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GSE17049
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Different strains of T. brucei induce different degrees of pathology in infected animals, and TREU927-infected mice display greater splenomegaly and anaemia than 247-infected mice. The analysis of differential host gene expression in infected spleens has allowed the identification of which pathways or processes are crucial in determining the progression of disease, for example IL10, LXR/RXR activation and alternative macrophage activation.
Publication Title
Role for parasite genetic diversity in differential host responses to Trypanosoma brucei infection.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 36 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The molecular chaperone HSP90 aids the maturation of a diverse but select set of metastable protein clients, many of which are key to a variety of signal transduction pathways. HSP90 function has been best investigated in animal and fungal systems, where inhibition of the chaperone has exceptionally diverse effects, ranging from reversing oncogenic transformation to facilitating the acquisition of drug resistance. Inhibition of HSP90 in the model plant Arabidopsis thaliana uncovers novel morphologies dependent on normally cryptic genetic variation and increases stochastic variation inherent to developmental processes. The biochemical activity of HSP90 is strictly conserved between animals and plants. However, the substrates and pathways dependent on HSP90 in plants are poorly understood. Progress has been impeded by reliance on light-sensitive HSP90 inhibitors due to redundancy in the A. thaliana HSP90 gene family. Here we present phenotypic and genome-wide expression analyses of A. thaliana with constitutively reduced HSP90 levels achieved by RNAi targeting. HSP90 reduction affects a variety of quantitative life-history traits, including flowering time and total seed set, and decreases developmental stability. Further, by quantitative analysis of morphological phenotypes, we demonstrate that HSP90-reduction increases phenotypic diversity in both seedlings and adult plants. Several morphologies are synergistically affected by HSP90 and growth temperature. Genome-wide expression analyses also suggest a central role for HSP90 in the genesis and maintenance of plastic responses. The expression results are substantiated by examination of the response of HSP90-reduced plants to attack by caterpillars of the generalist herbivore Trichoplusia ni. HSP90 reduction potentiates a more robust herbivore defense response. In sum, we propose that HSP90 exerts global effects on the environmental responsiveness of plants to many different stimuli. The comprehensive set of HSP90-reduced lines described here is a vital instrument to further examine the role of HSP90 as a central interface between organism, development, and environment.
Publication Title
Phenotypic diversity and altered environmental plasticity in Arabidopsis thaliana with reduced Hsp90 levels.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 299 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Activating mutations in tyrosine kinase (TK) genes (e.g. FLT3 and KIT) are found in more than 30% of patients with de novo acute myeloid leukemia (AML); many groups have speculated that mutations in other TK genes may be present in the remaining 70%. We performed high-throughput re-sequencing of the kinase domains of 26 TK genes (11 receptor TK and 15 cytoplasmic TK) that are expressed in most AML patients, using genomic DNA from the bone marrow (tumor) and matched skin biopsy samples (germline) from 94 patients with de novo AML; sequence variants were validated in an additional 94 AML tumor samples (14.3 million base pairs of sequence were obtained and analyzed). We identified known somatic mutations in FLT3, KIT, and JAK2 TK genes at the expected frequencies, and found four novel somatic mutations, JAK1V623A, JAK1T478S, DDR1A803V and NTRK1S677N, once each in four respective patients out of 188 tested. We also identified novel germline sequence changes encoding amino acid substitutions (i.e. non-synonymous changes) in 14 TK genes, including TYK2, which had the largest number of non-synonymous sequence variants (11 total detected). Additional studies will be required to define the roles that these somatic and germline TK gene variants play in AML pathogenesis.
Publication Title
Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Myelodysplastic syndromes (MDS) are a heterogenous group of hematopoietic stem cell disorders characterized by dysplastic blood cell formation and peripheral blood cytopenias. Up to 30% of patients with MDS will progress to a highly chemotherapy-resistant secondary acute myeloid leukemia (sAML). We identified mutations in U2AF1 in MDS patients and patients with U2AF1 mutations are at an increased risk of developing sAML.
Publication Title
Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Race
View Samples- Mus musculus
- 66 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Murine testis developmental time course created from tissue samples collected from birth through adulthood and hybridized to MGU74v2 A, B, and C chips in duplicate
Publication Title
The murine testicular transcriptome: characterizing gene expression in the testis during the progression of spermatogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Pharmacological inhibition of cyclooxygenase-2 (COX-2) is being explored as a chemotherapeutic option because COX-2 protein expression is often elevated in many cancers. Cancer cells treated with COX-2 inhibitors, such as the selective COX-2 inhibitor celecoxib, show growth inhibition and the induction of apoptosis, through alterations in inflammatory processes, angiogenesis, cell adhesion and transforming growth factor- signaling. This study was conducted to determine if the same processes are relevant to celecoxibs effects on human colorectal adenocarcinomas treated in vivo. A cohort of 23 patients with primary colorectal adenocarcinomas was randomized to receive a 7-day course of celecoxib (400 mg b.i.d.) or no drug prior to surgical resection. Gene expression profiling was performed on resected adenocarcinomas from patients with and without celecoxib pre-treatment. Using fold change (>1.5) and p-value (<0.05) cut-offs, 190 genes were differentially expressed between adenocarcinomas from patients receiving celecoxib and those that did not. Of the differentially expressed genes, multiple genes involved in cellular lipid and glutathione metabolism showed decreased expression levels in celecoxib pre-treated samples; changes associated with diminished cellular proliferation. Other observed gene expression changes consistent with reduced proliferation include: altered expression of genes involved in cell adhesion (including collagen, laminin, von Willebrand factor and tenascin C), increased expression of inflammatory modulators (including inerleukin-6, S100 calcium binding protein A8, and several chemokines) and decreased expression of the pro-angiogenic gene, angiogenin. Celecoxib pre-treatment for 7 days in vivo is associated with alterations in colorectal adenocarcinoma gene expression which are suggestive of diminished cellular proliferation.
Publication Title
Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation.
Sample Metadata Fields
Sex, Disease stage, Treatment
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Affymetrix human whole transcriptome array (HTA 2.0) completed on patients with Crohn's disease undergoing their first ileocolic resection
Publication Title
Predicting Risk of Postoperative Disease Recurrence in Crohn's Disease: Patients With Indolent Crohn's Disease Have Distinct Whole Transcriptome Profiles at the Time of First Surgery.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We are examining the genes that control initiation and progression of murine medulloblastomas that result from loss of patched. Approximately 25% of human medulloblastomas have mutations in patched or in other elements of the sonic hedgehog pathway. However, the cells from which these tumors originate (neural progenitors or stem cells), the cells that are responsible for tumor propagation (cancer stem cells), and the genes that are required for tumor progression are poorly understood. To address these questions, we have developed conditional patched knockout mice in which the gene is deleted in neural stem cells or progenitors. In addition, we have isolated a population of tumor-propagating cells from these tumors. By studying these models we will gain insight into the mechanisms of tumorigenesis and identify new targets for therapy.
Publication Title
Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli, Pseudomonas aeruginosa pao1
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Transcriptional profiles of Escherichia coli MG1655 in mixed culture with Pseudomonas aeruginosa PAO1 showed a number of E. coli genes to be upregulated including purA-F and other genes associated with purine synthesis. In contrast, genes associated with pyrimidine synthesis were unaffected. Competition experiments in both planktonic and biofilm cultures, using three purine synthesis mutants, purD, purH, and purT showed little difference in E. coli survival from the parent strain. As purines are components of the cell signals, cAMP and c-di-GMP, we conducted competition experiments with E. coli mutants lacking adenylate cyclase (cyaA), cAMP phosphodiesterase (cpdA), and the catabolite receptor protein (crp), as well as ydeH, an uncharacterized gene that has been associated with c-di-GMP synthesis. Survival of the cyaA and crp mutants during co-culture were significantly less than the parent strain. Supplementation of the media with 1mM cAMP could restore survival of the cyaA mutant but not the crp mutant. In contrast, survival of the cpdA mutant was similar to the parent strain. Survival of the ydeH mutant was moderately less than the parent, suggesting that cAMP has more impact on E. coli mixed culture growth than c-di-GMP. Addition of 1 mM indole restored the survival of both the cyaA and crp mutations. Mutants in genes for tryptophan synthesis (trpE) and indole production (tnaA) showed a loss of competition and recovery through indole supplementation, comparable to the cyaA and crp mutants. Overall, these results suggest indole and cAMP as major contributing factors to E. coli growth in mixed culture.
Publication Title
Indole production promotes Escherichia coli mixed-culture growth with Pseudomonas aeruginosa by inhibiting quorum signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli str. k-12 substr. mg1655, Pseudomonas aeruginosa pao1
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Transcriptional profiles of Escherichia coli MG1655 in mixed culture with Pseudomonas aeruginosa PAO1 showed a number of E. coli genes to be upregulated including purA-F and other genes associated with purine synthesis. In contrast, genes associated with pyrimidine synthesis were unaffected. Competition experiments in both planktonic and biofilm cultures, using three purine synthesis mutants, purD, purH, and purT showed little difference in E. coli survival from the parent strain. As purines are components of the cell signals, cAMP and c-di-GMP, we conducted competition experiments with E. coli mutants lacking adenylate cyclase (cyaA), cAMP phosphodiesterase (cpdA), and the catabolite receptor protein (crp), as well as ydeH, an uncharacterized gene that has been associated with c-di-GMP synthesis. Survival of the cyaA and crp mutants during co-culture were significantly less than the parent strain. Supplementation of the media with 1mM cAMP could restore survival of the cyaA mutant but not the crp mutant. In contrast, survival of the cpdA mutant was similar to the parent strain. Survival of the ydeH mutant was moderately less than the parent, suggesting that cAMP has more impact on E. coli mixed culture growth than c-di-GMP. Addition of 1 mM indole restored the survival of both the cyaA and crp mutations. Mutants in genes for tryptophan synthesis (trpE) and indole production (tnaA) showed a loss of competition and recovery through indole supplementation, comparable to the cyaA and crp mutants. Overall, these results suggest indole and cAMP as major contributing factors to E. coli growth in mixed culture.
Publication Title
Indole production promotes Escherichia coli mixed-culture growth with Pseudomonas aeruginosa by inhibiting quorum signaling.
Sample Metadata Fields
No sample metadata fields
View Samples