STAT3 Cooperates With Phospholipid Scramblase 2 to Suppress Type I Interferon Response

Type I interferon (IFN-I) is a pluripotent cytokine that modulates innate and adaptive immunity. We have previously shown that STAT3 suppresses IFN-I response in a manner dependent on its N-terminal domain (NTD), but independent of its DNA-binding and transactivation ability. Using the yeast two-hybrid system, we have identified phospholipid scramblase 2 (PLSCR2) as a STAT3 NTD-binding partner and a suppressor of IFN-I response. Overexpression of PLSCR2 attenuates ISRE-driven reporter activity, which is further aggravated by co-expression of STAT3. Moreover, PLSCR2 deficiency enhances IFN-I-induced gene expression and antiviral activity without affecting the activation or nuclear translocation of STAT1 and STAT2 or the assembly of ISGF3 complex. Instead, PLSCR2 impedes promoter occupancy by ISGF3, an effect further intensified by the presence of STAT3. Moreover, palmitoylation of PLSCR2 is required for its binding to STAT3 and for this suppressive activity. In addition to STAT3, PLSCR2 also interacts with STAT2, which facilitates the suppressive effect on ISGF3-mediated transcriptional activity. Together, these results define the role of a novel STAT3–PLSCR2 axis in fine-tuning IFN-I response

Signal Integration of IFN-I and IFN-II With TLR4 Involves Sequential Recruitment of STAT1-Complexes and NFkB to Enhance Pro-inflammatory Transcription

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Consistency of genetic inheritance mode and heritability patterns of triglyceride vs. high density lipoprotein cholesterol ratio in two Taiwanese family samples

BACKGROUND: Triglyceride/HDL cholesterol ratio (TG/HDL-C) is considered as a risk factor for cardiovascular events. Genetic components were important in controlling the variation in western countries. But the mode of inheritance and family aggregation patterns were still unknown among Asian-Pacific countries. This study, based on families recruited from community and hospital, is aimed to investigate the mode of inheritance, heritability and shared environmental factors in controlling TG/HDL-C. RESULTS: Two populations, one from community-based families (n = 988, 894 parent-offspring and 453 sibling pairs) and the other from hospital-based families (n = 1313, 76 parent-offspring and 52 sibling pairs) were sampled. The population in hospital-based families had higher mean age values than community-based families (54.7 vs. 34.0). Logarithmic transformed TG/ HDL-C values, after adjusted by age, gender and body mass index, were for genetic analyses. Significant parent-offspring and sibling correlations were also found in both samples. The parent-offspring correlation coefficient was higher in the hospital-based families than in the community-based families. Genetic heritability was higher in community-based families (0.338 ± 0.114, p = 0.002), but the common shared environmental factor was higher in hospital-based families (0.203 ± 0.042, p < 0.001). Commingling analyses showed that more than one-component distribution models were the best-fit models to explain the variance in both populations. Complex segregation analysis by regressive models revealed that in both samples the best-fit model of TG/HDL-C was the model of environmental effects plus familial correlation, in which significant parent-offspring and sibling correlations were demonstrated. Models of major gene effects were rejected in both samples. CONCLUSION: Variations of TG/HDL-C in the normal ranges were likely to be influenced by multiple factors, including environmental and genetic components. Higher genetic factors were proved in younger community-based families than in older hospital-based families

Simultaneous Penile Gangrene and Testicular Infarction Secondary to Calciphylaxis in a Uremic Patient

We report here a 46-year-old man with end stage renal disease (ESRD) secondary to type 2 diabetes, who had been on hemodialysis for 5 years. He had a painful glans lesion for 1 week. Five days later, he also complained of right testicular pain. Computed tomography of the pelvis demonstrated calcification of both penile arteries. Scrotal sonography revealed right testicular infarction. He received partial penectomy and right orchiectomy because of progressive lesions and intractable pain. Pathologic examination revealed testicular and penile tissue with necrotizing inflammation accompanied by multifocal calcification in the tunica media, compatible with calciphylaxis. This is the first report to document simultaneous penile gangrene and testicular infarction secondary to calciphylaxis

