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Circular RNAs (circRNAs) are a class of single-stranded RNAs with a contiguous structure that have enhanced stability and a lack of end motifs necessary for interaction with various cellular proteins. Here, we show that unmodified exogenous circRNA is able to bypass cellular RNA sensors and thereby avoid provoking an immune response in RIG-I and Toll-like receptor (TLR) competent cells and in mice. The immunogenicity and protein expression stability of circRNA preparations are found to be dependent on purity, with small amounts of contaminating linear RNA leading to robust cellular immune responses. Unmodified circRNA is less immunogenic than unmodified linear mRNA in vitro, in part due to the evasion of TLR sensing. Finally, we provide the first demonstration to our knowledge of exogenous circRNA delivery and translation in vivo, and we show that circRNA translation is extended in adipose tissue in comparison to unmodified and uridine-modified linear mRNAs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A captive pilot whale emptied as much as 88 percent of lung gas passively, without the aid of expiratory muscles. Level or decreasing pressures in the esophagus during expiration, and in the blowhole at the onset of expiration, revealed the driving force of expiration to be solely elastic recoil. Active muscular reexpansion of the lungs ensued immediately. Expiration and inspiration were completed in about I second.