A Chemokine Targets the Nucleus: Cxcl12-Gamma Isoform Localizes to the Nucleolus in Adult Mouse Heart

Chemokines are extracellular mediators of complex regulatory circuits involved principally in cell-to-cell communication. Most studies to date of the essential chemokine Cxcl12 (Sdf-1) have focused on the ubiquitously expressed secreted isoforms α and β. Here we show that, unlike these isoforms and all other known chemokines, the alternatively transcribed γ isoform is an intracellular protein that localizes to the nucleolus in differentiated mouse Cardiac tissue. Our results demonstrate that nucleolar transportation is encoded by a nucleolar-localization signal in the unique carboxy-terminal region of Sdf-1γ, and is competent both in vivo and in vitro. The molecular mechanism underlying these unusual chemokine properties involves cardiac-specific transcription of an mRNA containing a unique short-leader sequence lacking the signal peptide and translation from a non-canonical CUG codon. Our results provide an example of genome economy even for essential and highly conserved genes such as Cxcl12, and suggest that chemokines can exert tissue specific functions unrelated to cell-to-cell communication

CREB3 subfamily transcription factors are not created equal: Recent insights from global analyses and animal models

<p>Abstract</p> <p>The CREB3 subfamily of membrane-bound bZIP transcription factors has five members in mammals known as CREB3 and CREB3L1-L4. One current model suggests that CREB3 subfamily transcription factors are similar to ATF6 in regulated intramembrane proteolysis and transcriptional activation. Particularly, they were all thought to be proteolytically activated in response to endoplasmic reticulum (ER) stress to stimulate genes that are involved in unfolded protein response (UPR). Although the physiological inducers of their proteolytic activation remain to be identified, recent findings from microarray analyses, RNAi screens and gene knockouts not only demonstrated their critical roles in regulating development, metabolism, secretion, survival and tumorigenesis, but also revealed cell type-specific patterns in the activation of their target genes. Members of the CREB3 subfamily show differential activity despite their structural similarity. The spectrum of their biological function expands beyond ER stress and UPR. Further analyses are required to elucidate the mechanism of their proteolytic activation and the molecular basis of their target recognition.</p

Bridging Role Of Absorptive Capacity For Knowledge Management Systems Success

This paper aims to gain a better understanding of KMS success. Based on the absorptive capacity theory, we develop a research model to explain how the use of KMS increases organizational performance by increasing the organizational absorptive capacity and the higher order capabilities. The absorptive capacity plays an important role in transforming KMS usage into agility and innovativeness and the sequent organizational performance. The model is empirically tested with a survey. The results support the mediation effect of absorptive capacity on the use of KMS and the two higher order organizational capabilities, the mediation effects of the two superior organizational capabilities on the relationship between KMS usage and organizational performance and the mediation effect on the link between absorptive capacity and performance

Comparable Analysis of Long-term Memory of EUR/USD Based on Non-parametrical Statistics

Non-parameter statistical methods of classical R/S, revised R/S and V/S was proposed in long-term Memory of EUR/USD. It was concluded through comparable analysis that: (1) Through Normality Test of Return Sequences of EUR/USD Daily Closing Prices, the experimental results imply that bias of daily return sequences of EUR/USD is not equal to zero, and the curve appears to high peak and fat tail. (2) Jarque-Bera test is adopted. The estimated values reject the null hypothesis of normal distribution. (3) The paper estimates daily return series of EUR/USD using classical R/S method. The results show that Hurst exponent is equal to 0.612425; the statistical cycle is 160 days; the correlative scale is close to 1.3432. This study's conclusion was that long-term memory exists in daily return time series of EUR/USD is proved.Key words: rescaled range (R/S) analysis; rescaled variance (V/S) analysis; long-term memor

Hepatitis B Virus X Protein Impairs Hepatic Insulin Signaling Through Degradation of IRS1 and Induction of SOCS3

Hepatitis B virus (HBV) is a major cause of chronic liver diseases, and frequently results in hepatitis, cirrhosis, and ultimately hepatocellular carcinoma. The role of HCV in associations with insulin signaling has been elucidated. However, the pathogenesis of HBV-associated insulin signaling remains to be clearly characterized. Therefore, we have attempted to determine the mechanisms underlying the HBV-associated impairment of insulin signaling.The expressions of insulin signaling components were investigated in HBx-transgenic mice, HBx-constitutive expressing cells, and transiently HBx-transfected cells. Protein and gene expression was examined by Western blot, immunohistochemistry, RT-PCR, and promoter assay. Protein-protein interaction was detected by coimmunoprecipitation.HBx induced a reduction in the expression of IRS1, and a potent proteasomal inhibitor blocked the downregulation of IRS1. Additionally, HBx enhanced the expression of SOCS3 and induced IRS1 ubiquitination. Also, C/EBPalpha and STAT3 were involved in the HBx-induced expression of SOCS3. HBx interfered with insulin signaling activation and recovered the insulin-mediated downregulation of gluconeogenic genes.These results provide direct experimental evidences for the contribution of HBx in the impairment of insulin signaling