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Yang Liu

Publications and source records attributed to Yang Liu.

At least 73 records · Page 4Linked to original sources
PubMed2006

Damage to the oxygen-evolving complex by superoxide anion, hydrogen peroxide, and hydroxyl radical in photoinhibition of photosystem II.

Under strong illumination of a photosystem II (PSII) membrane, endogenous superoxide anion, hydrogen peroxide, and hydroxyl radical were successively produced. These compounds then cooperatively resulted in a release of manganese from the oxygen-evolving complex (OEC) and an inhibition of oxygen evolution activity. The OEC inactivation was initiated by an acceptor-side generated superoxide anion, and hydrogen peroxide was most probably responsible for the transportation of reactive oxygen species (ROS) across the PSII membrane from the acceptor-side to the donor-side. Besides ROS being generated in the acceptor-side induced manganese loss; there may also be a ROS-independent manganese loss in the OEC of PSII. Both superoxide anion and hydroxyl radical located inside the PSII membrane were directly identified by a spin trapping-electron spin resonance (ESR) method in combination with a lipophilic spin trap, 5-(diethoxyphosphoryl)-5-phenethyl-1-pyrroline N-oxide (DEPPEPO). The endogenous hydrogen peroxide production was examined by oxidation of thiobenzamide.

Electron Spin Resonance Spectroscopy↗
PubMed2006

Functional characterization of syncytin-A, a newly murine endogenous virus envelope protein. Implication for its fusion mechanism.

Trophoblast fusion in placenta is an important event for preservation of a healthy pregnancy. This process takes place throughout the pregnancy and is crucial for the formation of syncytiotrophoblast layer. Syncytin-1 and syncytin-2 are strong candidate regulators of fusion from retroviral origin. Syncytin-A and syncytin-B are other candidates from retroviral origin in Muridae. The active role of syncytin in driving fusion of trophoblast has been identified, but its fusion mechanism is still unclear. As an intact retroviral envelope protein, syncytin-A shares similar structure profiling with other viral envelope fusion proteins, especially in the regions of N- and C-terminal heptad repeats (NHR and CHR, respectively). In this paper, we showed that SynA 1 + 2 of syncytin-A (residues 445-536, including predicted NHR, CHR, and a natural linker) could form trimer and exhibited significant alpha-helix structure and high thermo-stability. Limited proteolysis result identified a stable protease-resistant core of SynA 1 + 2, which was in good agreement with computational modeling data. NHR and CHR could interact with each other in vitro, too. Different from the previous studies, the disulfide-bonded linker was apparently vital to the stability of fusion core structure. By biological assays, NHR was shown to be inhibitive to cell-cell fusion, with IC(50) value about 5.4 microm, but CHR seemed to have no inhibitory activity even at 50 microm. From both biochemical and functional data, we first gave an explanation how syncytin-A mediated cell fusion. The insight into the mechanism of syncytin-A-mediated cell-cell fusion may provide a crucial clue to placental cytotrophoblast morphogenesis.

Amino Acid Sequence↗
PubMed2006

Ionizing radiation stimulates secretion of pro-inflammatory cytokines: dose-response relationship, mechanisms and implications.

In previous studies we showed a marked increase in secretion of inflammatory cytokines TNFalpha and interleukin (IL)-1beta by mouse macrophages in response to different doses of ionizing radiation (IR). Here we show the stimulation of IL-12 and IL-18 secretion by mouse peritoneal macrophages after whole-body irradiation with exploration of the possible mechanisms and implications in cancer radiotherapy. Both low (0.075 Gy) and high (2 Gy) doses of IR were found to cause sustained stimulation of IL-12 and IL-18 secretion by mouse macrophages; this paralleled the activation of NF-kappaB as well as up-regulated expression of CD14 and TLR4-MD2 on the macrophage surface and MyD88 in the cytoplasm. The expression of CD14, TLR4-MD2 and MyD88 increased in a dose-dependent manner from radiation doses between 0.05 and 2 Gy. The secretion of IL-12 and IL-18 showed a dose-dependent increase from doses between 0.05 and 4 Gy. It is concluded that IR can stimulate the secretion of IL-12 and IL-18 presumably via activation of the Toll signaling pathway in macrophages. The potential harmful effect of repeated doses of radiation used in radiotherapy for certain cancers is discussed.

Animals↗
PubMed2006

Chemical functionalization of magnetic carbon-encapsulated nanoparticles based on acid oxidation.

