Biomedical subjects

Song Huang

Publications and source records attributed to Song Huang.

13 recordsLinked to original sources

PubMed2006

Mapping quantitative trait loci in noninbred mosquito crosses.

The identification of genes that affect quantitative traits has been of great interest to geneticists for many decades, and many statistical methods have been developed to map quantitative trait loci (QTL). Most QTL mapping studies in experimental organisms use purely inbred lines, where the two homologous chromosomes in each individual are identical. As a result, many existing QTL mapping methods developed for experimental organisms are applicable only to genetic crosses between inbred lines. However, it may be difficult to obtain inbred lines for certain organisms, e.g., mosquitoes. Although statistical methods for QTL mapping in outbred populations, e.g., humans, can be applied for such crosses, these methods may not fully take advantage of the uniqueness of these crosses. For example, we can generally assume that the two grandparental lines are homozygous at the QTL of interest, but such information is not be utilized through methods developed for outbred populations. In addition, mating types and phases can be relatively easy to establish through the analysis of adjacent markers due to the large number of offspring that can be collected, substantially simplifying the computational need. In this article, motivated by a mosquito intercross experiment involving two selected lines that are not genetically homozygous across the genome, we develop statistical methods for QTL mapping for genetic crosses involving noninbred lines. In our procedure, we first infer parental mating types and use likelihood-based methods to infer phases in each parent on the basis of genotypes of offspring and one parent. A hidden Markov model is then employed to estimate the number of high-risk alleles at marker positions and putative QTL positions between markers in each offspring, and QTL mapping is finally conducted through the inferred QTL configuration across all offspring in all crosses. The performance of the proposed methods is assessed through simulation studies, and the usefulness of this method is demonstrated through its application to a mosquito data set.

Alleles↗

PubMed2006

[Variation regularization algorithm in electrical impedance tomography].

In this paper, a variation function has been introduced as a regularization penalty term in electrical impedance tomography (EIT) image restoration, which becomes to be the variation regularization algorithm. The key difference with Tikhonov regularization algorithm is that the variation regularization algorithm not only ensures the inverse problem well-posed but also increase the dividing line between the goal region and the background region of restored image clearer. This made the restored image in good accord with the medical image. It has significance to utilize EIT technique.

Algorithms↗

PubMed2005

Whole-genome linkage analysis in mapping alcoholism genes using single-nucleotide polymorphisms and microsatellites.

There is currently a great interest in using single-nucleotide polymorphisms (SNPs) in genetic linkage and association studies because of the abundance of SNPs as well as the availability of high-throughput genotyping technologies. In this study, we compared the performance of whole-genome scans using SNPs with microsatellites on 143 pedigrees from the Collaborative Studies on Genetics of Alcoholism provided by Genetic Analysis Workshop 14. A total of 315 microsatellites and 10,081 SNPs from Affymetrix on 22 autosomal chromosomes were used in our analyses. We found that the results from the two scans had good overall concordance. One region on chromosome 2 and two regions on chromosome 7 showed significant linkage signals (i.e., NPL >or= 2) for alcoholism from both the SNP and microsatellite scans. The different results observed between the two scans may be explained by the difference observed in information content between the SNPs and the microsatellites.

Alcoholism↗

PubMed2005

Whole-genome association analysis to identify markers associated with recombination rates using single-nucleotide polymorphisms and microsatellites.

Recombination during meiosis is one of the most important biological processes, and the level of recombination rates for a given individual is under genetic control. In this study, we conducted genome-wide association studies to identify chromosomal regions associated with recombination rates. We analyzed genotype data collected on the pedigrees in the Collaborative Study on the Genetics on Alcoholism data provided by Genetic Analysis Workshop 14. A total of 315 microsatellites and 10,081 single-nucleotide polymorphisms from Affymetrix on 22 autosomal chromosomes were used in our association analysis. Genome-wide gender-specific recombination counts for family founders were inferred first and association analysis was performed using multiple linear regressions. We used the positive false discovery rate (pFDR) to account for multiple comparisons in the two genome-wide scans. Eight regions showed some evidence of association with recombination counts based on the single-nucleotide polymorphism analysis after adjusting for multiple comparisons. However, no region was found to be significant using microsatellites.

Female↗

PubMed2005

[Effect of dihydroartemisinin on ultrastructure of Giardia lamblia in vitro].

