The Coronaviridae is a family of positive-strand RNA viruses that includes SARS-CoV-2, the etiologic agent of the COVID-19 pandemic. Bearing the largest single-stranded RNA genomes in nature, ...coronaviruses are critically dependent on long-distance RNA-RNA interactions to regulate the viral transcription and replication pathways. Here we experimentally mapped the in vivo RNA-RNA interactome of the full-length SARS-CoV-2 genome and subgenomic mRNAs. We uncovered a network of RNA-RNA interactions spanning tens of thousands of nucleotides. These interactions reveal that the viral genome and subgenomes adopt alternative topologies inside cells and engage in different interactions with host RNAs. Notably, we discovered a long-range RNA-RNA interaction, the FSE-arch, that encircles the programmed ribosomal frameshifting element. The FSE-arch is conserved in the related MERS-CoV and is under purifying selection. Our findings illuminate RNA structure-based mechanisms governing replication, discontinuous transcription, and translation of coronaviruses and will aid future efforts to develop antiviral strategies.
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•Comprehensive RNA-RNA networks of the SARS-CoV-2 genome and subgenomes inside cells•Long-range structures spanning thousands of bases resulting in dynamic topologies•Multiple site-specific interactions between host and virus RNAs•An arch around the ribosomal frameshifting element is under purifying selection
Coronaviruses use RNA structure to regulate their function. Ziv et al. identified maps of RNA-RNA interactions along the SARS-CoV-2 genome and subgenomes inside cells, revealing long-range base-pairing between distal elements, alternative co-existing RNA topologies, and interactions between virus and host RNA and providing insights into the coronavirus modes of action.
Neuroglobin, recently discovered in the brain and in the retina of vertebrates, belongs to the class of hexacoordinate globins, in which the distal histidine coordinates the iron center in both the ...Fe(II) and Fe(III) forms. As for most other hexacoordinate globins, the physiological function of neuroglobin is still unclear, but seems to be related to neuronal survival following acute hypoxia. In this study, we have addressed the question whether human neuroglobin could act as a scavenger of toxic species, such as nitrogen monoxide, peroxynitrite, and hydrogen peroxide, which are generated at high levels in the brain during hypoxia; we have also investigated the kinetics of the reactions of its Fe(III) (metNGB) and Fe(II)NO forms with several reagents. Binding of cyanide or NO. to metNGB follows bi-exponential kinetics, showing the existence of two different protein conformations. In the presence of excess NO., metNGB is converted into NGBFe(II)NO by reductive nitrosylation, in analogy to the reactions of NO. with metmyoglobin and methemoglobin. The Fe(II)NO form of neuroglobin is oxidized to metNGB by peroxynitrite and dioxygen, two reactions that also take place in hemoglobin, albeit at lower rates. In contrast to myoglobin and hemoglobin, metNGB unexpectedly does not generate the cytotoxic ferryl form of the protein upon addition of either peroxynitrite or hydrogen peroxide. Taken together, our data indicate that human neuroglobin may be an efficient scavenger of reactive oxidizing species and thus may play a role in the cellular defense against oxidative stress.
Significance The human gut microbiota is a complex community of microbes with enormous metabolic potential. Recognition of the significance of bacterial metabolites in mediating host interactions and ...the impact of perturbations of this ecosystem on human health has increased dramatically. Antibiotic therapy eliminates not only pathogens but also some of the commensal enteric microbiota, sometimes leading to inflammation and diarrhea. Understanding how microbial imbalance actually causes disease is challenging. This study reveals how a gut resident is able to cause colitis during penicillin therapy. We show that a pyrrolobenzodiazepine metabolite produced by Klebsiella oxytoca directly damages the intestinal epithelium and disrupts its protective barrier function. The enterotoxicity of tilivalline provides a mechanism for antibiotic-induced colitis.
Particle therapy in Europe Grau, Cai; Durante, Marco; Georg, Dietmar ...
Molecular oncology,
July 2020, Volume:
14, Issue:
7
Journal Article
Peer reviewed
Open access
Particle therapy using protons or heavier ions is currently the most advanced form of radiotherapy and offers new opportunities for improving cancer care and research. Ions deposit the dose with a ...sharp maximum – the Bragg peak – and normal tissue receives a much lower dose than what is delivered by X‐ray therapy. Particle therapy has also biological advantages due to the high linear energy transfer of the charged particles around the Bragg peak. The introduction of particle therapy has been slow in Europe, but within the last decade, more than 20 clinical facilities have opened and facilitated access to this frontline therapy. In this review article, the basic concepts of particle therapy are reviewed along with a presentation of the current clinical indications, the European clinical research, and the established networks.
