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Biomedical subjects

Wei Zhang

Publications and source records attributed to Wei Zhang.

At least 199 records · Page 11Linked to original sources
PubMed2006

Decision forest analysis of large-scale sib-pair identical-by-decent profiles for locating the underlying disease genes for alcoholism in human.

OBJECTIVE: To extract the relevant SNPs for alcoholism using sib-pair IBD profiles of pedigrees. METHODS: We used the ensemble decision approach, a supervised learning approach based on decision forests, to locate alcoholism relevant SNPs using genome-wide SNP data. RESULTS: Application to a publicly available large dataset of 100 simulated replicates for three American populations (http://www.gaworkshop.org/) demonstrates that the proposed approach has successfully located all of the simulated true loci. CONCLUSION: The numerical results establish the proposed decision forest analysis to be a powerful and practical alternative for large-scale family-based association study.

Alcoholism↗
PubMed2006

Eosinophilic granuloma of the jaws: an analysis of clinical and radiographic presentation.

Eosinophilic granuloma (EG) is the localized and mildest form of histiocytosis-X group of diseases. In this study, 22 patients of pathologically proven EG involving the jaws were retrospectively studied concerning the clinical and radiographic presentation. The clinical and radiographic presentation of the 22 cases was quite varied, and the accuracy of clinical and radiographic diagnosis was low. However, the clinical and radiographic presentation correlated with the lesion site, and accordingly all the jaw lesions could be divided into three types (Alveolar Type, Intraosseous Type, and Mixed Type). Our classification based on the lesion sites reveals the correlation between the clinical and radiographic presentation of EG and the lesion sites, and may be useful in the identification of lesions of EG in the jaws.

Adolescent↗
PubMed2006

A normal mucin-binding lectin from the sponge Craniella australiensis.

A lectin, Craniella australiensis (CAL), was isolated from sponge C. australiensis by ion-exchange on DEAE-Sephacel and purified by gel filtration on Sephadex G-150 and HPLC on DEAE-5PW. The purified lectin was a trimeric protein as revealed by SDS-PAGE and MALDI-TOF analysis. SDS-PAGE showed that the CAL protein had a molecular mass of 54 kDa, and consisted of three 18 kDa subunits. Gel filtration of purified lectin on Sephadex G-200 indicates that it exists as a 54 kDa protein in its native state. The amino acid composition was rich in Thr and Glx. CAL was found to agglutinate native and trypsinized human A, B erythrocytes, and agglutinate native erythrocytes of mouse, sheep, rabbit and chicken, and trypsinized erythrocytes of sheep and rabbit. The hemagglutination activity was inhibited by glycoproteins such as PSM and asialo-PSM, but not by any of the monosaccharides tested. The activity was stable between 20 and 70 degrees C. Significant CAL activity was observed between pH 5 and 8. The lectin reaction is independent of the presence of divalent cations Ca2+ and Mg2+. The sequence of N-terminal residues of CAL was determined as TSSCQSIVVE. The lectin showed a potent mitogenic response towards BALB/c splenocytes.

Amino Acid Sequence↗
PubMed2006

Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases.

Miltirone analogues were synthesized and evaluated for inhibitory activity against Cdc25 and PTP1B. Most of the compounds demonstrated potent Cdc25 inhibitory activity, and several exhibited higher selectivity for Cdc25 than for PTP1B. In a cytotoxic assay, most of the compounds displayed cytotoxicity against the tumor cell lines A549 and HCT-116, producing IC(50) values in the micromolar range.

Cell Line, Tumor↗
PubMed2006

[Mechanism of reversion of myocardial interstitial fibrosis in diabetic cardiomyopathy by valsartan].

OBJECTIVE: To investigate the mechanism of reversion of myocardial interstitial fibrosis in diabetic cardiomyopathy (DCM) by valsartan. METHODS: Forty male wistar rats were randomly divided into 3 groups: DCM group, n = 16, fed with high-fat diet for 4 weeks and injected intraperitoneally with streptozocin (STZ) once to induce hyperglycemia so as to construct a DCM model, and then perfused into the stomach with normal saline; valsartan group, n = 16, to be constructed into DCM model and then perfused into the stomach with valsartan once daily; and control group (n = 8, fed with normal food and perfused into the stomach with normal saline. Four weeks after feeding (i.e., before injection of STZ), 1 week after STZ injection, and by the end of experiment after 12-hour fasting samples of venous blood were collected to detect the contents of triglyceride and fasting blood-glucose and insulin; by the end of experiment miniature cardiac catheter was inserted into the left ventricle to conduct hemodynamic examination. Then myocardium tissues were collected, collagen content was detected by Masson staining, real-time RT-PCR was used to detect the mRNA expression of thrombospondin (TSP)-1 and tumor growth factor (TGF)-beta(1) mRNA, expression, and Western blotting was used to detect the protein expression of TSP-1, active TGF-beta(1) (A-TGF-beta(1)) and latent TGF-beta(1) (L-TGF-beta(1)). RESULTS: By the end of the experiment, the body weights, and insulin sensitivity index were significantly lower and fasting blood-glucose, and serum triglyceride and cholesterol were significantly higher in the DCM group and valsartan group in comparison with those in the control group (all P < 0.01), however, there was no significant differences in fasting insulin among these 3 groups. The values of left ventricular systolic pressure (LVSP) and +/- dp/dt(max) were significantly lower and left ventricular end diastolic pressure were significantly higher in the DCM group in comparison with the control group (all P < 0.01). The LVSP and -dp/dt(max) were significantly higher and LVEDP was significantly lower in the valsartan group than in the DCM group (all P < 0.05). The LVEDP was significantly higher and -dp/dt(max) was significantly lower in the valsartan group than in the control group. Electron microscopy showed the distribution of a great amount of collagen in the myocardial interstitial tissue. The collagen content of the DCM group was 17 +/- 3, significantly higher than that of the control group (11 +/- 3, P < 0.05), and the collagen content of the valsartan group was 13 +/- 3, significantly lower than that of the DCM group (P < 0.05). The mRNA expression of TSP-1 and that of TGF-beta(1) were significant higher in the DCM group than in the control group (both P < 0.05), and were significantly lower in the valsartan group than in the DCM group (both P < 0.05); however, the TGF-beta(1) mRNA expression in the valsartan group was significantly higher in the valsartan group than in the control group (P < 0.05). The values of protein expression of TSP-1, A-TGF-beta(1) and L-TGF-beta(1) were all significantly higher in the DCM group than in the control group (all P < 0.05), and the values of protein expression of TSP-1 and A-TGF-beta(1) in the valsartan group were both significantly lower than those in the DCM group (both P < 0.05), however, there was no significant difference in the protein expression of L-TGF-beta(1) between the valsartan group and DCM group. CONCLUSION: Valsartan amelioorates myocardial interstitial fibrosis in DCM via TSP-1/TGF-beta(1) signaling pathway.

Animals↗
PubMed2006

Effects of a type of quenched randomness on car accidents in a cellular automaton model.

In this paper we numerically study the probability Pac of the occurrence of car accidents in the Nagel-Schreckenberg (NS) model with a defect. In the deterministic NS model, numerical results show that there exists a critical value of car density below which no car accident happens. The critical density Pc1 is not related only to the maximum speed of cars, but also to the braking probability at the defect. The braking probability at a defect can enhance, not suppress, the occurrence of car accidents when its value is small. Only the braking probability at the defect is very large, car accidents can be reduced by the bottleneck. In the nondeterministic NS model, the probability Pac exhibits the same behaviors with that in the deterministic model except the case of vmax=1 under which the probability Pac is only reduced by the defect. The defect also induces the inhomogeneous distribution of car accidents over the whole road. Theoretical analyses give an agreement with numerical results in the deterministic NS model and in the nondeterministic NS model with vmax=1 in the case of large defect braking probability.

Journal Article↗
PubMed2006

Leptin: a potential novel antidepressant.

Leptin, a hormone secreted from adipose tissue, was originally discovered to regulate body weight. The localization of the leptin receptor in limbic structures suggests a potential role for leptin in emotional processes. Here, we show that rats exposed to chronic unpredictable stress and chronic social defeat exhibit low leptin levels in plasma. Systemic leptin treatment reversed the hedonic-like deficit induced by chronic unpredictable stress and improved behavioral despair dose-dependently in the forced swim test (FST), a model widely used for screening potential antidepressant efficacy. The behavioral effects of leptin in the FST were accompanied by increased neuronal activation in limbic structures, particularly in the hippocampus. Intrahippocampal infusion of leptin produced a similar antidepressant-like effect in the FST as its systemic administration. By contrast, infusion of leptin into the hypothalamus decreased body weight but had no effect on FST behavior. These findings suggest that: (i) impaired leptin production and secretion may contribute to chronic stress-induced depression-like phenotypes, (ii) the hippocampus is a brain site mediating leptin's antidepressant-like activity, and (iii) elevating leptin signaling in brain may represent a novel approach for the treatment of depressive disorders.

Adipose Tissue↗
PubMed2006

Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex during defense response in mice.

We have previously shown that some features of the defense response, such as increases in arterial blood pressure (AP), heart rate (HR), and ventilation were attenuated in prepro-orexin knockout (ORX-KO) mice. Here, we examined whether the same was true in orexin neuron-ablated [orexin/ataxin-3 transgenic mice (ORX/ATX-Tg)] mice. In addition, we examined other features of the defense response: skeletal muscular vasodilation and shift of baroreceptor reflex. In both anesthetized and conscious conditions, basal AP in ORX/ATX-Tg mice was significantly lower by approximately 20 mmHg than in wild-type (WT) controls, as was the case in ORX-KO mice. The difference in AP disappeared after treatment with an alpha-blocker but not with a beta-blocker, indicating lower sympathetic vasoconstrictor outflow. Stimulation of the perifornical area (PFA) in urethane-anesthetized ORX/ATX-Tg mice elicited smaller and shorter-lasting increases in AP, HR, and ventilation, and skeletal muscle vasodilation than in WT controls. In addition, air jet stress-induced elevations of AP and HR were attenuated in conscious ORX/ATX-Tg mice. After pretreatment with a beta-blocker, atenolol, stimulation of PFA suppressed phenylephrine (50 microg/kg iv)-induced bradycardia (DeltaHR=-360+/-29 beats/min without PFA stimulation vs. -166+/-26 during stimulation) in WT. This demonstrated the resetting of the baroreflex. In ORX/ATX-Tg mice, however, no significant suppression was observed (-355+/-16 without stimulation vs. -300+/-30 during stimulation). The present study provided further support for our hypothesis that orexin-containing neurons in PFA play a role as a master switch to activate multiple efferent pathways of the defense response and also operate as a regulator of basal AP.

Adrenergic alpha-Antagonists↗
PubMed2006

Grow to Fit Molecular Dynamics (G2FMD): an ab initio method for protein side-chain assignment and refinement.

The rough energy landscapes and tight packing of protein interiors are two of the critical factors that have prevented the wide application of physics-based models in protein side-chain assignment and protein structure prediction in general. Complementing the rotamer-based methods, we propose an ab initio method that utilizes molecular mechanics simulations for protein side-chain assignment and refinement. By reducing the side-chain size, a smooth energy landscape was obtained owing to the increased distances between the side chains. The side chains then gradually grow back during molecular dynamics simulations while adjusting to their surrounding driven by the interaction energies. The method overcomes the barriers due to tight packing that limit conformational sampling of physics-based models. A key feature of this approach is that the resulting structures are free from steric collisions and allow the application of all-atom models in the subsequent refinement. Tests on a small set of proteins showed nearly 100% accuracy on both chi1 and chi2 of buried residues and 94% of them were within 20 degrees from the native conformation, 79% were within 10 degrees and 42% were within 5 degrees . However, the accuracy decreased when exposed side chains were involved. Further improvement and application of the method and the possible reasons that affect the accuracy on the exposed side chains are discussed.

Chemical Phenomena↗
PubMed2006

SOCS1 inhibits tumor necrosis factor-induced activation of ASK1-JNK inflammatory signaling by mediating ASK1 degradation.

We have previously shown that ASK1 undergoes ubiquitination and degradation in resting endothelial cells (EC) and that proinflammatory cytokine tumor necrosis factor (TNF) induces deubiquitination and stabilization, leading to ASK1 activation. However, the mechanism for the regulation of ASK1 stability is not known. In the present study, we have shown that SOCS1, a member of suppressor of cytokine signaling, induces ASK1 degradation. SOCS1 was constitutively expressed in EC and formed a labile complex with ASK1 that can be stabilized by proteasomal inhibitors. The phosphotyrosine-binding SH2 domain of SOCS1 was critical for its association with ASK1. Thus a SOCS1 mutant defective in phosphotyrosine binding failed to bind to and induce ASK1 degradation. Phosphotyrosine of ASK1 was induced in response to growth factors, and TNF induced dephosphorylation and dissociation of ASK1 from SOCS1. ASK1 with a mutation at Tyr-718 diminished the binding to SOCS1, suggesting that the phosphotyrosine-718 of ASK1 is critical for SOCS1 binding. Moreover, ASK1 expression and activity were up-regulated in SOCS1-deficient mice and derived EC, resulting in enhanced TNF-induced activation of JNK, expression of proinflammatory molecules, and apoptotic responses. We concluded that SOCS1 functions as a negative regulator in TNF-induced inflammation in EC, in part, by inducing ASK1 degradation.

