This SuperSeries is composed of the SubSeries listed below.
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Specimen part, Treatment
View SamplesUnderstanding toxicity pathways of engineered nanomaterials (ENM) has recently been brought forward as a key step in 21st century ENM risk assessment. Molecular mechanisms linked to phenotypic end points is a step towards the development of toxicity tests based on key events, which may allow for grouping of ENM according to their mechanisms of action. This study identified molecular mechanisms underlying mitochondrial dysfunction in human bronchial epithelial BEAS 2B cells following exposure to one of the most studied multi-walled carbon nanotubes (MWCNTs; Mitsui-7). Asbestos was used as a positive control and a non-carcinogenic glass wool material was included as a negative fibre control. Decreased mitochondrial membrane potential (MMP) was observed for MWCNTs at a biologically relevant dose (0.25 g/cm2) and for asbestos at 2 g/cm2, but not for glass wool. Extensive temporal transcriptomic and microRNA expression analyses identified a 330-gene signature related to MWCNT- and asbestos-induced MMP. Fourty-nine of the MMP-associated genes showed highly similar expression patterns over time (six time points) and the majority was found to be regulated by two transcription factors strongly involved in mitochondrial homeostasis, APP and NRF1. In addition, four miRNAs were associated with MMP and one of them, miR-1275, was found to negatively correlate with a large part of the MMP-associated genes. Cellular processes such as gluconeogenesis, glucose metabolism, mitochondrial LC-fatty acid -oxidation and spindle microtubule function were enriched among the MMP-associated genes and miRNAs. These results are expected to be useful in the identification of key events in ENM-related toxicity pathways for the development of molecular screening techniques.
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Specimen part, Treatment
View SamplesacLDL loading of mouse peritoneal macrophage is an in vitro foam cell model.
Cholesterol accumulation regulates expression of macrophage proteins implicated in proteolysis and complement activation.
No sample metadata fields
View SamplesHeparan sulfate (HS), a long linear polysaccharide, is implicated in various steps of tumorigenesis, including angiogenesis. We successfully interfered with HS biosynthesis using a peracetylated 4-deoxy analog of the HS constituent GlcNAc and studied the compounds metabolic fate and its effect on angiogenesis. The 4-deoxy analog was activated intracellularly into UDP-4-deoxy-GlcNAc and HS expression was inhibited up to ~96% (IC50 = 16 M). HS chain size was reduced, without detectable incorporation of the 4-deoxy analog, likely due to reduced levels of UDP-GlcNAc and/or inhibition of glycosyltransferase activity. Comprehensive gene expression analysis revealed reduced expression of genes regulated by HS binding growth factors as FGF-2 and VEGF. Cellular binding and signaling of these angiogenic factors was inhibited. Micro-injection in zebrafish embryos strongly reduced HS biosynthesis, and angiogenesis was inhibited in both zebrafish and chicken model systems. All these data identify 4-deoxy-GlcNAc as a potent inhibitor of HS synthesis which hampers pro-angiogenic signaling and neo-vessel formation.
Interfering with UDP-GlcNAc metabolism and heparan sulfate expression using a sugar analogue reduces angiogenesis.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Control of daily transcript oscillations in Drosophila by light and the circadian clock.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integration of light and temperature in the regulation of circadian gene expression in Drosophila.
No sample metadata fields
View SamplesCircadian clocks are temporally aligned to the environment via signals, or Zeitgebers, such as daily light and temperature cycles, food availability, and social behavior. In this study, we show that genome-wide expression profiles from temperature-entrained flies show a dramatic difference in the presence or absence of a thermocycle. Whereas transcription appears to be modified globally by changes in temperature, there is a specific set of transcripts that continue to oscillate in constant conditions following temperature entrainment. These transcripts show a significant overlap with a previously defined set of transcripts oscillating in response to a photocycle. Further, these overlapping transcripts maintain the same mutual phase relationships after entrainment by temperature or light. Comparison of the collective temperature- and light-entrained circadian phases indicates that natural environmental light and temperature cycles cooperatively entrain the circadian clock. These findings suggest that a single transcriptional clock in the adult fly head is able to integrate information from both light and temperature.
Integration of light and temperature in the regulation of circadian gene expression in Drosophila.
No sample metadata fields
View SamplesCircadian clocks are temporally aligned to the environment via signals, or Zeitgebers, such as daily light and temperature cycles, food availability, and social behavior. In this study, we show that genome-wide expression profiles from temperature-entrained flies show a dramatic difference in the presence or absence of a thermocycle. Whereas transcription appears to be modified globally by changes in temperature, there is a specific set of transcripts that continue to oscillate in constant conditions following temperature entrainment. These transcripts show a significant overlap with a previously defined set of transcripts oscillating in response to a photocycle. Further, these overlapping transcripts maintain the same mutual phase relationships after entrainment by temperature or light. Comparison of the collective temperature- and light-entrained circadian phases indicates that natural environmental light and temperature cycles cooperatively entrain the circadian clock. These findings suggest that a single transcriptional clock in the adult fly head is able to integrate information from both light and temperature.
Integration of light and temperature in the regulation of circadian gene expression in Drosophila.
No sample metadata fields
View SamplesCircadian clocks are temporally aligned to the environment via signals, or Zeitgebers, such as daily light and temperature cycles, food availability, and social behavior. In this study, we show that genome-wide expression profiles from temperature-entrained flies show a dramatic difference in the presence or absence of a thermocycle. Whereas transcription appears to be modified globally by changes in temperature, there is a specific set of transcripts that continue to oscillate in constant conditions following temperature entrainment. These transcripts show a significant overlap with a previously defined set of transcripts oscillating in response to a photocycle. Further, these overlapping transcripts maintain the same mutual phase relationships after entrainment by temperature or light. Comparison of the collective temperature- and light-entrained circadian phases indicates that natural environmental light and temperature cycles cooperatively entrain the circadian clock. These findings suggest that a single transcriptional clock in the adult fly head is able to integrate information from both light and temperature.
Integration of light and temperature in the regulation of circadian gene expression in Drosophila.
No sample metadata fields
View SamplesCircadian clocks are temporally aligned to the environment via signals, or Zeitgebers, such as daily light and temperature cycles, food availability, and social behavior. In this study, we show that genome-wide expression profiles from temperature-entrained flies show a dramatic difference in the presence or absence of a thermocycle. Whereas transcription appears to be modified globally by changes in temperature, there is a specific set of transcripts that continue to oscillate in constant conditions following temperature entrainment. These transcripts show a significant overlap with a previously defined set of transcripts oscillating in response to a photocycle. Further, these overlapping transcripts maintain the same mutual phase relationships after entrainment by temperature or light. Comparison of the collective temperature- and light-entrained circadian phases indicates that natural environmental light and temperature cycles cooperatively entrain the circadian clock. These findings suggest that a single transcriptional clock in the adult fly head is able to integrate information from both light and temperature.
Integration of light and temperature in the regulation of circadian gene expression in Drosophila.
No sample metadata fields
View Samples