“With This Disease, You Take Whatever Chances There Are”—A Study on Socio-Cultural and Psychological Aspects of Experiments Regarding Huntington’s Disease

Although relatively rare, Huntington’s disease (HD) has fatal consequences. There is no cure for the disease, which leads to an early death. Worldwide, scientists are trying to develop therapeutic methods that could cure the disease, including new molecular gene therapeutic methods. At Lund University, research on HD is now about to step from animal models to trials with humans. The project is special in its design since it involves both medical studies and socio-cultural and psychological research to explore and meet the many challenges that experimental trials with HD patients give rise to. The aim of the present study was to investigate the viewpoints of individuals affected by HD on the issues of participation and exerting influence if taking part in a medical study on gene therapy that has not previously been tested on humans. A total of 16 participants, recruited through the national association for HD and through the neurological clinic at Lund University in Sweden, took part in a focus group or in a survey study. A thematic analysis, to explore the transcribed text from the focus groups as well as from the written mail responses, was conducted by means of Nvivo, a program for qualitative data analysis. Results showed three main themes expressing reasons for participation: participation as a last resort, as an activity of hope, and as a way to take responsibility for the development of a cure that will benefit future generations. The responses relating to the question about affected individuals’ view of exerting influence resulted in two themes. The first theme was having a voice when researchers design experiments, which may give a sense of receiving respect. The second was that influence is an essential part of the information process before agreeing to take part in an experimental trail.

Insights into erlotinib action in pancreatic cancer cells using a combined experimental and mathematical approach

AIM:To gain insights into the molecular action of erlotinib in pancreatic cancer (PC) cells. METHODS:Two PC cell lines, BxPC-3 and Capan-1, were treated with various concentrations of erlotinib, the specific mitogen-activated protein kinase kinase (MEK) inhibitor U0126, and protein kinase B (AKT) inhibitor XIV. DNA synthesis was measured by 5-bromo-2'-deoxyuridine (BrdU) assays. Expression and phosphorylation of the epidermal growth factor receptor (EGFR) and downstream signaling molecules were quantified by Western blot analysis. The data were processed to calibrate a mathematical model, based on ordinary differential equations, describing the EGFRmediated signal transduction. RESULTS:Erlotinib significantly inhibited BrdU incorporation in BxPC-3 cells at a concentration of 1 mol/L, whereas Capan-1 cells were much more resistant. In both cell lines, MEK inhibitor U0126 and erlotinib attenuated DNA synthesis in a cumulative manner, whereas the AKT pathway-specific inhibitor did not enhance the effects of erlotinib. While basal phosphorylation of EGFR and extracellular signal-regulated kinase (ERK) did not differ much between the two cell lines, BxPC-3 cells displayed a more than five-times higher basal phospho-AKT level than Capan-1 cells. Epidermal growth factor (EGF) at 10 ng/mL induced the phosphorylation of EGFR, AKT and ERK in both cell lines with similar kinetics. In BxPC-3 cells, higher levels of phospho-AKT and phospho-ERK (normalized to the total protein levels) were observed. Independent of the cell line, erlotinib efficiently inhibited phosphorylation of EGFR, AKT and ERK. The mathematical model successfully simulated the experimental findings and provided predictions regarding phosphoprotein levels that could be verified experimentally. CONCLUSION:Our data suggest basal AKT phosphorylation and the degree of EGF-induced activation of AKT and ERK as molecular determinants of erlotinib efficiency in PC cells.

Seasonal occurrence of microplastics in sediment of two South African recreational reservoirs

Inland water systems are regarded as a pathway and sink of plastic pollutants from the terrestrial environment.Aquatic ecosystems are globally contaminated with microplastics,but the spatiotemporal occurrence and density of microplastics in freshwater ecosystems remain poorly understood.The present study seasonally assessed differences in microplastic density in the sediments from two South African recreational reservoirs associated with low human activities(macadamia orchards)and high human activities(communal areas).Microplastics were recovered from all of the reservoirs assessed,indicating their extensive occurrence and densities.Microplastic numbers were significantly higher in reservoirs associated with high anthropogenic activities during the hot-dry season(140.6 particles kg^(-1)dwt)and lower in reservoirs associated with low anthropogenic activities during the hot-wet and cool-dry seasons,i.e.,22.60 particles kg^(-1)dwt and 16.13 particles kg^(-1)dwt,respectively.Overall,polypropylene(31%)and polystyrene(30%)were identified as the dominant types of microplastic polymer in both reservoir types.Moreover,no correlative relationships were observed for environmental parameters and microplastic densities across reservoirs and seasons,suggesting a widespread and largely context-independent pollution level.These results show that microplastics are not evenly distributed between waters associated with low human activities and high human activities.Future work should seek greater sample sizes and centre around observing microplastic contamination in the region by examining their sources,transport,and impacts to freshwater environments,whilst informing management strategies.