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Biomedical subjects

X Dong

Publications and source records attributed to X Dong.

At least 19 recordsLinked to original sources

Hepatitis C virus p7 protein is localized in the endoplasmic reticulum when it is encoded by a replication-competent genome.

p7 protein is a small protein encoded by Hepatitis C virus (HCV) that functions as an ion channel in planar lipid bilayers. The function of p7 is vital for the virus life cycle. In this study, the p7 protein of genotype 2a (strain JFH1; the only strain that replicates and produces virus progeny in vitro) was tagged with either an enhanced green fluorescent protein (eGFP) or a haemagglutinin (HA) epitope to facilitate tracking of the protein in the intracellular environment. The tagged viral polyprotein was expressed transiently in the cells after transfection with the recombinant RNA transcripts. Confocal microscopy revealed that the tagged p7 protein was localized in the endoplasmic reticulum (ER) but not associated with mitochondria. Immunoelectron microscopy confirmed the p7 localization data and, moreover, showed that intracellular virus-like particles formed in the cells transfected with the wild-type, but not the recombinant, transcripts. Following a few passages of the transfected cells, the recombinant genome with the HA tag reverted to wild-type and the entire tag was deleted. Therefore, in this study, it has been demonstrated that the p7 protein in the context of the full-length polyprotein encoded by a replication competent genome is only localized to the ER and has a possible role in HCV particle formation.

Cell Line↗

A 2a/1b full-length p7 inter-genotypic chimeric genome of hepatitis C virus is infectious in vitro.

The p7 protein of hepatitis C virus (HCV) functions as an ion channel in planar lipid bilayers, and its function is vital for the virus life cycle. In this study, we replaced either the entire or partial p7 of genotype 2a (strain JFH1), an HCV strain that replicates and produces virus progeny in vitro, with the corresponding regions of the p7 protein from genotype 1b (Australian isolate, HCV-A). Compared to wild type, the chimeric viruses reached their peak of infectivity with a delay but they produced a comparable titer to the wild type virus and the progeny viruses were able to infect naive permissive cells. Amantadine treatment of wild type and chimeric viruses reduced the virus titers by about 50% and 45%, respectively. Therefore, in this study, for the first time, we demonstrated that genotype 2a (JFH1 strain) genome encoding a full-length genotype 1b p7 gene produces infectious particles in vitro. These chimeric viruses are valuable instruments for comparative studies of the p7 proteins.

Amantadine↗

Direct observation of dijets in central Au+Au collisions at sqrt[sNN]=200 GeV.

The STAR Collaboration at the Relativistic Heavy Ion Collider reports measurements of azimuthal correlations of high transverse momentum (pT) charged hadrons in Au+Au collisions at higher pT than reported previously. As (pT) is increased, a narrow, back-to-back peak emerges above the decreasing background, providing a clear dijet signal for all collision centralities studied. Using these correlations, we perform a systematic study of dijet production and suppression in nuclear collisions, providing new constraints on the mechanisms underlying partonic energy loss in dense matter.

Journal Article↗

Identified baryon and meson distributions at large transverse momenta from Au + Au collisions at square root sNN=200 GeV.

Transverse momentum spectra of pi+/-, p, and p up to 12 GeV/c at midrapidity in centrality selected Au + Au collisions at square root sNN=200 GeV are presented. In central Au + Au collisions, both pi +/- and p(p) show significant suppression with respect to binary scaling at pT approximately >4 GeV/c. Protons and antiprotons are less suppressed than pi+/-, in the range 1.5 approximately < pT approximately < 6 GeV/c. The pi-/pi+ and p/p ratios show at most a weak pT dependence and no significant centrality dependence. The p/pi ratios in central Au + Au collisions approach the values in p + p and d + Au collisions at pT approximately >5 GeV/c. The results at high pT indicate that the partonic sources of pi+/-, p, and p have similar energy loss when traversing the nuclear medium.

Journal Article↗

Forward neutral pion production in p + p and d + Au collisions at square root sNN=200 GeV.

