The highly conserved protein eIF5A found in archaea and all eucaryotes uniquely contains the posttranslationally formed amino acid hypusine. Despite being essential the functions of this protein and its modification remain unclear. To gain more insight into these functions temperature sensitive mutants of the human EIF5A1 were characterized in the yeast Saccharomyces cerevisiae.
Temperature-sensitive eIF5A mutant accumulates transcripts targeted to the nonsense-mediated decay pathway.
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View SamplesIt is becoming increasingly apparent that Staphylococcus aureus are able to survive engulfment by macrophages, and that the intracellular environment of these cells, which is essential to innate host defenses against invading microorganisms, may in fact provide a refuge for staphylococcal survival and dissemination. Based on this, we postulated that S. aureus might induce cytoprotective mechanisms by changing gene expression profiles inside macrophages similar to obligate intracellular pathogens, such as Mycobacterium tuberculosis.
Phagocytosis of Staphylococcus aureus by macrophages exerts cytoprotective effects manifested by the upregulation of antiapoptotic factors.
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View SamplesIRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Though regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function is still controversial. In order to investigate the role of IRAK-4 kinase function in vivo, knock-in mice were generated by replacing the wild type IRAK-4 gene with a mutant gene encoding kinase deficient IRAK-4 protein (IRAK-4 KD). Analysis of bone marrow macrophages obtained from WT and IRAK-4 KD mice with a number of experimental techniques demonstrated that the IRAK-4 KD cells greatly lack responsiveness to stimulation with the Toll-like receptor 4 (TLR4) agonist LPS. One of the techniques used, microarray analysis, identified IRAK-4 kinase-dependent LPS response genes and revealed that the induction of LPS-responsive mRNAs was largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in TLR4-mediated induction of inflammatory responses.
IRAK-4 kinase activity-dependent and -independent regulation of lipopolysaccharide-inducible genes.
No sample metadata fields
View SamplesFibroblasts from PRDM12 patients and unaffected wildtype relatives were cultured until near confluency. The transcriptional profile of those cells was determined by mRNA sequencing and uncovered differential expression in several known pain and neurodevelopmental genes. Overall design: Transcriptome comparison of human PRDM12 mutant and wildtype fibroblasts
The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception.
No sample metadata fields
View SamplesAsthma is a chronic inflammatory respiratory disease affecting over 300 million people around the world. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. While patients with severe, refractory disease represent a heterogeneous group, a feature shared by most includes glucocorticoid insensitivity. We sought to characterize differences in the airway smooth muscle transcriptome response to glucocorticoids in fatal asthma vs. non-asthma donors. RNA-Seq was used to measure airway smooth muscle transcript expression differences between 9 donors with fatal asthma and 8 non-asthma donors. Cells from each donor were treated with budesonide or with vehicle control. Poly(A)-selected RNA-Seq libraries were prepared with the Illumina TruSeq method. An Illumina HiSeq 2500 instrument was used to generate 125 base pair paired-end reads. Overall design: Transcriptome profiles obtained via RNA-Seq for airway smooth muscle cells from 9 fatal asthma and 8 non-asthma donors treated with budesonide (100nM for 24h) or vehicle control were compared
Airway Smooth Muscle-Specific Transcriptomic Signatures of Glucocorticoid Exposure.
Specimen part, Disease, Disease stage, Treatment, Subject
View SamplesIRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Though regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function is still controversial. In order to investigate the role of IRAK-4 kinase function in vivo, knock-in mice were generated by replacing the wild type IRAK-4 gene with a mutant gene encoding kinase deficient IRAK-4 protein (IRAK-4 KD). Analysis of embryonic fibroblasts and macrophages obtained from IRAK-4 KD mice with a number of experimental techniques demonstrated that they greatly lack responsiveness to stimulation with IL-1b or a Toll-like receptor 7 (TLR7) agonist. One of the techniques used, microarray analysis, identified IRAK-4 kinase-dependent IL-1b response genes in mouse embryonic fibroblasts and revealed that the induction of IL-1b-responsive mRNAs was largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in IL-1R/TLR7-mediated induction of inflammatory responses.
IRAK-4 kinase activity is required for interleukin-1 (IL-1) receptor- and toll-like receptor 7-mediated signaling and gene expression.
No sample metadata fields
View SamplesFoxp3+ T-regulatory cells (Tregs) are key to immune homeostasis such that their diminished numbers or function can cause autoimmunity and allograft rejection. Foxp3+ Tregs express histone/protein deacetylases (HDACs) that regulate chromatin remodeling, gene expression and protein function. Pan-HDAC inhibitors developed for oncology enhance Treg production and suppression but have limited non-oncologic applications given their broad effects. We show, using HDAC6-deficient mice and WT mice treated with HDAC6-specific inhibitors, that HDAC6 inhibition promotes Treg suppressive activity in models of inflammation and autoimmunity, including multiple forms of experimental colitis and fully MHC-incompatible cardiac allograft rejection. Many of the beneficial effects of HDAC6 targeting are also achieved by inhibition of the HDAC6-regulated protein, HSP90. Hence, selective targeting of a single HDAC isoform, HDAC6, or its downstream target, HSP90, can promote Treg-dependent suppression of autoimmunity and transplant rejection.
Histone deacetylase 6 and heat shock protein 90 control the functions of Foxp3(+) T-regulatory cells.
No sample metadata fields
View SamplesRationale: Asthma is a chronic inflammatory airway disease. Children with severe asthma have lower levels of vitamin D than children with moderate asthma, and among children with severe asthma, airway smooth muscle (ASM) mass is inversely related to vitamin D levels. Beta2 agonists are a common asthma medication that act partly by targetting the ASM. We used RNA-Seq to characterize the human ASM transcriptome of fatal and asthma vs. contols at baseline and under two treatment conditions. Methods: The Illumina TruSeq assay was used to prepare 75bp paired-end libraries for ASM cells from white donors, 6 with fatal asthma and 12 control donors under three treatment conditions: 1) no treatment; 2) treatment with a ß2-agonist (i.e. Albuterol, 1µM for 18h); 3) treatment with vitamin D 100 nM for 18h). Llibraries were sequenced with an Illumina Hi-Seq 2000 instrument. The Tuxedo Suite Tools were used to align reads to the hg19 reference genome, assemble transcripts, and perform differential expression analysis using the protocol described in https://github.com/blancahimes/taffeta Overall design: mRNA profiles obtained via RNA-Seq for primary human airway smooth muscle cell lines from fatal asthma or control donors that were treated with vitamin D, albuterol, or were left untreated.
Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma.
No sample metadata fields
View SamplesThe transcriptional profile of Kras;Rank +/+ and Kras;Rank fl/fl mouse primary pneumocytes were determined by mRNA sequencing and uncovered differences in their molecular signatures including genes involved in cell-cell junction, mitosis, mitochondrial homeostasis, TCA cycle and respiratory electron transport Overall design: Transcriptome comparison of primary pneumocytes purified from Kras;Rank+/+ and Kras;Rankfl/fl mice treated with Rankl ex vivo
RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development.
Specimen part
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