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SRP055410
Pseudomonas aeruginosa
9 Downloadable Samples
Illumina HiSeq 2500
Description
Extremely slow growth imposed by energy limitation is a ubiquitous but poorly understood physiological state for microbes. We used oxygen limitation to impose this state on Pseudomonas aeruginosa and measured newly synthesized proteins using a time-selective proteome labeling method (BONCAT) to identify relevant regulators and metabolic pathways. We further characterized one upregulated protein that has no homology to any known protein domains. This small, acidic protein is post-transcriptionally regulated and physically interacts with RNA polymerase, binding near the secondary channel during transcription elongation, and leading to widespread effects on gene expression. For some genes, the impacts on transcript and protein levels are different, suggesting possible modulation of translation as well. These effects have phenotypic consequences, as deletion of the gene affects biofilm formation, secondary metabolite production, and fitness in fluctuating conditions. Based on these phenotypes, we have designated the protein SutA (survival under transitions). Overall design: Profiles of rRNA-depleted total RNA from WT, ?sutA (PA14_69770), and SutA-overexpressing cells grown late exponential phase in minimal medium containing pyruate as the carbon source, in triplicate
Publication Title
SutA is a bacterial transcription factor expressed during slow growth in Pseudomonas aeruginosa.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We found that 5-Aza-dC/decitabine induces various prosurvival pathways (JAK-STAT-, NFkB-, MEK/ERK- and PI3K/AKTpathway) in cHL cell lines. Inhibition of these pathways with specific small molecular weight inhibitors potentiates the antitumor effect of 5-Aza-dC.
Publication Title
Activation of oncogenic pathways in classical Hodgkin lymphoma by decitabine: A rationale for combination with small molecular weight inhibitors.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The goal of this study was to identify the transcriptional mechanisms involved in the activation of the immune system by QS-21, a triterpene glycoside purified from the bark of Quillaja saponaria which has adjuvant activity in vivo. Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the Malaria and Zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169+ resident macrophages of the draining lymph node where it elicited a local innate immune response. Depletion of these cells abrogated QS-21-mediated innate cell recruitment to the lymph node, dendritic cell (DC) phenotypic maturation as well as the adjuvant effect on T cell and antibody responses to co-administered antigens. DCs rather than lymph node-resident macrophages were directly involved in T cell priming by QS-21 as revealed by the decrease in antigen-specific T cell response in Batf3/ mice. Further analysis showed that the adjuvant effect of QS-21 depended on the integration of Caspase-1 and MyD88 pathways, at least in part through the local release of HMGB1. Taken together, this work unravels the key role of lymph node sentinel macrophage in controlling the adjuvant effect of a molecule proven to improve vaccine response in humans
Publication Title
Central Role of CD169<sup>+</sup> Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CMPF is elevated in diabetes and is associated with impaired insulin secretion. We used microarrays to determine the effect of CMPF on gene expression in isolated islets.
