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Biomedical subjects

Wei Zhao

Publications and source records attributed to Wei Zhao.

At least 109 records · Page 6Linked to original sources

Electron affinities of 1,1-diaryl-2,3,4,5-tetraphenylsiloles: direct measurements and comparison with experimental and theoretical estimates.

We present a comprehensive experimental and theoretical characterization of the electronic structure of four 1,1-diaryl-2,3,4,5-tetraphenylsiloles (aryl = phenyl, 2-(9,9-dimethylfluorenyl), 2-thienyl, pentafluorophenyl). Solid-state electron affinities and ionization potentials of these siloles were measured using inverse-photoelectron spectroscopy (IPES) and photoelectron spectroscopy (PES), respectively; the density of electronic states obtained from calculations performed at the density functional theory (DFT) level corresponds very well to the PES and IPES data. The direct IPES measurements of electron affinity were then used to assess alternative estimates based on electrochemical and/or optical data. We also used DFT to calculate the reorganization energies for the electron-transfer reactions between these siloles and their radical anions. Additionally, optical data and ionization potential and electron affinity data were utilized to estimate the binding energies of excitons in these siloles.

Electrochemistry↗

Solution structure of Kti11p from Saccharomyces cerevisiae reveals a novel zinc-binding module.

Kti11p is a small, highly conserved CSL zinc finger-containing protein found in many eukaryotes. It was first identified as one of the factors required for maintaining the sensitivity of Saccharomyces cerevisiae to Kluyveromyces lactis zymocin. Then, it was found to be identical to Dph3, a protein required for diphthamide biosynthesis on eEF-2, the target of diphtheria toxin and Pseudomonas exotoxin A, in both yeast and higher eukaryotes. Furthermore, Kti11p/Dph3 was found to physically interact with core-Elongator, ribosomal proteins, eEF-2, two other proteins required for diphthamide modification on eEF-2, and DelGEF. Here, we determined the solution structure of Kti11p using NMR, providing the first structure of the CSL-class zinc-binding protein family. We present the first experimental evidence that Kti11p can bind a single Zn(2+) ion by its four conserved cysteine residues. The major structure of Kti11p comprises a beta sandwich as well as an alpha helix. Moreover, a structure-based similarity search suggests that it represents a novel structure and may define a new family of the zinc ribbon fold group. Therefore, our work provides a molecular basis for further understanding the multiple functions of Kti11p/Dph3 in different biological processes.

Amino Acid Sequence↗

Syntheses, crystal structures, and magnetic properties of novel manganese(II) complexes with flexible tripodal ligand 1,3,5-tris(imidazol-1-ylmethyl)-2,4,6-trimethylbenzene.

Two novel metal-organic frameworks (MOFs)--[Mn(titmb)(N3)2] x 1.5H2O (1) and [Mn3(titmb)2(C2O4)3(H2O)] x 10H2O (2)--were obtained by reactions of the flexible tripodal ligand 1,3,5-tris(imidazol-1-ylmethyl)-2,4,6-trimethylbenzene (titmb) with Mn(OAc)2 x 4H2O, together with NaN3 and K2C2O4, respectively. The structures of these MOFs were established by single-crystal X-ray diffraction analysis. The crystal data for 1 were as follows: monoclinic, C2/c, a = 20.956(13) A, b = 9.884(6) A, c = 24.318(14) A, beta = 95.87(5) degrees, Z = 8. The crystal data for 2 were as follows: triclinic, P1, a = 12.400(9) A, b = 16.827(12) A, c = 17.196(11) A, alpha = 66.35(5), beta = 95.87(5) degrees, gamma = 71.03(6), Z = 2. Complex 1 is a novel noninterpenetrating three-dimensional (3D) framework, in which the azide ligand connects Mn(II) atoms in an end-to-end (EE) mode to give [Mn-N-N-N-]n infinite one-dimensional (1D) chains, and complex 2 has a two-dimensional (2D) network structure in which the Mn(II) ions are linked by the oxalate anions to form 1D [Mn(C2O4)]n chains. Each titmb in these two complexes connects three metal atoms and serves as a three-connecting ligand. The magnetic properties of 1 and 2 were investigated. The results showed that the antiferromagnetic interactions occurred between the Mn(II) ions linked by the azide ligands in complex 1, and those linked by the oxalate anions and the carboxylate in syn-anti coordination mode in complex 2. The entirely different structures of complexes 1 and 2, on one hand, indicate that the azide and the oxalate ligands affected the structures of MOFs greatly, and on the other hand, reveals the potential applications of MOFs with the azide and oxalate ligands, which are efficient magnetic couplers.

