Filters
Technology
Platform
GSE13205
Homo sapiens
20 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Septic patients treated in the intensive care unit (ICU) often develop multiple organ failure including persistent skeletal muscle dysfunction which results in the patients protracted recovery process. We have demonstrated that muscle mitochondrial enzyme activities are impaired in septic ICU patients resulting in decreased cellular energy which will interfere with muscle function and metabolism. Here we use detailed phenotyping and genomics to elucidate mechanisms leading to these impairments. Methodology/Principle Findings Utilising biopsy material from seventeen patients and ten age-matched controls we demonstrate that neither mitochondrial in vivo protein synthesis nor expression of mitochondrial genes are compromised. Indeed, there was partial activation of the mitochondrial biogenesis pathway involving NRF2?/GABP and its target genes TFAM, TFB1M and TFB2M yet clearly this failed to maintain mitochondrial function. We therefore utilised transcript profiling and pathway analysis of ICU patient skeletal muscle to generate insight into the molecular defects driving loss of muscle function and metabolic homeostasis. Gene ontology analysis of Affymetrix analysis demonstrated substantial loss of muscle specific genes, a global oxidative stress response related to most probably cytokine signalling, altered insulin related signalling and a substantial overlap between patients and muscle wasting/inflammatory animal models. MicroRNA 21 processing appeared defective suggesting that post-transcriptional protein synthesis regulation is altered by disruption of tissue microRNA expression. Finally, we were able to demonstrate that the phenotype of skeletal muscle in ICU patients is not merely one of inactivity, it appears to be an actively remodelling tissue, influenced by several mediators, all of which may be open to manipulation with the aim to improve clinical outcome. Conclusions/Significance This first combined protein and transcriptome based analysis of human skeletal muscle obtained from septic patients demonstrated that losses of mitochondria and muscle mass are accompanied by sustained protein synthesis (anabolic process) while dysregulation of transcription programmes appears to fail to compensate for increased damage and proteolysis. Our analysis identified both validated and novel clinically tractable targets to manipulate these failing processes and pursuit of these could lead to new potential treatments.
Publication Title
Dysregulation of mitochondrial dynamics and the muscle transcriptome in ICU patients suffering from sepsis induced multiple organ failure.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rectus abdominis muscle biopsies were obtained from 65 upper gastrointestinal (UGI) cancer patients during open surgery and RNA profiling was performed on a subset of this cohort (n=21) using the Affymetrix U133+2 platform with the aim of identifying biomarkers of cancer related muscle wasting.
Publication Title
Using transcriptomics to identify and validate novel biomarkers of human skeletal muscle cancer cachexia.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Escherichia coli
- 15 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Comparison of gene expression profile of E. coli 83972 grown in minimal lab media, in urine and in 3 individual patients.
Publication Title
Global gene expression profiling of the asymptomatic bacteriuria Escherichia coli strain 83972 in the human urinary tract.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Identification of genes differentially expressed in roots of Arabidopsis Col-0 and ndr1-1 mutants 48 h post inoculation with the fungal pathogen Verticillium longisporum.
Publication Title
Susceptibility to Verticillium longisporum is linked to monoterpene production by TPS23/27 in Arabidopsis.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Hordeum vulgare
- 21 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
Detection of single feature polymorphisms comparing five barley genotypes. Gene expression under unstressed and drought stressed conditions.
Publication Title
Detecting single-feature polymorphisms using oligonucleotide arrays and robustified projection pursuit.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
The in vitro effect of infection with different strains of Toxoplasma gondii was tested 24 hours after infection of Human Foreskin Fibroblasts (HFF)
Publication Title
Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We used microarray to compare global gene expression profiles between 5 GNAQ/11 mutant uveal melanoma cell lines (GNAQ mutant: 92-1, omm1.3, mel270; GNA11 mutant: omm-gn11 and upmd-1) and 5 GNAQ/11 wild type melanoma cell lines(sk-mel-2, mm415, mm485, sk-mel-5 and mum2c). Uveal melanoma is the most common intraocular tumor that mainly metastasizes to the liver in about 50% patients. Over 80% of UMs harbor GNAQ or GNA11 activating mutation. Currently there is no effective treatment available for UM patients. Results provide insights into downstream signaling of oncogenic GNAQ/11 and identification of therapeutic targets in UM.
Publication Title
RasGRP3 Mediates MAPK Pathway Activation in GNAQ Mutant Uveal Melanoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 25 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Differential induction of TLR3-dependent innate immune signaling by closely related parasite species.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
The closely related protozoan parasites Toxoplasma gondii and Neospora caninum display similar life cycles, subcellular ultrastructure, invasion mechanisms, metabolic pathways, and genome organization, but differ in their host range and disease pathogenesis. Type II () interferon has long been known to be the major mediator of innate and adaptive immunity to Toxoplasma infection, but genome-wide expression profiling of infected host cells indicates that Neospora is a potent activator of the type I (/) interferon pathways typically associated with antiviral responses. Infection of macrophages from mice with targeted deletions in various innate sensing genes demonstrates that host responses to Neospora are dependent on the toll-like receptor Tlr3 and the adapter protein Trif. Consistent with this observation, RNA from Neospora elicits TLR3-dependent type I interferon responses when targeted to the host endo-lysosomal system. Although live Toxoplasma fail to induce type I interferon, heat-killed parasites do trigger this response, albeit much weaker than Neospora, and co-infection studies reveal that T. gondii actively suppresses the production of type I interferon. These findings reveal that eukaryotic pathogens can be potent inducers of type I interferon and that related parasite species interact with this pathway in distinct ways.
Publication Title
Differential induction of TLR3-dependent innate immune signaling by closely related parasite species.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
The closely related protozoan parasites Toxoplasma gondii and Neospora caninum display similar life cycles, subcellular ultrastructure, invasion mechanisms, metabolic pathways, and genome organization, but differ in their host range and disease pathogenesis. Type II () interferon has long been known to be the major mediator of innate and adaptive immunity to Toxoplasma infection, but genome-wide expression profiling of infected host cells indicates that Neospora is a potent activator of the type I (/) interferon pathways typically associated with antiviral responses. Infection of macrophages from mice with targeted deletions in various innate sensing genes demonstrates that host responses to Neospora are dependent on the toll-like receptor Tlr3 and the adapter protein Trif. Consistent with this observation, RNA from Neospora elicits TLR3-dependent type I interferon responses when targeted to the host endo-lysosomal system. Although live Toxoplasma fail to induce type I interferon, heat-killed parasites do trigger this response, albeit much weaker than Neospora, and co-infection studies reveal that T. gondii actively suppresses the production of type I interferon. These findings reveal that eukaryotic pathogens can be potent inducers of type I interferon and that related parasite species interact with this pathway in distinct ways.
Publication Title
Differential induction of TLR3-dependent innate immune signaling by closely related parasite species.
Sample Metadata Fields
Specimen part
View Samples