substantial number of people at risk to develop type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals who performed a controlled eight weeks cycling and walking training at 80 % individual VO2max. Participants identified as non-responders in insulin sensitivity (based on Matsuda index) did not differ in pre-intervention parameters compared to high responders. The failure to increase insulin sensitivity after training correlates with impaired up-regulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1 and AMPK2. The muscle transcriptome of the non-responders is further characterized by an activation of TGF and TGF target genes, which is associated with increases in inflammatory and macrophage markers. TGF1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGF1 signaling down-regulates the abundance of PGC1, AMPK2, mitochondrial transcription factor TFAM, and of mitochondrial enzymes. Thus, increased TGF activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity.
TGF-β Contributes to Impaired Exercise Response by Suppression of Mitochondrial Key Regulators in Skeletal Muscle.
Specimen part
View SamplesWe used microarrays to detail the global gene expression changes following apical infection of porcine choroid plexus epithelial cells (PCPEC) with Streptococcus suis (S. suis)
In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines.
Specimen part
View SamplesGene expression profile was analyzed after knockdown of PAEP in lung cancer cell lines 2106T and H1975 as well as in skin cancer cell line MeWo.
Glycodelin: A New Biomarker with Immunomodulatory Functions in Non-Small Cell Lung Cancer.
Specimen part, Cell line, Treatment
View SamplesHeterosis which is the improved vigor of F1-hybrids compared to their parents is widely exploited in maize (Zea mays L.) breeding to produce elite hybrids of superior yield. The transcriptomes of the maize inbred lines B73 and Mo17 and their reciprocal hybrid offspring were surveyed in the meristematic zone, the elongation zone, cortex and stele tissues of primary roots, prior to the developmental manifestation of heterosis. Single parent expression (SPE) is consistent with the dominance model for heterosis in that it denotes genes that are expressed in only one parent but in both reciprocal hybrids. In primary root tissues, between 1,027 (elongation zone) and 1,206 (stele) SPE patterns were observed. As a consequence, hybrids displayed in each tissue >400 active genes more than either parent. Analysis of tissue-specific SPE dynamics revealed that 1,233 of 2,233 SPE genes displayed SPE in all tissues in which they were expressed while 1,000 SPE genes displayed in at least one tissue a non-SPE pattern. In addition, 64% (17,351/ 27,164) of all expressed genes were assigned to the two subgenomes which are the result of an ancient genome duplication. By contrast, only between 18 and 25% of the SPE genes were assigned to a subgenome suggesting that a disproportionate number of SPE genes are evolutionary young and emerged after genome duplication. We hypothesize that this phenomenon is associated with human selection of favorable maize genotypes which might primarily affect younger genes rather than genes whose functions have been conserved for millions of years.
Nonsyntenic genes drive highly dynamic complementation of gene expression in maize hybrids.
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View SamplesIn this study we analyzed the myeloma cell contact-mediated changes on the transcriptome of skeletal precursor cells. Therefore, human mesenchymal stem cells (MSC) and osteogenic precursor cells (OPC) were co-cultured with the representative myeloma cell line INA-6 for 24 h. Afterwards, MSC and OPC were separated from INA-6 cells by fluorescence activated cell sorting. Total RNA of MSC and OPC fractions was used for whole genome array analysis.
Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells -Implications for myeloma bone disease.
Sex, Age, Specimen part, Disease stage
View SamplesType II testicular germ cell cancers (GCC) are the most frequently diagnosed tumors in young men (20 - 40 years) and are classified as seminoma or non-seminoma. GCCs are commonly treated by orchiectomy and chemo- or radiotherapy. However, a subset of metastatic non-seminomas display only incomplete remission or relapse and require novel treatment options. Recent studies have shown effective application of the small-molecule inhibitor JQ1 in tumor therapy, which interferes with the function of bromodomain and extra-terminal (BET)-proteins. Here, we demonstrate that upon JQ1 doses 250 nM GCC cell lines and Sertoli cells display compromised survival and induction of cell cycle arrest. JQ1 treated GCC cell lines display upregulation of genes indicative for DNA damage and a cellular stress response. Additionally, downregulation of pluripotency factors and induction of mesodermal differentiation was detected. GCCs xenografted in vivo showed a reduction in tumor size, proliferation and angiogenesis when subjected to JQ1 treatment. The combination of JQ1 and the histone deacetylase inhibitor romidepsin further enhanced the apoptotic effect in vitro and in vivo. Thus, we propose that JQ1 alone, or in combination with romidepsin may serve as a novel therapeutic option for GCCs.
The bromodomain inhibitor JQ1 triggers growth arrest and apoptosis in testicular germ cell tumours in vitro and in vivo.
Specimen part, Cell line, Time
View SamplesHearts of Myh6-MeCP2 transgenic mice and wildtype littermates were rapidly dissected and flash frozen.
Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac Adaptation in Chronic Heart Failure.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Treatment
View SamplesGenome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA damage induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16 mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Treatment
View SamplesGenome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA damage induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16 mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Treatment
View Samples