Crystal structure of F2NO+AsF6- and method for extracting meaningful geometries from oxygen/fluorine disordered crystal structures.
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Journal Article↗
Biomedical subjects
X Zhang
Publications and source records attributed to X Zhang.
A Baker-Figgis isomer of conventional sandwich polyoxometalates. H2Na14[FeIII2(NaOH2)2(P2W15O56)2], a diiron catalyst for catalytic H2O2-based epoxidation.
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Journal Article↗
Organic synthesis in ionic liquids: the Stille coupling.
[figure: see text] The Stille coupling reaction has been performed in 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM BF4), a room-temperature ionic liquid (RTIL). Use of this solvent system allows for facile recycling of the solvent and catalyst system, which can be used at least five times with little loss in activity. An interesting preference in starting catalyst oxidation state for use with aryl bromides and aryl iodides was observed.
Journal Article↗
Caveolin-1 interacts with androgen receptor. A positive modulator of androgen receptor mediated transactivation.
Androgen receptor (AR) belongs to the steroid hormone nuclear receptor superfamily. It functions as an androgen-dependent transcriptional factor that regulates genes for cell proliferation and differentiation. Caveolin is a principal component of caveolae membranes serving as a scaffold protein of many signal transduction pathways. Recent results correlate caveolin-1 expression with androgen sensitivity in murine prostate cancer. Furthermore, immunohistochemical staining of patient specimens suggests that caveolin expression may be an independent predictor of progression of prostate cancer. In this study, we investigate the potential interactions between AR signaling and caveolin-1 and demonstrate that overexpression of caveolin-1 potentiates ligand-dependent AR activation. Conversely, down-regulation of caveolin-1 expression by a caveolin-1 antisense expression construct can down-regulate ligand-dependent AR activation. Association between these two molecules is also demonstrated by co-localization of AR with caveolin-rich, low-density membrane fractions isolated by an equilibrium sucrose gradient centrifugation method. Co-immunoprecipitation and glutathione S-transferase fusion protein pull-down experiments demonstrate that interaction between AR and caveolin-1 is an androgen-dependent process, offering further evidence for a physiological role of this interaction. Using a mammalian two-hybrid assay system, we determine that the NH(2) terminus region of caveolin-1 is responsible for the interaction with both the NH(2)-terminal domain and the ligand-binding domain of AR.
Animals↗
Mutational analysis and reconstituted expression of the biosynthetic genes involved in the formation of 3-amino-5-hydroxybenzoic acid, the starter unit of rifamycin biosynthesis in amycolatopsis Mediterranei S699.
To investigate a novel branch of the shikimate biosynthesis pathway operating in the formation of 3-amino-5-hydroxybenzoic acid (AHBA), the unique biosynthetic precursor of rifamycin and related ansamycins, a series of target-directed mutations and heterologous gene expressions were investigated in Amycolatopsis mediterranei and Streptomyces coelicolor. The genes involved in AHBA formation were inactivated individually, and the resulting mutants were further examined by incubating the cell-free extracts with known intermediates of the pathway and analyzing for AHBA formation. The rifL, -M, and -N genes were shown to be involved in the step(s) from either phosphoenolpyruvate/d-erythrose 4-phosphate or other precursors to 3,4-dideoxy-4-amino-d-arabino-heptulosonate 7-phosphate. The gene products of the rifH, -G, and -J genes resemble enzymes involved in the shikimate biosynthesis pathway (August, P. R., Tang, L., Yoon, Y. J., Ning, S., Müller, R., Yu, T.-W., Taylor, M., Hoffmann, D., Kim, C.-G., Zhang, X., Hutchinson, C. R., and Floss, H. G. (1998) Chem. Biol. 5, 69-79). Mutants of the rifH and -J genes produced rifamycin B at 1% and 10%, respectively, of the yields of the wild type; inactivation of the rifG gene did not affect rifamycin production significantly. Finally, coexpressing the rifG-N and -J genes in S. coelicolor YU105 under the control of the act promoter led to significant production of AHBA in the fermented cultures, confirming that seven of these genes are indeed necessary and sufficient for AHBA formation. The effects of deletion of individual genes from the heterologous expression cassette on AHBA formation duplicated the effects of the genomic rifG-N and -J mutations on rifamycin production, indicating that all these genes encode proteins with catalytic rather than regulatory functions in AHBA formation for rifamycin biosynthesis by A. mediterranei.
