Using PESTEL analysis as a framework for analysing the VUCA environment in the Pretoria automotive industry

The term VUCA, is an acronym for volatility, uncertainty, complexity, and ambiguity. VUCA has become one of the “buzz words” in the business sector in the last few years. VUCA however is more than just an acronym, it is a concept that describes an environment in which business operates. It is an environment that is plagued with more volatility, uncertainty, complexity, and ambiguity than ever before. There are numerous factors which have contributed and continue to have an influence on the VUCA environment. PESTEL, another acronym, describes the macro-environment and its components namely: Political, Economic, Social, Technological, Environmental and Legal. The PESTEL analysis has become a tool used in business to effectively analyse the macro-environment in detail by grouping these factors into the six components. The Pretoria automotive industry has faced significant challenges in the last few years, and these challenges have been heightened in complexity. These challenges include volatility with customer demand, adapting to new technological advancements in automation and digital trends, political and labour uncertainty as well as supply chain constraints as a result of global geo-political pressure. The main objective of this paper is to use the PESTEL analysis as a framework for analysing the VUCA environment in the Pretoria automotive industry. The Pretoria automotive industry is the most important region for the automotive industry in South Africa and adds significant economic stimulation to the South African Gros Domestic Product (GDP) and economy according to Automotive Export Council, (2020).Thesis (MBA) -- Faculty of Business and Economic Sciences, 202

Using PESTEL analysis as a framework for analysing the VUCA environment in the Pretoria automotive industry

The term VUCA, is an acronym for volatility, uncertainty, complexity, and ambiguity. VUCA has become one of the “buzz words” in the business sector in the last few years. VUCA however is more than just an acronym, it is a concept that describes an environment in which business operates. It is an environment that is plagued with more volatility, uncertainty, complexity, and ambiguity than ever before. There are numerous factors which have contributed and continue to have an influence on the VUCA environment. PESTEL, another acronym, describes the macro-environment and its components namely: Political, Economic, Social, Technological, Environmental and Legal. The PESTEL analysis has become a tool used in business to effectively analyse the macro-environment in detail by grouping these factors into the six components. The Pretoria automotive industry has faced significant challenges in the last few years, and these challenges have been heightened in complexity. These challenges include volatility with customer demand, adapting to new technological advancements in automation and digital trends, political and labour uncertainty as well as supply chain constraints as a result of global geo-political pressure. The main objective of this paper is to use the PESTEL analysis as a framework for analysing the VUCA environment in the Pretoria automotive industry. The Pretoria automotive industry is the most important region for the automotive industry in South Africa and adds significant economic stimulation to the South African Gros Domestic Product (GDP) and economy according to Automotive Export Council, (2020).Thesis (MBA) -- Faculty of Business and Economic Sciences, 202

11-oxygenated C19 steroids are the predominant androgens in polycystic ovary syndrome

Abstract Context: Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), but the exact origin of hyperandrogenemia remains a matter of debate. Recent studies have highlighted the importance of the 11-oxygenated C19 steroid pathway to androgen metabolism in humans. In this study, we analyzed the contribution of 11-oxygenated androgens to androgen excess in women with PCOS. Methods: One hundred fourteen women with PCOS and 49 healthy control subjects underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. Twenty-four–hour urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for homeostatic model assessment of insulin resistance. Baseline demographic data, including body mass index, were recorded. Results: As expected, serum concentrations of the classic androgens testosterone (P &amp;lt; 0.001), androstenedione (P &amp;lt; 0.001), and dehydroepiandrosterone (P &amp;lt; 0.01) were significantly increased in PCOS. Mirroring this, serum 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone, and 11-ketotestosterone were significantly higher in PCOS than in control subjects, as was the urinary 11-oxygenated androgen metabolite 11β-hydroxyandrosterone. The proportionate contribution of 11-oxygenated to total serum androgens was significantly higher in patients with PCOS compared with control subjects [53.0% (interquartile range, 48.7 to 60.3) vs 44.0% (interquartile range, 32.9 to 54.9); P &amp;lt; 0.0001]. Obese (n = 51) and nonobese (n = 63) patients with PCOS had significantly increased 11-oxygenated androgens. Serum 11β-hydroxyandrostenedione and 11-ketoandrostenedione correlated significantly with markers of insulin resistance. Conclusions: We show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk. </jats:sec

