Filters
Technology
Platform
GSE33939
Homo sapiens
28 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are often caused by strains encoding Panton-Valentine leukocidin (PVL). PVL can cause lysis of polymorphonuclear leukocytes (PMNs) and other myeloid cells in vitro, a function considered widely as the primary means by which PVL might contribute to disease. However, at sublytic concentrations PVL can function as a PMN agonist. To better understand this phenomenon, we investigated the ability of PVL to alter human PMN function. PMNs exposed to PVL had enhanced capacity to produce superoxide in response to N-formyl-methionyl-leucyl-phenylalanine (fMLF), but unlike priming by lipopolysaccharide, this response did not require Toll-like receptor signal transduction. On the other hand, there was subcellular redistribution of NADPH oxidase components in PMNs following exposure of these cells to PVL - a finding consistent with priming. Priming of PMNs with other agonists such as IL-8 or GM-CSF altered the ability PVL to cause formation of pores in the plasma membranes of these cells. Microarray analysis revealed significant changes in the human PMN transcriptome following exposure to PVL, including up-regulation of molecules that regulate the inflammatory response. Consistent with the microarray data, mediators of the inflammatory response were released from PMNs after stimulation with PVL. We conclude that exposure of human PMNs to sublytic concentrations of PVL elicits a proinflammatory response that is regulated in part at the level of gene expression. We propose that PVL-mediated priming of PMNs enhances the host innate immune response.
Publication Title
Sublytic concentrations of Staphylococcus aureus Panton-Valentine leukocidin alter human PMN gene expression and enhance bactericidal capacity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Uremic media calcification is not only driven by systemic factors such as hyperphosphatemia, but also crticially dependent on vascular smooth muscle cells per se. We hypothesized that the different developmental origins of vscular smooth muscle cells might lead to a heterogeneous susceptibility to develop media calcification.
Publication Title
Heterogeneous susceptibility for uraemic media calcification and concomitant inflammation within the arterial tree.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Pseudomonas aeruginosa is an opportunistic pathogen that causes severe health problems. Despite intensive investigation, many aspects of microbial virulence remain poorly understood. We used a high-throughput, high-content, whole-organism, phenotypic screen to identify small molecules that inhibit P. aeruginosa virulence in C. elegans. Approximately half of the hits were known antimicrobials. A large number of hits were non-antimicrobial bioactive compounds, including the cancer chemotherapeutic 5-fluorouracil. We determined that 5-fluorouracil both transiently inhibits bacterial growth and reduces pyoverdine biosynthesis. Pyoverdine is a siderophore that regulates the expression of several virulence determinants and is critical for pathogenesis in mammals. We show that 5-fluorouridine, a downstream metabolite of 5-fluorouracil, is responsible for inhibiting pyoverdine biosynthesis. We also show that 5-fluorouridine, in contrast to 5-fluorouracil, is a genuine anti-virulent compound, with no bacteriostatic or bacteriocidal activity. To our knowledge, this is the first report utilizing a whole-organism screen to identify novel compounds with antivirulent properties effective against P. aeruginosa.
Publication Title
A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Zea mays
- 19 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
Aluminum toxicity is one of the major limiting factors for many crops worldwide. The primary symptom of Al toxicity syndrome is the inhibition of root growth, leading to poor water and nutrient absorption. The causes of this inhibition are still elusive, with several biochemical pathways being affected and with a significant variation between species. Most of the work done so far to investigate the genes responsible for Al tolerance used hydroponic culture. Here we evaluated plant responses using soil as substrate, which is a condition closer to the field reality.
