To investigate an unknown mechanism of cytotoxicity, A549 human lung-cancer cells were treated with compounds from a series of inhibitors developed against the human LIM kinases LIMK1 and LIMK2. Compounds 1 and 2 inhibit LIM kinase activity in vitro and affect cell proliferation and survival in vivo. Compounds 3 and 4 inhibit LIM kinases but do not affect cell survival or proliferation. Compounds 5 and 6 affect proliferation and survival but do not inhibit LIM kinases. Nocodazole was included as a comparator because the compounds were known to affect microtubule stability. A treatment of 7 hours was used to examine events prior to apoptosis, while the dose levels captured both cytotoxicity and inhibition of LIMKs (Compounds 1 and 2), LIMK inhibition alone ( Compounds 3 and 4) or cytotoxicity alone (Compounds 5, 6, and Nocodazole).
Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors.
Cell line, Subject, Compound
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Human pre-valvular endocardial cells derived from pluripotent stem cells recapitulate cardiac pathophysiological valvulogenesis.
Specimen part
View SamplesFor these data, we analyzed hippocampal gene expression of nine control and 22 AD subjects of varying severity on 31 separate microarrays. We then tested the correlation of each gene's expression with MiniMental Status Examination (MMSE) and neurofibrillary tangle (NFT) scores across all 31 subjects regardless of diagnosis. These tests revealed a major transcriptional response comprising thousands of genes significantly correlated with AD markers. Several hundred of these genes were also correlated with AD markers across only control and incipient AD subjects (MMSE > 20).
Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reprogramming of the microRNA transcriptome mediates resistance to rapamycin.
Specimen part, Cell line
View SamplesThe mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation. Inhibitors of mTOR are being evaluated as anti-tumor agents. Given the emerging role of microRNAs (miRNAs) in tumorgenesis we hypothesized that miRNAs could play important roles in the response of tumors to mTOR inhibitors. Rapamycin resistant myogenic cells developed by long-term rapamycin treatment showed extensive reprogramming of miRNAs expression, characterized by up-regulation of the mir-17~92 and related clusters and down-regulation of tumor-suppressor miRNAs. Antagonists of oncogenic miRNA families and mimics of tumor suppressor miRNAs (let-7) restored rapamycin sensitivity in resistant tumor cells. This study identified miRNAs as new downstream components of the mTOR-signaling pathway, which may determine the response of tumors to mTOR inhibitors.
Reprogramming of the microRNA transcriptome mediates resistance to rapamycin.
Specimen part, Cell line
View SamplesPlant respiration responses to elevated growth [CO2] are key uncertainties in predicting future crop and ecosystem function. In particular, the effects of elevated growth [CO2] on respiration over leaf development are poorly understood. This study tested the prediction that, due to greater whole-plant photoassimilate availability and growth, elevated [CO2] induces transcriptional reprogramming and a stimulation of nighttime respiration in leaf primordia, expanding leaves, and mature leaves of Arabidopsis thaliana. In primordia, elevated [CO2] altered transcript abundance, but not for genes encoding respiratory proteins. In expanding leaves, elevated [CO2] induced greater glucose content and transcript abundance for some respiratory genes, but did not alter respiratory CO2 efflux. In mature leaves, elevated [CO2] led to greater glucose, sucrose and starch content, plus greater transcript abundance for many components of the respiratory pathway, and greater respiratory CO2 efflux. Therefore, growth at elevated [CO2] stimulated dark respiration only after leaves transitioned from carbon sinks into carbon sources. This coincided with greater photoassimilate production by mature leaves under elevated [CO2] and peak respiratory transcriptional responses. It remains to be determined if biochemical and transcriptional responses to elevated [CO2] in primordial and expanding leaves are essential prerequisites for subsequent alterations of respiratory metabolism in mature leaves.
Developmental stage specificity of transcriptional, biochemical and CO2 efflux responses of leaf dark respiration to growth of Arabidopsis thaliana at elevated [CO2].
No sample metadata fields
View SamplesThe purpose of this study was to identify genes in keratinocytes and fibroblasts in human skin equivalents that changed expression in response to the burrowing of live scabies mites.
Sarcoptes scabiei mites modulate gene expression in human skin equivalents.
Specimen part, Treatment
View SamplesTranscriptional reprogramming and stimulation of leaf respiration by elevated CO2 concentration is diminished, but not eliminated, under limiting nitrogen supply.
Transcriptional reprogramming and stimulation of leaf respiration by elevated CO2 concentration is diminished, but not eliminated, under limiting nitrogen supply.
Age, Specimen part
View SamplesGenetic Manipulation to increase number of ISC (intestinal stem cells) and gene expression profiling to identify ISC regulators
Gene expression profiling identifies the zinc-finger protein Charlatan as a regulator of intestinal stem cells in Drosophila.
Sex, Specimen part
View SamplesThe aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from nave and BCG vaccinated mice. The differences between nave and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals.
Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb).
Sex, Age, Specimen part
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