https://vital.seals.ac.za/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://vital.seals.ac.za/vital/access/manager/Repository/vital:42919 Wed 26 May 2021 15:20:13 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65367 Wed 26 Jul 2023 09:58:27 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65774 Wed 26 Jul 2023 09:16:33 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65767 Wed 26 Jul 2023 09:09:34 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:45265 Wed 24 Nov 2021 15:28:04 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:26750 Wed 20 Jul 2022 08:42:27 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:42922 Wed 19 May 2021 10:55:23 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:30044 Wed 15 Mar 2023 13:14:02 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:29167 Wed 15 Mar 2023 11:50:00 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:20519 Wed 12 May 2021 22:26:56 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:38243 Wed 12 May 2021 20:52:22 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28296 Wed 12 May 2021 20:04:41 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4125 Wed 12 May 2021 19:54:17 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:37810 Wed 12 May 2021 19:28:59 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:34273 Wed 12 May 2021 19:20:56 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4095 Wed 12 May 2021 19:10:05 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4154 Wed 12 May 2021 19:07:50 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:29112 Wed 12 May 2021 18:53:14 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4146 Wed 12 May 2021 18:41:14 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4152 Wed 12 May 2021 18:36:22 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28598 Wed 12 May 2021 18:27:23 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4123 Wed 12 May 2021 18:24:18 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:20342 Wed 12 May 2021 18:22:41 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28433 Wed 12 May 2021 17:54:50 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4135 Wed 12 May 2021 17:44:30 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:26752 Wed 12 May 2021 17:42:52 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4149 Wed 12 May 2021 17:35:42 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:20679 Wed 12 May 2021 17:17:50 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:30574 Wed 12 May 2021 17:08:20 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:27435 Wed 12 May 2021 16:40:58 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:30011 Wed 12 May 2021 16:12:08 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28542 Wed 12 May 2021 16:09:18 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4172 Wed 12 May 2021 16:06:18 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:20503 Wed 12 May 2021 16:03:21 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:21049 Cu > Zn >>Fe. The binding capacity of the Spirulina for each of the metals was relatively low when compared to a range of other biosorbents. The toxicity thresholds of the algae was determined for copper and zinc. These were low (10umoles/g) and as such, the algae were not suitable for application in a treatment system in which they came into direct contact with the toxic metals. The algae were able to increase the pH of the surrounding medium. This occurred as a result of the accumulation of inorganic carbon, from bicarbonate, as a response to low concentrations of carbon dioxide in the medium. The resulting release of a hydroxide ion into solution led to the increase in pH. The increase in pH was shown to be due to a reduction in acidity, rather than an increase in alkalinity. The enzyme carbonic anhydrase was shown to be pivotal in this system. Attempts to determine the enzyme activity directly were unsuccessful, due to the inherent inaccuracy of the assay system. An indirect method of determining enzyme activity, by measuring changes in the carbonate species equilibrium, was developed. Under optimal conditions Spirulina was able to reduce the acidity by an amount equivalent to the addition of 3670umoles NaOH g·' h·'. Predictive modelling showed that this enhanced the potential of the medium to effect metal precipitation. For the algal system to be sustainable, a readily available source of bicarbonate was needed. This was achieved by the oxidation of organic carbon, under sulphidogenic conditions, by a bacterial consortium isolated from the anaerobic component of a facultative pond. The consortium was shown to consist of sulphate reducing (most likely Desulvovibrio and Desulfotomaculum)and acetogenic bacteria. Sulphate removal rates of 500mg 1·' day·' and 135mg 1·' day·' were achieved in a 21 agitated and 281 upflow reactor respectively. The bicarbonate generation rate in the 281 reactor was calculated as 4033umoles 1·' day·', which proved sufficient to act as a feed for the algal system. Sparging the anaerobic digester overflow with air and nitrogen resulted in a reduction in the aqueous sulphide concentration. Using nitrogen, a 70% recovery of sulphide, as H2S gas, was achieved in 60 minutes, while with air, this dropped to 40%, due to the oxidation of the aqueous sulphide. The stripping ofH2S resulted in an increase in pH. The H2S gas was used for the selective precipitation of copper and lead in the integrated system. The dynamics of metal precipitation was investigated. For simple reactions, between individual IV metal and base species, it was possible to generate an accurate predictive model and confirm the precipitating species using wavelength dispersive X-ray spectroscopy (WDS). In more complex systems, where precipitation of the artificial acid mine drainage was examined, the predictive modelling and WDS could not accurately describe the system. The addition of aqueous sulphide to copper and iron resulted in the formation of metastable, amorphous precipitates, which remained in suspension. Ageing of the copper precipitate resulted in the evolution of a stable crystalline structure (covellite) and the aggregation and settling of the precipitate. In the case of iron, the amorphous precipitate underwent oxidation before a stable iron sulphide could evolve and the settled precipitate was an iron oxide or oxyhydroxide. The artificial acid mine drainage