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Biomedical subjects

Ying Xu

Publications and source records attributed to Ying Xu.

At least 127 records · Page 7Linked to original sources
PubMed2005

[Electroluminescent device based on terbium complex].

Rare earth complex Tb(BA)3phen has been synthesized, which is used as an emitting material in electroluminescence. The properties of monolayer device with the rate of 1000 r x min(-1) and the impure concentration of 1:5 are the best. And the highest brightness of this device reached 26.8 cd x cm(-2) at a fixed bias of 21 V. Bright green emission can be obtained from the optimized double-layer device and the highest EL brightness of the device reaches 322cd x m(-2) at the voltage of 22 V.

English Abstract↗
PubMed2005

Prediction of functional modules based on gene distributions in microbial genomes.

We present a computational method for prediction of functional modules that can be directly applied to the newly sequenced microbial genomes for predicting gene functions and the component genes of biological pathways. We first quantify the functional relatedness among genes based on their distribution (i.e., their existences and orders) across multiple microbial genomes, and obtain a gene network in which every pair of genes is associated with a score representing their functional relatedness. We then apply a threshold-based clustering algorithm to this gene network, and obtain modules for each of which the number of genes is bounded from above by a pre-specified value and the component genes are more strongly functionally related to each other than genes across the predicted modules. Particularly, when the module size is bounded by 130, we obtain 167 functional modules covering 813 genes for Escherichia coli K12, and 138 functional modules covering 731 genes for Bacillus subtilis subsp. subtilis str. 168. We have used the gene ontology (GO) information to assess the prediction results. The GO similarities among the genes of the same functional module are compared with the GO similarities among the genes that are randomly clustered together. This comparison reveals that our predicted functional modules are statistically and biologically significant, and the genes of the same functional module share more commonality in terms of biological process than in terms of molecular function or cellular component. We have also examined the predicted functional modules that are common to both Escherichia coli K12 and Bacillus subtilis subsp. subtilis str. 168, and provide explanations for some functional modules.

Cluster Analysis↗
PubMed2004

Sluggish and brisk ganglion cells detect contrast with similar sensitivity.

Roughly half of all ganglion cells in mammalian retina belong to the broad class, termed "sluggish." Many of these cells have small receptive fields and project via lateral geniculate nuclei to visual cortex. However, their possible contributions to perception have been largely ignored because sluggish cells seem to respond weakly compared with the more easily studied "brisk" cells. By selecting small somas under infrared DIC optics and recording with a loose seal, we could routinely isolate sluggish cells. When a spot was matched spatially and temporally to the receptive field center, most sluggish cells could detect the same low contrasts as brisk cells. Detection thresholds for the two groups determined by an "ideal observer" were similar: threshold contrast for sluggish cells was 4.7 +/- 0.5% (mean +/- SE), and for brisk cells was 3.4 +/- 0.3% (Mann-Whitney test: P > 0.05). Signal-to-noise ratios for the two classes were also similar at low contrast. However, sluggish cells saturated at somewhat lower contrasts (contrast for half-maximum response was 14 +/- 1 vs. 19 +/- 2% for brisk cells) and were less sensitive to higher temporal frequencies (when the stimulus frequency was increased from 2 to 4 Hz, the response rate fell by 1.6-fold). Thus the sluggish cells covered a narrower dynamic range and a narrower temporal bandwidth, consistent with their reported lower information rates. Because information per spike is greater at lower firing rates, sluggish cells may represent "cheaper" channels that convey less urgent visual information at a lower energy cost.

Action Potentials↗
PubMed2004

Di-mu-iodo-bis{[1,1'-methylenebis(3,5-dimethyl-1H-pyrazole-kappaN2)]copper(I)}.

In the title compound, [Cu2I2(C11H16N4)2], each of the two crystallographically equivalent Cu atoms is tetrahedrally coordinated by two N atoms from one 1,1'-methylenebis(3,5-dimethyl-1H-pyrazole) ligand and two bridging iodide anions. The molecule has a crystallographic center of symmetry located at the mid-point of the Cu...Cu line. One H atom of the CH2 group of the 1,1'-methylenebis(3,5-dimethyl-1H-pyrazole) ligand interacts with an iodide ion in an adjacent molecule to afford pairwise intermolecular C-H...I contacts, thereby forming chains of molecules running along the [101] direction.

