Embarking on the paradigm journey

This book aims to be a timely and valuable resource for you, as a higher-degree research (HDR) scholar, as you explore the paradigm land-scape and seek to discover and engage with the paradigm that aligns with you as a researcher on your PhD journey. It provides a platform to learn about the paradigm journeys of other emerging scholars and to demonstrate ‘paradigms in action’

Research paradigm considerations for emerging scholars

This book provides insights into the lived experiences of researchers as they negotiate the undulating terrain of the world of paradigms and seek to find their niche. Each chapter presents the journeys of postgraduate candidates, early career researchers and established scholars, starting with an overview of their paradigm, the application of the paradigm to their specific research context, and concluding with the authors reflecting on their identification with and use of the paradigm. The volume acknowledges that determining the paradigm that best aligns with a scholar's personal ideologies and the underlying assumptions of the research can be rather daunting, challenging and perplexing to scholars who are starting their research journey. It offers an accessible exploration of research paradigms and will be a valuable resource for postgraduate researchers, emerging scholars and PhD supervisors

Research paradigm considerations for emerging scholars

This book provides insights into the lived experiences of researchers as they negotiate the undulating terrain of the world of paradigms and seek to find their niche. Each chapter presents the journeys of postgraduate candidates, early career researchers and established scholars, starting with an overview of their paradigm, the application of the paradigm to their specific research context, and concluding with the authors reflecting on their identification with and use of the paradigm. The volume acknowledges that determining the paradigm that best aligns with a scholar's personal ideologies and the underlying assumptions of the research can be rather daunting, challenging and perplexing to scholars who are starting their research journey. It offers an accessible exploration of research paradigms and will be a valuable resource for postgraduate researchers, emerging scholars and PhD supervisors

Embarking on the paradigm journey

This book aims to be a timely and valuable resource for you, as a higher-degree research (HDR) scholar, as you explore the paradigm land-scape and seek to discover and engage with the paradigm that aligns with you as a researcher on your PhD journey. It provides a platform to learn about the paradigm journeys of other emerging scholars and to demonstrate ‘paradigms in action’

Cholesterol Biosynthesis and Uptake in Developing Neurons

Brain cholesterol biosynthesis, a separate and distinct process from whole-body cholesterol homeostasis, starts during embryonic development. To gain a better understanding of the neuronal and glial contributions to the brain cholesterol pool, we studied this process in control, Dhcr7–/–, and Dhcr24–/– cell cultures. Our LC-MS/MS method allowed us to measure several different sterol intermediates and cholesterol during neuronal differentiation. We found that developing cortical neurons rely on endogenous cholesterol synthesis and utilize ApoE-complexed cholesterol and sterol precursors from their surroundings. Both developing neurons and astrocytes release cholesterol into their local environment. Our studies also uncovered that developing neurons produced significantly higher amounts of cholesterol per cell than the astrocytes. Finally, we established that both neurons and astroglia preferentially use the Bloch sterol biosynthesis pathway, where desmosterol is the immediate precursor to cholesterol. Overall, our studies suggest that endogenous sterol synthesis in developing neurons is a critical and complexly regulated homeostatic process during brain development

The effect of GIRK4 and RGS6 ablation on APD heterogeneity, μ.

(A) Average APD heterogeneity, μ, as a function of BCL in WT, Girk4-/-, and Rgs6-/- hearts. (B-D) The effect of CCh on μ at different BCL in WT, Girk4-/-, and Rgs6-/- hearts. n = 8, 5, 8 for WT, Rgs6-/-, and Girk4-/- respectively. Statistics performed using 1-way ANOVA.</p

The influence of M₂R-I_KACh signaling on in vivo HR and HRV.

<p>Summary of baseline and post-CCh (300nM CCh) in-vivo HR (A) and HRV (B) in WT, <i>Rgs6</i>^<i>-/-</i>, and <i>Girk4</i>^<i>-/-</i> mice. (‘*’ denotes statistical significance of p < 0.05 between baseline and CCh within the same genotype. ‘&’ denotes a statistically significant (p < 0.05) difference for both baseline and CCh when comparing between two genotypes). ‘#’ denotes statistical significance of p < 0.05 between WT and <i>Rgs6</i>^<i>-/-</i> mice post-CCh. ‘$’ denotes statistical significance of p < 0.05 between <i>Girk4</i>^<i>-/-</i> and <i>Rgs6</i>^<i>-/-</i> mice post-CCh. Statistics performed using 1-way ANOVA.) (C) Quantification of the total number of mice that exhibited arrhythmias post CCh. (‘*’ denotes statistical significance of p < 0.05 between <i>Girk4</i>^<i>-/-</i> and <i>Rgs6</i>^<i>-/-</i>. Statistics performed using Fisher’s exact test). (D) Representative examples of ECG data during control and demonstrating episodes of arrhythmia in WT and <i>Rgs6</i>^<i>-/-</i>, and no arrhythmia in <i>Girk4</i>^<i>-/-</i> mice post CCh. n = 8, 8, 6 for WT, <i>Rgs6</i>^<i>-/</i>-, and <i>Girk4</i>^<i>-/-</i>_, respectively.</p

The effect of GIRK4 and RGS6 ablation on APD₈₀.

<p>(A) Change in average APD₈₀ with decreasing BCL in WT, <i>Girk4</i>^<i>-/-</i>, and <i>Rgs6</i>^<i>-/-</i> hearts. (‘#’ denotes statistical significance of p < 0.05 between WT and <i>Girk4</i>^<i>-/-</i>. ‘$’ denotes statistical significance of p < 0.05 between WT and <i>Rgs6</i>^<i>-/-</i>). (B) Representative 2D APD₈₀ maps from WT, <i>Girk4</i>^<i>-/-</i>, and <i>Rgs6</i>^<i>-/-</i> hearts, constructed at BCL = 120 ms both at baseline and post-CCh injection. Representative action potential traces are shown at baseline (top panel, pixels marked by *) and post-CCh (bottom panel, pixels marked by Δ). (C-E) The effect of CCh on APD₈₀ at decreasing BCL in WT, <i>Girk4</i>^<i>-/-</i>, and <i>Rgs6</i>^<i>-/-</i> hearts. (‘*’ denotes statistical significance of p < 0.05 between baseline and 300nM CCh; ‘&’ denotes statistical significance of p < 0.05 between baseline and 3uM CCh). n = 8, 5, 8 for WT, <i>Rgs6</i>^<i>-/-</i>, and <i>Girk4</i>^<i>-/-</i>_, respectively. All statistics performed using 1-way ANOVA.</p

The effect of GIRK4 and RGS6 ablation on CV.

<p>(A) Average CV as a function of BCL in WT, <i>Girk4</i>^<i>-/-</i>, and <i>Rgs6</i>^<i>-/-</i> hearts. (B) Representative 2D activation maps from WT, <i>Girk4</i>^<i>-/-</i>, and <i>Rgs6</i>^<i>-/-</i> hearts, constructed at BCL = 150 ms both at baseline and post-CCh injection. (C-E) The effect of CCh on CV at different BCL in WT, <i>Girk4</i>^<i>-/-</i>, and <i>Rgs6</i>^<i>-/-</i>. n = 8, 5, 8 for WT, <i>Rgs6</i>^<i>-/-</i>, and <i>Girk4</i>^<i>-/-</i>_, respectively. Statistics performed using 1-way ANOVA.</p

The effect of GIRK4 and RGS6 ablation on S_max.

<p>Summary of the baseline and post-CCh maximum slopes of APD restitution, S_max, in WT (n = 8), <i>Girk4</i>^<i>-/-</i> (n = 8) and <i>Rgs6</i>^<i>-/-</i> (n = 5) mice. (‘*’ denotes statistical significance of p < 0.05 between post-CCh and baseline for the same genotype. Statistics performed using 1-way ANOVA).</p