The Structure of a Rigorously Conserved RNA Element within the SARS Virus Genome

We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m) RNA element of the SARS virus genome to 2.7-Å resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 3′ end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigorous sequence conservation in an otherwise rapidly mutable RNA genome. We find that this extreme conservation is clearly explained by the requirement to form a highly structured RNA whose unique tertiary structure includes a sharp 90° kink of the helix axis and several novel longer-range tertiary interactions. The tertiary base interactions create a tunnel that runs perpendicular to the main helical axis whose interior is negatively charged and binds two magnesium ions. These unusual features likely form interaction surfaces with conserved host cell components or other reactive sites required for virus function. Based on its conservation in viral pathogen genomes and its absence in the human genome, we suggest that these unusual structural features in the s2m RNA element are attractive targets for the design of anti-viral therapeutic agents. Structural genomics has sought to deduce protein function based on three-dimensional homology. Here we have extended this approach to RNA by proposing potential functions for a rigorously conserved set of RNA tertiary structural interactions that occur within the SARS RNA genome itself. Based on tertiary structural comparisons, we propose the s2m RNA binds one or more proteins possessing an oligomer-binding-like fold, and we suggest a possible mechanism for SARS viral RNA hijacking of host protein synthesis, both based upon observed s2m RNA macromolecular mimicry of a relevant ribosomal RNA fold

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Inhalation developmental toxicology studies: Teratology study of 1,3-butadiene in mice: Final report

Maternal toxicity, reproductive performance and developmental toxicology were evaluated in CD-1 mice following whole-body, inhalation exposures to 0, 40, 200 and 1000 ppM of 1,3-butadiene. The female mice, which had mated with unexposed males were exposed to the chemical for 6 hours/day on 6 through 15 dg and sacrificed on 18 dg. Maternal animals were weighed prior to mating and on 0, 6, 11 and 18 dg; the mice were observed for mortality, morbidity and signs of toxicity during exposure and examined for gross tissue abnormalities at necropsy. Live fetuses were weighed and subjected to external, visceral and skeletal examinations to detect growth retardation and morphologic anomalies. Significant concentration-related decreases were detected in a number of maternal body weight measures. There was a significant concentration-related depression of fetal body weights and placental weights. Body weights of male fetuses of all exposed groups were significantly lower than values for control fetuses; weights of female fetuses were significantly depressed in the mice exposed to 200 and 1000 ppM. In the 200- and 1000-ppM exposure groups, weights of placentas of male fetuses were significantly decreased, but placental weights of female fetuses were significantly affected only in litters exposed to the highest 1,3-butadiene concentration. This exposure regimen produced significant signs of maternal toxicity at concentrations of 200 and 1000 ppM 1,3-butadiene

Dominant lethal study in CD-1 mice following inhalation exposure to 1,3-butadiene: Final technical report

The effects of whole-body inhalation exposures to 1,3-butadiene on the reproductive system was evaluated. The results of dominant lethality in CD-1 male mice that were exposed to 1,3-butadiene are described. Subsequent to exposure, males were mated with two unexposed females. Mating was continued for 8 weeks with replacement of two females each week. Gravid uteri were removed, and the total number, position and status of implantations were determined. The mice were weighed prior to exposure and at 0, 1, 2, 3, 4, 5, 6, 7, and 8 weeks after exposure and at sacrifice. The animals were observed for mortality, morbidity and signs of toxicity throughout the study. 19 refs., 5 figs., 9 tabs

Attosecond Coherence Time Characterization in Hard X-Ray Free-Electron Laser

One of the key challenges in scientific researches based on free-electron lasers (FELs) is the characterization of the coherence time of the ultra-fast hard x-ray pulse, which fundamentally influences the interaction process between x-rays and materials. Conventional optical methods, based on autocorrelation, are very difficult to realize due to the lack of mirrors. Here, we experimentally demonstrate a novel method which yields a coherence time of 174.7 attoseconds for the 6.92 keV FEL pulses at the Linac Coherent Light Source. In our experiment, a phase shifter is adopted to control the cross-correlation between x-ray and microbunched electrons. This approach provides critical diagnostics for the temporal coherence of x-ray FELs and is universal for general machine parameters; applicable for wide range of photon energy, radiation brightness, repetition rate and FEL pulse duration.11Nsciescopu