Journal Article↗
PubMed2004

The Chinese rare minnow (Gobiocypris rarus) as an in vivo model for endocrine disruption in freshwater teleosts: a full life-cycle test with diethylstilbestrol.

Chinese rare minnow (Gobiocypris rarus), a freshwater teleost, was exposed to diethylstilbestrol (DES) at 0.05, 0.5, 1 and 5 microg/L from fertilized eggs for up to mature period under flow-through condition. Several endpoints that related to development, reproductive fitness and transgenerational effects were evaluated. It was found that body length and body weight were significantly reduced and vitellogenin (Vtg) levels were significantly increased for fish exposed to DES. Histological examination showed that the sex ratios of F0 fish skewed to female and about 2% of the fish exposed to 0.05 microg/L DES developed testes-ova. The reproductive success, as determined from data on egg production, was reduced in female fish exposed to 0.05, 0.5, 1 and 5 microg/L DES. The lowest-observed-effect concentrations (LOEC) for changes of sex ratios, reproductive success and histology alteration of F0 are 0.05 microg/L. In the offspring, transgenerational effects on egg hatching rate, egg fertilization and Vtg levels of juvenile individuals were not observed. However, survival of F1 generation fry significantly declined. The analysis of sex steroid levels revealed a significant decrease of testosterone (T) in the whole body homogenates (WBH) of male progeny and somewhat elevation of estradiol (E2) in the WBH of female offspring. These findings indicate that exposure to DES causes a variety of developmental, reproductive and transgenerational effects.

Animals↗
PubMed2004

Molecular modeling of the core of Abeta amyloid fibrils.

Amyloid fibrils, a key pathological feature of Alzheimer's disease (AD) and other amyloidosis implicated in neurodegeneration, have a characteristic cross-beta structure. Here we present a structural model for the core of amyloid fibrils formed by the Abeta peptide using computational approaches and experimental data. Abeta(15-36) was threaded against the parallel beta-helical proteins. Our multi-layer model was constructed using the top scoring template 1lxa, a left-handed parallel beta-helical protein. This six-rung helical model has in-register repeats of the Abeta(15-36) sequence. Each rung has three beta-strands separated by two turns. The model was tested using molecular dynamics simulations in explicit water, and is in good agreement with a number of experimental observations. In addition, a model based on right-handed helical proteins is also described. The core structural model described here might serve as the building block of the Abeta(1-40) amyloid fibril as well as some other amyloid fibrils.

Amyloid beta-Peptides↗
PubMed2004

The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway.

Paroxysmal non-kinesigenic dyskinesia (PNKD) is characterized by spontaneous hyperkinetic attacks that are precipitated by alcohol, coffee, stress and fatigue. We report mutations in the myofibrillogenesis regulator 1 (MR-1) gene causing PNKD in 50 individuals from eight families. The mutations cause changes (Ala to Val) in the N-terminal region of two MR-1 isoforms. The MR-1L isoform is specifically expressed in brain and is localized to the cell membrane while the MR-1S isoform is ubiquitously expressed and shows diffuse cytoplasmic and nuclear localization. Bioinformatic analysis reveals that the MR-1 gene is homologous to the hydroxyacylglutathione hydrolase (HAGH) gene. HAGH functions in a pathway to detoxify methylglyoxal, a compound present in coffee and alcoholic beverages and produced as a by-product of oxidative stress. Our results suggest a mechanism whereby alcohol, coffee and stress may act as precipitants of attacks in PNKD. Stress response pathways will be important areas for elucidation of episodic disease genetics where stress is a common precipitant of many common disorders like epilepsy, migraine and cardiac arrhythmias.

Animals↗
PubMed2004

[Application of separating brachial plexus block combined with preoperative analgesia by patient controlled intravenous analgesia in tendon repair].