Actinomycetales↗
Syntheses of the L-manno and some other analogs of the terminal determinants of the O-PS of Vibrio cholerae O:1.
Analogs of the methyl alpha-glycosides of the terminal residues of the O-specific polysaccharides (O-PS) of Vibrio cholerae O:1, serotype Inaba and Ogawa, have been prepared as probes to study their interaction with anti V. cholerae O:1 antibodies. They differ from the termini of the respective O-PSs in anomeric or absolute configuration of perosamine, position of the O-methyl group in D-perosamine, and nature of the N-acyl side chain.
Antigens, Bacterial↗
Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA.
DNMT2 is a human protein that displays strong sequence similarities to DNA (cytosine-5)-methyltransferases (m(5)C MTases) of both prokaryotes and eukaryotes. DNMT2 contains all 10 sequence motifs that are conserved among m(5)C MTases, including the consensus S:-adenosyl-L-methionine-binding motifs and the active site ProCys dipeptide. DNMT2 has close homologs in plants, insects and Schizosaccharomyces pombe, but no related sequence can be found in the genomes of Saccharomyces cerevisiae or Caenorhabditis elegans. The crystal structure of a deletion mutant of DNMT2 complexed with S-adenosyl-L-homocysteine (AdoHcy) has been determined at 1.8 A resolution. The structure of the large domain that contains the sequence motifs involved in catalysis is remarkably similar to that of M.HHAI, a confirmed bacterial m(5)C MTase, and the smaller target recognition domains of DNMT2 and M.HHAI are also closely related in overall structure. The small domain of DNMT2 contains three short helices that are not present in M.HHAI. DNMT2 binds AdoHcy in the same conformation as confirmed m(5)C MTases and, while DNMT2 shares all sequence and structural features with m(5)C MTases, it has failed to demonstrate detectable transmethylase activity. We show here that homologs of DNMT2, which are present in some organisms that are not known to methylate their genomes, contain a specific target-recognizing sequence motif including an invariant CysPheThr tripeptide. DNMT2 binds DNA to form a denaturant-resistant complex in vitro. While the biological function of DNMT2 is not yet known, the strong binding to DNA suggests that DNMT2 may mark specific sequences in the genome by binding to DNA through the specific target-recognizing motif.
Adenosine Triphosphate↗
The necessity to discriminate lipofuscin from melanins.
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Aging↗
Retinoic acid (RA) receptor transcriptional activation correlates with inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase (ODC) activity by retinoids: a potential role for trans-RA-induced ZBP-89 in ODC inhibition.
Evaluation of retinoic acid receptor (RAR) subtype-selective alpha and gamma agonists and antagonists and a retinoid X receptor (RXR) class-selective agonist for efficacy at inhibiting both induction of ornithine decarboxylase (ODC) by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis and rat tracheal epithelial cells and the appearance of papillomas in mouse epidermis treated in the 2-stage tumor initiation-promotion model indicated that (i) RXR class-selective transcriptional agonists, such as MM11246, were not involved in ODC inhibition; (ii) RAR-selective agonists that induce gene transcription from RA-responsive elements (RAREs) were active at low concentrations; (iii) RAR-selective antagonists that bind RARs and inhibit AP-1 activation on the collagenase promoter but do not activate RAREs to induce gene transcription were less effective inhibitors; and (iv) RARgamma-selective retinoid agonists were more effective inhibitors of TPA-induced ODC activity than RARalpha-selective agonists. These results suggest that RARE activation has a more important role in inhibition of ODC activity than RXR activation or AP-1 inhibition and that RARgamma-selective agonists would be the most useful inhibitors of epithelial cell proliferation induced by tumor promoters. The natural retinoid all-trans-RA induced expression of transcription factor ZBP-89, which represses activation of the GC box in the ODC promoter by the transcription factor Sp1.