Journal Article↗

Extended-range glucose biosensor via layer-by-layer assembly incorporating gold nanoparticles.

We report on a glucose oxidase (GOx)/polyelectrolyte (PE)/gold nanoparticle (AuNP) multilayer films that can be utilized as efficient glucose biosensors by layer-by-layer self-assembly method. Electrochemical impedance spectroscopy (EIS) and UV-visible spectroscopy were adopted to monitor the regular growth of the multilayer films. The role of gold nanoparticles integrated in the multilayer films not only increase the amount and activity of GOx, but also significantly improve the electron-transfer characteristics of the films. The performance of the multilayer films for sensing glucose could be tailored by controlling the gold nanoparticles loading in the film and the number of layers. A biosensor constructed by four poly(dimethyldiallylammonium chloride) (PDDA)/AuNP/PDDA/GOx multilayer films exhibited a wide linear calibration range from 0 to 60.0 mM with the detection limit of 3.0 microM for the detection of glucose. The dynamic range can be extended up to 120 mM. The biosensor has good stability and reproducibility.

Absorption↗

Optically sensing additional sonication effects on dispersed HiPco nanotubes in aerated water.

Ultrasonication is a necessary process to make single-walled carbon nanotubes (SWNTs) soluble in aqueous solution with surfactants such as sodium dodecyl sulfate (SDS). However, an understanding of the sonication effects on the electronic and optical properties of SWNTs in aqueous solution is still lacking. Here, we have observed that sonication-induced pH changes suppress the optical transitions of the first interband transition pair (S11) in the density of states of semiconducting SWNTs while other possible intermediates induced by sonication contribute less significantly to the observed spectral changes without the involvement of sonication-induced pH decrease. The suppressed S11 peaks can be restored by adding basic solution, suggesting that the lattice structure of SWNTs is undisrupted by the sonication used here. The absorbance of S11 peaks shows a nearly linear relationship with sonication-induced pH changes in the narrow pH range of 5.2 and 6.1. The results indicate that SDS-encased SWNTs may be used as an indicator for sonolysis-related applications.

Nanotubes, Carbon↗

A general model for detecting genetic determinants underlying longitudinal traits with unequally spaced measurements and nonstationary covariance structure.

A mixture model for determining quantitative trait loci (QTL) affecting growth trajectories has been proposed in the literature. In this article, we extend this model to a more general situation in which longitudinal traits for each subject are measured at unequally spaced time intervals, different subjects have different measurement patterns, and the residual correlation within subjects is nonstationary. We derive an EM-simplex hybrid algorithm to estimate the allele frequencies, Hardy-Weinberg disequilibrium, and linkage disequilibrium between QTL in the original population and parameters contained in the growth equation and in the covariance structure. A worked example of head circumference growth in 145 children is used to validate our extended model. A simulation study is performed to examine the statistical properties of the parameter estimation obtained from this example. Finally, we discuss the implications and extensions of our model for detecting QTL that affect growth trajectories.

Algorithms↗

Characterization of human LNX, a novel ligand of Numb protein X that is downregulated in human gliomas.

