The sarcosine oxidase locus is controlled by GbdR and SouR independently induced by glycine betaine and sarcosine, respectively. The goal of this study was to identify the members of the SouR regulon. Therefore, the comparison strains were a gbdR mutant and a gbdRsouR double mutant.
Sarcosine Catabolism in Pseudomonas aeruginosa Is Transcriptionally Regulated by SouR.
Treatment
View SamplesThe response of bacteria to the conditions at the site of infection is a key part of the transcriptional program that will determine the sucess of the infectious agent. To model the environment of the distal airway, we used bovine pulmonary surfactant (Survanta). P. aeruginosa transcript levels were measured in the presence or absence of Survanta in MOPS minimal medium to identify transcripts altered in response to surfactant. The most highly induced transcript in Survanta was PA5325, renamed sphA based on our findings that the gene was specifically induced by sphingosine derived from the sphingomyelin present in pulmonary surfactant. A divergently transcribed transcription factor, PA5324, was demonstrated to be critical for the sphingosine dependent induction of sphA and was therefore renamed SphR. Microarrays of the sphR mutant cells were compared to wild type to determine the likely SphR regulon.
Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.
Treatment
View SamplesPseudomonas aeruginosa is a common bacterium in the terminal plumbing system of buildings and it is from this niche that a substantial fraction of infections are acquired. To better understand P. aeruginosa biology in this environment, we examined the transcriptomes in tap water and pond water.
Transcriptional Responses of Pseudomonas aeruginosa to Potable Water and Freshwater.
No sample metadata fields
View SamplesPseudomonas aeruginosa displays tremendous metabolic diversity, controlled in part by the abundance of transcription regulators in the genome. We have been investigating P. aeruginosas response to the host, particularly changes regulated by the host-derived quaternary amines choline and glycine betaine (GB). We previously identified GbdR as an AraC-family transcription factor that directly regulates choline acquisition from host phospholipids (via binding to plcH and pchP promoters), is required for catabolism of the choline metabolite GB, and is an activator that induces transcription in response to GB or dimethylglycine. Our goal was to characterize the GbdR regulon in P. aeruginosa using genetics and chemical biology in combination with transcriptomics and in vitro DNA-binding assays. Here we show that GbdR activation regulates transcription of 26 genes from 12 promoters; 11 of which have measureable binding to GbdR in vitro. The GbdR regulon includes the genes encoding GB, dimethylglycine, sarcosine, glycine, and serine catabolic enzymes, and the BetX and CbcXWV quaternary amine transport proteins. . Additionally, identification of two uncharacterized regulon members suggests roles for these proteins in response to choline metabolites.
Characterization of the GbdR regulon in Pseudomonas aeruginosa.
Treatment
View SamplesTo study the immune response of the prostate tumor tissues after the leuprolide acetate plus ipilimumab, we compared the gene expression of 6 post-therapy with 3 pre-therapy samples. We identified 690 differential expressed genes (DEGs). Pathway analysis showed that these genes are associated with critical immune pathways such as CTLA4 signaling, antigen presenting etc.
VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer.
Specimen part
View SamplesImmune checkpoint blockade is able to achieve durable responses in a subset of patients, however we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4 and anti-PD-1 induced tumor rejection. To address these issues we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor infiltrating T cell populations. Anti-PD-1 predominantly induces the expansion of specific tumor infiltrating exhausted-like CD8 T cell subsets. In contrast, anti-CTLA-4 induces the expansion of an ICOS+ Th1-like CD4 effector population in addition to engaging specific subsets of exhausted-like CD8 T cells. Thus, our findings indicate that anti-CTLA-4 and anti-PD-1 checkpoint blockade induced immune responses are driven by distinct cellular mechanisms. Overall design: RNA profiles of a subset of tumor infiltrating T cell populations in anti-PD-1, anti-CTLA-r and control mice were generated by RNA sequencing, using Illumina HiSeq 4000. Mouse mutation background was assessed by whole exome sequencing data
Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade.
Specimen part, Cell line, Subject
View SamplesThough obesity is a global epidemic, the physiological mechanisms involved are little understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesized that maternal diet influences fetal 5-HT exposure, which then influences central appetite network development and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant low protein fed rat mothers exhibited elevated serum 5-HT, which was also evident in the placenta and fetal brains at E16.5. This increase was associated with reduced hypothalamic expression of 5-HT2CR - the primary 5-HT receptor influencing appetite. As expected, reduced 5-HT2CR expression was associated with impaired sensitivity to 5-HT-mediated appetite suppression. 5-HT primarily achieves effects on appetite via 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We reveal that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC and that 5-HT2AR mRNA is increased in the hypothalamus of in utero growth restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals are more sensitive to 5-HT2AR agonist-induced appetite suppression. These findings may not only reveal a 5-HT-mediated mechanism underlying programming of obesity susceptibility but also provide a promising means to correct it, via a 5-HT2AR agonist treatment.
5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.
Sex, Specimen part
View SamplesThree of the melanoma cell lines show higher expression fold change after stimulation than the other 3.
Loss of IFN-γ Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy.
Specimen part
View SamplesGene expression signatures were measured in logarithmic growing cultures
Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF.
Specimen part
View SamplesChanges in gene expression on MNV infection of RAW264.7 cells
Murine norovirus replication induces G0/G1 cell cycle arrest in asynchronously growing cells.
Cell line
View Samples