Biomedical subjects

Ying Xu

Publications and source records attributed to Ying Xu.

196 records · Page 11Linked to original sources

PubMed2002

An electrochemical DNA hybridization detection assay based on a silver nanoparticle label.

A novel, sensitive electrochemical DNA hybridization detection assay, using silver nanoparticles as the oligonucleotide labeling tag, is described. The assay relies on the hybridization of the target DNA with the silver nanoparticle-oligonucleotide DNA probe, followed by the release of the silver metal atoms anchored on the hybrids by oxidative metal dissolution and the indirect determination of the solubilized Ag(I) ions by anodic stripping voltammetry (ASV) at a carbon fiber ultramicroelectrode. The influence of the relevant experimental variables, including the surface coverage of the target oligonucleotide, the duration of the silver dissolution steps and the parameters of the electrochemical stripping measurement of the silver(I) ions, is examined and optimized. The combination of the remarkable sensitivity of the stripping metal analysis at the microelectrode with the large number of silver(I) ions released from each DNA hybrid allows detection at levels as low as 0.5 pmol L(-1) of the target oligonucleotides.

DNA Mutational Analysis↗

PubMed2002

Genomes to Life "Center for Molecular and Cellular Systems": a research program for identification and characterization of protein complexes.

Goal 1 of Department of Energy's Genomes to Life (GTL) program seeks to identify and characterize the complete set of protein complexes within a cell. Goal 1 forms the foundation necessary to accomplish the other objectives of the GTL program, which focus on gene regulatory networks and molecular level characterization of interactions in microbial communities. Together this information would allow cells and their components to be understood in sufficient detail to predict, test and understand the responses of a biological system to its environment. The Center for Molecular and Cellular Systems has been established to identify and characterize protein complexes using high through-put analytical technologies.A dynamic research program is being developed that supports the goals of the Center by focusing on the development new capabilities for sample preparation and complex separations, molecular level identification of the protein complexes by mass spectrometry, characterization of the complexes in living cells by imaging techniques, and bioinformatics and computational tools for the collection and interpretation of data and formation of databases and tools to allow the data to be shared by the biological community.

Animals↗

PubMed2002

Carbon sequestration in Synechococcus Sp.: from molecular machines to hierarchical modeling.

The U.S. Department of Energy recently announced the first five grants for the Genomes to Life (GTL) Program. The goal of this program is to "achieve the most far-reaching of all biological goals: a fundamental, comprehensive, and systematic understanding of life." While more information about the program can be found at the GTL website (www.doegenomestolife.org), this paper provides an overview of one of the five GTL projects funded, "Carbon Sequestration in Synechococcus Sp.: From Molecular Machines to Hierarchical Modeling." This project is a combined experimental and computational effort emphasizing developing, prototyping, and applying new computational tools and methods to elucidate the biochemical mechanisms of the carbon sequestration of Synechococcus Sp., an abundant marine cyanobacteria known to play an important role in the global carbon cycle. Understanding, predicting, and perhaps manipulating carbon fixation in the oceans has long been a major focus of biological oceanography and has more recently been of interest to a broader audience of scientists and policy makers. It is clear that the oceanic sinks and sources of CO(2) are important terms in the global environmental response to anthropogenic atmospheric inputs of CO(2) and that oceanic microorganisms play a key role in this response. However, the relationship between this global phenomenon and the biochemical mechanisms of carbon fixation in these microorganisms is poorly understood. The project includes five subprojects: an experimental investigation, three computational biology efforts, and a fifth which deals with addressing computational infrastructure challenges of relevance to this project and the Genomes to Life program as a whole. Our experimental effort is designed to provide biology and data to drive the computational efforts and includes significant investment in developing new experimental methods for uncovering protein partners, characterizing protein complexes, identifying new binding domains. We will also develop and apply new data measurement and statistical methods for analyzing microarray experiments. Our computational efforts include coupling molecular simulation methods with knowledge discovery from diverse biological data sets for high-throughput discovery and characterization of protein-protein complexes and developing a set of novel capabilities for inference of regulatory pathways in microbial genomes across multiple sources of information through the integration of computational and experimental technologies. These capabilities will be applied to Synechococcus regulatory pathways to characterize their interaction map and identify component proteins in these pathways. We will also investigate methods for combining experimental and computational results with visualization and natural language tools to accelerate discovery of regulatory pathways. Furthermore, given that the ultimate goal of this effort is to develop a systems-level of understanding of how the Synechococcus genome affects carbon fixation at the global scale, we will develop and apply a set of tools for capturing the carbon fixation behavior of complex of Synechococcus at different levels of resolution. Finally, because the explosion of data being produced by high-throughput experiments requires data analysis and models which are more computationally complex, more heterogeneous, and require coupling to ever increasing amounts of experimentally obtained data in varying formats, we have also established a companion computational infrastructure to support this effort as well as the Genomes to Life program as a whole.

Algorithms↗

PubMed2002

PRIMEGENS: robust and efficient design of gene-specific probes for microarray analysis.

MOTIVATION: DNA microarray is a powerful high-throughput tool for studying gene function and regulatory networks. Due to the problem of potential cross hybridization, using full-length genes for microarray construction is not appropriate in some situations. A bioinformatic tool, PRIMEGENS, has recently been developed for the automatic design of PCR primers using DNA fragments that are specific to individual open reading frames (ORFs). RESULTS: PRIMEGENS first carries out a BLAST search for each target ORF against all other ORFs of the genome to quickly identify possible homologous sequences. Then it performs optimal sequence alignment between the target ORF and each of its homologous ORFs using dynamic programming. PRIMEGENS uses the sequence alignments to select gene- specific fragments, and then feeds the fragments to the Primer3 program to design primer pairs for PCR amplification. PRIMEGENS can be run from the command line on Unix/Linux platforms as a stand-alone package or it can be used from a Web interface. The program runs efficiently, and it takes a few seconds per sequence on a typical workstation. PCR primers specific to individual ORFs from Shewanella oneidensis MR-1 and Deinococcus radiodurans R1 have been designed. The PCR amplification results indicate that this method is very efficient and reliable for designing specific probes for microarray analysis.

Algorithms↗

PubMed2002

Clustering gene expression data using a graph-theoretic approach: an application of minimum spanning trees.

MOTIVATION: Gene expression data clustering provides a powerful tool for studying functional relationships of genes in a biological process. Identifying correlated expression patterns of genes represents the basic challenge in this clustering problem. RESULTS: This paper describes a new framework for representing a set of multi-dimensional gene expression data as a Minimum Spanning Tree (MST), a concept from the graph theory. A key property of this representation is that each cluster of the expression data corresponds to one subtree of the MST, which rigorously converts a multi-dimensional clustering problem to a tree partitioning problem. We have demonstrated that though the inter-data relationship is greatly simplified in the MST representation, no essential information is lost for the purpose of clustering. Two key advantages in representing a set of multi-dimensional data as an MST are: (1) the simple structure of a tree facilitates efficient implementations of rigorous clustering algorithms, which otherwise are highly computationally challenging; and (2) as an MST-based clustering does not depend on detailed geometric shape of a cluster, it can overcome many of the problems faced by classical clustering algorithms. Based on the MST representation, we have developed a number of rigorous and efficient clustering algorithms, including two with guaranteed global optimality. We have implemented these algorithms as a computer software EXpression data Clustering Analysis and VisualizATiOn Resource (EXCAVATOR). To demonstrate its effectiveness, we have tested it on three data sets, i.e. expression data from yeast Saccharomyces cerevisiae, expression data in response of human fibroblasts to serum, and Arabidopsis expression data in response to chitin elicitation. The test results are highly encouraging. AVAILABILITY: EXCAVATOR is available on request from the authors.

Algorithms↗

PubMed2002

gp130-linked signal transduction promotes the differentiation and maturation of dendritic cells.

In order to explore the role of gp130-linked signal transduction in the differentiation and maturation of dendritic cells (DC), the mAb, B-S12, an agonist of gp130, was used for the activation of gp130 on DC. The effects of cytokines and of anti-gp130 mAb on the proliferation of DC, and their expression of IL-12 and CD80 (B7-1) by DC were evaluated. DC differentiating from peripheral blood mononuclear cells did not express the IL-6 receptor alpha chain, but expressed gp130. Anti-gp130 mAb promoted the proliferation of DC, induced by IL-4 and granulocyte macrophage colony stimulating factor (GM-CSF), by up-regulating the GM-CSF receptor on DC. DC induced by gp130 mAb and cytokines expressed DC-derived CC chemokine, as measured by RT-PCR. Induced DC also stimulated strong proliferation of autologous T cells in mixed lymphocyte reaction since an up-regulated expression of IL-12 and CD80 (B7-1) was observed in DC activated by anti-gp130 mAb. Thus, gp130 signal transduction is important for the differentiation and maturation of DC.

Adult↗

PubMed2002

Beta-hydroxyisovalerylshikonin is a novel and potent inhibitor of protein tyrosine kinases.

