Faculty of Science (Research Outputs)
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Item Dimethylformamide is a novel nitrilase inducer in Rhodococcus rhodochrous(Springer, 2018-09) Chhiba-Govindjee, V. P.; Brady, D.; Mathiba, K.; van der Westhuyzen, C. W.; Steenkamp, P.; Rashamuse, J. K.; Stoychev, S.Nitrilases are of commercial interest in the selective synthesis of carboxylic acids from nitriles. Nitrilase induction was achieved here in three bacterial strains through the incorporation of a previously unrecognised and inexpensive nitrilase inducer, dimethylformamide (DMF), during cultivation of two Rhodococcus rhodochrous strains (ATCC BAA-870 and PPPPB BD1780), as well as a closely related organism (Pimelobacter simplex PPPPB BD-1781). Benzonitrile, a known nitrilase inducer, was ineffective in these strains. Biocatalytic product profiling, enzyme inhibition studies and protein sequencing were performed to distinguish the nitrilase activity from that of sequential nitrile hydratase-amidase activity. The expressed enzyme, a 40-kDa protein with high sequence similarity to nitrilase protein Uniprot Q-03217, hydrolyzed 3-cyanopyridine to produce nicotinic acid exclusively in strains BD-1780 and BD-1781. These strains were capable of synthesising both the vitamin nicotinic acid as well as β-amino acids, a compound class of pharmaceutical interest. The induced nitrilase demonstrated high enantioselectivity (>99%) in the hydrolysis of 3-amino-3-phenylpropanenitrile to the corresponding carboxylic acid.Item Free field primaries in general dimensions: counting and construction with rings and modules(Springer, 2018-08) de Mello Koch, RobertWe define lowest weight polynomials (LWPs), motivated by so(d, 2) representation theory, as elements of the polynomial ring over d × n variables obeying a system of first and second order partial differential equations. LWPs invariant under Sn correspond to primary fields in free scalar field theory in d dimensions, constructed from n fields. The LWPs are in one-to-one correspondence with a quotient of the polynomial ring in d × (n − 1) variables by an ideal generated by n quadratic polynomials. The implications of this description for the counting and construction of primary fields are described: an interesting binomial identity underlies one of the construction algorithms. The product on the ring of LWPs can be described as a commutative star product. The quadratic algebra of lowest weight polynomials has a dual quadratic algebra which is non-commutative. We discuss the possible physical implications of this dual algebra.Item Genetic risk score for adult body mass index associations with childhood and adolescent weight gain in an African population(BioMed Central, 2018-08) Munthali, Richard J.; Sahibdeen, Venesa; Kagura, Juliana; Hendry, Liesl M.; Norris, Shane A.; Ong, Ken K.; Lombard, Zané; Day, Felix R.Background: Ninety-seven independent single nucleotide polymorphisms (SNPs) are robustly associated with adult body mass index (BMI kg/m2) in Caucasian populations. The relevance of such variants in African populations at different stages of the life course (such as childhood) is unclear. We tested whether a genetic risk score composed of the aforementioned SNPs was associated with BMI from infancy to early adulthood. We further tested whether this genetic effect was mediated by conditional weight gain at different growth periods. We used data from the Birth to Twenty Plus Cohort (Bt20+), for 971 urban South African black children from birth to 18 years. DNA was collected at 13 years old and was genotyped using the Metabochip (Illumina) array. The weighted genetic risk score (wGRS) for BMI was constructed based on 71 of the 97 previously reported SNPs. Results: The cross-sectional association between the wGRS and BMI strengthened with age from 5 to 18 years. The significant associations were observed from 11 to 18 years, and peak effect sizes were observed at 13 and 14 years of age. Results from the linear mixed effects models showed significant interactions between the wGRS and age on longitudinal BMI but no such interactions were observed in sex and the wGRS. A higher wGRS was associated with an increased relative risk of belonging to the early onset obese longitudinal BMI trajectory (relative risk = 1.88; 95%CI 1.28 to 2.76) compared to belonging to a normal longitudinal BMI trajectory. Adolescent conditional relative weight gain had a suggestive mediation effect of 56% on the association between wGRS and obesity risk at 18 years. Conclusions: The results suggest that genetic susceptibility to higher adult BMI can be tracked from childhood in this African population. This supports the notion that prevention of adult obesity should begin early in life. The genetic risk score combined with other non-genetic risk factors, such as BMI trajectory membership in our case, has the potential to be used to screen for early identification of individuals