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Articles by Wei Liu
Total Records ( 25 ) for Wei Liu
  Theodore M. Hammett , Zunyou Wu , Tran Tien Duc , David Stephens , Sheena Sullivan , Wei Liu , Yi Chen , Doan Ngu and Don C. Des Jarlais

Aims  This paper reviews the evolution of government policies in China and Vietnam regarding harm reduction interventions for human immunodeficiency virus (HIV) prevention, such as needle/syringe provision and opioid substitution treatment.

Methods  The work is based upon the authors` experiences in and observations of these policy developments, as well as relevant government policy documents and legislation.

Results  Both countries are experiencing HIV epidemics driven by injection drug use and have maintained generally severe policies towards injection drug users (IDUs). In recent years, however, they have also officially endorsed harm reduction. We sought to understand how and why this apparently surprising policy evolution took place. Factors associated with growing support for harm reduction were similar but not identical in China and Vietnam. These included the emergence of effective `champions` for such policies, an ethos of pragmatism and receptivity to evidence, growing collaboration across public health, police and other sectors, the influence of contingent events such as the severe acute respiratory syndrome (SARS) epidemic and pressure from donors and international organizations to adopt best practice in HIV prevention.

Conclusions  Ongoing challenges and lessons learned include the persistence of tensions between drug control and harm reduction that may have negative effects on programs until a fully harmonized policy environment is established. Excessive reliance on law enforcement and forced detoxification will not solve the problems of substance abuse or of HIV among drug users. Ongoing evaluation of harm reduction programs, as well as increased levels of multi-sectoral training, collaboration and support are also needed.

  Ahmed S. Attia , Jennifer L. Sedillo , Wei Wang , Wei Liu , Chad A. Brautigam , Wade Winkler and Eric J. Hansen
  The Hfq protein is recognized as a global regulatory molecule that facilitates certain RNA-RNA interactions in bacteria. BLAST analysis identified a 630-nucleotide open reading frame in the genome of Moraxella catarrhalis ATCC 43617 that was highly conserved among M. catarrhalis strains and which encoded a predicted protein with significant homology to the Hfq protein of Escherichia coli. This protein, containing 210 amino acids, was more than twice as large as the Hfq proteins previously described for other bacteria. The C-terminal half of the M. catarrhalis Hfq protein was very hydrophilic and contained two different types of amino acid repeats. A mutation in the M. catarrhalis hfq gene affected both the growth rate of this organism and its sensitivity to at least two different types of stress in vitro. Provision of the wild-type M. catarrhalis hfq gene in trans eliminated these phenotypic differences in the hfq mutant. This M. catarrhalis hfq mutant exhibited altered expression of some cell envelope proteins relative to the wild-type parent strain and also had a growth advantage in a continuous flow biofilm system. The presence of the wild-type M. catarrhalis hfq gene in trans in an E. coli hfq mutant fully reversed the modest growth deficiency of this E. coli mutant and partially reversed the stress sensitivity of this E. coli mutant to methyl viologen. The use of an electrophoretic mobility shift assay showed that this M. catarrhalis Hfq protein could bind RNA derived from a gene whose expression was altered in the M. catarrhalis hfq mutant.
  Wei Liu , Yuyue Du and Haichun Sun
  Interorganizational Logical Workflow Nets (ILWN) can efficiently model cooperative systems based on Petri nets, workflow techniques and temporal logic. But soundness of arbitrary ILWNs is hard to decide. This study defines the concept of T-restricted Logical Workflow Nets (LWN) and proposes an important subclass of ILWNs composed of n T-restricted LWNs: T-restricted ILWNs. The sufficient and necessary conditions of T-restricted ILWNs preserving soundness are obtained and the rigorous analysis approach is presented based on their static net structures only. Moreover, two approaches of combining n T-restricted LWNs into one T-restricted ILWN are given. The concepts and techniques proposed in this study are illustrated with a useful example of an auto gas station system.
  Wei Liu and Yuyue Du
  In this study, Logical Time Interaction Petri Nets (LTIPN) were designed to describe multimedia synchronization based on the previous models. In the model, we introduce logical expressions which are used to describe passing value indeterminacy in an logical time Petri net to model multimedia synchronization. And all multimedia synchronization events including multimedia objects are expressed by transitions of Petri nets, while the previous models mostly use places of Petri nets to express multimedia objects. This study provides users simple and intuitive modeling approaches. Basic temporal relations between multimedia objects, multimedia synchronization strategies and user interactive operations can be represented simply and explicitly by the LTIPN.