Publication Title
The furan fatty acid metabolite CMPF is elevated in diabetes and induces β cell dysfunction.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Dysfunctional mitochondria and generation of reactive oxygen species (ROS) promote chronic diseases, which have spurred interest in the molecular mechanisms underlying these conditions. Previously, we have demonstrated that disruption of post-translational modification of proteins with ß-linked N-acetylglucosamine (O- glcnAcylation) via overexpression of the O-glcnAc–regulating enzymes O- glcnAc transferase (OGT) or O- glcnAcase (OGA) impairs mitochondrial function. Here, we report that sustained alterations in O- glcnAcylation either by pharmacological or genetic manipulation also alters metabolic function. Sustained O-glcnAc elevation in SH-SY5Y neuroblastoma cells increased OGA expression and reduced cellular respiration and ROS generation. Cells with elevated O-glcnAc levels had elongated mitochondria and increased mitochondrial membrane potential, and RNA-Seq in SH-SY5Y cells indicated transcriptome reprogramming and down regulation of the NRF2-mediated antioxidant response. Sustained O-glcnAcylation in mice brain and liver validated the metabolic phenotypes observed in the cells, and OGT knockdown in the liver elevated ROS levels, impaired respiration, and increased the NRF2 antioxidant response. Moreover, elevated O-glcnAc levels promoted weight loss and lowered respiration in mice and skewed the mice toward carbohydrate-dependent metabolism as determined by indirect calorimetry. In summary, sustained elevation in O-glcnAcylation coupled with increased OGA expression reprograms energy metabolism, a finding that has potential implications for the etiology, development, and management of metabolic diseases. Overall design: SY5Y cells were adapted to long term O-glcnAcase (OGA) inhibition using the specific OGA inhibitor Thiamet-G (tmg) or glucosamine treatment for 3 weeks. After adaptation to the growth conditions, cells were harvest and RNA isolated for Next Generation RNA sequencing. Briefly, cDNA library was prepared using Illumina TruSeq Stranded mRNA sample preparation kit (Illumina) as manufacturer's instruction. Total RNA was isolated using the same method as previously described and 800 ng of the total RNA per reaction was used to initiate the protocol. The quality of RNA sequencing results was first assessed using FastQC (0.11.2). RSEM (1.2.22) was utilized to align the reads to the human reference genome HG38 and to calculate gene expression values. EdgeR (3.14.0) was then used to normalize the expression values using the TMM-method (weighted trimmed mean of M-values), and for differential expression analyses. First, the negative binomial conditional common likelihood was maximized to estimate a common dispersion value across all genes (estimateCommonDisp). Next, tagwise dispersion values were estimated by an empirical Bayes method based on weighted conditional maximum likelihood (estimateTagwiseDisp). Finally, the differentially gene expression was calculated by computing genewise exact tests for differences in the means between two groups of negative-binomially distributed counts. Hierarchical clustering analysis was determined using Euclidean distance. The following R-packages were utilized for calculations and visualizations: plots and edgeR.
Publication Title
Sustained <i>O-</i>GlcNAcylation reprograms mitochondrial function to regulate energy metabolism.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Studying dynamic transcripts in single cells (SC) requires large numbers of timed samples. We report an easy to use protocol to stabilize RNA in intact SCs without perturbing transcriptional patterns, and demonstrate its applicability for SC transcriptome assays with cells and tissue. We identify a gene-specific hierarchical pattern of all-or-none transcript induction elicited by different concentrations of pulsatile hormone stimuli in pituitary gonadotropes. Overall design: SC Mini Drop-seq experiments were performed on two samples from dissociated human cortical tissue: one is neocortex from a glioblastoma multiforme (GBM, tumor), the other is normal neocortex adjacent to the tumor.
Publication Title
Single-cell stabilization method identifies gonadotrope transcriptional dynamics and pituitary cell type heterogeneity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
FoxO6 is expressed in the brain, craniofacial region and somite, but the precise role of FoxO6 in craniofacial development remain unknown. We found that FoxO6 is expressed specifically in craniofacial tissues and FoxO6-/- mice undergo expansion of the face, frontal cortex, olfactory component and skull.
Publication Title
FoxO6 regulates Hippo signaling and growth of the craniofacial complex.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression was studied from the blood derived RNAs of the Finnish family members as well as from 10 controls using GeneChip Human Genome U133 Plus2 (Affymetrix). Eight out of 10 family members in the expression analysis are heterozygous for the NPAT c.2437-2438delAG, three of which are NLPHL cases.
Publication Title
Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 272 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This dataset is composed of the unique patients (276; at the Day 1 timepoint) that are present in the six other GEO datasets published by Hector Wong and the Genomics of Pediatric SIRS and Septic Shock Investigators. This dataset thus includes all unique patients from GSE4607, GSE8121, GSE9692, GSE13904, GSE26378, and GSE26440. These are only from the Day 1 timepoint.
Publication Title
A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set.
Sample Metadata Fields
Specimen part, Disease
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Examined the expression effects of supplementing Drosophila food on heart and nephrocyte complexes
Publication Title
Diet-Induced Podocyte Dysfunction in Drosophila and Mammals.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples