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GSE27626
Zea mays
12 Downloadable Samples
Affymetrix Maize Genome Array (maize)
Description
Phytophthora cinnamomi is a devastating soil-borne oomycete with a very broad host range however there remains a major gap in the understanding of plant resistance responses to the pathogen, furthermore, necrotrophic plant-pathogen interactions, particularly those of root pathogens, remain poorly understood. Zea mays exhibits non-host resistance to the pathogen and has been well characterised as a model species. Using the maize Affymetrix GeneChip array we conducted genome-wide gene expression profiling to elucidate the defence genes and pathways which are induced in the root tissue of a resistant plant species to the pathogen.
Publication Title
Transcriptional profiling of Zea mays roots reveals roles for jasmonic acid and terpenoids in resistance against Phytophthora cinnamomi.
Sample Metadata Fields
Specimen part, Time
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
Illumina HiSeq 4000
Description
How artificial environmental cues are biologically integrated and transgenerationally inherited is still poorly understood. Here, we investigate the mechanisms of inheritance of reproductive outcomes elicited by the model environmental chemical Bisphenol A (BPA) in C. elegans. We show that BPA exposure causes the derepression of an epigenetically silenced transgene in the germline for 5 generations, regardless of ancestral response. ChIP-seq, histone modifications quantitation, and immunofluorescence assays revealed that this effect is associated with a reduction of the repressive marks H3K9me3 and H3K27me3 in whole worms and in germline nuclei in the F3 as well as with reproductive dysfunctions including germline apoptosis and embryonic lethality. Furthermore, targeting of the Jumonji demethylases JMJD-2 and JMJD-3/UTX-1 restores H3K9me3 and H3K27me3 levels, respectively, and fully alleviates the BPA-induced transgenerational effects. Together, our results demonstrate the central role of repressive histone modifications in the inheritance of reproductive defects elicited by a common environmental chemical exposure. Overall design: First generation C. elegans were exposed to either water, DMSO or BPA for for 48 hours, third generation (F3) worms were used for RNA-seq experiments.Total RNA was extracted from needle-dissected gonads of F3 adult worms in 4 replicates of H2O, DMSO, and BPA-exposed P0 nematodes.
Publication Title
The Memory of Environmental Chemical Exposure in C. elegans Is Dependent on the Jumonji Demethylases jmjd-2 and jmjd-3/utx-1.
Sample Metadata Fields
Treatment, Subject
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We used Arabidopsis full-genome microarrays to characterize plant transcript accumulations at different stages of infection with the biotrophic oomycete downy mildew pathogen, Hyaloperonospora arabidopsidis : initiation (< 1 dpi) and maintenance of infection (> 4 dpi).
Publication Title
An Arabidopsis (malectin-like) leucine-rich repeat receptor-like kinase contributes to downy mildew disease.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Temporal changes of the expression levels of the complete human transcriptome during the first 24 hours following infection of IFN-pre-treated macrophages. This approach has allowed us to identify genes involved in the IFN signaling that have an impact on HIV-1 infection of macrophages
Publication Title
TRAF6 and IRF7 control HIV replication in macrophages.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Mice representing phenotypic extremes of airway hyperreactivity and goblet cell metaplasia post-Sendai virus infection were identified from a 500 mouse F2 cohort (CB6F2/J). Whole lung RNA from 3 mice at each extreme was analyzed via microarray for gene expression. Subsequent pairwise comparisons between arrays allowed the identification of genes differentially expressed with respect to the disease phenotypes (airway hyperreactivity and goblet cell metaplasia).
Publication Title
Genetic segregation of airway disease traits despite redundancy of calcium-activated chloride channel family members.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca fascicularis
- 124 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TSLP pathway blockade is a potential strategy for asthma treatment, as TSLP modulates cytokine production by mast cells and regulates the activation of dendritic cells (DCs), which prime the differentiation of nave T cells into inflammatory Th2 cells. To assess the effect of TSLPR blockade on the development of allergic inflammation and bronchoconstriction in Cynomolgus monkeys after Ascaris suum allergen challenge. Antibodies against human TSLPR were generated and confirmed to be cross-reactive to cynomolgus. Animals were dosed weekly with either vehicle (n=8) or TSLPR HuMAb (n=8) for 6 weeks and their responses to A.Suum challenge at baseline, week 2 and week 6 were assessed. Antibody-treated animals showed reduced bronchoalveolar lavage (BAL) eosinophil counts (p=0.04), reduced lung resistance (RL) area under the curve (p=0.04), and reduced IL-13 cytokine levels in BAL fluid (p=0.03) in response to challenge at 6 weeks compared to vehicle-treated animals. To understand the molecular changes underlying these differences, BAL fluid samples pre- and post-challenge were profiled using microarrays. Genes up-regulated by allergen challenge overlapped strongly with 11 genes up-regulated in DCs when stimulated by TSLP (TSLP-DC signature). The number of genes differentially expressed in response to challenge was reduced in aTSLPR-treated animals after 6 weeks relative to vehicle-treated animals. Expression of the TSLP-DC gene signature was also significantly reduced in aTSLPR-treated animals (p = 0.05). These results demonstrate promising efficacy for TSLPR blockade in an allergen challenge model where TSLP activation of DCs may play a key role.