9,10-Dimethyl-1,2-benzanthracene↗
The SH2 domain of bcr-Abl is not required to induce a murine myeloproliferative disease; however, SH2 signaling influences disease latency and phenotype.
Bcr-Abl plays a critical role in the pathogenesis of chronic myelogenous leukemia (CML). It was previously shown that expression of Bcr-Abl in bone marrow cells by retroviral transduction efficiently induces a myeloproliferative disorder (MPD) in mice resembling human CML. This in vivo experimental system allows the direct determination of the effect of specific domains of Bcr-Abl, or specific signaling pathways, on the complex in vivo pathogenesis of CML. In this report, the function of the SH2 domain of Bcr-Abl in the pathogenesis of CML is examined using this murine model. It was found that the Bcr-Abl SH2 mutants retain the ability to induce a fatal MPD but with an extended latency compared with wild type (wt) Bcr-Abl. Interestingly, in contrast to wt Bcr-Abl-induced disease, which is rapid and monophasic, the disease caused by the Bcr-Abl SH2 mutants is biphasic, consisting of an initial B-lymphocyte expansion followed by a fatal myeloid proliferation. The B-lymphoid expansion was diminished in mixing experiments with bcr-abl/DeltaSH2 and wt bcr-abl cells, suggesting that the Bcr-Abl-induced MPD suppresses B-lymphoid expansion.
3T3 Cells↗
Phase transitions of hydroxyapatite coatings during post-heat treatment and their performances under ultrasonic tests.
Highly or completely crystalline hydroxyapatite (HA) coatings can be obtained by post-heat treatment. We have developed a high-temperature (490 degrees C) and a low-temperature (125 degrees C) heat treatment to improve the crystallinity of HA coatings. Both methods transform entirely the amorphous phase into crystalline HA. However, the microstructure of the coating is dependent on the post-heating method. Nanocrystalline HA is about half of the component of the low-temperature heated coating while highly crystalline HA dominates the high-temperature heated coating, as detected by X-ray diffraction. The effects of both methods on the disintegration of the coatings were tested by ultrasonic treatment. The high-temperature heated coatings exhibited poor integrity while the low-temperature heated coatings exhibited better integrity, possibly due to their different microstructure. SEM revealed that the coatings disintegrated via different mechanisms: the high-temperature heated coatings failed via crack initiation and propagation while the low-temperature heated coatings failed via pit formation and subsequent widening.
Coated Materials, Biocompatible↗
Induction of oral tolerance to cellular immune responses in the absence of Peyer's patches.
Systemic hyporesponsiveness occurs following oral administration of antigen (oral tolerance) and involves the uptake and processing of antigen by the gut-associated lymphoid tissue (GALT), which includes Peyer's patches (PP) lamina propria lymphocytes and mesenteric lymph nodes (MLN). Animals with targeted mutations of genes in the tumor necrosis factor (TNF) family have differential defects in the development of peripheral lymphoid organs including PP and MLN, and provide a unique opportunity to investigate the role of GALT structures in the induction of oral tolerance. Oral tolerance could not be induced in TNF/lymphotoxin (LT) alpha-/- mice, which are devoid of both PP and MLN, although these animals could be tolerized by intraperitoneal administration of antigen, demonstrating the requirement for GALT for oral tolerance induction. LTbeta-/- mice and LTalpha/LTbeta+/- animals do not have PP but could be orally tolerized, as measured by IFN-gamma production and delayed-type hypersensitivity responses by administration of both low or high doses of ovalbumin. To further investigate the requirement for PP, we tested the progeny of LTbeta-receptor-IgG-fusion-protein (LTbetaRigG)-treated mice, which do not form PP but have an otherwise intact immune system. Although these animals had decreased fecal IgA production, they could be orally tolerized. Our results demonstrate that PP are not an absolute requirement for the induction of either high- or low-dose oral tolerance, although oral tolerance could not be induced in animals devoid of both PP and MLN.
Administration, Oral↗
Temporal characteristics of event-related BOLD response and visual-evoked potentials from checkerboard stimulation of human V1: a comparison between different control features.
This work is concerned with the temporal characteristics of event-related blood oxygenation level-dependent (ER-BOLD) and visual-evoked potential (VEP) signals produced by checkerboard stimulation of human V1. The study investigated whether different control features produce different amplitude VEPs, and if so, whether this corresponds to different ER-BOLD responses. The results showed that there was a difference in the amplitude of the P1-N1 components of the VEPs, and also in the magnitude and extent of the ER-BOLD responses. These results suggest the possibility that the P1-N1 components may be related to the difference in the magnitude and extent of the ER-BOLD response. Magn Reson Med 45:212-216, 2001.
Adult↗
Improved method for measuring the ensemble average of strand breaks in genomic DNA.
The cis-syn cyclobutane pyrimidine dimer (CPD) is the major photoproduct induced in DNA by low wavelength ultraviolet radiation. An improved method was developed to detect CPD formation and removal in genomic DNA that avoids the problems encountered with the standard method of endonuclease detection of these photoproducts. Since CPD-specific endonucleases make single-strand cuts at CPD sites, quantification of the frequency of CPDs in DNA is usually done by denaturing gel electrophoresis. The standard method of ethidium bromide staining and gel photography requires more than 10 microg of DNA per gel lane, and correction of the photographic signal for the nonlinear film response. To simplify this procedure, a standard Southern blot protocol, coupled with phosphorimage analysis, was developed. This method uses random hybridization probes to detect genomic sequences with minimal sequence bias. Because of the vast linearity range of phosphorimage detection, scans of the signal profiles for the heterogeneous population of DNA fragments can be integrated directly to determine the number-average size of the population.
Animals↗
Gas-phase basicities for ions from bradykinin and its des-arginine analogues.
Apparent gas-phase basicities (GB(app)s) for [M + H]+ of bradykinin, des-Arg1-bradykinin and des-Arg9-bradykinin have been assigned by deprotonation reactions of [M + 2H]2+ in a Fourier transform ion cyclotron resonance mass spectrometer. With a GB(app) of 225.8 +/- 4.2 kcal x mol(-1), bradykinin [M + H]+ is the most basic of the ions studied. Ions from des-Arg1-bradykinin and des-Arg9-bradykinin have GB(app) values of 222.8 +/- 4.3 kcal x mol(-1) and 214.9 +/- 2.3 kcal x mol(-1), respectively. One purpose of this work was to determine a suitable reaction efficiency 'break point' for assigning GB(app) values to peptide ions using the bracketing method. An efficiency value of 0.1 (i.e. approximately 10% of all collisions resulting in a deprotonation reaction) was used to assign GB(app)s. Support for this criterion is provided by the fact that our GB(app) values for des-Arg1-bradykinin and des-Arg9-bradykinin are identical, within experimental error, to literature values obtained using a modified kinetic method. However, the GB(app)s for bradykinin ions from the two studies differ by 10.3 kcal x mol(-1). The reason for this is not clear, but may involve conformation differences produced by experimental conditions. The results may be influenced by salt-bridge conformers and/or by conformational changes caused by the use of a proton-bound heterodimer in the kinetic method. Factors affecting the basicities of these peptide ions are also discussed, and molecular modeling is used to provide information on protonation sites and conformations. The presence of two highly basic arginine residues on bradykinin results in its high GB(app), while the basicity of des-Arg1-bradykinin ions is increased by the presence of two proline residues at the N-terminus. The proline residue in the second position folds the peptide chain in a manner that increases intramolecular hydrogen bonding to the protonated N-terminal amino group of the proline at the first position.
