STEP (striatal-enriched tyrosine phosphatase) is a brain-specific phosphatase named for its robust expression in striatum. Brains from homozygous and heterozygous STEP knockout mice and wild-type littermates were harvested, and striatum microdissected. RNA was extracted and hybridized to Affymetrix 230_2 microarray chips.
Downstream effects of striatal-enriched protein tyrosine phosphatase reduction on RNA expression in vivo and in vitro.
Sex, Specimen part, Treatment
View SamplesSchizophrenia is a complex psychiatric disorder encompassing a range of symptoms and etiology dependent upon the interaction of genetic and environmental factors. Several risk genes, such as DISC1, have been associated with schizophrenia as well as bipolar disorder (BPD) and major depressive disorder (MDD), consistent with the hypothesis that a shared genetic architecture could contribute to divergent clinical syndromes. The present study compared gene expression profiles across three brain regions in post-mortem tissue from matched subjects with schizophrenia, BPD or MDD and unaffected controls. Post-mortem brain tissue was collected from control subjects and well-matched subjects with schizophrenia, BPD, and MDD (n=19 from each group). RNA was isolated from hippocampus, Brodmann Area 46, and associative striatum and hybridized to U133_Plus2 Affymetrix chips. Data were normalized by RMA, subjected to pairwise comparison followed by Benjamini and Hochberg False Discovery Rate correction (FDR). Samples derived from patients with schizophrenia exhibited many more changes in gene expression across all brain regions than observed in BPD or MDD. Several genes showed changes in both schizophrenia and BPD, though the magnitude of change was usually larger in schizophrenia. Several genes that have variants associated with schizophrenia were found to have altered expression in multiple regions of brains from subjects with schizophrenia. Continued evaluation of circuit-level alterations in gene expression and gene-network relationships may further our understanding of how genetic variants may be influencing biological processes to contribute to psychiatric disease.
STEP levels are unchanged in pre-frontal cortex and associative striatum in post-mortem human brain samples from subjects with schizophrenia, bipolar disorder and major depressive disorder.
Sex, Age, Specimen part, Disease, Disease stage, Race
View SamplesHypersensitivity reactions are rare, but potentially severe adverse effects of sulfonamide antibiotics. Increased in vitro toxicity of lymphocytes, primarily CD8+ T cells, to sulfonamide drug metabolites as been proposed as a marker for sulfonamide hypersensitivity, but the mechanisms underlying this marker are unknown.
RNA expression profiling in sulfamethoxazole-treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes.
Specimen part
View SamplesThe original objectives of the study were to identify surface markers specifically expressed in motor neurons. We now use the data to profile the expression of Cdk family members in motor neurons.
Dual Inhibition of GSK3β and CDK5 Protects the Cytoskeleton of Neurons from Neuroinflammatory-Mediated Degeneration In Vitro and In Vivo.
Specimen part
View SamplesEndogenous oligodendrocyte progenitor cells (OPCs) are a promising target to improve functional recovery after spinal cord injury (SCI) by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neuron. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation. Overall design: DEG analysis of primary OPC and OL populations, 5 biological replicates per population
Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation <i>In Vitro</i>.
No sample metadata fields
View SamplesBACKGROUND: Climate change will lead in the future to an occurrence of heat waves with a higher frequency and duration than observed today, which has the potential to cause severe damage to seedlings of temperate maize genotypes. In this study, we aimed to (I) assess phenotypic variation for heat tolerance of temperate European Flint and Dent maize inbred lines, (II) investigate the transcriptomic response of temperate maize to linearly increasing heat levels and, (III) identify genes associated with heat tolerance in a set of genotypes with contrasting heat tolerance behaviour. RESULTS: Strong phenotypic differences with respect to heat tolerance were observed between the examined maize inbred lines on a multi-trait level. We identified 607 heat responsive genes as well as 39 heat tolerance genes. CONCLUSION: Our findings indicate that individual inbred lines developed different genetic mechanisms in response to heat stress. We applied a novel statistical approach enabling the integration of multiple genotypes and stress levels in the analysis of abiotic stress expression studies. Overall design: Identifcation of differentially expressed genes between 8 genotypes and 3 heat levels
Genome-wide expression profiling and phenotypic evaluation of European maize inbreds at seedling stage in response to heat stress.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Prospective identification of resistance mechanisms to HSP90 inhibition in KRAS mutant cancer cells.
Cell line
View SamplesInhibition of the HSP90 chaperone results in depletion of many signaling proteins that drive tumorigenesis, such as downstream effectors of KRAS, the most commonly mutated human oncogene. As a consequence, several small-molecule HSP90 inhibitors are being evaluated in clinical trials as anticancer agents. To prospectively identify mechanisms through which HSP90-dependent cancer cells evade pharmacologic HSP90 blockade, we generated multiple mutant KRAS-driven cancer cell lines with acquired resistance to the purine-scaffold HSP90 inhibitor PU-H71. All cell lines retained dependence on HSP90 function, as evidenced by sensitivity to short hairpin RNA-mediated suppression of HSP90AA1 or HSP90AB1 (also called HSP90 and HSP90, respectively), and exhibited two types of genomic alterations that interfere with the effects of PU-H71 on cell viability and proliferation: (i) a Y142N missense mutation in the ATP-binding domain of HSP90 that co-occurred with amplification of the HSP90AA1 locus, (ii) genomic amplification and overexpression of the ABCB1 gene encoding the MDR1 drug efflux pump. In support of a functional role for these alterations, exogenous expression of HSP90 Y142N conferred PU-H71 resistance to HSP90-dependent cells, and pharmacologic MDR1 inhibition with tariquidar or lowering ABCB1 expression restored sensitivity to PU-H71 in ABCB1-amplified cells. Finally, comparison with structurally distinct HSP90 inhibitors currently in clinical development revealed that PU-H71 resistance could be overcome, in part, by ganetespib (also known as STA9090) but not tanespimycin (also known as 17-AAG). Together, these data identify potential mechanisms of acquired resistance to small molecules targeting HSP90 that may warrant proactive screening for additional HSP90 inhibitors or rational combination therapies.
Prospective identification of resistance mechanisms to HSP90 inhibition in KRAS mutant cancer cells.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Disease, Cell line, Treatment
View SamplesThe goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia).
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Disease, Cell line
View Samples