We employ a structural global VAR model to analyze whether U.S. unconventional monetary policy shocks, identified through changes in the central bank’s balance sheet, have an impact on financial and ...economic conditions in emerging market economies (EMEs). Moreover, we study whether international capital flows are an important channel of shock transmission. We find that an expansionary policy shock significantly increases portfolio flows from the U.S. to EMEs for almost two quarters, accompanied by a persistent movement in real and financial variables in recipient countries. Moreover, EMEs on average respond to the shock with an easing of their own monetary policy stance. The findings appear to be independent of heterogeneous country characteristics like the underlying exchange rate arrangement, the quality of institutions, or the degree of financial openness.
Documenting an average drop of the labor share of eight percentage points for eight European countries and the US between 1980 and 2007, we analyze the role of technological progress and labor market ...frictions. According to our results, while capital-labor substitution in general was not crucial, Information Communication Technology (ICT) explains more than half of the decline in the labor share, given an estimated elasticity of substitution with the labor input of 1.18. Considering hiring costs slightly dampens the estimated substitution effect at aggregate level. Additionally, by modeling the substitution between ICT and labor with a set of key labor market variables, we find it to be linked to both the share of routine occupations (positively) and the share of high-skill workers (negatively) with a similar strength.
•Persistent drop of the global labor share between 1980 and 2007.•Substitution between computer technologies and labor is the key driver, no role for general capital-labor elasticity.•Search frictions play a minor role in capital-labor competition.•ICT-labor substitution is connected to both the share of routine occupations and the share of high-skill workers.•Labor market institutions matter for the elasticity and dampen the ICT-labor substitution.
This paper investigates whether German or synthetic European pre-EMU data provides the appropriate empirical basis for evaluating Euro/Dollar exchange rate behavior. Monetary exchange rate equations ...are estimated for both data sets over the pre-EMU period, and out-of-sample forecasts are evaluated to assess their ability to explain the Euro/Dollar exchange rate from 1999 to 2004. While forecast accuracy tests confirm the usefulness of synthetic European data for Euro exchange rate analysis, forecasts based on the German pre-EMU experience cannot even beat a random walk. Our results indicate that the Euro does not simply follow the German Mark, but that it has its origins in the other pre-EMU currencies as well.
The European overnight rate (Eonia) is the operational target of the European Central Bank (ECB) that signals the monetary policy stance and anchors the term structure of interest rates. This paper ...empirically investigates the transmission of Eonia volatility to longer term money market rates. Distinguishing between seasonal Eonia volatility due to, e.g., calendar effects and non-seasonal volatility which may be closer related to uncertainty about the policy intentions of the ECB reveals a significant volatility transmission even for the twelve-month rate. We also examine how the ECB’s new operational framework introduced in March 2004 has influenced the Eonia and the transmission of volatility along the yield curve.
RATIONALE:Activated cardiac fibroblasts (CF) are crucial players in the cardiac damage response; excess fibrosis, however, may result in myocardial stiffening and heart failure development. ...Inhibition of activated CF has been suggested as a therapeutic strategy in cardiac disease, but whether this truly improves cardiac function is unclear.
OBJECTIVE:To study the effect of CF ablation on cardiac remodeling.
METHODS AND RESULTS:We characterized subgroups of murine CF by single-cell expression analysis and identified periostin as the marker showing the highest correlation to an activated CF phenotype. We generated bacterial artificial chromosome–transgenic mice allowing tamoxifen-inducible Cre expression in periostin-positive cells as well as their diphtheria toxin-mediated ablation. In the healthy heart, periostin expression was restricted to valvular fibroblasts; ablation of this population did not affect cardiac function. After chronic angiotensin II exposure, ablation of activated CF resulted in significantly reduced cardiac fibrosis and improved cardiac function. After myocardial infarction, ablation of periostin-expressing CF resulted in reduced fibrosis without compromising scar stability, and cardiac function was significantly improved. Single-cell transcriptional analysis revealed reduced CF activation but increased expression of prohypertrophic factors in cardiac macrophages and cardiomyocytes, resulting in localized cardiomyocyte hypertrophy.
