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  • 1
    Publication Date: 2012-04-25
    Description: Upregulation of miR-34a by p53 is recently believed to be a key mediator in the pro-apoptotic effects of this tumor suppressor. We sought to determine whether restoration of miR-34a levels in p53 deficient cells could rescue the response to DNA damage. Compared with the p53 wildtype U2OS cells, miR-34a expression was much lower in p53 deficient Saos2 cells upon cisplatin treatment. Unexpectedly, delivery of miR-34a in Saos2 cells does not increase the cell sensitivity to apoptosis. This effect was mediated by direct downregulation of SirT1 expression by miR-34a, which in turn increased the NFκB activity. Inhibition of NFκB activity in Saos2 cells by Aspirin sensitized the miR-34a overexpressing cells to cell death. Thus, in tumors with p53 deficiency, miR-34a restoration alone confers drug resistance through Sirt1-NFκB pathway and combination of miR-34a and NFκB inhibitor could be considered as a promising therapeutic strategy. J. Cell. Biochem. © 2012 Wiley Periodicals, Inc.
    Electronic ISSN: 0091-7419
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Published by Wiley
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  • 2
    Publication Date: 2021-03-25
    Description: Background As the use of nanopore sequencing for metagenomic analysis increases, tools capable of performing long-read taxonomic classification (ie. determining the composition of a sample) in a fast and accurate manner are needed. Existing tools were either designed for short-read data (eg. Centrifuge), take days to analyse modern sequencer outputs (eg. MetaMaps) or suffer from suboptimal accuracy (eg. CDKAM). Additionally, all tools require command line expertise and do not scale in the cloud. Results We present BugSeq, a novel, highly accurate metagenomic classifier for nanopore reads. We evaluate BugSeq on simulated data, mock microbial communities and real clinical samples. On the ZymoBIOMICS Even and Log communities, BugSeq (F1 = 0.95 at species level) offers better read classification than MetaMaps (F1 = 0.89–0.94) in a fraction of the time. BugSeq significantly improves on the accuracy of Centrifuge (F1 = 0.79–0.93) and CDKAM (F1 = 0.91–0.94) while offering competitive run times. When applied to 41 samples from patients with lower respiratory tract infections, BugSeq produces greater concordance with microbiological culture and qPCR compared with “What’s In My Pot” analysis. Conclusion BugSeq is deployed to the cloud for easy and scalable long-read metagenomic analyses. BugSeq is freely available for non-commercial use at https://bugseq.com/free.
    Electronic ISSN: 1471-2105
    Topics: Biology , Computer Science
    Published by BioMed Central
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