OBJECTIVE: To study the in vitro effect of dihydroartemisinin (DHA) on Giardia lamblia. METHODS: Trophozoites of G. lamblia were cultivated with modified TYI-S-33 medium that contains dihydroartemisinin (DHA). The trophozoites were morphologically observed respectively with light and electron microscopes after treated with the drug. RESULTS: The mortality increased with the prolongation of the time of the drug action and the increase of drug concentration (P<0.01). While at the same concentration of 100 microg/ml, the mortality increased from 46.6% for 12 h to 100% for 24 h (P<0.05). For 12 h, the mortality of G. lamblia was from 46.6% at concentration of 100 microg/ml to 100% at 200microg/ml. Under optical microscope, deformation and swelling of the parasites were observed when treated with DHA for 12, 24 and 48 h. Movement of the flagella became slow or stopped. Under electron microscope, the trophozoites were swollen and deformed, vacuoles were seen in the cytoplasm, and the cell membrane ruptured and fell off. The cytoplasm protrusions appeared on the surface of the plasma membrane. The adhesive disc changed into large bubbles and the perinuclear space became wider and the deformed nucleus was seen. CONCLUSION: DHA shows a strong impairment on the plasma membrane and cytoskeleton of Giardia lamblia.

Animals↗

PubMed2005

Epitope mapping and biological function analysis of antibodies produced by immunization of mice with an inactivated Chinese isolate of severe acute respiratory syndrome-associated coronavirus (SARS-CoV).

Inactivated severe acute respiratory syndrome-associated coronavirus (SARS-CoV) has been tested as a candidate vaccine against the re-emergence of SARS. In order to understand the efficacy and safety of this approach, it is important to know the antibody specificities generated with inactivated SARS-CoV. In the current study, a panel of twelve monoclonal antibodies (mAbs) was established by immunizing Balb/c mice with the inactivated BJ01 strain of SARS-CoV isolated from the lung tissue of a SARS-infected Chinese patient. These mAbs could recognize SARS-CoV-infected cells by immunofluorescence analysis (IFA). Seven of them were mapped to the specific segments of recombinant spike (S) protein: six on S1 subunit (aa 12-798) and one on S2 subunit (aa 797-1192). High neutralizing titers against SARS-CoV were detected with two mAbs (1A5 and 2C5) targeting at a subdomain of S protein (aa 310-535), consistent with the previous report that this segment of S protein contains the major neutralizing domain. Some of these S-specific mAbs were able to recognize cleaved products of S protein in SARS-CoV-infected Vero E6 cells. None of the remaining five mAbs could recognize either of the recombinant S, N, M, or E antigens by ELISA. This study demonstrated that the inactivated SARS-CoV was able to preserve the immunogenicity of S protein including its major neutralizing domain. The relative ease with which these mAbs were generated against SARS-CoV virions further supports that subunit vaccination with S constructs may also be able to protect animals and perhaps humans. It is somewhat unexpected that no N-specific mAbs were identified albeit anti-N IgG was easily identified in SARS-CoV-infected patients. The availability of this panel of mAbs also provided potentially useful agents with applications in therapy, diagnosis, and basic research of SARS-CoV.

Animals↗

PubMed2005

Cloning and characterization a novel human 1-acyl-sn-glycerol-3-phosphate acyltransferase gene AGPAT7.

The 1-Acylglycerolphosphate acyltransferase is crucial enzyme for synthesis of glycerolipids as well as triacylglylcerol biosynthesis in eukaryotes. Six members of 1-acyl-sn-glycerol-3-phosphate acyltransferase family in human have been described, which were AGPAT1, 2, 3, 4, 5 and 6. Here we report the cloning and characterization of another novel human 1-acyl-sn-glycerol-3-phosphate acyltransferase member AGPAT7 (1-acyl-sn-glycerol-3-phosphate acyltransferase 7) gene, which was mapped to human chromosome 15q14. The AGPAT7 cDNA is 1898 bp in length, encoding a putative protein with 524 amino acid residues, which contains an acyltransferase domain in 123-234 aa. RT PCR amplification in 18 human tissues indicated that human AGPAT7 gene was widely expressed in uterus, thymus, pancreas, skeletal muscle, bladder, stomach, lung and testis. AGPAT7 protein was mainly localized to the endoplasmic reticulum (ER) in Hela cells.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗

PubMed2005

Identification of two neutralizing regions on the severe acute respiratory syndrome coronavirus spike glycoprotein produced from the mammalian expression system.

The Spike (S) protein of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) plays important roles in viral pathogenesis and potentially in the development of an effective vaccine against this virulent infectious disease. In this study, the codon-optimized S gene of SARS-CoV was synthesized to construct DNA vaccine plasmids expressing either the full-length or segments of the S protein. High titer S-specific immunoglobulin G antibody responses were elicited in rabbits immunized with DNA against various segments of the S protein. Two neutralizing domains were identified on the S protein, one at the N terminus (Ser12-Thr535) and the other near the C terminus (Arg797-Ile1192).

Animals↗

PubMed2004

[Simulation of inverse recovery of epicardial potentials under incomplete boundary conditions].