Measurements of the production of forward pi0 mesons from p + p and d + Au collisions at square root sNN=200 GeV are reported. The p + p yield generally agrees with next-to-leading order perturbative QCD calculations. The d + Au yield per binary collision is suppressed as eta increases, decreasing to approximately 30% of the p + p yield at eta =4.00, well below shadowing expectations. Exploratory measurements of azimuthal correlations of the forward pi0 with charged hadrons at eta approximately 0 show a recoil peak in p + p that is suppressed in d + Au at low pion energy. These observations are qualitatively consistent with a saturation picture of the low-x gluon structure of heavy nuclei.

Journal Article↗

Transient and stable expression of the HCV envelope glycoproteins in cell lines and primary hepatocytes transduced with a recombinant baculovirus.

A recombinant baculovirus, RecBV-E, encoding the hepatitis C virus (HCV) envelope proteins, E1 and E2, controlled by the cytomegalovirus promoter was constructed. RecBVs can infect mammalian cells, but fail to express proteins or replicate because the viral DNA promoters are not recognised. The RecBV-E transduced 86% of Huh7 cells and 22% of primary marmoset hepatocytes compared with 35% and 0.4%, respectively, after DNA transfection. Several stable cell lines were generated that constitutively expressed E1/E2 in every cell. No evidence of E1/E2-related apoptosis was noted, and the doubling times of cells were similar to that of the parental cells. A proportion of the E1/E2 was expressed on the surface of the stable cells as determined by flow cytometry and was detected by a conformation-dependent monoclonal antibody. It is likely that the continued expression of E1/E2 in the stable cells resulted from integration of the RecBV DNA. Infection of Huh7 cells, in the absence of G418 selection, failed to result in expression of the foreign gene (in this case, eGFP) beyond 14-18 days. RecBVs that express HCV genes from a CMV promoter represent an effective means by which to transduce primary hepatocytes for expression and replication studies.

Animals↗

Strange baryon resonance production in sqrt s NN=200 GeV p+p and Au+Au collisions.

We report the measurements of Sigma(1385) and Lambda(1520) production in p+p and Au+Au collisions at sqrt[s{NN}]=200 GeV from the STAR Collaboration. The yields and the p(T) spectra are presented and discussed in terms of chemical and thermal freeze-out conditions and compared to model predictions. Thermal and microscopic models do not adequately describe the yields of all the resonances produced in central Au+Au collisions. Our results indicate that there may be a time span between chemical and thermal freeze-out during which elastic hadronic interactions occur.

Journal Article↗

Long-term outcome of combined penetrating keratoplasty and vitreoretinal surgery using temporary keratoprosthesis.

PURPOSE: To evaluate the long-term outcome of combined penetrating keratoplasty (PKP) and vitreoretinal surgery using temporary keratoprosthesis (TKP). METHODS: A retrospective study of 107 eyes with coexisting corneal and vitreoretinal diseases that underwent combined PKP and vitreoretinal surgery using TKP. Corneal graft clarity, intraocular pressure, and anatomical reattachment of retina were followed. RESULTS: The mean follow-up time was 25 months, the longest being 8 years. Successful surgical outcome was defined as maintenance of clear graft, anatomic reattachment of retina, and controlled intraocular pressure. A total of 78 eyes (72.9%) fulfilled these criteria. Surgical intervention within 1 month of ocular injury was associated with higher success rate (81.9%) than intervention at 1 month or more after injury (54.3%). Success rate for reattachment of retina was 95.8% when preoperative proliferative vitreoretinal retinopathy (PVR) was absent compared with 83.1% when preoperative PVR was present. Unsatisfactory postoperative visual acuity was due to graft failure, recurrent PVR, or secondary glaucoma. CONCLUSION: Combined PKP and vitreoretinal surgery is best performed within 1 month of ocular injury for best surgical outcome. Careful selection of cases plays an important role in reducing the risks of complications. TKP is a useful adjunct in the surgery.

Adolescent↗

The metabolism of fatty alcohols in lipid nanoparticles by alcohol dehydrogenase.

