Biomedical subjects

Dong Xu

Publications and source records attributed to Dong Xu.

At least 55 records · Page 3Linked to original sources

PubMed2005

BSS-HMM3s: an improved HMM method for identifying transcription factor binding sites.

Today, an important problem in molecular biology is the study of gene expression mechanism. The first step in determining differential gene expression is the binding of sequence specific transcription factors to regulatory regions of the genes. An important aspect to understand how a given transcription factor functions is to know the entire gamut of binding sites and potential target genes that the factor may regulate. In this paper, we presented an improved prediction method based on hidden Markov model (HMM) called BSS-HMM(3)s (binding site search based on third-order HMMs) for transcription factor binding sites. The results show that the predicted sensitivity and specificity of BSS-HMM(3)s increased 11.95 and 12.97%, respectively, compared with Match.

Animals↗

PubMed2005

More reliable protein NMR peak assignment via improved 2-interval scheduling.

Protein NMR peak assignment refers to the process of assigning a group of "spin systems" obtained experimentally to a protein sequence of amino acids. The automation of this process is still an unsolved and challenging problem in NMR protein structure determination. Recently, protein NMR peak assignment has been formulated as an interval scheduling problem (ISP), where a protein sequence P of amino acids is viewed as a discrete time interval I (the amino acids on P one-to-one correspond to the time units of I), each subset S of spin systems that are known to originate from consecutive amino acids from P is viewed as a "job" j(s), the preference of assigning S to a subsequence P of consecutive amino acids on P is viewed as the profit of executing job j(s) in the subinterval of I corresponding to P, and the goal is to maximize the total profit of executing the jobs (on a single machine) during I. The interval scheduling problem is max SNP-hard in general; but in the real practice of protein NMR peak assignment, each job j(s) usually requires at most 10 consecutive time units, and typically the jobs that require one or two consecutive time units are the most difficult to assign/schedule. In order to solve these most difficult assignments, we present an efficient 13/7-approximation algorithm for the special case of the interval scheduling problem where each job takes one or two consecutive time units. Combining this algorithm with a greedy filtering strategy for handling long jobs (i.e., jobs that need more than two consecutive time units), we obtain a new efficient heuristic for protein NMR peak assignment. Our experimental study shows that the new heuristic produces the best peak assignment in most of the cases, compared with the NMR peak assignment algorithms in the recent literature. The above algorithm is also the first approximation algorithm for a nontrivial case of the well-known interval scheduling problem that breaks the ratio 2 barrier.

Algorithms↗

PubMed2005

Proteomic analysis of soybean root hairs after infection by Bradyrhizobium japonicum.

Infection of soybean root hairs by Bradyrhizobium japonicum is the first of several complex events leading to nodulation. In the current proteomic study, soybean root hairs after inoculation with B. japonicum were separated from roots. Total proteins were analyzed by two-dimensional (2-D) polyacrylamide gel electrophoresis. In one experiment, 96 protein spots were analyzed by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to compare protein profiles between uninoculated roots and root hairs. Another 37 spots, derived from inoculated root hairs over different timepoints, were also analyzed by tandem MS (MS/MS). As expected, some proteins were differentially expressed in root hairs compared with roots (e.g., a chitinase and phosphoenolpyruvate carboxylase). Out of 37 spots analyzed by MS/MS, 27 candidate proteins were identified by database comparisons. These included several proteins known to respond to rhizobial inoculation (e.g., peroxidase and phenylalanine-ammonia lyase). However, novel proteins were also identified (e.g., phospholipase D and phosphoglucomutase). This research establishes an excellent system for the study of root-hair infection by rhizobia and, in a more general sense, the functional genomics of a single, plant cell type. The results obtained also indicate that proteomic studies with soybean, lacking a complete genome sequence, are practical.

Bradyrhizobium↗

PubMed2005

Protective effect of membrane cofactor protein against complement-dependent injury.

AIM: To evaluate the protective role of membrane cofactor protein (MCP, CD46) on complement-dependent injury. METHODS: MCP was separated by ion exchange chromatography on a DEAE sephadex A-50 column from pig erythrocyte ghosts. Its protective effect was tested in models such as cobra venom factor (CVF)-induced platelet metamorphosis and aggregation, human serum-induced injury in isolated working guinea pig heart and reverse passive Arthus reaction. RESULTS: MCP inhibited CVF-induced platelet metamorphosis with an IC50 of 56.7 mg/L+/-2.6 mg/L, and prevented injury induced by activated complement in isolated working guinea pig hearts. In the rat model of reverse Arthus reaction, MCP relieved the skin lesions induced by immune complexes. CONCLUSION: MCP has a protective effect against complement-dependent injury.

Animals↗

PubMed2005

Epigenetic modulation of gene expression in mammalian cells.

