North Sea Oil and Genuine Saving in the Scottish Economy

The World Bank has published estimates of sustainability of consumption paths by adjusting saving rates to take account of the depletion of non-renewable resources. During the period of North Sea oil production Scotland has been in a fiscal union with the rest of the UK. The present paper adjusts the World Bank data to produce separate genuine saving estimates for Scotland and the rest of the UK for 1970-2009, based on a ‘derivation’ principle for oil revenues. The calculations indicate that Scotland has had a negative genuine saving rate for most of the period of exploitation of North Sea oil resources, with genuine saving being positive in the rest of the UK during this period.

A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

Targeted cancer therapy aims to disrupt aberrant cellular signalling pathways. Biomarkers are surrogates of pathway state, but there is limited success in translating candidate biomarkers to clinical practice due to the intrinsic complexity of pathway networks. Systems biology approaches afford better understanding of complex, dynamical interactions in signalling pathways targeted by anticancer drugs. However, adoption of dynamical modelling by clinicians and biologists is impeded by model inaccessibility. Drawing on computer games technology, we present a novel visualisation toolkit, SiViT, that converts systems biology models of cancer cell signalling into interactive simulations that can be used without specialist computational expertise. SiViT allows clinicians and biologists to directly introduce for example loss of function mutations and specific inhibitors. SiViT animates the effects of these introductions on pathway dynamics, suggesting further experiments and assessing candidate biomarker effectiveness. In a systems biology model of Her2 signalling we experimentally validated predictions using SiViT, revealing the dynamics of biomarkers of drug resistance and highlighting the role of pathway crosstalk. No model is ever complete: the iteration of real data and simulation facilitates continued evolution of more accurate, useful models. SiViT will make accessible libraries of models to support preclinical research, combinatorial strategy design and biomarker discovery.

The importance of improving diet in "Securing Scotland's Health" : progress towards the Scottish dietary goals

Background: In 2013, the Revised Dietary Goals for Scotland (SDGs) were published to “indicate the direction of travel, and assist policy development to reduce the burden of obesity and diet-related disease in Scotland”. They include recommendations for foods (fruit and vegetables, oily fish and red meat) and nutrients (energy, energy density, total fat, saturated fat, trans fatty acids, sugar, salt and fibre). Progress towards the SDGs is monitored using a combination of surveys, principally the secondary analysis of the Living Costs and Food Survey (LCFS). Objective: To obtain estimates of food consumption and nutrient intake for Scotland using LCFS data from 2001 to 2013. Results: For SDGs measured using LCFS data there was little progress towards meeting the goals between 2001 and 2013. This was apparent even amongst least deprived households. Despite evidence of progress for fruit and vegetables up to 2010, consumption subsequently dropped; and there was no change in oil rich fish consumption. Mean total red meat consumption meets the SDG and a significant reduction was found between 2001 and 2013, which was partly accounted for by a fall in red meat products such as sausages and burgers. Energy density increased significantly over time despite a dip in 2012. Saturated fat, total fat and sugar intakes remained considerably higher than the SDGs. Overall there were small but significant decreases in the percentage of food energy from saturated fat and sugars, although intakes appear to have risen since 2011. There was no change in fibre intake. Conclusion: The results presented support work by Food Standards Scotland and the Scottish Government to facilitate improvements to the diet to help prevent obesity. Whilst some very small improvements were observed however, new approaches are required to encourage the population towards a healthier diet to secure Scotland’s health in the future. Funded by Food Standards Scotland, Project Number FS424018. Data provided by DEFRA, Scottish Neighbourhood Statistics, ONS and the UK Data Archive.

Playing popular science

This was a peer-reviewed event that took place at the DiGRA-FDG conference in August 2016. While it has a paper component (the attached proposal), the output was a demonstration of games rather than a conference paper. As such, this entry should be considered an Event or Exhibition.

A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells

Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic detoxification and crosstalk with growth promoting pathways. HER2 receptor tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled receptor activation and signaling. A combination of HER2 targeting monoclonal antibodies shows greater anticancer efficacy than the single targeting antibodies, however, its mechanism of action is largely unclear. Here we report novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2. HER2 targeting by antibodies inhibited growth in association with persistent generation of reactive oxygen species (ROS), glutathione (GSH) depletion, reduction in NRF2 levels and inhibition of NRF2 function in ovarian cancer cell lines. The combination of antibodies produced more potent effects than single alone; downregulated NRF2 substrates by repressing the Antioxidant Response (AR) pathway with concomitant transcriptional inhibition of NRF2. We showed the antibody combination produced increased methylation at the NRF2 promoter consistent with repression of NRF2 antioxidant function, as HDAC and methylation inhibitors reversed such produced transcriptional effects. These findings demonstrate a novel mechanism and role for NRF2 in mediating the response of cancer cells to the combination of Trastuzumab and Pertuzumab and reinforce the importance of NRF2 in drug resistance and as a key anticancer target.