at increased risk of obesity and other related NCD risk factors in order to reduce the adverse health risk outcomes later.Item Knock-down of LRP/LR promotes apoptosis in early and late stage colorectal carcinoma cells via caspase activation(BioMed Central, 2018-05) Vania, Leila; Rebelo, Thalia M.; Ferreira, Eloise; Weiss, Stefan F. T.Background: Cancer remains one of the leading causes of death around the world, where incidence and mortality rates are at a constant increase. Tumourigenic cells are characteristically seen to over-express the 37 kDa/67 kDa laminin receptor (LRP/LR) compared to their normal cell counterparts. This receptor has numerous roles in tumourigenesis including metastasis, angiogenic enhancement, telomerase activation, cell viability and apoptotic evasion. This study aimed to expose the role of LRP/LR on the cellular viability of early (SW-480) and late (DLD-1) stage colorectal cancer cells. Methods: siRNA were used to down-regulate the expression of LRP/LR in SW-480 and DLD-1 cells which was assessed using western blotting. Subsequently, cell survival was evaluated using the MTT cell survival assay and confocal microscopy. Thereafter, Annexin V-FITC/PI staining and caspase activity assays were used to investigate the mechanism underlying the cell death observed upon LRP/LR knockdown. The data was analysed using Student’s ttest with a confidence interval of 95%, with p-values of less than 0.05 seen as significant. Results: Here we reveal that siRNA-mediated knock-down of LRP led to notable decreases in cell viability through increased levels of apoptosis, apparent by compromised membrane integrity and significantly high caspase-3 activity. Down-regulated LRP resulted in a significant increase in caspase-8 and -9 activity in both cell lines. Conclusions: These findings show that the receptor is critically implicated in apoptosis and that LRP/LR downregulation induces apoptosis in early and late stage colorectal cancer cells through both apoptotic pathways. Thus, this study suggests that siRNA-mediated knock-down of LRP could be a possible therapeutic strategy for the treatment of early and late stage colorectal carcinoma.Item Kondo effect and enhanced magnetic properties in gadolinium functionalized carbon nanotube supramolecular complex(Nature Research, 2018-05) Ncube, S.; Coleman, C.; Strydom, A.; Flahaut, E.; de Sousa, A.We report on the enhancement of magnetic properties of multiwalled carbon nanotubes (MWNTs) functionalized with a gadolinium based supramolecular complex. By employing a newly developed synthesis technique, we find that the functionalization method of the nanocomposite enhances the strength of magnetic interaction, leading to a large effective moment of 15.79µB and nonsuperparamagnetic behavior, unlike what has been previously reported. Saturating resistance at low temperatures is ftted with the numerical renormalization group formula, verifying the Kondo effect for magnetic impurities on a metallic electron system. Magnetoresistance shows devices fabricated from aligned gadolinium functionalized MWNTs (Gd-Fctn-MWNTs) exhibit spin-valve switching behaviour of up to 8%. This study highlights the possibility of enhancing magnetic interactions in carbon systems through chemical modification, moreover, we demonstrate the rich physics that might be useful for developing spin based quantum computing elements based on one-dimensional (1D) channels.Item Compositions with a fixed number of inversions(Springer, 2018-05) Knopfmacher, A.; Mays, M. E.; Wagner, S.A composition of the positive integer n is a representation of n as an ordered sum of positive integers n = a1 + a2 + ··· + am. There are 2n−1 unrestricted compositions of n, which can be sorted according to the number of inversions they contain. (An inversion in a composition is a pair of summands {ai, aj} for which i aj .) The number of inversions of a composition is an indication of how far the composition is from a partition of n, which by convention uses a sequence of nondecreasing summands and thus has no inversions. We count compositions of n with exactly r inversions in several ways to derive generating function identities, and also consider asymptotic results.Item Evidence for igneous differentiation in Sudbury Igneous Complex and impact-driven evolution of terrestrial planet proto-crusts(Nature Research, 2019-01) Latypov, Rais; Chistyakova, Sofya; Grieve, Richard; Huhma, HannuBolide impact is a ubiquitous geological process in the Solar System, which produced craters and basins filled with impact melt sheets on the terrestrial planets. However, it remains controversial whether these sheets were able to undergo large-scale igneous differentiation, or not. Here, we report on the discovery of large discrete bodies of melanorites that occur throughout almost the entire stratigraphy of the 1.85-billion-year-old Sudbury Igneous Complex (SIC) – the best exposed impact melt sheet on Earth – and