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Now showing items 1 - 16 of 24

  • The biological content of ballast water in China: A review

    Wu, Huixian   Chen, Chen   Wang, Qiong   Lin, Junda   Xue, Junzeng  

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  • Structure of the human κ-opioid receptor in complex with JDTic

    Wu, Huixian   Wacker, Daniel   Mileni, Mauro   Katritch, Vsevolod   Han, Gye Won   Vardy, Eyal   Liu, Wei   Thompson, Aaron A.   Huang, Xi-Ping   Carroll, F. Ivy   Mascarella, S. Wayne   Westkaemper, Richard B.   Mosier, Philip D.   Roth, Bryan L.   Cherezov, Vadim   Stevens, Raymond C.  

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  • Survivorship characteristics and adaptive mechanisms of phytoplankton assemblages in ballast water

    Wu, Huixian   Shen, Chen   Wang, Qiong   Aronson, Richard B.   Chen, Chen   Xue, Junzeng  

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  • Structural Basis for Molecular Recognition at Serotonin Receptors

    Wang, Chong   Jiang, Yi   Ma, Jinming   Wu, Huixian   Wacker, Daniel   Katritch, Vsevolod   Han, Gye Won   Liu, Wei   Huang, Xi-Ping   Vardy, Eyal   McCorvy, John D.   Gao, Xiang   Zhou, X. Edward   Melcher, Karsten   Zhang, Chenghai   Bai, Fang   Yang, Huaiyu   Yang, Linlin   Jiang, Hualiang   Roth, Bryan L.   Cherezov, Vadim   Stevens, Raymond C.   Xu, H. Eric  

    Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs.
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  • A high-resolution genomic composition-based method with the ability to distinguish similar bacterial organisms

    Zhou, Yizhuang   Zhang, Wenting   Wu, Huixian   Huang, Kai   Jin, Junfei  

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  • Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator.

    Wu, Huixian   Wang, Chong   Gregory, Karen J   Han, Gye Won   Cho, Hyekyung P   Xia, Yan   Niswender, Colleen M   Katritch, Vsevolod   Meiler, Jens   Cherezov, Vadim   Conn, P Jeffrey   Stevens, Raymond C  

    The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs. =20
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  • Structure of an Agonist-Bound Human A(2A) Adenosine Receptor RID A-1530-2009

    Xu, Fei   Wu, Huixian   Katritch, Vsevolod   Han, Gye Won   Jacobson, Kenneth A.   Gao, Zhan-Guo   Cherezov, Vadim   Stevens, Raymond C.  

    Activation of G protein-coupled receptors upon agonist binding is a critical step in the signaling cascade for this family of cell surface proteins. We report the crystal structure of the A(2A) adenosine receptor (A(2A)AR) bound to an agonist UK-432097 at 2.7 angstrom resolution. Relative to inactive, antagonist-bound A(2A)AR, the agonist-bound structure displays an outward tilt and rotation of the cytoplasmic half of helix VI, a movement of helix V, and an axial shift of helix III, resembling the changes associated with the active-state opsin structure. Additionally, a seesaw movement of helix VII and a shift of extracellular loop 3 are likely specific to A(2A)AR and its ligand. The results define the molecule UK-432097 as a "conformationally selective agonist" capable of receptor stabilization in a specific active-state configuration.
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  • Global convergence of modified augmented Lagrangian methods for nonlinear semidefinite programming

    Wu, Huixian   Luo, Hezhi   Ding, Xiaodong   Chen, Guanting  

    We investigate in this paper global convergence properties of the augmented Lagrangian method for nonlinear semidefinite programming (NLSDP). Four modified augmented Lagrangian methods for solving NLSDP based on different algorithmic strategies are proposed. Possibly infeasible limit points of the proposed methods are characterized. It is proved that feasible limit points that satisfy the Mangasarian-Fromovitz constraint qualification are KKT points of NLSDP without requiring the boundedness condition of the multipliers. Preliminary numerical results are reported to compare the performance of the modified augmented Lagrangian methods.
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  • Climate changes reconstructed from a glacial lake in High Central Asia over the past two millennia

    Lan, Jianghu   Xu, Hai   Sheng, Enguo   Yu, Keke   Wu, Huixian   Zhou, Kangen   Yan, Dongna   Ye, Yuanda   Wang, Tianli  

