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GSE62169
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
NS1 proteins from avian influenza viruses like the 1918 pandemic NS1 are capable of inhibiting the key signaling integrator c-Abl (Abl1), resulting in massive cytopathic cell alterations. In the current study, we addressed the consequences of NS1-mediated alteration of c-Abl on acute lung injury and pathogenicity. Comparing isogenic strains that differ only in their ability to inhibit c-Abl, we observed elevated pathogenicity for the c-Abl-inhibiting virus. NS1-mediated block of c-Abl resulted in severe lung pathology and massive edema formation and facilitated secondary bacterial pneumonia. This phenotype was independent of differences in replication and immune responses, defining it as an NS1 virulence mechanism distinct from its canonical functions. Microarray analysis revealed extensive down-regulation of genes involved in cell integrity and vascular endothelial regulation. In conclusion, NS1 protein-mediated blockade of c-Abl signaling drives acute lung injury and primes for bacterial co-infections revealing potential insights into the pathogenicity of the 1918 pandemic virus.
Publication Title
Nonstructural protein 1 (NS1)-mediated inhibition of c-Abl results in acute lung injury and priming for bacterial co-infections: insights into 1918 H1N1 pandemic?
Sample Metadata Fields
Specimen part, Time
View Samples- Drosophila melanogaster
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Effect of LUBEL catalytic dead mutation in immune response Overall design: Mutation was introduced in the LUBEL catalytic region by CRISPR/Cas9 techonology in Drosophila melanogaster and their transcriptome was compared in control (sample 23930 to 23941) and e.coli pricked samples (sample 28984 to 28995).
Publication Title
Linear ubiquitination by LUBEL has a role in Drosophila heat stress response.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Effect of LUBEL catalytic dead mutation upon Heastshock Overall design: Mutation was introduced in CG11321 catalytic region by CRISPR/Cas9 techonology in Drosophila melanogaster and transcriptome was compared in untreated and heatshocked samples
Publication Title
Linear ubiquitination by LUBEL has a role in Drosophila heat stress response.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Sel1L is an adaptor protein for the E3 ligase Hrd1 in the endoplasmic reticulum-associated degradation (ERAD), but its physiological role in a cell-type-specific manner remains unclear. Here we show that mice with adipocyte-specific Sel1L deficiency are resistant to diet-induced obesity and exhibit postprandial hypertriglyceridemia. Mechanistically, our data demonstrate a critical requirement of Sel1L for the secretion of lipoprotein lipase (LPL), independently of its role in Hrd1-mediated ERAD and ER homeostasis. Further biochemical analyses revealed that Sel1L physically interacts and stabilizes the LPL maturation complex consisted of LPL and lipase-maturation factor 1 (LMF1). In the absence of Sel1L, LPL is retained in the ER and prone to the formation of protein aggregates, which are degraded by autophagy-mediated degradation. The Sel1L-mediated control of LPL secretion is seen in other LPL-expressing cell types as well such as cardiac muscle and macrophages. Thus, our study reports a novel role of Sel1L in LPL secretion and systemic lipid metabolism.
Publication Title
The ER-associated degradation adaptor protein Sel1L regulates LPL secretion and lipid metabolism.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Aging and neurodegeneration are often accompanied by a functionally impaired ubiquitin-proteasome system (UPS). In tauopathies and polyglutamine diseases a mutant form of Ubiquitin B, UBB+1, accumulates in disease-specific aggregates. UBB+1 mRNA is generated at low levels in vivo during transcription from the Ubiquitin B locus by molecular misreading. The resulting mutant protein has been shown to inhibit proteasome function. To elucidate causative effects and neuropathological consequences of UBB+1 accumulation, we used a UBB+1 expressing transgenic mouse line, that models UPS inhibition in neurons and exhibits behavioral phenotypes reminiscent of Alzheimers disease (AD). In order to reveal affected organs and functions, young and aged UBB+1 transgenic mice were comprehensively phenotyped for more than 240 parameters. This revealed unexpected changes in spontaneous breathing patterns and an altered response to hypoxic conditions. Our findings point to a central dysfunction of respiratory regulation in transgenic mice in comparison to wildtype littermate mice. Accordingly, UBB+1 was strongly expressed in brainstem regions of transgenic mice controlling respiration. These regions included, for example, the medial part of the nucleus of the tractus solitarius and the lateral subdivisions of the parabrachial nuclei. In addition, UBB+1 was also strongly expressed in these anatomical structures of AD patients (Braak stage #6) and was not expressed in non-demented controls. We conclude that long-term UPS inhibition due to UBB+1 expression causes central breathing dysfunction in a transgenic mouse model of AD. The UBB+1 expression pattern in humans is consistent with the contribution of bronchopneumonia as a cause of death in AD patients.
Publication Title
Long-term proteasomal inhibition in transgenic mice by UBB(+1) expression results in dysfunction of central respiration control reminiscent of brainstem neuropathology in Alzheimer patients.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Illumina HiSeq 4000
Description
The transition of skotomorphogenesis to photomorphogenesis is induced by the perception of light and is characterized by the inhibition of hypocotyl elongation and opening of cotyledons. Although it is known that the plant hormone cytokinin, when applied in high concentrations, inhibits hypocotyl elongation in the dark-grown Arabidopsis plants, it is unclear to what extent this response is the result of cytokinin alone or cytokinin-induced ethylene production. We show that treatment of etiolated seedlings in presence of ethylene inhibitors (eg. AgNO3) or treatment of the ethylene-resistant mutant ein2, resulted in a significant inhibition of hypocotyl elongation. This indicates that cytokinin induced de-etiolation is largely independent of ethylene and suggests a close connection between the cytokinin two component system and the light singalling networks. We show that this cytokinin signal is mainly mediated through the cytokinin receptor ARIBIDOPSIS HISTIDIN KINASE 3 (AHK3) and the ARABIDOPSIS RESPONSE REGULATORS 1 (ARR1) in combination with ARR12. Interestingly, mutation of COP1, DET1 and CIN4/COP10 renders plants insensitive to cytokinin and these factors are indispensable for the transcriptional response during cytokinin induced de-etiolation which indicates that a functional light signaling pathway is essential for this cytokinin response. In addition, the cytokinin effect on hypocotyl elongation is highly dependent on the ambient light conditions where higher light intensities causes a switch in the response to CK from an inhibitor to a promoter of hypocotyl elongation. Overall design: Investigation of the effect of 3 µM BA in presence of 10 µM AgNO3 on hypocotyl elongation in 4-days-old etiolated Arabidopsis seedlings, in triplicate, using RNA-seq analysis
Publication Title
Ethylene-independent promotion of photomorphogenesis in the dark by cytokinin requires COP1 and the CDD complex.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Comparison of gene expression in post-mortem hippocampus from 20 alcoholics and 19 controls.
Publication Title
Stress-response pathways are altered in the hippocampus of chronic alcoholics.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The thymic microenvironment is essential for proper differentiation and selection of thymocytes.Thymic involution in aged mice results in decreased T cell output and immune function. Here we use gene expression profiling of FACS sorted thymic stromal subsets to identify molecular mediators of thymocyte: stromal cell interactions, as well as gene expression changes thymic stromal subsets during early stages of thymic involution .
Publication Title
Global transcriptional profiling reveals distinct functions of thymic stromal subsets and age-related changes during thymic involution.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Plasticity between adhesive and less-adhesive states is important for mammalian cell behaviour. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of MDA-MB-468 breast carcinoma cells which grows in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices.
Publication Title
A dual phenotype of MDA-MB-468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Abstract: Transcriptome analysis was applied to characterize the physiological activities of Pseudomonas aeruginosa grown for three days in drip-flow biofilm reactors. Conventional applications of transcriptional profiling often compare two paired data sets that differ in a single experimentally controlled variable. In contrast this study obtained the transcriptome of a single biofilm state, ranked transcript signals to make the priorities of the population manifest, and compared rankings for a priori identified physiological marker genes between the biofilm and published data sets.
Publication Title
Physiology of Pseudomonas aeruginosa in biofilms as revealed by transcriptome analysis.
Sample Metadata Fields
Treatment
View Samples