Cerebral malaria (CM) is a leading cause of death in the world. Better understanding of the pathogenesis of this disease is critical for the development of novel therapies. In this work, we investigated temporal gene expression profiles in the brains of CM-susceptible and CM-resistant mice during infection with P. Berghia ANKA (PbA).
Expression microarray analysis implicates apoptosis and interferon-responsive mechanisms in susceptibility to experimental cerebral malaria.
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View SamplesChanges in endothelial phenotype induced by E. coli-derived Shiga toxins (Stx) are believed to play a critical role in the pathogenesis of hemolytic uremic syndrome. Stx inactivate host ribosomes, but also alter gene expression at concentrations that minimally affect global protein synthesis. The effect of Stx on the gene expression profile of human microvascular endothelial cells was examined using the Affymetrix HG-U133A platform. Data were processed using 13 different methods and revealed 369 unique differentially expressed genes, 318 of which were up-regulated and 51 of which were down-regulated. These studies implicated activation of the CXCR4/CXCR7/SDF-1 chemokine pathway in Stx-mediated pathogenesis.
The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice.
Sex
View SamplesWe have shown that removal of Lkb1 in chondorcytes results in enchondroma-like structure in postnatal mouse long bones. To furhter understand the role of Lkb1 in this process, we performed microarrrays to compare the transcriptional profile between control and conditional Lkb1 mutant (Col2a1-Cre; Lkb1c/c) chondrocytes.
Lkb1/Stk11 regulation of mTOR signaling controls the transition of chondrocyte fates and suppresses skeletal tumor formation.
Specimen part
View SamplesRNA microarray profiling of 45 tissue samples was carried out using the Affymetrix (U133) gene expression platform. Laser capture microdissection (LCM) was employed to isolate cancer cells from the tumors of 18 serous ovarian cancer patients (Cepi). For 7 of these patients, a matched set of surrounding cancer stroma (CS) was also collected. For controls, surface ovarian epithelial cells (OSE) were isolated from the normal (non-cancerous) ovaries of 12 individuals including matched sets of samples of OSE and normal stroma (NS) from 8 of these patients. Unsupervised hierarchical clustering of the microarray data resulted in the expected separation between the OSE and Cepi samples. Consistent with models of stromal activation, we also observed significant separation between the NS and CS samples. Unexpectedly, the CS samples sub-divided into two distinct groups. Analysis of expression patterns of genes encoding signaling molecules and compatible receptors in the CS and Cepi samples are consistent with the hypothesis that the two CS sub-groups differ significantly in their relative propensities to support tumor growth.The results indicate the existence of distinct categories of ovarian cancer stroma and suggest that functionally significant variability exists among ovarian cancer patients in the ability of the microenvironment to modulate cancer development.
Molecular profiling predicts the existence of two functionally distinct classes of ovarian cancer stroma.
Age, Specimen part, Disease stage, Subject
View SamplesAllergen exposure induces the airway epithelium to produce chemoattractants, proallergic interleukins, matrix-modifying proteins, and proteins that influence the growth and activation state of airway structural cells. These proteins, in turn, contribute to the influx of inflammatory cells and changes in structure that characterize the asthmatic airway. To use the response of the airway epithelium to allergen to identify genes not previously associated with allergic responses, we compared gene expression in cytokeratin-positive cells before and after segmental allergen challenge. After challenge with concentrations of allergen in the clinically relevant range, 755 (6%) of the detectable sequences had geometric mean fold-changes in expression, with 95% confidence intervals that excluded unity. Using a prospectively defined conservative filtering algorithm, we identified 141 sequences as upregulated and eight as downregulated, with confirmation by conventional polymerase chain reaction in all 10 sequences studied. Using this approach, we identified asthma-associated sequences including interleukin (IL-)-3, IL-4, and IL-5 receptor subunits, the p65 component of nuclear factor-kappaB, and lipocortin. The genomic response of the human airway to concentrations of allergen in the clinically relevant range involves a greater number of genes than previously recognized, including many not previously associated with asthma that are differentially expressed after airway allergen exposure.
Effects of allergen challenge on airway epithelial cell gene expression.
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View SamplesWe report the application of RNA-Seq analysis to determine the transcriptional responses to Mn dose, ranging from physiological to toxicological levels in human SH-SY5Y neuroblastoma cells. We find that Mn dose showed widespread effects in abundance of protein coding genes for metabolism of reactive oxygen species, energy sensing, glycolysis, protein homeostasis including the unfolded protein response and transcriptional regulation. Adaptive responses at physiological Mn concentration-10 µM Mn for 5 h, a concentration that did not result in cell death after 24 h increased abundance of differentially expressed genes (DEGs) in the protein secretion pathway that function in protein trafficking and cellular homeostasis.These include BET1 (Golgi vesicular membrane trafficking protein), ADAM10 (ADAM metallopeptidase domain 10) and ARFGAP3 (ADP-ribosylation factor GTPase activating protein 3). In contrast, 5 h exposure to 100 µM Mn, a concentration that caused cell death after 24 h, increased abundance of DEGs for components of the mitochondrial oxidative phosphorylation pathway. In conclusion, this study provides a framework for Mn dose dependent exposure in a human in vitro cell culture model and provides a testable hypothesis for in vivo studies. Importantly, the transcriptome responses at toxic Mn dose demonstrated patterns observed with neurological diseases and suggest that differential functions of the secretory pathway and mitochondria could provide a basis to improve detection and management of adverse environmental and occupational Mn exposures. Overall design: Examination of transcriptomic responses to Mn dose (0,1,5,10,50,100 µM MnCl2 for 5 h) in human SH-SY5Y neuroblastoma cells with three biological replicates per Mn treatment using Illumina HiSeq 2500.
Transcriptome Analysis Reveals Distinct Responses to Physiologic <i>versus</i> Toxic Manganese Exposure in Human Neuroblastoma Cells.
Specimen part, Cell line, Subject
View SamplesPeripheral whole blood-based gene expression profiling has become one of the most common strategies exploited in the development of clinically relevant biomarkers. However, the ability to identify biologically meaningful conclusions from gene expression patterns in whole blood is highly problematic. First, it is difficult to know whether or not expression patterns in whole blood capture those in primary tissues. Second, if explicit steps are not taken to accommodate the extremely elevated expression levels of globin in blood then large-scale multi-probe microarray-based studies can be severely compromised. Many studies consider the use of mouse blood as a model for human blood in addition to considering blood gene expression levels as a general surrogate for gene expression levels in other tissues. We explored the effects of globin reduction on peripheral mouse blood in the detection of genes known to be expressed in human tissues. Globin reduction resulted in 1.) a significant increase in the number of probes detected (5840 944 vs 12411 1904); 2.) increased expression for 4128 probe sets compared to non-globin reduced blood (p < .001, two-fold); 3.) improved detection of genes associated with many biological pathways and diseases; and 4.) an increased ability to detect genes expressed in 27 human tissues (p < 10-4). This study suggests that although microarray-based mouse blood gene expression studies that do not consider the effects of globin are severely compromised, globin-reduced mouse whole blood gene expression studies can be used to capture the expression profiles of genes known to contribute to various human diseases.
The effects of globin on microarray-based gene expression analysis of mouse blood.
Sex, Age, Specimen part
View SamplesBiofilm formation and type III secretion have been shown to be reciprocally regulated in P. aeruginosa, and it has been suggested that factors related to acute infection may be incompatible
Biofilms and type III secretion are not mutually exclusive in Pseudomonas aeruginosa.
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View SamplesBackground: Moderate hypothermia (32oC for 12 72 hours) has therapeutic applications, but the mechanisms by which it affects cellular function are unclear. We tested the hypothesis that moderate hypothermia produces broad changes in gene expression by human cells at the level of mRNA.
Effect of moderate hypothermia on gene expression by THP-1 cells: a DNA microarray study.
No sample metadata fields
View SamplesThe molecular mechanisms regulating endothelial to hematopoietic transition (EHT) of hemogenic endothelium (HE) are poorly understood. Here we profile the transcriptional changes resulting from SOX7 overexpression during EHT Overall design: FLK1+ cells were sorted from day 3.5 iSox7 EBs and cultured in liquid blast media for 48hours. Dox was added for 6, 12 and 24 hours to induce SOX7 expression, before samples were harvested for RNAseq.
Interplay between SOX7 and RUNX1 regulates hemogenic endothelial fate in the yolk sac.
Specimen part, Treatment, Subject, Time
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