Copper homeostasis in human mammary epithelial cells

Adequate amounts of copper in milk are critical for normal neonatal development, however the mechanisms regulating copper supply to milk have not been clearly defined. This thesis analysed copper transporting proteins in mammary epithelial cells and the impact of copper and lactational hormones upon the regulation these proteins was measured.

Skeletal muscle nitric oxide signalling and exercise: a focus on glucose metabolism

Nitric oxide (NO) is an important vasodilator and regulator in the cardiovascular system, and this link was the subject of a Nobel prize in 1998. However, NO also plays many other regulatory roles, including thrombosis, immune function, neural activity, and gastrointestinal function. Low concentrations of NO are thought to have important signaling effects. In contrast, high concentrations of NO can interact with reactive oxygen species, causing damage to cells and cellular components.

A less-recognized site of NO production is within skeletal muscle, where small increases are thought to have beneficial effects such as regulating glucose uptake and possibly blood flow, but higher levels of production are thought to lead to deleterious effects such as an association with insulin resistance.

This review will discuss the role of NO in skeletal muscle during and following exercise, including in mitochondrial biogenesis, muscle efficiency, and blood flow with a particular focus on its potential role in regulating skeletal muscle glucose uptake during exercise.

Exercise-induced muscle glucose uptake in mice with graded, muscle-specific GLUT-4 deletion

To investigate the importance of the glucose transporter GLUT-4 for muscle glucose uptake during exercise, transgenic mice with skeletal muscle GLUT-4 expression approximately 30–60% of normal (CON) and approximately 5–10% of normal (KO) were generated using the Cre/Lox system and compared with wild-type (WT) mice during approximately 40 min of treadmill running (KO: 37.7 ± 1.3 min; WT: 40 min; CON: 40 min, P = 0.18). In WT and CON animals, exercise resulted in an overall increase in muscle glucose uptake. More specifically, glucose uptake was increased in red gastrocnemius of WT mice and in the soleus and red gastrocnemius of CON mice. In contrast, the exercise-induced increase in muscle glucose uptake in all muscles was completely abolished in KO mice. Muscle glucose uptake increased during exercise in both red and white quadriceps of WT mice, while the small increases in CON mice were not statistically significant. In KO mice, there was no change at all in quadriceps muscle glucose uptake. No differences in muscle glycogen use during exercise were observed between any of the groups. However, there was a significant increase in plasma glucose levels after exercise in KO mice. The results of this study demonstrated that a reduction in skeletal muscle GLUT-4 expression to approximately 10% of normal levels completely abolished the exercise-induced increase in muscle glucose uptake.

Telomere dynamics and homeostasis in a transmissible cancer

Devil Facial Tumour Disease (DFTD) is a unique clonal cancer that threatens the world's largest carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii) with extinction. This transmissible cancer is passed between individual devils by cell implantation during social interactions. The tumour arose in a Schwann cell of a single devil over 15 years ago and since then has expanded clonally, without showing signs of replicative senescence; in stark contrast to a somatic cell that displays a finite capacity for replication, known as the “Hayflick limit”.

Intervention efficacy among 'At Risk' adolescents: a test of subjective wellbeing homeostasis theory

 This study tests a number of theoretical predictions based on subjective wellbeing (SWB) Homeostasis Theory. This theory proposes that SWB is actively maintained and defended within a narrow, positive range of values around a 'set-point' for each person. Due to homeostatic control, it is predicted to be very difficult to substantially increase SWB in samples operating normally within their set-point-range. However, under conditions of homeostatic defeat, where SWB is lower than normal, successful interventions should be accompanied by a substantial increase as each person's SWB returns to lie within its normal range of values. This study tests these propositions using a sample of 4,243 participants in an Australian Federal Government Program for 'at-risk' adolescents. SWB was measured using the Personal Wellbeing Index and results are converted to a metric ranging from 0 to 100 points. The sample was divided into three sub-groups as 0-50, 51-69, and 70+ points. The theoretical prediction was confirmed. The largest post-intervention increase in SWB was in the 0-50 group and lowest in the 70+ group. However, a small increase in SWB was observed in the normal group, which was significant due to the large sample size. The implications of these findings for governments, schools and policy makers are discussed.

Personal resilience in times of crisis : the implications of SWB homeostasis and set-points

Our companion paper (Cummins et al. in J Happiness Stud, 2013) describes the statistical process used to demonstrate set-points and set-point-ranges for subjective wellbeing. The implications of set-points and homeostasis are now considered in the context of resilience. This discussion leads with a brief overview of resilience definitions and is followed by a description of subjective wellbeing (SWB) homeostasis. This addresses, in particular, the issue of SWB malleability under homeostatic control. The link between resources and resilience is then considered, in terms of predictions made by homeostasis theory. Finally, discussion focuses on the implications of such understanding for future directions in SWB research. It is concluded that an understanding of set-points and homeostasis allows new insights into the resilience construct.