Reactive oxygen species, generated in vivo or exogenously encountered, constantly challenge living organisms. Oxidation of polyunsaturated fatty acids (PUFA), which are susceptible to oxidant attack, can lead to initiation of lipid peroxidation and in turn rapid production of toxic lipid hydroperoxides. Eukaryotic microorganisms such as Saccharomyces cerevisiae can survive harsh industrial conditions that contain high levels of the PUFA linoleic acid and its oxidised derivative, linoleic acid hydroperoxide (LoaOOH). The precise signalling and response mechanisms induced by yeast to overcome lipid hydroperoxide stress are ill understood.
Transcriptomic insights into the molecular response of Saccharomyces cerevisiae to linoleic acid hydroperoxide.
No sample metadata fields
View SamplesConsiderable variation in gene expression data from different DNA microarray platforms has been demonstrated. However, no characterization of the source of variation arising from labeling protocols has been performed. To analyze the variation associated with T7-based RNA amplification/labeling methods, aliquots of the Stratagene Human Universal Reference RNA were labeled using 3 eukaryotic target preparation methods and hybridized to a single array type (Affymetrix U95Av2). Variability was measured in yield and size distribution of labeled products, as well as in the gene expression results. All methods showed a shift in cRNA size distribution, when compared to un-amplified mRNA, with a significant increase in short transcripts for methods with long IVT reactions. Intra-method reproducibility showed correlation coefficients >0.99, while inter-method comparisons showed coefficients ranging from 0.94 to 0.98 and a nearly two-fold increase in coefficient of variation. Fold amplification for each method was positively correlated with the number of present genes. Two factors that introduced significant bias in gene expression data were observed: a) number of labeled nucleotides that introduces sequence dependent bias, and b) the length of the IVT reaction that introduces a transcript size dependent bias. This study provides evidence of amplification method dependent biases in gene expression data.
In vitro transcription amplification and labeling methods contribute to the variability of gene expression profiling with DNA microarrays.
No sample metadata fields
View Samples4 chorionic villus sampling specimens in pregnancies destined for preeclampsia and 8 matched controls were analyzed
Altered global gene expression in first trimester placentas of women destined to develop preeclampsia.
No sample metadata fields
View SamplesLong-term memory formation in Drosophila melanogaster is an important neuronal function shaping the insect's behavioral repertoire by allowing an individual to modify behaviors on the basis of previous experiences. In conditioned courtship or courtship suppression, male flies that have been repeatedly rejected by mated females during courtship advances are less likely than na ve males to subsequently court another mated female. This long-term courtship suppression can last for several days after the initial rejection period. Although genes with known functions in many associative learning paradigms, including those that function in cyclic AMP signaling and RNA translocation, have been identified as playing critical roles in long-term conditioned courtship, it is clear that additional mechanisms also contribute. We have used RNA sequencing to identify differentially expressed genes and transcript isoforms between na ve males and males subjected to courtship-conditioning regimens that are sufficient for inducing long-term courtship suppression. Transcriptome analyses 24 hours after the training regimens revealed differentially expressed genes and transcript isoforms with predicted and known functions in nervous system development, chromatin biology, translation, cytoskeletal dynamics, and transcriptional regulation. A much larger number of differentially expressed transcript isoforms were identified, including genes previously implicated in associative memory and neuronal development, including fruitless, that may play functional roles in learning during courtship conditioning. Our results shed light on the complexity of the genetics that underlies this behavioral plasticity and reveal several new potential areas of inquiry for future studies.
Identification of gene expression changes associated with long-term memory of courtship rejection in Drosophila males.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeast Saccharomyces cerevisiae.
No sample metadata fields
View SamplesMisfolded membrane proteins are retained in the endoplasmic reticulum (ER) and are subject to the ER associated degradation pathway, which clears the secretory pathway of potentially toxic species. While the transcriptional response to environmental stressors has been extensively studied, limited data exist describing the cellular response to misfolded membrane proteins. To this end, we expressed and then compared the transcriptional profiles elicited by the synthesis of three ER retained, misfolded ion channels: The subunit of the epithelial sodium channel, ENaC, the cystic fibrosis transmembrane conductance regulator, CFTR, and an inwardly rectifying potassium channel, Kir2.1, which vary in their mass, membrane topologies, and quaternary structures. To examine transcriptional profiles in a null background, the proteins were expressed in yeast, which was previously used to examine the degradation requirements for each substrate. Surprisingly, the proteins failed to induce a canonical unfolded protein response or heat shock response, although messages encoding several cytosolic and ER lumenal protein folding factors rose when ENaC or CFTR were expressed. In contrast, the levels of these genes were unaltered by Kir2.1 expression; instead, the yeast iron regulon was activated. Nevertheless, a significant number of genes that respond to various environmental stressors were upregulated by all three substrates, and when compared to previous microarray data we deduced the existence of a group of genes that reflect a novel misfolded membrane protein response. These data indicate that aberrant proteins in the ER elicit profound yet unique cellular responses.
Expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeast Saccharomyces cerevisiae.
No sample metadata fields
View SamplesMisfolded membrane proteins are retained in the endoplasmic reticulum (ER) and are subject to the ER associated degradation pathway, which clears the secretory pathway of potentially toxic species. While the transcriptional response to environmental stressors has been extensively studied, limited data exist describing the cellular response to misfolded membrane proteins. To this end, we expressed and then compared the transcriptional profiles elicited by the synthesis of three ER retained, misfolded ion channels: The subunit of the epithelial sodium channel, ENaC, the cystic fibrosis transmembrane conductance regulator, CFTR, and an inwardly rectifying potassium channel, Kir2.1, which vary in their mass, membrane topologies, and quaternary structures. To examine transcriptional profiles in a null background, the proteins were expressed in yeast, which was previously used to examine the degradation requirements for each substrate. Surprisingly, the proteins failed to induce a canonical unfolded protein response or heat shock response, although messages encoding several cytosolic and ER lumenal protein folding factors rose when ENaC or CFTR were expressed. In contrast, the levels of these genes were unaltered by Kir2.1 expression; instead, the yeast iron regulon was activated. Nevertheless, a significant number of genes that respond to various environmental stressors were upregulated by all three substrates, and when compared to previous microarray data we deduced the existence of a group of genes that reflect a novel misfolded membrane protein response. These data indicate that aberrant proteins in the ER elicit profound yet unique cellular responses.
Expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeast Saccharomyces cerevisiae.
No sample metadata fields
View SamplesMisfolded membrane proteins are retained in the endoplasmic reticulum (ER) and are subject to the ER associated degradation pathway, which clears the secretory pathway of potentially toxic species. While the transcriptional response to environmental stressors has been extensively studied, limited data exist describing the cellular response to misfolded membrane proteins. To this end, we expressed and then compared the transcriptional profiles elicited by the synthesis of three ER retained, misfolded ion channels: The subunit of the epithelial sodium channel, ENaC, the cystic fibrosis transmembrane conductance regulator, CFTR, and an inwardly rectifying potassium channel, Kir2.1, which vary in their mass, membrane topologies, and quaternary structures. To examine transcriptional profiles in a null background, the proteins were expressed in yeast, which was previously used to examine the degradation requirements for each substrate. Surprisingly, the proteins failed to induce a canonical unfolded protein response or heat shock response, although messages encoding several cytosolic and ER lumenal protein folding factors rose when ENaC or CFTR were expressed. In contrast, the levels of these genes were unaltered by Kir2.1 expression; instead, the yeast iron regulon was activated. Nevertheless, a significant number of genes that respond to various environmental stressors were upregulated by all three substrates, and when compared to previous microarray data we deduced the existence of a group of genes that reflect a novel misfolded membrane protein response. These data indicate that aberrant proteins in the ER elicit profound yet unique cellular responses.
Expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeast Saccharomyces cerevisiae.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process.
Age, Specimen part, Race
View SamplesProstate cancer is characterized by heterogeneity in the clinical course that often does not to correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. The metastatic samples are highly heterogeneous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodeling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer.
Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process.
Specimen part
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