The inverse relation between risks and benefits: The impact of individual differences in information processing style.

Existing research shows that evaluations of the risks and benefits of various hazards (i.e., technologies and activities) are inversely related. The affect heuristic explains the negative relation between risks and benefits, as based on the strength of positive or negative affect associated with a hazard. Research on the affect heuristic previously investigated under which conditions people judge risk and benefits independently, focusing on expertise as a factor that might exempt from inversely related judgements of risk and benefits. Measurements within Dual Process Theories have been found to be associated with rational, analytical decision making and accurate judgments. In this paper we investigated the extent to which rational information processing styles can predict the risk-benefit relation of technologies in a medical and food applications and whether the attitudes influence the strength or direction of the relationship. Using the Need for Cognition Scale (NFC), a psychometric-based risk scale and an explicit measure of attitude, in a representative sample of 3228 Swedes, we found that the high NFC group judged the risks and benefits of technologies to be inversely related. In contrast, the low NFC group judged the risks and benefits to be positively related. These results were confirmed across all studied technologies by applying moderation analysis. We discuss the results in light of recent research on cognitive processing and polarization over technologies' risks.

Gene doping: gene delivery for olympic victory.

With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place.

Hippocampus-specific deletion of tissue plasminogen activator "tPA" in adult mice impairs depression- and anxiety-like behaviors.

Anxiety and depression are multifactorial disorders that have become prominent health problems all over the world. Neurotrophic factors have emerged underlying pathogenesis of these diseases. Although a number of studies indicate that the hippocampus-brain-derived neurotrophic factor (BDNF) may be involved in these psychiatric illnesses, little is known about the molecular mediators of these disorders. In this study we further investigate the role of tissue plasminogen activator (tPA), a serine protease involved in pro-BDNF cleavage to BDNF, in depression and anxiety-like behaviors in adult mice. To address this issue, we investigated the effect of hippocampus tPA manipulation, using viral vectors, on anxiety- and depression-like behaviors, including the marble burying test (MBT), elevated plus maze (EPM), tail suspension test (TST), novelty suppressed feeding (NSF) and forced swim test (FST). Our results showed that tPA knock-down - using lentiviral vectors expressing specific short hairpin RNAs (LV-shRNA) - increased the number of buried marbles together with the digging time in the MBT and decreased the time spent in open the arms of an EPM. In addition, tPA-knock down in the hippocampus increased immobility in the FST and TST, and increased time to feed in the NSF test. These effects were reversed when tPA-over-expressing vectors (LV-tPA) were injected in the hippocampus. We also found that BDNF protein levels were elevated in the hippocampus of mice receiving tPA-expressing vectors. Together, our results imply that tPA manipulation may provide an effective therapeutic intervention for depression and anxiety disorders.

Reduction of ethanol consumption in alcohol-preferring rats by dual expression gene transfer.

AIMS: To mimic, in an animal model of alcoholism, the protective phenotype against alcohol consumption observed in humans carrying a fast alcohol dehydrogenase (ADH1B*2) and an inactive aldehyde dehydrogenase (ALDH2*2). METHODS: We developed a multiple expression cassette adenoviral vector (AdV-ADH/asALDH2) encoding both a fast rat ADH and an antisense RNA against rat ALDH2. A control adenoviral vector (AdV-C) containing intronic non-coding DNA was also developed. These adenoviral vectors were administered intravenously to rats bred as high alcohol-drinkers (University of Chile bibulous) that were previously rendered alcohol dependent by a 75-day period of voluntary 10% ethanol intake. RESULTS: Animals administered AdV-ADH/asALDH2 showed a 176% increase in liver ADH activity, whereas liver ALDH2 activity was reduced by 24%, and upon the administration of a dose of ethanol (1 g/kg, i.p.), these showed arterial acetaldehyde levels that were 400% higher than those of animals administered AdV-C. Rats that received the AdV-ADH/asALDH2 vector reduced by 60% their voluntary ethanol intake versus controls. CONCLUSION: This study provides evidence that the simultaneous increase of liver ADH and a reduction of ALDH activity by gene transfer could constitute a potential therapeutic strategy for the treatment of alcoholism.

Volunteering for early phase gene transfer research in Parkinson disease.

BACKGROUND: For early phase trials of novel interventions-such as gene transfer for Parkinson disease (PD)--whose focus is primarily on safety and tolerability, it is important that participants have a realistic understanding of the goals of such research. Recently, some have expressed concern that patients with PD may have unrealistic expectations. METHODS: The authors examined why patients with PD might volunteer for invasive early phase research by interviewing 92 patients with PD and comparing those who would (n = 46) and those who would not (n = 46) participate in a hypothetical phase I gene-transfer study. RESULTS: The two groups' demographic, clinical, functional, and quality of life measures, as well as their understanding of the research protocol, were similar. The groups did not differ on their perception of potential for personal benefit nor on the level of likelihood of benefit they saw as a precondition for volunteering. However, those willing to participate tended to perceive lower probability of risk, were tolerant of greater probability of risk, and were more optimistic about the phase I study's potential benefits to society. They also appeared more decisive and action-oriented than the unwilling group. CONCLUSIONS: It is likely that the decision whether to participate in early phase PD gene transfer studies will depend mostly on patients' attitudes regarding risk, optimism about science, and an action orientation, rather than on their clinical, functional, or demographic characteristics.

Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum.

Given that cocaine induces neuroadaptations through regulation of gene expression, we investigated whether chromatin remodeling at specific gene promoters may be a key mechanism. We show that cocaine induces specific histone modifications at different gene promoters in striatum, a major neural substrate for cocaine's behavioral effects. At the cFos promoter, H4 hyperacetylation is seen within 30 min of a single cocaine injection, whereas no histone modifications were seen with chronic cocaine, consistent with cocaine's ability to induce cFos acutely, but not chronically. In contrast, at the BDNF and Cdk5 promoters, genes that are induced by chronic, but not acute, cocaine, H3 hyperacetylation was observed with chronic cocaine only. DeltaFosB, a cocaine-induced transcription factor, appears to mediate this regulation of the Cdk5 gene. Furthermore, modulating histone deacetylase activity alters locomotor and rewarding responses to cocaine. Thus, chromatin remodeling is an important regulatory mechanism underlying cocaine-induced neural and behavioral plasticity.