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GSE34141
Pseudomonas aeruginosa
12 Downloadable Samples
Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Background Small colony variants (SCVs) are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch. Methodology/Principal findings One SCV (termed PAO-SCV) was isolated, showing high resistance to gentamicin and to the cephalosporine cefotaxime. PAO-SCV was prone to reversion as evidenced by emergence of large colonies with a frequency of 10-5 on media without antibiotics while it was stably maintained in presence of gentamicin. PAO-SCV showed a delayed growth, defective motility, and strongly reduced levels of the quorum sensing Pseudomonas quinolone signal (PQS). Whole genome expression analysis further suggested a multi-layered antibiotic resistance mechanism, including simultaneous over-expression of two drug efflux pumps (MexAB-OprM, MexXY-OprM), the LPS modification operon arnBCADTEF, and the PhoP-PhoQ two-component system. Conversely, the genes for the synthesis of PQS were strongly down-regulated in PAOSCV. Finally, genomic analysis revealed the presence of mutations in phoP and phoQ genes as well as in the mexZ gene encoding a repressor of the mexXY and mexABoprM genes. Only one mutation occurred only in REV, at nucleotide 1020 of the tufA gene, a paralog of tufB, both encoding the elongation factor Tu, causing a change of the rarely used aspartic acid codon GAU to the more common GAC, possibly causing an increase of tufA mRNA translation. High expression of phoP and phoQ was confirmed for the SCV variant while the revertant showed expression levels reduced to wild-type levels. Conclusions By combining data coming from phenotypic, gene expression and proteome analysis, we could demonstrate that resistance to aminoglycosides in one SCV mutant is multifactorial including overexpression of efflux mechanisms, LPS modification and is accompanied by a drastic down-regulation of the Pseudomonas quinolone signal quorum sensing system.
Publication Title
Phenotypic and genome-wide analysis of an antibiotic-resistant small colony variant (SCV) of Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
Argonaute (Ago) proteins, which act in post-transcriptional gene regulation directed by small RNAs, are vital for normal stem cell biology. Here we report the genomic characterization of stable Ago-deficient mouse embryonic stem cells (mESC) and determine the direct, primary and system level response to loss of Ago-mediated regulation. We find mESCs lacking all four Ago proteins are viable, do not repress microRNA (miRNA)-targeted cellular RNAs, and show distinctive gene network signatures. Profiling of RNA expression and epigenetic activity in an Ago mutant genetic series indicates that early responses to Ago loss are driven by transcriptional regulatory networks, in particular the Tgf-ß/Smad transcriptional network. This finding is confirmed using a time course analysis of Ago depletion and Ago rescue experiments. Detailed analysis places Tgf-ß/Smad activation upstream of cell cycle regulator activation, such as Cdkn1a, and repression of the c-Myc transcriptional network. The Tgf-ß/Smad pathway is directly controlled by multiple low-affinity miRNA interactions with Tgf-ß/Activin receptor mRNAs and receptor-mediated activation is required for Tgf-ß/Smad target induction with Ago loss. Our characterization reveals the interplay of post-transcriptional regulatory pathways with transcriptional networks in maintaining cell state and likely coordinating cell state transitions. Overall design: mRNA seq from stable genetic Dicer and Dgcr8 mutant mouse embryonic stem cells.
Publication Title
Temporal Control of the TGF-β Signaling Network by Mouse ESC MicroRNA Targets of Different Affinities.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Humoral responses of mice specifically deleted for Moz (a histone acetyltransferase) or c-Myb (a transcription factor) in B cells were aberrant. RNA-sequencing analysis was performed to assess gene expression differences compared to wild-type controls in germinal center B cells or plasmablasts. Overall design: Moz f/f Aicda1-Cre, Aicda1-Cre, Myb f/f Cd23-Cre, Mybf/f (no cre) mice were immunized with NP-KLH precipitated in alum and germinal center B cells were sort-purified. Secondary plasmablasts were sort-purified from immunized mice boosted with NP-KLH in PBS (Myb experiment). Two independent experiments were conducted.
Publication Title
Regulation of germinal center responses and B-cell memory by the chromatin modifier MOZ.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
C.pn potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of Ldlr/ mice. We discovered that C.pn-induced extracellular IL-1 triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. Gpr109a and Abca1 were both upregulated in plaque lesions in Nlrp3/ mice in both hyperlipidemic and C.pn infection models.
Publication Title
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Local renin antiotensin systems have been identified for many extra-renal sites. Bone marrow has been proposed as one such site, although the nature of the renin-expressing cell type(s) has not been established.
Publication Title
Identification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR
Publication Title
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
mRNA profiling of mouse spleens comparing wild type spleens vs. spleens from mice having deletion of RBP-J in cells of the renin lineage which results in B-cell leukemia
Publication Title
Identification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
assess the efficacy of Pimasertib to characterize its mechanism of action
Publication Title
Combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors is active in preclinical models of aggressive lymphomas.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 88 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human prostate cancer tissues analyses
Publication Title
In silico dissection of cell-type-associated patterns of gene expression in prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples