The world-wide used herbicide alachlor is among the priority substances listed in the European Water Framework Directive. We aimed at finding molecular biomarkers in the model yeast Saccharomyces cerevisiae that may be used to predict potential cytotoxic effects of this xenobiotic while providing mechanistic clues possibly relevant for experimentally less accessible non-target eukaryotes.
Transcriptional profiling in Saccharomyces cerevisiae relevant for predicting alachlor mechanisms of toxicity.
No sample metadata fields
View SamplesCoupling immunity and development is essential to ensure survival despite changing internal conditions in the organism. The metamorphosis of the fruit fly represents a striking example of drastic and systemic physiological changes that need to be integrated with the innate immune system. However, the mechanisms that coordinate development and immune cell activity in the transition from larva to adult in Drosophila remain to elucidate. The steroid hormone ecdysone is known to act as a key coordinator of metamorphosis. This hormone activates a nuclear receptor, the Ecdysone Receptor (EcR), which acts as a heterodimer with its partner Ultraspiracle (USP). Together, they activate the transcription of primary response genes, which in turn activate the transcription of a battery of late response genes. We have revealed that regulation of macrophage-like cells (hemocytes) by the steroid hormone ecdysone is essential for an effective innate immune response over metamorphosis. We have shown that in response to ecdysone signalling, hemocytes rapidly up regulate actin dynamics, motility and phagocytosis of apoptotic corpses, and acquire the ability to chemotax to damaged epithelia. Most importantly, individuals lacking ecdysone-activated hemocytes are defective in bacterial phagocytosis and are fatally susceptible to infection by bacteria ingested at larval stages, despite the normal systemic production of antimicrobial peptides. This decrease in survival is comparable to the one observed in pupae lacking immune cells altogether, indicating that ecdysone-regulation is essential to hemocyte immune functions and survival after infection.
Steroid hormone signaling is essential to regulate innate immune cells and fight bacterial infection in Drosophila.
Specimen part
View SamplesRNA from wt and SIN1 knock-out MEF cell lines were compared
mTORC2 Responds to Glutamine Catabolite Levels to Modulate the Hexosamine Biosynthesis Enzyme GFAT1.
Specimen part
View SamplesWe report the expression profiles of the nuclear receptor family of transcription factors, known regulators of metabolism, during iPSC generation. Unique but overlapping expression patterns were found in iPSCs derived from adipose derived stem cells (ADSCs) and embryonic fibroblasts (human and mouse) that correlate with developmental transitions in the cell.
ERRs Mediate a Metabolic Switch Required for Somatic Cell Reprogramming to Pluripotency.
Specimen part, Cell line, Time
View SamplesSkeletal muscle atrophy is a debilitating condition associated with weakness, fatigue, and reduced functional capacity. Nuclear factor-kappaB (NF-B) transcription factors play a critical role in atrophy. Knockout of genes encoding p50 or the NF-B co-transactivator, Bcl-3, abolish disuse atrophy and thus they are NF-B factors required for disuse atrophy. We do not know however, the genes targeted by NF-B that produce the atrophied phenotype. Here we identify the genes required to produce disuse atrophy using gene expression profiling in wild type compared to Nfkb1 (gene encodes p50) and Bcl-3 deficient mice. There were 185 and 240 genes upregulated in wild type mice due to unloading, that were not upregulated in Nfkb1-/- and Bcl-3-/- mice, respectively, and so these genes were considered direct or indirect targets of p50 and Bcl-3. All of the p50 gene targets were contained in the Bcl-3 gene target list. Most genes were involved with protein degradation, signaling, translation, transcription, and transport. To identify direct targets of p50 and Bcl-3 we performed chromatin immunoprecipitation of selected genes previously shown to have roles in atrophy. Trim63 (MuRF1), Fbxo32 (MAFbx), Ubc, Ctsl, Runx1, Tnfrsf12a (Tweak receptor), and Cxcl10 (IP-10) showed increased Bcl-3 binding to B sites in unloaded muscle and thus were direct targets of Bcl-3. p50 binding to the same sites on these genes either did not change or increased, supporting the idea of p50:Bcl-3 binding complexes. p65 binding to B sites showed decreased or no binding to these genes with unloading. Fbxo9, Psma6, Psmc4, Psmg4, Foxo3, Ankrd1 (CARP), and Eif4ebp1 did not show changes in p65, p50, or Bcl-3 binding to B sites, and so were considered indirect targets of p50 and Bcl-3. This work represents the first study to use a global approach to identify genes required to produce the atrophied phenotype with disuse.
Identification of genes that elicit disuse muscle atrophy via the transcription factors p50 and Bcl-3.
Sex, Specimen part
View Samples4-Hydroxynonenal (HNE), a cytotoxic and diffusible electrophile generated by the spontaneous decomposition of oxidized lipids, has a suspected role in neurodegenerative and inflammatory disease processes. In addition to promoting cell death, elevated levels of HNE lead to the engagement of cytoprotective signaling pathways, including the heat shock, antioxidant, DNA damage, and ER stress responses. Activation of the heat shock response, mediated by the transcription factor heat shock factor 1 (HSF1), is critical for maintaining cellular viability in the presence of HNE. Accordingly, silencing HSF1 expression using siRNA enhances the toxicity of HNE. Microarray analysis of samples from control and HSF1-silenced cells was performed to investigate which associated changes in gene could be responsible for the decrease in cellular viability.
HSF1-mediated BAG3 expression attenuates apoptosis in 4-hydroxynonenal-treated colon cancer cells via stabilization of anti-apoptotic Bcl-2 proteins.
No sample metadata fields
View SamplesTo identify atrophy genes directly targeted by Bcl-3 transactivator at a genome wide level, we performed whole transcript expression array and ChIP-seq for muscles from weight bearing or 5-day hind limb unloaded mice.
The ChIP-seq-defined networks of Bcl-3 gene binding support its required role in skeletal muscle atrophy.
Age, Specimen part
View SamplesThe sexually dimorphic expression of genes across 26 somatic rat tissues was using Affymetrix RAE-230 genechips. We considered probesets to be sexually dimorphically expressed (SDE) if they were measurably expressed above background in at least one sex, there was at least a two-fold difference in expression (dimorphism) between the sexes, and the differences were statistically significant after correcting for false discovery. 14.5% of expressed probesets were SDE in at least one tissue, with higher expression nearly twice as prevalent in males compared to females. Most were SDE in a single tissue. Surprisingly, nearly half of the probesets that were (SDE) in multiple tissues were oppositely sex biased in different tissues, and most SDE probesets were also expressed without sex bias in other tissues. Two genes were widely SDE: Xist (female-only) and Eif2s3y (male-only). The frequency of SDE probesets varied widely between tissues, and was highest in the duodenum (6.2%), whilst less than 0.05% in over half of the surveyed tissues. The occurrence of SDE probesets was not strongly correlated between tissues. Within individual tissues, however, relational networks of SDE genes were identified. In the liver, networks relating to differential metabolism between the sexes were seen. The estrogen receptor was implicated in differential gene expression in the duodenum. To conclude, sexually dimorphic gene expression is common, but highly tissue-dependent. Sexually dimorphic gene expression may provide insights into mechanisms underlying phenotypic sex differences.
The incidence of sexually dimorphic gene expression varies greatly between tissues in the rat.
Sex, Specimen part
View SamplesMany heavy metals, including nickel (Ni), cadmium (Cd), and chromium (Cr) are toxic industrial chemicals with an exposure risk in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects leading to disease or health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the of toxicity of nickel, cadmium, and chromium at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with soluble salts of each metal using concentrations derived from viability assays, and gene expression patterns were determined with DNA microarrays.
Exposure to nickel, chromium, or cadmium causes distinct changes in the gene expression patterns of a rat liver derived cell line.
No sample metadata fields
View SamplesThe goal of this set of experiments was to identify transcripts that are differentially expressed upon reactivation of NMD in an nmd2::HIS3 strain by galactose-induced expression of the NMD2 gene.
Association of yeast Upf1p with direct substrates of the NMD pathway.
No sample metadata fields
View Samples