  Wei Liu , Yu Yue Du , Bao Qi Guo , Chun Yan and Qiang Xu
  Dynamic Description Logic (DDL) is an extension of description logic. In dynamic description logic, both services and the service composition can be expressed in formulae, but there is still much room to promote the efficiency. In this study, a fast and effective method for web service composition is proposed for the services which perform in sequence. This method takes advantage of the partial order relation among services, dividing the service composition into two phases:on the first stage, the partial order diagram is generated in the registration server; on the second stage, the fast algorithm is run based on the partial order diagram to return web service composition to meet requests of users. By analysis and verification, the fast algorithm for web service composition presented in this study can be implemented in a linear time complexity, greatly shortening response time of the system.
  Wei Liu , Wenjie Xu , Dong Wang , Zongtian Liu and Xujie Zhang
  As the unit of human knowledge, event is used to describe all kinds of knowledge in the world. Action which is one of the main factors in event describes the changing processes of world states in a specific period of time. As we know, there are different states in different time and the main reason of states changes is caused by action. Therefore, it is necessary to embrace temporal information into the representation about action to describe these changes. In this study, we first proposed a temporal description logic T-ALC, in which the temporal information as a constraint of instances was added to ABox. It provided a kind of decidable approach to deal with the states changes of objects in action. Then, we defined the syntax and semantics of action based on T-ALC. Especially, the semantics of action can be transformed into the changing processes of interpretations and the calculation of new interpretations and ABox were also given. Finally, several inference services of action in different time were studied.
  Shu-quan Xin , Zi Wang , Wei-Nan Hao , Xiao-Tong Yan , Qi Xu , Ying Liu , Wei Liu , Yan-Fei Li , Xin-Dian Li and Wei Li
  Background and Objective: The roots of Codonopsis lanceolata have been used in traditional medicine for treatment of many diseases in China. Till now, there is no evidence on the liver protection effect of C. lanceolata on alcohol-induced liver injury. The purpose of this study was to investigate the hepatoprotective effect of steamed C. lanceolata (SCL) on ethanol induced liver injury in mice. Materials and Methods: Experimental mice were pretreated with different doses of SCL (100-400 mg kg1) for 2 weeks by gavage feeding. Biochemical markers and enzymatic antioxidants from serum, liver tissue were determined. Results: The results showed that the activities of ALT, AST and TG in serum, MDA level in liver tissue, decreased significantly (p<0.05) in the SCL-treated group compared with the alcohol group. On the contrary, the GSH level was increased markedly (p<0.05). Histopathological examination revealed that SCL (400 mg kg1) pre-treatment noticeably prevented alcohol-induced hepatocyte apoptosis and fatty degeneration. Moreover, LC-MS/MS analysis of SCL showed that it mainly contain Lobetyolin, Tangshenoside, Lancemasides F, Lancemasides B (Lancemasides E, Codonolaside), Lancemasides G, Lancemasides A (Codonoposide, Codonolaside) and Codonoposide. Conclusion: These results provide the evidence on possible application of SCL on acute alcohol-induced oxidative stress and liver damage in clinic.
  Fan Wang , Chonglei Li , Wei Liu and Yihe Jin
  Volatile Organic Compounds (VOCs) are one of the main substances causing multiple chemical sensitivity reactions in human indoors. In order to investigate the effect of short-term of VOCs mixture on oxidative stress responses in mice, researchers exposed male Kunming mice to filtered air (0) and four kinds of VOCs mixture treated air. The concentrations of VOCs were following about: Form Aldehyde (FA), Benzene, Toluene and Xylene (BTX) 1.0 + 1.1 + 2.0 + 2.0, 3.0 + 3.3 + 6.0 + 6.0, 5.0 + 5.5 + 10.0 + 10.0 and 10.0 + 11.0 + 20.0 + 20.0 mg m-3, respectively which corresponded to 10, 30, 50 and 100 times of indoor air quality standard in China for 2 h day-1 for 5 days/week for 2 weeks in the whole body exposure chamber. One day following the last VOCs mixture exposure researchers collected liver, serum, lung and Bronchia Alveolus Lavage Fluid (BALF) from each mouse and examined LDH in BALF, ROS in lung, antioxidant enzyme activities, ROS, lipid and protein peroxidation and Reactive Nitrogen Species (RNS) in liver, DNA damage marker in serum. LDH release in BALF indicated cell impairment in the alveolar area. There was a positive correlation between LDH release in BALF and ROS production in lung (r = 0.636, p<0.001). The oxidative stress and injury in the liver occurred as VOCs mixture appeared to trigger a cascade of reactions such as lipid and protein peroxidation. Total antioxidation capacity and activities of antioxidative enzymes other than CAT were significantly decreased and nitric oxide was increased in liver in mice exposure to VOCs. The 8-OHdg in serum exposure to a high dose of VOCs was significantly higher than control. These results showed that inhalation of short-term VOCs mixture influence oxidative stress of the mice so as to induce a variety of oxidative products. ROS, GSH, GSH-Px, T-AOC, iNOS in liver could be used as sensitive biological makers of oxidative damage under short-term VOCs mixture condition. These findings also provide the occupational exposure limit concentrations for VOCs with valuable reference.
  Xiao-Hui Si , Yong-Fang Yao , Shuan-Ling Zhang , Wei Liu , Liang Zhou and Huai-Liang Xu
  The Duffy Antigen Receptor for Chemokines (DARC) gene also called Duffy or FY, Plasmodium vivax and Plasmodium knowlesi use DARC to trigger internalization into red blood cells and cause malaria, the malaria life cycle in humans and nonhuman primates. In order to investigate DARC gene in golden snub-nosed monkey (Rhinopithecus roxellanae), two pairs of primers were designed based on DARC gene sequence of the Macaca mulatta (HQ285849.1) and used to amplify approximately 1.0 and 1.1 kb DNA fragments respectively by PCR technique from genomic DNA sample of golden monkey. The DNA, sequencing and combing results showed that the DARC gene of the golden monkey was 1593 bp in length and contained a 47 bp 5 flanking region, two extrons (21 and 990 bp), one complete intron (478 bp) and a 57 bp 3 flanking region. The Open Reading Fragment (ORF) was 1011 bp and encoded 336 amino acid residues. The DARC was a hydrophobic protein with less hydrophilic components. The prediction of topological structure for the protein indicated that it contained 16 potential function sites: three N-glycosylation sites, one protein kinase C phosphorylation site, two casein kinase II phosphorylation sites and ten N-myristoylation sites. In addition, the protein comprised seven transmembrane helix regions and four extracellular regions and four intracellular regions. Alignment analysis revealed that the homologies of DARC gene nucleotide sequence of golden snub-nosed monkey with other primate species and human was 95-99% and the homologies of amino acid sequence was 80-99%. These results would provide the molecular basis for golden monkey against human malarias.
  Kang-Kang Guo , Qing-Hai Tang , Peng-Bo Ning , He-Lin Li , Wei Liu , Qi-Zhuang Lv , Wu-Long Liang , Zhi Lin , Cheng-Cheng Zhang and Yan-Ming Zhang
  The Nonstructural 2 (NS2) protein plays an important role in the infection process of Classical Swine Fever Virus (CSFV), it is an autoprotease cleaving the NS2-3 polyprotein for the NS3 protein release. The NS2 protein is an easily biodegradable protein in cells and the biogradation pathways are not still very clear at present. The Swine Umbilical Vein Endothelial Cell (SUVEC) constucted by the lab is a good cell line model for studying the pathogenic mechanism of CSFV. In this study, the degradation of CSFV NS2 were observed by detecting the NS2 protein expression in SUVEC and PK-15 cells. The recombinant plasmid pEGFP-NS2 with complete NS2 gene of CSFV was transfected into SUVEC and PK-15 cells, respectively. The NS2 RNA was determined by RT-PCR and expression of NS2 protein in cells were analyzed by fluorescence microscopy and western blot assay after transfected. The degradation of NS2 protein also were observed by fluorescence microscopy and Western-blot assay. The results shown that the NS2 protein is short-lived in cells, the biodegradation process could be inhibited by a proteasomal inhibitor (MG132), hinting the NS2 protein is degraded via proteasome pathway in cells and this degradation process was related to the phosphorylation of NS2 protein. This is a primary study on the degradation of CSFV NS2 protein. The future experiments will address the degradation mechanism of CSFV NS2 and find the phosphorylation amino acids of NS2 protein which maybe relate to protein degadation in cells.
