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:65368 Wed 26 Jul 2023 10:33:21 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:50127 Wed 20 Jul 2022 10:18:38 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:45195 Wed 16 Mar 2022 16:08:28 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:29198 Wed 15 Mar 2023 15:47:55 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:65760 Wed 12 Jul 2023 17:20:28 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65724 Wed 12 Jul 2023 09:37:51 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:65721 Wed 12 Jul 2023 09:19:30 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:27448 Wed 12 Apr 2023 14:17:39 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:41030 Wed 05 Apr 2023 11:50:25 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:41018 Tue 30 Nov 2021 08:34:14 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:56806 Tue 27 Sep 2022 09:15:51 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:4147 Tue 15 Aug 2023 11:05:20 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:28347 Tue 14 Mar 2023 10:19:10 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28475 Tue 14 Mar 2023 08:48:02 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:27230 Thu 22 Jul 2021 14:38:29 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:3878 Thu 13 May 2021 10:53:07 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4140 Thu 13 May 2021 09:31:13 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:4153 Thu 13 May 2021 07:14:07 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:4069 Thu 13 May 2021 07:10:21 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:29539 Thu 13 May 2021 06:24:12 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4150 Thu 13 May 2021 06:17:59 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4151 Thu 13 May 2021 06:08:57 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:27439 Thu 13 May 2021 06:06:15 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4279 Thu 13 May 2021 05:55:08 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:20734 Thu 13 May 2021 05:08:47 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:37825 Thu 13 May 2021 04:44:54 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4077 Thu 13 May 2021 04:40:54 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:20316 Thu 13 May 2021 04:32:33 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:27479 Thu 13 May 2021 04:15:02 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:4163 Thu 13 May 2021 03:59:49 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:20744 Thu 13 May 2021 03:51:11 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:65780 Thu 13 Jul 2023 11:50:00 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:65778 Thu 13 Jul 2023 11:29:37 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:27485 Thu 13 Apr 2023 12:46:26 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:72174 Sun 21 Apr 2024 07:59:48 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:72172 Sun 21 Apr 2024 07:45:15 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:57234 Sun 09 Oct 2022 18:07:39 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:71965 Sat 06 Apr 2024 15:13:22 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:71964 Sat 06 Apr 2024 15:13:06 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28298 Sat 01 Jul 2023 12:28:13 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:34034 Mon 29 Nov 2021 19:44:55 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:45409 Mon 24 Apr 2023 15:12:54 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28557 60 cm in well-prepared soils, microbial enzyme activities in the soil depth intervals corresponding to the lower rootzone, were also investigated. This research was carried out in a randomized field trial. Finally, to gain a broader understanding of the effects of contrasting soil management systems on soil microbiology under a greater variety of environmental conditions, arbuscular mycorrhizal (AM) fungal dynamics were explored in a survey of commercial apple orchards. These orchards were selected to span the range of environmental conditions that occur in the apple production areas of the Western Cape. Orchard soils under ORG management promoted richer microbial ecosystems, and appeared to be better able to sustain community metabolic diversity and, by inference, the functions mediated by soil microbial communities, than those under CON management. This implies that ORG approaches possibly afford a better option to sustain critical ecosystem functions than CON management. This possibly explains why use of straw mulches and compost in accordance with ORG practices, compared with CON practices, promoted β-glucosidase, acid phosphatase and urease activities rather than affecting the abundance of the micro-organisms that produce these enzymes. Enzyme activities in the 0–30 cm soil intervals were also more effectively promoted by ORG than CON practices, although no differences were observed at lower depth intervals. ORG practices promoted functional AM associations more effectively than CON practices, but the abundance of glomalin, a beneficial by-product of AM fungi, was unaffected. The greater enzyme activities and higher root colonisation levels in the ORG treatments probably contributed to improved nutritional effects that caused greater vegetative growth, but lower yields, in the ORG treatments. Yield suppression was conceivably due to excessive vegetative growth induced by oversupply of compost and the mineral nutrients contained therein. The survey of Western Cape apple orchards suggested that neither glomalin nor root colonisation bore any specific relationship to production area, cultivation practice, scion x rootstock combination, or, in the case of root colonisation, with any chemical parameters. However, the effect of season on glomalin was conclusively shown, being higher in summer than in spring, as was the lack of any effect of year on glomalin and root colonisation. Collectively, these results showed that ORG soil management promote soil microbiology, soil nutrient status, and apple tree performance compared to CON management.]]> Mon 24 Apr 2023 10:18:55 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:28063 90%) sequence similarity between BSCOMT and human soluble COMT (HSCOMT). BSCOMT was partially purified to 7.78 fold, 1.65% yield and had a specific activity of 0.052 U/mg. It had pH and temperature optima of 8.5 and 40oC, respectively. The Km, Vmax, Kcat and Kcat/Km towards esculetin methylation were respectively 1.475±0.130 pM, 0.0353±0.001 pmol/ml/min, 1.748 x 10-2±5.0x10-4 min-1 and 1.18x10-2 M-1. min-1. HSCOMT was expressed in Escherichia coli BL21(DE3) which showed optimal activity for esculetin methylation at pH and temperature of 7.0 and 30°C, respectively. It was purified to 5.62 fold, 22.6% yield with a specific activity of 3.85 U/mg. HSCOMT kinetic plots, upon incubation of the reaction mixture at 30°C for 5 min before addition of SAM was hyperbolic with Km, Vmax, Kcat and Kcat/Km values of 1.79 pM, 0.412 pmol/ml/min, 2.08 min-1 and 1.165 M-1. min-1, respectively. AuNPs and AgNPs showed a concentration dependent inhibition of HSCOMT activity upon increasing the 5 min incubation time to 1 h. Interestingly, HSCOMT kinetics, with 1 h incubation at 30°C, showed a sigmoidal curve, as well as increased activity. Incubation of the reaction mixture in the presence of 60 pM AuNPs and/or AgNPs for 1 hreversed the observed sigmoidal to a hyperbolic curve, with kinetic parameters comparable to those of 5 min incubation. SDS-PAGE analyses of HSCOMT after the kinetic experiments showed the enzyme incubated for 5 min as a monomer, while that which was incubated for 1 h migrated substantially as dimer. However, the HSCOMT incubated for 1 h in the presence of 60 pM AuNPs and/or AgNPs migrated as a monomer. This indicated that the extension of the incubation period allowed the dimerization of HSCOMT, which exhibited sigmoidal kinetics and higher activity. The presence of NPs impeded the HSCOMT dimerization which decreased the activity. Varying the concentration of SAM suggested that SAM had an allosteric modulatory effect on HSCOMT. Absorption spectroscopy indicated adsorption of HSCOMT on the gold and silver NP surfaces and the formation of NPs-HSCOMT corona. Fluorescence spectroscopy showed that the interaction of HSCOMT with both gold and silver NPs was governed by a static quenching mechanism, implying the formation of a non-fluorescent fluorophore-NP complex at the ground state. Further fluorometric analyses indicated that both gold and silver NPs had contact with Trp143; that the interactions were spontaneous and were driven by electrostatic interactions. Fourier transform infrared spectroscopic studies showed the adsorption of HSCOMT of the NPs surfaces to cause relaxation of the enzyme’s B-sheet structures. Molecular docking studies indicated involvement of largely hydrophilic amino acids, with the interacting distances of less than 3.5A. These findings signify the potential of nanotechnology in the control of COMT catalytic activity for the management of the COMT-related disorders.]]> Mon 13 Mar 2023 14:31:23 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:50129 Mon 10 Oct 2022 08:54:24 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 ]]>