Molecular and morphological approaches reveal hidden diversity in the genus hippopotamyrus pappenheim, 1906 (teleostei: mormyridae) in southern Africa
- Authors: Mutizwa, Tadiwa, Isaac
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164546 , vital:41128
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Department of Icthyology and Fisheries Science, 2020
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- Date Issued: 2020
Multiplexed Mass Spectrometry: Single, On-Bead, Detection Analysis Using MALDI-TOF MS
- Authors: Twala, Busisiwe Victoria
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164693 , vital:41155 , doi:10.21504/10962/164693
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
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- Date Issued: 2020
Nutrient impacts on grasses and legumes growing in communal pasture soil in relation to mycorrhizal activity
- Authors: Mkile, Zolani
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164512 , vital:41125 , doi:10.21504/10962/164512
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
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- Date Issued: 2020
Orchid mycorrhizal and endophytic fungal diversity of three cooccurring terrestrial orchids in the large African genus Disa (Orchidaceae)
- Authors: Le Du, Bridgitte M
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MA
- Identifier: http://hdl.handle.net/10962/163363 , vital:41033
- Description: Thesis (MA)--Rhodes University, Faculty of Humanities, English Language and Linguistics, 2020.
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- Date Issued: 2020
Production, purification and characterization of a multifunctional, thermostable and acido/alkaline stable putative xylanase from the psychrotrophic bacterium, Sphingomonas aerolata
- Authors: Mathibe, Brian Nkanyiso
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164478 , vital:41122
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
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- Date Issued: 2020
Repurposing a polymer precursor scaffold for medicinal application: Synthesis, characterization and biological evaluation of ferrocenyl 1,3-benzoxazine derivatives as potential antiprotozoal and anticancer agents
- Authors: Mbaba, Mziyanda
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/164502 , vital:41124 , DOI 10.21504/10962/164502
- Description: The benzoxazines are a prominent class of heterocyclic compounds that possess a multitude of properties. To this end, benzoxazine derivatives have been used as versatile compounds for various utilities ranging from biological applications to the fabrication of polymers. Particularly, the 1,3-benzoxazine scaffold has featured in several bioactive compounds showing antimalarial, anticancer and antibacterial activities. Traditionally, it has been employed as a substrate in the synthesis of polymers with appealing physical and chemical properties. Due to the increasing interest in the polymer application of 1,3-benzoxazines, research of the 1,3-benzoxazine motif for polymer synthesis has been prioritized over other applications including its medicinal potential. The continuous development of resistance to clinical anticancer and antimalarial drugs has necessitated the need for the search of innovative bioactive compounds as potential alternative medicinal agents. To address this, the field of medicinal chemistry is adapting new approaches to counter resistance by incorporating nonconventional chemical moieties such as organometallic complexes, like ferrocene, into bioactive chemical motifs to serve as novel compounds with medicinal benefits. Incorporation of ferrocene into known bioactive chemical moieties has been shown to impart beneficial biological effects into the resultant compounds, which include the introduction of novel, and sometimes varied, mechanistic modalities and enhanced potency. Presented with the benefits of this strategy, the current work aims to design and evaluate the pharmaceutical capacity of novel derivatives containing 1,3-benzoxazine scaffold (traditionally applied in polymer synthesis) hybridized with the organometallic ferrocene unit as bioactive agents. Using a combination of expedient synthetic procedures such as the Burke three-component Mannich-type condensation, Vilsmeier-Haack formylation and reductive amination, four series of ferrocenyl 1,3-benzoxazine derivatives were synthesized and their structures confirmed by common spectroscopic techniques: nuclear magnetic resonance (NMR), infrared spectroscopy (IR) and high-resolution mass spectrometry (HRMS). The target compounds were evaluated in vitro for potential antimalarial and anticancer activities against strains of the malaria parasite (Plasmodium falciparum 3D7 and Dd2) and the triple-negative breast cancer cell line HCC70. Compounds exhibited higher potency towards the Plasmodium falciparum strains with IC50 values in the low and sub-micromolar range in comparison to the breast cancer cell line against for which mid-molar activities were observed. To gain insight into the possible mode of action of ferrocenyl 1,3-benzoxazines, representative compounds showing most efficacy from each series were assessed for DNA binding affinity by employing UV-Vis and fluorescence DNA titration experiments. The selected compounds were found to interact with the DNA by binding to the minor groove, and these findings