OBJECTIVE: To investigate whether the separating brachial plexus block combined with preoperative analgesia by patient controlled analgesia (PCA) can be applied in tendon repair and postoperative active or passive functional exercise. METHODS: Two hundred and ten cases with tendon injury were randomly divided into 3 groups and all of the patients were administered Bupivacaine (0.25%), Papaverine (0.0625 mg/ml), and Dexamethasone (0.25 mg/ml) in separating brachial plexus block through axillary approach. Group A was control group, and preoperative analgesia was not applied. Preoperative analgesia was applied in group B and C. Tramadol and Ondansetron were administered in group B, Midazolam was administered besides Tramadol and Ondansetron in group C. The injection volume in the PCIA pump was increased to 100 ml by mixing physiologic saline. The pump was started after separating brachial plexus block in velocity of 2 ml/h, and its maintenance time was 48 h. The effect of separating brachial plexus block at 1, 2, 3, 6 and 12 h after finishing brachial plexus block was compared. The VAS, Ramesay assessment scoring were recorded at 0, 12, 24 and 48 h after starting pump. RESULTS: In each group, the effect of motor block became greater in the ascending order from 1, 2 to 3 h after finishing brachial plexus block, and less in the descending order from 3, 6 to 12 h after finishing brachial plexus block. Only at 6 and 12 h after finishing brachial plexus block, the effect of motor block of group B and group C was significantly less than that of group A (P < 0.05, < 0.01), the effect of motor block of group C was less than that of group B (P > 0.05). The effect of sensory block in the patients of all 3 groups was satisfactory. The VAS, Ramesay assessment scoring, effect of analgesia and sedation at 24 and 48 h after starting pump became greater in the ascending order from group A to group C, in which group B and group C were significantly greater than group A (P < 0.01). CONCLUSIONS: The separating brachial plexus block combined with preoperative analgesia by 2 kinds of PCIA dispensation can be both applied in tendon repair, but the separating effect of brachial plexus block of group B was superior to the group C.

Adolescent↗
PubMed2004

A graph-theoretic approach for the separation of b and y ions in tandem mass spectra.

MOTIVATION: Ion-type identification is a fundamental problem in computational proteomics. Methods for accurate identification of ion types provide the basis for many mass spectrometry data interpretation problems, including (a) de novo sequencing, (b) identification of post-translational modifications and mutations and (c) validation of database search results. RESULTS: Here, we present a novel graph-theoretic approach for solving the problem of separating b ions from y ions in a set of tandem mass spectra. We represent each spectral peak as a node and consider two types of edges: type-1 edge connecting two peaks probably of the same ion types and type-2 edge connecting two peaks probably of different ion types. The problem of ion-separation is formulated and solved as a graph partition problem, which is to partition the graph into three subgraphs, representing b, y and others ions, respectively, through maximizing the total weight of type-1 edges while minimizing the total weight of type-2 edges within each partitioned subgraph. We have developed a dynamic programming algorithm for rigorously solving this graph partition problem and implemented it as a computer program PRIME (PaRtition of Ion types in tandem Mass spEctra). The tests on a large amount of simulated mass spectra and 19 sets of high-quality experimental Fourier transform ion cyclotron resonance tandem mass spectra indicate that an accuracy level of approximately 90% for the separation of b and y ions was achieved. AVAILABILITY: The executable code of PRIME is available upon request. CONTACT: xyn@bmb.uga.edu.

Algorithms↗
PubMed2004

Retrieving sequences of enzymes experimentally characterized but erroneously annotated : the case of the putrescine carbamoyltransferase.

BACKGROUND: Annotating genomes remains an hazardous task. Mistakes or gaps in such a complex process may occur when relevant knowledge is ignored, whether lost, forgotten or overlooked. This paper exemplifies an approach which could help to resuscitate such meaningful data. RESULTS: We show that a set of closely related sequences which have been annotated as ornithine carbamoyltransferases are actually putrescine carbamoyltransferases. This demonstration is based on the following points : (i) use of enzymatic data which had been overlooked, (ii) rediscovery of a short NH2-terminal sequence allowing to reannotate a wrongly annotated ornithine carbamoyltransferase as a putrescine carbamoyltransferase, (iii) identification of conserved motifs allowing to distinguish unambiguously between the two kinds of carbamoyltransferases, and (iv) comparative study of the gene context of these different sequences. CONCLUSIONS: We explain why this specific case of misannotation had not yet been described and draw attention to the fact that analogous instances must be rather frequent. We urge to be especially cautious when high sequence similarity is coupled with an apparent lack of biochemical information. Moreover, from the point of view of genome annotation, proteins which have been studied experimentally but are not correlated with sequence data in current databases qualify as "orphans", just as unassigned genomic open reading frames do. The strategy we used in this paper to bridge such gaps in knowledge could work whenever it is possible to collect a body of facts about experimental data, homology, unnoticed sequence data, and accurate informations about gene context.