The precisely controlled regulation of gene expression plays an important role in normal cellular function, whereas abnormalities of gene expression can contribute to cancer and other diseases. Thus, the ability to selectively regulate gene expression is of tremendous importance, both as a basic research tool and as a potential therapeutic approach. Over the last two decades, several different strategies have been used for controlling expression of specific genes at the transcriptional and post-transcriptional levels. The best-known approach involves antisense oligonucleotides that downregulate gene expression through various mechanisms, most importantly by triggering the degradation of mRNA. The use of designed transcription factors has also developed into an interesting technology since it allows either the enhancement or the reduction of expression of a targeted gene. Recently RNA interference has emerged as a powerful tool for selective inhibition of gene expression. This review examines the basic aspects, advantages, and liabilities of these three approaches to gene modulation.

Animals↗

PubMed2005

Computational methods for remote homolog identification.

As more and more protein sequences are available, homolog identification becomes increasingly important for functional, structural, and evolutional studies of proteins. Many homologous proteins were separated a very long time ago in their evolutionary history and thus their sequences share low sequence identity. These remote homologs have become a research focus in bioinformatics over the past decade, and some significant advances have been achieved. In this paper, we provide a comprehensive review on computational techniques used in remote homolog identification based on different methods, including sequence-sequence comparison, and sequence-structure comparison, and structure-structure comparison. Other miscellaneous approaches are also summarized. Pointers to the online resources of these methods and their related databases are provided. Comparisons among different methods in terms of their technical approaches, their strengths, and limitations are followed. Studies on proteins in SARS-CoV are shown as an example for remote homolog identification application.

Animals↗

PubMed2005

Genome-scale protein function prediction in yeast Saccharomyces cerevisiae through integrating multiple sources of high-throughput data.

As we are moving into the post genome-sequencing era, various high-throughput experimental techniques have been developed to characterize biological systems at the genome scale. Discovering new biological knowledge from high-throughput biological data is a major challenge for bioinformatics today. To address this challenge, we developed a Bayesian statistical method together with Boltzmann machine and simulated annealing for protein function prediction in the yeast Saccharomyces cerevisiae through integrating various high-throughput biological data, including protein binary interactions, protein complexes and microarray gene expression profiles. In our approach, we quantified the relationship between functional similarity and high-throughput data. Based on our method, 1802 out of 2280 unannotated proteins in the yeast were assigned functions systematically. The related computer package is available upon request.

Bayes Theorem↗

PubMed2005

[Experiment study on the estrogen-like effect of compounds of mercury, chromium and manganese].

OBJECTIVE: In order to study estrogen-like effect of compounds of Mercury, Chromium and Manganese. METHODS: Mercury Chloride, Manganese Sulfate, Chromium Chloride and Chromium trioxide were selected to perform proliferation assay of MCF-7 human breast cancer cells and binding assay of estrogen receptor for rat uterine. RESULTS: Mercury Chloride could stimulate the proliferation of MCF-7 cell, the maximal increase of MCF-7 cells was measured by Mercury Chloride at 10(-7) mol/L. The effect was blocked completely by a pure antigestrogen ICI182, 780; but Mercury Chloride could not bind to ER by competing with E2. Chromium Chloride, Chromium Trioxide and Manganese Sulfate were not able to stimulate the proliferation of MCF-7 cell and bind to ER through competing against 3H-E2 in vitro. CONCLUSION: Mercury Chloride exhibited the estrogenicity through binding and activating ER; Chromium Chloride, Chromium trioxide and Manganese Sulfate did not show any estrogenicity.

Animals↗

PubMed2005

Understanding the unique characteristics of suicide in China: national psychological autopsy study.

OBJECTIVE: To compare the characteristics of suicides in the four main demographic groups: urban males, urban females, rural males and rural females in order to help clarify the demographic pattern of suicides in China. METHODS: A detailed psychological autopsy survey instrument was independently administered to 895 suicide victims in family members and close associates from 23 geographically representative locations from around the country. RESULTS: Pesticide ingestion accounted for 58% (519) of all suicides and 61% (318/519) of deaths were due to unsuccessful medical resuscitation. A substantial proportion (37%) of suicide victims did not have a mental illness. Among the 563 victims with mental illness, only 13% (76/563) received psychiatric treatment. Compared to other demographic groups, young rural females who died from suicide had the highest rate of pesticide ingestion (79%), the lowest prevalence of mental illness (39%), and the highest acute stress from precipitating life events just prior to the suicide. CONCLUSION: Many suicides in China are impulsive acts of deliberate self-harm following acute interpersonal crises. Prevention of suicides in China must focus on improving awareness of psychological problems, improving mental health services, providing alternative social support networks for managing acute interpersonal conflicts, limiting access to pesticides, and improving the resuscitation skills of primary care providers.

