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Exploring pre-service teachers’ reflective practice in the context of video-based lesson analysis

- Chikiwa, Samukeliso

Authors: Chikiwa, Samukeliso
Date: 2020-04-30
Subjects: Uncatalogued
Language: English
Type: Academic theses , Doctoral theses , text
Identifier: http://hdl.handle.net/10962/355357 , vital:64492
Description: This study explored the development of reflective practice in foundation phase pre-service teachers in the context of video-based lesson analysis at a university in South Africa. The study was conducted in the field of mathematics education, responding to the urgent need to equip pre-service South African teachers with the knowledge and skills for effective mathematics teaching. The research is foregrounded by the continuing poor performance of South African learners in mathematics at all levels of education in the country, which has been linked to the inadequate knowledge and skills of mathematics teachers. Pre-service teacher education is putting considerable effort into improving the preparation of mathematics teachers and developing their ability to reflect on their teaching practice is one of the strategies being employed for this purpose. Research has demonstrated the importance of reflective practice (RP) in both developing and extending teachers’ mathematical knowledge for teaching. This study therefore contributes to current research that supports the development of RP as a professional skill for promoting the acquisition of knowledge for teaching in pre-service teacher education. The study adopted a qualitative case study approach with two phases of data collection. In Phase 1 I collected and analysed three sets of 19 pre-service teachers’ written reflections to establish the nature of the reflections that they developed when analysing video-recorded mathematics lessons of experienced teachers’ practice. Phase 2 was conducted with four PSTs who reflected on video-recorded mathematics lessons of their own practice, and similarly sought to investigate the nature of the reflections they developed when reflecting on practice. The four PSTs wrote one set of reflections on their own lessons, went through three sessions of facilitator-guided reflections, then wrote another set of reflections to establish if the support provided in small group facilitator-guided sessions improved their reflections. Iterative content analysis was employed to analyse the PSTs’ written reflections, using an analytic tool that I developed for this purpose through merging Lee’s (2007) and Muir and Beswick’s (2007) levels of reflection frameworks. My model had four levels of reflection: description, explanation, suggestion and reflectivity. The names of each of the levels connect to the key indicator for that level. PSTs’ written reflections were coded and analysed according to these levels. The study found that PSTs’ initial reflections were mostly description of general classroom events with little reflection at the levels of explanation and suggestion, and an absence of reflectivity. Most reflections focused on general events in the lesson rather than mathematical events, even though the six lens framework they were given to guide their reflections prompted them to steer their attention towards mathematical events. The second and third sets of reflections, although mostly still at level 1, showed some shifts towards explanation and suggestion, although an increased focus on mathematical events though reflectivity was still largely absent. No PST reached the fourth level of reflectivity in Phase 1. However, in Phase 2, the PSTs’ reflections after the three small group facilitator-guided sessions included some evidence of reflectivity. The findings suggest the need for pre-service teacher educators to make a concerted effort to teach PSTs what reflection is and how to reflect on their practice. The findings also showed the need for small group facilitator-guided support in the development of PSTs’ reflective practice. , Thesis (PhD) -- Faculty of Education, Education, 2020
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Date Issued: 2020-04-30

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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

- Mbaba, Mziyanda

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

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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

- Boёl, Natasha Marie-Eraine

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
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Date Issued: 2020

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The Role of HSP70/HSP90 Organizing Protein (Hop) in the Heat Shock Factor 1 (HSF1)-mediated Stress Response

- Chakraborty, Abantika

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

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