Genetic disruption of 21-hydroxylase in zebrafish causes interrenal hyperplasia

Congenital adrenal hyperplasia is a group of common inherited disorders leading to glucocorticoid deficiency. Most cases are caused by 21-hydroxylase deficiency (21OHD). The systemic consequences of imbalanced steroid hormone biosynthesis due to severe 21OHD remains poorly understood. Therefore, we have developed a zebrafish model for 21OHD, which focuses on the impairment of glucocorticoid biosynthesis. A single 21-hydroxylase gene (cyp21a2) is annotated in the zebrafish genome based on sequence homology. Our in silico analysis of the Cyp21a2 protein sequence suggests a sufficient degree of similarity for the usage of zebrafish cyp21a2 to model aspects of human 21OHD in vivo. We determined the spatio-temporal expression patterns of cyp21a2 by whole mount in situ hybridisation and RT-PCR throughout early development. Early cyp21a2 expression is restricted to the interrenal gland (zebrafish adrenal counterpart) and the brain. To further explore the in vivo consequences of 21-hydroxylase deficiency we created several cyp21a2 null-allele zebrafish lines employing a transcription activator-like effector nuclease genomic engineering strategy. Homozygous mutant zebrafish larvae showed an upregulation of the hypothalamic-pituitary-interrrenal axis and interrenal hyperplasia. Furthermore, Cyp21A2-deficient larvae had a typical steroid profile with reduced concentrations of cortisol and increased concentrations of 17-hydroxyprogesterone and 21-deoxycortisol. Affected larvae showed an upregulation of the hypothalamic-pituitary-interrrenal axis and interrenal hyperplasia. Downregulation of the glucocorticoid-responsive genes pck1 and fkbp5 indicated systemic glucocorticoid deficiency. Our work demonstrates the crucial role of Cyp21a2 in glucocorticoid biosynthesis in zebrafish larvae and establishes a novel in vivo model allowing for studies of systemic consequences of altered steroid hormone synthesis

Gender transformation in the work place and the role of trade unions in South Africa: A case study of rand water

The central point in this research is that some public-sector organisations are making accelerated progress in gender transformation in the post-apartheid South African workplace. The research showed that Rand Water was previously a male-dominated workplace with a strong patriarchal culture. It also showed that Rand Water took a cue from the various legislative provisions of the democratic era and made conscious efforts towards general workplace transformation, with a profound commitment to gender transformation from 2007 onward. This success story of Rand Water and gender transformation was linked to union, worker and management partnership and participation in the workplace. The major partners in the transformation process were the South African Municipal Workers’ Union (SAMWU) through the individual and collective contributions of its members. The research adopted a qualitative research approach, and used structured, semi-structured and in-depth interviews with 26 respondents from Rand Water, SAMWU and the South African Department of Labour in Johannesburg. The study investigated the sociological experiences, employment profiles and gendered perceptions of the participants. The findings indicate that although the respondents’ experiences and perceptions were diverse, both men and women appreciated the gender transformation process at Rand Water. However, there were different views that cut across gender, race and occupation levels. Significantly, the findings also illustrate a heterogeneity of views in terms of how gender transformation is understood. Nevertheless, there was an overwhelming belief that accelerated gender transformation processes are going on at Rand Water because of the promulgation of the Employment Equity Act of 1998. The study also reveals that SAMWU members are the major partners in the process through worker mobilisation. In conclusion the study shows that the role of trade unions in the gender transformation process is crucial. Trade union contributions to the process would be more effective if unions could be restructured with a focus on improving internal structural democracy. By so doing, both women and men would experience equitable representation so that a non-gendered solid front could be used to propel the transformation process

The characterisation of the catalytic activity of human steroid 5α-reductase towards novel C19 substrates

Thesis (MSc)--Stellenbosch University, 2015.ENGLISH ABSTRACT: This study describes: • The UPLC-MS/MS analyses and quantification of novel 5α-reduced steroids using response factors. • The kinetic characterisation of human steroid 5α-reductase type 1 (SRD5A1), expressed in HEK-293 cells, towards 11OHA4 and 11OHT and their keto derivatives by progress curve analysis. • The subcloning, transformation and functional expression of SRD5A1 in the yeast expression system, P. pastoris. • The conversion of 11OHA4 and 11OHT and their keto derivatives by SRD5A1 expressed in P. pastoris. • The endogenous enzymatic activity in P. pastoris towards the 5α-reduced metabolites in the 11OHA4- and alternate 5α-dione pathways. • The potential application of P. pastoris as a biocatalyst in the production of 5α- reduced C19 steroids.AFRIKAANSE OPSOMMING: Hierdie ondersoek beskryf: • Die UPLC-MS/MS analise en kwantifisering van nuut-ondekte 5α-gereduseerde steroïede met behulp van responsfaktore. • Die kinetiese karakterisering van menslike steroïed 5α-reduktase tipe 1 (SRD5A1), uitgedruk in HEK-293 selle, vir 11OHA4 en 11OHT en hul ketoderivate deur middel van progressiekurwe-analise. • Die subklonering, transformasie en funksionele uitdrukking van SRD5A1 in die gis P. pastoris. • Die omsetting van 11OHA4 en 11OHT en hul ketoderivate deur SRD5A1 uitgedruk in P. pastoris. • Die omsetting van 5α-gereduseerde steroïede in die 11OHA4 en alternatiewe 5α-dioon paaie deur endogene ensieme in P. pastoris • ‘n Ondersoek na die toepassing van die gisuitdrukkingstelsel as ‘n moontlike OR potensiële biokatalis vir die produksie van 5α-gereduseerde C19 steroïede

