, 2022
Full Text:
Date Issued: 2022-04-06

Quick View

Exploring the use of in vitro colorimetric and bioluminescence assays to distinguish between Arf GTPase isoforms and detect Arf GTPase activity

- Woolf, Alexander Robert

Authors: Woolf, Alexander Robert
Date: 2021-10-29
Subjects: Uncatalogued
Language: English
Type: Master's theses , text
Identifier: http://hdl.handle.net/10962/192582 , vital:45240
Description: ADP-ribosylation factors (Arfs), part of the Ras superfamily of small GTPases, are involved in various key cellular processes such as the regulation of membrane trafficking and organelle structure. Arfs cycle between a GDP-bound ‘inactive’ conformation and a GTP-bound ‘active’ conformation, with the latter exerting its functions on various downstream effector proteins. In eukaryotic organisms, Arf6 regulates traffic in the endocytic pathway and contributes the reorganisation of actin cytoskeleton. Due to its ability to affect health and disease in many ways, Arf6 has been a viable drug target for many diseases, with this study focusing mainly on cancer and malaria. In the P. falciparum parasite genome are two genes encoding for Arf GTPase. The first (PfArf1) has been designated as an Arf1 homologue, and the second shares sequence similarities with both human Arf1 and Arf6 but is otherwise uncharacterised. The potential of the second putative malarial Arf sequence to be a homologue of human Arf6 is important as it would further our understanding of the unusual mechanisms behind malarial endocytosis of the red blood cell cytoplasm. To assign this second putative malarial Arf (PfArf6) as a human Arf6 or Arf1 homologue, a novel plate-based colorimetric assay system was used involving the Arf effector binding domains of “golgi-localised gamma adaptin ear-containing ARF-binding protein 3” (GGA3), which interacts with Arf1 and Arf6, and “c-Jun NH2-terminal kinase-interacting protein 4” (JIP4), which interacts with Arf6 only. It was shown that PfArf6 was able to bind to both GGA3 and JIP4 and that PfArf6 was distinguishable from PfArf1. Initial data obtained designated “PfArf6” as an Arf6 homologue, despite the higher sequence similarity between PfArf6 and human Arf1. Arf GTPases display notoriously slow intrinsic GTPase activity and so their activity is tightly regulated by their cognate guanine nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs), which cycle Arfs between their GDP- and GTP-bound conformations. Arf6 and its closely associated regulators are involved extensively in the promotion of tumour growth, invasion, and metastasis stages of cancer. Simple and reproducible GTPase activity assays, that are simultaneously amenable to screening compound libraries for Arf inhibitors, are limited in availability due to the difficulties surrounding accurate GTP detection. A novel in vitro plate-based bioluminescence assay format developed in this study to detect Arf GTPase activity in the presence of its regulators namely “ARF nucleotide-binding site opener” (ARNO) and ArfGAP1. In cells “nucleoside diphosphate kinase” (NDPK) functions to regulate the available nucleoside triphosphate (NTP) pools to maintain homeostasis. Given the relative ease for accurate ATP detection using firefly luciferase and the ability for NDPK the convert GTP to ATP, NDPK and luciferase were utilised in this coupled assay to detect GTP consumption by Arf. Regulator stimulated Arf GTPase activity was eventually detectable to varying degrees for human Arf1 and Arf6, as well as malarial Arf1. Thus, the groundwork for a simple, plate-based assay system has been laid for the detection of the full Arf GTPase activity cycle, the screening of compound libraries for Arf inhibitors, as well as a means of determining Arf GTPase specificity for regulators (and vice versa) in vitro. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
Full Text:
Date Issued: 2021-10-29

Quick View

Identification of potential inhibitors of the folate biosynthesis enzymes HPPK of Salmonella enterica and Escherichia coli and pteridine reductase of Trypanosoma brucei through molecular docking and enzyme assays

- Gerwel, Tiaan Marc

Authors: Gerwel, Tiaan Marc
Date: 2021-10-29
Subjects: Uncatalogued
Language: English
Type: Master's theses , text
Identifier: http://hdl.handle.net/10962/192419 , vital:45224
Description: Antimicrobial resistance has become a serious threat to the survival of the human species especially those living in rural areas where access to medicine and the knowledge for proper use is scarce. It has been estimated that the number of extreme untreatable resistant infections in Africa will increase to as much as 10 million by the year 2050. Thus the need for novel drugs to act as therapeutic agents is becoming more compelling each year. The subspecies of Trypanosoma brucei (T. brucei) is responsible for the Human African Trypanosomiasis (HAT) also known as sleeping sickness and results in large numbers of deaths and loss of income for many homes. Resistance to current therapeutic agents has been observed and is on the rise increasing the difficulty to treat the infection. Salmonella enterica (S. enterica) serotypes are responsible for acute diarrhoeal disease in humans ranging from invasive typhoid to non-invasive non-typhoid disease, resulting in a large number of deaths, with an estimated 180 million people falling ill annually. The pathogen is spread via the faecal-oral route or through food contaminated with bacterium and prepared in an unsanitary environment. The chance of recovery in rural populations is low. Escherichia coli (E. coli), forming part of commensal gut flora, spread via the faecal-oral route or unhygienic practices, causes a diarrhoeal disease which can progress to a haemorrhagic phase. More than 241 million annual infections are caused by enterotoxigenic E. coli. A common strategy to develop antimicrobial agents is to target the biosynthesis of essential biological molecules, thereby rendering the microbes less viable. One such group of molecules are folates, which are generally synthesised de novo by bacteria. Higher organisms have a scavenger mechanism to obtain their folates from the extracellular environment and in some cases, organisms have both mechanisms. In this study, two enzymes falling into the folate scavenger and de novo synthesis groups were examined to identify potential agents to act as inhibitors. Pteridine reductase 1 (PTR1) is a scavenger enzyme used by a variety of trypanosomes and 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is an enzyme that overlaps the kingdoms of protozoa and bacteria forming part of the de novo biosynthetic pathway. Homology modelling was performed on the HPPK enzyme of S. enterica using Yersinia pestis (Y. pestis) as a template providing a model to use for docking studies. The E. coli HPPK enzyme structure was retrieved from the Protein Data Bank (PDB) and bound molecules were removed to render the enzyme in an apo-state. Docking studies using the generated S. enterica homology model and apo E. coli HPPK was performed using the ZINC 15 database and resulted in 9 hit compounds which showed high binding affinities and binding energy to the enzyme. The HPPK and PTR1 enzyme coding sequences were cloned into pET-28a(+) plasmids and supplied by GenScript, to enable the expression of histidine-tagged proteins in T7 Express lysY competent E. coli cells. Analytical scale expression studies showed the recombinant proteins to be in a soluble form and purification was achieved using nickel-NTA affinity chromatography. The purified PTR1 recombinant protein was used to establish and optimise an NADPH absorbance microplate assay to screen compounds previously identified in docking studies by Kimuda, Laming, Hoppe, & Bishop, (2019). The assay yielded a Z´-factor of above 0.8 indicating an excellent assay to use for screening. An unsuccessful attempt was made to use resazurin reduction as an alternative method to demonstrate PTR1 enzyme activity. HPPK purified recombinant proteins were used to establish and optimise a luminescence microplate assay for the screening of compounds identified in in silico docking studies against the HPPK enzymes of S. enterica and E. coli. The Z´-factor of the luminescence assay was above 0.5, indicative of a functional assay with good separation between enzyme activity signal and negative control of reaction without enzyme. The target-based enzyme screening resulted in the confirmation of compound 3 (3-chloro-N-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzamide) as an inhibitor of S. enterica HPPK with an IC₅₀ of 10.4 μM. At 50 μM none of the compounds decreased E. coli HPPK enzyme activity by 50%. Further bacterial studies would provide more compelling data to motivate the optimisation of compound 3 as an S. enterica inhibitor. This study demonstrated the effectiveness of using computational methods in the drug discovery process, correlating in silico results with those obtained from target-based assays producing a hit compound that can be used for future drug optimisation. , Thesis (MSc (Pharm)) -- Faculty of Pharmacy, Pharmacy, 2021
Full Text:
Date Issued: 2021-10-29

Quick View

Showing items 141 - 160 of 534