  Feida Sun , Wenye Chen , Ye Qing , Lin Liu and Wei Liu
  Understanding the relationships between degrees of Plateau pika density and plants biomass is essential for improving the management of pika populations in alpine meadow ecosystems. Twelve survey sites with active burrow of plateau pika were classified into four degrees of density: approximately zero-density, low-density, medium-density and high-density to evaluate pika populations and biomass allocation interactions. The results revealed that plant composition, overall vegetation height and cover, dominant species were significantly different among the four sites. Additionally, plant functional groups, aboveground, belowground and total biomass, root:shoot ratios and the proportion of living roots were greatest at the zero-density site and those at the medium-density site were the lowest. Researchers postulate that pika activities may not be the source of the differences but a symptom of grassland degradation. As such, a reduction of livestock numbers, a variable rotational grazing system, restorative management techniques and community participation in co-management of the meadows are likely to effectively improve grassland productivity and deter pika outbreaks. Further, pika population fluctuations should be monitored and when the population exceeds the economic threshold of low-density (110 pikas or/and 512 active burrows ha-1) or reaches high-density (200 pikas or/and 1360 active burrows ha-1) integrated management strategies should be implemented to protect damage.
  De-Ming Yin , Fen Li , Xi-Jun Wang , Yuan Lin , Zeng-Zai Liu , Ning-Bo Xia , Xiao-Feng Sheng , Ting Wang , Yi Liu and Wei Liu
  Little information is available about prevalence of helminthes in pigs in Hunan Province. In the present study, the prevalence of helminths in adult pigs was investigated in Hunan Province, People’s Republic of China between 2009 and 2012. A total of 690 pigs slaughtered in local abattoirs from ten representative administrative regions in Hunan Province were examined for the presence of helminths using traditional helminthological approach. The worms were examined, counted and identified to species according to existing keys and descriptions. A total of eight species of helminths were found in pigs which represent three classes. The results of the present investigation have important implications for the control of helminth infections in pigs in Hunan Province, China.
  Wei Liu and Ling Chen
  The identification of communities is significant for the understanding of network structures and functions. In this study, we propose a framework to address the problem of community detection in bipartite networks based on principal components analysis. We apply the algorithm to real-world network data, showing that the algorithm successfully finds meaningful community structures of bipartite networks.
  Lei Yang , Chunqing Wang and Wei Liu
  Surface tension driven self-assembly has been demonstrated to be a promising method for mass production of highly 3-D MEMS structures. However, factors and their mechanisms affecting the self-assembly precision of the hingeless structures are still barely understood. This study addresses and analyzes some of the factors, including the inherent instability of the hingeless structures, scale effect and the deformations of the limiter structure which limits the self-assembly precision of hingeless structures. An energy based model, verified by the experimental results, was introduced to evaluate the adverse effect of each factor on the precision. This precision study can serve as an optimum guideline for the designs of self-assembly MEMS microstructures and allow the creation of high precise MEMS applications.
  Wei Liu , Yu-Yue Du and Chun Yan
  Service selection is an essential issue in service discovery based on Web service clusters. The ratio of trust value to price is introduced to select the most suitable service in a cluster. The method of computing the initial trust, the direct trust and the recommendation trust are, respectively presented and the overall trust is derived based on them. The proposed method keeps the balance between the price and service quality.
  Jianbo Cai , G. Liu , Ye Tuo , Wei Liu and Duanwei Zhu
  In this study, aerobic granular sludge was utilized as an effective biosorbent to remove Zn2+ from the aqueous solution. The results showed that the initial pH, contact time and Zn2+ concentration affected the biosorption process significantly. Typically, the adsorption capacity of Zn2+ by aerobic granular sludge increased with increasing pH in the ranges of 5.0-7.0 and decreased with increasing of pH in the ranges of 7.0-9.0, which indicated that pH at 7.0 was optimal choice for the Zn2+ adsorption by the aerobic granular sludge. The maximum removal of Zn2+ at pH 7.0 was found to be 131.47 mg g-1 at initial Zn2+ ion concentration of 120 mg L-1 by the aerobic granular sludge. In addition, the adsorption ability of two kind of anaerobic granular sludge from different reaction stage at one reactor for Zn2+ remove was compared. It was founded that the anaerobic granular sludge from the end of aerobic stage had better adsorption ability than that from the end of anaerobic stage, which could be attributed to be the species and quantity of microbial in the aerobic granular sludge.
  Chun Yan , Wei Liu and Fang Li
  Analyzing on change factors of China open-end funds scale and founding economic model which can explain the size of the fund changing. Analyzing and forecasting changes on China open fund scale can provide decision-making basis for management and risk control of China open-end fund investment which will have very theoretical and realistic significance. This study on the external factors which effects the fund investment flows. Based on season serial data it found the error correction model to analysis the change of fund size by the example of the open-end stock equity mutual funds in China. This model extends the size of sample data. The results shows us there exists a long-term cointegration relationship among the fund scale changing Y, the net growth rate of the final fund share X1 and the percentage of the Shanghai index changing X2. It analyzes the long term equilibrium relationship and short term fluctuate forecast of the fund flows. From the coefficient estimation, we can see that the adjustment effort is large.