Carbon-encapsulated nickel nanoparticles were used as the representative magnetic carbon-encapsulated nanoparticles for chemical functionalization. After oxidation with the mixed acid of H2SO4/HNO3 under a moderate ultrasonic bath, carboxylic acid groups (-COOH) were effectively generated on the fullerene-like carbon shells, which in turn were utilized to covalently link octadecylamine through an amide reaction. The whole chemical process is well characterized by many methods such as Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetry-differential scanning calorimetry, transmission electron microscopy, and so on, and the self-consistent experimental results were obtained. The results suggested that the magnetic nanoparticles could be well protected, while their magnetic properties could be utilized to guide the transfer of the grafted functional species on the particle surface. This provides many possibilities for potential applications in chemical and biochemical fields.

Journal Article↗
PubMed2006

Gastrodin interaction with human fibrinogen: anticoagulant effects and binding studies.

In an effort to identify the anticoagulant activity of gastrodin (GAS) and to investigate the possibility of its use as a novel anticoagulant drug, the binding characteristics of GAS to human fibrinogen (Fg) were studied by using a quartz crystal microbalance (QCM) biosensor, anticoagulant animal experiments, and a molecular docking simulation. Real-time kinetic analysis with the QCM biosensor revealed that the in vitro binding of GAS to Fg was strong under physiological ionic conditions as the determined equilibrium dissociation constant (KD) was 1.94 x 10(-6) M. To check whether this strong binding may influence the natural coagulation function of Fg, the in vivo effect of GAS on the coagulation system of rats was examined. The results showed that GAS can significantly prolong the coagulation time (CT) and decrease the Fg content, while it had no effect on the activated kaolin partial thromboplastin time (KPTT) or prothrombin time (PT) in rats. To clarify the mechanism of the specific interaction, a molecular docking simulation was also performed to provide reasonable binding models for the interaction of GAS with Fg at the atomic level. GAS binds strongly to the inherent polymerization sites "a" and "b" (holes) on the Fg molecule with similar binding free energies of about -34 kJ mol(-1). Altogether, these findings confirmed first that GAS possesses anticoagulant activity and that the possible anticoagulation mechanism of GAS mainly involves its interference with the knob-to-hole interactions between fibrin molecules, thereby effectively inhibiting the formation of clots and decreasing the risk of thrombosis. The study has also shown the potential usefulness of QCM biosensor technology for the rapid screening of drug-protein interactions.

Animals↗
PubMed2006

Integration of curated databases to identify genotype-phenotype associations.

BACKGROUND: The ability to rapidly characterize an unknown microorganism is critical in both responding to infectious disease and biodefense. To do this, we need some way of anticipating an organism's phenotype based on the molecules encoded by its genome. However, the link between molecular composition (i.e. genotype) and phenotype for microbes is not obvious. While there have been several studies that address this challenge, none have yet proposed a large-scale method integrating curated biological information. Here we utilize a systematic approach to discover genotype-phenotype associations that combines phenotypic information from a biomedical informatics database, GIDEON, with the molecular information contained in National Center for Biotechnology Information's Clusters of Orthologous Groups database (NCBI COGs). RESULTS: Integrating the information in the two databases, we are able to correlate the presence or absence of a given protein in a microbe with its phenotype as measured by certain morphological characteristics or survival in a particular growth media. With a 0.8 correlation score threshold, 66% of the associations found were confirmed by the literature and at a 0.9 correlation threshold, 86% were positively verified. CONCLUSION: Our results suggest possible phenotypic manifestations for proteins biochemically associated with sugar metabolism and electron transport. Moreover, we believe our approach can be extended to linking pathogenic phenotypes with functionally related proteins.

Computational Biology↗
PubMed2006

An integrative genomic approach to uncover molecular mechanisms of prokaryotic traits.