    Climatic changes in Arid Central Asia (ACA) over the past two millennia have been widely concerned. However, less attention has been paid to those in the High Central Asia (HCA), where the Asian water tower nurtures the numerous oases by glacier and/or snow melt. Here, we present a new reconstruction of the temperature and precipitation change over the past two millennia based on grain size of a well-dated glacial lake sediment core in the central of southern Tianshan Mountains. The results show that the glacial lake catchment has experienced cold-wet climate conditions during the Dark Age Cold Period (similar to 300-600 AD; DACP) and the Little Ice Age (similar to 1300-1870 AD; LIA), whereas warm-dry conditions during the Medieval Warm Period (similar to 700-1270 AD; MWP). Integration of our results with those of previously published lake sediment records, stalagmite delta O-18 records, ice core net accumulation rates, tree-ring based temperature reconstructions, and mountain glacier activities suggest that there has a broadly similar hydroclimatic pattern over the HCA areas on centennial time scale during the past two millennia. Comparison between hydroclimatic pattern of the HCA and that of the ACA areas suggests a prevailing 'warm-dry and cold-wet' hydroclimatic pattern over the whole westerlies-dominated central Asia areas during the past two millennia. We argue that the position and intensity of the westerlies, which are closely related to the phase of the North Atlantic Oscillation (NAO), and the strength of the Siberian High pressure (SH), could have jointly modulated the late Holocene central Asia hydroclimatic changes. (C) 2017 Elsevier Ltd and INQUA. All rights reserved.
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  • Isolation and characterization of 12 polymorphic microsatellite loci in Eurasian perch (Perca fluviatilus L.)

    Yang, Xinxin   Wang, Jun   Ma, Yuqing   Yin, Jianguo   Wu, Huixian  

    The Eurasian perch (Perca fluviatilis L.) is a very important freshwater species in the Eurasian Continent. We characterized 12 microsatellite markers in this species and evaluated their usefulness for identifying genetic variation in 40 perch individuals from the Ulungur and Taitun-4 Lakes in the Xinjiang province of China. The number of alleles per locus ranged from 2 to 7, the observed (H-O) and expected (H-E) heterozygosities were 0.053-1.000 and 0.053-0.813, respectively. These microsatellite loci will be useful for assessment of genetic variation in Perca fluviatilus.
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  • Population differentiation, bottleneck and selection of Eurasian perch (Perca fluviatilis L.) at the Asian edge of its natural range

    Yang, Xinxin   Qian, Long   Wu, Huixian   Fan, Zhenming   Wang, Chenghui  

    The Eurasian perch (Perca fluviatilis L.) is widely distributed in the European continent and restrictedly ranges at the lrtse River drainage in China. To understand the population structure of this species in China, the Asian edge of its natural range, samples of eight natural populations and one colonized population were analyzed using microsatellite markers. The Eurasian perch in China was found to possess high allelic richness (7.097-8.662) and heterozygosities (H-O = 0.734-0.856, H-E = 0.798-0.876). Significant bottleneck signatures for six populations were found. Significant genetic differentiation among populations was revealed from pairwise F-ST values, as well as analysis of molecular variance (AMOVA), Bayesian clustering in STRUCTURE, and Principal coordinate analysis (PCA). The hierarchical analysis for selection sweep suggested local adaptation to habitat conditions. The current results imply the occurrence of habitat fragmentation in the Eurasian perch in China. Management and conservation implications are also presented in this study. (C) 2011 Elsevier Ltd. All rights reserved.
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  • Evaluation of Molecular Modeling of Agonist Binding in Light of the Crystallographic Structure of an Agonist-Bound A(2A) Adenosine Receptor

    Deflorian, Francesca   Kumar, T. Santhosh   Phan, Khai   Gao, Zhan-Guo   Xu, Fei   Wu, Huixian   Katritch, Vsevolod   Stevens, Raymond C.  

    Molecular modeling of agonist binding to the human A(2A) adenosine receptor (AR) was assessed and extended in light of crystallographic structures. Heterocyclic adenine nitrogens of cocrystallized agonist overlaid corresponding positions of the heterocyclic base of a bound triazolotriazine antagonist, and ribose moiety was coordinated in a hydrophilic region, as previously predicted based on modeling using the inactive receptor. Automatic agonist docking of 20 known potent nucleoside agonists to agonist-bound A(2A)AR crystallographic structures predicted new stabilizing protein interactions to provide a structural basis for previous empirical structure activity relationships consistent with previous mutagenesis results. We predicted binding of novel C2 terminal amino acid conjugates of A(2A)AR agonist CGS21680 and used these models to interpret effects on binding affinity of newly synthesized agonists. D-Amino acid conjugates were generally more potent than L-stereoisomers and free terminal carboxylates more potent than corresponding methyl esters. Amino acid moieties were coordinated close to extracellular loops 2 and 3. Thus, molecular modeling is useful in probing ligand recognition and rational design of GPCR-targeting compounds with specific pharmacological profiles.
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  • Community structure of benthic macroinvertebrates in reclaimed and natural tidal flats of the Yangtze River estuary