Amino Acid Motifs↗
PubMed2004

Sml1p is a dimer in solution: characterization of denaturation and renaturation of recombinant Sml1p.

Sml1p is a small 104-amino acid protein from Saccharomyces cerevisiae that binds to the large subunit (Rnr1p) of the ribonucleotide reductase complex (RNR) and inhibits its activity. During DNA damage, S phase, or both, RNR activity must be tightly regulated, since failure to control the cellular level of dNTP pools may lead to genetic abnormalities, such as genome rearrangements, or even cell death. Structural characterization of Sml1p is an important step in understanding the regulation of RNR. Until now the oligomeric state of Sml1p was unknown. Mass spectrometric analysis of wild-type Sml1p revealed an intermolecular disulfide bond involving the cysteine residue at position 14 of the primary sequence. To determine whether disulfide bonding is essential for Sml1p oligomerization, we mutated the Cys14 to serine. Sedimentation equilibrium measurements in the analytical ultracentrifuge show that both wild-type and C14S Sml1p exist as dimers in solution, indicating that the dimerization is not a result of a disulfide bond. Further studies of several truncated Sml1p mutants revealed that the N-terminal 8-20 residues are responsible for dimerization. Unfolding/refolding studies of wild-type and C14S Sml1p reveal that both proteins refold reversibly and have almost identical unfolding/refolding profiles. It appears that Sml1p is a two-domain protein where the N-terminus is responsible for dimerization and the C-terminus for binding and inhibiting Rnr1p activity.

Amino Acid Sequence↗
PubMed2004

PROSPECT-PSPP: an automatic computational pipeline for protein structure prediction.

Knowledge of the detailed structure of a protein is crucial to our understanding of the biological functions of that protein. The gap between the number of solved protein structures and the number of protein sequences continues to widen rapidly in the post-genomics era due to long and expensive processes for solving structures experimentally. Computational prediction of structures from amino acid sequence has come to play a key role in narrowing the gap and has been successful in providing useful information for the biological research community. We have developed a prediction pipeline, PROSPECT-PSPP, an integration of multiple computational tools, for fully automated protein structure prediction. The pipeline consists of tools for (i) preprocessing of protein sequences, which includes signal peptide prediction, protein type prediction (membrane or soluble) and protein domain partition, (ii) secondary structure prediction, (iii) fold recognition and (iv) atomic structural model generation. The centerpiece of the pipeline is our threading-based program PROSPECT. The pipeline is implemented using SOAP (Simple Object Access Protocol), which makes it easier to share our tools and resources. The pipeline has an easy-to-use user interface and is implemented on a 64-node dual processor Linux cluster. It can be used for genome-scale protein structure prediction. The pipeline is accessible at http://csbl.bmb.uga.edu/protein_pipeline.

Computational Biology↗
PubMed2004

Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone.

The factors directing marginal zone B cells to the splenic marginal zone are not well understood. Here we report that FTY720, a drug that targets sphingosine 1-phosphate (S1P) receptors, induced marginal zone B cell migration into follicles. Marginal zone B cells expressed S1P receptors 1 and 3 (S1P(1) and S1P(3), respectively). Using gene-targeted mice, we show that S1P(1) but not S1P(3) was required for localization in the marginal zone. In mice lacking the chemokine CXCL13, S1P(1)-deficient marginal zone B cells reacquired a marginal zone distribution. Exposure to lipopolysaccharide or antigen caused marginal zone B cells to downregulate S1P(1) and S1P(3) and to migrate into the splenic white pulp. These data suggest that marginal zone B cell localization to the marginal zone depends on responsiveness to the blood lysophospholipid S1P, with S1P(1) signaling overcoming the recruiting activity of CXCL13.

Animals↗
PubMed2004

Poly[iron(II)-di-mu-imidazole-4,5-dicarboxylato-kappa3N3,O4:O5].

In the title compound, [Fe(C(5)H(3)N(2)O(4))(2)](n), each Fe atom lies on a centre of symmetry, in an octahedral coordination environment consisting of two chelate rings [Fe-N = 2.154 (3) A and Fe-O = 2.180 (3) A] and two carboxylate O atoms [Fe-O = 2.111 (2) A] from imidazole-4,5-dicarboxylate ligands. Extensive hydrogen-bonding interactions exist between layers constructed of Fe(4) squares, forming tunnels along the a axis with large voids.

