78 research outputs found

    NF90 Binds the Dengue Virus RNA 3â€Č Terminus and is a Positive Regulator of Dengue Virus Replication

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    Background Viral RNA translation and replication are regulated by sequence and structural elements in the 5â€Č and 3â€Č untranslated regions (UTR) and by host cell and/or viral proteins that bind them. Dengue virus has a single-stranded RNA genome with positive polarity, a 5â€Č m7GpppG cap, and a conserved 3â€Č-terminal stem loop (SL) that is linked to proposed functions in viral RNA transcription and translation. Mechanisms explaining the contributions of host proteins to viral RNA translation and replication are poorly defined, yet understanding host protein-viral RNA interactions may identify new targets for therapeutic intervention. This study was directed at identifying functionally significant host proteins that bind the conserved dengue virus RNA 3â€Č terminus. Methodology/Principal Findings Proteins eluted from a dengue 3â€Č SL RNA affinity column at increasing ionic strength included two with double-strand RNA binding motifs (NF90/DRBP76 and DEAH box polypeptide 9/RNA helicase A (RHA)), in addition to NF45, which forms a heterodimer with NF90. Although detectable NF90 and RHA proteins localized to the nucleus of uninfected cells, immunofluorescence revealed cytoplasmic NF90 in dengue virus-infected cells, leading us to hypothesize that NF90 has a functional role(s) in dengue infections. Cells depleted of NF90 were used to quantify viral RNA transcript levels and production of infectious dengue virus. NF90 depletion was accompanied by a 50%-70% decrease in dengue RNA levels and in production of infectious viral progeny. Conclusions/Significance The results indicate that NF90 interacts with the 3â€Č SL structure of the dengue RNA and is a positive regulator of dengue virus replication. NF90 depletion diminished the production of infectious dengue virus by more than 50%, which may have important significance for identifying therapeutic targets to limit a virus that threatens more than a billion people worldwide.Ruth L. Kirschstein National Research Service Award (NIH-NRSA GM64985)UNCF-Merck Postdoctoral FellowshipNational Institute of Allergy and Infectious Diseases (U.S.)Ellison Medical Foundatio

    International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

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    Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

    Land surface Data Assimilation

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    Accurate knowledge of spatial and temporal land surface storages and fluxes are essential for addressing a wide range of important, socially relevant science, education, application and management issues. Improved estimates of land surface conditions are directly applicable to agriculture, ecology, civil engineering, water resources management, rainfall-runoff prediction, atmospheric process studies, climate and weather prediction, and disaster management (Houser et al. 2004). © 2010 Springer-Verlag Berlin Heidelberg.status: publishe

    Precipitation uncertainty How well do we know this critical hydrological variable

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    Humans can only survive three days without water -- Human health depends on an adequate supply of clean drinking water, and society depends on water for everything from agriculture to recreation. In 1990, 1.1 billion people did not have access to safe drinking water, mostly in underdeveloped nations. Ultimately, our access to fresh water relies on the fact that water will fall from the sky. However, our ability to measure precipitation is amazingly inadequate. Globally, we measure rainfall over land with an uneven distribution of about 40,000 rain gauges, which together have a total surface area smaller than a football field. We also measure precipitation with ground-based radars and satellites, but these are know to disagree by a factor of two. Measurement of solid precipitation can be off by a factor of five due to gage undercatch, and inadequate satellite wavelengths and algorithms. Further, it is not only the abount of precitation that determines surface water availability, but knowing its timing and duration is also critical for how that precipitation is partitioned into runoff, recharge, and evaporation. This study compares the precipitation averages, variability, and timing for various regions around the world in an attempt to determine how well we currently know this critical hydrological variable
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