Fatty alcohols are commonly used in lipid-based drug delivery systems including parenteral emulsions and solid lipid nanoparticles (NPs). The purpose of these studies was to determine whether horse liver alcohol dehydrogenase (HLADH), a NAD-dependent enzyme, could metabolize the fatty alcohols within the NPs and thus serve as a mechanism to degrade these NPs in the body. Solid nanoparticles (<100 nm) were engineered from oil-in-water microemulsion precursors using emulsifying wax NF as the oil phase and polyoxyethylene 20-stearyl ether (Brij 78) as the surfactant. Emulsifying wax contains both cetyl and stearyl alcohols. NPs were incubated with the enzyme and NAD+ at 37 degrees C for up to 48 h, and the concentrations of fatty alcohols were quantitatively determined over time by gas chromatography (GC). The concentrations of cetyl alcohol and stearyl alcohol within the NPs decreased to only 10-20% remaining after 15-24 h of incubation. In parallel, NP size, turbidity and the fluorescence intensity of NADH all increased over time. It was concluded that horse liver alcohol dehydrogenase/NAD+ was able to metabolize the fatty alcohols within the NPs, suggesting that NPs made of fatty alcohols may be metabolized in the body via endogenous alcohol dehydrogenase enzyme systems.

Alcohol Dehydrogenase↗

Amyloid precursor protein regulates differentiation of human neural stem cells.

Although amyloid beta (Abeta) deposition has been a hallmark of Alzheimer's disease (AD), the absence of a phenotype in the beta amyloid precursor protein (APP) knockout mouse, tends to detract our attention away from the physiological functions of APP. Although much attention has been focused on the neurotoxicity of Abeta, many studies suggest the involvement of APP in neuroplasticity. We found that secreted amyloid precursor protein (sAPP) increased the differentiation of human neural stem cells (hNSCs) in vitro, while an antibody-recognizing APP dose-dependently inhibited these activities. With a high dose of sAPP treatment or wild-type APP gene transfection, hNSCs were differentiated into astrocytes rather than neurons. In vivo, hNSCs transplanted into APP-transgenic mouse brain exhibited glial differentiation rather than neural differentiation. Our results suggest that APP regulates neural stem cell biology in the adult brain, and that altered APP metabolism in Down syndrome or AD may have implications for the pathophysiology of these diseases.

Amyloid beta-Protein Precursor↗

Distributions of charged hadrons associated with high transverse momentum particles in pp and Au+Au collisions at sqrt[sNN]=200 GeV.

Charged hadrons in [EQUATION: SEE TEXT] associated with particles of [EQUATION: SEE TEXT] are reconstructed in pp and Au+Au collisions at sqrt[sNN]=200 GeV. The associated multiplicity and p magnitude sum are found to increase from pp to central Au+Au collisions. The associated p distributions, while similar in shape on the nearside, are significantly softened on the awayside in central Au+Au relative to pp and not much harder than that of inclusive hadrons. The results, consistent with jet quenching, suggest that the awayside fragments approach equilibration with the medium traversed.

Journal Article↗

Multistrange Baryon elliptic flow in Au+Au collisions at square root of sNN=200 GeV.

We report on the first measurement of elliptic flow v2(pT) of multistrange baryons Xi- +Xi+ and Omega- + Omega+ in heavy-ion collisions. In minimum-bias Au+Au collisions at square root of s(NN)=200 GeV, a significant amount of elliptic flow, comparable to other nonstrange baryons, is observed for multistrange baryons which are expected to be particularly sensitive to the dynamics of the partonic stage of heavy-ion collisions. The pT dependence of v2 of the multistrange baryons confirms the number of constituent quark scaling previously observed for lighter hadrons. These results support the idea that a substantial fraction of the observed collective motion is developed at the early partonic stage in ultrarelativistic nuclear collisions at the Relativistic Heavy Ion Collider.

Journal Article↗

Multiplicity and pseudorapidity distributions of photons in Au+Au collisions at square root of (S(NN)) = 62.4 GeV.

We present the first measurement of pseudorapidity distribution of photons in the region 2.3 < or = eta < or = 3.7 for different centralities in Au+Au collisions at square root of (S(NN)) = 62.4 GeV. We find that the photon yield scales with the number of participating nucleons at all collision centralities studied. The pseudorapidity distribution of photons, dominated by pi0 decays, has been compared to those of charged pions, photons, and inclusive charged particles from heavy-ion and nucleon-nucleon collisions at various energies. The photon production has been shown to be consistent with the energy and centrality independent limiting fragmentation scenario.

Journal Article↗

A remarkable permeability of canalicular tight junctions might facilitate retrograde, non-viral gene delivery to the liver via the bile duct.

AIMS: To establish the extent of retrograde bile duct infusion at an ultrastructural level, as a preliminary step before evaluating the efficacy of gene delivery to the rat liver via a branch of the bile duct. METHODS: The extent of retrograde infusion into the biliary tree was established by light and electron microscopy, following infusion of 10 nm gold particles into the right lateral lobe. Canalicular permeability was further assessed by the infusion of a 67 kDa protein. For gene delivery, both naked DNA and a synthetic peptide vector system were evaluated. Because canalicular tight junction permeability can be compromised in damaged livers, both normal rats and rats recovering from the hepatotoxin D-galactosamine were studied. RESULTS: The gold particles penetrated the peripheral one third of the hepatic lobules and, surprisingly, reached the space of Disse in normal rats. Equally surprisingly, blood levels of a 67 kDa protein were identical after bile duct infusion and portal vein injection. Gene delivery with peptide/DNA complexes was much more effective in rats treated with D-galactosamine. However, gene delivery with naked DNA was equally effective in normal and damaged livers. Localisation of gene expression showed a scattering of positive hepatocytes restricted to the right lateral lobe. CONCLUSIONS: Retrograde infusion into the bile duct advances well into the hepatic lobule and reveals a remarkable permeability of the canalicular or cholangiole tight junctions in normal rats. It is an effective approach for delivering genes to a small population (approximately 1%) of hepatocytes.

Animals↗

Molecular orientation and film morphology of pentacene on native silicon oxide surface.

The growth morphology and mechanism of pentacene films on native Si oxide surface have been studied by using high-resolution electron energy loss spectroscopy (HREELS), X-ray diffraction (XRD), and atomic force microscopy (AFM). Despite the good agreement between our own and the reported XRD results, the previous XRD interpretation that the pentacene molecules are tilt-standing on the substrate cannot explain our HREELS data. The HREELS results show that a substantial portion of the first two layers of pentacene molecules are tilted-standing or randomly oriented, whereas the upper-layer molecules are mostly lying flat to the substrate. AFM reveals that the first two layers of molecules form a flat and smooth surface, but the upper layers show a rough terrace structure with a mean-square roughness equal to the average thickness (without counting the first two layers). This relationship is explained by a theoretical model which assumes the pentacene molecules to remain on a particular molecule layer after arrival. The observed film growth morphology may have significant implication on the performance of electronic devices based on pentacene thin films. A plausible explanation was proposed for the discrepancy between the HREELS-indicated and the XRD-derived molecular orientations.

Journal Article↗

Open charm yields in d+Au collisions at squareroot[sNN]=200 GeV.

Midrapidity open charm spectra from direct reconstruction of D0(D0)-->K-/+pi+/- in d+Au collisions and indirect electron-positron measurements via charm semileptonic decays in p+p and d+Au collisions at squareroot[sNN]=200 GeV are reported. The D0(D0) spectrum covers a transverse momentum (pT) range of 0.1<pT<3 GeV/c, whereas the electron spectra cover a range of 1<pT<4 GeV/c. The electron spectra show approximate binary collision scaling between p+p and d+Au collisions. From these two independent analyses, the differential cross section per nucleon-nucleon binary interaction at midrapidity for open charm production from d+Au collisions at BNL RHIC is dsigma(NN)cc/dy=0.30+/-0.04(stat)+/-0.09(syst) mb. The results are compared to theoretical calculations. Implications for charmonium results in A+A collisions are discussed.

Journal Article↗

Azimuthal anisotropy and correlations at large transverse momenta in p + p and Au + Au collisions at square root sNN=200 GeV.

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au + Au collisions at square root s(NN)=200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au + Au collisions to those in p + p at the same energy. The elliptic anisotropy v(2) is found to reach its maximum at p(t) approximately 3 GeV/c, then decrease slowly and remain significant up to p(t) approximately 7-10 GeV/c. Stronger suppression is found in the back-to-back high-p(t) particle correlations for particles emitted out of plane compared to those emitted in plane. The centrality dependence of v(2) at intermediate p(t) is compared to simple models based on jet quenching.

Journal Article↗