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  • 1
    Publication Date: 2017-05-26
    Description: MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression. The pathways that mediate mature miRNA decay are less well understood than those that mediate miRNA biogenesis. We found that functional miRNAs are degraded in human cells by the endonuclease Tudor-SN (TSN). In vitro, recombinant TSN initiated the decay of both protein-free and Argonaute 2–loaded miRNAs via endonucleolytic cleavage at CA and UA dinucleotides, preferentially at scissile bonds located more than five nucleotides away from miRNA ends. Cellular targets of TSN-mediated decay defined using microRNA sequencing followed this rule. Inhibiting TSN-mediated miRNA decay by CRISPR-Cas9 knockout of TSN inhibited cell cycle progression by up-regulating a cohort of miRNAs that down-regulates mRNAs that encode proteins critical for the G 1 -to-S phase transition. Our study indicates that targeting TSN nuclease activity could inhibit pathological cell proliferation.
    Keywords: Molecular Biology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2019-07-13
    Description: To investigate ophthalmic changes in spaceflight, we would like to predict the impact of blood dysregulation and elevated intracranial pressure (ICP) on Intraocular Pressure (IOP). Unlike other physiological systems, there are very few lumped parameter models of the eye. The eye model described here is novel in its inclusion of the human choroid and retrobulbar subarachnoid space (rSAS), which are key elements in investigating the impact of increased ICP and ocular blood volume. Some ingenuity was required in modeling the blood and rSAS compartments due to the lack of quantitative data on essential hydrodynamic quantities, such as net choroidal volume and blood flowrate, inlet and exit pressures, and material properties, such as compliances between compartments.
    Keywords: Aerospace Medicine; Systems Analysis and Operations Research
    Type: GRC-E-DAA-TN20061 , Human Research Program Investigators'' Workshop: Integrated Pathways to Mars; Jan 13, 2015 - Jan 15, 2015; Galveston, TX; United States
    Format: application/pdf
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