Biomedical subjects

Q Zhang

Publications and source records attributed to Q Zhang.

At least 127 records · Page 7Linked to original sources

PubMed2001

Hydrogen-enhanced local plasticity in aluminum: an ab initio study.

Dislocation core properties of Al with and without H impurities are studied using the Peierls-Nabarro model with parameters determined by ab initio calculations. We find that H not only facilitates dislocation emission from the crack tip but also enhances dislocation mobility dramatically, leading to macroscopically softening and thinning of the material ahead of the crack tip. We observe strong binding between H and dislocation cores, with the binding energy depending on dislocation character. This dependence can directly affect the mechanical properties of Al by inhibiting dislocation cross-slip and developing slip planarity.

Journal Article↗

PubMed2001

Mesoderm formation in Eleutherodactylus coqui: body patterning in a frog with a large egg.

The direct developing frog, Eleutherodactylus coqui, develops from a large egg (diameter 3.5 mm). To investigate the effect of egg size on germ-layer formation, we studied mesoderm formation in E. coqui and compared it to that of Xenopus laevis (diameter 1.3 mm). First, we identified the position of prospective mesoderm in the 16-cell E. coqui embryo by cell-lineage tracing. Although the animal blastomeres are small, they form most of the blastocoel roof and make extensive contributions to some mesodermal tissues. Second, we performed recombinant analysis with X. laevis animal caps to define the distribution of mesoderm-inducing activity. Mesoderm-inducing activity in E. coqui was restricted around the marginal zone with strong activity in the superficial cells. Neither the vegetal pole nor the blastocoel floor had activity, although these same regions from X. laevis induced mesoderm. Third, we cloned Ecbra, a homologue of Xbra, an early mesoderm marker in X. laevis. Ecbra was expressed in the marginal ring close to the surface, similar to X. laevis, but E. coqui had weaker expression on the dorsal side. Our results suggest that mesoderm formation is shifted more animally and superficially in E. coqui compared to X. laevis.

Animals↗

PubMed2001

Mechanistic investigation of UDP-galactopyranose mutase from Escherichia coli using 2- and 3-fluorinated UDP-galactofuranose as probes.

The galactofuranose moiety found in many surface constituents of microorganisms is derived from UDP-D-galactopyranose (UDP-Galp) via a unique ring contraction reaction catalyzed by UDP-Galp mutase. This enzyme, which has been isolated from several bacterial sources, is a flavoprotein. To study this catalysis, the cloned Escherichia coli mutase was purified and two fluorinated analogues, UDP-[2-F]Galf (9) and UDP-[3-F]Galf (10), were chemically synthesized. These two compounds were found to be substrates for the reduced UDP-Galp mutase with the Km values determined to be 65 and 861 microM for 9 and 10, respectively, and the corresponding kcat values estimated to be 0.033 and 5.7 s(-1). Since the fluorine substituent is redox inert, a mechanism initiated by the oxidation of 2-OH or 3-OH on the galactose moiety can thus be firmly ruled out. Furthermore, both 9 and 10 are poorer substrates than UDP-Galf, and the rate reduction for 9 is especially significant. This finding may be ascribed to the inductive effect of the 2-F substituent that is immediately adjacent to the anomeric center, and is consistent with a mechanism involving formation of oxocarbenium intermediates or transition states during turnover. Interestingly, under nonreducing conditions, compounds 9 and 10 are not substrates, but instead are inhibitors for the mutase. The inactivation by 10 is time-dependent, active-site-directed, and irreversible with a K(I) of 270 microM and a k(inact) of 0.19 min(-1). Since the K(I) value is similar to Km, the observed inactivation is unlikely a result of tight binding. To our surprise, the inactivated enzyme could be regenerated in the presence of dithionite, and the reduced enzyme is resistant to inactivation by these fluorinated analogues. It is possible that reduction of the enzyme-bound FAD may induce a conformational change that facilitates the breakdown of the putative covalent enzyme-inhibitor adduct to reactivate the enzyme. It is also conceivable that the reduced flavin bears a higher electron density at N-1, which may play a role in preventing the formation of the covalent adduct or facilitating its breakdown by charge stabilization of the oxocarbenium intermediates/transition states. Clearly, this study has led to the identification of a potent inactivator (10) for this enzyme, and study of its inactivation has also shed light on the possible mechanism of this mutase.