Adolescent↗

PubMed2004

Global protein function annotation through mining genome-scale data in yeast Saccharomyces cerevisiae.

As we are moving into the post genome-sequencing era, various high-throughput experimental techniques have been developed to characterize biological systems on the genomic scale. Discovering new biological knowledge from the high-throughput biological data is a major challenge to bioinformatics today. To address this challenge, we developed a Bayesian statistical method together with Boltzmann machine and simulated annealing for protein functional annotation in the yeast Saccharomyces cerevisiae through integrating various high-throughput biological data, including yeast two-hybrid data, protein complexes and microarray gene expression profiles. In our approach, we quantified the relationship between functional similarity and high-throughput data, and coded the relationship into 'functional linkage graph', where each node represents one protein and the weight of each edge is characterized by the Bayesian probability of function similarity between two proteins. We also integrated the evolution information and protein subcellular localization information into the prediction. Based on our method, 1802 out of 2280 unannotated proteins in yeast were assigned functions systematically.

Bayes Theorem↗

PubMed2004

Understanding protein dispensability through machine-learning analysis of high-throughput data.

MOTIVATION: Protein dispensability is fundamental to the understanding of gene function and evolution. Recent advances in generating high-throughput data such as genomic sequence data, protein-protein interaction data, gene-expression data and growth-rate data of mutants allow us to investigate protein dispensability systematically at the genome scale. RESULTS: In our studies, protein dispensability is represented as a fitness score that is measured by the growth rate of gene-deletion mutants. By the analyses of high-throughput data in yeast Saccharomyces cerevisiae, we found that a protein's dispensability had significant correlations with its evolutionary rate and duplication rate, as well as its connectivity in protein-protein interaction network and gene-expression correlation network. Neural network and support vector machine were applied to predict protein dispensability through high-throughput data. Our studies shed some lights on global characteristics of protein dispensability and evolution. AVAILABILITY: The original datasets for protein dispensability analysis and prediction, together with related scripts, are available at http://digbio.missouri.edu/~ychen/ProDispen/ CONTACT: xudong@missouri.edu.

Artificial Intelligence↗

PubMed2004

Inhibition of MDR1 gene expression by chimeric HNA antisense oligonucleotides.

Hexitol nucleic acids (HNAs) are nuclease resistant and provide strong hybridization to RNA. However, there is relatively little information on the biological properties of HNA antisense oligonucleotides. In this study, we compared the antisense effects of a chimeric HNA 'gapmer' oligonucleotide comprising a phosphorothioate central sequence flanked by 5' and 3' HNA sequences to conventional phosphorothioate oligonucleotides and to a 2'-O-methoxyethyl (2'-O-ME) phosphorothioate 'gapmer'. The antisense oligomers each targeted a sequence bracketing the start codon of the message of MDR1, a gene involved in multi-drug resistance in cancer cells. Antisense and control oligonucleotides were delivered to MDR1-expressing cells using transfection with the cationic lipid Lipofectamine 2000. The anti-MDR1 HNA gapmer was substantially more potent than a phosphorothioate oligonucleotide of the same sequence in reducing expression of P-glycoprotein, the MDR1 gene product. HNA and 2'-O-ME gapmers displayed similar potency, but a pure HNA antisense oligonucleotide (lacking the phosphorothioate 'gap') was ineffective, indicating that RNase H activity was likely required. Treatment with anti-MDR1 HNA gapmer resulted in increased cellular accumulation of the drug surrogate Rhodamine 123 that correlated well with the reduced cell surface expression of P-glycoprotein. Thus, HNA gapmers may provide a valuable additional tool for antisense-based investigations and therapeutic approaches.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

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

ProteinDBS: a real-time retrieval system for protein structure comparison.

We have developed a web server (ProteinDBS) for the life science community to search for similar protein tertiary structures in real time. This system applies computer visualization techniques to extract the predominant visual patterns encoded in two-dimensional distance matrices generated from the three-dimensional coordinates of protein chains. When meaningful contents, represented in a multi-dimensional feature space, have been extracted from distance matrices, an advanced indexing structure, Entropy Balanced Statistical (EBS) k-d tree, is utilized to index the data. Our system is able to return search results in ranked order from a database with 46 075 chains in seconds, exhibiting a reasonably high degree of precision. To our knowledge, this is the first real-time search engine for protein structure comparison. ProteinDBS provides two types of query method: query by Protein Data Bank protein chain ID and by new structures uploaded by users. The system is hosted at http://ProteinDBS.rnet.missouri.edu.

Computer Graphics↗

PubMed2004

Quantitative relationship between synonymous codon usage bias and GC composition across unicellular genomes.

