3 research outputs found
Stability Studies of Ricin, Staphyloccocal Enterotoxin B and Trichothecene Mycotoxins on Office Matrices
Master'sMASTER OF SCIENC
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Differential effects of microRNAs miR‐21, miR‐99 and miR‐145 on lung regeneration and inflammation during recovery from influenza pneumonia
Publication status: PublishedFunder: National University of Singapore; doi: http://dx.doi.org/10.13039/501100001352Funder: Ministry of Education ‐ Singapore; doi: http://dx.doi.org/10.13039/501100001459AbstractIn a mouse model of influenza pneumonia, we previously documented that proliferating alveolar type II (AT2) cells are the major stem cells involved in early lung recovery. Profiling of microRNAs revealed significant dysregulation of specific ones, including miR‐21 and miR‐99a. Moreover, miR‐145 is known to exhibit antagonism to miR‐21. This follow‐up study investigated the roles of microRNAs miR‐21, miR‐99a, and miR‐145 in the murine pulmonary regenerative process and inflammation during influenza pneumonia. Inhibition of miR‐21 resulted in severe morbidity, and in significantly decreased proliferating AT2 cells due to impaired transition from innate to adaptive immune responses. Knockdown of miR‐99a culminated in moderate morbidity, with a significant increase in proliferating AT2 cells that may be linked to PTEN downregulation. In contrast, miR‐145 antagonism did not impact morbidity nor the proliferating AT2 cell population, and was associated with downregulation of TNF‐alpha, IL1‐beta, YM1, and LY6G. Hence, a complex interplay exists between expression of specific miRNAs, lung regeneration, and inflammation during recovery from influenza pneumonia. Inhibition of miR‐21 and miR‐99a (but not miR‐145) can lead to deleterious cellular and molecular effects on pulmonary repair and inflammatory processes during influenza pneumonia.</jats:p
Quantitative mass spectrometry of DENV-2 RNA-interacting proteins reveals that the DEAD-box RNA helicase DDX6 binds the DB1 and DB2 3′ UTR structures
Dengue virus (DENV) is a rapidly re-emerging flavivirus that causes dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), diseases for which there are no available therapies or vaccines. The DENV-2 positive-strand RNA genome contains 5′ and 3′ untranslated regions (UTRs) that have been shown to form secondary structures required for virus replication and interaction with host cell proteins. In order to comprehensively identify host cell factors that bind the DENV-2 UTRs, we performed RNA chromatography, using the DENV-2 5′ and 3′ UTRs as “bait”, combined with quantitative mass spectrometry. We identified several proteins, including DDX6, G3BP1, G3BP2, Caprin1 and USP10, implicated in P body (PB) and stress granule (SG) function, and not previously known to bind DENV RNAs. Indirect immunofluorescence microscopy showed these proteins to colocalize with the DENV replication complex. Moreover, DDX6 knockdown resulted in reduced amounts of infectious particles and viral RNA in tissue culture supernatants following DENV infection. DDX6 interacted with DENV RNA in vivo during infection and in vitro this interaction was mediated by the DB1 and DB2 structures in the 3′ UTR, possibly by formation of a pseudoknot structure. Additional experiments demonstrate that, in contrast to DDX6, the SG proteins G3BP1, G3BP2, Caprin1 and USP10 bind to the variable region (VR) in the 3′ UTR. These results suggest that the DENV-2 3′ UTR is a site for assembly of PB and SG proteins and, for DDX6, assembly on the 3′ UTR is required for DENV replication