Combining DNA barcoding and morphology to identify larval fishes from the nearshore environment off the south-east coast of South Africa
- Authors: Somana, Zinzi Sinazo
- Date: 2020
- Subjects: Fishes -- Larvae -- South Africa -- Identification , Fishes -- Genetics -- Research -- Technique , Fishes -- South Africa -- Classification , Genetic markers
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/144605 , vital:38362
- Description: The early life history stages of most marine fish species are undescribed. The problem is, most of these fishes have pelagic larvae which are minute, delicate forms. Linking the larval stage to an adult counterpart is extremely challenging as larvae are morphologically different from the adults. Historically, larval fish identification relied solely on distinguishing morphological characteristics and meristic measurements, which has resulted in taxonomic confusion and misidentification. The introduction of the deoxyribonucleic acid (DNA) barcoding technique as an alternative approach has been successful in positively identifying larval fishes. The correct identification of larval specimens is the key to a better understanding of larval ecology, which underpins the success of any adult fish population. This study aimed to positively identify larval fishes of the south-east coast of South Africa using morphological characteristics and DNA barcoding. Larval and eggs specimens for this study were collected from the shallow nearshore waters of the south-east coast of South Africa. A total of 177 larval specimens were used for morphological analysis. Body shape, gut shape, pigmentation and morphometric measurements (such as body depth, preanal length and total body length) were used to identify each specimen to the family level. In addition, a fragment of mitochondrial cytochrome c oxidase subunit 1 gene (COI) was adopted for sequencing to identify larval fish specimens and fish eggs. Sequences generated from this study were compared to those in the Barcode of Life Database (BOLD). When there were no close matches to a sequence, the GenBank nucleic acid sequence database, maintained by the National Center for Biotechnology Information (NCBI), was used as an alternative. A total of 18 different families were identified through morphology. Seventy-seven of the 177 larval specimens were not subjected to morphological identification due to physical damage. The majority of larvae identified using morphological characteristics belonged to either the Sparidae, Tripterygiidae or Gobiesocidae fish families. Through DNA barcoding, 12 fish families, 16 genera and 18 different species were identified. Ten DNA barcodes (categorised as ‘no match’) from 10 different larval specimens were not identified through any of the online databases. Therefore, the 2% threshold value was used to identify members of the same species. The K2P genetic distance relationships were calculated among the no match sequences and downloaded probability matches from NCBI. This resulted in two unknown specimens assigned to the Blenniidae and Gobiidae. All other taxa were identified to species level, except specimens representing the Gobiidae and Tripterygiidae families. Based on the K2P genetic distances Gobiidae representatives were categorised as members of the Caffrogobius genus. Twenty-eight barcodes represented specimens from the Tripterygiidae. DNA barcode data from COI was analysed using the standard phylogenetic procedures in MEGA6 to examine relationships and differentiation among sequences. These could not be identified to the lowest taxonomic rank due to limited sequence data to compare them with. The sequence data from these specimens gave different results in the two online databases. BOLD results were to family level (Tripterygiidae) and NCBI to the species level (Clinidae: Pavoclinus profundus). Results in this study confirmed the efficiency of the DNA barcoding technique in species level identification of fish larvae. The evidence from genetic barcodes of the Tripterygiidae specimens, supported by morphological characteristics, suggests the need for thorough research to identify the individuals to the species level. The fact that this study identified taxonomically problematic Gobiidae and Tripterygiidae specimens suggests that studies similar to this may highlight additional diversity and help to resolve the taxonomy of other species in these families. However, the lack of reference sequence data from the adult specimens, and especially those with cryptic diversity, were both shortcomings for the positive identification of larvae. With that being said, it shows the necessity for more research to be conducted on barcoding of larvae in general as to accommodate all kinds of species from biodiversity to economic perspectives.
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Default in payment, an application of statistical learning techniques
- Authors: Gcakasi, Lulama
- Date: 2020
- Subjects: Credit -- South Africa -- Risk assessment , Risk management -- Statistical methods -- South Africa , Credit -- Management -- Statistical methods , Commercial statistics
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/141547 , vital:37984
- Description: The ability of financial institutions to detect whether a customer will default on their credit card payment is essential for its profitability. To that effect, financial institutions have credit scoring systems in place to be able to estimate the credit risk associated with a customer. Various classification models are used to develop credit scoring systems such as k-nearest neighbours, logistic regression and classification trees. This study aims to assess the performance of different classification models on the prediction of credit card payment default. Credit data is usually of high dimension and as a result dimension reduction techniques, namely principal component analysis and linear discriminant analysis, are used in this study as a means to improve model performance. Two classification models are used, namely neural networks and support vector machines. Model performance is evaluated using accuracy and area under the curve (AUC). The neuarl network classifier performed better than the support vector machine classifier as it produced higher accuracy rates and AUC values. Dimension reduction techniques were not effective in improving model performance but did result in less computationally expensive models.
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Design, formulation and evalauation of liposomes co-loaded with human serum Albumin and Rifampicin
- Authors: Bapolisi, Alain Murhimalika
- Date: 2020
- Subjects: Liposomes , Serum albumin , Rifampin , Mycobacterium tuberculosis
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/161780 , vital:40670
- Description: Tuberculosis (TB) is a devastating infectious disease caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious agent. The high morbidity and mortality rates of TB are partly due to factors such as the lengthy regimen (of 6–24 months), the development of drug resistance, and the pathogen location within the macrophages. These, with poor physiochemical properties of existing drugs hamper the effectiveness of the treatment despite the existence of potent antibiotics such as Rifampicin (Rif). Hydrophobicity plagues many drugs, including Rif, which are then particularly affected due to inherently poor intracellular availability. Novel drug delivery approaches are therefore needed in order to optimize the cytotoxic potential of said antitubercular drugs. To improve the bioavailability of hydrophobic drugs, numerous delivery strategies have been developed. Amongst these, the coordination of cytotoxic drugs to therapeutic proteins have shown some success for improved efficacy in the management of illnesses including infectious diseases. Of therapeutic proteins, Human Serum Albumin (HSA) is an attractive drug carrier with interestingbenefits such as low immunogenicity, antioxidant properties and improving cellular uptake ofdrugs through HSA-specific binding sites which are expressed on most cells including macrophages, where M. tuberculosis often resides. Hence, combination of Rif to HSA (Rif-HSA)seems a promising approach for improved intracellular delivery of Rif. However, the in vivo stability of colloidal protein-based therapeutics is mostly challenging and an effective vehicle is needed to control the biological fate of such conjugates.Liposomes seem to be appropriate carriers for the Rif-HSA complex due to their reputable applicability for encapsulating diverse materials (i.e., hydrophobic and hydrophilic compounds or small and complex molecules) and preventing chemical and biological degradation of the cargo. Therefore, the main objective of this study was to simultaneously encapsulate Rif and HSA in liposomes, which, to the best of our knowledge, has not been done before. The dual liposomes (Rif-HSA-lip) were made by a modified “Reverse Phase Evaporation” method (REV), following a Design of Experiments (DOE) approach to determine which factors impact the formulation. In addition, liposomes were made from crude soybean lecithin (CSL), rather than expensive and highly purified lipids. The liposomes were fully characterised, and the encapsulation efficiency (î) was monitored using high-performance liquid chromatography (HPLC). The results were correlated with factors such as organic and aqueous phase composition, as well as the in vitro release profile of Rif. Transmission electron microscopy (TEM) results confirmed the formation of spherical dual liposomes nanoparticles of roughly 200 nm. Dynamic light scattering (DLS) and Zeta potential measurements showed a negative charge (<–45 mV) and with satisfactory polydispersity (PDI<0.5). HSA dramatically improved the aqueous solubility of Rif (from1.9 mg/ml in water to around 4.3 mg/ml in HSA 10% solution) mainly due to Rif-HSA hydrophobic interactions. This resulted in a good î of almost 60% for Rif, despite the presence of bulky HSA in the lipid bilayer. These details were confirmed using proton nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FTIR). Furthermore, energy dispersive X-ray (EDX) and DLS data suggested the presence of HSA poking out on the surface of liposomes, which is encouraging for potential targeted delivery in the future. The in vitro release studies also depicted a substantial improvement in the diffusion of Rif in dual liposomes versus free Rif, from 65% after 12 hours for free Rif to 95% after only 5 hours for Rif- HSA-lip. Finally, stability studies conducted over 30 days at room temperature, showed that the freeze-dried formulations of Rif-HSA-lip exhibited good shelf stability over liposomes with no HSA. This study represents an illustrative example of co-loading of antibiotics and proteins into liposomes, which could encourage further development of novel nanoparticulate tools for the effective management of both drug-susceptible and -resistant infectious diseases such as TB.
- Full Text:
Design, formulation and evaluation of liposomes co-loaded with human serum albumin and rifampicin
- Authors: Bapolisi, Alain Murhimalika
- Date: 2020
- Subjects: Liposomes , Rifampin , Antitubercular agents , Serum albumin , Albumins , Tuberculosis -- Treatment
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163179 , vital:41016
- Description: Tuberculosis (TB) is a devastating infectious disease caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious agent. The high morbidity and mortality rates of TB are partly due to factors such as the lengthy regimen (of 6–24 months), the development of drug resistance, and the pathogen location within the macrophages. These, with poor physiochemical properties of existing drugs hamper the effectiveness of the treatment despite the existence of potent antibiotics such as Rifampicin (Rif). Hydrophobicity plagues many drugs, including Rif, which are then particularly affected due to inherently poor intracellular availability. Novel drug delivery approaches are therefore needed in order to optimize the cytotoxic potential of said antitubercular drugs. To improve the bioavailability of hydrophobic drugs, numerous delivery strategies have been developed. Amongst these, the coordination of cytotoxic drugs to therapeutic proteins have shown some success for improved efficacy in the management of illnesses including infectious diseases. Of therapeutic proteins, Human Serum Albumin (HSA) is an attractive drug carrier with interesting benefits such as low immunogenicity, antioxidant properties and improving cellular uptake of drugs through HSA-specific binding sites which are expressed on most cells including macrophages, where M. tuberculosis often resides. Hence, combination of Rif to HSA (Rif-HSA) seems a promising approach for improved intracellular delivery of Rif. However, the in vivo stability of colloidal protein-based therapeutics is mostly challenging and an effective vehicle is needed to control the biological fate of such conjugates. Liposomes seem to be appropriate carriers for the Rif-HSA complex due to their reputable applicability for encapsulating diverse materials (i.e., hydrophobic and hydrophilic compounds or small and complex molecules) and preventing chemical and biological degradation of the cargo. Therefore, the main objective of this study was to simultaneously encapsulate Rif and HSA in liposomes, which, to the best of our knowledge, has not been done before. The dual liposomes (Rif-HSA-lip) were made by a modified “Reverse Phase Evaporation” method (REV), following a Design of Experiments (DOE) approach to determine which factors impact the formulation. In addition, liposomes were made from crude soybean lecithin (CSL), rather than expensive and highly purified lipids. iv The liposomes were fully characterised, and the encapsulation efficiency (î) was monitored using high-performance liquid chromatography (HPLC). The results were correlated with factors such as organic and aqueous phase composition, as well as the in vitro release profile of Rif. Transmission electron microscopy (TEM) results confirmed the formation of spherical dual liposomes nanoparticles of roughly 200 nm. Dynamic light scattering (DLS) and Zeta potential measurements showed a negative charge (<–45 mV) and with satisfactory polydispersity (PDI<0.5). HSA dramatically improved the aqueous solubility of Rif (from1.9 mg/ml in water to around 4.3 mg/ml in HSA 10% solution) mainly due to Rif-HSA hydrophobic interactions. This resulted in a good î of almost 60% for Rif, despite the presence of bulky HSA in the lipid bilayer. These details were confirmed using proton nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FTIR). Furthermore, energy dispersive X-ray (EDX) and DLS data suggested the presence of HSA poking out on the surface of liposomes, which is encouraging for potential targeted delivery in the future. The in vitro release studies also depicted a substantial improvement in the diffusion of Rif in dual liposomes versus free Rif, from 65% after 12 hours for free Rif to 95% after only 5 hours for Rif- HSA-lip. Finally, stability studies conducted over 30 days at room temperature, showed that the freeze-dried formulations of Rif-HSA-lip exhibited good shelf stability over liposomes with no HSA. This study represents an illustrative example of co-loading of antibiotics and proteins into liposomes, which could encourage further development of novel nanoparticulate tools for the effective management of both drug-susceptible and -resistant infectious diseases such as TB.
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Development and assessment of a fixed dose combination of perindopril arginine and indapamide loaded microparticles
- Authors: Mandava, Tavonga Tyomai
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164413 , vital:41116
- Description: Thesis (MSc)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
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.
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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
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Development of graphene materials and phthalocyanines for application in dye-sensitized solar cells
- Authors: Chindeka, Francis
- Date: 2020
- Subjects: Dye-sensitized solar cells , Graphene , Phthalocyanines , Molecular orbitals , Impedance spectroscopy
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166092 , vital:41328
- Description: Two sets of dye-sensitized solar cells (DSSCs) were fabricated. In the first set, dye-sensitized solar cells (DSSC) were fabricated by incorporating graphene materials as catalysts at the counter electrode. Platinum was also used as a catalyst for comparative purposes. Different phthalocyanines: hydroxyl indium tetracarboxyphenoxy phthalocyanine (1), chloro indium octacarboxy phthalocyanine (2) and dibenzoic acid silicon phthalocyanine (3) were used as dyes. Complex 3 gave the highest power conversion efficiency (η) of 3.19% when using nitrogen doped reduced graphene oxide nanosheets (NrGONS) as a catalyst at the counter electrode, and TiO2 containing rGONS at the anode. The value obtained is close to 3.8% obtained when using Pt catalyst instead of NrGONS at the cathode, thus confirming that NrGONS is a promising candidate to replace the more expensive Pt. The study also shows that placing rGONS on both the anode and cathode improves efficiency. In the second set, DSSCs were fabricated by using 2(3,5-biscarboxyphenoxy), 9(10), 16(17), 23(24)-tri(tertbutyl) phthalocyaninato Cu (4) and Zn (5) complexes as dyes on the ITO-TiO2 photoanodes containing reduced graphene oxide nanosheets (rGONS) or nitrogen-doped rGONS (NrGONS). The evaluation of the assembled DSSCs revealed that using ITO-TiO2-NrGONS-CuPc (4) photoanode had the highest fill factor (FF) and power conversion efficiency (ɳ) of 69 % and 4.36 % respectively. These results show that the asymmetrical phthalocyanine complexes (4) and (5) showed significant improvement on the performance of the DSSC compared to previous work on symmetrical carboxylated phthalocyanines with ɳ = 3.19%.
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Do submarine canyons influence the structure and diversity of benthic fish assemblages on the continental shelf edge?
- Authors: Nyawo, Mpilonhle Aura June-Rose
- Date: 2020
- Subjects: Submarine valleys , iSimangaliso Wetland Park (South Africa) , Biotic communities -- South Africa -- iSimangaliso Wetland Park , Groundfishes -- South Africa -- iSimangaliso Wetland Park , Marine ecology -- South Africa -- iSimangaliso Wetland Park
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167264 , vital:41462
- Description: Marine ecosystems play an important role in human welfare, such as providing food security and providing social, economic and environmental benefits to an increasing human population. However, due to the deleterious impact of overfishing as well as habitat degradation, pollution and climate change, many marine ecosystems and the substantial biodiversity they support, are under increasing threats. Submarine canyon ecosystems cut into the continental margin in all our oceans and are considered regions of enhanced diversity, abundance and biomass for many marine communities, including fish. In South Africa, the tropical Delagoa Ecoregion is characterised by numerous submarine canyons that are home to coelacanths Latimeria chalumnae, and a variety of commercially important line fish species. However, there is currently a lack of information on the ecological structure and functioning of these canyons, in relation to nearby non-canyon ecosystems. The aim of this thesis was to generate knowledge on the role of submarine canyons in influencing the benthic fish assemblage structure and diversity on the continental shelf and shelf edge within the high-latitude coral reef ecosystems in the tropical Delagoa Ecoregion of South Africa. First, a systematic literature review was conducted to examine the current knowledge on the role of submarine canyons on the benthic fish assemblages occurring on continental margins, as well as outline the trends in canyon research. For the fieldwork component of this thesis, baited remote underwater stereo-video systems were utilised to gather data. The first research chapter, chapter 3, investigated the effect of ecosystem and depth on the diversity and structure of benthic fish assemblages within iSimangaliso Wetland Park in the Delagoa Ecoregion. Data were collected in 2017 from Wright Canyon (canyon ecosystem) and adjacent slope ecosystems around the canyon (non-canyon ecosystem) at depths ranging between 70–240 m. The second research chapter, chapter 4, data were collected in 2018, from 60–100 m depths in three ubmarine canyons (Wright, Diepgat,Levens) and their adjacent habitat within iSimangaliso Wetland Park to investigate the diversity patterns and community structure of benthic fish and cons ider location as a factor. The systematic review showed that canyon research is still very much in its infancy, however more papers are expected to be published in the future. There were clear location associated biases detected, with more than 90% of the canyon research being concentrated in the Mediterranean Sea, while only one study was published from South Africa. Most of the reviewed literature focused on invertebrates, with benthic fish (including cartilaginous fish) being the second most studied taxa. A wide range of methods from both fishery- dependent and fishery-independent categories were used to gather the data of benthic fish from the canyons and adjacent areas. With over 8500 submarine canyons mapped globally, the number of submarine canyon research published and the detected location bias is of great concern. More studies are needed in order to understand the role of submarine canyons on adjacent slope habitats Overall, the results from the research chapters indicated that there were higher a bundances in the canyon ecosystem compared to the non-canyon ecosystem. In contrast, evenness and beta-diversity were higher in the non-canyon ecosystem. Relief, bottom type as well as depth played a major role in explaining the observed abundance and diversity patterns. Both evenness and beta-diversity decreased with increase in depth. The canyon and non-canyon also differed in terms of habitat structure. The canyon ecosystem was characterised by patched reef and reef habitats with high relief whereas the non-canyon ecosystem was characterised by flats and habitats, especially at shallower depths. Additionally, there were clear differences in terms of the fish community structure between the canyon and the non-canyon ecosystem. The heterogeneous and complex habitats of the canyon ecosystem were typified by species such as Epinephelus poecilonotus, Polysteganus coeruleopunctatus and Chrysoblephus puniceus in comparison to the less complex habitats outside the canyons that were preferred by species such as Lagocephalus sceleratus, and Rhinobatos leucospilus. The different locations sampled demonstrated that the canyon effect was not onsistent at all locations, with varying results detected in the different sample locations. This research demonstrates that clea r differences exists between the benthic fish assemblages associated with canyon and non-canyon ecosystems and provides important information on the role of submarine canyons in the iSimangaliso Wetland Park. From this thesis, it is clear that a ‘canyon effect’ exists in the continental shelf and shelf edge. The results suggested that heterogeneity of habitats was the most important environmental factor that differed between the canyon and non-canyon ecosystems and these differences in the habitat were driving the observed patterns. This thesis has provided a reference point, with regards to investigating the role and influence of these canyons on benthic fish assemblages occurring on the continental shelf edge. The information provided by this thesis can ultimately be used in other studies investigating benthic fish assemblages in other submarine canyons within iSimangaliso Wetland Park and the rest of South Africa./
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Ecological engineering: an assessment of the ecological impact of Reno mattress structures used in erosion control in the Keurbooms Estuary, South Africa
- Authors: De Villiers, Nina
- Date: 2020
- Subjects: Sediments (Geology) -- Management , Sediments (Geology) -- South Africa -- Keurboomstrand , Coast changes -- South Africa -- Keurboomstrand , Shore protection -- South Africa -- Keurboomstrand , Coastal engineering-- South Africa -- Keurboomstrand , Coastal zone management-- South Africa -- Keurboomstrand , Estuarine ecology-- South Africa -- Keurboomstrand , Eelgrass -- South Africa -- Keurboomstrand , Reno Mattresses
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166138 , vital:41332
- Description: Global climate changes have been associated with ocean warming and sea-level rise. Armouring of coastlines has become common practice with the increasing threat of coastal erosion. The transformation of soft sediment habitats to hard, artificial habitats because of coastline armouring can lead to changes in species diversity, composition and distribution. It is, therefore, essential to assess changes to habitats from coastal development as well as the ecological impact erosion control structures have within coastal systems. Ecological engineering attempts to combine engineering principals and ecological processes to reduce environmental impacts from coastal development and the implementation of artificial structures. Estuaries are particularly vulnerable to anthropogenic impacts through development, and are extremely important systems offering nursery and foraging grounds for many species. These systems are, however, particularly vulnerable to anthropogenic impacts from urbanisation and development. Within South Africa many estuaries are being transformed by the addition of artificial structures to combat erosion, one such structure is the Reno mattress (a flattened wire box filled with rocks). This study compared the fish diversity and abundances of existing Reno mattress structures and natural eelgrass (Zostera capensis) habitat in the Keurbooms Estuary, South Africa. Benthic invertebrates were sampled using standard core sampling and an adapted suction sampling approach within the two habitats. The non-destructive method of mini Baited Remote Underwater Video Systems (BRUVs) was used to sample fish. Seasonal benthic invertebrate and fish abundances and assemblages were assessed from winter 2018 to spring 2019 with greater abundances of both recorded in summer. Significantly greater abundances, diversity, and richness of fish were found in the Reno mattress habitat compared to Z. capensis. Invertebrate taxa displayed some overlap between habitats, however, three higher taxonomic groups were only recorded within Reno mattress habitat and one only within the eelgrass habitat. Fish assemblages differed significantly between the two established habitats. A Before-After-Control-Impact (BACI) investigation was used to assess the ecological impact of newly installed Reno mattresses in the Keurbooms Estuary. Zostera capensis extent was sampled by determining the percentage cover of 0.5 m X 0.5 m quadrats and measurements of eelgrass blades. Percentage cover and blade length decreased during the installation of Reno mattress, but then recovered shortly after completion of the installation. Abundances, richness and diversity of invertebrates and fish were found to be similar before and after the installation which suggests that the installation had no net negative impact on the site. The Reno mattresses were found to attract fauna typical of rocky shore environments as well as a few invasive alien invertebrate species. This study noted that a hybrid habitat of Reno mattress and eelgrass was created and may in fact provide the positives of both to a system. In any coastal development it will be important to balance the demands of a growing population and the protection of natural habitats. The results of this study suggest that complex artificial structures such as Reno mattresses do provide habitat for fish and invertebrates. However, the use of these structures should be in combination with natural vegetation (e.g. as a hybrid habitat) and not one that replaces intertidal and subtidal natural habitat especially eelgrass. There is limited information regarding the ecological impacts of using Reno mattresses in estuaries and this study provides new information on their ecological efficacy that should be valuable for future coastal erosion control practices.
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Effect of the nature of nanoparticles on the photophysicochemical properties and photodynamic antimicrobial chemotherapy of phthalocyanines
- Authors: Magadla, Aviwe
- Date: 2020
- Subjects: Nanoparticles , Phthalocyanines , Anti-infective agents -- Therapeutic use , Photochemotherapy , Photochemistry
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/123107 , vital:35406
- Description: In this work, the syntheses and characterisation of Zn monocaffeic acid tri–tert–butyl phthalocyanine (1), Zn monocarboxyphenoxy tri– tert–butylphenoxyl phthalocyanine (2), tetrakis phenoxy N,N-dimethyl-4-(methylimino) phthalocyanine indium (III) chloride (3) and tetrakis N,N-dimethyl-4-(methylimino) phthalocyanine indium (III) chloride (5) are presented. Complexes 3 and 5 were further quartenised with 1,3- propanesultone to form corresponding complexes (4) and (6), respectively. Complexes 1 and 2 were covalently linked to amino functionalised nanoparticles (NPs). Complexes 3, 4, 5 and 6 where linked to oleic acid/oleylamine capped (OLA/OLM) silver-iron dimers (Ag-Fe3O4 OLA/OLM) and silver-iron core shell (Ag@Fe3O4 OLA/OLM) NPs via interaction between the nanoparticles and the imino group on the phthalocyanines. The phthalocyanine-NP conjugates afforded an increase in triplet quantum yields with a corresponding decrease in fluorescence quantum yield as compared to the phthalocyanine complexes alone. Complexes 3, 4 and their conjugates were then used for photodynamic antimicrobial chemotherapy on E. coli. The zwitterionic photosensitiser 4 and its conjugates showed better efficiency for photodynamic antimicrobial chemotherapy compared to their neutral counterparts.
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Effectiveness of different interventions to reduce occupational sitting among office administrators at Rhodes University
- Authors: Malesa, Thato
- Date: 2020
- Subjects: Standing position , Sedentary behavior , Work environment , Employee health promotion , Office furniture -- Design , Industrial hygiene , Employees -- Health risk assessment , Human engineering , Compliance
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166403 , vital:41360
- Description: Background: Sitting for prolonged periods is common in the working environment. Office workers are exposed to long periods of sitting time at work. Research has reported associations between prolonged sitting and negative health implications. As such studies have proposed different interventions aimed at reducing sitting times in the workplace. The aim of the current study was to evaluate the effectiveness of two different interventions, physical intervention (sit-stand worktables) and personal intervention (instruction to stretch) on compliance and reducing occupational sitting behaviour. The study also aimed to investigate the effectiveness of interventions in improving or impairing mood. Methods: The study took the form of a fieldbased study atRhodes University, Makhanda, South Africa. Fifteen full–time office workers in different divisions participated in the study. Participants were randomly allocated to either the physical or personal intervention group. In both intervention groups, partic ipants were prompted to stand for five minutes every hour during the workday to either work in a standing position or perform stretches. Over the course of the experiment, desk occupancy, sitting/standing time and mood effect were recorded in both intervention groups Both intervention groups were monitored for a period of three months (58 days). Results: The study found that the physical intervention group was an effective approach to reduce prolonged sitting in the workplace in comparison to the personal intervention group. Over the course of the experiment, there was sustain usage of interventions in both groups, however, in the physical intervention group desk usage decreased overtime. The findings of the study also show that some participants were more compliant with the study procedures than others. It was also found that mood improved upon introducing interventions in the workplace. However, with the outcomes of the results, the study acknowledges that several factors emerged which are likely to impact compliance, which future studies may investigate. Conclusion: Although sit-stand worktables are expensive, it seems like introducing them was successful in reducing sitting time and changing sitting behaviour in comparison to an intervention that instruct s individuals to stand up and stretch.
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Evaluation of an NADPH-dependent assay for inhibition screening of Salmonella enterica DOXP Reguctoisomerase for identification of novel drug hit compounds
- Authors: Ngcongco, Khanyisile
- Date: 2020
- Subjects: 1-Deoxy-D-xylulose 5-phosphate , Antibiotics , Drug development , Salmonella , Enterobacteriaceae , Vaccines , Plasmodium falciparum , Mycobacterium tuberculosis
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167132 , vital:41440
- Description: Invasive non-typhoidal Salmonella, caused by the intracellular pathogen Salmonella enterica, has emerged as a major cause of bloodstream infections. It remains a neglected infection responsible for many deaths in Africa, as it fails to receive the level of support that is given to most better known infections. There are currently no vaccines against invasive non-typhoidal Salmonella. First-line antibiotics have been used for treatment, however, the rise in the resistance of the bacteria against these antibiotics has made treatment of invasive salmonellosis into a clinical problem. Therefore, the discovery of new compounds for the development of antibiotic drugs is required. Central metabolic pathways can be a useful source for identifying drug targets and among these is the non-mevalonate pathway, one of the pathways used for the biosynthesis of isoprenoid precursors. The second step of the non-mevalonate pathway involves the NADPH-dependent reduction of 1-deoxy-D-xylulose 5-phosphate (DOXP) into 2-C-methyl-D-erythritol 4-phosphate (MEP). 1-Deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase plays a vital role in the catalysis of this reaction and requires NADPH and divalent metal cations as co-factors for its activity. In this investigation recombinant DOXP reductoisomerase from Salmonella enterica, Plasmodium falciparum and Mycobacterium tuberculosis were biochemically characterized as potential targets for developing drugs that could be used as treatment of the disease. The expression and nickel-chelate affinity purification of S. enterica DOXP reductoisomerase in a fully functional native state was successfully achieved. However, the expression and purification of P. falciparum DXR and M. tuberculosis DXR was unsuccessful due to the formation of insoluble inclusion bodies. Although alternative purification strategies were explored, including dialysis and slow dilution, these proteins remained insoluble, making their functional analysis not possible. An NADPH-dependent enzyme assay was used to determine the activity of S. enterica DXR. This assay monitors the reduction of DOXP to MEP by measuring the absorbance at 340 nm, which reflects the concentration of NADPH. An alternative assay, resazurin reduction, which monitors the NADPH-dependent reduction of resazurin to resorufin, was explored for detecting enzyme activity. The recombinant S. enterica DOXP reductoisomerase had a specific activity of 0.126 ± 0.0014 μmol/min/mg protein and a Km and Vmax of 881 μM and 0.249 μmol/min/mg respectively. FR900098, a derivative of fosmidomycin, is a well-known inhibitor of DXR, however, the sensitivity of S. enterica DXR towards FR900098 has not yet been reported. The NADPH dependent enzyme and resazurin reduction assays were used to determine whether FR900098 has enzyme inhibitory effects against S. enterica DXR. Upon confirming that FR900098 is able to inhibit S. enterica DXR, FR900098 was used as a control compound in the screening of novel compounds. The S. enterica DXR enzyme was screened for inhibition by the collection of compounds from the Pathogen Box. Compounds that exhibited the desired inhibitory activity, referred to as ‘hits’ were selected for further investigation. These hits were confirmed using the NADPH-dependent enzyme assay, resulting in the identification of two different DXR inhibitor compounds, MMV002816, also known as diethylcarbamazine, and MMV228911. The inhibitory concentration (IC50) values of FR900098, MMV002816 and MMV228911 against S. enterica DXR were 1.038 μM, 2.173 μM and 6.861 μM respectively. The binding mode of these compounds to S. enterica DXR could lead to the discovery of novel druggable sites on the enzyme and stimulate the development of new antibiotics that can be used for treating Salmonella infections.
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Finite precision arithmetic in Polyphase Filterbank implementations
- Authors: Myburgh, Talon
- Date: 2020
- Subjects: Radio interferometers , Interferometry , Radio telescopes , Gate array circuits , Floating-point arithmetic , Python (Computer program language) , Polyphase Filterbank , Finite precision arithmetic , MeerKAT
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/146187 , vital:38503
- Description: The MeerKAT is the most sensitive radio telescope in its class, and it is important that systematic effects do not limit the dynamic range of the instrument, preventing this sensitivity from being harnessed for deep integrations. During commissioning, spurious artefacts were noted in the MeerKAT passband and the root cause was attributed to systematic errors in the digital signal path. Finite precision arithmetic used by the Polyphase Filterbank (PFB) was one of the main factors contributing to the spurious responses, together with bugs in the firmware. This thesis describes a software PFB simulator that was built to mimic the MeerKAT PFB and allow investigation into the origin and mitigation of the effects seen on the telescope. This simulator was used to investigate the effects in signal integrity of various rounding techniques, overflow strategies and dual polarisation processing in the PFB. Using the simulator to investigate a number of different signal levels, bit-width and algorithmic scenarios, it gave insight into how the periodic dips occurring in the MeerKAT passband were the result of the implementation using an inappropriate rounding strategy. It further indicated how to select the best strategy for preventing overflow while maintaining high quantization effciency in the FFT. This practice of simulating the design behaviour in the PFB independently of the tools used to design the DSP firmware, is a step towards an end-to-end simulation of the MeerKAT system (or any radio telescope using nite precision digital signal processing systems). This would be useful for design, diagnostics, signal analysis and prototyping of the overall instrument.
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Formulation and evaluation of liposomal films for buccal delivery of antiretroviral drug
- Authors: Okafor, Nnamdi Ikemefuna
- Date: 2020
- Subjects: Liposomes , Highly active antiretroviral therapy , Antiretroviral agents , HIV infections -- Prevention
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/117161 , vital:34485
- Description: The human immune deficiency virus (HIV) infection has been ranked as one of the most devastating microbial infections in the world. This status is a result of the HIV rapid genetic variation, which limits discovery of a vaccine. Use application of antiretroviral therapy (ARVT) in treatment of the disease caused by the HIV infection (known as acquired immunodeficiency syndrome, HIV-AIDS) is frequently compromised by several factors such as the low bioavailability and severe adverse effects associated with the existing antiretroviral drugs (ARVDs). This underlines the need for controlling the pharmacokinetics profiles of ARVD using effective vehicles that can modify drug biodistribution. The same is true for many other conditions, where delivery systems can determine the success or failure of treatment by controlling pharmacokinetic and dynamic properties. The mucosal linings of the oral cavities in addition offer adorable route of administration for systematic drug delivery, improving drug therapeutic performance and often preferred by clinicians and patients. Liposomes are tiny spherical sacs of phospholipid molecules enclosing water droplets, formed (artificially) to carry drugs or other substances into the tissues by crossing and targeting to specific organelles. This work therefore focused on preparation of liposomes and liposomal buccal films (BFs) for potential buccal delivery of efavirenz, an ARVD model endowed with poor solubility and several side effects. The liposomes were prepared by thin film hydration method using crude soybean lecithin (CL) and cholesterol. Efavirenz loaded liposomes were evaluated for particle size, Zeta potential (ZP), morphology, encapsulation efficiency (EE%) and release kinetics studies. The physiochemical properties of the liposomes were also evaluated using Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD), energy dispersity spectroscopy (EDS), and Fourier transform infrared (FTIR), while the formulation with the best encapsulation efficiency was used as the solvent medium for the buccal film formation. The buccal films were prepared using solvent casting method, where the liposomal suspension was used as the dispersing medium. The films were optimized for physical properties (thickness, weight variation and folding endurance) using digital Vernier calliper and digital weighing balance. The physiochemical properties of the selected BFs films made of Carbopol (CP) and its combination with Pluronic F127 (PF127) were further characterized using XRD, DSC, FTIR, Transmission Electron Microscopy (TEM), EDS and Scanning Electron Microscopy (SEM). The permeation study of the selected BFs was investigated using Franz diffusion cell. The BFs composed of CP alone or its combination with PF127 demonstrated much better bio-adhesive properties than the films made of other polymers (like Hydroxyl propyl methyl cellulose, HPMC) alone or in combination with PF127. The developed liposome formulation showed high encapsulation 98.8 ± 0.01 % in CL to cholesterol mass ratio of 1:1 and total lipid to drug mass ratio of 2:1. The average particle size 104.82 ± 2.29 nm and Zeta potential -50.33 ± 0.95 mV of these liposomes were found to be attractive for targeted delivery to the HIV infected cells. The CP based BFs (without and with PF127) exhibited good film thickness 0.88 ± 0.10 and 0.76 ± 0.14 mm, with weight uniformity 68.22 ± 1.04 and 86.28 ± 2. 16 mg, satisfactory flexibility values 258 and 321, and slightly acidic pH 6.43 ± 0.76 and 6.32 ± 0.01. The swelling percentage was found to be 50 % for CP film alone and 78 % for CP film with PF127. The cumulative amount of drug that permeated through the buccal epithelium over 24 hours was about 66 % from CP film alone and 75 % from CP film with PF127. Since no evidence of the liposomal encapsulation of EFV have been reported to our knowledge, we find the insights from the present study valuable as a set of preliminary data to encourage further investigations of the encapsulation and delivery of EFV like antiretrovirals for enhanced solubility, site targeting and prolonged release using crude soybean lecithin and mucoadhesive polymers, which holds some added economical values as naturally occurring lipid and polymeric mixtures as a promising delivery systems for buccal delivery of ARVDs.
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Generation of a virtual library of terpenes using graph theory, and its application in exploration of the mechanisms of terpene biosynthesis
- Authors: Dendera, Washington
- Date: 2020
- Subjects: Terpenes , Plants -- Metabolism , Computational biology , Bioinformatics , Organic compounds -- Synthesis , Monoterpenes , Molecular biology -- Computer simulation
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/123453 , vital:35439
- Description: Terpenes form a large group of organic compounds which have proven to be of use to many living organisms being used by plants for metabolism (Pichersky and Gershenzon, 1934; McGarvey and Croteau, 1995; Gershenzon and Dudareva, 2007), defence or as a means to attract pollinators and also used by humans in medical, pharmaceutical and food industry (Bicas, Dionísio and Pastore, 2009; Marmulla and Harder, 2014; Kandi et al., 2015). Following on literature methods to generate chemical libraries using graph theoretic techniques, complete libraries of all possible terpene isomers have been constructed with the goal of construction of derivative libraries of possible carbocation intermediates which are important in the elucidation of mechanisms in the biosynthesis of terpenes. Virtual library generation of monoterpenes was first achieved by generating graphs of order 7, 8, 9 and 10 using the Nauty and Traces suite. These were screened and processed with a set of collated Python scripts written to recognize the graphs in text format and translate them to molecules, minimizing through Tinker whilst discarding graphs that violate chemistry laws. As a result of the computational time required only order 7 and order 10 graphs were processed. Out of the 873 graphs generated from order seven, 353 were converted to molecules and from the 11,7 million produced from order 10 half were processed resulting in the production of 442928 compounds (repeats included). For screening, 55 366 compounds were docked in the active site of limonene synthase; of these 2355 ligands had a good Vina docking score with a binding energy of between -7.0 and -7.4 kcal.mol-1. When these best docked molecules were overlaid in the active site a map of possible ligand positions within the active site of limonene synthase was traced out.
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Get sleep or get stumped: sleep behaviour in elite South African cricket players during competition
- Authors: McEwan, Kayla
- Date: 2020
- Subjects: Sleep -- Physiological aspects , Cricket players -- Health and hygiene , Cricket players -- South Africa -- Health and hygiene , Cricket -- Health aspects
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/147950 , vital:38696
- Description: Introduction: Good sleep behaviour is associated with achieving optimal athletic performance and reducing the risk of injury. Elite cricket players have unique physical and cognitive demands, and must accommodate for congested competition and travel schedules (all of which increase the risk of disruptive sleep). Further, the political pressures and socioeconomic barriers in South African cricket could affect the sleep of the country’s elite players. Previous research in cricket has focussed on the impact that nutrition, equipment specifications, movement physiology and psychology could elicit on performance (where many professional teams hire support staff to supervise these disciplines); however, there is limited empirical application of sleep research in elite cricket players. Therefore, this study aimed to characterise the sleep behaviours of elite South African cricket players during periods of competition and investigate the relationship between pre-match sleep and cricket performance. Methods: A longitudinal field-based investigation was implemented to monitor the sleep behaviour of 26 elite South African cricket players (age: 28.6 ± 4.0 years; height: 1.8 ± 0.1 m; weight: 85.7 ± 10.8 kg; elite experience: 3.7 ± 4.0 years) during home and away competitive tours. The Morningness-Eveningness Questionnaire and Athlete Sleep Behaviour Questionnaire were administered to identify chronotype and poor sleep behaviours. Players completed an altered version of the Core Consensus Sleep Diary every morning post-travel, pre-match and post-match. Linear mixed model regression was used to compare differences in sleep variables between time-periods, match venues, player roles, match formats, sleep medication and racial groups. Spearman’s correlation (rs) was used to assess the relationship of substance use (alcohol and caffeine), age, elite experience and match performance with selected sleep indices. Statistical significance for all measures was accepted at p < 0.05. Hedge’s (g) were used as the measure of effect size. Results: Light-emitting technology use, effects of travel, late evening alcohol consumption and muscle soreness were the main factors that impacted sleep. Post-match total sleep time (06:31 ± 01:09) was significantly (p < 0.05) shorter compared to post-travel (07:53 ± 01:07; g = 1.19 [0.81;1.57]) and pre-match (08:43 ± 01:03; g = 1.97 [1.55;2.39]) total sleep time. Post-travel sleep onset latency and sleep efficiency were significantly (p < 0.05) shorter (g = 0.74 [0.29;1.29]) and higher (g = 1.35 [0.76;1.94]) at home than away. Although not significant (p > 0.05), allrounders took longer to fall asleep (g = 0.90 [0.23;1.57]), obtained less total sleep (0.76 [0.29;1.42]) and had lower morning freshness scores (g = 1.10 [0.42;1.78]) the night before a match compared to batsmen. Wake after sleep onset and get up time were moderately longer (g = 0.61 [0.22;1.26]) and later (g = 0.62 [0.27;1.17]) before. Twenty20 matches compared to One-Day International matches respectively. Further, sleep duration significantly declined from pre-match to post-match during the multi-day Test format (p = 0.04, g= 0.75 [0.40;1.12]). Late alcohol consumption was significantly (p < 0.05) correlated with a decrease in total sleep time, regardless of match venue (home: rs (49) = -0.69; away: rs (27) = -0.57). During the away condition, an increase in age was significantly associated with longer wake after sleep onset durations (rs (13) = 0.52, p = 0.0003), while greater elite experience was significantly associated with longer total sleep time (rs (72) = 0.36, p = 0.02). The non-sleep medication group took significantly longer to fall asleep compared to the sleep medication group during the first week of the away condition (p = 0.02, g = 0.75 [0.25;1.26]) particularly on nights following transmeridian travel. Although not significant ( p > 0.05), Asian/Indian players had moderately longer sleep onset latencies (g = 1.07 [0.66;1.47]), wake after sleep onset durations (g = 0.86 [0.42;1.29]), and lower subjective sleep quality (g = 0.86 [0.46;1.26]) and morning freshness scores (g = 0.89 [0.47;1.27]) compared to Whites. Similarly, Black Africans had moderately lower subjective sleep quality scores compared to Whites (g = 0.71 [0.43;0.97]). Longer sleep onset latencies and shorter total sleep times were significantly (p < 0.05) associated with poorer One-Day International (rs (28) = -0.57) and Test (rs (12) = 0.59) batting performances respectively. Higher subjective sleep quality scores were significantly associated with better Twenty20 bowling economies (rs (8) = -0.52). Discussion: There was no evidence of poor pre-match sleep behaviour, irrespective of venue; however, the most apparent disruption to sleep occurred post-match (similar to that found in other team-sports). Most disparities in sleep between match venues existed post-travel, with better sleep behaviour observed during the home condition. The differences in sleep patterns found in all three match formats were expected given the variations in format scheduling and duration. Although sleep medication was shown to promote better sleep, its long-term effectiveness was limited. The results promote the implementation of practical strategies aimed to reduce bedtime light-emitting technology use, late evening alcohol consumption and muscle pain. Inter-individual sleep behaviour was found between player roles, age, experience level and race. Moderate associations existed between sleep and markers of batting performance, specifically for the longer, strategic formats of the game. Conclusion: The current study provided new insight of the sleep behaviour in elite South African cricket players during competition. Individualized sleep monitoring practices are encouraged, with specific supervision over older, less experienced players as well as the racial minorities and allrounders of the team. The poor post-match sleep behaviour, together with the sleep and performance correlations, provide ideal opportunities for future interventions to focus on match recovery and the use sleep monitoring as a competitive advantage.
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Growth and photosynthetic responses of Acacia (Vachellia) seedlings to atmospheric CO2 increased from glacial to current concentrations: underlying mechanisms and ecological implications
- Authors: Anderson, Bruce Maurice
- Date: 2020
- Subjects: Acacia vachellia , Acacia vachellia -- Growth , Acacia -- South Africa
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/138182 , vital:37604
- Description: The African Acacia species Vachellia karroo, V. robusta, V. nilotica, and V. tortilis are some of the most invasive species implicated in bush encroachment and woody thickening of historically open savannas in southern Africa. This is partially explained by historic increases in atmospheric CO2 concentrations, which are proposed to have promoted the growth and survivorship of C3 tree seedlings relative to C4 grasses. However, the uniformity of CO2 responsiveness and differences among Vachellia species remain largely undetermined. Here we investigate the growth and photosynthetic responses of four Vachellia species, all implicated in woody encroachment, but originating from distinct climatic niches. Exposing these species to a range of sub-ambient CO2 concentrations (12 – 40 Pa) showed that V. karroo, V. robusta, V. nilotica and V. tortilis all responded strongly and fairly consistently to increasing CO2 concentrations, acting as a ‘functional type’ despite being selected from different geographic regions and having different climatic niches. Combined average net CO2 assimilation rates increased by 130% despite significant, but low levels of down-regulation and decreased stomatal conductance. The increased photosynthetic rates stimulated growth and biomass production in all compartments, with no significant differences in interspecific above and below ground allocation. Growth rates and dry biomass increased by 50% and 186%, respectively, while leaf level water use efficiency (ratio of net CO2 assimilation rate to transpiration rate) increased by an average of 218%. When this was scaled to the whole plant level, this stimulation was decreased to 80%. The decrease was the result of the CO2 stimulated increase in canopy areas, which increased leaf area for water loss. The seedlings’ total number of spinescent physical defenses, as well as the average mass and spine mass fraction also increased with rising CO2. These thicker spines could act as better deterrents against vertebrate browsers. Spine density was unchanged, however, showing that the increased spine numbers were associated with larger seedlings at higher CO2 rather than an increase in the number of spines per stem length. The stimulatory effects of increasing CO2 concentrations since the last glacial maximum and resultant increases in seedling growth and biomass are likely to have had important consequences for the survival and establishment of Acacia seedlings. Tolerance of drought and disturbance has been related to seedling size, hence stimulating the growth rate could confer disturbance tolerance and this tolerance would develop more rapidly with increasing CO2 concentrations. Furthermore, increased nitrogen and water use efficiency have the potential to support seedling establishment in environments where these resources would otherwise be limited at lower atmospheric CO2 concentrations. Resulting in a larger proportion of CO2 fertilization responsive woody seedlings surviving the seedling size classes, and persisting within historically open savannas. Where interspecific differences occurred they are likely to have arisen from adaptation to specific climates where these species are native and selection would have been driven by factors such climate, resource availability, levels of disturbance and competitive interactions. V. karroo had the highest growth rates and strong CO2 driven increases in biomass accumulation, despite having the lowest inherent photosynthetic rates. V. karroo also had the lowest increase in water use efficiency and high transpiration rates could potentially increase access to soil nutrients through mass flow. This species had the highest mean spine mass and showed significant increases in spine mass fraction at elevated CO2 concentrations, which may be important for deterring herbivores. V. robusta’s distribution to the mesic east coast of Africa suggests that water is an important limitation to its distribution. Hence, the CO2 stimulated increase in water use efficiency at both leaf and whole canopy level allows speculation that this may be an important driver of this species’ range expansion, which might continue if increasing levels of CO2 continue to promote water use efficiency. V. nilotica occupies a broad range of habitats, inhabiting large areas of the subtropics both north and south of the equator, with the strongest climatic correlates being the precipitation of the wettest quarter followed by high temperature seasonality. In response to increasing CO2, V. nilotica showed overall strong increases in growth, water use efficiency, and physical defenses. These responses may explain why V. nilotica has been such a successful encroacher in a broad range of habitats where limitations are likely to include multiple climatic factors and disturbances. V. tortilis has the widest distribution of all the species studied, covering broad ranges of Africa and only being excluded from the wettest parts of the equator and driest parts of the deserts. In these experiments this species showed the lowest biomass responsiveness to CO2, but had especially large increases in water use efficiency at both the leaf and canopy level. This may have been an important driver for this species’ encroachment into the more arid parts of its distribution, however this link will need to be verified with further experimentation.
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Identification of SANCDB compounds against G2019S and I2020T variants of leucine-rich repeat Kinase 2 (LRRK2) for the development of drugs against Parkinson’s Disease
- Authors: Baye, Bertha Cinthia
- Date: 2020
- Subjects: Antiparkinsonian agents , Parkinson's disease -- Treatment , Protein kinases , Parkinson's disease -- Chemotherapy , Molecules -- Models
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/138764 , vital:37671
- Description: Parkinson’s disease is a type of movement disorder that occurs when nerve cells in the brain stop producing dopamine. It is the second neurodegenerative disease affecting 1-2% of people above the ages of 65 years old. There is a worldwide prevalence of 7 to 10 million affected people of all cultures and race. Studies have shown that mutation that causes Parkinson’s disease result in increased kinase activity. The c.6055 G > A in exon 41 is the most prevalent LRRK2 variation which causes a substitution of glycine to serine in G2019S in the highly activated loop of its MAP kinase domain. The LRRK2 G2019S variant is the most common genetic determinant of Parkinson’s disease identified to date. This work focused on building accurate 3D models of the LRRK2 kinase domain, that were used for large-scale in silico docking against South African natural compounds from the South African Natural Compounds Database (SANCDB; https://sancdb.rubi.ru.ac.za/). Molecular docking was performed to identify compounds that formed interactions with the active site of the protein and had the lowest binding energy scores. Molecular dynamics simulations showed different movements of the protein-ligand complexes and behavioural difference of the wildtype and the variants, all three structures proved to be compact. Network analysis was done to study residue interactions, contact maps, dynamic cross correlations, average BC and average L were used to study the residue interactions and general residue contribution to the functioning of the protein..
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In vitro susceptibility of Staphylococcus aureus to porphyrin-silver mediated photodynamic antimicrobial chemotherapy
- Authors: Shabangu, Samuel Malewa
- Date: 2020
- Subjects: Porphyrins , Nanoparticles , Photochemotherapy , Drug resistance in microorganisms , Staphylococcus aureus
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167476 , vital:41484
- Description: This work reports on the syntheses and characterization of symmetrical and unsymmetrical porphyrin complexes namely, 5,10,15,20-tetra(4-pyridyl)-porphyrinato zinc(II) (1), 5,10,15,20-tetrathienyl porphyrinato zinc(II) (2), 5-(4-hydroxyphenyl)-10, 15, 20-tris(2-thienyl) porphyrinato zinc(II) (3), 5-(4-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)- porphyrinato zinc(II) (4), 5-(4-carboxyphenyl)-10,15,20-triphenyl-porphyrinato zinc(II) (5) and 5-(4-carboxyphenyl)-10, 15, 20-tris(2-thienyl)-porphyrinato zinc(II) (6). The synthesis of silver nanoparticles (AgNPs) was also undertaken in this research work. Complexes 1, 2, 3 and 6 were linked to oleic acid/oleylamine functionalized nanoparticles via self-assembly and 4-6 were linked via covalent interaction through an amide bond to glutathione capped AgNPs. The effect of nature of bond along with symmetry were investigated, of interest were the five membered thienyl substituents. The photophysical and photochemical behaviour of the complexes and their conjugates with AgNPs were investigated in dimethylformamide. The porphyrin and AgNPs conjugates afforded an increase in singlet oxygen quantum yield. Complexes 1-6 and their conjugates were used for photodynamic antimicrobial chemotherapy of Staphylococcus aureus. The antimicrobial studies were done in two different concentrations of 0.36 and 2.0 μg/mL. The thienyl substituted porphyrin complexes and their conjugates gave better photodynamic activity as compared to phenyl analogues
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