Gliomas are major tumors of the central nervous system with a wide spectrum of different tumor types. Ligand of Numb protein X (LNX) is PDZ domain containing protein that interacts with cell fate determinant Numb. cDNA microarray analysis was used to determine the expression of 13,939 genes in a set of 18 gliomas. It showed that human LNX was downregulated in 100% of gliomas including low- and high-grade ones, which was confirmed by Northern blot. In situ hybridization analysis revealed that LNX was lowly expressed in cytoplasm of glioma cells. Thus, LNX might act as a diagnostic marker and a potential therapeutic target for glioma. Two-hybrid screen in yeast was used to identify human LNX interacting proteins important for LNX function. It showed that human LNX interacted with Ski interacting protein (SKIP) via PDZ domains. The co-immunoprecipitation results suggested that LNX interacted with SKIP in HEK293 cells. LNX could affect the subcellular localization of Numb, which indicated that LNX might function as a molecular anchor that localized Numb to the subcellular site of its interaction with Notch. The presence of multiple protein binding domains involved in signal transduction and interaction with Numb and SKIP suggested an important role for LNX in tumorogenesis.

Adaptor Proteins, Signal Transducing↗

Mutations of PIK3CA in gastric adenocarcinoma.

BACKGROUND: Activation of the phosphatidylinositol 3-kinase (PI3K) through mutational inactivation of PTEN tumour suppressor gene is common in diverse cancer types, but rarely reported in gastric cancer. Recently, mutations in PIK3CA, which encodes the p110alpha catalytic subunit of PI3K, have been identified in various human cancers, including 3 of 12 gastric cancers. Eighty percent of these reported mutations clustered within 2 regions involving the helical and kinase domains. In vitro study on one of the "hot-spot" mutants has demonstrated it as an activating mutation. METHODS: Based on these data, we initiated PIK3CA mutation screening in 94 human gastric cancers by direct sequencing of the gene regions in which 80% of all the known PIK3CA mutations were found. We also examined PIK3CA expression level by extracting data from the previous large-scale gene expression profiling study. Using Significance Analysis of Microarrays (SAM), we further searched for genes that show correlating expression with PIK3CA. RESULTS: We have identified PIK3CA mutations in 4 cases (4.3%), all involving the previously reported hotspots. Among these 4 cases, 3 tumours demonstrated microsatellite instability and 2 tumours harboured concurrent KRAS mutation. Data extracted from microarray studies showed an increased expression of PIK3CA in gastric cancers when compared with the non-neoplastic gastric mucosae (p < 0.001). SAM further identified 2910 genes whose expression levels were positively associated with that of PIK3CA. CONCLUSION: Our data suggested that activation of the PI3K signalling pathway in gastric cancer may be achieved through up-regulation or mutation of PIK3CA, in which the latter may be a consequence of mismatch repair deficiency.

Adenocarcinoma↗

Syntheses, crystal structures and properties of novel copper(II) complexes obtained by reactions of copper(II) sulfate pentahydrate with tripodal ligands.

Three novel metal-organic frameworks (MOFs), [Cu(1)SO4].H2O (4), [Cu2(2)2(SO4)2].4H2O (5) and [Cu(3)(H2O)]SO4.5.5H2O (6), were obtained by hydrothermal reactions of CuSO4.5H2O with the corresponding ligands, which have different flexibility. The structures of the synthesized complexes were determined by single-crystal X-ray diffraction analyses. Complex 4 has a 2D network structure with two types of metallacycles. Complex 5 also has a 2D network structure in which each independent 2D sheet contains two sub-layers bridged by oxygen atoms of the sulfate anions. Complex 6 has a 2D puckered structure in which the sulfate anions serve as counter anions, which are different from those in complexes 4 (terminators) and 5 (bridges). The different structures of complexes 4, 5 and 6 indicate that the nature of organic ligands affected the structures of the assemblies greatly. The magnetic behavior of complex 5 and anion-exchange properties of complex 6 were investigated.

Journal Article↗

A non-stationary model for functional mapping of complex traits.