Bacterial Proteins↗

PubMed2001

Biosynthesis of D-alanyl-lipoteichoic acid: the tertiary structure of apo-D-alanyl carrier protein.

The D-alanylation of lipoteichoic acid (LTA) allows the Gram-positive organism to modulate its surface charge, regulate ligand binding, and control the electromechanical properties of the cell wall. The incorporation of D-alanine into LTA requires the D-alanine:D-alanyl carrier protein ligase (AMP-forming) (Dcl) and the carrier protein (Dcp). The high-resolution solution structure of the 81-residue (8.9 kDa) Dcp has been determined by multidimensional heteronuclear NMR. An ensemble of 30 structures was calculated using the torsion angle dynamics approach of DYANA. These calculations utilized 3288 NOEs containing 1582 unique nontrivial NOE distance constraints. Superposition of residues 4-81 on the mean structure yields average atomic rmsd values of 0.43 +/- 0.08 and 0.86 +/- 0.09 A for backbone and non-hydrogen atoms, respectively. The solution structure is composed of three alpha-helices in a bundle with additional short 3(10)- and alpha-helices in intervening loops. Comparisons of the three-dimensional structure with the acyl carrier proteins involved in fatty acid, polyketide, and nonribosomal peptide syntheses support the conclusion that Dcp is a homologue in this family. While there is conservation of the three-helix bundle fold, Dcp has a higher enthalpy of unfolding and no apparent divalent metal binding site(s), features that distinguish it from the fatty acid synthase acyl carrier protein of Escherichia coli. This three-dimensional structure also provides insights into the D-alanine ligation site recognized by Dcl, as well as the site which may bind the poly(glycerophosphate) acceptor moiety of membrane-associated LTA.

Acyl Carrier Protein↗

PubMed2001

Human chromosome 19 and related regions in mouse: conservative and lineage-specific evolution.

To illuminate the function and evolutionary history of both genomes, we sequenced mouse DNA related to human chromosome 19. Comparative sequence alignments yielded confirmatory evidence for hypothetical genes and identified exons, regulatory elements, and candidate genes that were missed by other predictive methods. Chromosome-wide comparisons revealed a difference between single-copy HSA19 genes, which are overwhelmingly conserved in mouse, and genes residing in tandem familial clusters, which differ extensively in number, coding capacity, and organization between the two species. Finally, we sequenced breakpoints of all 15 evolutionary rearrangements, providing a view of the forces that drive chromosome evolution in mammals.

Animals↗

PubMed2001

The Friend of GATA proteins U-shaped, FOG-1, and FOG-2 function as negative regulators of blood, heart, and eye development in Drosophila.

Friend of GATA (FOG) proteins regulate GATA factor-activated gene transcription. During vertebrate hematopoiesis, FOG and GATA proteins cooperate to promote erythrocyte and megakaryocyte differentiation. The Drosophila FOG homologue U-shaped (Ush) is expressed similarly in the blood cell anlage during embryogenesis. During hematopoiesis, the acute myeloid leukemia 1 homologue Lozenge and Glial cells missing are required for the production of crystal cells and plasmatocytes, respectively. However, additional factors have been predicted to control crystal cell proliferation. In this report, we show that Ush is expressed in hemocyte precursors and plasmatocytes throughout embryogenesis and larval development, and the GATA factor Serpent is essential for Ush embryonic expression. Furthermore, loss of ush function results in an overproduction of crystal cells, whereas forced expression of Ush reduces this cell population. Murine FOG-1 and FOG-2 also can repress crystal cell production, but a mutant version of FOG-2 lacking a conserved motif that binds the corepressor C-terminal binding protein fails to affect the cell lineage. The GATA factor Pannier (Pnr) is required for eye and heart development in Drosophila. When Ush, FOG-1, FOG-2, or mutant FOG-2 is coexpressed with Pnr during these developmental processes, severe eye and heart phenotypes result, consistent with a conserved negative regulation of Pnr function. These results indicate that the fly and mouse FOG proteins function similarly in three distinct cellular contexts in Drosophila, but may use different mechanisms to regulate genetic events in blood vs. cardial or eye cell lineages.

