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Escherichia coli str. k-12 substr. mg1655
12 Downloadable Samples
Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Bacteria are extremely versatile organisms which rapidly adapt to changing environments. When Escherichia coli cells switch from planktonic growth to biofilm, flagellum formation is turned off, and the production of fimbriae and extracellular polysaccharides is switched on. Here we show that BolA protein is a new bacterial transcription factor which modulates the switch from planktonic to sessile lifestyle. BolA negatively modulates flagella biosynthesis and thus swimming capacity. Furthermore, BolA overexpression favors biofilm formation and involvesinvolving fimbriae-like adhesins and curli production. Our results unraveled for the first time that BolA is a protein with high affinity to DNA, involved in the regulation of several genes of E. coli at a genome-wide scale level. Moreover, this observation further demonstrated that the most significant targets of this protein involved a complex network of genes encoding proteins extremely necessary in biofilm development processes. Herein we propose that BolA is a motile/adhesive transcriptional switch, specifically involved in the transition between the planktonic and the attachment stage of biofilm formation process.
Publication Title
BolA is a transcriptional switch that turns off motility and turns on biofilm development.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE57801- Mus musculus, Drosophila melanogaster
- 71 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 31 Downloadable Samples
Illumina HiSeq 2500
Description
We report a pilot investigation for poly-A RNAs differentially expressed during Mycobacterium tuberculosis infection. Participation in this investigation from March 2010 to July 2013 was voluntary, only subjects that were >18 years old and that informed written consent were considered eligible. The recruitment of tuberculosis (TB) patients was done at public hospitals in Rio de Janeiro, Brazil. The diagnostic criteria for active pulmonary tuberculosis was at least one AFB (acid-fast bacilli) -positive sputum sample for M. tuberculosis and/or positive sputum culture and/or compatible clinical evolution for pulmonary TB and less than 15 days of anti-TB treatment and was in accordance with those of the Brazilian Ministry of Health. Blood was collected from recent close contacts (rCt) and active tuberculosis (TB) index cases (n=6). Latent TB infection (LTBI) was accessed by both tuberculin skin test (TST, cut-off = 5mm) and in house interferon-gamma release assays (IGRA, cut-off = 100 pg/ml), therefore, 12 rCt were classified as uninfected controls and 16 with LTBI. Subsequently, the sequencing was performed following the standard protocols on Illumina HiSeq® 2500 Sequencing System (Illumina, San Diego, CA) running 100 bp paired-end reads (PE100) and generating approximately 30 million reads passing filter for each sample to produce the mRNA reads. Mining these RNAseq data, highly prominent modulation of DOCK9, EPHA4, and NPC2 mRNA expression was observed in the TB samples, indicating that they might have a role in TB pathogenesis. These differential modulations upon M. Tuberculosis infection were further validated by additional evidences in larger cohorts from different geographical areas. Overall design: We collected blood samples from the recent close contacts (rCt) at the recruitment and monitored them for 1-year. All TB participants were treatment-naïve. An infection mRNA signature was derived from whole blood RNA sequencing data by comparing TB and uninfected rCt. We selected the 3 most prominent genes, by area under the ROC curve analysis, for additional validations. Some of the LTBI participants also showed the mRNA infection profile.
Publication Title
Transcriptomic Biomarkers for Tuberculosis: Evaluation of <i>DOCK9. EPHA4</i>, and <i>NPC2</i> mRNA Expression in Peripheral Blood.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recognition and response to gram-positive bacteria by macrophages and dendritic cells is mediated in part through TLR2. We found that that Streptococcus pneumoniae cell wall fragments, containing primarily peptidoglycan and teichoic acids, induced prodigious secretion of IL-10 from macrophages and dendritic cells and was dependent on TLR2 and NOD2, a cytoplasmic CARD-NACHT-LRR protein encoded by Card15. IL-10 secretion in response to cell walls was also dependent on RICK/RIP2, a kinase associated with NOD2, and MYD88 but independent of the ERK/p38 pathway. The reduction of IL-10 secretion by cell wall-activated NOD2-deficient myeloidderived cells translated into downstream effects on IL-10 target gene expression and elevations in subsets of pro-inflammatory cytokine expression normally restrained by autocrine/paracrine effects of IL-10. Since NOD2 is linked to aberrant immune responses in Crohns Disease patients bearing mutations in CARD15, the temporal and quantitative effects of the TLR2/NOD/RICK pathway on IL-10 secretion may affect homeostatic control of immune responses to gram-positive bacteria.
