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SRP018317
Homo sapiens
4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
AGO-PAR-CLIP was employed to identify microRNA binding sites in BCBL-1, a Kaposi's sarcoma-associated herpesvirus (KSHV) infected B-cell line and DG75, a KSHV negative B-cell line as a control. By using our novel computational method (PARma) and differential analysis of PAR-CLIP data, highly accurate target sites of KSHV microRNAs can be defined. Overall design: Examination of microRNA target sites in two different cell lines using replicate PAR-CLIP experiments
Publication Title
PARma: identification of microRNA target sites in AGO-PAR-CLIP data.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina Genome Analyzer
Description
We analyzed small RNAs from three mammalian species, and found that in all these species piRNA-directed targeting is accompanied by the generation of short sequences that have a very precisely defined length and a specific spatial relationship with the guide piRNAs. Overall design: small RNA-seq of testes lysate (beta-eliminated)
Publication Title
Conserved generation of short products at piRNA loci.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Relative contribution of sequence and structural features to the mRNA-binding of Argonaute/miRNA complexes and the degradation of miRNA targets
Publication Title
Relative contribution of sequence and structure features to the mRNA binding of Argonaute/EIF2C-miRNA complexes and the degradation of miRNA targets.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Crosslinking and immunoprecipitation (CLIP) is increasingly used to map transcriptome-wide binding sites of RNA-binding proteins (RBPs). We developed a method for CLIP data analysis and applied it to compare 254 nm CLIP with PAR-CLIP, which involves crosslinking of photoreactive nucleotides with 365 nm UV light. We found small differences in the accuracy of these methods in identifying binding sites of HuR, a protein that binds low-complexity sequences and Argonaute 2, which has a complex binding specificity. We show that crosslink-induced mutations lead to single-nucleotide resolution for both PAR-CLIP and CLIP. Our results confirm the expectation from original CLIP publications that RNA-binding proteins do not protect sufficiently their sites under the denaturing conditions used during the CLIP procedure, and we show that extensive digestion with sequence-specific ribonucleases strongly biases the set of recovered binding sites. We finally show that this bias can be substantially reduced by milder nuclease digestion conditions. Overall design: We performed duplicate experiments for each variant of the CLIP protocol (CLIP, PAR-CLIP), each protein (HuR, Ago2), and enzymatic digestion (complete T1 digestion, mild MNase digestion). In addition, we performed a single PAR-CLIP experiment with mild T1 digestion.
Publication Title
A quantitative analysis of CLIP methods for identifying binding sites of RNA-binding proteins.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarray profiling to document the difference between telomerase+ vs. ALT+ T-cell lymphomas developed on G3 Atm-/-TERT-ER genetic background.
Publication Title
Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene copy numbers of prostate tumors of G3 and G4 generations of LSL-mTert PB-Pten/p53 mouse model
Publication Title
Telomerase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Clinical and genomic evidence support the view that the metastatic potential of a primary tumor may be dictated by transforming events acquired early in the tumorigenic process. It has been proposed that the presence of such pro-metastatic events in early-stage tumors reflects their additional capability to function as oncogenes. Here, to test this deterministic hypothesis and identify potential pro-metastasis oncogenes, we adopted a comparative oncogenomics-guided functional genetic screening strategy involving (i) global transcriptomic data from two genetically engineered mouse models of melanoma with contrasting metastatic potential, (ii) genomic and transcriptomic profiles of human primary and metastatic melanoma and (iii) an invasion screen in TERT-immortalized human melanocytes and melanoma cells in vitro as well as (iv) evidence of expression selection in human melanoma tissues. This integrated effort led to the identification of 6 genes that are both potently pro-invasive and oncogenic. Further, we show that one such pro-invasion oncogene, ACP5, can confer spontaneous metastasis in vivo, engages a key pathway governing metastasis and is prognostic in human primary melanomas.