SUMMARY: Understanding the genetic control of growth is fundamental to agricultural, evolutionary and biomedical genetic research. In this article, we present a statistical model for mapping quantitative trait loci (QTL) that are responsible for genetic differences in growth trajectories during ontogenetic development. This model is derived within the maximum likelihood context, implemented with the expectation-maximization algorithm. We incorporate mathematical aspects of growth processes to model the mean vector and structured antedependence models to approximate time-dependent covariance matrices for longitudinal traits. Our model has been employed to map QTL that affect body mass growth trajectories in both male and female mice of an F2 population derived from the Large and Small mouse strains. The results from this model are compared with those from the autoregressive-based functional mapping approach. Based on results from computer simulation studies, we suggest that these two models are alternative to one another and should be used simultaneously for the same dataset.

Aging↗

Effect of Helicobacter pylori VacA on gene expression of gastric cancer cells.

AIM: To determine the effect of Helicobacter pylori VacA on gene expression of gastric cancer cells. METHODS: Gene expression profile of a gastric cancer cell line, SGC7901, after challenged by VacA+ and VacA- H pylori broth culture supernatants (BCS), was detected by the cDNA microarray technique. Cytoskeleton changes of SGC7901 and HeLa cells were observed through high-resolution laser scanning confocal microscopy. RESULTS: A total of 16,000 cDNA clones were detected. The percentage of genes with heterogeneous expression in SGC7901 cells challenged by VacA+ BCS reached 5%, compared with that challenged by VacA- BCS. There were 865 genes/EST with 2-fold differential expression levels and 198 genes/EST with 3-fold differential expression levels. Most of these genes were involved in vital cell events including signal transduction, regulation of gene expression, cytoskeleton, apoptosis, stress response and inflammation, cell cycle and tumor development. Cells co-cultured with VacA+ BCS showed collapsed and disrupted microtubular cytoarchitecture. CONCLUSION: VacA+ BCS can disrupt cytoskeletal architecture, likely through affecting the expression of cytoskeleton-associated genes, directly induce the expression of tumor promoter-related genes and inhibit the expression of tumor suppressor genes, thus favoring the development of tumors. VacA+ BCS can also alter the expression of inflammation and stress response genes. This suggests that VacA may play an important role in the pathogenicity of H pylori.

Bacterial Proteins↗

Facile synthesis of the heptasaccharide repeating unit of O-deacetylated GXM of C. neoformans serotype B.

A heptasaccharide, beta-D-Xylp-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp-(1-->3)-[beta-D-GlcpA-(1-->2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp, the repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar B, was synthesized as its methyl glycoside. Thus 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-d-mannopyranosyl trichloroacetimidate (7) and allyl 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-4,6-di-O-benzoyl-alpha-D-mannopyranoside (8), readily obtained from the corresponding monosaccharide derivatives via simple transformation, were coupled to give a (1-->3)-linked tetrasaccharide 9. Deallylation of 9 followed by trichloroacetimidate formation produced the tetrasaccharide donor 11. Condensation of methyl 2,3,4-tri-O-benzoyl-beta-d-xylopyranosyl-(1-->4)-2-O-acetyl-6-O-benzoyl-alpha-D-mannopyranoside (18) with 11 followed by selective deacetylation yielded hexasaccharide acceptor 20. Coupling of 20 with methyl 2,3,4-tri-O-acetyl-alpha-D-glucopyranosyluronate bromide (21) and subsequent deprotection furnished the target heptaoside. A hexasaccharide fragment, alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp-(1-->3)-[beta-D-GlcpA-(1-->2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp, was also similarly synthesized as its methyl glycoside.

Acetylation↗

Trends of HIV risk behaviors in a cohort of injecting drug users and their sex partners in Miami, Florida, 1988-1998.

