Programmed -1 ribosomal frameshifting (-1 PRF) stimulated by mRNA pseudoknots regulates gene expression in many viruses, making pseudoknots potential targets for anti-viral drugs. The mechanism by which pseudoknots trigger -1 PRF, however, remains controversial, with several competing models. Recent work showed that high -1 PRF efficiency was linked to high pseudoknot conformational plasticity via the formation of alternate conformers. We tested whether pseudoknots bound with an anti-frameshifting ligand exhibited a similar correlation between conformational plasticity and -1 PRF efficiency by measuring the effects of a ligand that was found to inhibit -1 PRF in the SARS coronavirus on the conformational dynamics of the SARS pseudoknot. Using single-molecule force spectroscopy to unfold pseudoknots mechanically, we found that the ligand binding effectively abolished the formation of alternate conformers. This result extends the connection between -1 PRF and conformational dynamics and, moreover, suggests that targeting the conformational dynamics of pseudoknots may be an effective strategy for anti-viral drug design.

Smoking-related emphysema is a chronic inflammatory disease driven by T helper 17 (TH17) cells through molecular mechanisms that remain obscure. Here we have explored the role of microRNA-22 (miR-22) in emphysema. MiR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism involving NF-κB. MiR-22-deficient mice, but not wild-type, showed attenuated TH17 responses and failed to develop emphysema after exposure to either smoke or nCB. We further show that miR-22 controls APC activation and TH17 responses through activation of AP-1 transcription factor complexes and histone deacetylase (HDAC) 4. Thus, miR-22 is a critical regulator of both emphysema and TH17 responses.

Anti-icing and deicing are the two major pathways for suppressing adhesion of ice on surfaces, yet materials with dual capabilities are rare. In this work, we have designed a perfluorododecylated graphene nanoribbon (FDO-GNR) film that takes advantage of both the low polarizability of perfluorinated carbons and the intrinsic conductive nature of graphene nanoribbons. The FDO-GNR films are superhydrophobic with a sheet resistance below 8 kΩ·sq(-1) and then exhibit an anti-icing property that prevents freezing of incoming ice-cold water down to -14 °C. After that point, voltage can be applied to the films to resistively heat and deice the surface. Further a lubricating liquid can be employed to create a slippery surface to improve the film's deicing performance. The FDO-GNR films can be easily switched between the superhydrophobic anti-icing mode and the slippery deicing mode by applying the lubricant. A spray-coating method makes it suitable for large-scale applications. The anti-icing and deicing properties render the FDO-GNR films with promise for use in extreme environments.

Viral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated. Our work revealed that mouse and human lung epithelial cells could be stimulated to generate robust antiviral responses that both reduce viral burden and enhance survival of isolated cells and intact animals. The antiviral protection required concurrent induction of epithelial reactive oxygen species (ROS) from both mitochondrial and dual oxidase sources, although neither type I interferon enrichment nor type I interferon signaling was required for the inducible protection. Taken together, these findings establish the sufficiency of lung epithelial cells to generate therapeutically inducible antiviral responses, reveal novel antiviral roles for ROS, provide mechanistic insights into inducible resistance, and may provide an opportunity to protect patients from viral pneumonia during periods of peak vulnerability.

Metal nanowires are twisted to form yarns that are strong (0.4 to 1.1 GPa), pliable, and more conductive (3 × 106 S m−1) than carbon nanotube yarns. Niobium nanowire fibers are extracted by etching a copper‐niobium nano‐composite material fabricated using the severe plastic deformation process. When impregnated with paraffin wax, the niobium (Nb) nanowire yarns produce fast rotational actuation as the wax is heated. The heated wax expands, untwisting the yarn, which then re‐twists upon cooling. Normalized to yarn length, 12 deg mm−1 of torsional rotation was achieved along with twist rates in excess of 1800 rpm. Tensile modulus of 19 ± 5 GPa was measured for the Nb yarns, which is very similar to those of carbon multiwalled nanotubes.