Beta-hydroxyisovalerylshikonin (beta-HIVS), a compound isolated from Lithospermium radix, most efficiently induced cell-death in two lines of lung cancer cells, namely, NCI-H522 and DMS114, whereas shikonin was effective against a wide variety of tumor cell lines. During our studies of the mechanism of action of beta-HIVS on tumor cells, we found that this compound inhibited protein tyrosine kinase (PTK) activity. The tyrosine kinase activities of a receptor for EGF (EGFR) and v-Src were strongly inhibited and that of KDR/Flk-1 was weakly inhibited by beta-HIVS. The inhibition by beta-HIVS of the activities of EGFR and v-Src was much stronger than that by shikonin. The IC50 values of beta-HIVS for EGFR and v-Src were approximately 0.7 microM and 1 microM, respectively. Moreover, the inhibition of v-Src by beta-HIVS was non-competitive with respect to ATP. These results strongly suggest that the action of beta-HIVS, as well as that of shikonin, involves the inhibition of PTK, and they also suggest the possibility of producing a novel group of PTK inhibitors based on shikonin as the parent compound.

3T3 Cells↗

PubMed2002

An exploratory analysis of behavioral health care use within families.

OBJECTIVES: The authors studied enrollees in employer-sponsored managed health plans to determine the extent of multiple behavioral health consumers within families, use of behavioral health services by employees who have another family member using such services, congruence of diagnoses between two family members using behavioral health services, and the effect on covered charge per behavioral health consumer when other family members use behavioral health services. METHODS: Claims data from 911 plans sold or managed by a single managed behavioral health care company were examined. The plans provided coverage for 724,789 employees and covered about 1.7 million lives. Family members of employees were identified by the relationship codes on the claims. Service utilization rates were calculated for employees overall and for employees who had spouses or children who used behavioral health services. Mean and median covered charges were determined and were examined by number and type of consumers in the family. RESULTS: The use of behavioral health services was greater among employees whose children or spouses used behavioral health services. Utilization rates varied by the child's or spouse's diagnoses. More than 50 percent of male employees whose children received treatment for a depressive disorder also received such treatment. Congruence of diagnoses within families was noted. Covered charges per person generally increased with the number of family members who used behavioral health services. CONCLUSION: Greater knowledge about patterns of use of behavioral health services within families may help in improving access to care and developing more effective family interventions.

Adult↗

PubMed2002

Recombinant human Flt3 ligand exerts both direct and indirect effects on hematopoiesis.

OBJECTIVE: To investigate the direct effects of the Flt3 ligand (FL) on hematopoiesis, such as the stimulation of the formation of hematopoietic colonies and the proliferation of dendritic cells, as well as the indirect stimulation of hematopoiesis, especially via the proliferation of endothelial cells. METHODS: Mononuclear cells from human cord blood were plated in methylcellulose medium containing different cytokines to induce hematopoietic colony formation. Dendritic cells (DCs) were induced from the mononuclear cells with a cytokine cocktail with or without recombinant human soluble FL (rhFL; 100 ng/ml). The Flt3 receptors on the surface of a human microvascular endothelial cell line (ECV) were analyzed by flow cytometry. The proliferation of ECV stimulated by rhFL was measured with the microculture tetrazolium assay. The levels of FL, IL-6, IL-8, G-CSF and GM-CSF in the supernatant of ECV cultures were measured by enzyme linked immunoabsorbent assay (ELISA). RESULTS: rhFL stimulates colony formation from cord blood when used as a sole stimulant. FL in combination with other cytokines increased colony formation significantly. The number of DCs was approximately 2.5 times higher when rhFL was used. rhFL stimulates the proliferation of ECV on which Flt3 receptors are expressed. Furthermore, ECV secretes FL, IL-6, IL-8, G-CSF and GM-CSF, which were augmented by tumor necrosis factor-alpha and rhFL. CONCLUSIONS: rhFL enhances hematopoietic colony formation and DC proliferation from human cord blood cells. FL not only stimulates the proliferation of ECV, but is also secreted by ECV. FL may exert direct and indirect effects on hematopoiesis.

Cell Division↗

PubMed2002

[The establishment of a guinea pig model of inflammatory pleural effusion and the effect of batroxobin in the prevention of pleural encapsulation].

