Structure insights into mechanisms of ATP hydrolysis and the activation of human heat-shock protein 90

The activation of molecular chaperone heat-shock protein 90 (Hsp90) is dependent on ATP binding and hydrolysis, which occurs in the N-terminal domains of protein. Here, we have determined three crystal structures of the N-terminal domain of human Hsp90 in native and in complex with ATP and ATP analog, providing a clear view of the catalytic mechanism of ATP hydrolysis by Hsp90. Additionally, the binding of ATP leads the N-terminal domains to be an intermediate state that could be used to partially explain why the isolated N-terminal domain of Hsp90 has very weak ATP hydrolytic activity.     

Bio-Plex悬浮芯片系统检测两种实验兔白介素基因的差异表达

目的采用液相悬浮芯片系统同时测定实验兔圆小囊中IL-1β、IL-1R1、IL=8、IL-8RA和IL=15各基因的表达情况,并对该方法进行评价。方法利用Affymetrix的Panomics QuantiGene Plex2．0Assay中bDNA信号放大和多磁珠分析技术,来同时检测两种实验兔圆小囊中多重mRNA并定量。建立实验兔免疫相关白介素基因的液相悬浮芯片检测方法。结果可同时检测IL-1β、IL=1R1、IL-8、IL=8RA和IL-15各基因的含量,并发现WHBE兔IL-15基因的相对表达量显著高于JW兔（P〈0．05）,IL-1R1基因的相对表达量显著高于JW兔（P〈0．01）,IL-8RA基因在WHBE兔中的相对表达量也高于JW兔（P〈0．05）。结论建立了实验兔白介素基因的液相悬浮芯片检测方法,WHBE兔的IL-15、IL-1R1和IL-8RA基因表达量较高,可能与WHBE兔独特的免疫学特性有关。     

Immobilization of cellulases on the reversibly soluble polymer Eudragit S‐100 for cotton treatment

Cellulases can penetrate into the fiber, causing tensile strength loss of the cellulosic fibers or fabrics. To minimize the tensile strength loss, we have immobilized cellulases on Eudragit S‐100. The characteristics of covalent Eudragit cellulase were evaluated using gel filtration analysis and UV spectra. Gel filtration analysis revealed that the cellulases were covalently bound to the polymer. Covalent Eudragit cellulase was loaded with the enzyme of about 40% and had a relative activity about 80% at a Eudragit S‐100 concentration of 15 g/L. When cellulase is bound to the polymer, the solubility profile becomes similar to the one of Eudragit. In addition, the effects of the enzyme on the cotton yarns and fabric using cellulases have been investigated. Native and immobilized cellulases caused improvements in whiteness and wrinkle recovery angle of the fabric in comparison to the control samples. The bending stiffness results show that native and immobilized cellulase treated cotton fabric has an improved softness than the control samples. It was found that using the immobilized cellulase reduced the weight and tensile strength, because the hydrolytic attack is only limited to the surfaces of cotton fibers.     

东亚似鮈类鱼类的起源和演化

本文采用分支扩散法和分支离散法两种生物地理学方法分析了似　类的起源和演化。结果说明似类于第三纪末起源于中国北方的原始类,逐步向南扩散。在其物种分化过程中可能存在南北两个分化中心。     

河南鲤科鱼类脑的形态学研究(Ⅱ)

本文就河南省10个亚科13种鲤科鱼类脑的显微结构作了观察,并就栖息于不同水层的鱼类作了比较。端脑的最外层是一层没有神经细胞的原脑皮,纹状体成为端脑本部的主要组成部分。鱼类脑的形态学构造与其生活环境、捕食习性等具有一定的相关性。     

Chaperone-Like Activity of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> Hsp16.3 Does Not Require Its Intact (Native) Structures

Small heat shock proteins (sHsps) were found to exhibit efficient chaperone-like activities under stress conditions although their native structures are severely disturbed. Here, using an alternative approach (site-directed mutagenesis), we obtained two structurally and functionally distinct Mycobacterium tuberculosis Hsp16.3 single-site mutant proteins. The G59W mutant protein (with Gly59 substituted by Trp) is capable of exhibiting efficient chaperone-like activity even under non-stress conditions although its secondary, tertiary, and quaternary structures are very different from that of the wild type protein. By contrast, the G59A mutant protein (with Gly59 substituted by Ala) resembles with the wild type protein in structure and function. These observations suggest that the Gly59 of the Hsp16.3 protein is critical for its folding and assembly. In particular, we propose that the exhibition of chaperone-like activity for Hsp16.3 does not require its intact (native) structures but requires the disturbance of its native structures (i.e., the native structure-disturbed Hsp16.3 retains its chaperone-like activity or even becomes more active). In addition, the behavior of such an active mutant protein (G59W) also strongly supports our previous suggestion that Hsp16.3 exhibits chaperone-like activity via oligomeric dissociation.     

