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GSE46246
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Transcription profiling by array of mouse male retinas to investigate IGF-I-induced chronic gliosis and retinal stress
Publication Title
Insulin-like growth factor I (IGF-I)-induced chronic gliosis and retinal stress lead to neurodegeneration in a mouse model of retinopathy.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
While blood transcriptional profiling has improved diagnosis and understanding of disease pathogenesis of adult tuberculosis (TB), no studies applying gene expression profiling of children with TB have been described so far. In this study, we have compared whole blood gene expression in childhood TB patients, as well as in healthy latently infected (LTBI) and uninfected (HC) children in a cohort of Warao Amerindians in the Delta Amacuro in Venezuela. We identified a 116-gene signature set by means of random forest analysis that showed an average prediction error of 11% for TB vs. LTBI and for TB vs. LTBI vs. HC in our dataset. Furthermore, a minimal set of only 9 genes showed a significant predictive value for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. Additionally, a minimal gene set of 42 genes with a comparable predictive value to the 116-gene set in both our dataset and the previously published literature cohorts for the comparsion of TB vs. LTBI vs. HC was identified. In order to identify a robust representative gene set that would hold stand among different ethnic populations, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these ten genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to diagnose 78% of the TB cases correctly with 100% specificity. We conclude that our data justify the further exploration of our signature set as biomarkers to diagnose childhood TB. Furthermore, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts.
Publication Title
A predictive signature gene set for discriminating active from latent tuberculosis in Warao Amerindian children.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Natural Killer (NK) cells present natural cytotoxicity against tumor cells, although their activity is increased after activation. NK cell activation depends on a complex intracellular signaling process mediated by activating and inhibitory receptors and the functional outcome depends on the integration of the activating and inhibitory signals received. Soluble cytokines and/or ligands on target cells bind the NK cell receptors, and hence, influence the final NK cell response: attack versus ignorance.
Publication Title
All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Macaca mulatta, Mus musculus, Homo sapiens, Rattus norvegicus
- 46 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina ratRef-12 v1.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Conserved and species-specific molecular denominators in mammalian skeletal muscle aging.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Aging is a complex phenomenon involving functional decline in multiple physiological systems. We focused on skeletal muscle to identify pathways that modulate function and healthspan by global expression profiles and specific mechanisms fundamental to aging processes. Our experimental design integrated comparative analysis of mice, rats, rhesus monkeys and humans and targeted three key time points during their lifespans. Pathways related to oxidative stress, inflammation and nutrient signaling, which function collectively to affect the quality and status of mitochondria, emerged across all species with age. Notably, mitochondrial transcript levels were better preserved in aging human muscle, suggesting an evolution-driven fitness more robust than in other species. The identification of these conserved pathways uncovers common molecular mechanisms intrinsic to health and lifespan, while unveiling of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.
Publication Title
Conserved and species-specific molecular denominators in mammalian skeletal muscle aging.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Aging is a complex phenomenon involving functional decline in multiple physiological systems. We focused on skeletal muscle to identify pathways that modulate function and healthspan by global expression profiles and specific mechanisms fundamental to aging processes. Our experimental design integrated comparative analysis of mice, rats, rhesus monkeys and humans and targeted three key time points during their lifespans. Pathways related to oxidative stress, inflammation and nutrient signaling, which function collectively to affect the quality and status of mitochondria, emerged across all species with age. Notably, mitochondrial transcript levels were better preserved in aging human muscle, suggesting an evolution-driven fitness more robust than in other species. The identification of these conserved pathways uncovers common molecular mechanisms intrinsic to health and lifespan, while unveiling of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.
Publication Title
Conserved and species-specific molecular denominators in mammalian skeletal muscle aging.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Aging is a complex phenomenon involving functional decline in multiple physiological systems. We focused on skeletal muscle to identify pathways that modulate function and healthspan by global expression profiles and specific mechanisms fundamental to aging processes. Our experimental design integrated comparative analysis of mice, rats, rhesus monkeys and humans and targeted three key time points during their lifespans. Pathways related to oxidative stress, inflammation and nutrient signaling, which function collectively to affect the quality and status of mitochondria, emerged across all species with age. Notably, mitochondrial transcript levels were better preserved in aging human muscle, suggesting an evolution-driven fitness more robust than in other species. The identification of these conserved pathways uncovers common molecular mechanisms intrinsic to health and lifespan, while unveiling of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.
Publication Title
Conserved and species-specific molecular denominators in mammalian skeletal muscle aging.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF- dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy. Examining the very early molecular events of T. cruzi cellular infection may provide disease biomarkers which will aid clinicians in patient assessment and identification of patient subpopulation at risk of developing Chagasic cardiomyopathy.
Publication Title
Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Double-stranded RNA-binding proteins are key elements in the intracellular localization of mRNA and its local translation. Staufen is a double-stranded RNA binding protein involved in the localised translation of specific mRNAs during Drosophila early development and neuronal cell fate. The human homologue Staufen1 forms RNA-containing complexes that include proteins involved in translation and motor proteins to allow their movement within the cell, but the mechanism underlying translation repression in these complexes is poorly understood. Here we show that human Staufen1-containing complexes contain essential elements of the gene silencing apparatus, like Ago1-3 proteins, and we describe a set of miRNAs specifically associated to complexes containing human Staufen1. Among these, miR124 stands out as particularly relevant because it appears enriched in human Staufen1 complexes and is over-expressed upon differentiation of human neuroblastoma cells in vitro. In agreement with these findings, we show that expression of human Staufen1 is essential for proper dendritic arborisation during neuroblastoma cell differentiation, yet it is not necessary for maintenance of the differentiated state, and suggest potential human Staufen1 mRNA targets involved in this process.
Publication Title
Human Staufen1 associates to miRNAs involved in neuronal cell differentiation and is required for correct dendritic formation.
Sample Metadata Fields
Cell line
View Samples