Particle therapy using protons, or heavier ions, is the most advanced form of radiotherapy today and offers new opportunities for improving cancer care and research. Within the last decade, more than 20 new clinical facilities have opened in Europe, facilitating access to this frontline therapy. This review presents the physics, biology, and clinical aspects of particle therapy.
A relatively unknown natural fiber extracted from the leaves of the fique plant, native of the South American Andes, has recently shown potential as reinforcement of polymer composites for ...engineering applications. Preliminary investigations indicated a promising substitute for synthetic fibers, competing with other well-known natural fibers. The fabric made from fique fibers have not yet been investigated as possible composite reinforcement. Therefore, in the present work a more thorough characterization of fique fabric as a reinforcement of composites with a polyester matrix was performed. Thermal mechanical properties of fique fabric composites were determined by dynamic mechanical analysis (DMA). The ballistic performance of plain woven fique fabric-reinforced polyester matrix composites was investigated as a second layer in a multilayered armor system (MAS). The results revealed a sensible improvement in thermal dynamic mechanical behavior. Both viscoelastic stiffness and glass transition temperature were increased with the amount of incorporated fique fabric. In terms of ballistic results, the fique fabric composites present a performance similar to that of the much stronger Kevlar
as an MAS second layer with the same thickness. A cost analysis indicated that armor vests with fique fabric composites as an MAS second layer would be 13 times less expensive than a similar creation made with Kevlar™.
Smart Products for Sharing Weber, Thomas A.
Journal of management information systems,
04/2017, Volume:
34, Issue:
2
Journal Article
Peer reviewed
Open access
Sharing markets create mutual insurance for consumers who are unsure about their future needs for goods, thus rendering products more valuable both before and after the purchase. By embedding ...intelligence in their products, enabling them to sense, monitor, and authorize transfers between users, firms can economically participate in the collaborative consumption of their goods after they have been sold. Building on a dynamic model with overlapping generations of heterogeneous agents, we determine a firm's jointly optimal product price and sharing tariff. The active use of product intelligence as a gatekeeper for collaborative consumption can narrow the gap between the retail and the equilibrium price in the sharing market. Because of its tendency to decrease the demand for ownership, the use of smart products with a positive sharing tariff does not always maximize the firm's overall expected profits. A positive sharing tariff tends to be profitable with relatively high unit production cost and impatient consumers.
In the pursuit of surpassing the energy density of conventional lithium ion cells, significant efforts have been made to develop lithium metal cells. However, many reports in the literature utilize ...Li-metal cells with significant excess lithium, resulting in a dramatically reduced practical energy density. In contrast, anode-free cells do not utilize excess lithium; instead, a lithium metal anode is formed in-situ from the stored lithium within the positive electrode during the first charge. Here, we evaluate anode-free lithium metal pouch cells (NMC532||Cu) with operando pressure measurements constrained to different stack pressures between 75-2205 kPa with two different electrolytes, 1M LiPF6 FEC:DEC (1:2) and 1M LiPF6 FEC:TFEC (1:2). Increasing the initial average pressure from 75-2200 kPa was found to generally improve cycle life, with the most significant benefits achieved up to 1200 kPa. Cells containing FEC:TFEC electrolyte exhibited a superior initial performance compared to FEC:DEC cells, as evidenced by cycling data and SEM analysis of the lithium morphology. Although generally beneficial, we found that the effect of increased pressure on the performance of cells with different solvent systems was not equal, indicating that the physical properties of electrolyte play an important roll in cells constrained to higher pressures between 1200-2200 kPa.
Inertial confinement fusion seeks to create burning plasma conditions in a spherical capsule implosion, which requires efficiently absorbing the driver energy in the capsule, transferring that energy ...into kinetic energy of the imploding DT fuel and then into internal energy of the fuel at stagnation. We report new implosions conducted on the National Ignition Facility (NIF) with several improvements on recent work Phys. Rev. Lett. 120, 245003 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.245003; Phys. Rev. E 102, 023210 (2020)PRESCM2470-004510.1103/PhysRevE.102.023210: larger capsules, thicker fuel layers to mitigate fuel-ablator mix, and new symmetry control via cross-beam energy transfer; at modest velocities, these experiments achieve record values for the implosion energetics figures of merit as well as fusion yield for a NIF experiment.
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