Biomedical subjects

Yun Anna Cao

Publications and source records attributed to Yun Anna Cao.

4 recordsLinked to original sources

PubMed2004

Analysis of the major patterns of B cell gene expression changes in response to short-term stimulation with 33 single ligands.

We examined the major patterns of changes in gene expression in mouse splenic B cells in response to stimulation with 33 single ligands for 0.5, 1, 2, and 4 h. We found that ligands known to directly induce or costimulate proliferation, namely, anti-IgM (anti-Ig), anti-CD40 (CD40L), LPS, and, to a lesser extent, IL-4 and CpG-oligodeoxynucleotide (CpG), induced significant expression changes in a large number of genes. The remaining 28 single ligands produced changes in relatively few genes, even though they elicited measurable elevations in intracellular Ca(2+) and cAMP concentration and/or protein phosphorylation, including cytokines, chemokines, and other ligands that interact with G protein-coupled receptors. A detailed comparison of gene expression responses to anti-Ig, CD40L, LPS, IL-4, and CpG indicates that while many genes had similar temporal patterns of change in expression in response to these ligands, subsets of genes showed unique expression patterns in response to IL-4, anti-Ig, and CD40L.

Animals↗

PubMed2004

Current issues for DNA microarrays: platform comparison, double linear amplification, and universal RNA reference.

DNA microarray technology has been widely used to simultaneously determine the expression levels of thousands of genes. A variety of approaches have been used, both in the implementation of this technology and in the analysis of the large amount of expression data. However, several practical issues still have not been resolved in a satisfactory manner, and among the most critical is the lack of agreement in the results obtained in different array platforms. In this study, we present a comparison of several microarray platforms [Affymetrix oligonucleotide arrays, custom complementary DNA (cDNA) arrays, and custom oligo arrays printed with oligonucleotides from three different sources] as well as analysis of various methods used for microarray target preparation and the reference design. The results indicate that the pairwise correlations of expression levels between platforms are relative low overall but that the log ratios of the highly expressed genes are strongly correlated, especially between Affymetrix and cDNA arrays. The microarray measurements were compared with quantitative real-time-polymerase chain reaction (QRT-PCR) results for 23 genes, and the varying degrees of agreement for each platform were characterized. We have also developed and tested a double amplification method which allows the use of smaller amounts of starting material. The added round of amplification produced reproducible results as compared to the arrays hybridized with single round amplified targets. Finally, the reliability of using a universal RNA reference for two-channel microarrays was tested and the results suggest that comparisons of multiple experimental conditions using the same control can be accurate.

Benchmarking↗

PubMed2004

A bioinformatics analysis of memory consolidation reveals involvement of the transcription factor c-rel.

Consolidation of long-term memory (LTM) is a complex process requiring synthesis of new mRNAs and proteins. Many studies have characterized the requirement for de novo mRNA and protein synthesis; however, few studies have comprehensively identified genes regulated during LTM consolidation. We show that consolidation of long-term contextual memory in the hippocampus triggers altered expression of numerous genes encompassing many aspects of neuronal function. Like contextual memory formation, this altered gene expression required NMDA receptor activation and was specific for situations in which the animal formed an association between a physical context and a sensory stimulus. Using a bioinformatics approach, we found that regulatory elements for several transcription factors are over-represented in the upstream region of genes regulated during consolidation of LTM. Using a knock-out mouse, we found that c-rel, one of the transcription factors identified in our bioinformatics study, is necessary for hippocampus-dependent long-term memory formation.

Animals↗

PubMed2004

Gene expression profiling of anti-GBM glomerulonephritis model: the role of NF-kappaB in immune complex kidney disease.

BACKGROUND: Immune complexes may cause an irreversible onset of chronic renal disease. Most patients with chronic renal disease undergo a final common pathway, marked by glomerulosclerosis and interstitial fibrosis. We attempted to draw a molecular map of anti-glomerular basement membrane (GBM) glomerulonephritis in mice using oligonucleotide microarray technology. METHODS: Kidneys were harvested at days 1, 3, 7, 11, and 16 after inducing glomerulonephritis by using anti-GBM antibody. In parallel with examining the biochemical and histologic changes, gene expression profiles were acquired against five pooled control kidneys. Gene expression levels were cross-validated by either reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, or immunohistochemistry. RESULTS: Pathologic changes in anti-GBM glomerulonephritis were confirmed in both BALB/c and C57BL/6 strains. Among the 13,680 spotted 65mer oligonucleotides, 1112 genes showing significant temporal patterns by permutation analysis of variance (ANOVA) with multiple testing correction [false discovery ratio (FDR) < 0.05] were chosen for cluster analysis. From the expression profile, acute inflammatory reactions characterized by the elevation of various cytokines, including interleukin (IL)-1 and IL-6, were identified within 3 days of disease onset. After 7 days, tissue remodeling response was prominent with highly induced extracellular-matrix (ECM) genes. Although cytokines related to lymphocyte activation were not detected, monocyte or mesangial cell proliferation-related genes were increased. Tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB) pathway were consistently activated along the entire disease progression, inducing various target genes like complement 3, IL-1b, IL-6, Traf1, and Saa1. CONCLUSION: We made a large-scale gene expression time table for mouse anti-GBM glomerulonephritis model, providing a comprehensive overview on the mechanism governing the initiation and the progression of inflammatory renal disease.

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