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Biomedical subjects

Ling Zhang

Publications and source records attributed to Ling Zhang.

At least 37 records · Page 2Linked to original sources
PubMed2006

Expression of T-STAR gene is associated with regulation of telomerase activity in human colon cancer cell line HCT-116.

AIM: To investigate the effects on telomerase activity of transfection of human T-STAR gene full-length sense cDNA or partial antisense cDNA into human colon cancer cell line HCT-116. METHODS: mRNA and protein expression levels of T-STAR gene were determined by RT-PCR and western blot, and telomerase activity was measured by PCR-ELISA, after transfection of T-STAR sense or antisense gene into HCT-116 cells with lipofectamine. RESULTS: T-STAR gene expression was enhanced or knocked down both at mRNA and protein levels, and telomerase activity was significantly increased or decreased. CONCLUSION: The T-STAR gene may participate in regulation of telomerase activity in human colon cancer HCT-116 cells in a parallel fashion.

DNA, Antisense↗
PubMed2006

Mutagenic nucleotide incorporation and hindered translocation by a food carcinogen C8-dG adduct in Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): modeling and dynamics studies.

Bulky carcinogen-DNA adducts commonly cause replicative polymerases to stall, leading to a switch to bypass polymerases. We have investigated nucleotide incorporation opposite the major adduct of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the DinB family polymerase, Dpo4, using molecular modeling and molecular dynamics (MD) simulations. PhIP, the most prevalent heterocyclic aromatic amine formed by cooking of proteinaceous food, is mutagenic in mammalian cells and is implicated in mammary and colon tumors. Our results show that the dG-C8-PhIP adduct can be accommodated in the spacious major groove Dpo4 open pocket, with Dpo4 capable of incorporating dCTP, dTTP or dATP opposite the adduct reasonably well. However, the PhIP ring system on the minor groove side would seriously disturb the active site, regardless of the presence and identity of dNTP. Furthermore, the simulations indicate that dATP and dTTP are better incorporated in the damaged system than in their respective mismatched but unmodified controls, suggesting that the PhIP adduct enhances incorporation of these mismatches. Finally, bulky C8-dG adducts, situated in the major groove, are likely to impede translocation in this polymerase (Rechkoblit et al. (2006), PLoS Biol., 4, e11). However, N2-dG adducts, which can reside on the minor groove side, appear to cause less hindrance when in this position.

Binding Sites↗
PubMed2006

Chain conformation and solvent partitioning in reversed-phase liquid chromatography: Monte Carlo simulations for various water/methanol concentrations.

Many structural models for the stationary phase in reversed-phase liquid chromatography (RPLC) systems have been suggested from thermodynamic and spectroscopic measurements and theoretical considerations. To provide a molecular picture of chain conformation and solvent partitioning in a typical RPLC system, a particle-based Monte Carlo simulation study is undertaken for a dimethyl octadecyl (C(18)) bonded stationary phase on a model siliceous substrate in contact with mobile phases having different methanol/water concentrations. Following upon previous simulations for gas-liquid chromatography and liquid-liquid phase equilibria, the simulations are conducted using the configurational-bias Monte Carlo method in the Gibbs ensemble and the transferable potentials for phase equilibria force field. The simulations are performed for a chain surface density of 2.9 micromol/m(2), which is a typical bonded-phase coverage for mono-functional alkyl silanes. The solvent concentrations used here are pure water, approximately 33 and 67% mole fraction of methanol and pure methanol. The simulations show that the chain conformation depends only weakly on the solvent composition. Most chains are conformationally disordered and tilt away from the substrate normal. The interfacial width increases with increasing methanol content and, for mixtures, the solvent shows an enhancement of the methanol concentration in a 10 Angstrom region outside the Gibbs dividing surface. Residual surface silanol groups are found to provide hydrogen bonding sites that lead to the formation of substrate bound water and methanol clusters, including bridging clusters that penetrate from the solvent/chain interfacial region all the way to the silica surface.

Chromatography, Liquid↗
PubMed2006

Genetic diversity and geographic differentiation in Tacca chantrieri (Taccaceae): an autonomous selfing plant with showy floral display.

BACKGROUND AND AIMS: Despite considerable investment in elaborate floral displays, Tacca chantrieri populations are predominantly selfing. It is hypothesized that this species might possess considerable spatial or temporal variation in outcrossing rates among populations. To test this hypothesis, genetic variability and genetic differentiation within and among T. chantrieri populations were investigated to find out if they are in agreement with expectations based on a predominantly inbred mating system. METHODS: Genetic diversity was quantified using inter-simple sequence repeats (ISSR) in 303 individuals from 13 populations taken from known locations of T. chantrieri in China, and from one population in Thailand. KEY RESULTS: Of the 113 primers screened, 24 produced highly reproducible ISSR bands. Using these primers, 160 discernible DNA fragments were generated, of which 145 (90.62 %) were polymorphic. This indicated considerable genetic variation at the species level. However, there were relatively low levels of polymorphism at population levels, with percentages of polymorphic bands (PPB) ranging from 8.75 % to 55 %. A high level of genetic differentiation among populations was detected based on different measures (Nei's genetic diversity analysis: G(ST) = 0.5835; AMOVA analysis: F(ST) = 0.6989). Furthermore, based on levels of genetic differentiation, the 14 populations clustered into two distinct groups separated by the Tanaka Line. CONCLUSIONS: High levels of differentiation among populations and low levels of diversity within populations at large spatial scales are consistent with earlier small-scale studies of mating patterns detected by allozymes which showed that T. chantrieri populations are predominantly selfing. However, it appears that T. chantrieri has a mixed-mating system in which self-fertilization predominates, but there is occasional outcrossing. Significant genetic differences between the two distinct regions might be attributed to vicariance along the Tanaka Line. Finally, possible mechanisms of geographic patterns based on genetic differentiation of T. chantrieri are discussed.

Dioscoreaceae↗
PubMed2006

Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells.

The Bmi-1 oncoprotein regulates proliferation and oncogenesis in human cells. Its overexpression leads to senescence bypass in human fibroblasts and immortalization of human mammary epithelial cells. In this study, we report that compared with normal nasopharyngeal epithelial cells (NPEC), Bmi-1 is overexpressed in nasopharyngeal carcinoma cell lines. Importantly, Bmi-1 was also found to be overexpressed in 29 of 75 nasopharyngeal carcinoma tumors (38.7%) by immunohistochemical analysis. In contrast to nasopharyngeal carcinoma, there was no detectable expression of Bmi-1 in noncancerous nasopharyngeal epithelium. Moreover, high Bmi-1 expression positively correlated with poor prognosis of nasopharyngeal carcinoma patients. We also report that the overexpression of Bmi-1 leads to bypass of senescence and immortalization of NPECs, which normally express p16(INK4a) and exhibit finite replicative life span. Overexpression of Bmi-1 in NPECs led to the induction of human telomerase reverse transcriptase activity and reduction of p16(INK4a) expression. Mutational analysis of Bmi-1 showed that both RING finger and helix-turn-helix domains of it are required for immortalization of NPECs. Our findings suggest that Bmi-1 plays an important role in the development and progression of nasopharyngeal carcinoma, and that Bmi-1 is a valuable marker for assessing the prognosis of nasopharyngeal carcinoma patients. Furthermore, this study provides the first cellular proto-oncogene immortalized nasopharyngeal epithelial cell line, which may serve as a cell model system for studying the mechanisms involved in the tumorigenesis of nasopharyngeal carcinoma.

Biomarkers, Tumor↗
PubMed2006

IL-6 signaling via the STAT3/SOCS3 pathway: functional analysis of the conserved STAT3 N-domain.

The conserved N-domain of the STAT proteins has been implicated in several activities crucial to cytokine signaling including receptor recruitment and STAT activation, cooperative DNA binding and STAT-dependent gene expression. We evaluated the role of the STAT3 N-domain in the IL-6 signal transduction pathway leading to Socs3 gene expression, an essential mechanism that controls the quality and magnitude of IL-6-dependent transcriptional responses. Based on the model for STAT N-domain function in cooperative gene expression and the presence of tandem STAT binding motifs in the murine Socs3 promoter, we anticipated that stabilizing interactions between adjacent STAT3 dimers via N-domain sequences might be essential for Socs3 gene expression. This was underscored by the tight conservation in the location and sequence of the tandem STAT binding sites between the murine and human Socs3 promoters. Using reconstitution into Stat3-/- mouse embryonic fibroblasts (Stat3-/- MEFs), we find that a STAT3 N-domain deletion mutant (Delta 133STAT3) is activated by tyrosine phosphorylation in response to IL-6 and then undergoes dephosphorylation with kinetics similar to full-length STAT3. These results highlight important differences compared to other STATs where the N-domain has been shown to mediate activation (STAT4) or dephosphorylation (STAT1). STAT3 binds predominantly to a single STAT consensus site in the Socs3 promoter, despite the presence of an adjacent STAT motif. Significantly, Delta 133STAT3 stimulates expression of the endogenous Socs3 gene in Stat3-/- MEFs upon IL-6 treatment with an activity similar to reconstituted STAT3, demonstrating that the N-domain is dispensable for Socs3 gene expression. We propose that the Socs3 gene in its chromosomal context is activated by the IL-6/STAT3 pathway independent of STAT3 N-domain sequences.