BACKGROUND: Codon usage bias has been widely reported to correlate with GC composition. However, the quantitative relationship between codon usage bias and GC composition across species has not been reported. RESULTS: Based on an informatics method (SCUO) we developed previously using Shannon informational theory and maximum entropy theory, we investigated the quantitative relationship between codon usage bias and GC composition. The regression based on 70 bacterial and 16 archaeal genomes showed that in bacteria, SCUO = -2.06 * GC3 + 2.05*(GC3)2 + 0.65, r = 0.91, and that in archaea, SCUO = -1.79 * GC3 + 1.85*(GC3)2 + 0.56, r = 0.89. We developed an analytical model to quantify synonymous codon usage bias by GC compositions based on SCUO. The parameters within this model were inferred by inspecting the relationship between codon usage bias and GC composition across 70 bacterial and 16 archaeal genomes. We further simplified this relationship using only GC3. This simple model was supported by computational simulation. CONCLUSIONS: The synonymous codon usage bias could be simply expressed as 1+ (p/2)log2(p/2) + ((1-p)/2)log2((l-p)/2), where p = GC3. The software we developed for measuring SCUO (codonO) is available at http://digbio.missouri.edu/~wanx/cu/codonO.

Base Composition↗

PubMed2004

MHC class II-independent and -dependent T cell expansion and B cell hyperactivity in vivo in mice deficient in CD152 (CTLA-4).

One of the key downregulators of T cell activation is CD152 (CTLA-4). Mice genetically deficient in CD152 (cd152(-/-) mice) develop massive expansion of both CD4(+) and CD8(+) T cells as well as increased numbers of splenic Ig-secreting cells and serum Ig levels. To determine the dependence of the lymphoproliferation and B cell hyperactivity on MHC class II (MHCII), MHCII-deficient (mhcii(-/-)) cd152(-/-) mice were generated. Compared to that in their mhcii(+/+) counterparts, expansion of CD4(+) cells in mhcii(-/-)cd152(-/-) mice was markedly attenuated. Nonetheless, expansion of CD8(+) cells was identical in both sets of mice, demonstrating that the effects of CD152 deficiency on CD4(+) cells can quantitatively be dissociated from those on CD8(+) cells, and pointing to a critical downregulatory role for CD152 in MHCII-independent CD8(+) cell activation in vivo. B cell hyperactivity also developed in mhcii(-/-)cd152(-/-) mice, albeit in a manner less rapid and less intense than that in their mhcii(+/+) counterparts, demonstrating an underlying MHCII-independent diathesis to B cell dysregulation and pointing to a critical downregulatory role for CD152 in MHCII-independent B cell activation in vivo. When human DQ8 was introduced as a transgene into mhcii(-/-)cd152(-/-) mice, B cell hyperactivity was restored to levels observed in mhcii(+/+)cd152(-/-) mice, pointing to a critical downregulatory role for CD152 in MHCII-dependent B cell activation in vivo superimposed upon its downregulatory role on MHCII-independent B cell activation.

Animals↗

PubMed2004

Structure evaluation and highly enhanced luminescence of Dy3+ -doped ZnO nanocrystals by Li+ doping via combustion method.

In this paper, Dy3+ -doped ZnO nanocrystals have been synthesized via a simple combustion method. The as-prepared cuboid-like ZnO nanocrystals appear to be single hexagonal crystalline phase with an average diameter of 20 nm. The characteristic luminescence of doped Dy3+ ions has been evaluated, and the highly enhanced photoluminescence of Dy3+ ions can be obtained by Li+ doping.

Letter↗

PubMed2004

Effect of SEN virus coinfection on outcome of lamivudine therapy in patients with hepatitis B.

AIM: Interactions between hepatitis B virus (HBV) and other viral hepatitis infections are well known, whether the newly discovered SEN virus (SENV) has any effect on lamivudine antiHBV activity is unclear. Our aim was to clarify the effect on treatment outcome of coinfection with SEN virus in patients with hepatitis B during lamivudine therapy. METHODS: Nested polymerase chain reaction (PCR) amplification was used to detect SENV-D and SENV-H strains in serum from 45 patients with chronic hepatitis B treated with lamivudine 100 mg daily for 12 mo. HBV DNA load was detected with fluorescence quantitative PCR (FQ-PCR) and YMDD (tyrosine, methionine, aspartate, aspartate) motif mutation of HBV DNA was investigated with cDNA microarray. RESULTS: SENV DNA was detected in 5 of 45(11.1%) cases after 12 mo they received lamivudine treatment. SENV-D and SENV-H were 4.4% and 6.7% respectively. HBV DNA failed to respond to lamivudine therapy in 4 of 5 SENV coinfected patients while only 10 of 40 patients became SENV positive and the difference was statistically significant. Response of ALT and HBeAg to lamivudine had no significant difference between coinfection patients and single HBV infection ones. CONCLUSION: Coinfection with SEN virus in chronic hepatitis B patients may adversely affect the outcome of lamivudine treatment.

Adult↗