Publication Title
Thymic stromal lymphopoietin receptor blockade reduces allergic inflammation in a cynomolgus monkey model of asthma.
Sample Metadata Fields
Disease, Subject, Time
View Samples- Mus musculus
- 84 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Polyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is used to exacerbate inflammation in lung injury models. Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice. Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of COPD patients. These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways. Poly I:C induced increased numbers of neutrophils and NK cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively. Using gene set variation analysis on representative data sets, gene sets defined by poly I:C-induced DEGs were enriched in the molecular profiles of chronic obstructive pulmonary disease (COPD), but not idiopathic pulmonary fibrosis patients. Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.
Publication Title
Double-stranded RNA induces molecular and inflammatory signatures that are directly relevant to COPD.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We used Arabidopsis full-genome microarrays to characterize plant transcript accumulations in map65-3 and ugt76b1 mutants, 3 days after water treatment and inoculation with the biotrophic oomycete downy mildew pathogen, Hyaloperonospora arabidopsidis (Hpa)
Publication Title
The Arabidopsis microtubule-associated protein MAP65-3 supports infection by filamentous biotrophic pathogens by down-regulating salicylic acid-dependent defenses.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Store operated calcium entry (SOCE) downstream of T cell receptor (TCR) activation in T lymphocytes has been shown to be mediated mainly through the Calcium Release Activated Calcium (CRAC) channel. Here, we compared the effects of a novel, potent and selective CRAC inhibitor, 2,6-Difluoro-N-{5-[4-methyl-1-(5-methyl-thiazol-2-yl)-1,2,5,6-tetrahydro-pyridin-3-yl]-pyrazin-2-yl}-benzamide (RO2959), on T cell effector functions with that of a previously reported CRAC channel inhibitor, YM-58483, and a calcineurin inhibitor Cyclosporin A (CsA). Using both electrophysiological and calcium-based fluorescence measurements, we showed that RO2959 is a potent SOCE inhibitor that blocked an IP3-dependent current in CRAC-expressing RBL-2H3 cells and CHO cells stably expressing human Orai1 and Stim1, as well as SOCE in human primary CD4+ T cells triggered by either TCR stimulation or thapsigargin treatment. Furthermore, we demonstrated that RO2959 completely inhibited cytokine production as well as T cell proliferation mediated by TCR stimulation or MLR (Mixed Lymphocyte Reaction). Lastly, we showed by gene expression array analysis that RO2959 potently blocked TCR triggered gene expression and T cell functional pathways similar to CsA and FK506. Thus, both from a functional and transcriptional level, our data provide evidence that RO2959 is a novel and selective CRAC inhibitor that potently inhibits human T cell functions.
Publication Title
Characterization of a novel CRAC inhibitor that potently blocks human T cell activation and effector functions.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Sustained Ca2+ entry into CD4+CD8+ double-positive thymocytes is required for positive selection. We identified a voltage-gated Na+ channel (VGSC), essential for positive selection of CD4+ T cells. Pharmacological inhibition of VGSC activity inhibited sustained Ca2+ influx induced by positive-selecting ligands and in vitro positive selection of CD4+ but not CD8+ T cells. In vivo shRNA knockdown of Scn5a specifically inhibited positive selection of CD4+ T cells. Ectopic expression of VGSC in peripheral AND CD4+ T cells bestowed the ability to respond to a positively selecting ligand, directly demonstrating VGSC expression was responsible for increased sensitivity. Thus active VGSCs in thymocytes provides a mechanism by which a weak positive selecting signal can induce sustained Ca2+ signals required for CD4+ T cell development.
Publication Title
A voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells.
Sample Metadata Fields
Specimen part
View Samples