Publication Title
Proinvasion metastasis drivers in early-stage melanoma are oncogenes.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
DEP exposure is linked to increases in cardiovascular effects. This effect is enhanced in individuals with pre-existing disease. Animal models of cardiovascular disease are used to study this susceptibility. The heart is rich in mitochondria, which produce high levels of free radicals, leading to inactivation of tricarboxylic acid cycle enzymes. We hypothesized that a 4-wk DEP inhalation would result in strain-related structural impairment of cardiac mitochondria and changes in these enzyme activities in WKY and SHR. Male rats (12-14 wks age) were exposed whole body to air or 0.5 or 2.0 mg/m3 DEP for 6h/d, 5 d/wk for 4 wks. Neutrophilic influx was noted in the bronchoalveolar lavage fluid in both strains. A slightly lower level of baseline cardiac mitochondrial aconitase activity was seen in SHR than WKY. Aconitase activity appeared to be decreased in an exposure related manner in both strains. Significantly higher baseline levels of cardiac cytosolic ferritin and aconitase activity were seen in the SHR than WKY. No exposure-related changes were noted in either of these measures. Mitochondrial succinate and isocitrate dehydrogenase activities were not changed following DEP exposure in either strain. Transmission electron microscopy images of the heart indicated abnormalities in cardiac mitochondria of control SHR but not control WKY. No exposure related ultrastructural changes were induced by DEP in either strain. In conclusion, strain differences in cardiac biomarkers of oxidative stress and structure of mitochondria exist between SHR and WKY. DEP exposure results in small changes in cardiac mitochondrial and cytosolic markers of oxidative stress. (Abstract does not represent USEPA policy.)
Publication Title
One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Zinc (Zn) is a major elemental component of respirable ambient particulate matter (PM) detected often at alarming levels in urban air. Exposure to PM has been widely associated with increased cardiovascular morbidity and mortality, however, it is not known what components or sources of PM are causative. We recently demonstrated that long-term episodic inhalation of combustion PM, having similar amount of Zn found in urban PM, caused myocardial lesions in rats. We further demonstrated that a single pulmonary exposure to Zn at high concentration is associated with disturbances in cardiac mitochondrial function, ion channel regulation, calcium homeostasis, and cell signaling. Therefore, in this study we investigated the role of PM-associated Zn in cardiac injury using multiple exposure scenarios. Male Wistar-Kyoto (WKY) rats of 12-14 wks age were intratracheally exposed (once per wk x 8 or16 wks) to either (1) saline (control); (2) PM having no soluble Zn; (3) combustion PM suspension containing 14.5 ug/mg water-soluble Zn at high and (4) low dose levels, (5) the aqueous fraction of this suspension devoid of solid insoluble particulate fraction (14.5 ug/mg soluble Zn), or (6) Zn sulfate. Zn concentrations were identical in groups 3, 5 and 6. Pulmonary toxicity was apparent in all exposure groups when compared to saline as determined by recovery of cells in bronchoalveolar lavage fluid. Long-term exposure to PM with or without soluble Zn, or Zn sulfate caused distinct myocardial lesions characterized by subepicardial and randomly distributed myocardial inflammation, degeneration, and fibrosis. The lesion severity was higher in those groups receiving Zn PM. Because cardiac mitochondria are likely the primary target of inhaled metal or other absorbed PM components, we analyzed mitochondrial DNA damage using QPCR and found that all exposure groups except those exposed to PM without Zn caused variable degree of damage. Aconitase activity, sensitive to inhibition by oxidative stress was inhibited slightly but significantly in rats receiving zinc sulfate. Although modest, microarray (Affymetrix) analysis revealed expression changes in the heart reflective of effects on cell signaling, inflammation/oxidative stress, mitochondrial fatty acid metabolisms and cell cycle regulation in rats exposed to zinc sulfate. However, these changes were minimal following exposure to PM devoid of soluble metals. We demonstrate that episodic subchronic pulmonary exposure to zinc sulfate causes cardiac injury and mitochondrial DNA damage. Thus, water-soluble PM-associated zinc may be one of the PM components responsible for cardiovascular morbidity.
Publication Title
The role of particulate matter-associated zinc in cardiac injury in rats.
Sample Metadata Fields
No sample metadata fields
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