With mounting availability of genomic and phenotypic databases, data integration and mining become increasingly challenging. While efforts have been put forward to analyze prokaryotic phenotypes, current computational technologies either lack high throughput capacity for genomic scale analysis, or are limited in their capability to integrate and mine data across different scales of biology. Consequently, simultaneous analysis of associations among genomes, phenotypes, and gene functions is prohibited. Here, we developed a high throughput computational approach, and demonstrated for the first time the feasibility of integrating large quantities of prokaryotic phenotypes along with genomic datasets for mining across multiple scales of biology (protein domains, pathways, molecular functions, and cellular processes). Applying this method over 59 fully sequenced prokaryotic species, we identified genetic basis and molecular mechanisms underlying the phenotypes in bacteria. We identified 3,711 significant correlations between 1,499 distinct Pfam and 63 phenotypes, with 2,650 correlations and 1,061 anti-correlations. Manual evaluation of a random sample of these significant correlations showed a minimal precision of 30% (95% confidence interval: 20%-42%; n = 50). We stratified the most significant 478 predictions and subjected 100 to manual evaluation, of which 60 were corroborated in the literature. We furthermore unveiled 10 significant correlations between phenotypes and KEGG pathways, eight of which were corroborated in the evaluation, and 309 significant correlations between phenotypes and 166 GO concepts evaluated using a random sample (minimal precision = 72%; 95% confidence interval: 60%-80%; n = 50). Additionally, we conducted a novel large-scale phenomic visualization analysis to provide insight into the modular nature of common molecular mechanisms spanning multiple biological scales and reused by related phenotypes (metaphenotypes). We propose that this method elucidates which classes of molecular mechanisms are associated with phenotypes or metaphenotypes and holds promise in facilitating a computable systems biology approach to genomic and biomedical research.

Algorithms↗
PubMed2006

Immunomodulatory and anticancer activities of flavonoids extracted from litchi (Litchi chinensis Sonn) pericarp.

The litchi pericarp extract was subjected to partition by hexane, ethyl acetate and water. Epicatechin, proanthocyanidin B2 and proanthocyanidin B4 were isolated and purified from the ethyl acetate fraction by reverse-phase high performance liquid chromatography. The immunomodulatory activities of epicatechin, proanthocyanidin B2, proanthocyanidin B4 and the ethyl acetate fraction were examined using proliferation of mouse splenocytes. The results showed all these samples had much higher stimulatory effects on splenocyte proliferation than that of the reference, rutin. Epicatechin and the ethyl acetate fraction showed a significantly (P<0.05) stimulatory effect when the concentration was up to 12.5 micro g/ml. Proanthocyanidin B2 and proanthocyanidin B4 exhibited little lower stimulatory effects than epicatechin and the ethyl acetate fraction. The anti-breast cancer activities of epicatechin, proanthocyanidin B2, proanthocyanidin B4 and the ethyl acetate fraction were also evaluated. Epicatechin and proanthocyanidin B2 had lower cytotoxicities to human breast cancer cell MCF-7 and human embryolic lung fibroblast than paclitaxel.

Acetates↗
PubMed2006

Effect of the phosphoryl substituent in the linear nitrone on the spin trapping of superoxide radical and the stability of the superoxide adduct: combined experimental and theoretical studies.

A new phosphorylated linear nitrone N-(4-hydroxybenzyliene)-1-diethoxyphosphoryl-1-methylethylamine N-oxide (4-HOPPN) was synthesized, and its X-ray structure was determined. The spin trapping ability of various kinds of free radicals by 4-HOPPN was evaluated. Kinetic study of decay of the superoxide spin adduct (4-HOPPN-OOH) shows the half-life time of 8.8 min. On the basis of the X-ray structural coordinates, theoretical analyses using density functional theory (DFT) calculations at the B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) level were performed on spin-trapping reactions of superoxide radical with 4-HOPPN and PBN and three possible decay routes for their corresponding superoxide adducts. The comparative calculations on the spin-trapping reactions with superoxide radical predicted that both spin traps share an identical reaction type and have comparable potency when spin trapping superoxide radical. Analysis of the optimized geometries of 4-HOPPN-OOH and PBN-OOH reveals that an introduction of the phosphoryl group can efficiently stabilize the spin adduct through the intramolecular H-bonds, the intramolecular nonbonding attractive interactions, as well as the bulky steric protection. Examination of the decomposition thermodynamics of 4-HOPPN-OOH and PBN-OOH further supports the stabilizing role of the phosphoryl group to a linear phosphorylated spin adduct.

Crystallography, X-Ray↗
PubMed2006

Prediction of protein orientation upon immobilization on biological and nonbiological surfaces.

