Discovery of intramolecular signal transduction network based on a new protein dynamics model of energy dissipation

A novel approach to reveal intramolecular signal transduction network is proposed in this work. To this end, a new algorithm of network construction is developed, which is based on a new protein dynamics model of energy dissipation. A key feature of this approach is that direction information is specified after inferring protein residue-residue interaction network involved in the process of signal transduction. This enables fundamental analysis of the regulation hierarchy and identification of regulation hubs of the signaling network. A well-studied allosteric enzyme, E. coli aspartokinase III, is used as a model system to demonstrate the new method. Comparison with experimental results shows that the new approach is able to predict all the sites that have been experimentally proved to desensitize allosteric regulation of the enzyme. In addition, the signal transduction network shows a clear preference for specific structural regions, secondary structural types and residue conservation. Occurrence of super-hubs in the network indicates that allosteric regulation tends to gather residues with high connection ability to collectively facilitate the signaling process. Furthermore, a new parameter of propagation coefficient is defined to determine the propagation capability of residues within a signal transduction network. In conclusion, the new approach is useful for fundamental understanding of the process of intramolecular signal transduction and thus has significant impact on rational design of novel allosteric proteins.     

Angiotensin IV upregulates the activity of protein phosphatase 1α in Neura-2A cells

The peptide angiotensin IV (Ang IV) is a derivative of angiotensin II. While insulin regulated amino peptidase (IRAP) has been proposed as a potential receptor for Ang IV, the signalling pathways of Ang IV through IRAP remain elusive. We applied high-resolution mass spectrometry to perform a systemic quantitative phosphoproteome of Neura-2A (N2A) cells treated with and without Ang IV using sta ble-isotope labeling by amino acids in cell culture (SILAC), and identified a reduction in the phosphorylation of a major Ser/Thr protein phosphorylase 1 (PP1) upon Ang IV treatment. In addition, spinophilin (spn), a PP1 regulatory protein that plays important functions in the neural system, was expressed at higher levels. Immunoblotting revealed decreased phosphorylation of p70S6 kinase (p70^S6K) and the major cell cycle modulator retinoblastoma protein (pRB). These changes are consistent with an observed decrease in cell proliferation. Taken together, our study suggests that Ang IV functions via regulating the activity of PP1.     

Present state and perspective of downstream processing of biologically produced 1,3-propanediol and 2,3-butanediol

1,3-Propanediol and 2,3-butanediol are two promising chemicals which have a wide range of applications and can be biologically produced. The separation of these diols from fermentation broth makes more than 50% of the total costs in their microbial production. This review summarizes the present state of methods studied for the recovery and purification of biologically produced diols, with particular emphasis on 1,3-propoanediol. Previous studies on the separation of 1,3-propanediol primarily include evaporation, distillation, membrane filtration, pervaporation, ion exchange chromatography, liquid–liquid extraction, and reactive extraction. Main methods for the recovery of 2,3-butanediol include steam stripping, pervaporation, and solvent extraction. No single method has proved to be simple and efficient, and improvements are especially needed with regard to yield, purity, and energy consumption. Perspectives for an improved downstream processing of biologically produced diols, especially 1,3-propanediol are discussed based on our own experience and recent work. It is argued that separation technologies such as aqueous two-phase extraction with short chain alcohols, pervaporation, reverse osmosis, and in situ extractive or pervaporative fermentations deserve more attention in the future.     

PNN-curve: a new 2D graphical representation of DNA sequences and its application

We introduce a novel 2D graphical representation of DNA sequences based on the pairs of the neighboring nucleotides (PNNs). Then we get the PNNs' distributions and obtain a y-M. The construction of the PNN-curve has some important advantages (1) It avoids loss of information and the PNN-curve standing for DNA sequences does not overlap or intersect with itself. (2) The novel 2D representation is more sensitive. The utility of this method can be illustrated by the examination of similarities/dissimilarities among the coding sequences of the first exon of beta-globin gene of eleven different species in Table 2.     

