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GSE35558
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Background: Clinical trial and epidemiological data support that the cardiovascular effects of estrogen are complex, including a mixture of both potentially beneficial and harmful effects. In animal models, estrogen protects females from vascular injury and inhibits atherosclerosis. These effects are mediated by estrogen receptors (ERs), which when bound to estrogen can bind to DNA to directly regulate transcription. ERs can also activate several cellular kinases by inducing a rapid non-nuclear signaling cascade. However, the biologic significance of this rapid signaling pathway has been unclear.
Publication Title
Rapid estrogen receptor signaling is essential for the protective effects of estrogen against vascular injury.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa pao1
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Anticipating the risk for infectious disease during space exploration and habitation is a critical factor to ensure safety, health and performance of the crewmembers. As a ubiquitous environmental organism that is occasionally part of the human flora, Pseudomonas aeruginosa could pose a health hazard for the immuno-compromised astronauts. In order to gain insights in the behavior of P. aeruginosa in spaceflight conditions, two spaceflight-analogue culture systems, i.e. the rotating wall vessel (RWV) and the random position machine (RPM), were used. Microarray analysis of P. aeruginosa PAO1 grown in the low shear modeled microgravity (LSMMG) environment of the RWV compared to the normal gravity control (NG), revealed a regulatory role for AlgU (RpoE). Specifically, P. aeruginosa cultured in LSMMG exhibited increased alginate production and up-regulation of AlgU-controlled transcripts, including those encoding stress-related proteins. This study also shows the involvement of Hfq in the LSMMG response, consistent with its previously identified role in the Salmonella LSMMG- and spaceflight response. Furthermore, cultivation in LSMMG increased heat- and oxidative stress resistance and caused a decrease in the culture oxygen transfer rate. Interestingly, the global transcriptional response of P. aeruginosa grown in the RPM was similar to that in NG. The possible role of differences in fluid mixing between the RWV and RPM is discussed, with the overall collective data favoring the RWV as the optimal model to study the LSMMG-response of suspended cells. This study represents a first step towards the identification of specific virulence mechanisms of P. aeruginosa activated in response to spaceflight-analogue conditions, and could direct future research regarding the risk assessment and prevention of Pseudomonas infections for the crew in flight and the general public.
Publication Title
Response of Pseudomonas aeruginosa PAO1 to low shear modelled microgravity involves AlgU regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of an interleukin 13-induced epigenetic signature in allergic airway inflammation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Asthma is a common chronic inflammatory airway condition with a strong genetic and inheritability component, as siblings and first-degree relatives of those with the disease are often affected.
Publication Title
Identification of an interleukin 13-induced epigenetic signature in allergic airway inflammation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
E-cig use is continuing to increase, particularly among youth never-smokers, and is used by some smokers to quit. The acute and chronic toxicity of e-cig use is unclear generally in the context of increasing reports of inflammatory-type pneumonia in some e-cig users. To assess lung effects of e-cigs without nicotine or flavors, we conducted a pilot study with serial bronchoscopies over 4 weeks in 30 never-smokers, randomized either to a four-week intervention with the use of e-cigs containing only 50% propylene glycol (PG) and 50% vegetable glycerine (VG) or to a no-use control group. Compliance to the e-cig intervention was assessed by participants sending daily puff counts and by urinary propylene glycol (PG). Inflammatory cell counts and cytokines were determined in bronchoalveolar lavage (BAL) fluids. Genome-wide expression, microRNA, and mRNA were determined from bronchial epithelial cells. There were no significant differences in changes of BAL inflammatory cell counts or cytokines between baseline and follow-up, comparing the control and e-cig groups. However, in the intervention but not the control group, change in urinary PG as a marker of e-cig use and inhalation, was significantly correlated with change in cell counts (cell concentrations, macrophages, and lymphocytes) and cytokines (IL-8, IL-13, and TNF-α), although the absolute magnitude of changes was small. There were no significant changes in mRNA or microRNA gene expression. Although limited by study size and duration, this is the first experimental demonstration of an impact of e-cig use on inflammation in the human lung among never-smokers.
