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Financial markets are central banks' gateway to the economy. After the global financial crisis and the Great Recession, the Federal Reserve came to the rescue of financial markets with an [...]

BACKGROUND: Adipocyte FABP4 (fatty acid-binding protein 4) is augmented in the epicardial stroma of patients with longstanding persistent atrial fibrillation. Because this molecule is released mainly by adipocytes, our objective was to study its role in atrial cardiomyopathy, focusing our attention on fibrosis, metabolism, and electrophysiological changes. These results might clarify the role of adiposity as a mediator of atrial cardiomyopathy. METHODS: We used several preclinical cellular models, epicardial and subcutaneous stroma primary cell cultures from patients undergoing open heart surgery, human atrial fibroblasts, atrial cardiomyocytes derived from human induced pluripotent stem cells and isolated from adult mice, and Nav1.5 transfected Chinese hamster ovary cells. Fibrosis, glucose, mitochondrial and adipogenesis activity, gene expression, and proteomics were determined by wound healing, enzymatic, colorimetric, fluorescence assays, real-time quantitative polymerase chain reaction, and TripleTOF proteomics. Molecular changes were analyzed by Raman confocal microspectroscopy, calcium dynamics by confocal microscopy, and ion currents by patch clamp. Epicardial, subcutaneous, and atrial fibroblasts and cardiomyocytes were incubated with FABP4 at 100 ng/mL. RESULTS: Our results showed that FABP4 induced fibrosis, glucose metabolism, and lipid accumulation on epicardial and subcutaneous stroma cells and atrial fibroblasts. Besides, it modified lipid content and calcium dynamics in atrial cardiomyocytes without effects on INa. CONCLUSIONS: FABP4 exerts fibrotic and metabolic changes on epicardial stroma and modifies lipid content and calcium dynamic on atrial cardiomyocytes. These results suggest its possible role as an atrial cardiomyopathy mediator. [ABSTRACT FROM AUTHOR]

A safe asset is a simple debt instrument that is expected to preserve its value during adverse systemic events. The supply of safe assets, private and public, has historically been concentrated in a small number of advanced economies, most prominently the United States. Over the last few decades, with minor cyclical interruptions, the supply of safe assets has not kept up with global demand. The reason is straightforward: the collective growth rate of the advanced economies that produce safe assets has been lower than the world's growth rate, which has been driven disproportionately by the high growth rate of high-saving emerging economies such as China. The signature of this growing shortage is a steady increase in the price of safe assets; equivalently, global safe interest rates must decline, as has been the case since the 1980s. The early literature, brought to light by Ben Bernanke's famous “savings glut” speech of 2005, focused on a general shortage of assets without isolating its safe asset component. The distinction, however, has become increasingly important over time, particularly in the aftermath of the subprime mortgage crisis and its sequels. We begin by describing the main facts and macroeconomic implications of safe asset shortages. Faced with such a structural conundrum, what are the likely short- to medium-term escape valves? We analyze four of them, each with its own macroeconomic and financial trade-offs.

The secular decline in safe interest rates since the early 1980s has been the subject of considerable attention. In this short paper, we argue that it is important to consider the evolution of safe real rates in conjunction with three other first-order macroeconomic stylized facts: the relative constancy of the real return to productive capital, the decline in the labor share, and the decline and subsequent stabilization of the earnings yield. Through the lens of a simple accounting framework, these four facts offer suggestive insights into the economic forces that might be at work.

In warm climates with high levels of solar irradiation, solar shading plays a determinant role on buildings' envelope performance, both during summer and winter conditions. In this research, an evaluation of the solar shading effect on sunny façades through IR thermography non-destructive testing was performed. Sunny and shaded areas revealed temperature differences of 7.4 °C in summer conditions and up to 1.2 °C in wintertime. Moreover, solar shading was shown to be beneficial not only for decreasing surface temperature in summertime but also for reducing convective air flow in wintertime. In addition, it was found that the prevalence of dense shadows, especially with non-reflective materials in louvres, is favorable. External Thermal Insulation Constructive Systems (ETICS) must be shadowed and the use of clear colors is recommended to reinforce homogeneity in the surface in wintertime and reduce solar absorptance in summertime. Under steady-state calculations, thermal losses can be reduced up to 30% at night in wintertime and up to 50–60% at daytime in summertime because of the shadowing. However, another important finding lied in the confirmation of the performance gap that arises between using air temperature, sol-air temperature and the actual surface temperature data, in such a way that the two former implied high levels of inaccuracy and overestimated the performance of the buildings compared to the actual behavior. Some of the main conclusions can be extrapolated to other circumstances. [ABSTRACT FROM AUTHOR]

We explore the consequences of safe asset scarcity on aggregate demand in a stylized IS-LM/Mundell Fleming style environment. Acute safe asset scarcity forces the economy into a “safety trap” recession. In the open economy, safe asset scarcity spreads from one country to the other via capital flows, equalizing interest rates. Acute global safe asset scarcity forces the economy into a global safety trap. The exchange rate becomes indeterminate but plays a crucial role in both the distribution and the magnitude of output adjustment across countries. Policies that increase the net supply of safe assets somewhere are output enhancing everywhere.

A novel rare mutation in the pore region of Nav1.5 channels (p.L889V) has been found in three unrelated Spanish families that produces quite diverse phenotypic manifestations (Brugada syndrome, conduction disease, dilated cardiomyopathy, sinus node dysfunction, etc.) with variable penetrance among families. We clinically characterized the carriers and recorded the Na+ current (INa) generated by p.L889V and native (WT) Nav1.5 channels, alone or in combination, to obtain further insight into the genotypic–phenotypic relationships in patients carrying SCN5A mutations and in the molecular determinants of the Nav1.5 channel function. The variant produced a strong dominant negative effect (DNE) since the peak INa generated by p.L889V channels expressed in Chinese hamster ovary cells, either alone (−69.4 ± 9.0 pA/pF) or in combination with WT (−62.2 ± 14.6 pA/pF), was significantly (n ≥ 17, p < 0.05) reduced compared to that generated by WT channels alone (−199.1 ± 44.1 pA/pF). The mutation shifted the voltage dependence of channel activation and inactivation to depolarized potentials, did not modify the density of the late component of INa, slightly decreased the peak window current, accelerated the recovery from fast and slow inactivation, and slowed the induction kinetics of slow inactivation, decreasing the fraction of channels entering this inactivated state. The membrane expression of p.L889V channels was low, and in silico molecular experiments demonstrated profound alterations in the disposition of the pore region of the mutated channels. Despite the mutation producing a marked DNE and reduction in the INa and being located in a critical domain of the channel, its penetrance and expressivity are quite variable among the carriers. Our results reinforce the argument that the incomplete penetrance and phenotypic variability of SCN5A loss-of-function mutations are the result of a combination of multiple factors, making it difficult to predict their expressivity in the carriers despite the combination of clinical, genetic, and functional studies. [ABSTRACT FROM AUTHOR]