use them to reaffirm that conspicuous norite-gabbro-granophyre stratigraphy of the SIC is produced by fractional crystallization of an originally homogeneous impact melt of granodioritic composition. This implies that more ancient and compositionally primitive Hadean impact melt sheets on the Earth and other terrestrial planets also underwent large-volume igneous differentiation. The near-surface differentiation of these giant impact melt sheets may therefore have contributed to the evolution and lithological diversity of the proto-crust on terrestrial planets.Item Temporal shifts in landscape connectivity for an ecosystem engineer, the roe deer, across a multiple-use landscape(Springer, 2018-04) Martin, Jodie; Vourc’h, Gwenae¨l; Bonnot, Nade`ge; Cargnelutti, Bruno; Chaval, Yannick; Lourte, Bruno; Goulard, Michel; Hoch, Thierry; Plantard, Olivier; Hewison, A. J. Mark; Morellet, NicolasContext: Routine movements of large herbivores, often considered as ecosystem engineers, impact key ecological processes. Functional landscape connectivity for such species influences the spatial distribution of associated ecological services and disservices. Objectives: We studied how spatio-temporal variation in the risk-resource trade-off, generated by fluctuations in human activities and environmental conditions, influences the routine movements of roedeer across a heterogeneous landscape, generating shifts in functional connectivity at daily and seasonal time scales. Methods: We used GPS locations of 172 adult roedeer and step selection functions to infer landscape connectivity. In particular, we assessed the influence of six habitat features on fine scale movements across four biological seasons and three daily periods, based on variations in the risk-resource trade-off. Results: The influence of habitat features on roe deer movements was strongly dependent on proximity to refuge habitat, i.e. woodlands. Roe deer confined their movements to safe habitats during daytime and during the hunting season, when human activity is high.Item Platinum-bearing chromite layers are caused by pressure reduction during magma ascent(Nature Research, 2018) Latypov, Rais; Costin, Gelu; Chistyakova, Sofya; Hunt, Emma J.; Mukherjee, Ria; Naldrett, TonyPlatinum-bearing chromitites in mafic-ultramafic intrusions such as the Bushveld Complex are key repositories of strategically important metals for human society. Basaltic melts saturated in chromite alone are crucial to their generation, but the origin of such melts is controversial. One concept holds that they are produced by processes operating within the magma chamber, whereas another argues that melts entering the chamber were already saturated in chromite. Here we address the problem by examining the pressure-related changes in the topology of a Mg2SiO4–CaAl2Si2O8–SiO2–MgCr2O4 quaternary system and by thermodynamic modelling of crystallisation sequences of basaltic melts at 1–10 kbar pressures. We show that basaltic melts located adjacent to a so-called chromite topological trough in deep-seated reservoirs become saturated in chromite alone upon their ascent towards the Earth’s surface and subsequent cooling in shallow-level chambers. Large volumes of these chromite-only-saturated melts replenishing these chambers are responsible for monomineralic layers of massive chromitites with associated platinum-group elements.Item Assessing runs of Homozygosity: a comparison of SNP Array and whole genome sequence low coverage data(BMC, 2018) Ceballos, Francisco C.; Hazelhurst, Scott; Ramsay, MichèleBackground: Runs of Homozygosity (ROH) are genomic regions where identical haplotypes are inherited from each parent. Since their first detection due to technological advances in the late 1990s, ROHs have been shedding light on human population history and deciphering the genetic basis of monogenic and complex traits and diseases. ROH studies have predominantly exploited SNP array data, but are gradually moving to whole genome sequence (WGS) data as it becomes available. WGS data, covering more genetic variability, can add value to ROH studies, but require additional considerations during analysis. Results: Using SNP array and low coverage WGS data from 1885 individuals from 20 world populations, our aims were to compare ROH from the two datasets and to establish software conditions to get comparable results, thus providing guidelines for combining disparate datasets in joint ROH analyses. By allowing heterozygous SNPs per window, using the PLINK homozygosity function and non-parametric analysis, we were able to obtain non-significant differences in number ROH, mean ROH size and total sum of ROH between data sets using the different technologies for almost all populations. Conclusions: By allowing 3 heterozygous SNPs per ROH when dealing with WGS low coverage data, it is possible to establish meaningful comparisons between data using SNP array and WGS low coverage technologies.