A cohort of 111 injection drug users (IDUs) and their sex partners was assessed in 1988 concerning risk behaviors for HIV and knowledge of HIV/AIDS. Ten years later, in 1998, the cohort was reassessed using the same instrument. All who were HIV negative in 1988 were retested by blood draw for antibodies to HIV. A paired analysis was utilized to determine individual changes in risk behaviors for three serostatus groups--those who remained HIV negative (long-term HIV negatives), seroconverters, and those positive in 1988 (long-term HIV positives). Incidence was twice as high for sex partners (37.5%) as for IDUs (18.0%). Drug and needle use risk behaviors, except crack use, showed decreases; sexual risk behaviors were less amenable to change. Knowledge significantly increased among the long-term HIV negatives and seroconverters but not among those HIV positive in 1988. This analysis demonstrates the need for continued intervention among IDUs and their sex partners.

Adult↗

Comparison of cryopreservation and standard needle biopsy for gene expression profiling of human breast cancer specimens.

Given the growing importance of molecular profiling of breast cancer, we initiated a small study to test whether human breast biopsies obtained via cryopreservation large core needle biopsy (C-LCNB) provided similar gene expression profiles compared with 'optimally handled' standard large core needle biopsy (S-LCNB) specimens. Five matched pairs of C-LCNB versus S-LCNB were obtained at the same visit, and subjected to gene array expression analysis using the Affymetrix system with U133A chips. No significant changes in gene expression were identified comparing the C-LCNB versus the matched S-LCNB from individual patients. This was corroborated by a paired t-test analysis, which supported the hypothesis that the S/C biopsies measured equivalent samples. A small number of genes (17) showed decreased expression when second biopsies were compared with first biopsies, suggesting a slight patient response to the first biopsy. A scatter plot analysis comparing first biopsy versus second biopsy values disclosed a slope of 0.859, further indicating that the first biopsy affects the second biopsy measurement. It therefore appears that conventional biopsies, when handled appropriately, provide RNA which is equivalent to RNA from biopsies which are frozen immediately, but that multiple biopsy protocols may introduce additional complexities.

Biopsy, Needle↗

Tissue-dependent distribution and accumulation of chlorobenzenes by vegetables in urban area.

Five seasonal vegetables from three growing sites in Hangzhou city, Zhejiang Province, were studied for the levels of four chlorobenzenes(CBs): o-dichlorobenzene (o-DCB), p-dichlorobenzene (p-DCB), m-dichlorobenzene (m-DCB), and 1,2,4-trichlorobenzene (1,2,4-TCB). Samples of each vegetable from each site were subdivided into leaves, stems, and roots, and these subsamples were analyzed separately for the levels of accumulated CBs. Relations between the levels of CBs in vegetables with the total organic carbon (TOC) of the soil, the lipid content of the vegetable, and the physicochemical properties of CBs were established. Results showed that o-DCB, p-DCB, m-DCB, 1,2,4-TCB were present in all vegetables analyzed. For spinaches (Spinacia oleracea), Chinese cabbages (Brassica rapa var. pekinensis), and celery (Apium graveolens var. dulce), the highest level of CBs was with roots, followed by leaves. While for radishes (Raphanus sativus), and carrots (Daucus carota subsp. sativus), the highest level was with leaves, followed by stems. The accumulation of CBs was found to have a good correlation with the plant-tissue lipid content, the contaminant air-water Henry's coefficient (H), the contaminant octanol-water partition coefficient (K(ow)), and the physiological characteristics of the vegetables.

1-Octanol↗

Surface CD88 functionally distinguishes the MCTC from the MCT type of human lung mast cell.