11-Oxygenated androgen precursors are the preferred substrates for aldo-keto reductase 1C3 (AKR1C3):Implications for castration resistant prostate cancer

The progression of castration resistant prostate cancer (CRPC) is driven by the intratumoral conversion of adrenal androgen precursors to potent androgens. The expression of aldo-keto reductase 1C3 (AKR1C3), which catalyses the reduction of weak androgens to more potent androgens, is significantly increased in CRPC tumours. The oxidation of androgens to their inactive form is catalysed by 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2), but little attention is given to the expression levels of this enzyme. In this study, we show that the 11-oxygenated androgen precursors of adrenal origin are the preferred substrate for AKR1C3. In particular we show that the enzymatic efficiency of AKR1C3 is 8- and 24-fold greater for 11-ketoandrostenedione than for the classic substrates androstenedione and 5α-androstanedione, respectively. Using three independent experimental systems and a computational model we subsequently show that increased ratios of AKR1C3:17βHSD2 significantly favours the flux through the 11-oxygenated androgen pathway as compared to the classical or 5α-androstanedione pathways. Our findings reveal that the flux through the classical and 5α-androstanedione pathways are limited by the low catalytic efficiently of AKR1C3 towards classical androgens combined with the high catalytic efficiency of 17βHSD2, and that the expression of the oxidative enzyme therefore plays a vital role in determining the steady state concentration of active androgens. Using microarray data from prostate tissue we confirm that the AKR1C3:17βHSD2 ratio is significantly increased in patients undergoing androgen deprivation therapy as compared to benign tissue, and further increased in patients with CRPC. Taken together this study therefore demonstrates that the ratio of AKR1C3:17βHSD2 is more important than AKR1C3 expression alone in determining intratumoral androgen levels and that 11-oxygenated androgens may play a bigger role in CRPC than previously anticipated

11-ketotestosterone and 11-ketodihydrotestosterone in castration resistant prostate cancer : potent androgens which can no longer be ignored

CITATION: Pretorius, E., et al. 2016. 11-ketotestosterone and 11-ketodihydrotestosterone in castration resistant prostate cancer : potent androgens which can no longer be ignored. PLoS ONE, 11(7):1-17, doi:10.1371/journal.pone.0159867.The original publication is available at http://journals.plos.org/plosonePublication of this article was funded by the Stellenbosch University Open Access Fund.Dihydrotestosterone (DHT) is regarded as the most potent natural androgen and is implicated in the development and progression of castration resistant prostate cancer (CRPC). Under castrate conditions, DHT is produced from the metabolism of the adrenal androgen precursors, DHEA and androstenedione. Recent studies have shown that the adrenal steroid 11β-hydroxyandrostenedione (11OHA4) serves as the precursor to the androgens 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). In this study we comprehensively assess the androgenic activity of 11KT and 11KDHT. This is the first study, to our knowledge, to show that 11KT and 11KDHT, like T and DHT, are potent and efficacious agonists of the human androgen receptor (AR) and induced both the expression of representative AR-regulated genes as well as cellular proliferation in the androgen dependent prostate cancer cell lines, LNCaP and VCaP. Proteomic analysis revealed that 11KDHT regulated the expression of more AR-regulated proteins than DHT in VCaP cells, while in vitro conversion assays showed that 11KT and 11KDHT are metabolized at a significantly lower rate in both LNCaP and VCaP cells when compared to T and DHT, respectively. Our findings show that 11KT and 11KDHT are bona fide androgens capable of inducing androgen-dependant gene expression and cell growth, and that these steroids have the potential to remain active longer than T and DHT due to the decreased rate at which they are metabolised. Collectively, our data demonstrates that 11KT and 11KDHT likely play a vital, but overlooked, role in the development and progression of CRPC.Publisher's versio