Prediction model for high glycated hemoglobin concentration among ethnic Chinese in Taiwan

<p>Abstract</p> <p>Background</p> <p>This study aimed to construct a prediction model to identify subjects with high glycated hemoglobin (HbA1c) levels by incorporating anthropometric, lifestyle, clinical, and biochemical information in a large cross-sectional ethnic Chinese population in Taiwan from a health checkup center.</p> <p>Methods</p> <p>The prediction model was derived from multivariate logistic regression, and we evaluated the performance of the model in identifying the cases with high HbA1c levels (> = 7.0%). In total 17,773 participants (age > = 30 years) were recruited and 323 participants (1.8%) had high HbA1c levels. The study population was divided randomly into two parts, with 80% as the derivation data and 20% as the validation data.</p> <p>Results</p> <p>The point-based clinical model, including age (maximal 8 points), sex (1 point), family history (3 points), body mass index (2 points), waist circumference (4 points), and systolic blood pressure (3 points) reached an area under the receiver operating characteristic curve (AUC) of 0.723 (95% confidence interval, 0.677- 0.769) in the validation data. Adding biochemical measures such as triglycerides and HDL cholesterol improved the prediction power (AUC, 0.770 [0.723 - 0.817], <it>P </it>= < 0.001 compared with the clinical model). A cutoff point of 7 had a sensitivity of 0.76 to 0.96 and a specificity of 0.39 to 0.63 for the prediction model.</p> <p>Conclusions</p> <p>A prediction model was constructed for the prevalent risk of high HbA1c, which could be useful in identifying high risk subjects for diabetes among ethnic Chinese in Taiwan.</p

The Effect of the Curvature-Rate on the Response of Local Sharp-Notched SUS304 Stainless Steel Tubes under Cyclic Bending

In this study, the response of local sharp-notched SUS304 stainless steel tubes with different notch depths of 0.2, 0.4, 0.6, 0.8 and 1.0 mm subjected to cyclic bending at different curvature-rates of 0.0035, 0.035 and 0.35 m-1s-1 were experimentally investigated. The tube bending machine and curvature-ovalization measurement apparatus, which was designed by Pan et al. [1], were used for conducting the curvature-controlled cyclic bending. For a constant curvature-rate, the moment-curvature curve revealed that the cyclic hardening and became a steady loop after a few bending cycles; the notch depth had almost no influence on the curves. Moreover, the ovalization-curvature curve increased in an increasing and ratcheting manner with the number of bending cycles. Large notch depths resulted in larger ovalization of the tube cross-section. In addition, for a constant notch depth, higher curvature-rates led to larger cyclic hardening and faster increasing of ovalization

Arbitrage, Covered Interest Parity and Cointegration Analysis on the NTD/USD Forex Market Revisited

This study applies interest parity theory including Covered Interest Parity (CIP) to examine the 30-, 60-.90-, and 180-day maturities for the NTD/USD foreign exchange (FX) market. In the empirical unit root tests, we find that NTD/USD forward premium and interest rate spread present I(0) property. Empirical results are provided that interest rate differential appears stationary component; imply the stable relationship between Taiwan and USA on monetary policy. Using Taylor (1989)'s covered interest arbitrage model, the empirical results exhibit the absence of excess profit opportunities on New Taiwan Dollar (NTD) or US Dollar (USD) returns. Additionally, theoretical innovation approach of the cost-of-carry model is considered to evaluate the arbitrage opportunities in FX study. Accordingly, the covered interest parity condition generally continue to hold that almost zero-arbitrage results support FX market efficiency although the Federal Reserve implemented several rounds of quantitative easing after the peak of the 2008 financial crisis. Ultimately, Taiwanese FX market emerges to have been little affected by the increased crisis risks during the turbulent times because of the its limited development and market integration. Keywords: Covered Interest Parity, Market Integration, Granger Causality Tests, Cost-of-Carry model JEL Classifications: G1, G12, F3