Extraneuronal serotonin accumulation in peripheral arteries of the rat

Accumulations of serotonin (5-HT) and norepinephrine (NE) were compared in control and 6-hydroxydopamine (6-OHDA) pretreated rat aorta, mesenteric and tail arteries. The distribution of these amines was corrected by subtracting tissue uptake of tritiated sorbitol in the extracellular space. 5-HT greatly accumulated both in control and 6-OHDA pretreated arteries. In contrast, NE accumulation in mesenteric and tail arteries was substantially decreased after 6-OHDA treatment. In the aorta 6-OHDA pretreatment did not affect the accumulation of both amines. These findings suggest that 5-HT accumulation in these arteries is mainly extraneuronal, and NE mainly neuronal. Since the accumulation of 5-HT in the aorta was not influenced by pretreatment with 10 microM NE, the extraneuronal uptake mechanisms for 5-HT and NE appear to be different.     

Variety Membership Problem for Two Classes of Non-Finitely Based Semigroups

The variety membership problem for two classes of non-finitely based semigroups is considered. It is shown that a finite semigroup S belongs to the variety generated by one of these non-finitely based semigroups if and only if S satisfies four certain equations that involve at most 2│S│+1 distinct variables.     

The human pseudoautosomal GM-CSF receptor alpha subunit gene is autosomal in mouse.

The gene encoding the granulocyte macrophage colony stimulating factor receptor alpha subunit (CSF2RA) has previously been mapped to the pseudoautosomal region of the human sex chromosomes. In contrast, we report that the murine locus, Csf2ra, maps to an autosome in the laboratory mouse. By in situ hybridization and genetic mapping, Csf2ra maps at telomeric band D2 of mouse chromosome 19. This first instance of a pseudoautosomal locus in human being autosomal in mouse, indicates incomplete conservation between the human and mouse X chromosomes and suggests that the genetic content of the pseudoautosomal region may differ between species of eutherian mammals due to chromosomal rearrangements.     

Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes.

Marfan syndrome (MFS), one of the most common genetic disorders of connective tissue, is characterized by skeletal, cardiovascular and ocular abnormalities. The incidence of the disease is about 1 in 20,000, with life expectancy severely reduced because of cardiovascular complications. As the underlying defect is unknown, MFS diagnosis is based solely on clinical criteria. Certain phenotypic features of MFS are also shared by other conditions, which may be genetically distinct entities although part of a clinical continuum. Immunohistochemical studies have implicated fibrillin, a major component of elastin-associated microfibrils, in MFS aetiology. Genetic linkage analysis with random probes has independently localized the MFS locus to chromosome 15. Here we report that these two experimental approaches converge with the cloning and mapping of the fibrillin gene to chromosome 15q15-21, and with the establishment of linkage to MFS. We also isolated a second fibrillin gene and mapped it to chromosome 5q23-31. We linked this novel gene to a condition, congenital contractural arachnodactyly, that shares some of the features of MFS. Thus, the cosegregation of two related genes with two related syndromes implies that fibrillin mutations are likely to be responsible for different MFS phenotypes.     

Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A

Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1.     

PPARδ inhibits IL-1β-stimulated proliferation and migration of vascular smooth muscle cells via up-regulation of IL-1Ra

Activation of peroxisome proliferator-activated receptor (PPAR) δ by GW501516, a specific PPARδ ligand, significantly inhibited interleukin (IL)-1β-induced proliferation and migration of vascular smooth muscle cells (VSMCs). This effect of GW501516 was dependent on transforming growth factor-β, and was mediated through the up-regulation of IL-1 receptor antagonist. The inhibitory effect of GW501516 on VSMC proliferation was associated with cell cycle arrest at the G1 to S phase transition, which was accompanied by the induction of p21 and p53 along with decreased cyclin-dependent kinase 4 expression. Inhibition of cell migration by GW501516 was associated with the down-regulation of matrix metalloproteinase (MMP)-2 and MMP-9 in IL-1β-treated VSMCs. Inhibition of extracellular signal-regulated kinase significantly reduced the GW501516-mediated inhibition of IL-1β-stimulated VSMC proliferation. These results suggest that PPARδ plays an important role in the pathophysiology of diseases associated with the proliferation and migration of VSMCs.     

Using CAViaR Models with Implied Volatility for Value‐at‐Risk Estimation

This paper proposes value‐at risk (VaR) estimation methods that are a synthesis of conditional autoregressive value at risk (CAViaR) time series models and implied volatility. The appeal of this proposal is that it merges information from the historical time series and the different information supplied by the market's expectation of risk. Forecast‐combining methods, with weights estimated using quantile regression, are considered. We also investigate plugging implied volatility into the CAViaR models—a procedure that has not been considered in the VaR area so far. Results for daily index returns indicate that the newly proposed methods are comparable or superior to individual methods, such as the standard CAViaR models and quantiles constructed from implied volatility and the empirical distribution of standardised residuals. We find that the implied volatility has more explanatory power as the focus moves further out into the left tail of the conditional distribution of S&P 500 daily returns. Copyright © 2012 John Wiley & Sons, Ltd.