Background and Purpose
Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: an emerging regulative role of Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors.
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View SamplesTo address the role of INO80/SWR-type remodeling complexes, we deleted Ep400 at defined times of mouse oligodendrocyte development. Whereas oligodendrocyte precursors are specified and develop normally without Ep400, terminal differentiation is dramatically impaired resulting in hypomyelination. RNA-Seq studies were performed on cultured and FACS sorted control and Ep400-deficient mouse oligodendrocytes to analyze changes in gene expression. These revealed that genes associated with the myelination program and with response to DNA damage are altered in Ep400-deficient oligodendrocytes. Overall design: OPC mRNA profiles of 6-day old control (ctrl) and Ep400 cko mice were generated using the Illumina HiSeq 2500 platform.
Chromatin remodeler Ep400 ensures oligodendrocyte survival and is required for myelination in the vertebrate central nervous system.
Specimen part, Cell line, Subject
View SamplesThe widespread use of electricity raises the question of whether or not 50 Hz (power line frequency in Europe) magnetic fields (MFs) affect organisms. We investigated the transcription of Escherichia coli K-12 MG1655 in response to extremely low-frequency (ELF) MFs. Fields generated by three signal types (sinusoidal continuous, sinusoidal intermittent, and power line intermittent; all at 50 Hz, 1 mT), were applied and gene expression was monitored at the transcript level using an Affymetrix whole-genome microarray. Bacterial cells were grown continuously in a chemostat (dilution rate D = 0.4 h-1) fed with glucose-limited minimal medium and exposed to 50 Hz MFs with a homogenous flux density of 1 mT. For all three types of MFs investigated, neither bacterial growth (determined using optical density) nor culturable counts were affected. Likewise, no statistically significant change (fold-change > 2, P 0.01) in the expression of 4,358 genes and 714 intergenic regions represented on the gene chip was detected after MF exposure for 2.5 h (1.4 generations) or 15 h (8.7 generations). Moreover, short-term exposure (8 min) to the sinusoidal continuous and power line intermittent signal neither affected bacterial growth nor showed evidence for reliable changes in transcription. In conclusion, our experiments did not indicate that the different tested MFs (50 Hz, 1 mT) affected the transcription of E. coli.
Genome-wide transcription analysis of Escherichia coli in response to extremely low-frequency magnetic fields.
Treatment
View SamplesOncogenic tyrosine kinases, such as BCR-ABL, TEL-ABL, TEL-PDGF-beta-R and FLT3-ITD, play a major role in the development of hematopoietic malignancy. They activate many of the same signal transduction pathways.
Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells.
No sample metadata fields
View SamplesMesenchymal stromal cells (MSC) are multipotent cells that potentially promote angiogenesis. Especially MSC derived from the amnionic membrane of human term placentas (hAMSC) are promising candidates for a therapeutic use in vascular diseases, as cells can be isolated using non-invasive methods and are immunologically tolerated in vivo. In this study, we wanted to evaluate the endothelial differentiation potential of hAMSC.
Amnion-derived mesenchymal stromal cells show angiogenic properties but resist differentiation into mature endothelial cells.
Specimen part
View SamplesAnalysis of differential gene expression. The influence of a constitutively activated mutant Kit receptor on gene expression in fetal hematopoietic cells was analyzed. Results provide information of genes and cellular processes that are influenced by Kit signaling.
Kit transduced signals counteract erythroid maturation by MAPK-dependent modulation of erythropoietin signaling and apoptosis induction in mouse fetal liver.
Specimen part
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.
The transcription factor prospero homeobox protein 1 is a direct target of SoxC proteins during developmental vertebrate neurogenesis.
Specimen part
View SamplesThe HMG-domain containing SoxC transcription factors Sox4 and Sox11 are expressed in the vertebrate central nervous system in neuronal precursors and neuroblasts. They are required during early stages of neurogenesis.
The transcription factor prospero homeobox protein 1 is a direct target of SoxC proteins during developmental vertebrate neurogenesis.
Specimen part
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