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GSE12254
Macaca mulatta
19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rhesus macaques (Macaca mulatta) infected with a lethal dose of lymphocytic choriomeningitis virus-strain WE (LCMV-WE) provide a model for Lassa fever virus infection of man. Like Lassa fever in human beings, disease begins with flu-like symptoms but can progress to morbidity fairly rapidly. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al. J. Virol. 2007: PMID 17522210) showing distinct pre-viremic and viremic stages that discriminated between virulent and benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased. We observed gene expression changes that occurred before the viremic stage of the disease, and could potentially serve as biomarkers that discriminate between exposure to a hemorrhagic fever virus and exposure to a benign virus. Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a much broader effect on liver cell function than non-virulent virus. During the first few days of infection, virulent virus impacted gene expression associated with the generation of energy, such as fatty acid metabolism and glucose metabolism, with the complement and coagulation cascades, and with steroid metabolism, MAPK signaling and cell adhesion. For example, the energy profile resembled that of an organism entering starvation: acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis, was shut down and gene products involved in gluconeogenesis were up-regulated. In conclusion, this study identifies several potential gene markers of LCMV-WE-associated liver disease and contributes to the database of gene expression changes correlated with LCMV pathogenesis in primates.
Publication Title
Gene expression in primate liver during viral hemorrhagic fever.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The virulent Lassa fever virus (LASV) and the non-pathogenic Mopeia virus (MOPV) infect rodents and incidentally people in West Africa. The mechanism of LASV damage in human beings is unclear. A live-attenuated reassortant of MOPV and LASV protects rodents and primates from Lassa fever disease. Peripheral blood mononuclear cells from healthy human subjects were expose to either LASV or ML29 in order to identify early cellular responses that could be attributed to the difference in virulence between both viruses. Differential expression of interferon-related genes as well as coagulation-related genes could lead to an explanation for Lassa fever pathogenesis and lead to protective treatments for Lassa fever disease.
Publication Title
Transcriptome analysis of human peripheral blood mononuclear cells exposed to Lassa virus and to the attenuated Mopeia/Lassa reassortant 29 (ML29), a vaccine candidate.
Sample Metadata Fields
Specimen part
View Samples- Macaca mulatta
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Lassa fever virus is a zoonotic pathogen that plagues the endemic areas of West Africa. Rhesus macaques infected with a related arenavirus, LCMV-WE, serve as a model for Lassa-infection of human beings. Using a dose similar to that expected from a needle-stick, monkeys experience an early pre-viremic phase (day 1-3), a viremic phase with febrile onset (day 4-7), and, like human beings who succumb, they die within two weeks. Our goal was to monitor changes in gene expression that parallel disease progression in an effort to 1) identify genes with altered expression after infection, 2) identify genes that could discriminate between a virulent and non-virulent infection, and 3) identify genes encoding products that could serve as treatment targets for FDA-approved pharmaceuticals. Genes related to all three of these categories have been identified and some have been given preliminary validation by quantitative PCR and proteomic studies. These genes will be valuable candidates for future validation as prognostic biomarkers
Publication Title
Early blood profiles of virus infection in a monkey model for Lassa fever.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 34 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Here we present a strategy to adapt hESCs to high-throughput screening (HTS) conditions, resulting in an assay suitable for the discovery of small molecules that drive hESC self-renewal or differentiation. Use of this new assay has led to the identification of several currently marketed drugs and natural compounds promoting short-term hESC maintenance and compounds directing early lineage choice. Global gene expression analysis upon drug treatment reveals overlapping and novel pathways correlated to hESC self-renewal and differentiation. Our results demonstrate feasibility of hESC-based HTS and enhance the available repertoire of chemical compounds for manipulating hESC fate.
Publication Title
High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Zea mays
- 9 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
Anthocyanin induction in plant is considered a general defense response against biotic and abiotic stresses. The infection by Ustilago maydis, the corn smut pathogen, is accompanied with anthocyanin induction in leaf tissue. We revealed that anthocyanin is intentionally induced by the virulence promoting secreted effector protein Tin2. Tin2 protein functions inside plant cells where it interacts with cytoplasmic maize protein kinase ZmTTK1. Tin2 masks an ubiquitin-proteasome degradation motif in ZmTTK1 leading to a more stable active kinase. Active ZmTTK1 controls transcriptional activation of genes in the anthocyanin biosynthesis pathway rerouting phenylalanine away from lignin biosynthesis.
Publication Title
A secreted Ustilago maydis effector promotes virulence by targeting anthocyanin biosynthesis in maize.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Analysis of Early Myogenesis Reveals an Extensive Set of Transcriptional Regulators Whose Knock-down Can Inhibit Differentiation
Publication Title
Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 142 Downloadable Samples
Illumina HiSeq 4000, Illumina HiSeq 2500
Description
Excessive mRNA translation downstream of group I metabotropic glutamate receptors (mGlu1/5) is a core pathophysiology of fragile X syndrome (FX), however the differentially translating mRNAs that contribute to altered neural function are not known. We used Translating Ribosome Affinity Purification (TRAP) and RNA-seq to identify mistranslating mRNAs in CA1 pyramidal neurons of the FX mouse model (Fmr1-/y) hippocampus, which exhibit exaggerated mGlu1/5-induced long-term synaptic depression (LTD). In these neurons, we find the Chrm4 transcript encoding muscarinic acetylcholine receptor 4 (M4) is excessively translated, and synthesis of M4 downstream of mGlu5 activation is mimicked and occluded. Surprisingly, enhancement rather than inhibition of M4 activity normalizes core phenotypes in the Fmr1-/y, including excessive protein synthesis, exaggerated mGluR-LTD, and audiogenic seizures. These results suggest that not all excessively translated mRNAs in the Fmr1-/y brain are detrimental, and some may be candidates for enhancement to correct pathological changes in the FX brain. Overall design: 6 biological replicates of total hippocampal mRNA (Input) from WT and Fmr1 KO littermate pairs and CA1-TRAP-IP (IP) from the same 6 WT and KO littermate pairs.
Publication Title
Cell-Type-Specific Translation Profiling Reveals a Novel Strategy for Treating Fragile X Syndrome.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
Accute stretch and tachycardia are capable of inducing pathological excitation transcription coupling - an early invent before structural cardiac remodeling which transitions to heart failure. The sodium calcium exchanger is a key player in maintaining calcium homeostasis and is implicated in pathological signaling during heart failure.
Publication Title
The role of stretch, tachycardia and sodium-calcium exchanger in induction of early cardiac remodelling.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 48 Downloadable Samples
- NextSeq 500
Description
Primary human foreskin fibroblasts (HFF) were exposed to either salt stress (80mM KCl) or heat stress (44ºC). Newly transcribed RNA was labelled by adding 500µM 4-thiouridine (4sU) to the cell culture media for 1h. Total cellular RNA was isolated using Trizol. Newly transcribed RNA was purified following the protocol described in Raedle et al. JoVE 2013. Overall design: Newly transcribed RNA was labelled in one hour intervals during either salt or heat stress (prior to stress, 0-1h or 1-2h). All 4sU-RNA samples were sent for sequencing. Two independent biological replicates were analysed.
Publication Title
HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples