Auditory interference and phonological encoding in reading for meaning

A thesis Submitted to the Faculty of Arts, University of the, Witwatersrand, Johannesburg,, in fulfilment of the requirements for the degree of Master of Arts. Johannesburg 1983The main aim of the present research was zo investigate the effects of auditory interfering stimuli and an articulatory suppression task on pre- and postlexical phonological encoding during reading. Sixty undergraduate students performed a Prose Comprehension task (Experiment 1) and a Nonword-rhyming task (Experiment 2) under conditions of INTERFERENCE and NO INPUT. An analysis of covariance and post-hoc t-tests revealed that semanticslly and syntactically complex verbal auditory input had the greatest interfering effect on the speed of performance of the Prose Comprehension task, No other results were statistically significant, Twenty undergx-aduate students (Experiment 3) and twenty children (ten dyslexics, ten normal readers - Experiment 4) performed a Magnitude Judgment task under conditions of INTERFERENCE and NO INPUT. Prose auditory interference and an articulatory suppression task did not significantly slow down the performance of skilled readers while prose input did slow down the performance of both dyslexic and normal children. Magnitude Judgment accuracy data was not analysed due to the low error rate. The results of. the present research ware interpreted within the framework of a neuro-cognitive model of reading based largely on Luria's neuropsychological model of the "working brain" and Morton's "Logogen" model of word recognition

Insulin as an immunomodulatory hormone

CITATION: van Niekerk, G. et al. 2020. Insulin as an immunomodulatory hormone. Cytokine & Growth Factor Reviews, 52:34-44. doi:10.1016/j.cytogfr.2019.11.006The original publication is available at https://www.sciencedirect.com/journal/cytokine-and-growth-factor-reviewsInsulin plays an indispensable role in the management of hyperglycaemia that arises in a variety of settings, including Type I and II diabetes, gestational diabetes, as well as is in hyperglycaemia following a severe inflammatory insult. However, insulin receptors are also expressed on a range of cells that are not canonically implicated in glucose homeostasis. This includes immune cells, where the anti-inflammatory effects of insulin have been repeatedly reported. However, recent findings have also implicated a more involved role for insulin in shaping the immune response during an infection. This includes the ability of insulin to modulate immune cell differentiation and polarisation as well as the modulation of effector functions such as biocidal ROS production. Finally, inflammatory mediators can through both direct and indirect mechanisms also regulate serum insulin levels, suggesting that insulin may be co-opted by the immune system during an infection to direct immunological operations. Collectively, these observations implicate insulin as a bona fide immune-modulating hormone and suggest that a better understanding of insulin’s immunological function may aid in optimising insulin therapy in a range of clinical settings.https://www.sciencedirect.com/science/article/pii/S1359610119300644Publishers versio

Mechanisms of doxorubicin-induced drug resistance and drug resistant tumour growth in a murine breast tumour model

CITATION: Christowitz, C., et al. 2019. Mechanisms of doxorubicin-induced drug resistance and drug resistant tumour growth in a murine breast tumour model. BMC Cancer, 19:757, doi:10.1186/s12885-019-5939-z.The original publication is available at https://bmccancer.biomedcentral.comBackground: Doxorubicin is currently the most effective chemotherapeutic drug used to treat breast cancer. It has, however, been shown that doxorubicin can induce drug resistance resulting in poor patient prognosis and survival. Studies reported that the interaction between signalling pathways can promote drug resistance through the induction of proliferation, cell cycle progression and prevention of apoptosis. The aim of this study was therefore to determine the effects of doxorubicin on apoptosis signalling, autophagy, the mitogen-activated protein kinase (MAPK)- and phosphoinositide 3-kinase (PI3K)/Akt signalling pathway, cell cycle control, and regulators of the epithelial-mesenchymal transition (EMT) process in murine breast cancer tumours. Methods: A tumour-bearing mouse model was established by injecting murine E0771 breast cancer cells, suspended in Hank’s Balances Salt Solution and Corning® Matrigel® Basement Membrane Matrix, into female C57BL/ 6 mice. Fourty-seven mice were randomly divided into three groups, namely tumour control (received Hank’s Balances Salt Solution), low dose doxorubicin (received total of 6 mg/ml doxorubicin) and high dose doxorubicin (received total of 15 mg/ml doxorubicin) groups. A higher tumour growth rate was, however, observed in doxorubicin-treated mice compared to the untreated controls. We therefore compared the expression levels of markers involved in cell death and survival signalling pathways, by means of western blotting and fluorescencebased immunohistochemistry. Results: Doxorubicin failed to induce cell death, by means of apoptosis or autophagy, and cell cycle arrest, indicating the occurrence of drug resistance and uncontrolled proliferation. Activation of the MAPK/ extracellularsignal- regulated kinase (ERK) pathway contributed to the resistance observed in treated mice, while no significant changes were found with the PI3K/Akt pathway and other MAPK pathways. Significant changes were also observed in cell cycle p21 and DNA replication minichromosome maintenance 2 proteins. No significant changes in EMT markers were observed after doxorubicin treatment. Conclusions: Our results suggest that doxorubicin-induced drug resistance and tumour growth can occur through the adaptive role of the MAPK/ERK pathway in an effort to protect tumour cells. Previous studies have shown that the efficacy of doxorubicin can be improved by inhibition of the ERK signalling pathway and thereby treatment failure can be overcome.https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5939-zPublisher's versio