    Xue, Junzeng   Yang, Jiqiang   Wang, Qiong   Aronson, Richard B.   Wu, Huixian  

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  • Small-molecule inhibitors directly target CARD9 and mimic its protective variant in inflammatory bowel disease

    Leshchiner, Elizaveta S.   Rush, Jason S.   Durney, Michael A.   Cao, Zhifang   Dancik, Vlado   Chittick, Benjamin   Wu, Huixian   Petrone, Adam   Bittker, Joshua A.   Phillips, Andrew   Perez, Jose R.   Shamji, Alykhan F.   Kaushik, Virendar K.   Daly, Mark J.   Graham, Daniel B.   Schreiber, Stuart L.   Xavier, Ramnik J.  

    Advances in human genetics have dramatically expanded our understanding of complex heritable diseases. Genome-wide association studies have identified an allelic series of CARD9 variants associated with increased risk of or protection from inflammatory bowel disease (IBD). The predisposing variant of CARD9 is associated with increased NF-kappa B-mediated cytokine production. Conversely, the protective variant lacks a functional C-terminal domain and is unable to recruit the E3 ubiquitin ligase TRIM62. Here, we used biochemical insights into CARD9 variant proteins to create a blueprint for IBD therapeutics and recapitulated the mechanism of the CARD9 protective variant using small molecules. We developed a multiplexed bead-based technology to screen compounds for disruption of the CARD9-TRIM62 interaction. We identified compounds that directly and selectively bind CARD9, disrupt TRIM62 recruitment, inhibit TRIM62-mediated ubiquitinylation of CARD9, and demonstrate cellular activity and selectivity in CARD9-dependent pathways. Taken together, small molecules targeting CARD9 illustrate a path toward improved IBD therapeutics.
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  • Climate change and soil erosion in a small alpine lake basin on the Loess Plateau,China

    Yu, Keke   Xu, Hai   Lan, Jianghu   Sheng, Enguo   Liu, Bin   Wu, Huixian   Tan, Liangcheng   Yeager, Kevin M.  

    Multi-proxy indices retrieved from sediments in Lake Chaonaqiu, an alpine lake on the western Loess Plateau (LP) of China, were used to reconstruct a precipitation history over the last similar to 300 years. The results correlate well with records from tree rings and historical documents in neighboring regions. We show that the lake oscillated between two states, i.e. wetter climatic conditions, which favored denser vegetation cover, and promoted weaker catchment soil erosion; and drier climatic conditions, which lead to less vegetation coverage, correlate with stronger surface soil erosion. Several intensive soil erosion events were identified in the sediment cores, and most of these occurred during decadal/multi-decadal dry periods, and correlate well with flood events documented in historical literature. The results of this study show that soil erosion by flood events is particularly intense during dry periods, and further highlights the role of vegetation cover in the conservation of water and soil in small lake basins on the Chinese LP. Copyright (c) 2016 John Wiley & Sons, Ltd.
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  • Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs.

    Wang, Chong   Wu, Huixian   Evron, Tama   Vardy, Eyal   Han, Gye Won   Huang, Xi-Ping   Hufeisen, Sandy J   Mangano, Thomas J   Urban, Dan J   Katritch, Vsevolod   Cherezov, Vadim   Caron, Marc G   Roth, Bryan L   Stevens, Raymond C  

    The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumours; however, mutations at SMO have been found to abolish their antitumour effects, a phenomenon known as chemoresistance. Here we report three crystal structures of human SMO bound to the antagonists SANT1 and Anta XV, and the agonist, SAG1.5, at 2.6-2.8A resolution. The long and narrow cavity in the transmembrane domain of SMO harbours multiple ligand binding sites, where SANT1 binds at a deeper site as compared with other ligands. Distinct interactions at D473(6.54f) elucidated the structural basis for the differential effects of chemoresistance mutations on SMO antagonists. The agonist SAG1.5 induces a conformational rearrangement of the binding pocket residues, which could contribute to SMO activation. Collectively, these studies reveal the structural basis for the modulation of SMO by small molecules. =20
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