Animals↗
PubMed2006

Stochastic resonance is applied to quantitative analysis for weak chromatographic signal of roxithromycin in beagle dog plasma.

Based on the theory of stochastic resonance, the signal to noise ratio (SNR) of HPLC/UV chromatographic signal of roxithromycin is enhanced by cooperation of signal, noise and nonlinear system. A simple new method for the determination of low concentration of roxithromycin in beagle dog plasma is presented. Using signal enhancement by stochastic resonance, this method extends the limit of quantitation from the reported 0.5 to 0.1 microg/ml. During validation of the new method, HPLC/MS was used as a comparison technique. The results indicate that the recovery and low concentrations of roxithromycin in beagle dog plasma were equivalent between the two methods (P>0.05). Stochastic resonance may be a promising tool for improving detection limits in trace analysis.

Animals↗
PubMed2006

The Arabidopsis thaliana PARTING DANCERS gene encoding a novel protein is required for normal meiotic homologous recombination.

Recent studies of meiotic recombination in the budding yeast and the model plant Arabidopsis thaliana indicate that meiotic crossovers (COs) occur through two genetic pathways: the interference-sensitive pathway and the interference-insensitive pathway. However, few genes have been identified in either pathway. Here, we describe the identification of the PARTING DANCERS (PTD) gene, as a gene with an elevated expression level in meiocytes. Analysis of two independently generated transferred DNA insertional lines in PTD showed that the mutants had reduced fertility. Further cytological analysis of male meiosis in the ptd mutants revealed defects in meiosis, including reduced formation of chiasmata, the cytological appearance of COs. The residual chiasmata in the mutants were distributed randomly, indicating that the ptd mutants are defective for CO formation in the interference-sensitive pathway. In addition, transmission electron microscopic analysis of the mutants detected no obvious abnormality of synaptonemal complexes and apparently normal late recombination nodules at the pachytene stage, suggesting that the mutant's defects in bivalent formation were postsynaptic. Comparison to other genes with limited sequence similarity raises the possibility that PTD may present a previously unknown function conserved in divergent eukaryotic organisms.

Amino Acid Sequence↗
PubMed2006

PERK (eIF2alpha kinase) is required to activate the stress-activated MAPKs and induce the expression of immediate-early genes upon disruption of ER calcium homoeostasis.

The eIF2alpha (eukaryotic initiation factor-2alpha) kinase PERK (doublestranded RNA-activated protein kinase-like ER kinase) is essential for the normal function of highly secretory cells in the pancreas and skeletal system, as well as the UPR (unfolded protein response) in mammalian cells. To delineate the regulatory machinery underlying PERK-dependent stress-responses, gene profiling was employed to assess global changes in gene expression in PERK-deficient MEFs (mouse embryonic fibroblasts). Several IE (immediate-early) genes, including c-myc, c-jun, egr-1 (early growth response factor-1), and fra-1 (fos-related antigen-1), displayed PERK-dependent expression in MEFs upon disruption of calcium homoeostasis by inhibiting the ER (endoplasmic reticulum) transmembrane SERCA (sarcoplasmic/ER Ca2+-ATPase) calcium pump. Induction of c-myc and egr-1 by other reagents that elicit the UPR, however, showed variable dependence upon PERK. Induction of c-myc expression by thapsigargin was shown to be linked to key signalling enzymes including PLC (phospholipase C), PI3K (phosphatidylinositol 3-kinase) and p38 MAPK (mitogen-activated protein kinase). Analysis of the phosphorylated status of major components in MAPK signalling pathways indicated that thapsigargin and DTT (dithiothreitol) but not tunicamycin could trigger the PERK-dependent activation of JNK (c-Jun N-terminal kinase) and p38 MAPK. However, activation of JNK and p38 MAPK by non-ER stress stimuli including UV irradiation, anisomycin, and TNF-alpha (tumour necrosis factor-alpha) was found to be independent of PERK. PERK plays a particularly important role in mediating the global cellular response to ER stress that is elicited by the depletion of calcium from the ER. We suggest that this specificity of PERK function in the UPR is an extension of the normal physiological function of PERK to act as a calcium sensor in the ER.

Animals↗
PubMed2006

Production of galacto-oligosaccharides by immobilized recombinant beta-galactosidase from Aspergillus candidus.

