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Depression has been linked with seasonal affective disorder (SAD), a condition that affects many people during the seasons of relatively fewer hours of daylight. Experimental research in psychology has documented a clear link between depression and lowered risktaking behavior in a wide range of settings, including those of a nancial nature. Through the links between SAD and depression and between depression and risk aversion, seasonal variation in length of day can translate into seasonal variation in equity returns. Based on supportive evidence from psychology which suggests SAD is linked closely with hours of daylight, we consider stock market index data from countries at various latitudes and on both sides of the equator. We model differences in the seasonal variation of daylight across countries to capture the in uence of daylight on human sentiment, risk tolerance, and hence stock returns. Our results strongly support a SAD effect in the seasonal cycle of stock returns that is both signi cant and substantial, even after controlling for well-known market seasonals and other environmental factors. Patterns at different latitudes and in both hemispheres provide compelling evidence of a link between seasonal depression and seasonal variation in stock returns: higher-latitude markets show more pronounced SAD effects and results in the Southern Hemisphere are six months out of phase, as are the seasons.The remainder of the paper is organized as follows. In Section I, we discuss SAD, depression, and equilibrium market returns. In Section II, we introduce the international data sets. In Section III, we explain the construction of the variables intended to capture the in uence of SAD on the stock market. We document in Section IV the signi cance of the SAD effect, both statistical and economic, and provide an example of the excess returns that arise from trading strategies based on the SAD effect. In Section V, we explore the robustness of the SAD effect to changes in variable de nitions and estimation methods. Section VI considers SAD in the context of segmented versus integrated capital markets. Section VII concludes.

Upon stimulation with Th1 cytokines or bacterial lipopolysaccharides, resting macrophages shift their phenotype toward a pro-inflammatory state as part of the innate immune response. LPS-activated macrophages undergo profound metabolic changes to adapt to these new physiological requirements. One key step to mediate this metabolic adaptation is the stabilization of HIF1α, which leads to increased glycolysis and lactate release, as well as decreased oxygen consumption. HIF1 abundance can result in the induction of the gene encoding pyruvate dehydrogenase kinase 1 (PDK1), which inhibits pyruvate dehydrogenase (PDH) via phosphorylation. Therefore, it has been speculated that pyruvate oxidation through PDH is decreased in pro-inflammatory macrophages. However, to answer this open question, an in-depth analysis of this metabolic branching point was so far lacking. In this work, we applied stable isotope-assisted metabolomics techniques and demonstrate that pyruvate oxidation is maintained in mature pro-inflammatory macrophages. Glucose-derived pyruvate is oxidized via PDH to generate citrate in the mitochondria. Citrate is used for the synthesis of the antimicrobial metabolite itaconate and for lipogenesis. An increased demand for these metabolites decreases citrate oxidation through the tricarboxylic acid cycle, whereas increased glutamine uptake serves to replenish the TCA cycle. Furthermore, we found that the PDH flux is maintained by unchanged PDK1 abundance, despite the presence of HIF1. By pharmacological intervention, we demonstrate that the PDH flux is an important node for M(LPS) macrophage activation. Therefore, PDH represents a metabolic intervention point that might become a research target for translational medicine to treat chronic inflammatory diseases.

(2002) revisits the issue of daylight-saving-time changes impacting nan

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The signaling impact of a human beta1-adrenergic receptor (beta1 AR) polymorphism at residue 49 of the aminoterminus (Ser-to-Gly substitution) was studied by recombinantly expressing each receptor. The two receptors displayed identical agonist and antagonist binding affinities. Furthermore, basal and agonist-stimulated adenylyl cyclase activities were the same for these receptors as assessed in both cell types. Although short-term agonist exposure resulted in similar degrees of receptor internalization, long-term agonist-promoted downregulation was greater for Gly49 compared with Ser49. The Gly49 receptor underwent a 24 +/- 3% loss of receptor density after exposure to isoproterenol for 18 h, whereas Ser49 underwent no such loss. In studies in which receptor synthesis was inhibited, agonist-promoted downregulation for Gly49 was 55 +/- 3% compared with 36 +/- 5% for Ser49. In the absence of agonist, degradative turnover of each receptor was the same. Immunoblotting revealed that some of the Ser49 receptor exists as a highly N-glycosylated form (approximately 105-kD molecular mass), which is not present with Gly49. Thus the phenotype of the Gly49 polymorphic receptor is that of wild-type coupling with enhanced agonist-promoted downregulation, which is associated with altered N-glycosylation. Based on this cellular phenotype, the beta1 AR Gly49 polymorphism may impart a beneficial effect in chronic heart failure.

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