Hop as an anti-cancer drug target
- Vaaltyn, Michaelone Chantelle
- Authors: Vaaltyn, Michaelone Chantelle
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164704 , vital:41156 , doi:10.21504/10962/164704
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Vaaltyn, Michaelone Chantelle
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164704 , vital:41156 , doi:10.21504/10962/164704
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Livelihood implications of a possible Ramsar declaration of the Swartkops estuary, Eastern Cape, South Africa
- Authors: Vembo, Glen Muchengeti
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164715 , vital:41157
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Environmental Science, 2020
- Full Text:
- Date Issued: 2020
- Authors: Vembo, Glen Muchengeti
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164715 , vital:41157
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Environmental Science, 2020
- Full Text:
- 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
- Full Text:
- Date Issued: 2020
- 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
- Full Text:
- Date Issued: 2020
Design of immunosensor for the detection of C-reactive protein using oriented antibody immobilization
- Authors: Adesina, Abiola Olanike
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163080 , vital:41010 , https://dx.doi.org/10.21504/10962/163080
- Description: Thesis (PhD)--Rhodes University, Science Faculty, Department of Chemistry, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Adesina, Abiola Olanike
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163080 , vital:41010 , https://dx.doi.org/10.21504/10962/163080
- Description: Thesis (PhD)--Rhodes University, Science Faculty, Department of Chemistry, 2020.
- Full Text:
- Date Issued: 2020
Development of a low-cost bioprinting system for engineering of Human Tumour Models
- Authors: Fanucci, Sidne
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163295 , vital:41026
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Fanucci, Sidne
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163295 , vital:41026
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020.
- Full Text:
- Date Issued: 2020
An investigation into the application of Distributed Endpoint Processing to 3D Immersive Audio Rendering
- Authors: Devonport, Robin Sean
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163258 , vital:41022
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Computer Science, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Devonport, Robin Sean
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163258 , vital:41022
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Computer Science, 2020.
- Full Text:
- Date Issued: 2020
Development of paper-based aptasensors for detection of Plasmodium falciparum lactate dehydrogenase in malaria
- Ogunmolasuyi, Adewoyin Martin
- Authors: Ogunmolasuyi, Adewoyin Martin
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164601 , vital:41147 , doi:10.21504/10962/164601
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020
- Full Text:
- Date Issued: 2020
- Authors: Ogunmolasuyi, Adewoyin Martin
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164601 , vital:41147 , doi:10.21504/10962/164601
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020
- Full Text:
- Date Issued: 2020
Investigating the relationship between Heat Shock Proteins and HIV Transactivator of Transcription
- Authors: Flax, Lili Marie
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163307 , vital:41027
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Flax, Lili Marie
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163307 , vital:41027
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
Investigating cell culture models for improved understanding of adipose tissue and co-morbidities in vitro
- Authors: Stoffels, Mihlali
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164674 , vital:41154
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020
- Full Text:
- Date Issued: 2020
- Authors: Stoffels, Mihlali
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164674 , vital:41154
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020
- Full Text:
- Date Issued: 2020
Development of a protocol for extracting and quantifying the concentration of thiafentanil in blesbok (Damaliscus pygargus phillipsi) matrices 72-74 hours post administration
- Authors: Webber, Judith Tracy
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164738 , vital:41159
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
- Authors: Webber, Judith Tracy
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164738 , vital:41159
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Chemistry, 2020
- Full Text:
- 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
- Full Text:
- Date Issued: 2020
- 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
- Full Text:
- 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
- Full Text:
- Date Issued: 2020
- 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
- Full Text:
- Date Issued: 2020
Application of In Vitro Release Testing (IVRT) and a dermatopharmacokinetic approach (tape stripping) for the assessment of Metronidazole topical formulations
- Rath, Seeprarani Prabirkumar
- Authors: Rath, Seeprarani Prabirkumar
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164617 , vital:41148 , doi:10.21504/10962/164617
- Description: Thesis (PhD)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
- Authors: Rath, Seeprarani Prabirkumar
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164617 , vital:41148 , doi:10.21504/10962/164617
- Description: Thesis (PhD)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
Formulation, development and assessment of devil’s claw loaded phyto-elastosomes in thermo-responsive hydrogels
- Authors: Ntemi, Pascal Vitalis
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164568 , vital:41139 , doi:10.21504/10962/164568
- Description: Thesis (PhD)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
- Authors: Ntemi, Pascal Vitalis
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164568 , vital:41139 , doi:10.21504/10962/164568
- Description: Thesis (PhD)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- 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
- 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
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
- Full Text:
- Date Issued: 2020
- 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
- Full Text:
- 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
- Full Text:
- Date Issued: 2020
- 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
- Full Text:
- Date Issued: 2020
Taxonomic revision of the Natal mountain catfish, Amphilius natalensis (Siluriformes, Amphiliidae) in southern Africa
- Mazungula, Daniel Nkosinathi
- 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
- Full Text:
- Date Issued: 2020
- 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
- Full Text:
- Date Issued: 2020
Formulation and characterisation of a combination captopril and hydrochlorothiazide microparticulate dosage form for paediatric use
- Chikukwa, Mellisa Tafadzwa Ruramai
- Authors: Chikukwa, Mellisa Tafadzwa Ruramai
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163216 , vital:41019 , doi:10.21504/10962/163216
- Description: Thesis (PhD)--Rhodes University, Pharmacy Faculty, Department of Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
- Authors: Chikukwa, Mellisa Tafadzwa Ruramai
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163216 , vital:41019 , doi:10.21504/10962/163216
- Description: Thesis (PhD)--Rhodes University, Pharmacy Faculty, Department of Pharmaceutics, 2020
- Full Text:
- 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
- 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