Publication Title
Transcriptional profile of maize roots under acid soil growth.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Pseudomonas aeruginosa is a re-emerging opportunistic pathogen with broad antimicrobial resistance. We have previously reported that the major siderophore pyoverdine from this pathogen disrupts mitochondrial networks and induces a lethal hypoxic response in model host Caernorhabditis elegans. However, the mechanism of such cytotoxicity remained unclear. Here, we demonstrate that pyoverdine translocates into host cells, binding to host ferric iron sources. The reduction of host iron content disrupts mitochondrial function such as NADH oxidation and ATP production and activates mitophagy. This activates a specific immune response that is distinct from colonization-based pathogensis and exposure to downstream pyoverdine effector Exotoxin A. Host response to pyoverdine resembles that of a hypoxic crisis or iron chelator treatment. Furthermore, we demonstrate that pyoverdine is a crucial virulence factor in P. aerguinosa pathogenesis against cystic fibrosis patients; F508 mutation in human CFTR increases susceptibility to pyoverdine-mediated damage.
Publication Title
Pyoverdine, a siderophore from Pseudomonas aeruginosa, translocates into C. elegans, removes iron, and activates a distinct host response.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ikaros hypomorphic mice (IkL/L) show plasmacytoid dendritic cell (pDC) defects with an absence of pDCs in the peripheral organs and a reduction of pDCs in the bone marrow (BM). Moreover in vitro differentiation of pDC from IkL/L total BM cells is also defective.
Publication Title
Ikaros cooperates with Notch activation and antagonizes TGFβ signaling to promote pDC development.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To assess the importance of the Wnt pathway during T cell develoment, we generated a mouse line (R26-cat) in which high levels of active -catenin are maintained throughout T cell development. Young R26-cat mice (6-week-old) show a differentiation block at the CD4+CD8+ DP stage. All R26-cat mice develop T cell leukemias with a DP phenotype at 5-6 months of age.
Publication Title
β-Catenin activation synergizes with Pten loss and Myc overexpression in Notch-independent T-ALL.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
IlluminaHiSeq2000
Description
Deletions at 15q11.2 have been established to increase risk for multiple neurodevelopmental disorders (NDDs) including schizophrenia and epilepsy, yet show variable expressivity between individuals. To investigate the potential role of CYFIP1, a gene within the locus, we carried out knockdown experiments in human neural progenitor cells derived from 15q11.2 neutral induced pluripotent stem cells. Transcriptional profiling and cellular assays support a prominent role for CYFIP1 in cytoskeletal remodeling across all lines examined. Validating the utility of this model for study of disease, genes implicated in schizophrenia and epilepsy but not other disorders or traits unrelated to the deletion, were enriched among mRNAs dysregulated following knockdown. Importantly, and consistent with the variable expressivity of 15q11.2 deletions, the magnitude of disease-related effects varied between donor lines. Towards mechanisms, FMRP targets and synaptic genes were overrepresented among dysregulated mRNAs and as such may contribute to the schizophrenia and epilepsy effects we observe. Further model validation, and new candidate epilepsy genes, comes from machine-learning analyses showing a striking similarity between a subset of dysregulated transcripts and well-established epilepsy genes. Results provide support for an important contribution of CYFIP1 in 15q11.2 mediated risk for NDDs and demonstrate that disease-related biological signatures are evident prior to neuronal differentiation. This new human model of disease will be useful in identifying compounds that could ameliorate outcomes in deletion carriers. Overall design: Investigation of CYFIP1 shRNA knockdown in three neural progenitor cell lines derived from induced pluripotent stem cells (3 control samples and 3 knockdown samples analyzed in each line)
Publication Title
Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail gene expression changes in Hs 294T human melanoma cells after treatment with elesclomol alone, or in combination with paclitaxel, to aide in identifing the mechnism of action of elesclomol.
Publication Title
Elesclomol induces cancer cell apoptosis through oxidative stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail gene expression changes in Hs 294T human melanoma cells after treatment with elesclomol alone, or in combination with NAC, to aide in identifing the mechnism of action of elesclomol.
Publication Title
Elesclomol induces cancer cell apoptosis through oxidative stress.
Sample Metadata Fields
No sample metadata fields
View Samples