BACKGROUND: MC(T) and MC(TC) types of human mast cells (MCs) are distinguished from one another on the basis of the protease compositions of their secretory granules, but their functional and developmental relationships have been uncertain. OBJECTIVE: These studies better define the functional properties and developmental relationship of MC(T) and MC(TC) cells. METHODS: Mast cells were dispersed from human skin and lung, purified with anti-Kit antibody, and separated into CD88+ and CD88- populations by cell sorting. These cells were evaluated by immunocytochemistry with antitryptase and antichymase mAbs; for chymase and tryptase mRNA by real-time RT-PCR; for conversion of MC(T) to MC(TC) cells during cell culture with recombinant human stem cell factor and recombinant human IL-6; and for degranulation and leukotriene C 4 (LTC 4 ) secretion when stimulated with anti-FcepsilonRI, substance P, C5a, and compound 48/80. RESULTS: Mature MC(T) and MC(TC) cells were separated from one another on the basis of selective expression of CD88, the C5aR, on MC(TC) cells. Lung MC(T) cells had negligible levels of chymase mRNA and retained their MC(T) phenotype in culture. Mature MC(TC) cells from skin and lung degranulated in response to FcepsilonRI cross-linking, C5a, compound 48/80, and substance P. Lung MC(TC) cells released LTC 4 on activation, but no LTC 4 was detected when skin-derived MC(TC) cells were activated. MC(T) cells from lung degranulated and released LTC 4 in response to anti-FcepsilonRI and substance P, but not to C5a and compound 48/80. CONCLUSION: These observations functionally distinguish MC(T) from MC(TC) types of human mast cells and suggest important differences that may affect their participation in diseases such as asthma and urticaria.

Cell Degranulation↗

CD11b may be a less satisfactory indicator for cardiac ischemia-reperfusion injury in coronary artery bypass graft surgery with cardiopulmonary bypass than cardiac troponin I.

STUDY OBJECTIVE: To investigate whether CD11b on neutrophils can be used as a marker to predict myocardial ischemia-reperfusion injury for patients undergoing coronary artery bypass graft (CABG) surgery on cardiopulmonary bypass (CPB). DESIGN: Prospective, observational study. SETTING: University teaching hospital and university hospital laboratories. PATIENTS: Twelve adults, physical status II and III (American Society of Anesthesiologists) patients scheduled for elective CABG surgery on CPB. INTERVENTIONS: Anesthesia and surgical interventions were performed according to standard procedures. Coronary sinus was cannulated for retrograde cardioplegia perfusion and for coronary sinus blood sampling. The blood samples were collected from systemic and coronary venous sinus blood respectively at several time points before CPB, during CPB, and after declamping of the ascending aorta. MEASUREMENTS AND MAIN RESULTS: CD11b expressions in systemic circulation blood increased significantly during CPB and maintained higher levels after cardiac reperfusion (P < .05); on the other hand, CD11b expressions in coronary sinus blood declined gradually and reached their lowest level at 5 minutes after aortic declamping. The differences in CD11b expressions between systemic circulatory blood and coronary sinus blood after cardiac reperfusion were significant (P < .05). Cardiac troponin I (cTnI) concentrations in both systemic circulatory blood and coronary sinus blood increased significantly after cardiac reperfusion (P < .05), and the concentrations of cTnI in coronary sinus blood increased much higher than the corresponding concentrations of cTnI at each time point (P < .05). CONCLUSION: CD11b expression on neutrophils may not be a reliable predictor for myocardial ischemia-reperfusion injury in CABG surgery on CPB because of the possible sequestration of neutrophils in myocardium.

Adult↗

Molecular cloning and characterization of monoamine oxidase A and B genes in pig.

Monoamine oxidase (MAO) is a key enzyme in the degradation of monoamine neurotransmitters, which are physiologically and pathologically important for animals and humans. MAO exists in two forms, coded by separate genes. Here we cloned and sequenced full length cDNAs of MAO-A and MAO-B in pig. The putative proteins include 527 and 520 amino acids, respectively. The sequences alignment and homology analysis showed that MAO-A and MAO-B are conserved among mammals. The amino acid residues and domains, which have been demonstrated to be important for MAO-A and MAO-B binding of ligands, substrates and inhibitors, were conserved in the pig.

Amines↗