We report on a rapid simulation method for predicting protein orientation on a surface based on electrostatic interactions. New methods for predicting protein immobilization are needed because of the increasing use of biosensors and protein microarrays, two technologies that use protein immobilization onto a solid support, and because the orientation of an immobilized protein is important for its function. The proposed simulation model is based on the premise that the protein interacts with the electric field generated by the surface, and this interaction defines the orientation of attachment. Results of this model are in agreement with experimental observations of immobilization of mitochondrial creatine kinase and type I hexokinase on biological membranes. The advantages of our method are that it can be applied to any protein with a known structure; it does not require modeling of the surface at atomic resolution and can be run relatively quickly on readily available computing resources. Finally, we also propose an orientation of membrane-bound cytochrome c, a protein for which the membrane orientation has not been unequivocally determined.

Animals↗
PubMed2006

Luminescent behavior of two novel thermo-sensitive poly(N-isopropylacrylamide) hydrogels incorporated with rare earth complexes.

Two novel luminescent temperature-sensitive poly(N-isopropylacrylamide) hydrogels fabricated with rare earth (Eu, Tb) picolinic acid complexes were in-situ synthesized within the interpenetration networks. Fluorescence spectra indicate the two functional gels exhibit red for Eu3+ species and green emissions for Tb3+ ones, respectively, whose luminescence intensities are changed due to temperature increasing from 5 to 30 degrees C until totally quenched at lower critical solution temperature (33 degrees C). In addition, the decreasing luminescence behavior obeys the simple linear equations. The releasing experiment substantiates that there may be complexation between O=C-NH- moieties of P-NIPAA and Eu3+ ions for the prolonged released time.

Journal Article↗
PubMed2006

Dimerization of Laforin is required for its optimal phosphatase activity, regulation of GSK3beta phosphorylation, and Wnt signaling.

Epilepsy of progressive myoclonus type 2 gene A (EPM2A) encodes a dual specificity protein phosphatase called Laforin. Laforin is also a tumor suppressor that dephosphorylates GSK3beta at the critical Ser9 position and regulates Wnt signaling. The epilepsy-causing mutations have a deleterious effect on phosphatase activity, regardless of whether they locate in the carbohydrate-binding domain (CBD) at the N terminus or the dual specificity phosphatase domain (DSPD) at the C terminus. How mutations outside the DSPD reduce the phosphatase activity of Laforin remains unexplained. Here we report that Laforin expressed in mammalian cells forms dimers that are highly resistant to SDS treatment. Deleting CBD completely abolished the dimerization and phosphatase activity of Laforin. Moreover, all of the naturally occurring Laforin mutations tested impaired laforin GSK3beta dephosphorylation at Ser9 dimerization, and beta-catenin accumulation in nucleus. Our results demonstrate a critical role of dimerization in Laforin function and suggest an important new dimension in protein phosphatase function and in molecular pathogenesis of Lafora's disease.

Animals↗
PubMed2006

Lack of neutralizing antibody response to HIV-1 predisposes to superinfection.

Occurrences of HIV-1 superinfection offer a unique opportunity to investigate the correlates of immune protection. Here we describe the neutralizing antibody responses of a cohort of recently infected individuals who were screened for HIV superinfection. Three individuals identified with HIV superinfection had less cross-protective and autologous neutralizing antibody response than their non-superinfected case-controls. Neutralizing antibody may be crucial in the protection against superinfection and may explain why superinfection has only been documented following recent infection or treatment interruption. These data have considerable implications for vaccine development.

Adult↗
PubMed2006

Identification of a novel nonstructural protein, VP9, from white spot syndrome virus: its structure reveals a ferredoxin fold with specific metal binding sites.

White spot syndrome virus (WSSV) is a major pathogen in shrimp aquaculture. VP9, a full-length protein of WSSV, encoded by open reading frame wsv230, was identified for the first time in the infected Penaeus monodon shrimp tissues, gill, and stomach as a novel, nonstructural protein by Western blotting, mass spectrometry, and immunoelectron microscopy. Real-time reverse transcription-PCR demonstrated that the transcription of VP9 started from the early to the late stage of WSSV infection as a major mRNA species. The structure of full-length VP9 was determined by both X-ray and nuclear magnetic resonance (NMR) techniques. It is the first structure to be reported for WSSV proteins. The crystal structure of VP9 revealed a ferredoxin fold with divalent metal ion binding sites. Cadmium sulfate was found to be essential for crystallization. The Cd2+ ions were bound between the monomer interfaces of the homodimer. Various divalent metal ions have been titrated against VP9, and their interactions were analyzed using NMR spectroscopy. The titration data indicated that VP9 binds with both Zn2+ and Cd2+. VP9 adopts a similar fold as the DNA binding domain of the papillomavirus E2 protein. Based on our present investigations, we hypothesize that VP9 might be involved in the transcriptional regulation of WSSV, a function similar to that of the E2 protein during papillomavirus infection of the host cells.

Animals↗
PubMed2006

The budding yeast Pichia pastoris has a novel Sec23p homolog.

In Pichia pastoris, coat protein complex II (COPII) vesicles form at discrete transitional ER (tER) sites. Analyzing COPII coat proteins in this yeast will help to reveal the mechanisms of tER organization. Here, we show that like Saccharomyces cerevisiae, P. pastoris contains essential SEC23 and SEC24 genes, as well as the non-essential SEC24 homolog LST1. In addition, P. pastoris contains a novel non-essential SEC23 homolog that we have designated SHL23. The products of all four genes are concentrated at tER sites. Deletion of SHL23 does not disrupt tER morphology. As judged by two-hybrid analysis, Sec23p associates with both Sec24p and Lst1p, whereas Shl23p associates selectively with Lst1p. These results suggest that P. pastoris COPII vesicles contain an Shl23p/Lst1p complex that is absent in S. cerevisiae.

Amino Acid Sequence↗
PubMed2006

TGF-beta2 inhibition augments the effect of tumor vaccine and improves the survival of animals with pre-established brain tumors.

TGF-beta2 secretion by high grade gliomas has been implicated as one of the major factors contributing to tumor growth, alterations in the host immune response to tumor, and failure of gliomas to respond to current immunotherapy strategies. We hypothesized that targeted delivery and inhibition of TGF-beta2 by TGF-beta2 antisense oligonucleotides (AS-ODNs) would overcome tumor-induced immunosuppression and enhance the capacity of tumor vaccines to eradicate established brain tumors. Utilizing the mRNA sequences of TGF-beta2, specific AS-ODNs were constructed and tested for their ability to inhibit TGF-beta2 production in 9L glioma cells. The effect of combining local intracranial administration of antisense ODNs with systemic tumor vaccine was examined. Fisher 344 rats were vaccinated subcutaneously with irradiated 9L tumor cells 3 days after intracranial tumor implantation. Four days after vaccination, ODNs were administered into the tumor mass and survival was followed. ODNs delivered locally distributed widely within the brain tumor mass and inhibited TGF-beta2 expression. Survival of tumor-bearing rats treated with the combination of local antisense and systemic tumor vaccine was significantly enhanced (mean survival time (MST): 48.0 days). In contrast, MST for animals treated with nonsense plus vaccine, vaccine alone, antisense alone or PBS showed no survival advantage and no statistical differences between groups (33.5 days, 29.0 days, 37.5 days, and 31.5 days, respectively). Our data supports the hypothesis that local administration of antisense TGF-beta2 ODNs combined with systemic vaccination can increase efficacy of immunotherapy and is a novel, potentially clinically applicable, strategy for high-grade glioma treatment.

Animals↗
PubMed2006

Characterization of three types of ATP-activated current in relation to P2X subunits in rat trigeminal ganglion neurons.

In the present study, ATP-activated currents (I(ATP)s) recorded from rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique are classified into three types (F, I and S) based on the characteristics of their activation and desensitization. The time of rising phase (R(10-90)) of types F, I and S of I(ATP) is measured to be 33.6+/-4.5, 62.2+/-9.9 and 302.1+/-62.0 ms respectively, and positively correlated to cell size. The time of decaying phases (D(10-90)) of types F and S is 399.4+/-58.2 and >1500 ms, respectively. The dose-response curves for the three types of I(ATP) show that their EC(50) values are close (3.44 x 10(-5), 4.89 x 10(-5) and 4.14 x 10(-5) M for types F, I and S respectively, P>0.05). Their reversal potentials are basically the same, varying from +4 to +10 mV. In addition, using whole-cell patch clamp technique in combination with single cell immunohistochemical staining for P2X receptor subunits, our results suggest that the type distinction of ATP-activated current was associated with cell size and P2X receptor subunits: small-sized cells with type F of I(ATP) express only P2X1 and/or P2X3 subunits, while cells with types S and I of I(ATP) express P2X2 or P2X4 in addition to P2X1 and P2X3.

Adenosine Triphosphate↗