The role of Vitamin D and the Vitamin D receptor in skeletal muscle function and exercise adaptation

Vitamin D deficiency remains prevalent throughout the world, with severe deficiencies resulting in skeletal muscle myopathies. Within skeletal muscle, a dynamic network of mitochondria exists primarily functioning to produce ATP via oxidative phosphorylation. Recent investigations have proposed that vitamin D related metabolites are able to modulate mitochondrial function within skeletal muscle cell lines and human populations with severe vitamin D deficiencies. Therefore, the aims of this thesis were to further explore the role of vitamin D related signalling via the VDR and diet-induced vitamin D deficiency in modulating skeletal muscle mitochondrial function. It was demonstrated that a reduction in the VDR significantly reduced mitochondrial respiration in the C2C12 skeletal muscle cell line without altering mitochondrial protein content. Furthermore, in vivo investigations revealed a reduction in skeletal muscle mitochondrial respiration following 3-months of diet-induced vitamin D deficiency in mice. Finally, we also demonstrated an impairment in voluntary wheel running performance and the subsequent adaptive response following diet-induced vitamin D deficiency in mice. In summary, this thesis contributes novel data towards the understanding of the role of the vitamin D and the VDR in modulating skeletal muscle mitochondrial function

Tuning the thermal conductivity of graphene nanoribbons by edge passivation and isotope engineering: a molecular dynamics study

Using classical molecular dynamics simulation, we have studied the effect of edge-passivation by hydrogen (H-passivation) and isotope mixture (with random or supperlattice distributions) on the thermal conductivity of rectangular graphene nanoribbons (GNRs) (of several nanometers in size). We found that the thermal conductivity is considerably reduced by the edge H-passivation. We also find that the isotope mixing can reduce the thermal conductivities, with the supperlattice distribution giving rise to more reduction than the random distribution. These results can be useful in nanoscale engineering of thermal transport and heat management using GNRs.Comment: 4 pages, 4 figure

Molecular Analysis of ATP-sensitive K Channel Gating and Implications for Channel Inhibition by ATP

The β cell KATP channel is an octameric complex of four pore-forming subunits (Kir6.2) and four regulatory subunits (SUR1). A truncated isoform of Kir6.2 (Kir6.2ΔC26), which expresses independently of SUR1, shows intrinsic ATP sensitivity, suggesting that this subunit is primarily responsible for mediating ATP inhibition. We show here that mutation of C166, which lies at the cytosolic end of the second transmembrane domain, to serine (C166S) increases the open probability of Kir6.2ΔC26 approximately sevenfold by reducing the time the channel spends in a long closed state. Rundown of channel activity is also decreased. Kir6.2ΔC26 containing the C166S mutation shows a markedly reduced ATP sensitivity: the Ki is reduced from 175 μM to 2.8 mM. Substitution of threonine, alanine, methionine, or phenylalanine at position C166 also reduced the channel sensitivity to ATP and simultaneously increased the open probability. Thus, ATP does not act as an open channel blocker. The inhibitory effects of tolbutamide are reduced in channels composed of SUR1 and Kir6.2 carrying the C166S mutation. Our results are consistent with the idea that C166 plays a role in the intrinsic gating of the channel, possibly by influencing a gate located at the intracellular end of the pore. Kinetic analysis suggests that the apparent decrease in ATP sensitivity, and the changes in other properties, observed when C166 is mutated is largely a consequence of the impaired transition from the open to the long closed state