Publication Title
The TLR2-MyD88-NOD2-RIPK2 signalling axis regulates a balanced pro-inflammatory and IL-10-mediated anti-inflammatory cytokine response to Gram-positive cell walls.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
Understanding the mechanisms by which cells respond to chemotherapeutics is key to identifying means to improve therapy effiicacy while reducing systemic toxicity of these widely used classes of drugs. While determining the role of NRF2-GSH and ER stress in cells exposed to alkylating compounds such as methyl-methanesulfonate (MMS), we asked if these pathways could also be a general cell damage response relevant to other clinically used chemotherapeutics or if it is an alkylation specific response. With this intent, we performed RNA sequencing of MDA-MB231 breast cancer and U2OS osteosarcoma cells lines treated for 8 hours with a topoisomerase II inhibitor etoposide (20 µM), the antimitotic beta-tubulin-interacting drug paclitaxel (0.2 µM), doxorubicin (1 µM) and compared to MMS (40 µg/mL) treated cells. Doses represent IC50 level after 72 hours exposure. We observed that even though non-alkylating drugs, especially etoposide, caused an increase in the mRNA expression of some NRF2 and ER stress signaling markers, the number and magnitude of upregulation of genes markers in either pathway was more pronounced in alkylation treatments compared to other drugs. This indicates that alterations in NRF2 and ER stress pathways could be more likely associated with differential sensitivity to alkylating chemotherapies. Overall design: MDA-MB231 breast cancer and U2OS osteosarcoma cells lines were treated with the 72 h IC50 dose of etoposide (20 µM), paclitaxel (0.2 µM), doxorubicin (1 µM) or MMS (40 µg/mL) for 8 h, and RNA was extracted and analyzed.
Publication Title
Alkylating Agent-Induced NRF2 Blocks Endoplasmic Reticulum Stress-Mediated Apoptosis via Control of Glutathione Pools and Protein Thiol Homeostasis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 192 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Listeriosis is an infectious disease caused by the intracellular bacterium Listeria monocytogenes. To control the infection effectively, the host immune response is directed by intercellular signalling molecules called cytokines that are produced by immune cells following sensing of the bacteria. In this study we used gene expression analysis to examine complex immune signalling networks in the blood and tissues of mice infected with L. monocytogenes. We show that a large set of genes are perturbed in both blood and tissue upon infection and that the transcriptional responses in both are enriched for pathways of the immune response. From these data we also observe an important signalling network emerge from a group of cytokines called interferons (IFNs). Previous findings suggest that different IFN family members can determine the balance between successful and impaired immune responses to L. monocytogenes and several other bacterial infections. Using mice deficient for the detrimental type I IFN signalling pathway we show that IFN-inducible genes are differentially regulated at different times upon infection but also present at much lower levels in uninfected mice highlighting how dysregulation of this network in the steady state may determine the outcome of this bacterial infection.
Publication Title
Analysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumor cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of oxygen. This metabolic reprogramming, known as the Warburg effect, provides tumor cells with the substrates and redox potential required for the generation of biomass. Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. SIRT3 loss promotes a metabolic profile consistent with high glycolysis required for anabolic processes in vivo and in vitro. Mechanistically, SIRT3 mediates metabolic reprogramming independently of mitochondrial oxidative metabolism and through HIF1a, a transcription factor that controls expression of key glycolytic enzymes. SIRT3 loss increases reactive oxygen species production, resulting in enhanced HIF1a stabilization. Strikingly, SIRT3 is deleted in 40% of human breast cancers, and its loss correlates with the upregulation of HIF1a target genes. Finally, we find that SIRT3 overexpression directly represses the Warburg effect in breast cancer cells. In sum, we identify SIRT3 as a regulator of HIF1a and a suppressor of the Warburg effect.
Publication Title
SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumor cells that give rise to metastatic disease are a primary cause of cancer-related death and have not been fully elucidated in patients with lung cancer. Here, we addressed this question by using tissues from a mouse that develops metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. We identified a metastasis-prone population of tumor cells that differed from those with low metastatic capacity on the basis of having sphere-forming capacity in Matrigel cultures, increased expression of CD133 and Notch ligands, and relatively low tumorigenicity in syngeneic mice. Knockdown of jagged1 or pharmacologic inhibition of its downstream mediator phosphatidylinositol 3-kinase abrogated the metastatic but not the tumorigenic activity of these cells. We conclude from these studies on a mouse model of lung adenocarcinoma that CD133 and Notch ligands mark a population of metastasis-prone tumor cells and that the efficacy of Notch inhibitors in metastasis prevention should be explored.
Publication Title
The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200-dependent pathway in mice.
Sample Metadata Fields
Specimen part
View Samples