Consumer neuroscience: usability of brain imaging methods in marketing research

Consumer neuroscience (neuromarketing) is an emerging field of marketing research which uses brain imaging techniques to study neural conditions and processes that underlie consumption. The purpose of this study was to map this fairly new and growing field in Finland by studying the opinions of both Finnish consumers and marketing professionals towards it and comparing the opinions to the current consumer neuroscience literature, and based on that evaluate the usability of brain imaging techniques as a marketing research method. Mixed methods research design was chosen for this study. Quantitative data was collected from 232 consumers and 28 marketing professionals by means of online surveys. Both respondent groups had either neutral opinions or lacked knowledge about the four themes chosen for this study: benefits, limitations and challenges, ethical issues and future prospects of consumer neuroscience. Qualitative interview data was collected from 2 individuals from Finnish neuromarketing companies to deepen insights gained from quantitative research. The four interview themes were the same as in the surveys and the interviewees’ answers were mostly in line with the current literature, although more optimistic about the future of the field. The interviews also exposed a gap between academic consumer neuroscience research and practical level applications. The results of this study suggest that there are still many unresolved challenges and relevant populations either have neutral opinions or lack information about consumer neuroscience. The practical level applications are, however, already being successfully used and this new field of marketing research is growing both globally and in Finland.

Targeting oncogenic signaling proteins : new insights using a FRET-based chemical biology approach

Cancer affects more than 20 million people each year and this rate is increasing globally. The Ras/MAPK-pathway is one of the best-studied cancer signaling pathways. Ras proteins are mutated in almost 20% of all human cancers and despite numerous efforts, no effective therapy that specifically targets Ras is available to date. It is now well established that Ras proteins laterally segregate on the plasma membrane into transient nanoscale signaling complexes called nanoclusters. These Ras nanoclusters are essential for the high-fidelity signal transmission. Disruption of nanoclustering leads to reduction in Ras activity and signaling, therefore targeting nanoclusters opens up important new therapeutic possibilities in cancer. This work describes three different studies exploring the idea of membrane protein nanoclusters as novel anti-cancer drug targets. It is focused on the design and implementation of a simple, cell-based Förster Resonance Energy Transfer (FRET)-biosensor screening platform to identify compounds that affect Ras membrane organization and nanoclustering. Chemical libraries from different sources were tested and a number of potential hit molecules were validated on full-length oncogenic proteins using a combination of imaging, biochemical and transformation assays. In the first study, a small chemical library was screened using H-ras derived FRET-biosensors. Surprisingly from this screen, commonly used protein synthesis inhibitors (PSIs) were found to specifically increase H-ras nanoclustering and downstream signalling in a H-ras dependent manner. Using a representative PSI, increase in H-ras activity was shown to induce cancer stem cell (CSC)-enriched mammosphere formation and tumor growth of breast cancer cells. Moreover, PSIs do not increase K-ras nanoclustering, making this screening approach suitable for identifying Ras isoform-specific inhibitors. In the second study, a nanoncluster-directed screen using both H- and K-ras derived FRET biosensors identified CSC inhibitor salinomycin to specifically inhibit K-ras nanocluster organization and downstream signaling. A K-ras nanoclusteringassociated gene signature was established that predicts the drug sensitivity of cancer cells to CSC inhibitors. Interestingly, almost 8% of patient tumor samples in the The Cancer Genome Atlas (TCGA) database had the above gene signature and were associated with a significantly higher mortality. From this mechanistic insight, an additional microbial metabolite screen on H- and K-ras biosensors identified ophiobolin A and conglobatin A to specifically affect K-ras nanoclustering and to act as potential breast CSC inhibitors. In the third study, the Ras FRET-biosensor principle was used to investigate membrane anchorage and nanoclustering of myristoylated proteins such as heterotrimeric G-proteins, Yes- and Src-kinases. Furthermore, Yes-biosensor was validated to be a suitable platform for performing chemical and genetic screens to identify myristoylation inhibitors. The results of this thesis demonstrate the potential of the Ras-derived FRETbiosensor platform to differentiate and identify Ras-isoform specfic inhibitors. The results also highlight that most of the inhibitors identified predominantly perturb Ras subcellular distribution and membrane organization through some novel and yet unknown mechanisms. The results give new insights into the role of Ras nanoclusters as promising new molecular targets in cancer and in stem cells.

Cardiac Imaging in the Diagnosis of Coronary Artery Disease: The Value of Quantitative Imaging of Myocardial Perfusion and Deformation

Atherosclerosis is a chronic and progressive disease of the vasculature. Increasing coronary atherosclerosis can lead to obstructive coronary artery disease (CAD) or myocardial infarction. Computed tomography angiography (CTA) allows noninvasive assessment of coronary anatomy and quantitation of atherosclerotic burden. Myocardial blood flow (MBF) can be accurately measured in absolute terms (mL/g/min) by positron emission tomography (PET) with [15O] H O as a radiotracer. We studied the coronary microvascular dysfunction as a risk factor for future coronary calcification in healthy young men by measuring the coronary flow reserve (CFR) which is the ratio between resting and hyperemic MBF. Impaired vasodilator function was not linked with accelerated atherosclerosis 11 years later. Currently, there is a global interest in quantitative PET perfusion imaging. We established optimal thresholds of [15O] H O PET perfusion for diagnosis of CAD (hyperemic MBF of 2.3 mL/g/min and CFR of 2.5) in the first multicenter study of this type (Turku, Amsterdam and Uppsala). In myocardial bridging a segment of the coronary artery travels inside the myocardium and can be seen as intramural course (CTA) or systolic compression (invasive coronary angiography). Myocardial bridging is frequently linked with proximal atherosclerotic plaques. We used quantitative [15O] H O PET perfusion to evaluate the hemodynamic effects of myocardial bridging. Myocardial bridging was not associated with decreased absolute MBF or increased atherosclerotic burden. Speckle tracking allows quantitative echocardiographic imaging of myocardial deformation. Speckle tracking during dobutamine stress echocardiography was feasible and comparable to subjective wall motion analysis in the diagnosis of CAD. In addition, it correctly risk stratified patients with multivessel disease and extensive ischemia.

Consumer neuroscience: usability of brain imaging methods in marketing research

Consumer neuroscience (neuromarketing) is an emerging field of marketing research which uses brain imaging techniques to study neural conditions and processes that underlie consumption. The purpose of this study was to map this fairly new and growing field in Finland by studying the opinions of both Finnish consumers and marketing professionals towards it and comparing the opinions to the current consumer neuroscience literature, and based on that evaluate the usability of brain imaging techniques as a marketing research method. Mixed methods research design was chosen for this study. Quantitative data was collected from 232 consumers and 28 marketing professionals by means of online surveys. Both respondent groups had either neutral opinions or lacked knowledge about the four themes chosen for this study: benefits, limitations and challenges, ethical issues and future prospects of consumer neuroscience. Qualitative interview data was collected from 2 individuals from Finnish neuromarketing companies to deepen insights gained from quantitative research. The four interview themes were the same as in the surveys and the interviewees’ answers were mostly in line with the current literature, although more optimistic about the future of the field. The interviews also exposed a gap between academic consumer neuroscience research and practical level applications. The results of this study suggest that there are still many unresolved challenges and relevant populations either have neutral opinions or lack information about consumer neuroscience. The practical level applications are, however, already being successfully used and this new field of marketing research is growing both globally and in Finland.