Atorvastatin Improves Plaque Stability in ApoE-Knockout Mice by Regulating Chemokines and Chemokine Receptors

It is well documented that statins protect atherosclerotic patients from inflammatory changes and plaque instability in coronary arteries. However, the underlying mechanisms are not fully understood. Using a previously established mouse model for vulnerable atherosclerotic plaque, we investigated the effect of atorvastatin (10 mg/kg/day) on plaque morphology. Atorvastatin did not lower plasma total cholesterol levels or affect plaque progression at this dosage; however, vulnerable plaque numbers were significantly reduced in the atorvastatin-treated group compared to control. Detailed examinations revealed that atorvastatin significantly decreased macrophage infiltration and subendothelial lipid deposition, reduced intimal collagen content, and elevated collagenase activity and expression of matrix metalloproteinases (MMPs). Because vascular inflammation is largely driven by changes in monocyte/macrophage numbers in the vessel wall, we speculated that the anti-inflammatory effect of atorvastatin may partially result from decreased monocyte recruitment to the endothelium. Further experiments showed that atorvastatin downregulated expression of the chemokines monocyte chemoattractant protein (MCP)-1, chemokine (C-X3-C motif) ligand 1 (CX3CL1) and their receptors CCR2 and, CX3CR1, which are mainly responsible for monocyte recruitment. In addition, levels of the plasma inflammatory markers C-reactive protein (CRP) and tumor necrosis factor (TNF)-α were also significantly decrease in atorvastatin-treated mice. Collectively, our results demonstrate that atorvastatin can improve plaque stability in mice independent of plasma cholesterol levels. Given the profound inhibition of macrophage infiltration into atherosclerotic plaques, we propose that statins may partly exert protective effects by modulating levels of chemokines and their receptors. These findings elucidate yet another atheroprotective mechanism of statins.     

猪血超氧化物歧化酶分离纯化工艺改进及其抗氧化活性研究

以新鲜猪血为原料,首次利用改进的新工艺提取分离超氧化物歧化酶,经过溶血,热变,丙酮沉淀,超滤浓缩,SephadexG-75凝胶过滤层析和DEAE-sepharose-fast flow离子交换层析纯化,冷冻干燥等步骤,得到高纯度酶,并对酶的相关性能进行研究。试验结果显示产品粗酶活性在3 000 U/mg左右,分别经SephadexG-75和DEAE-sepharose-fast flow层析纯化后,酶活分别达到5 585 U/mg和6 148 U/mg产品得率分别为13.4%和10.32%,SDS-PAGE凝胶电泳显示为单一条带达到电泳纯,其分子量在31 kD附近,其临苯三酚抗氧化活性明显。     

Weighted change-point method for detecting differential gene expression in breast cancer microarray data

In previous work, we proposed a method for detecting differential gene expression based on change-point of expression profile. This non-parametric change-point method gave promising result in both simulation study and public dataset experiment. However, the performance is still limited by the less sensitiveness to the right bound and the statistical significance of the statistics has not been fully explored. To overcome the insensitiveness to the right bound we modified the original method by adding a weight function to the D(n) statistic. Simulation study showed that the weighted change-point statistics method is significantly better than the original NPCPS in terms of ROC, false positive rate, as well as change-point estimate. The mean absolute error of the estimated change-point by weighted change-point method was 0.03, reduced by more than 50% comparing with the original 0.06, and the mean FPR was reduced by more than 55%. Experiment on microarray Dataset I resulted in 3974 differentially expressed genes out of total 5293 genes; experiment on microarray Dataset II resulted in 9983 differentially expressed genes among total 12576 genes. In summary, the method proposed here is an effective modification to the previous method especially when only a small subset of cancer samples has DGE.     

Interaction sites between the Slo1 pore and the NH2 terminus of the beta2 subunit, probed with a three-residue sensor

Calcium- and voltage-gated (BK) K(+) channels encoded by Slo1 play an essential role in nervous systems. Although it shares many common features with voltage-dependent K(V) channels, the BK channel exhibits differences in gating and inactivation. Using a mutant in which FWI replaces three residues (FIW) in the NH(2) terminus of wild-type beta2-subunits, in conjunction with alanine-scanning mutagenesis of the Slo1 S6 segment, we identify that the NH(2) terminus of beta2-subunits interacts with the residues near the cytosolic superficial mouth of BK channels during inactivation. The cytosolic blockers did not share the sites with NH(2) terminus of beta2-subunits. A novel blocking-inactivating scheme was proposed to account for the observed non-competition inactivation. Our results also suggest that the residue Ile-323 plays a dual role in interacting with the NH(2) terminus of beta2-subunits and modulating the gating of BK channels.     

Development of microsatellite markers and construction of genetic map in rice blast pathogen Magnaporthe grisea

Magnaporthe grisea is the most destructive fungal pathogen of rice and a model organism for studying plant-pathogen interaction. Molecular markers and genetic maps are useful tools for genetic studies. In this study, based on the released genome sequence data of M. grisea, we investigated 446 simple sequence repeat (SSR) loci and developed 313 SSR markers, which showed polymorphisms among nine isolates from rice (including a laboratory strain 2539). The number of alleles of each marker ranged 2-9 with an average of 3.3. The polymorphic information content (PIC) of each marker ranged 0.20-0.89 with an average of 0.53. Using a population derived from a cross between isolates Guy11 and 2539, we constructed a genetic map of M. grisea consisting of 176 SSR markers. The map covers a total length of 1247 cM, equivalent to a physical length of about 35.0 Mb or 93% of the genome, with an average distance of 7.1cM between adjacent markers. A web-based database of the SSR markers and the genetic map was established (http://ibi.zju.edu.cn/pgl/MGM/index.html).     

Expression Profile and Function Analysis of Long Non-coding RNAs in the Infection of Coxsackievirus B3

The roles of lnc RNAs in the infection of enteroviruses have been barely demonstrated. In this study, we used coxsackievirus B3(CVB3), a typical enterovirus, as a model to investigate the expression profiles and functional roles of lnc RNAs in enterovirus infection. We profiled lnc RNAs and m RNA expression in CVB3-infected He La cells by lnc RNA-m RNA integrated microarrays. As a result, 700 differentially expressed lnc RNAs(431 up-regulated and 269 down-regulated) and665 differentially expressed m RNAs(299 up-regulated and 366 down-regulated) were identified in CVB3 infection. Then we performed lnc RNA-m RNA integrated pathway analysis to identify potential functional impacts of the differentially expressed m RNAs, in which lnc RNA-m RNA correlation network was built. According to lnc RNA-m RNA correlation, we found that XLOC-001188, an lnc RNA down-regulated in CVB3 infection, was negatively correlated with NFAT5 m RNA,an anti-CVB3 gene reported previously. This interaction was supported by q PCR detection following si RNA-mediated knockdown of XLOC-001188, which showed an increase of NFAT5 m RNA and a reduction of CVB3 genomic RNA. In addition, we observed that four most significantly altered lnc RNAs, SNHG11, RP11-145 F16.2, RP11-1023 L17.1 and RP11-1021 N1.2 share several common correlated genes critical for CVB3 infection, such as BRE and IRF2 BP1. In all, our studies reveal the alteration of lnc RNA expression in CVB3 infection and its potential influence on CVB3 replication,providing useful information for future studies of enterovirus infection.