Animals↗

PubMed2001

Modulation of docetaxel-induced apoptosis and cell cycle arrest by all- trans retinoic acid in prostate cancer cells.

We report that all- trans retinoic acid (ATRA) enhanced the toxicity of docetaxel against DU145 and LNCaP prostate cancer cells, and that the nature of the interaction between ATRA and docetaxel was highly synergistic. Docetaxel-induced apoptotic cell death was associated with phosphorylation and hence inactivation of Bcl-2. ATRA enhanced docetaxel-induced apoptosis and combined treatment with ATRA and docetaxel resulted in down-regulation of Bcl-2. Docetaxel caused phosphorylation and hence inactivation of cdc2 kinase result ing in G2/M arrest. ATRA inhibited docetaxel-induced phosphorylation of cdc2 resulting in activation of cdc2 kinase and partial reversal of the G2/M arrest. ATRA also inhibited docetaxel-induced activation of MAPK indicating that the effects of docetaxel and ATRA on cdc2 phosphorylation are dependent on MAPK. We conclude that ATRA synergistically enhances docetaxel toxicity by down-regulating Bcl-2 expression and partially reverses the docetaxel-induced G2/M arrest by inhibiting docetaxel-induced cdc2 phosphorylation in a pathway that is dependent on MAPK.

Antineoplastic Agents↗

PubMed2001

Pannier is a transcriptional target and partner of Tinman during Drosophila cardiogenesis.

During Drosophila embryogenesis, the homeobox gene tinman is expressed in the dorsal mesoderm where it functions in the specification of precursor cells of the heart, visceral, and dorsal body wall muscles. The GATA factor gene pannier is similarly expressed in the dorsal-most part of the mesoderm where it is required for the formation of the cardial cell lineage. Despite these overlapping expression and functional properties, potential genetic and molecular interactions between the two genes remain largely unexplored. Here, we show that pannier is a direct transcriptional target of Tinman in the heart-forming region. The resulting coexpression of the two factors allows them to function combinatorially in the regulation of cardiac gene expression, and a physical interaction of the proteins has been demonstrated in cultured cells. We also define functional domains of Tinman and Pannier that are required for their synergistic activation of the D-mef2 differentiation gene in vivo. Together, these results provide important insights into the genetic mechanisms controlling heart formation in the Drosophila model system.

Animals↗

PubMed2001

Prolonged hypoglycemic effect of insulin-loaded polybutylcyanoacrylate nanoparticles after pulmonary administration to normal rats.

Insulin-loaded polybutylcyanoacrylate nanoparticles were prepared by emulsion polymerization. The mean diameter of the nanoparticles was 254.7 nm with a polydispersity of 0.064. The associating ratio of insulin to the nanoparticles reached 79.1%. Studies on in vitro release kinetics showed that release profiles can be modeled using a biexponential function and the burst effect was obvious. After various doses of insulin-loaded nanoparticles were intratracheally given to normal rats, significant decrease of glucose level was achieved at each dose group from 5 to 20 IU kg-1. The minimum blood glucose concentration reached 46.9%, 30.4% and 13.6% of the initial level after pulmonary delivery of 5, 10 and 20 IU kg-1 insulin-loaded nanoparticles to normal rats, respectively. The time to reach the minimum blood glucose level (Tmin) was 4, 4 and 8 h for three doses, respectively. The duration of glucose level below 80% of insulin-loaded nanoparticles was much longer than that of insulin solution at every dose. Relative pharmacological bioavailability of insulin-loaded nanoparticles by pulmonary administration was 57.2% over the same formulation by subcutaneous administration.