  Chun Yan , Yi-wei Qiu , Xin-min Liu and Wei Liu
  Research on differences of medical expenses in Qingdao could provide reference to take control of medical expenses reasonably. This study uses hierarchical cluster analysis of two variables, outpatient costs for each people and hospitalization expenses for each day of Qingdao in the first half of 2012. According to the medical cost, the 22 governmental hospitals in Qingdao are divided into four grades: "lowest cost", "lower cost", "higher cost", "highest cost". Then make the clustering results for significant test using the single factor variance, LSD method and S-N-K method. It shows that the four levels have obvious differences. Finally, the countermeasure for controlling medical expenses is put forward in Qingdao, China.
  Chun Yan , Xianghui Chen , Wei Liu and Yuan Tian
  This study argues that for importing the economical factor, introducing insurance mechanism into supervision of coal mining safety production can fully arouse enthusiasm of all parties, supervise and urge coal mining enterprise to increase the safety input, lower the probability of safety accidents in advance, after the accident increase the capital source of remedying lose in safety production and provide the more reasonable compensation for injured miners and their family. Game analysis on insurance companies intervention in coal worker safety supervision using the principal-agent model is done and many problems such as supervision dynamics, supervision cost and penalties in condition of information asymmetry is discussed. It is demonstrated in the sight of game theory that the differential rate and floating rate of coal worker safety insurance are necessary.
  Chen-Yi Chu , Wei Liu , Bao-Gui Jiang , Ding-Ming Wang , Wei-Jia Jiang , Qiu-Min Zhao , Pan-He Zhang , Zhao-Xiao Wang , Guang-Peng Tang , Hong Yang and Wu-Chun Cao
  By using multilocus sequence analysis, five Borrelia valaisiana-related strains isolated from rodents and ticks in southwestern China were eventually classified as a new genospecies of B. burgdorferi sensu lato rather than B. valaisiana. The finding explained the differences in transmission cycle and phenotype between B. valaisiana strains from Europe and B. valaisiana-related strains from eastern Asia.
  Jinshu Wang , Wei Liu , Fei Gao , Zhiyuan Ren and Meiling Zhou
  La2O3–Mo, Y2O3–Mo, Gd2O3–Mo and Ce2O3–Mo were prepared by liquid–liquid doping combined with spark plasma sintering. The microstructure and surface behaviour of rare earth oxide of the cathode have been studied by microscope, Auger Electron Spectroscopy (AES) and X-ray Photoelectron Spectroscopy (XPS) methods. Among these four kinds of cathode, Y2O3–Mo cathode exhibits the best secondary emission property, i.e., the maximum secondary emission yield could reach 5.24. The penetration depth of primary electrons and escape depth of secondary electrons have been calculated and the energy distribution of primary electrons in the cathode has been simulated by Monte Carlo method. Y2O3–Mo cathode has the largest penetration depth and escape depth, which could be attributed to the highest secondary electron emission yield of the cathode.
  Xiang Wei Liao , Wei Liu , Wen Fang Dong , Bao He Guan , Shi Zhi Chen and Zhan Zhu Liu
  (–)-Renieramycin G was synthesized in 21 steps for the longest linear sequences employing L-tyrosine methyl ester as the chiral starting material in 8.5% overall yield. Two of the four chiral centers came from l-tyrosine methyl ester, and the other two were induced through an intermolecular and an intramolecular Pictet&150;Spengler reaction, respectively.