Publication Title
Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identifying Nuclear Matrix-Attached DNA Across the Genome.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Experimental approaches to define the relationship between gene expression and nuclear matrix attachment regions (MARs) have given contrasting and method-specific results. We have developed a next generation sequencing strategy to identify MARs across the human genome (MAR-Seq). The method is based on crosslinking chromatin to its nuclear matrix attachment sites to minimize changes during biochemical processing. We used this method to compare nuclear matrix organization in MCF-10A mammary epithelial-like cells and MDA-MB-231 breast cancer cells and evaluated the results in the context of global gene expression (array analysis) and positional enrichment of gene-regulatory histone modifications (ChIP-Seq). In the normal-like cells, nuclear matrixattached DNA was enriched in expressed genes, while in the breast cancer cells, it was enriched in non-expressed genes. In both cell lines, the chromatin modifications that mark transcriptional activation or repression were appropriately associated with gene expression. Using this new MAR-Seq approach, we provide the first genome-wide characterization of nuclear matrix attachment in mammalian cells and reveal that the nuclear matrixassociated genome is highly cell-context dependent.
Publication Title
Identifying Nuclear Matrix-Attached DNA Across the Genome.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Using the novel BTK inhibitor PF-303, we model the clinical phenotype of BTK inhibition by systematically examining the impact of PF-303 on the mature immune system in mice autoimmune indications. However, our current knowledge of the role of BTK in immune competence has been gathered in the context of genetic inactivation of btk in both mice and man. Using the novel BTK inhibitor PF-303, we model the clinical phenotype of BTK inhibition by systematically examining the impact of PF-303 on the mature immune system in mice. We implicate BTK in tonic BCR signaling, demonstrate dependence of the T3 B cell subset and IgM surface expression on BTK activity, and find that B1 cells survive and function independently of BTK. While BTK inhibition does not impact humoral memory survival, antigen-driven clonal expansion of memory B cells and antibody secreting cell generation are inhibited. These data define the role of BTK in the mature immune system and mechanistically predict the clinical phenotype of BTK inhibition.
Publication Title
Modeling the clinical phenotype of BTK inhibition in the mature murine immune system.
Sample Metadata Fields
Specimen part
View Samples- Pseudomonas aeruginosa pao1
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Characterization of bacterial behavior in the microgravity environment of spaceflight is of importance towards risk assessment and prevention of infectious disease during long-term missions. Further, this research field unveils new insights into connections between low fluid-shear regions encountered by pathogens during their natural infection process in vivo, and bacterial virulence. This study is the first to characterize the global transcriptomic and proteomic response of an opportunistic pathogen that is actually found in the space habitat, Pseudomonas aeruginosa. Overall, P. aeruginosa responded to spaceflight conditions through differential regulation of 167 genes and 28 proteins, with Hfq identified as a global transcriptional regulator in the response to this environment. Since Hfq was also induced in spaceflight-grown Salmonella typhimurium, Hfq represents the first spaceflight-induced regulator across the bacterial species border. The major P. aeruginosa virulence-related genes induced in spaceflight conditions were the lecA and lecB lectins and the rhamnosyltransferase (rhlA), involved in the production of rhamnolipids. The transcriptional response of spaceflight-grown P. aeruginosa was compared with our previous data of this organism grown in microgravity-analogue conditions using the rotating wall vessel (RWV) bioreactor technology. Interesting similarities were observed, among others with regard to Hfq regulation and oxygen utilization. While LSMMG-grown P. aeruginosa mainly induced genes involved in microaerophilic metabolism, P. aeruginosa cultured in spaceflight adopted an anaerobic mode of growth, in which denitrification was presumably most prominent. Differences in hardware between spaceflight and LSMMG experiments, in combination with more pronounced low fluid shear and mixing in spaceflight when compared to LSMMG conditions, were hypothesized to be at the origin of these observations. Collectively, our data suggest that spaceflight conditions could induce the transition of P. aeruginosa from an opportunistic organism to potential pathogen, results that are of importance for infectious disease risk assessment and prevention, both during spaceflight missions and in the clinic.
Publication Title
Transcriptional and proteomic responses of Pseudomonas aeruginosa PAO1 to spaceflight conditions involve Hfq regulation and reveal a role for oxygen.
Sample Metadata Fields
No sample metadata fields
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