Based on a 3-D inhomogeneous simulative body torso model, the influence of various boundary conditions on inverse recovered epicardial potential maps (EPM) was studied by boundary element method (BEM). The result shows that the precision of EPM calculated under incomplete boundary conditions will meet the clinical requirements, as long as the incomplete boundary conditions still contain the extremum area which often appears at the breast area.

Action Potentials↗

PubMed2003

[Construction and expression of the recombinant plasmid pcDNA3.1/Ts87 of Trichinella spiralis].

OBJECTIVE: To construct and express DNA plasmid of Trichinella spiralis. METHODS: The BamHI and HindIII enzyme sites and KOZAK sequences were introduced at both ends of Ts87 gene by PCR. Ts87 gene was ligated into pcDNA3.1(+) vector with T4 ligase. The recombinant plasmid pcDNA3.1/Ts87 and plasmid pcDNA3.1 were transfected into an eukaryotic cell line COS7 through Lipofectamine, respectively. The BALB/c mice were immunized with the purified plasmid DNA pcDNA3.1/Ts87 through two routes: intramuscular injection and gene-gun injection. RESULTS AND CONCLUSION: The pcDNA3.1/Ts87 was expressed both in COS7 and in the BALB/c mice.

Animals↗

PubMed2003

[Studies on constituents of Rosa bracteata fruits(II)].

OBJECTIVE: To find the active constituents of Rosa bracteata Wendl. to antagonize withdrawal syndrome in morphinedependent mice. METHODS: The constituents were isolated and purified by silica gel chromatography repeatedly. Their structures were made clear by chemical reactions and on the evidence of spectroscopy. RESULTS AND CONCLUSIONS: Five compounds were isolated from the fruits and four of them were determined as trimethly citrate, dimethyl 3-carboxyl-3-hydroxypentanedioate, 3-hydroxy-3-methoxycarbonyl-pentanedioic acid, calcium citrate, which were found from the Rose genus plant for the first time.

Calcium Citrate↗

PubMed2002

Defective activation of c-Src in cystic fibrosis airway epithelial cells results in loss of tumor necrosis factor-alpha-induced gap junction regulation.

Tumor necrosis factor-alpha (TNF-alpha) signaling is central to the transmission of the innate immune response and subsequent activation of the adaptive immune system. The functioning of both systems is required for optimal clearance of pathogens from the airways. In cystic fibrosis (CF), dysfunction of the CF transmembrane conductance regulator (CFTR) is associated with recurrent pulmonary infections despite an intense inflammatory and immune response. We reported recently that TNF-alpha decreased gap junction connectivity in non-CF airway cells, a mechanism that was absent in CF cells expressing the DeltaPhe-508 mutant of CFTR. We have now identified the tyrosine kinase c-Src as a possible pathway between the mediators of inflammation and the gap junction protein connexin43 (Cx43). Indeed, TNF-alpha increased the proportion of activated c-Src in non-CF airway cells. Moreover, pharmacological antagonists and expression in non-CF cells of a dominant negative construct of c-Src prevented Cx43 channel closure by TNF-alpha. Finally, gap junction channel closure was prevented by expression of a Cx43 mutant lacking tyrosine phosphorylation sites for c-Src. Additional experiments showed that activation of c-Src was defective in CF airway cells but rescued in CFTR-corrected CF cells. These data suggest that CFTR dysfunction is associated with altered TNF-alpha signaling, resulting in the persistence of gap junction connectivity in CF airway cells. We propose that altered regulation of c-Src may contribute to the dysregulated inflammatory response that is characteristic of the CF phenotype.

Cell Line↗

PubMedDate not supplied

Src signaling links mediators of inflammation to Cx43 gap junction channels in primary and transformed CFTR-expressing airway cells.

Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) is associated with recurrent pulmonary infections and inflammation. We previously reported that tumor necrosis factor (TNF)-alpha decreases gap junction connectivity in cell lines derived from the airway epithelium of non-cystic fibrosis (non-CF) subjects, a mechanism that was defective in cells derived from CF patients, and identified the tyrosine kinase c-Src as a possible bridge between TNF-alpha and Cx43. To examine whether this modulation also takes place in primary epithelial cells, the functional expression of Cx43 was studied in non-CF and CF airway cells, obtained from surgical polypectomies and turbinectomies, which were grown either on culture dishes or permeable filters. Expression of Cx43 was detected by immunofluorescence on cells grown under both culture conditions. Non-CF and CF airway cells also showed intercellular diffusion of Lucifer Yellow. Dye coupling was rapidly abolished in non-CF cells in the presence of TNF-alpha, lipopolysaccharide and lysophosphatidic acid, and could be prevented by tyrphostin47, an inhibitor of Src tyrosine kinases. This down-regulation, however, was not detected in CF airway cells. These data indicate that CFTR dysfunction is associated with altered Src signaling, resulting in the persistence of gap junction connectivity in primary and transformed CF airway cells.

Caveolin 1↗