Bacteria respond to osmotic stress by a substantial increase in the intracellular osmolality, adjusting their cell turgor for altered growth conditions. Using E. coli as a model organism we demonstrate here that bacterial responses to hyperosmotic stress specifically depend on the nature of osmoticum used. We show that increasing acute hyperosmotic NaCl stress above ~1.0 Os kg-1 causes a dose-dependent K+ leak from the cell, resulting in a substantial decrease in cytosolic K+ content and a concurrent accumulation of Na+ in the cell. At the same time, isotonic sucrose or mannitol treatment (non-ionic osmotica) results in a gradual increase of the net K+ uptake. Ion flux data is consistent with growth experiments showing that bacterial growth is impaired by NaCl at the concentration resulting in a switch from net K+ uptake to efflux. Microarray experiments reveal that about 40% of up-regulated genes shared no similarity in their responses to NaCl and sucrose treatment, further suggesting specificity of osmotic adjustment in E. coli to ionic- and non-ionic osmotica The observed differences are explained by the specificity of the stress-induced changes in the membrane potential of bacterial cells highlighting the importance of voltage-gated K+ transporters for bacterial adaptation to hyperosmotic stress.
Ion transport and osmotic adjustment in Escherichia coli in response to ionic and non-ionic osmotica.
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View SamplesPurpose: Majority of pancreatic cancer (PDAC) patient deaths are associated to the metastatic progression of disease. To identify novel targeted-therapies, a complete understanding of transformation in genetic landscape in tumors during disease progression is needed. Widely in use, the artificially immortalized PDAC cell lines do not rightly represent the progression because of multiple donors and disparate genetic characteristics. To identify key genes underlying the progression of PDAC from localized disease to a metastatic form, we performed whole transcriptome RNA-Sequencing analysis of cell models representing localised to metaststic stage through paired-end deep sequencing Method: Mouse expressing a Cre-activated KrasG12D allele inserted into the endogenous Kras locus, and these mice were crossed with mice expressing Cre recombinase in pancreatic tissue by virtue of a PDX-1 promoter-driven transgene. Next a cross between K-rasG12D Pdx-Cre and p16-/- mice, transgenic K-rasG12D Pdx-Cre p16-/- mice were generated harboring tissue specific mutant Kras and p16 deletion resulting in an earlier appearance of PanIN lesions followed by rapid progression into highly invasive and metastatic pancreatic cancers. Results: Transgenic K-rasG12D Pdx-Cre p16-/- mice developed spontaneous- localized, invasive and metastatic pancreatic tumors and transcriptome of these cell models representing localized, invasive and metastatic pancreatic tumors were sequenced. Conclusions: Based on genetic analysis of a same-lineage genetic background cell models, this study identifies a novel molecular pathway underlying the progression of pancreatic cancer disease. This study shows that Intestine Specific Homeobox (ISX) gene is a novel biomarker unique to pancreatic cancer progression. Overall design: By using tumors from K-rasG12D/p16-/- transgenic mice, we generated a spectrum of spontaneous (without immortalization) murine cell models representing localized (HI-Panc-L), invaise (HI-Panc-I) and metastatic (HI-Panc-M) stages. HI-Panc progression model is a valuable tool and by studying gene expression during progression of pancaretic cancer from localised to metaststic stage in a genetically same linaege wll be beneificail for pancartic cancer reaserch.
Characterization of Novel Murine and Human PDAC Cell Models: Identifying the Role of Intestine Specific Homeobox Gene ISX in Hypoxia and Disease Progression.
Specimen part, Subject
View SamplesThe goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling of exosomal RNA isolated from breast cancer patients before, during and after radiation therapy.
Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.
Subject
View SamplesThe goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling for exosomal RNA isolated from stroma cell (MRC5) or stroma/breast cancer cell co-culture (MRC5 and 1833).
Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PrtT-regulated proteins secreted by Aspergillus fumigatus activate MAPK signaling in exposed A549 lung cells leading to necrotic cell death.
Specimen part, Cell line, Treatment
View SamplesResponse of A549 cells treated with Aspergillus fumigatus wild type germinating conidia (WT_GC) or PrtT protease deficient mutant conidia (PrtT-GC) or inert acrylic 2-4 micron beads (Beads) for 8h
PrtT-regulated proteins secreted by Aspergillus fumigatus activate MAPK signaling in exposed A549 lung cells leading to necrotic cell death.
Specimen part, Cell line, Treatment
View SamplesResponse of A549 cells treated with Aspergillus fumigatus wild type culture filtrate (WT-CF) or PrtT protease deficient mutant culture filtrate (PrtT-CF) for 8h
PrtT-regulated proteins secreted by Aspergillus fumigatus activate MAPK signaling in exposed A549 lung cells leading to necrotic cell death.
Specimen part, Cell line, Treatment
View SamplesResponse of A549 cells treated with Aspergillus fumigatus germinating conidia (WT-GC) or culture filtrate (WT-CF) for 8h
PrtT-regulated proteins secreted by Aspergillus fumigatus activate MAPK signaling in exposed A549 lung cells leading to necrotic cell death.
Specimen part, Cell line, Treatment
View SamplesMicroarrays were used to examine gene expression changes that may be present in the fallopian tube epithelium of morphologically normal BRCA1 mutation positive and negative subjects. Fallopian tube epithelia has been implicated as an early point of origin for serous carcninoma. By examining the early events present in the microenvironment of this tissue between BRCA1 mutation carriers and non-carriers, we hoped to elucidate mechanisms that may lead to the development of epithelial ovarian cancer.
Identification of abrogated pathways in fallopian tube epithelium from BRCA1 mutation carriers.
Specimen part
View SamplesUsing gene expression profiling we characterize the global effect of p53 on the TLR5-mediated transcription in MCF7 cells. We found that combined activation of p53 and TLR5 pathways synergistically increases expression of over 200 genes, mostly associated with immunity and inflammation. The synergy was observed in several human cancer cells and primary lymphocytes.
p53 amplifies Toll-like receptor 5 response in human primary and cancer cells through interaction with multiple signal transduction pathways.
Cell line
View Samples