OBJECTIVE: To establish an animal model of inflammatory pleural effusion and to investigate the role of batroxobin in preventing encapsulation of pleural effusion. METHODS: (1) Forty guinea pigs were divided into two groups: the animal model group received injection of 1% carrageenan (0.8 approximately 1.0 ml) in the right chest cavity; the control animals received injection of normal saline (1 ml). (2) Sixty guinea pigs were injected with 1% carrageenan (0.8 approximately 1.0 ml) in the right chest cavity, and then divided into a treatment group and a control group. Batroxobin (3 BU) was injected into the right chest cavity of the animals in the treatment group, while normal saline was used in the control group. The animals were killed at different time points. RESULTS: In the animal model group, pleural effusion appeared in 24 hours and reached maximum amount within 2 approximately 3 days. Neutrophils accumulated in the effusion and pleural inflammation intensified at the same time. Fibrosis and pleural adhesion appeared by the seventh day, became prominent by the tenth day, and encapsulated pleurisy was evident by the fourteenth day. With batroxobin treatment, pleural effusion and inflammation attenuated. The fibrinogen (Fbg) level decreased, and the levels of tissue plasminogen activator (t-PA) and D-dimer increased in the effusion. No pleural encapsulation was observed. CONCLUSIONS: Carrageenan was successfully used to establish an animal model of inflammatory pleural effusion in guinea pigs. Batroxobin was effective in reducing inflammation and pleural effusion and in preventing pleural fibrosis and encapsulation.

Animals↗

PubMed2002

[Processing of optic flow information during self-motion].

For human beings and animals, the observer encounters the so-called optic flow during locomotion, the image motion pattern of the environment on the retina, which includes three basic modes of motion: rotation, expansion/contraction and translation. The analysis of optic flow information is vital for determining the direction and velocity of locomotion and has been a hotspot of the studies on visual information processing in recent years. In this article, some progresses in psychophysics and electrophysiology studies on optic flow are introduced and the neural mechanism of optic flow processing in mammalian brain is discussed.

Animals↗

PubMed2002

An efficient branch-and-bound algorithm for the assignment of protein backbone NMR peaks.

NMR resonance assignment is one of the key steps in solving an NMR protein structure. The assignment process links resonance peaks to individual residues of the target protein sequence, providing the prerequisite for establishing intra- and inter-residue spatial relationships between atoms. The assignment process is tedious and time-consuming, which could take many weeks. Though there exist a number of computer programs to assist the assignment process, many NMR labs are still doing the assignments manually to ensure quality. This paper presents a new computational method based on our recent work towards automating the assignment process, particularly the process of backbone resonance peak assignment. We formulate the assignment problem as a constrained weighted bipartite matching problem. While the problem, in the most general situation, is NP-hard, we present an efficient solution based on a branch-and-bound algorithm with effective bounding techniques and a greedy filtering algorithm for reducing the search space. Our experimental results on 70 instances of (pseudo) real NMR data derived from 14 proteins demonstrate that the new solution runs much faster than a recently introduced (exhaustive) two-layer algorithm and recovers more correct peak assignments than the two-layer algorithm.

Algorithms↗

PubMed1998

Aspartate carbamoyltransferase from a psychrophilic deep-sea bacterium, Vibrio strain 2693: properties of the enzyme, genetic organization and synthesis in Escherichia coli.

The aspartate carbamoyltransferase (ATCase) genes of psychrophilic Vibrio strain 2693 were cloned by complementation in Escherichia coli and the enzyme was partly characterized. The genes constitute a pyrBI operon homologous to the cognate structure in E. coli where pyrB and pyrI respectively encode the catalytic and the regulatory chains of ATCase. The strong sequence similarities noted between Vibrio and E. coli ATCases include extensive conservation of residues involved in interactions between subunits, suggesting that the two enzymes have very similar tertiary and quaternary structures. Vibrio ATCase is, however, not activated by ATP and not synergistically inhibited by CTP and UTP. It is also much more thermolabile than E. coli ATCase. With respect to Pyrococcus abyssi and E. coli ATCases, Vibrio ATCase presents marked differences in composition which could be related to its psychrophilic character. The results of these structural and functional comparisons indicate that Vibrio 2693 ATCase is a suitable model for biochemical studies on structure-function relationships in a 'cold' allosteric enzyme. The operon is expressed from a promoter which is immediately followed by a pyrimidine-rich leader ORF terminating within a putative transcription attenuator. These genetic and enzymic data strengthen the evolutionary relationship already noted between Vibrionaceae and Enterobacteriaceae.

Amino Acid Sequence↗

PubMedDate not supplied

Efficient parameterized algorithms for biopolymer structure-sequence alignment.