EFFECT OF HABITAT AND FORAGING HEIGHT ON BAT ACTIVITY IN THE COASTAL PLAIN OF SOUTH CAROLINA

Double-crested cormorant (Phalacrocorax auritus) populations on the Great Lakes expanded greatly during the past 2 decades. On Lake Erie, the number of breeding cormorants increased from 174 birds (87 nests) in 1979 to 26,542 (13,271 nests) in 2000. In 2000, 81% of the breeding population was on 2 western-basin islands (East Sister and Middle Islands). The plant communities on these islands represent some of the last remnants of Carolinian vegetation in Canada. Our study is the first to quantitatively assess the relationship between the distribution of nesting cormorants and forest health. On East Sister Island, 2 measures of forest cover were obtained using infrared aerial photographs and ground-based measurements of leaf area index. These measures of forest cover were correlated (rs = 0.70, P < 0.001), which validated the use of remotely sensed data to assess forest cover. Cormorant nest density was negatively correlated with tree cover on both East Sister and Middle Islands. Temporal comparisons of Middle Island data indicated a reduction in tree cover from 1995 to 2001, and these reductions coincided with a large increase in the island's cormorant population. Although correlational in nature, our results suggest that cormorants may be detrimentally affecting island forests

The floods: Where do we go from here?

"Support, recovery and lessons learned" from 2015 Cumbria floods. Two months on from devastating flooding in the county various key figures and leaders give their responses to the next stage of recovery, including looking towards strategic solutions for flood prevention

Pharmacological characterisation of the antihyperglycaemic properties of Tinospora crispa extract

The efficacy of Tinospora crispa (Menispermaceae) extract for the treatment of diabetes has previously been verified in animal models. In order to substantiate the antidiabetic effect, we characterised the antihyperglycaemic properties by studying its effect on intestinal glucose absorption and glucose uptake into adipocytes. We also performed experiments to characterise in more detail the mechanism of T. crispa-evoked insulin release by challenging it with insulin secretory antagonists viz. adrenaline, somatostatin, verapamil and nifedipine. In addition, we also performed experiments to determine the effect of the extract on cAMP content. The results clearly showed that the antihyperglycaemic effect is not due to interference with intestinal glucose uptake or uptake of the sugar into the peripheral cells. Rather, the antihyperglycaemic effect of T. crispa is probably due to stimulation of insulin release via modulation of β-cell Ca2+concentration. That the insulinotropic effect of T. crispa is physiological suggests that the extract contains compounds which could be purified for use in the treatment of type II diabetes

Understanding the informal aspects of medication processes to maintain patient safety in hospitals:a sociotechnical ethnographic study in paediatric units

Adverse drug events (ADEs) are common in hospitals, affecting one in six child in-patients. Medication processes are complex systems. This study aimed to explore the work-as-done of medication safety in three English paediatric units using direct observation and semi-structured interviews. We found that a combination of the physical environment, traditional work systems and team norms were among the systemic barriers to medicines safety. The layout of wards discouraged teamworking and reinforced professional boundaries. Workspaces were inadequate, and interruptions were uncontrollable. A less experienced workforce undertook prescribing and verification while more experienced nurses undertook administration. Guidelines were inadequate, with actors muddling through together. Formal controls against ADEs included checking (of prescriptions and administration) and barcode administration systems, but these did not integrate into workflows. Families played an important part in the safe administration of medication and provision of information about their children but were isolated from other parts of the system.</p

Understanding the informal aspects of medication processes to maintain patient safety in hospitals:a sociotechnical ethnographic study in paediatric units

Adverse drug events (ADEs) are common in hospitals, affecting one in six child in-patients. Medication processes are complex systems. This study aimed to explore the work-as-done of medication safety in three English paediatric units using direct observation and semi-structured interviews. We found that a combination of the physical environment, traditional work systems and team norms were among the systemic barriers to medicines safety. The layout of wards discouraged teamworking and reinforced professional boundaries. Workspaces were inadequate, and interruptions were uncontrollable. A less experienced workforce undertook prescribing and verification while more experienced nurses undertook administration. Guidelines were inadequate, with actors muddling through together. Formal controls against ADEs included checking (of prescriptions and administration) and barcode administration systems, but these did not integrate into workflows. Families played an important part in the safe administration of medication and provision of information about their children but were isolated from other parts of the system.</p

The challenge of ageing populations and patient frailty: can primary care adapt?

Health care systems worldwide are having to adapt to ageing populations and increasing numbers of older people with frailty with complex health and social needs, and in the UK primary care is at the frontline of policy attempts to meet this challenge, but achieving the goal of making frailty an integral part of primary care practice is not without considerable challenge