were confirmed by in silico ligand docking studies using a B-DNA structure as the receptor. Compound 3.16c (IC50: 0.261 μM [3D7], 0.599 μM [Dd2], 11.0 μM [HCC70]), which emerged as the most promising compound, was found to induce DNA damage in HCC70 cancer cells when investigated for effects of DNA interaction. Additionally, compound 3.16c displayed a higher binding constant (Kb) against DNA isolated from 3D7 Plasmodium falciparum trophozoites (Kb = 1.88×106 M-1) than the mammalian DNA (Kb = 6.33×104 M-1) from calf thymus, thus explaining the preferred selectivity of the compounds for the malaria parasite. Moreover, the investigated compounds demonstrated binding affinity for synthetic hemozoin, β-hematin. Collectively, these data suggest that the compounds possess a dual mode of action for antimalarial activity involving DNA interaction and hemozoin inhibition. , Thesis (PhD) -- Faculty of Science, Chemistry, 2020
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- Date Issued: 2020
Softboi
- Authors: Mall, Shireen
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MA
- Identifier: http://hdl.handle.net/10962/164373 , vital:41113
- Description: Thesis (MA)--Rhodes University, Faculty of Humanities, School of Languages, 2020
- Full Text:
- Date Issued: 2020
Taxonomic revision of the Natal mountain catfish, Amphilius natalensis (Siluriformes, Amphiliidae) in southern Africa
- Authors: Mazungula, Daniel Nkosinathi
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164490 , vital:41123
- Description: Thesis (MSc)--Rhodes University, Department of Ichthyology and Fisheries Science, 2020
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- Date Issued: 2020
The Integration of Personally-owned Information and Communication Technologies (PICTs) for Teaching and Learning in Resource-Constrained Higher Education Environments – The Case of a Nigerian University
- Authors: Lewis, Oláñrewájú Olúrotimi
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163582 , vital:41050 , doi:10.21504/10962/163582
- Description: Thesis (PhD)--Rhodes University, Faculty of Commerce, Information Systems, 2020
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- 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
The Role of HSP70/HSP90 Organizing Protein (Hop) in the Heat Shock Factor 1 (HSF1)-mediated Stress Response
- Authors: Chakraborty, Abantika
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/163204 , vital:41018 , doi:10.21504/10962/163204
- Description: Molecular chaperones regulate cellular proteostasis. They control protein conformation and prevent misfolding and aggregation under both normal and stressful environments, ultimately resulting in cell survival. The project aimed to understand the role of the HSP70 – HSP90 Organizing Protein (Hop/STIP1) in the survival of stressed cells and the function of the stress-responsive transcription factor, Heat Shock Factor 1 (HSF1). HSF1 protein levels were significantly reduced in Hop-depleted HEK293T cells compared to controls by ELISA, western blot, and mass spectrometry. HSF1 transcriptional activity at the HSP70 promoter, and binding of a biotinylated HSE oligonucleotide under basal conditions were significantly reduced, consistent with the reduced levels of HSF1. In response to heat shock, HSF1 levels in Hop-depleted cells increased to that of controls, but there was still significantly lowerHSF1 transcriptional activity and HSE binding. Hop-depleted HEK293T cells were more sensitive than controls to the HSF1 inhibitor KRIBB11 and showed reduced short-term and long-term proliferation. Unlike the HSP90 inhibitor 17-DMAG, which had no effect, the HSP70 inhibitor JG98, further decreased the levels of HSF1 in Hop-depleted cells, suggesting a role for HSP70 in the Hop-mediated effects. There was punctate nuclear staining for HSF1 in Hop-depleted cells under both basal and heat shock conditions, as well as reduced nuclear localization and increased cytoplasmic accumulation of HSF1 in response to heat shock. Hop and HSF1 colocalized in cells, and HSF1 could be isolated in complex with Hop and HSP70. Loss of Hop reduced HSF1 in HSP70complexes but did not affect HSF1 abundance in HSP90 complexes. Hop-depleted cells showed reduced short-term and long-term survival compared to controls, an effect that was potentiated by the JG98 HSP70 inhibitor. Taken together, these data suggest that Hop regulation of HSF1activity is via a mechanism involving reductions in HSP70 interaction, as well as reduced nuclear localization, and DNA binding, and is consistent with reduced cellular fitness under basal and stress conditions. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
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- Date Issued: 2020
The role of the Hop co-chaperone in the formation of Hsp90 complexes: chaperone link to glycolysis
- Authors: Maharaj, Shantal
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163593 , vital:41051 , doi:10.21504/10962/163593
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Volatility spillovers and determinants of contagion: a case of BRICS equity and foreign exchange markets
- Authors: Nyopa, Tšepiso
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MCOM
- Identifier: http://hdl.handle.net/10962/164590 , vital:41146
- Description: Thesis (MSc)--Rhodes University, Faculty of Commerce, Economics and Economic History, 2020
- Full Text:
- Date Issued: 2020