Rapamycin Augments Immunomodulatory Properties of Bone Marrow-Derived Mesenchymal Stem Cells in Experimental Autoimmune Encephalomyelitis

The immunomodulatory and anti-inflammatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) have been considered as an appropriate candidate for treatment of autoimmune diseases. Previous studies have revealed that treatment with BM-MSCs may modulate immune responses and alleviate the symptoms in experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis. Therefore, the present study was designed to examine immunomodulatory effects of BM-MSCs in the treatment of myelin oligodendrocyte glycoprotein (MOG) 35-55-induced EAE in C57BL/6 mice. MSCs were obtained from the bone marrow of C57BL mice, cultured with DMEM/F12, and characterized with flow cytometry for the presence of cell surface markers for BM-MSCs. Following three passages, BM-MSCs were injected intraperitoneally into EAE mice alone or in combination with rapamycin. Immunological and histopathological effects of BM-MSCs and addition of rapamycin to BM-MSCs were evaluated. The results demonstrated that adding rapamycin to BM-MSCs transplantation in EAE mice significantly reduced inflammation infiltration and demyelination, enhanced the immunomodulatory functions, and inhibited progress of neurological impairments compared to BM-MSC transplantation and control groups. The immunological effects of rapamycin and BM-MSC treatments were associated with the inhibition of the Ag-specific lymphocyte proliferation, CD8+ cytolytic activity, and the Th1-type cytokine (gamma-interferon (IFN-γ)) and the increase of Th-2 cytokine (interleukin-4 (IL-4) and IL-10) production. Addition of rapamycin to BM-MSCs was able to ameliorate neurological deficits and provide neuroprotective effects in EAE. This suggests the potential of rapamycin and BM-MSC combined therapy to play neuroprotective roles in the treatment of neuroinflammatory disorders.     

Salusin-α attenuates inflammatory responses in vascular endothelial cells

Atherosclerosis accounts for numerous cardiovascular diseases, and cytokines have a critical role in acceleration or suppression of disease. Salusin-α presents a new class of bioactive peptides that can have anti-atherogenic properties. Therefore, the effects of salusin-α on the expression of some pro- and anti-inflammatory cytokines and on TNF-α-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs) were examined. The involvement of the NF-κB pathway in effects of salusin-α in HUVECs was checked using Bay 11-7082 as an NF-κB inhibitor. The mRNA expression of pro-inflammatory cytokines including IL-6, IL-8, and IL-18 and anti-inflammatory cytokine IL-1Ra was assessed by real-time PCR. The protein levels of cytokines were measured by the ELISA method. Salusin-α suppressed both mRNA and protein expression of pro-inflammatory cytokines and induced mRNA and protein expression of IL-1Ra in HUVECs. Salusin-α suppressed TNF-α-induced inflammatory responses in HUVECs. The down-regulatory or up-regulatory effects of salusin-α on expression of cytokines could not be influenced by Bay 11-7082 pretreatment. Our findings indicate anti-inflammatory effects of salusin-α and suggest a novel peptide-based therapeutic strategy for atherosclerosis.     

Methylated DNA/RNA in Body Fluids as Biomarkers for Lung Cancer

DNA/RNA methylation plays an important role in lung cancer initiation and progression. Liquid biopsy makes use of cells, nucleotides and proteins released from tumor cells into body fluids to help with cancer diagnosis and prognosis. Methylation of circulating tumor DNA (ctDNA) has gained increasing attention as biomarkers for lung cancer. Here we briefly introduce the biological basis and detection method of ctDNA methylation, and review various applications of methylated DNA in body fluids in lung cancer screening, diagnosis, prognosis, monitoring and treatment prediction. We also discuss the emerging role of RNA methylation as biomarkers for cancer.     

Laplacian normalization and bi-random walks on heterogeneous networks for predicting lncRNA-disease associations

Background

Evidences have increasingly indicated that lncRNAs (long non-coding RNAs) are deeply involved in important biological regulation processes leading to various human complex diseases. Experimental investigations of these disease associated lncRNAs are slow with high costs. Computational methods to infer potential associations between lncRNAs and diseases have become an effective prior-pinpointing approach to the experimental verification.

Results

In this study, we develop a novel method for the prediction of lncRNA-disease associations using bi-random walks on a network merging the similarities of lncRNAs and diseases. Particularly, this method applies a Laplacian technique to normalize the lncRNA similarity matrix and the disease similarity matrix before the construction of the lncRNA similarity network and disease similarity network. The two networks are then connected via existing lncRNA-disease associations. After that, bi-random walks are applied on the heterogeneous network to predict the potential associations between the lncRNAs and the diseases. Experimental results demonstrate that the performance of our method is highly comparable to or better than the state-of-the-art methods for predicting lncRNA-disease associations. Our analyses on three cancer data sets (breast cancer, lung cancer, and liver cancer) also indicate the usefulness of our method in practical applications.

Conclusions

Our proposed method, including the construction of the lncRNA similarity network and disease similarity network and the bi-random walks algorithm on the heterogeneous network, could be used for prediction of potential associations between the lncRNAs and the diseases.