Journal Article↗
PubMed2004

DNA damage recognition of mutated forms of UvrB proteins in nucleotide excision repair.

The DNA repair protein UvrB plays an indispensable role in the stepwise and sequential damage recognition of nucleotide excision repair in Escherichia coli. Our previous studies suggested that UvrB is responsible for the chemical damage recognition only upon a strand opening mediated by UvrA. Difficulties were encountered in studying the direct interaction of UvrB with adducts due to the presence of UvrA. We report herein that a single point mutation of Y95W in which a tyrosine is replaced by a tryptophan results in an UvrB mutant that is capable of efficiently binding to structure-specific DNA adducts even in the absence of UvrA. This mutant is fully functional in the UvrABC incisions. The dissociation constant for the mutant-DNA adduct interaction was less than 100 nM at physiological temperatures as determined by fluorescence spectroscopy. In contrast, similar substitutions at other residues in the beta-hairpin with tryptophan or phenylalanine do not confer UvrB such binding ability. Homology modeling of the structure of E. coli UvrB shows that the aromatic ring of residue Y95 and only Y95 directly points into the DNA binding cleft. We have also examined UvrB recognition of both "normal" bulky BPDE-DNA and protein-cross-linked DNA (DPC) adducts and the roles of aromatic residues of the beta-hairpin in the recognition of these lesions. A mutation of Y92W resulted in an obvious decrease in the efficiency of UvrABC incisions of normal adducts, while the incision of the DPC adduct is dramatically increased. Our results suggest that Y92 may function differently with these two types of adducts, while the Y95 residue plays an unique role in stabilizing the interaction of UvrB with DNA damage, most likely by a hydrophobic stacking.

Adenosine Triphosphatases↗
PubMed2004

Protein structure prediction using sparse dipolar coupling data.

Residual dipolar coupling (RDC) represents one of the most exciting emerging NMR techniques for protein structure studies. However, solving a protein structure using RDC data alone is still a highly challenging problem. We report here a computer program, RDC-PROSPECT, for protein structure prediction based on a structural homolog or analog of the target protein in the Protein Data Bank (PDB), which best aligns with the (15)N-(1)H RDC data of the protein recorded in a single ordering medium. Since RDC-PROSPECT uses only RDC data and predicted secondary structure information, its performance is virtually independent of sequence similarity between a target protein and its structural homolog/analog, making it applicable to protein targets beyond the scope of current protein threading techniques. We have tested RDC-PROSPECT on all (15)N-(1)H RDC data (representing 43 proteins) deposited in the BioMagResBank (BMRB) database. The program correctly identified structural folds for 83.7% of the target proteins, and achieved an average alignment accuracy of 98.1% residues within a four-residue shift.

Computational Biology↗
PubMed2004

Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1.

Adaptive immunity depends on T-cell exit from the thymus and T and B cells travelling between secondary lymphoid organs to survey for antigens. After activation in lymphoid organs, T cells must again return to circulation to reach sites of infection; however, the mechanisms regulating lymphoid organ exit are unknown. An immunosuppressant drug, FTY720, inhibits lymphocyte emigration from lymphoid organs, and phosphorylated FTY720 binds and activates four of the five known sphingosine-1-phosphate (S1P) receptors. However, the role of S1P receptors in normal immune cell trafficking is unclear. Here we show that in mice whose haematopoietic cells lack a single S1P receptor (S1P1; also known as Edg1) there are no T cells in the periphery because mature T cells are unable to exit the thymus. Although B cells are present in peripheral lymphoid organs, they are severely deficient in blood and lymph. Adoptive cell transfer experiments establish an intrinsic requirement for S1P1 in T and B cells for lymphoid organ egress. Furthermore, S1P1-dependent chemotactic responsiveness is strongly upregulated in T-cell development before exit from the thymus, whereas S1P1 is downregulated during peripheral lymphocyte activation, and this is associated with retention in lymphoid organs. We find that FTY720 treatment downregulates S1P1, creating a temporary pharmacological S1P1-null state in lymphocytes, providing an explanation for the mechanism of FTY720-induced lymphocyte sequestration. These findings establish that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs.

Adoptive Transfer↗