Bradykinin↗
Dextran-methylprednisolone succinate as a prodrug of methylprednisolone: plasma and tissue disposition.
Plasma and tissue disposition of a macromolecular prodrug of methylprednisolone (MP), dextran (70 kDa)-methylprednisolone succinate (DMP), was studied in rats. Single 5-mg/kg doses of DMP or unconjugated MP were administered into the tail veins of different groups of rats (n = 4/group/time point). Blood (cardiac puncture) and tissues (liver, spleen, kidney, heart, lung, thymus, and brain) were collected at various times after DMP (0-96 h) or MP (0-2 h) injections. Concentrations of DMP and MP in samples were analyzed by size-exclusion chromatography (SEC) and reversed-phase high-performance liquid chromatography (HPLC), respectively. Conjugation of MP with 70-kDa dextran resulted in 22-, 300-, and 30-fold decreases in the steady-state volume of distribution, clearance, and terminal plasma rate constant of the steroid, respectively. As for tissue distribution, the conjugate delivered the steroid primarily to the spleen and liver as indicated by 19- and 3-fold increases, respectively, in the tissue/plasma area under the curve (AUC) ratios of the steroid. On the other hand, the tissue/plasma AUC ratios of the prodrug in other organs were negligible. Active MP was released from DMP slowly in the spleen and liver, and AUCs of the regenerated MP in these tissues were 55- and 4.8-fold, respectively, higher than those after the administration of the parent drug. In contrast, no parent drug was detected in the plasma of DMP-injected rats. These results indicate that DMP may be useful for the targeted delivery of MP to the spleen and liver where the active drug is slowly released.
Animals↗
Bayesian technique for investigating linearity in event-related BOLD fMRI.
Event-related BOLD fMRI data is modeled as a linear time-invariant system. Together with Bayesian inference techniques, a statistical test is developed for rigorously detecting linearity/nonlinearity in the BOLD response system. The test is applied to data collected from eight subjects using an event-related paradigm with a switching checkerboard as the visual stimulus. Analyzed as a group, the results clearly find the response to be nonlinear. When each subject is analyzed individually, however, the results are predominantly nonlinear, but there is some evidence to suggest that there may be a crossover from a linear to a nonlinear regime and vice versa. This could be important when estimating physiological parameters for individuals. Additionally, estimates of the hemodynamic response function and corresponding response were obtained, but there was no consistent appearance of a poststimulus undershoot in the event-related BOLD response.
Adult↗
Microstrip RF surface coil design for extremely high-field MRI and spectroscopy.
A new type of high-frequency RF surface coil was developed for in vivo proton or other nuclei NMR applications at 7T. This is a purely distributed-element and transmission line design. The coil consists of a thin strip conductor (copper or silver) and a ground plane separated by a low-loss dielectric material with a thickness (H). Due to its specific semi-open transmission line structure, substantial electromagnetic energy is stored in the dielectric material between the thin conductor and the ground plane, which results in a reduced radiation loss and a reduced perturbation of sample loading to the RF coil compared to conventional surface coils. The coil is characterized by a high Q factor, no RF shielding, small physical coil size, lower cost, and easy fabrication. A brief theoretical description of the microstrip RF coil is given that can be used to guide the coil designs. A set of gradient-recalled echo images were acquired by using the single- and two-turn microstrip RF surface coils from both phantom and human brain at 7T, which show good penetration and sensitivity. The two-turn coil design significantly improves the B1 symmetry as predicted by the microstrip theory. The optimum H for microstrip surface coils is approximately 7 mm. This coil geometry yields a B1 penetration similar to that of conventional surface coils. SNR comparison was made between the microstrip coil and conventional surface coils with and without RF shielding. The results reveal that the novel surface coil design based on the microstrip concept makes very high-field MRI/MRS more convenient and efficient in research and future clinics.
Artifacts↗