应用RAPD技术对蜘蛛系统演化的初步研究

利用随机扩增多态ＤＮＡ 技术检测了３ 类不同蜘蛛的系统发生关系．用１２ 个随机引物对各实验蜘蛛的基因组ＤＮＡ 进行扩增,选择其中扩增谱带清晰的８ 个引物进行分析并计算不同类蜘蛛间的遗传距离．结果表明：所有８ 个引物获得的ＲＡＰＤ谱带均表现为不同程度的多态性;地穴型蜘蛛与结网型蜘蛛间的遗传距离及结网型与游猎型之间的遗传距离,均比地穴型与游猎型之间的遗传距离近,体现了蜘蛛由地穴→结网→游猎的系统演化进程．这一结论与根据古生物学、胚胎学、形态学及生态学等得出的结论一致,从而进一步从ＤＮＡ 分子水平上为蜘蛛系统演化提供了新的证据．     

对数生长与G0期人包皮成纤维细胞Stat1对INF—α刺激反应的差异

Stat1（信号转导与转录活化子1）的激活与刺激因子和细胞组织类型有关,它的活化受体有组织分布特异性,本研究比较G0期和对数生长周期两个不同状态体外培养的人包皮成纤维细胞受到干扰素（INF－α）刺激后Stat1基因mRNA、蛋白质表达以及蛋白质合成效率的差异。结果表明：成对数生长的细胞Stat1的mRNA表达量较对照组增加达10倍左右,蛋白质表达增加3－4倍左右;G0期细胞Stat1的mRNA表达量较对照组增加约3－4倍,蛋白质表达增加约3－4倍;对数生长细胞Stat1蛋白质合成效率明显降低,在翻译水平可能有调控,以上结果提示对数生长和G0细胞对INF－α刺激反应有差异。     

Cytotoxic T-lymphocyte associated antigen 4 polymorphisms and asthma risk: a meta-analysis

Background

A number of studies assessed the association of cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms with asthma in different populations. However, the results were contradictory. We performed a meta-analysis to examine the association between CTLA-4 polymorphisms and asthma susceptibility.

Methods

Pubmed, EMBASE, HuGE Navigator, and Wanfang Database were searched. Data were extracted independently by two reviewers. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

Seventeen studies involving 6378 cases and 8674 controls were included. Significant association between +49 A/G polymorphism and asthma was observed for AA vs. AG+GG (OR = 1.18, 95% CI 1.01–1.37, P = 0.04). There were no significant associations between −318 C/T, −1147 C/T, CT60 A/G, −1722 C/T, or rs926169 polymorphisms and asthma risk.

Conclusions

This meta-analysis suggested that the +49 A/G polymorphism in CTLA-4 was a risk factor for asthma.     

Multiplicity and stability analysis of microorganisms in continuous culture: effects of metabolic overflow and growth inhibition

Metabolic overflow (enhanced uptake of substrate and secretion of intermediates) is a phenomenon often observed for cells grown under substrate excess. Growth inhibition by substrate and/or product is also normally found for this kind of culture. An effort is made in this work to analyze the dynamic behavior of a continuous culture subject to metabolic overflow and growth inhibition by substrate and/or product. Analysis of a model system shows that in a certain range of operating conditions three nonwashout steady state solutions are possible. Local stability analysis indicates that only two of them are stable thus leading to multiplicity and hysteresis. Further analysis of the intrinsic effects of different terms describing the metabolic overflow and growth inhibitions reveals that for the model system and the parameters considered, the combined effects of product inhibition and an enhanced formation rate of product under substrate excess cause the multiplicity and hysteresis. Growth inhibition by substrate and/or an enhanced substrate uptake appear not to be necessary conditions. The combined effects of enhanced product formation and product inhibition can also lead to unusual dynamic behavior such as a prolonged time period to reach a steady state, oscillatory transition from one steady state to another, and sustained oscillations. Using the occurrence of multiplicity and oscillation as criteria, the operating regime of a continuous culture can be divided into four domains: one with multiplicity and oscillation, one with unique steady state but possible oscillatory behavior, the other two with unique and stable steady state. The model predictions are in accordance with recent experimental results. The results presented in this work may be used as guidelines for choosing proper operating conditions of similar culture systems to avoid undesired instability and multiplicity. Copyright 1998 John Wiley & Sons, Inc.     

硒对自由基损伤的红细胞引起微循环紊乱的保护作用--动物实验及临床研究

为研究硒保护实验动物大脑表面微循环免受自由基损伤红细胞的干扰作用,以及术前服硒对心脏手术病人在体外循环过程中皮肤和肌肉微循环的保护效果,在动物实验中利用荧光标记的图象分析法观察大鼠脑微小动静脉直径,流速和通透性的改变,并在临床观察中用激光多普乐法对服硒组心脏手术病人皮肤和肌肉微循环的变化与对照组进行比较研究。