was treated with sulphide, hydroxide, anaerobic digester overflow and algal overflow. The best metal removal was achieved with the sulphide and hydroxide, while the algal overflow outperformed the anaerobic digester overflow. The precipitate generated by the addition of sulphide was the most compact, followed by the algal overflow, the anaerobic digester overflow and the hydroxide. Efficient precipitation of all the heavy metals, except manganese, was achieved using the algal overflow at an acidity to alkalinity ratio of 1 :2. This ratio was selected for use in the pilot system. The Spirulina based pilot system was effectively used to treat an effluent from the Black Mountain base metal mine. The necessity to maintain the algae in suspension and avoid biomass washout were practical considerations which counted against this system. The replacement of the Spirulina by Oscillatoria, which adhered to a solid support, overcame these problems. The integrated biological system was able to effectively treat an artificial acid mine drainage for 90 days, reducing the concentration of all metals, except manganese, to below the acceptable environmental risk levels. The treatment of the final effluent in a second anaerobic digester reduced the manganese concentration to 4.5uM and proved that the sulphate reducing bacteria could be cultivated on enriched, partially treated acid mine drainage. The integrated biological treatment system performed well, effectively treating an effluent modelled closely on the quality of the water being discharged from the East Rand Basin. The cost of such a system would be considerably less than a "high tech" physico-chemical system. This, coupled with the potential long term sustainability of a biological system, would make it a potentially attractive option for the treatment of future acid mine drainage discharges.]]> Wed 12 May 2021 16:00:34 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28536 Wed 12 May 2021 15:52:54 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4165 Wed 12 May 2021 15:45:50 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:41028 Wed 12 May 2021 15:08:19 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:42950 Wed 12 May 2021 14:46:17 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:41142 Wed 12 May 2021 14:21:50 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:41029 Wed 12 May 2021 14:19:55 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:41156 Wed 12 May 2021 14:04:32 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:42944 Wed 12 May 2021 14:03:03 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:41108 Wed 12 May 2021 13:56:41 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:41440 Wed 12 May 2021 13:53:32 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:42898 Wed 12 May 2021 13:51:19 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:42951 Wed 12 May 2021 13:46:56 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65760 Wed 12 Jul 2023 17:20:28 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65723 Wed 12 Jul 2023 09:31:05 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65719 Wed 12 Jul 2023 09:10:21 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:36758 Wed 12 Apr 2023 09:51:36 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:45073 Wed 06 Jul 2022 08:47:38 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65777 Tue 30 Jan 2024 21:24:18 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:45415 Tue 25 Apr 2023 09:58:18 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:49985 Tue 19 Jul 2022 09:37:26 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65378 Tue 16 Jan 2024 14:38:10 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65377 Tue 16 Jan 2024 14:30:59 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28061 Tue 15 Aug 2023 11:05:18 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:50170 Thu 21 Apr 2022 17:19:02 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:50169 Thu 21 Apr 2022 17:09:08 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4072 Thu 13 May 2021 08:50:19 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4161 Thu 13 May 2021 08:18:59 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:20355 Thu 13 May 2021 08:11:45 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28523 Thu 13 May 2021 07:20:26 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:34282 Thu 13 May 2021 07:18:46 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:29165 Thu 13 May 2021 07:11:47 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:27449 Thu 13 May 2021 06:54:36 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4059 Thu 13 May 2021 06:25:55 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:34035 Thu 13 May 2021 05:52:57 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28406 Thu 13 May 2021 05:46:15 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:27820 Thu 13 May 2021 04:39:10 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4120 Thu 13 May 2021 04:30:31 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:20808 Thu 13 May 2021 04:26:39 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4162 Thu 13 May 2021 04:21:21 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:38089 3000 cases and controls) are required. Macrophage migration inhibitory factor (MIF) is a cytokine that is important in both innate and adaptive immunity that has been shown to play a role in T. brucei pathogenicity using murine models. A total of 27 missense SNVs were modelled using homology modelling to create MIF protein mutants that were investigated using in silico effect prediction tools, molecular dynamics (MD), Principal Component Analysis (PCA), and Dynamic Residue Network (DRN) analysis. Our results demonstrate that mutations P2Q, I5M, P16Q, L23F, T24S, T31I, Y37H, H41P, M48V, P44L, G52C, S54R, I65M, I68T, S75F, N106S, and T113S caused significant conformational changes. Further, DRN analysis showed that residues P2, T31, Y37, G52, I65, I68, S75, N106, and T113S are part of a similar local residue interaction network with functional significance. These results show how polymorphisms such as missense SNVs can affect protein conformation, dynamics, and function. Trypanosomes are auxotrophic for folates and pterins but require them for survival. They scavenge them from their hosts. PTR1 is a multifunctional enzyme that is unique to trypanosomatids that reduces