The preparation of galacto-oligosaccharides (GOSs) was studied using the immobilized recombinant beta-galactosidase from Aspergillus candidus CGMCC3.2919. The optimal pH and temperature for the immobilized enzyme were observed at pH 6.5 and 40 degrees C, respectively. Increasing the initial lactose concentration increased the yield of GOSs. The dilution rate was found to be a key factor during the continuous production of GOSs. The maximum productivity, 87 g/L.h was reached when 400 g/L lactose was fed at dilution rate of 0.8/h. The maximum GOS yield reached 37% at dilution rate of 0.5/h. Continuous operation was maintained for 20 days in a packed-bed reactor without apparent decrease in GOS production. The average yield of GOSs was 32%, corresponding to the average productivity of 64 g/L.h, which implied that the immobilized recombinant beta-galactosidase has potential application for GOS production.

Aspergillus↗
PubMed2006

Surface antibacterial characteristics of plasma-modified polyethylene.

The antibacterial characteristics of triclosan- or bronopol-coated and plasma-modified polyethylene (PE) are investigated. The modified PE samples exhibit excellent bactericidal effects against Escherichia coli and Staphylococcus aureus even when the bacteria concentration in the suspension is 10(6) colony forming units (CFU)/mL. However, when the concentration exceeds 10(8) CFU/mL, the materials fail to develop noticeable resistance to large amount of bacteria because of the formation of a bacterial biofilm on their surfaces. The PE treated by this relatively simple technique possesses excellent antimicrobial properties and is useful in biomedical and disinfection applications because the bacteria concentrations in most situations are well below 10(6) CFU/mL.

Anti-Bacterial Agents↗
PubMed2006

Expression of qBrn-1, a new member of the POU gene family, in the early developing nervous system and embryonic kidney.

It has been shown that POU domain genes play critical roles in the development of the nervous system. We have obtained a new member of the class III POU domain genes, qBrn-1, from the cDNA library of embryonic day 5 quail and have made an extensive expression pattern analysis of qBrn-1 and qBrn-2 throughout the early embryonic development by in situ hybridization. With a specific antibody we prepared, further analysis by immunohistochemistry showed that the location of qBrn-1 protein was consistent with that of the transcripts in the early developing quail. Our results showed that both qBrn-1 and qBrn-2 were preferentially expressed in the developing central nervous system, and their transcripts were initially detected in the neural plate and later in the distinct regions of the neural tube with a stage-dependent pattern. Moreover, their expression was also detected in both notochord and neural crests. However, qBrn-1 signal, different from qBrn-2, was more widely found in the auditory pits, branchial arches, and in the mesodermal components of the developing kidney. And the expression of qBrn-1 in nephric region was earlier and wider than that of mouse Brn-1, suggesting the characteristic function of qBrn-1 in the kidney formation. The distinct dynamic expression patterns of qBrn-1 and qBrn-2 indicate multiple roles of the class III POU genes in quail neurogenesis and organogenesis.

Amino Acid Sequence↗
PubMed2006

Recombinase-mediated cassette exchange to rapidly and efficiently generate mice with human cardiac sodium channels.

SCN5A encodes the predominant voltage-gated sodium channel isoform in human heart and nearly 100 variants have now been described and studied in vitro. However, development of animal models to analyze function of such large numbers of human gene variants represents a continuing challenge in translational medicine. Here, we describe the implementation of a two stage procedure, recombinase-mediated cassette exchange (RMCE), to efficiently and rapidly generate mice in which a full-length human cDNA replaces expression of the murine ortholog. In the first step of RMCE, conventional homologous recombination in mouse ES cells was used to replace scn5a exon 2 (that contains the translation start site) with a cassette acceptor that includes the thymidine kinase gene, flanked by loxP/inverted loxP sites. In the second step, the cassette acceptor site was replaced by the full-length wild-type human SCN5A cDNA by Cre/loxP-mediated recombination. The exchange event occurred in 7/29 (24%) colonies, and the time from electroporation to first homozygotes was only 8 months. PCR-restriction fragment length polymorphism (RFLP) showed that the murine isoform was replaced by the human one, and functional studies indicated that mice with human cardiac sodium channels have wild-type sodium current density, action potential durations, heart rates, and QRS durations. These data demonstrate that RMCE can be used to generate mice in which a targeted allele can be rapidly and efficiently replaced by variants of choice, and thereby can serve as an enabling approach for the functional characterization of ion channel and other DNA variants.

Animals↗