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Xiaohua Zhang

Publications and source records attributed to Xiaohua Zhang.

17 recordsLinked to original sources
PubMed2026

Unraveling the coastal marine plastisphere archaeome.

Plastic pollution has created an expanding anthropogenic microbial niche, the plastisphere, raising questions about microbial ecology and associated impacts. Archaea, the third domain of life with fundamental ecological and evolutionary significance, remain poorly understood in this habitat. Here, using paired plastic debris and bulk-water samples from coastal marine ecosystems, key archaeal habitats increasingly threatened by plastic pollution, we characterize the plastisphere archaeome through archaeal amplicon sequencing and metagenomics. We show that the archaeome is significantly reshaped in the plastisphere, exhibiting higher taxonomic diversity, greater community heterogeneity, and selective enrichment of Euryarchaeota and Crenarchaeota. Archaeal genes involved in methane, nitrogen, and sulfur cycling are enriched in the plastisphere. Taxonomic and functional divergence between the plastisphere and bulk water increases with anthropogenic chemical stress. These findings suggest that plastic pollution could alter marine archaeal diversity, biogeography, and biogeochemical potential, extending understanding of plastisphere impacts to the archaeal domain.

Archaea↗
PubMed2005

The proficiency of a thermophilic chorismate mutase enzyme is solely through an entropic advantage in the enzyme reaction.

A study of the Thermus thermophilus chorismate mutase (TtCM) is described by using quantum mechanics (self-consistent-charge density-functional tight binding)/molecular mechanics, umbrella sampling, and the weighted histogram analysis method. The computed free energies of activation for the reactions in water and TtCM are comparable to the experimental values. The free energies for formation of near attack conformer have been determined to be 8.06 and 0.05 kcal/mol in water and TtCM, respectively. The near attack conformer stabilization contributes approximately 90% to the proficiency of the enzymatic reaction compared with the reaction in water. The transition state (TS) structures and partial atom charges are much the same in the enzymatic and water reactions. The difference in the electrostatic interactions of Arg-89 with O13 in the enzyme-substrate complex and enzyme-TS complex provides the latter with but 0.55 kcal/mol of 1.92 kcal/mol total TS stabilization. Differences in electrostatic interactions between components at the active site in the enzyme-substrate complex and enzyme-TS complex are barely significant, such that TS stabilization is of minor importance and the enzymatic catalysis is through an entropic advantage.

Binding Sites↗
PubMed2005

Statins and PPARalpha agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment.

Statins and fibrates (weak PPARalpha agonists) are prescribed for the treatment of lipid disorders. Both drugs cause myopathy, but with a low incidence, 0.1-0.5%. However, combined statin and fibrate therapy can enhance myopathy risk. We tested the myotoxic potential of PPAR subtype selective agonists alone and in combination with statins in a differentiated rat myotube model. A pharmacologically potent experimental PPARalpha agonist, Compound A, induced myotoxicity as assessed by TUNEL staining at a minimum concentration of 1 nM, while other weaker PPARalpha compounds, for example, WY-14643, Gemfibrozil and Bezafibrate increased the percentage of TUNEL-positive nuclei at micromolar concentrations. In contrast, the PPARgamma agonist Rosiglitazone caused little or no cell death at up to 10 muM and the PPARdelta ligand GW-501516 exhibited comparatively less myotoxicity than that seen with Compound A. An experimental statin (Compound B) and Atorvastatin also increased the percentage of TUNEL-positive nuclei and co-treatment with WY-14643, Gemfibrozil or Bezafibrate had less than a full additive effect on statin-induced cell killing. The mechanism of PPARalpha agonist-induced cell death was different from that of statins. Unlike statins, Compound A and WY-14643 did not activate caspase 3/7. In addition, mevalonate and geranylgeraniol reversed the toxicity caused by statins, but did not prevent the cell killing induced by WY-14643. Furthermore, unlike statins, Compound A did not inhibit the isoprenylation of rab4 or rap1a. Interestingly, Compound A and Compound B had differential effects on ATP levels. Taken together, these observations support the hypothesis that in rat myotube cultures, PPARalpha agonism mediates in part the toxicity response to PPARalpha compounds. Furthermore, PPARalpha agonists and statins cause myotoxicity through distinct and independent pathways.

Adenosine Triphosphate↗
PubMed2005

A definitive mechanism for chorismate mutase.

In previous research presentations, we have described the important features of the chorismate --> prephenate reaction using molecular dynamics (MD) and thermodynamic integration studies. This investigation of the reaction in Escherichia coli and water involves QM/MM procedures (SCCDFTB/MM two-dimensional reaction coordinates to identify transition state structures in the water, enzyme, and gas phase followed by B3LYP/6-31+G* single-point computations which allow the determination of activation energies in water and in the E. coli enzyme). Computed activation energies of 11.3 kcal/mol in enzyme and 20.3 kcal/mol in water may be compared to the experimental values of 12.7 and 20.7 kcal/mol, respectively. The transition state structures in the gas phase, water, and enzyme are much the same. The transition states are characteristic of a concerted pericyclic rearrangement. The very small differences in the partial charges of O13 in NAC and TS support only a small preferential (10%) electrostatic stabilization of TS. The free energy of NAC formation in water exceeds that in enzyme by 8.5 kcal/mol, and it is this favored formation of NAC that provides the major kinetic advantage to the enzymatic reaction. These findings compare most favorably with those previous observations of this laboratory employing molecular dynamics and thermodynamic integrations. A definitive mechanism for the chorismate mutase enzymes is provided.

Bacillus subtilis↗
PubMed2005

White-light photorefractive phase mask.

A volume photorefractive phase mask has been fabricated with incoherent white light from an incandescent source in LiNbO3:Fe self-defocusing photorefractive crystal for the first time, to our knowledge. It can guide and modulate a probe white light or a laser beam and can be used to transmit an incoherent dark image as the guided modes of the waveguides induced by white-light dark spatial solitons. This also proves the existence of photorefractive nonlinearity of white light.

Journal Article↗
PubMed2005

Oxytocin-receptor binding: why divalent metals are essential.

Biologists have observed that the presence of divalent metal is essential for the binding of the hormone oxytocin (OT) to its cellular receptor. However, this interaction is not understood on the molecular level. Because conformation is a key factor controlling ligand binding in biomolecule systems, we have used ion mobility experiments and molecular modeling to probe the conformation of the oxytocin-zinc complex. Results show that Zn2+ occupies an octahedral site in the interior of the OT peptide that frees the N-terminus and creates a structured hydrophobic binding site on the peptide exterior; both factors are conducive to binding oxytocin to its receptor.

Cations, Divalent↗
PubMed2005

Genome-wide array-based CGH for mantle cell lymphoma: identification of homozygous deletions of the proapoptotic gene BIM.

Mantle cell lymphoma (MCL) is characterized by 11q13 chromosomal translocation and CCND1 overexpression, but additional genomic changes are also important for lymphomagenesis. To identify the genomic aberrations of MCL at higher resolutions, we analysed 29 patient samples and seven cell lines using array-based comparative genomic hybridization (array CGH) consisting of 2348 artificial chromosome clones, which cover the whole genome at a 1.3 mega base resolution. The incidence of identified genomic aberrations was generally higher than that determined with chromosomal CGH. The most frequent imbalances detected by array CGH were gains of chromosomes 3q26 (48%), 7p21 (34%), 6p25 (24%), 8q24 (24%), 10p12 (21%) and 17q23 (17%), and losses of chromosomes 2p11 (83%), 11q22 (59%), 13q21 (55%), 1p21-p22 (52%), 13q34 (52%), 9q22 (45%), 17p13 (45%), 9p21 (41%), 9p24 (41%), 6q23-q24 (38%), 1p36 (31%), 8p23 (34%), 10p14 (31%), 19p13 (28%), 5q21 (21%), 22q12 (21%), 1q42 (17%) and 2q13 (17%). Our analyses also detected several novel recurrent regions of loss located at 1p36, 1q42.2-q43, 2p11.2, 2q13, 17p13.3 and 19p13.2-p13.3, as well as recurrent regions of homozygous loss such as 2p11 (Ig(kappa)), 2q13 and 9p21.3-p24.1 (INK4a/ARF). Of the latter, we investigated the 2q13 loss, which led to identification of homozygous deletions of the proapoptotic gene BIM. The high-resolution array CGH technology allowed for the precise identification of genomic aberrations and identification of BIM as a novel candidate tumor suppressor gene in MCL.

Aged↗
PubMed2005

Analysis of single-locus tests to detect gene/disease associations.