both pterins and folates. In the presence of DHFR inhibitors, PTR1 is over-expressed thus providing an escape from the effects of DHFR inhibition. Both TbPTR1 and TbDHFR are pharmacologically and genetically validated drug targets. In this study 5742 compounds were screened using molecular docking, and 13 promising binding modes were further analysed using MD simulations. The trajectories were analysed using RMSD, Rg, RMSF, PCA, Essential Dynamics Analysis (EDA), Molecular Mechanics Poisson–Boltzmann surface area (MM-PBSA) binding free energy calculations, and DRN analysis. The computational screening approach allowed us to identify five of the compounds, named RUBi004, RUBi007, RUBi014, RUBi016 and RUBi018 that exhibited antitrypanosomal growth activities against trypanosomes in culture with IC50 values of 12.5 ± 4.8 μM, 32.4 ± 4.2 μM, 5.9 ± 1.4 μM, 28.2 ± 3.3 μM, and 9.7 ± 2.1 μM, respectively. Further when used in combination with WR99210 a known TbDHFR inhibitor RUBi004, RUBi007, RUBi014 and RUBi018 showed antagonism while RUBi016 showed an additive effect. These results indicate that the four compounds might be competing with TbDHFR while RUBi016 might be more specific for TbPTR1. These compounds provide scaffolds that can be further optimised to improve their potency and specificity. Lastly, using a systematic approach we derived CHARMM force-field parameters to accurately describe the TbrPDEB1 bi-metal catalytic center. For dynamics, we employed mixed bonded and non-bonded approach. We optimised the structure using a two-layer QM/MM ONIOM (B3LYP/6-31(g): UFF). The TbrPDEB1 bi-metallic center bonds, angles, and dihedrals were parameterized by fitting the energy profiles from Potential Energy Surface (PES) scans to the CHARMM potential energy function. The parameters were validated by means of MD simulations and analysed using RMSD, Rg, RMSF, hydrogen bonding, bond/angle/dihedral evaluations, EDA, PCA, and DRN analysis. The force-field parameters were able to accurately reproduce the geometry and dynamics of the TbrPDEB1 bi-metal catalytic center during MD simulations. Molecular docking was used to identify 6 potential hits, that inhibited trypanosome growth in vitro. The derived force-field parameters were used to simulate the 6 protein-ligand complexes with the aim of elucidating crucial protein-ligand residue interactions. Using the most potent ligand RUBi022 that had an IC50 of 14.96 μM we were able to identify key residue interactions that can be of use in in silico prediction of potential TbrPDEB1 inhibitors. Overall we demonstrate how bioinformatics tools can complement current disease eradication strategies. Future work will focus on identifying variants identified in Genome Wide Association Studies and partnering with wet labs to carry out further enzyme-ligand activity relationship studies, structure determination or characterisation of appropriate protein-ligand complexes by crystallography, and site specific mutation studies]]> Thu 13 May 2021 04:20:49 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:26583 Thu 13 May 2021 03:30:11 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:26588 Thu 13 May 2021 03:30:04 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:26764 Thu 13 May 2021 02:18:22 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:30022 Thu 13 May 2021 01:46:09 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28105 Thu 13 May 2021 01:32:49 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4127 Thu 13 May 2021 01:14:51 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65779 Thu 13 Jul 2023 11:36:46 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65776 Thu 13 Jul 2023 10:47:08 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65775 100 kDa through ultracentrifugation. Mass spectrometry also detected the most abundant peak for all fucoidans to be around 700 Da (m/z). Extracted fucoidans inhibited the activity of α-glucosidase more strongly than the commercial anti-diabetic agent acarbose but were inactive on α-amylase. Fucoidans were also shown to be mixed inhibitors of α-glucosidase. Compellingly, fucoidans synergistically inhibited α-glucosidase in combination with the anti-diabetic agent acarbose, highlighting prospects for combination therapy. Finally, fucoidans demonstrated some anti-proliferative characteristics on HCT116 cancer cells by inhibiting their ability to adhere to the tissue culture plate matrix. Furthermore, some fucoidan extracts inhibited the migration of HCT116 cancer cells from 3D spheroids. Some of our fucoidan extracts also inhibited HCT116 colony formation, demonstrating inhibition of long-term cell survival. The E. maxima water extract also inhibited glucose uptake by HCT116 cells, thereby influencing the glycolytic flux. In conclusion, biologically active fucoidans were successfully extracted from South African brown seaweeds. These fucoidans demonstrated anti-diabetic and anti-cancer properties, revealing their relevance as potential drugs for these diseases.]]> Thu 11 Jan 2024 18:08:05 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28128 Thu 09 Mar 2023 13:00:25 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28533 Thu 09 Mar 2023 09:44:15 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:71940 Thu 04 Apr 2024 19:46:33 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:71939 Thu 04 Apr 2024 19:46:24 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28216 Thu 01 Jun 2023 09:58:06 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:72175 Sun 21 Apr 2024 08:14:12 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:72173 Sun 21 Apr 2024 07:52:16 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:45336 Mon 22 Nov 2021 14:59:04 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:45240 Mon 15 Nov 2021 10:55:11 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:45229 Mon 15 Nov 2021 10:05:51 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:45227 Mon 15 Nov 2021 09:59:03 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28065 Mon 05 Jun 2023 15:41:21 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:45193 Fri 18 Feb 2022 12:59:54 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:57007 Fri 11 Nov 2022 08:55:16 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28297 Fri 10 Mar 2023 12:46:15 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:19947 Fri 06 Aug 2021 11:40:35 SAST ]]>