DAF-16 and Δ9 Desaturase Genes Promote Cold Tolerance in Long-Lived Caenorhabditis elegans age-1 Mutants

In Caenorhabditis elegans, mutants of the conserved insulin/IGF-1 signalling (IIS) pathway are long-lived and stress resistant due to the altered expression of DAF-16 target genes such as those involved in cellular defence and metabolism. The three Δ9 desaturase genes, fat-5, fat-6 and fat-7, are included amongst these DAF-16 targets, and it is well established that Δ9 desaturase enzymes play an important role in survival at low temperatures. However, no assessment of cold tolerance has previously been reported for IIS mutants. We demonstrate that long-lived age-1(hx546) mutants are remarkably resilient to low temperature stress relative to wild type worms, and that this is dependent upon daf-16. We also show that cold tolerance following direct transfer to low temperatures is increased in wild type worms during the facultative, daf-16 dependent, dauer stage. Although the cold tolerant phenotype of age-1(hx546) mutants is predominantly due to the Δ9 desaturase genes, additional transcriptional targets of DAF-16 are also involved. Surprisingly, survival of wild type adults following a rapid temperature decline is not dependent upon functional daf-16, and cellular distributions of a DAF-16::GFP fusion protein indicate that DAF-16 is not activated during low temperature stress. This suggests that cold-induced physiological defences are not specifically regulated by the IIS pathway and DAF-16, but expression of DAF-16 target genes in IIS mutants and dauers is sufficient to promote cross tolerance to low temperatures in addition to other forms of stress

Carrot or Stick? Modelling How Landowner Behavioural Responses Can Cause Incentive-Based Forest Governance to Backfire

Mitigating the negative impacts of declining worldwide forest cover remains a significant socio-ecological challenge, due to the dominant role of human decision-making. Here we use a Markov chain model of land-use dynamics to examine the impact of governance on forest cover in a region. Each land parcel can be either forested or barren (deforested), and landowners decide whether to deforest their parcel according to perceived value (utility). We focus on three governance strategies: yearly incentive for conservation, one-time penalty for deforestation and one-time incentive for reforestation. The incentive and penalty are incorporated into the expected utility of forested land, which decreases the net gain of deforestation. By analyzing the equilibrium and stability of the landscape dynamics, we observe four possible outcomes: a stationary-forested landscape, a stationary-deforested landscape, an unstable landscape fluctuating near the equilibrium, and a cyclic-forested landscape induced by synchronized deforestation. We find that the two incentive-based strategies often result in highly fluctuating forest cover over decadal time scales or longer, and in a few cases, reforestation incentives actually decrease the average forest cover. In contrast, a penalty for deforestation results in the stable persistence of forest cover (generally >30%). The idea that larger conservation incentives will always yield higher and more stable forest cover is not supported in our findings. The decision to deforest is influenced by more than a simple, “rational” cost-benefit analysis: social learning and myopic, stochastic decision-making also have important effects. We conclude that design of incentive programs may need to account for potential counter-productive long-term effects due to behavioural feedbacks

Pharmacotherapy of acute coronary syndromes: medical economics with an emphasis on clopidogrel

Acute coronary syndromes account worldwide for a significant burden of hospital- and societal costs. Pharmacotherapy of acute coronary syndromes consists of a combined antithrombotic therapy. Remarkable therapeutic advances have been made with the introduction of glycoprotein IIb/IIIa receptor inhibitors, low molecular weight heparins and thienopyridines, such as clopidogrel. Based on positive clinical data of large randomized trials numerous cost studies have been undertaken to analyse the cost-effectiveness of these new drugs. Most of them are showing an acceptable level of cost-effectiveness for the new treatments. Taking all available cost-studies into account, we conclude that new antithrombotic treatments are cost-effective as long as their use is limited to selected patient populations