Animals↗
PubMed2006

Diode-pumped continuous-wave Nd:LuVO4 laser operating at 916 nm.

We realized an efficient diode-pumped Nd:LuVO4 continuous-wave (CW) laser operating at 916 nm. Laser experiments with 0.5 at. % Nd-doped Nd:LuVO4 crystals of various lengths and cutting directions were also investigated. The maximum output power of 930 mW was obtained with a slope efficiency of 27.2% and an optical conversion efficiency of 20.8% at the absorbed pump power of 4.5 W. The laser experiment shows that Nd:LuVO4 crystal can be used for an efficient diode-pumped laser system.

Journal Article↗
PubMed2006

k-space inherited parallel acquisition (KIPA): application on dynamic magnetic resonance imaging thermometry.

In this study, a novel method for dynamic parallel image acquisition and reconstruction is presented. In this method, called k-space inherited parallel acquisition (KIPA), localized reconstruction coefficients are used to achieve higher reduction factors, and lower noise and artifact levels compared to that of generalized autocalibrating partially parallel acquisition (GRAPPA) reconstruction. In KIPA, the full k-space for the first frame and the partial k-space for later frames are required to reconstruct a whole series of images. Reconstruction coefficients calculated for different segments of k-space from the first frame data set are used to estimate missing k-space lines in corresponding k-space segments of other frames. The local determination of KIPA reconstruction coefficients is essential to adjusting them according to the local signal-to-noise ratio characteristics of k-space data. The proposed algorithm is applicable to dynamic imaging with arbitrary k-space sampling trajectories. Simulations of magnetic resonance thermometry using the KIPA method with a reduction factor of 6 and using dynamic imaging studies of human subjects with reduction factors of 4 and 6 have been performed to prove the feasibility of our method and to show apparent improvement in image quality in comparison with GRAPPA for dynamic imaging.

Algorithms↗
PubMed2006

A high efficiency strategy for binding property characterization of peptide-binding domains.

A large proportion of protein-protein interactions is mediated by families of peptide-binding domains. Comprehensive characterization of each of these domains is critical for understanding the mechanisms and networks of protein interaction at the domain level. However, existing methods are all based on large scale screenings for each domain that are inefficient to deal with hundreds of members in major domain families. We developed a systematic strategy for efficient binding property characterization of peptide-binding domains based on high throughput validation screening of a specialized candidate ligand library using yeast two-hybrid mating array. Its outstanding feature is that the overall efficiency is dramatically improved compared with that of traditional screening, and it will be higher as the system cycles. PDZ domain family was first used to test the strategy. Five PDZ domains were rapidly characterized. Broader binding properties were identified compared with other methods, including novel recognition specificities that provided the basis for major revision of conventional PDZ classification. Several novel interactions were discovered, serving as significant clues for further functional investigation. This strategy can be easily extended to a variety of peptide-binding domains as a powerful tool for comprehensive analysis of domain binding property in proteomic scale.

Animals↗
PubMed2006

Heavy metals associated with reduced sulfur in sediments from different deposition environments in the Pearl River estuary, China.

Distribution of acid volatile sulfur (AVS) and the simultaneously extracted metals (SEM: Cu, Pb, Zn, Cd, Ni) in sediment profiles has been studied at five sites in Pearl River estuary, China. Of the five sampling locations, Nos.1 and 2 are in the middle shoal, Nos.3 and 4 in the west shoal and No. 5 locates to the south of the estuary. The AVS content in the sediments of the middle shoal varies in a small range (0.25-4.06 micromol g(-1)), while that of west shoal increases with depth from 0 to ultimately 26.09 micromol g(-1). The SEM concentration in the sediment profiles at location Nos. 1, 2 and 5 is generally in the range of 0.95+/-0.2 micromol g(-1) with a slight upward increase, while that in the sediment of west shallows are much higher (1.43-2.42 micromol g(-1)) with a significant upward increase, especially in the upper layer of ca. 15 cm. The observed upward increase of SEM content at all the sites implies that heavy metal contamination of sediment in the Pearl River estuary is increasing. Calculations of the excess heavy metal content which is defined by SEM-AVS molar difference suggests that the upper sediment in the Pearl River estuary, especially on the west shallows, could be a source of heavy metal contaminants and may cause toxicity to the benthos. The site-specific distribution patterns in the AVS and SEM profiles were interpreted according to the hydrogeochemistry of deposition environments.

China↗
PubMed2006

Influence of composition on the photorefractive centers in pure LiNbO3 at low light intensity.

The influence of composition on the photorefractive effect in pure LiNbO3 crystals at low light intensity was investigated. The experimental results indicate that different defects dominate the photorefractive centers of pure LiNbO3 with various compositions. Bipolarons are considered to be responsible for the enhanced photovoltaic field in reduced near-stoichiometric LiNbO3, and their bulk photovoltaic constant kappa is estimated to be approximately 6.95 x 10(-32) m3/V. Q polarons (composed of two bipolarons) are introduced to explain the photorefractive effect of congruent LiNbO3 at both low and high light intensities.

Journal Article↗
PubMed2006

An integrated machine learning system to computationally screen protein databases for protein binding peptide ligands.

A fairly large set of protein interactions is mediated by families of peptide binding domains, such as Src homology 2 (SH2), SH3, PDZ, major histocompatibility complex, etc. To identify their ligands by experimental screening is not only labor-intensive but almost futile in screening low abundance species due to the suppression by high abundance species. An ideal way of studying protein-protein interactions is to use high throughput computational approaches to screen protein sequence databases to direct the validating experiments toward the most promising peptides. Predictors with only good cross-validation were not good enough to screen protein databases. In the current study we built integrated machine learning systems using three novel coding methods and screened the Swiss-Prot and GenBank protein databases for potential ligands of 10 SH3 and three PDZ domains. A large fraction of predictions has already been experimentally confirmed by other independent research groups, indicating a satisfying generalization capability for future applications in identifying protein interactions.

Amino Acid Motifs↗
PubMed2006

Short courses of low dose dexamethasone delay bleomycin-induced lung fibrosis in rats.

After comparing mortality and clinical signs in rats receiving different dexamethasone treatments, we investigated whether 0.5 mg/kg/d dexamethasone could delay pulmonary fibrosis induced by bleomycin and its time course (1, 3, 7, 14, 21 and 28 days). Tissue injury was assessed by apoptosis, lactate dehydrogenase (LDH) release, malondialdehyde content, and protein content; and inflammation was measured in terms of myeloperoxidase (MPO) activity, inflammatory cell count, and the mRNA expression of pro/inflammatory cytokines. Fibrogenic activity was analyzed by measuring the mRNA expression of fibrotic cytokines in tissue, and the promotion of fibroproliferation and synthesis of collagen type I by bronchoalveolar lavage fluids in vitro; and fibrosis was assessed by measuring the hydroxyproline content and collagen-I mRNA expression, and by histology. Bleomycin treatment induced tissue injury, inflammation and fibrogenic activity in lung, and led to fibrosis. Treatment with dexamethasone diminished the extent of fibrosis by strongly reducing inflammation, lung damage, and fibrogenic activity. These results demonstrate that the progression of bleomycin-induced pulmonary fibrosis in rats can be delayed by dexamethasone treatment, which appeared to alleviate not only inflammation but also lung damage and fibrogenic activity, indicating a possible new role for dexamethasone in the treatment of fibrosis.

Animals↗
PubMed2006

Evaluation of the stress-inducible production of choline oxidase in transgenic rice as a strategy for producing the stress-protectant glycine betaine.

Glycine betaine (GB) is a compatible solute that is also capable of stabilizing the structure and function of macromolecules. Several GB-producing transgenic rice lines were generated in which the Arthrobacter pascens choline oxidase (COX) gene, fused to a chloroplast targeting sequence (TP) was expressed under the control of an ABA-inducible promoter (SIP; stress-inducible promoter) or a ubiquitin (UBI) gene promoter that is considered to be constitutive. This comparison led to interesting observations that suggest complex regulation with respect to GB synthesis and plant growth response under stress. In spite of the use of the well-studied stress-inducible promoter, the highest level of GB accumulation (up to 2.60 micromol g(-1) DW) in the SIP lines grown under saline conditions was not as high as in the UBI lines (up to 3.12 micromol g(-1) DW). Therefore, the use of an ABA-inducible promoter was not more beneficial for de novo production of GB. Interestingly, saline growth conditions enhanced GB accumulation by up to 89% in the SIP lines, whereas up to 44% increase was seen in a UBI line. In all these cases the GB levels were many-fold below the range reported for plant species that produce GB naturally. In spite of lower GB concentrations, statistically greater levels of stress tolerance were found in SIP lines than in UBI lines, suggesting that the stress protection observed in SIP plants cannot be totally explained by the increase in the GB content.

Abscisic Acid↗
PubMed2006

The clinical significance of twist expression in nasopharyngeal carcinoma.

The present study was aimed to determine twist expression in nasopharyngeal carcinoma (NPC) and to investigate the clinicopathological significance in the progress of NPC. Semiquantitative RT-PCR and Western blotting were carried out to investigate the expression of Twist in NPC cell lines and normal nasopharyngeal epithelial cell line, which showed that both Twist mRNA and protein were up-regulated in the tumor cells in comparison with the normal cells. We then examined Twist mRNA expression in non-cancerous nasopharyngeal mucosa (10 cases) and NPC (95 cases) using in situ hybridization. The results showed that Twist was overexpressed in 59 of 95 (62.1%) NPC samples. In contrast, there was no obvious expression of Twist mRNA in non-cancerous tissues. In addition, another 75 NPC samples were analyzed by immunohistochemistry, and 33 of the 75 samples were shown to be positive for Twist protein. Both Twist mRNA expression and Twist protein expression were positively associated with lymph-node metastasis and distant metastasis. Furthermore, expression of Twist protein was correlated with the NPC prognosis. Patients with NPC who were Twist protein-positive had a worse 5-year survival rate. These findings demonstrate that the Twist may play an important role in the invasion and metastasis of NPC. Twist protein is valuable marker for assessing the prognosis of NPC.

Biomarkers, Tumor↗
PubMed2006

Characterization of kynurenine aminotransferase III, a novel member of a phylogenetically conserved KAT family.

Kynurenine aminotransferase (KAT) is an enzyme responsible for synthesis of kynurenic acid (KYNA), a well established neuroprotective and anticonvulsant agent, involved in synaptic transmission and implicated in the pathophysiology of schizophrenia, Huntington's disease and other neurological disorders. We have shown previously that kat2-/- mice had lower hippocampal KYNA levels and were more hyperactive than wild-type mice. However, these abnormalities occur early and are transitory coinciding with restoration of KYNA levels, suggesting that compensatory changes or ontogenetic expression of another unknown homolog may account for the normalization of KYNA levels in the adult kat2-/- mice brain. Here, we report the isolation of a novel KAT molecule, kat3, from mouse and human brain cDNA libraries. The encoded 454 amino acids of human KAT III share 64.8% similarity to that of KAT I and 30.1% to KAT II. Northern blot analysis demonstrated that kat3 mRNA is widely expressed but with higher expression levels in liver, kidney, heart, and neuroendocrine tissues. RT-PCR and Northern analysis showed that kat3 expression starts as early as postnatal day (PND) 7 and peaks in adult. The mRNA level of kat3 and kat1 when measured together is significantly higher at PND 60 in kat2-/- mice than those of wild-type mice indicating possible co-regulation of expression levels. RNA-interference (RNAi) directed towards transcripts for either R03A10.4 or F28H6.3 in Caenorhabditis elegans which are kat1 and kat3 orthologs, respectively, did not result in any gross abnormalities. Our results show that upregulation of kat3 and kat1 may be responsible for the phenotypic rescue on kat2-/- mice.

5' Untranslated Regions↗
PubMed2006

Manufacture of multimicrotubule chitosan nerve conduits with novel molds and characterization in vitro.

Multimicrotubule chitosan conduits (M-conduits) were fabricated using novel molds and a thermal-induced phase-separation technique. Hollow chitosan conduits (H-conduits) with an inner diameter of 1-5 mm and a wall thickness of 0.2-1.0 mm were made, and then a novel mold composed of a styrofoam insulating pedestal with several holes and a stainless steel cover plate was used to make M-conduits. In brief, corresponding H-conduits were inserted upright into the holes of the styrofoam pedestal, and filled with chitosan solution, then rapidly covered with the precooled stainless steel cover plate, and then placed in a freezer. The styrofoam insulating pedestal enclosing the conduits could reduce the heat transfer through the side wall of the conduits. Gradual phase separation then occurred uniaxially in the presence of a unidirectional temperature gradient from the top end to the bottom end of the chitosan conduits. The phase-separated polymer/solvent systems were then dried in a freeze-dryer. The microtubule diameters were controlled by adjusting the polymer concentration and cooling temperature. In vitro characterization demonstrated that the mold-based multimicrotubule chitosan conduits possessed suitable mechanical strength, microtubule diameter distribution, porosity, swelling, biodegradability, and nerve cell affinity, and so they showed potential for application as nerve tissue engineering scaffolds.

Absorbable Implants↗