A goal of association analysis is to determine whether variation in a particular candidate region or gene is associated with liability to complex disease. To evaluate such candidates, ubiquitous Single Nucleotide Polymorphisms (SNPs) are useful. It is critical, however, to select a set of SNPs that are in substantial linkage disequilibrium (LD) with all other polymorphisms in the region. Whether there is an ideal statistical framework to test such a set of 'tag SNPs' for association is unknown. Compared to tests for association based on frequencies of haplotypes, recent evidence suggests tests for association based on linear combinations of the tag SNPs (Hotelling T(2) test) are more powerful. Following this logical progression, we wondered if single-locus tests would prove generally more powerful than the regression-based tests? We answer this question by investigating four inferential procedures: the maximum of a series of test statistics corrected for multiple testing by the Bonferroni procedure, T(B), or by permutation of case-control status, T(P); a procedure that tests the maximum of a smoothed curve fitted to the series of of test statistics, T(S); and the Hotelling T(2) procedure, which we call T(R). These procedures are evaluated by simulating data like that from human populations, including realistic levels of LD and realistic effects of alleles conferring liability to disease. We find that power depends on the correlation structure of SNPs within a gene, the density of tag SNPs, and the placement of the liability allele. The clearest pattern emerges between power and the number of SNPs selected. When a large fraction of the SNPs within a gene are tested, and multiple SNPs are highly correlated with the liability allele, T(S) has better power. Using a SNP selection scheme that optimizes power but also requires a substantial number of SNPs to be genotyped (roughly 10-20 SNPs per gene), power of T(P) is generally superior to that for the other procedures, including T(R). Finally, when a SNP selection procedure that targets a minimal number of SNPs per gene is applied, the average performances of T(P) and T(R) are indistinguishable.

Computer Simulation↗
PubMed2004

Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone.

Statins are widely used to treat lipid disorders. These drugs are safe and well tolerated; however, in <1% of patients, myopathy and/or rhabdomyolysis can develop. To better understand the mechanism of statin-induced myopathy, we examined the ability of structurally distinct statins to induce apoptosis in an optimized rat myotube model. Compound A (a lactone) and Cerivastatin (an open acid) induced apoptosis, as measured by TUNEL and active caspase 3 staining, in a concentration- and time-dependent manner. In contrast, an epimer of Compound A (Compound B) exhibited a much weaker apoptotic response. Statin-induced apoptosis was completely prevented by mevalonate or geranylgeraniol, but not by farnesol. Zaragozic acid A, a squalene synthase inhibitor, caused no apoptosis on its own and had no effect on Compound-A-induced myotoxicity, suggesting the apoptosis was not a result of cholesterol synthesis inhibition. The geranylgeranyl transferase inhibitors GGTI-2133 and GGTI-2147 caused apoptosis in myotubes; the farnesyl transferase inhibitor FTI-277 exhibited a much weaker effect. In addition, the prenylation of rap1a, a geranylgeranylated protein, was inhibited by Compound A in myotubes at concentrations that induced apoptosis. A similar statin-induced apoptosis profile was seen in human myotube cultures but primary rat hepatocytes were about 200-fold more resistant to statin-induced apoptosis. Although the statin-induced hepatotoxicity could be attenuated with mevalonate, no effect was found with either geranylgeraniol or farnesol. In studies assessing ubiquinone levels after statin treatment in rat and human myotubes, there was no correlation between ubiquinone levels and apoptosis. Taken together, these observations suggest that statins cause apoptosis in myotube cultures in part by inhibiting the geranylgeranylation of proteins, but not by suppressing ubiquinone concentration. Furthermore, the data from primary hepatocytes suggests a cell-type differential sensitivity to statin-induced toxicity.

Alkyl and Aryl Transferases↗
PubMed2004

A microarray platform comparison for neuroscience applications.

To address the need for high sensitivity in gene expression profiling of small neural tissue samples ( approximately 100 ng total RNA), we compared a novel RT-PCR-IVT protocol using fluor-reverse pairs on inkjet oligonucleotide microarrays and an RT-IVT protocol using 33P labeling on nylon cDNA arrays. The comparison protocol was designed to evaluate these systems for sensitivity, specificity, reproducibility, and linearity. We developed parameters, thresholds, and testing conditions that could be used to differentiate various systems that spanned detection chemistry and instrumentation; probe number and selection criteria; and sample processing protocols. We concluded that the inkjet system had better performance in sensitivity, specificity, and reproducibility than the nylon system, and similar performance in linearity. Between these two platforms, the data indicates that the inkjet system would perform better for the transcriptional profiling of 100 ng total RNA samples for neuroscience studies.