CONCLUSIONS:Modulation of the activated CF population is a promising approach to prevent adverse cardiac remodeling in response to angiotensin II and after myocardial infarction.
Nicotinic acid (niacin), a vitamin of the B complex, has been used for almost 50 years as a lipid-lowering drug. The pharmacological effect of nicotinic acid requires doses that are much higher than ...those provided by a normal diet. Its primary action is to decrease lipolysis in adipose tissue by inhibiting hormone-sensitive triglyceride lipase. This anti-lipolytic effect of nicotinic acid involves the inhibition of cyclic adenosine monophosphate (cAMP) accumulation in adipose tissue through a G(i)-protein-mediated inhibition of adenylyl cyclase. A G-protein-coupled receptor for nicotinic acid has been proposed in adipocytes. Here, we show that the orphan G-protein-coupled receptor, 'protein upregulated in macrophages by interferon-gamma' (mouse PUMA-G, human HM74), is highly expressed in adipose tissue and is a nicotinic acid receptor. Binding of nicotinic acid to PUMA-G or HM74 results in a G(i)-mediated decrease in cAMP levels. In mice lacking PUMA-G, the nicotinic acid-induced decrease in free fatty acid (FFA) and triglyceride plasma levels was abrogated, indicating that PUMA-G mediates the anti-lipolytic and lipid-lowering effects of nicotinic acid in vivo. The identification of the nicotinic acid receptor may be useful in the development of new drugs to treat dyslipidemia.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
An early step in pancreas development is marked by the expression of the transcription factor Pdx1 within the pancreatic endoderm, where it is required for the specification of all endocrine cell ...types. Subsequently, Pdx1 expression becomes restricted to the β-cell lineage, where it plays a central role in β-cell function. This pivotal role of Pdx1 at various stages of pancreas development makes it an attractive target to enhance pancreatic β-cell differentiation and increase β-cell function. In this study, we used a newly generated zebrafish reporter to screen over 8000 small molecules for modulators of
expression. We found four hit compounds and validated their efficacy at different stages of pancreas development. Notably, valproic acid treatment increased pancreatic endoderm formation, while inhibition of TGFβ signaling led to α-cell to β-cell transdifferentiation. HC toxin, another HDAC inhibitor, enhances β-cell function in primary mouse and human islets. Thus, using a whole organism screening strategy, this study identified new
expression modulators that can be used to influence different steps in pancreas and β-cell development.
Lysophosphatidylinositol (LPI) is a novel regulator of peripheral sensory neuron function and pathological pain. The roles of GPCR and non-GPCR components to the biological function of LPI are ...delineated.
The rich diversity of lipids and the specific signalling pathways they recruit provides tremendous scope for modulation of biological functions. Lysophosphatidylinositol (LPI) is emerging as a key modulator of cell proliferation, migration, and function, and holds important pathophysiological implications due to its high levels in diseased tissues, such as in cancer. Here we report a novel role for LPI in sensitization of peripheral sensory neurons, which was evident as exaggerated sensitivity to painful and innocuous pressure. Histopathological analyses indicated lack of involvement of myelin pathology and immune cell recruitment by LPI. Using pharmacological and conditional genetic tools in mice, we delineated receptor-mediated from non-receptor-mediated effects of LPI and we observed that GPR55, which functions as an LPI receptor when heterologously expressed in mammalian cells, only partially mediates LPI-induced actions in the context of pain sensitization in vivo; we demonstrate that, in vivo, LPI functions by activating Gα13 as well as Gαq/11 arms of G-protein signalling in sensory neurons. This study thus reports a novel pathophysiological function for LPI and elucidates underlying molecular mechanisms.
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