Animals↗

PubMed2001

Theoretical characterization of photoisomerization channels of dimethylpyridines on the singlet and triplet potential energy surfaces.

Photoexcitations and photoisomerizations due to low-lying n pi* and pi pi* excited states of dimethylpyridines are investigated by density functional theory, CASSCF, CASPT2 and MRCI methodologies. Mechanistic details for the formation of Dewar dimethylpyridines and the interconversions of dimethylpyridines are rationalized through the characterization of minima and transition states on the singlet and triplet potential energy surfaces of relevant intermediates. Our present theoretical schemes suggest that Mobius dimethylpyridine intermediate 14 and azabenzvalene intermediate 10 can serve as possible precursors to Dewar dimethylpyridines and singlet phototransposition products, respectively. The calculations suggest that an S1(pi pi*)/S0 conical intersection in dimethylpyridines 2 is involved in the formation of 14. An azabenzvalene 10 might be formed through S2(pi pi*)/S1(n pi*) interaction followed by an S1/S0 decay in dimethylpyridine 6. Calculated barriers of isomerizations from 14 to Dewar dimethylpyridine 7 and from 10 to 4 are 8.4 and 28.5 kcal mol(-1) at the B3LYP/6-311 G** level, respectively. In the suggested triplet multistage transposition mechanism, an out-of-plane distorted geometry 19 due to vibrational relaxation of the T1(3B1) excited state of 3,5-dimethylpyridine 6 is a precursor of the interconversion of 6 to 2.4-dimethylpyridine 4. The formation of a triplet azaprefulvene 21 with a barrier of 20.7 kcal mol(-1) is a key step during the triplet migration process leading to another out-of-plane distorted structure 27. Subsequent rearomatization of 27 completes the interconversion of 6 with 4. Present calculations provide some insight into the photochemistry of dimethylpyridines at 254 nm.

Journal Article↗

PubMed2001

[Clinical use of interlocking intramedullary nail treating in complex and nonunion fracture of femur and tibia].

Fifty-one complex and nonunion fractures of femur and tibia in forty eight patients were treated with interlocking intramedullary nail. All patients were followed-up for 6 to 29 months to evaluate the curative effect. Forty-nine fractures in forty-six patients were healed(95.8%). The time of healing was 16 weeks(10-24 weeks) in femur and 18 weeks (12-28 week) in tibia in fresh fracture, and 20 weeks(14-46 weeks) in femur nonunion and 18 weeks (12-28 weeks) in tibia nonunion. In femur, the efficacy of 28 cases was excellent or good (93.3%), and 2 cases mediate (6.7%); in tibia, 18 cases were all assessed as excellent or good. The complications were observed in 8 patients (16.67%), including distal screw misinserting, extremity shortening, screw loosening, distal shaft fracture and fracture nonunion. The results suggest that interlocking intramedullary nail can be used in many kinds of femur and tibia fracture with satisfactory result, especially in the complex fracture and nonunion after fixation failure.

Adult↗

PubMed2001

Infection density of Wolbachia and incompatibility level in two planthopper species, Laodelphax striatellus and Sogatella furcifera.

Wolbachia, a bacterial endosymbiote of arthropods, causes cytoplasmic incompatibility (CI) in many insect species. CI traits were studied in two planthopper species, Laodelphax striatellus and Sogatella furcifera, and Wolbachia densities in these planthopper species were calculated by quantitative PCR methods. The CI level of L. striatellus was quite high and even aged males strongly caused CI. In contrast, S. furcifera showed partial CI, and males lost their ability to cause CI with age. Wolbachia infecting these two planthopper species were the same with respect to the nucleotide sequences of Wolbachia genes, 16S rDNA, ftsZ gene, groE genes, and wsp gene. Two methods for quantitative PCR, one using a DNA sequencer and the other a real-time sequence detection system, were established to calculate the amount of Wolbachia in the planthoppers. The density of Wolbachia in S. furcifera males was quite low. The difference in CI levels between the two planthopper species seems to be due to different amounts of Wolbachia infecting males.

Animals↗

PubMed2001

Expressed sequence tags from a NaCl-treated Suaeda salsa cDNA library.

Past efforts to improve plant tolerance to osmotic stress have had limited success owing to the genetic complexity of stress responses. The first step towards cataloging and categorizing genetically complex abotic stress responses is the rapid discovery of genes by the large-scale partial sequencing of randomly selected cDNA clones or expressed sequence tags (ESTs). Suaeda salsa, which can survive seawater-level salinity, is a favorite halophytic model for salt tolerant research. We constructed a NaCl-treated cDNA library of Suaeda salsa and sequenced 1048 randomly selected clones, out of which 1016 clones produced readable sequences (773 showed homology to previously identified genes, 227 matched unknown protein coding regions, 16 anomalous sequences or sequences of bacterial origin were excluded from further analysis). By sequence analysis we identified 492 unique clones: 315 showed homology to previously identified genes, 177 matched unknown protein coding regions (101 of which have been found before in other organisms and 76 are completely novel). All our EST data are available on the Internet. We believe that our dbEST and the associated DNA materials will be a useful source to scientists engaging in stress-tolerance study.

Blotting, Northern↗

PubMed2001

beta-Endorphin-containing memory-cells and mu-opioid receptors undergo transport to peripheral inflamed tissue.

Immunocyte-derived beta-endorphin can activate peripheral opioid receptors on sensory neurons to inhibit pain within inflamed tissue. This study examined mu-opioid receptors (MOR) on sensory nerves and beta-endorphin (END) in activated/memory CD4(+) cells (the predominant population homing to inflamed tissue). We found an upregulation of MOR in dorsal root ganglia, an increased axonal transport of MOR in the sciatic nerve and an accumulation of MOR in peripheral nerve terminals in Freund's adjuvant-induced hindpaw inflammation. A large number of CD4(+) cells containing beta-endorphin, but very few naive cells (CD45RC(+)), were observed in inflamed tissue, suggesting that this opioid is mainly present in activated/memory cells (CD4(+)/CD45RC(-)). Taken together, our results indicate an enhanced transport of both MOR and of the endogenous ligand beta-endorphin to injured tissue. This unique simultaneous upregulation of both receptors and ligands may serve to prevent excessive and/or chronic inflammatory pain.

Animals↗

PubMed2001

[Cloning and identifying renal cell carcinoma differentially expressed genes and their significance].

OBJECTIVE: To Clone study the differentially expressed new genes in renal cell carcinoma (RCC). METHODS: Using a technique known as suppression subtractive hybridization to construct the library which contains the differently expressing cDNAs between RCC and normal kidney cells. Then the RCC specifically expressed genes were cloned. RESULTS: Human RCC subtractive library with high subtractive efficiency was set up successfully. The amplified library contained 350 positive clones. Sequence analysis were performed for 5 clones. All the sequences were unknown previously and the cDNA insert GYLZ-RCC18 had three copies. Northern blot analysis showed that GYLZ-RCC18 cDNA expressed highly in RCC, but no signal could be detected in normal kidney. Using SMART RACE technique, the full length of novel gene of GYLZ-RCC18 was obtained. CONCLUSIONS: The highly efficient cDNA subtractive library may have formed solid foundation for screening and cloning new and specific oncogenes or tumor suppressor genes of RCC. The novel differentially expressed genes may provide an important clue for studying the mechanism of occurrence and development of RCC.

Carcinoma, Renal Cell↗

PubMed2001

Does simplifying transport and exposure yield reliable results? An analysis of four risk assessment methods.

Four approaches for predicting the risk of chemicals to humans and fish under different scenarios were compared to investigate whether it is appropriate to simplify risk evaluations in situations where an individual is making environmentally conscious manufacturing decisions or interpreting toxics release inventory (TRI) data: (1) the relative risk method, that compares only a chemical's relative toxicity; (2) the toxicity persistence method, that considers a chemical's relative toxicity and persistence; (3) the partitioning, persistence toxicity method, that considers a chemical's equilibrium partitioning to air, land, water, and sediment, persistence in each medium, and its relative toxicity; and (4) the detailed chemical fate and toxicity method, that considers the chemical's relative toxicity, and realistic attenuation mechanisms such as advection, mass transfer and reaction in air, land, water, and sediment. In all four methods, the magnitude of the risk was estimated by comparing the risk of the chemical's release to that of a reference chemical. Three comparative scenarios were selected to evaluate the four approaches for making pollution prevention decisions: (1) evaluation of nine dry cleaning solvents, (2) evaluation of four reaction pathways to produce glycerine, and (3) comparison of risks for the chemical manufacturing and petroleum industry. In all three situations, it was concluded that ignoring or simplifying exposure calculations is not appropriate, except in cases where either the toxicity was very great or when comparing chemicals with similar fate. When the toxicity is low to moderate and comparable for chemicals, the chemicals' fate influences the results; therefore, we recommend using a detailed chemical fate and toxicity method because the fate of chemicals in the environment is assessed with consideration of more realistic attenuation mechanisms than the other three methods. In addition, our study shows that evaluating the risk associated with industrial release of chemicals (e.g., the toxics release inventory) may be misleading if only mass emissions are considered.

Animals↗

PubMed2001

Complete genomic sequence of Pasteurella multocida, Pm70.

We present here the complete genome sequence of a common avian clone of Pasteurella multocida, Pm70. The genome of Pm70 is a single circular chromosome 2,257,487 base pairs in length and contains 2,014 predicted coding regions, 6 ribosomal RNA operons, and 57 tRNAs. Genome-scale evolutionary analyses based on pairwise comparisons of 1,197 orthologous sequences between P. multocida, Haemophilus influenzae, and Escherichia coli suggest that P. multocida and H. influenzae diverged approximately 270 million years ago and the gamma subdivision of the proteobacteria radiated about 680 million years ago. Two previously undescribed open reading frames, accounting for approximately 1% of the genome, encode large proteins with homology to the virulence-associated filamentous hemagglutinin of Bordetella pertussis. Consistent with the critical role of iron in the survival of many microbial pathogens, in silico and whole-genome microarray analyses identified more than 50 Pm70 genes with a potential role in iron acquisition and metabolism. Overall, the complete genomic sequence and preliminary functional analyses provide a foundation for future research into the mechanisms of pathogenesis and host specificity of this important multispecies pathogen.

Base Sequence↗

PubMed2001

Fluorous mixture synthesis: a fluorous-tagging strategy for the synthesis and separation of mixtures of organic compounds.

The solution-phase synthesis of organic compounds as mixtures rather than in individual pure form offers efficiency advantages that are negated by the difficulty in separating and identifying the components of the final mixture. Here, a strategy for mixture synthesis that addresses these separation and identification problems is presented. A series of organic substrates was tagged with a series of fluorous tags of increasing fluorine content. The compounds were then mixed, and multistep reactions were conducted to make enantiomers or analogs of the natural product mappicine. The resulting tagged products were then demixed by fluorous chromatography (eluting in order of increasing fluorine content) to provide the individual pure components of the mixture, which were detagged to release the final products.

Alkaloids↗