Animals↗
PubMed2004

Comparison of genetic aberrations in CD10+ diffused large B-cell lymphoma and follicular lymphoma by comparative genomic hybridization and tissue-fluorescence in situ hybridization.

CD10 is one of the hallmarks of germinal center B-cells where follicular lymphomas (FL) originate. It has not been clearly established, however, whether CD10(+) diffuse B-cell lymphomas (DLBCL) are genetically similar to FL. We therefore examined 19 CD10(+) DLBCL and 40 FL by means of comparative genomic hybridization (CGH) and tissue-fluorescence in situ hybridization (T-FISH). Chromosomal imbalance was more frequently detected in CD10(+) DLBCLs (19/19) than in FLs (24/40). Significant differences were found in eight frequently imbalanced regions, namely those with gains of chromosomes 7q and 12 and those with losses of chromosomes 1p, 4p, 6q, 15q, 16p and 17. Amplification of the 3q region where BCL6 is located is reported to occur frequently in DLBCL, but it was only found in one of the 19 CD10(+) DLBCL cases we examined. The involvement of t(14;18) in CD10(+)+ DLBCL (31%) and in FL (73%) was significantly different (P = 0.0064). The CGH pattern of CD10(+) DLBCL with t(14;18) was also different from that of FL with t(14;18). Taken together, our results indicate that CD10(+) DLBCL constitutes a unique subtype entity with genetic characteristics significantly different from those of FL and DLBCL.

Aged↗
PubMed2003

Integration of association statistics over genomic regions using Bayesian adaptive regression splines.

In the search for genetic determinants of complex disease, two approaches to association analysis are most often employed, testing single loci or testing a small group of loci jointly via haplotypes for their relationship to disease status. It is still debatable which of these approaches is more favourable, and under what conditions. The former has the advantage of simplicity but suffers severely when alleles at the tested loci are not in linkage disequilibrium (LD) with liability alleles; the latter should capture more of the signal encoded in LD, but is far from simple. The complexity of haplotype analysis could be especially troublesome for association scans over large genomic regions, which, in fact, is becoming the standard design. For these reasons, the authors have been evaluating statistical methods that bridge the gap between single-locus and haplotype-based tests. In this article, they present one such method, which uses non-parametric regression techniques embodied by Bayesian adaptive regression splines (BARS). For a set of markers falling within a common genomic region and a corresponding set of single-locus association statistics, the BARS procedure integrates these results into a single test by examining the class of smooth curves consistent with the data. The non-parametric BARS procedure generally finds no signal when no liability allele exists in the tested region (ie it achieves the specified size of the test) and it is sensitive enough to pick up signals when a liability allele is present. The BARS procedure provides a robust and potentially powerful alternative to classical tests of association, diminishes the multiple testing problem inherent in those tests and can be applied to a wide range of data types, including genotype frequencies estimated from pooled samples.

Algorithms↗
PubMed2003

[Effects of investment materials on cast shrinkage of base metal alloys].

OBJECTIVE: To compare the influence of different investment materials, methods and crown height on the cast shrinkage of full crowns made of dental base metal alloy. METHODS: All of the 288 wax patterns were made and divided into three groups according to their crown height. In every group, wax patterns were invested in metal rings and paper rings with three types investment material and cast with base metal alloys. Then the inside diameters of castings were measured and analyzed by statistical package SPSS. RESULTS: Differences between groups invested with the three types of material were significant(P < 0.01). There were significant difference between the groups investing with metal rings and paper rings(P < 0.01). CONCLUSION: The component of investment material and invested ring can affect the cast shrinkage of dental base metal alloy apparently.

Crowns↗
PubMed2002

Performance evaluation of plasma fractionation membrane.

Membrane plasma fractionation is an important part of double filtration plasmapheresis. We evaluated a newly developed polyethersulfone (PES) hollow-fiber plasma fractionation membrane, using 3 parameters: abnormal protein ratio (APRR), different protein ratio (DPR), and plasma filtration efficiency, except sieving coefficients. The APRR of the fractionation membrane was over 0.90, and the DPR changed after the plasma fractionation. We also compared the sieving coefficients of the PES hollow membrane with some commercial plasma fractionation membranes. The data were significant for the clinical use of the PES hollow-fiber fractionation membrane.

Cell Separation↗