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GSE79930
Mus musculus
24 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ribosome stalling during translation has recently been shown to cause neurodegeneration, yet the signaling pathways triggered by stalled elongation complexes are unknown. To investigate these pathways we analyzed the brain of B6J-nmf205-/- mice in which neuronal elongation complexes are stalled at AGA codons due to deficiencies in a tRNA Arg(UCU) tRNA and GTPBP2, a mammalian ribosome rescue factor. Increased levels of phosphorylation of eIF2 (Ser51) were detected prior to neurodegeneration in these mice and transcriptome analysis demonstrated activation of ATF4, a key transcription factor in the integrated stress response (ISR) pathway. Genetic experiments showed that this pathway was activated by the eIF2 kinase, GCN2, in an apparent deacylated tRNA-independent fashion. Further we found that the ISR attenuates neurodegeneration in B6J-nmf205-/- mice, underscoring the importance of cellular and stress context on the outcome of activation of this pathway. These results demonstrate the critical interplay between translation elongation and initiation in regulating neuron survival during cellular stress.
Publication Title
Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 9 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Malignant catarrhal fever of cattle is associated with low abundance of IL-2 transcript and a predominantly latent profile of ovine herpesvirus 2 gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 9 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
We hypothesized that the relative abundances of host cell transcripts in lymph nodes of animals with malignant catarrhal fever (MCF), compared to healthy controls, may be used to identify pathways that may help to explain the pathogenesis of MCF. Therefore, an abundance of host cell gene expression patterns in lymph nodes of animals with MCF and healthy controls were analyzed by microarray. Indeed, a vast number of genes related to inflammatory processes, lymphocyte activation, cell proliferation and apoptosis were detected at different abundances. However, the IL-2 transcript was eminent among the transcripts, which were, compared to healthy controls, less abundant in animals with MCF. Compared to healthy cattle, bovines with MCF appear to mimic an IL-2 knockout phenotype that has been described in mice. This supports the hypothesis that immunopathogenic events are linked to the pathogenesis of MCF. IL-2-deficiency may play an important role in the process.
Publication Title
Malignant catarrhal fever of cattle is associated with low abundance of IL-2 transcript and a predominantly latent profile of ovine herpesvirus 2 gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MHCaCre induced knockout of Fog2flox.
Publication Title
Fog2 is critical for cardiac function and maintenance of coronary vasculature in the adult mouse heart.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Preterm birth is an important unsolved clinical problem. Despite advanced treatments, infants who survive prematurity remain at increased risk for permanent disabilities. In approximately one-third of cases, prematurity is related to infection and/or inflammation, which renders hostile the normally receptive intrauterine environment. Proinflammatory cytokines provoke up-regulation of genes that promote uterine contractions. Using monolayer cultures of human decidual cells as a model, we profiled the global pattern of gene expression in response to cytokine challenge.
Publication Title
Inflammatory gene networks in term human decidual cells define a potential signature for cytokine-mediated parturition.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Premature birth continues to be a challenging pregnancy complication, and a body of literature indicates that inflammation can contribute to premature delivery by converting a receptive uterine environment to a hostile one. Cytokines have been demonstrated to provoke up-regulation of inflammatory genes (e.g. interleukin-1, 6, and 8, tumor necrosis factor-alpha, cyclooxygenase-2, and microsomal prostaglandin E synthase-1).
Publication Title
Inflammatory gene regulatory networks in amnion cells following cytokine stimulation: translational systems approach to modeling human parturition.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The metabolic enzyme diglyceride acyltransferase (DGAT) is responsible for the synthesis of triglycerides. Loss of its expression may sensitize cells to conditions of nutrient and oxygen that are commonly present in tumors. This study is designed to identify stress response pathways that may be induced following the shRNA-mediated knockdown of the two genes coding for the DGAT enzymes. In vitro growth conditions lacking serum and oxygen were used to mimic growth conditions commonly found in poorly perfused tumor domains
Publication Title
Triglycerides Promote Lipid Homeostasis during Hypoxic Stress by Balancing Fatty Acid Saturation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The metabolic enzyme diglyceride acyltransferase (DGAT) is responsible for the synthesis of triglycerides. Loss of its expression may sensitize cells to conditions of nutrient and oxygen that are commonly present in tumors. This study is designed to identify stress response pathways that may be induced following the shRNA-mediated knockdown of the two genes coding for the DGAT enzymes.
Publication Title
Triglycerides Promote Lipid Homeostasis during Hypoxic Stress by Balancing Fatty Acid Saturation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
In higher eukaryotes, the large numbers of nuclear-encoded tRNA genes partially ensure the robustness of cytoplasmic protein translation. Here we discover that a loss-of-function in n-Tr20, a member of the nuclear-encoded tRNA Arg UCU family that is expressed specifically in the central nervous systems leads to low but detectable levels of ribosome stalling. In the absence of GTPBP2, a novel binding partner of the ribosome recycling protein Pelota, ribosome stalling increases, leading to widespread neurodegeneration. Our results not only define GTPBP2 as a ribosome rescue factor, but also unmask the disease potential of mutations in nuclear-encoded tRNA genes. In this submission we provide ribosome footprinting data from the cerebella of four strains derived from the C57BL/6J strain with combinations of n-Tr20 and GTPBP2 mutations. Overall design: Examination of ribosome stalling in cerebella from 4 mouse strains derived from the: C57BL/6J (B6J) strain. The nmf205-/- strain has a homozygous mutation in the gene GTPBP2 while the B6J strain has normal GTPBP2. The n-Tr20 J/J strain has a defect in the n-Tr20 tRNA while the n-Tr20 N/N strain has a functional n-Tr20 tRNA. The 4 strains are the 2x2 combinations of these defects and correctly functioning sequences. 2 replicates for each strain. Please note that only BAM files are included in the records since they form the basis of the study''s conclusions. The raw data ribosomal RNA have been filtered and then unique reads mapping to mm10 were computed using tophat and igenome annotations.
Publication Title
RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration.
Sample Metadata Fields
No sample metadata fields
View Samples