Computational alignment of a biopolymer sequence (e.g., an RNA or a protein) to a structure is an effective approach to predict and search for the structure of new sequences. To identify the structure of remote homologs, the structure-sequence alignment has to consider not only sequence similarity, but also spatially conserved conformations caused by residue interactions and, consequently, is computationally intractable. It is difficult to cope with the inefficiency without compromising alignment accuracy, especially for structure search in genomes or large databases. This paper introduces a novel method and a parameterized algorithm for structure-sequence alignment. Both the structure and the sequence are represented as graphs, where, in general, the graph for a biopolymer structure has a naturally small tree width. The algorithm constructs an optimal alignment by finding in the sequence graph the maximum valued subgraph isomorphic to the structure graph. It has the computational time complexity O[k(t)N(2)] for the structure of N residues and its tree decomposition of width t. Parameter k, small in nature, is determined by a statistical cutoff for the correspondence between the structure and the sequence. This paper demonstrates a successful application of the algorithm to RNA structure search used for noncoding RNA identification. An application to protein threading is also discussed.

Algorithms↗

PubMedDate not supplied

Decreased use of adjuvant breast cancer therapy in a randomized controlled trial of a decision aid with individualized risk information.

OBJECTIVE: Oncology patients often seek involvement in their medical consultations. Such involvement is endorsed by most health care providers and mirrored in practice guidelines. However, oncologists exhibit great variation in how they provide patients with disease-relevant information, and many remain reluctant to do so at all. The authors examined the impact of a patient-specific decision aid on women's decisions about adjuvant therapy for breast cancer. METHOD: 386 women with breast cancer were randomized to receive either an informational pamphlet about adjuvant therapy (usual care) or a patient-specific, evidence-based decision aid about adjuvant therapy. The authors compared rates of adjuvant therapy between the groups controlling for age, education, marital status, race, tumor severity, and practice type of their physician (university-based or community-based). RESULTS: Among women with low tumor severity, only 58% (35/60) of women in the decision aid group chose adjuvant therapy, compared to 87% (33/38) of their counterparts in usual care (P<0.01). CONCLUSIONS: This study illustrates the important impact of medical decision aids on treatment choices, particularly for patients for whom treatment has little benefit. In the case of adjuvant therapy for breast cancer, providing individualized, evidence-based risk information for shared decision making resulted in fewer women with low tumor severity choosing adjuvant treatment.

Aged↗

PubMedDate not supplied

Negotiated care improves fluid status in diabetic peritoneal dialysis patients.

BACKGROUND: Volume overload is common in diabetic patients on continuous ambulatory peritoneal dialysis (PD), especially when the patient's residual renal function decreases with time on PD. Due to the higher dietary salt and fluid intake, diabetic PD patients tend to use more hypertonic glucose solution to remove excess fluid, which in turn may lead to increased membrane permeability. In the present study, we investigated the effect of negotiated care on fluid status in diabetic PD patients. METHODS: All diabetic PD patients who had been on PD for at least 3 months by the end of year 2002 in the First Hospital of Peking University were included in the present study. A primary nurse was assigned to each patient and intensive patient education was implemented, focusing on the importance of dietary salt and fluid restriction, the detrimental effect of using more hypertonic glucose solution, and the consequence of fluid overload. Decisions on dialysis prescriptions were made after extensive discussion among the primary nurse, nephrologists, patients, and patients' families. A patient support group was also involved when it was necessary. All the patients were followed for 1 year and fluid status, compliance to dietary restriction, and dialysis prescription were evaluated before the start and at the end of the study. RESULTS: There were 30 diabetic PD patients (age 65.4 +/- 10.3 years; on PD for 24.5 +/- 19.9 months, range 3 - 66 months) included in the study when it was started. During the 1 year of follow-up, 4 patients died of diabetic complications, 3 patients were transferred to hemodialysis due to resistant peritonitis, and 2 patients were transplanted. By the end of follow-up, 21 patients remained on PD, among whom 15 had improved fluid status, 4 did not change, and 2 had worsened fluid status as assessed by clinical and bio-impedance evaluation. Patient compliance to dietary salt and fluid restriction had increased from 19.5% to 76.2%. During the follow-up, 8 patients were anuric at the beginning of the study and the remaining 22 patients had declining residual renal function. Only 4 patients increased their use of hypertonic solution including 2.5% (3 patients) and 4.25% (1 patient) glucose, whereas 5 patients decreased their use of 2.5% dialysis solution. By the end of follow-up, only 1 of the 21 patients was using 4.25% glucose solution and all the patients had good blood glucose control. CONCLUSIONS: Our results suggest that negotiated care can be successfully used in diabetic PD patients. It helps to minimize the use of hypertonic glucose solution and improves patient compliance to dietary restriction of salt and fluid intake, and thus improves their fluid status.

Aged↗