  Zailian Lu , Wei Liu , Huizhe Huang , Ying He , Ying Han , Yanning Rui , Yanhai Wang , Qinxi Li , Ka Ruan , Zhiyun Ye , Boon Chuan Low , Anming Meng and Sheng-Cai Lin
  Axin plays an architectural role in many important signaling pathways that control various aspects of development and tumorigenesis, including the Wnt, transforming growth factor-β, MAP kinase pathways, as well as p53 activation cascades. It is encoded by the mouse Fused (Fu) locus; the AxinFu allele is caused by insertion of an IAP transposon. AxinFu/Fu mice display varying phenotypes ranging from embryonic lethality to relatively normal adulthood with kinky tails. However, the protein product(s) has not been identified or characterized. In the present study, we conducted immunoprecipitation using brain extracts from the AxinFu mice with specific antibodies against different regions of Axin and found that a truncated Axin containing amino acids 1–596 (designated as AxinFu-NT) and the full-length complement of Axin (AxinWT) can both be generated from the AxinFu allele. When tested for functionality changes, AxinFu-NT was found to abolish Axin-mediated activation of JNK, which plays a critical role in dorsoventral patterning. Together with a proteomics approach, we found that AxinFu-NT contains a previously uncharacterized dimerization domain and can form a heterodimeric interaction with AxinWT. The AxinFu-NT/AxinWT is not conducive to JNK activation, providing a molecular explanation for the dominant negative effect of AxinFu-NT on JNK activation by wild-type Axin. Importantly, AxinFu-NT exhibits no difference in the inhibition of Wnt signaling compared with AxinWT as determined by reporter gene assays, interaction with key Wnt regulators, and expression of Wnt marker genes in zebrafish embryos, suggesting that altered JNK signaling contributes, at least in part, to the developmental defects seen in AxinFu mice.
  Jingsong Cao , Dandan Shan , Tracy Revett , Dongmei Li , Leeying Wu , Wei Liu , James F. Tobin and Ruth E. Gimeno
  Acyl-CoA-dependent lysophospholipid acyltransferases play an important role in attaining the appropriate molecular species of phospholipids. A number of genes encoding these activities were recently identified. It has become clear that multiple genes can encode one enzymatic activity and that a given gene may encode multiple activities. Here we report the identification of a gene encoding a mammalian acyl-CoA-dependent lysophospholipid acyltransferase with prominent activity toward ethanolamine-containing lysophospholipids, which we termed acyl-CoA:lysophosphatidylethanolamine acyltransferase 2, LPEAT2 (previously annotated as AYTL3 or AGPAT7). LPEAT2 is predominantly expressed in brain, coinciding with an enrichment of phosphatidylethanolamine in this tissue. Ectopic expression of LPEAT2 in mammalian HEK293T cells led to a dramatic increase (up to 9-fold) in LPEAT activity when compared with cells transfected with empty vector or an unrelated acyltransferase. LPEAT2 also exhibited significant acyl-CoA-dependent acyltransferase activity toward 1-O-alkenyl-lysophosphatidylethanolamine, lysophosphatidylglycerol, 1-O-alkyl-lysophosphatidylcholine, lysophosphatidylserine, and lysophosphatidylcholine but lacked appreciable acylating activity toward glycerol 3-phosphate, lysophosphatidic acid, lysophosphatidylinositol, and diacylglycerol, demonstrating multiple but selective functions of LPEAT2 as an enzyme involved in phospholipid remodeling. LPEAT2 recognizes a broad range of medium and long chain fatty acyl-CoA, and its activity was not affected by Ca2+. When overexpressed in mammalian cells, LPEAT2 is localized to the endoplasmic reticulum. siRNA-mediated knockdown of LPEAT2 in HEK293T cells significantly decreased LPEAT and 1-alkenyl-LPEAT activities but did not affect other lysophospholipid acylating activities. These findings identify LPEAT2 as an important enzyme in the biosynthesis of ethanolamine-containing phospholipids, especially in brain.
  Wenyu Wen , Wei Liu , Jing Yan and Mingjie Zhang
  Rho kinase (ROCK), a downstream effector of Rho GTPase, is a serine/threonine protein kinase that regulates many crucial cellular processes via control of cytoskeletal structures. The C-terminal PH-C1 tandem of ROCKs has been implicated to play an autoinhibitory role by sequestering the N-terminal kinase domain and reducing its kinase activity. The binding of lipids to the pleckstrin homology (PH) domain not only regulates the localization of the protein but also releases the kinase domain from the close conformation and thereby activates its kinase activity. However, the molecular mechanism governing the ROCK PH-C1 tandem-mediated lipid membrane interaction is not known. In this study, we demonstrate that ROCK is a new member of the split PH domain family of proteins. The ROCK split PH domain folds into a canonical PH domain structure. The insertion of the atypical C1 domain in the middle does not alter the structure of the PH domain. We further show that the C1 domain of ROCK lacks the diacylglycerol/phorbol ester binding pocket seen in other canonical C1 domains. Instead, the inserted C1 domain and the PH domain function cooperatively in binding to membrane bilayers via the unconventional positively charged surfaces on each domain. Finally, the analysis of all split PH domains with known structures indicates that split PH domains represent a unique class of tandem protein modules, each possessing distinct structural and functional features.
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