RNA binding properties of the US11 protein from four primate simplexviruses

<p>Abstract</p> <p>Background</p> <p>The protein encoded by the Us11 gene of herpes simplex viruses is a dsRNA binding protein which inhibits protein kinase R activity, thereby preventing the interferon-induced shut down of protein synthesis following viral infection. Us11 protein is not essential for infectivity <it>in vitro </it>and in mice in herpes simplex virus type 1 (HSV1), however this virus has a second, and apparently more important, inhibitor of PKR activity, the γ₁34.5 protein. Recently sequenced simian simplexviruses SA8, HVP2 and B virus do not have an ORF corresponding to the γ₁34.5 protein, yet they have similar, or greater, infectivity as HSV1 and HSV2.</p> <p>Methods</p> <p>We have expressed the US11 proteins of the simplexviruses HSV1, HSV2, HVP2 and B virus and measured their abilities to bind dsRNA, in order to investigate possible differences that could complement the absence of the γ₁34.5 protein. We employed a filter binding technique that allows binding of the Us11 protein under condition of excess dsRNA substrate and therefore a measurement of the true Kd value of Us11-dsRNA binding.</p> <p>Results and Conclusions</p> <p>The results show a Kd of binding in the range of 0.89 nM to 1.82 nM, with no significant difference among the four Us11 proteins.</p

Regulation of Civilian Possession of Small Arms and Light Weapons

yesThe majority of small arms and light weapons currently in circulation are in civilian possession1. An estimated fifty-nine percent of weapons around the world are in civilian hands and in some regions such as Europe this is closer to eighty per cent.2 While the majority of these arms are used for lawful purposes a significant percentage are not. The misuse of these arms by civilians can cause major damage to people¿s livelihoods, health and security as well as broader repercussion such as hampering economic, social and political development and the provision of health care. One of the more controversial outcomes of the UN Small Arms conference was the failure of states to explicitly commit to more effective regulation of civilian possession and use of small arms and light weapons (SALW). Despite clear evidence of the opportunities for diversion of SALW from civilian possession to illicit trade and the serious impact of this on human security, opposition from some states to any mention of this issue within the Programme of Action (PoA) prevented the inclusion of language concerning the regulation of privately owned SALW. Nevertheless, the Programme of Action does contain limited provisions including the criminalisation of illicit possession of SALW and a requirement that states ensure responsibility for SALW issued by them. This Policy Briefing elaborates on how these and other international commitments should be interpreted and implemented so as to enhance human security

Strong coupling theory for driven tunneling and vibrational relaxation

We investigate on a unified basis tunneling and vibrational relaxation in driven dissipative multistable systems described by their N lowest lying unperturbed levels. By use of the discrete variable representation we derive a set of coupled non-Markovian master equations. We present analytical treatments that describe the dynamics in the regime of strong system-bath coupling. Our findings are corroborated by ``ab-initio'' real-time path integral calculations.Comment: 4 LaTeX pages including 3 figure

Arabidopsis seedlings display a remarkable resilience under severe mineral starvation using their metabolic plasticity to remain self-sufficient for weeks

During the life cycle of plants, seedlings are considered vulnerable because they are at the interface between the highly stress tolerant seed embryos and the established plant, and must develop rapidly, often in a challenging environment, with limited access to nutrients and light. Using a simple experimental system, whereby the seedling stage of Arabidopsis is considerably prolonged by nutrient starvation, we analysed the physiology and metabolism of seedlings maintained in such conditions up to 4 weeks. Although development was arrested at the cotyledon stage, there was no sign of senescence and seedlings remained viable for weeks, yielding normal plants after transplantation. Photosynthetic activity compensated for respiratory carbon losses, and energy dissipation by photorespiration and alternative oxidase appeared important. Photosynthates were essentially stored as organic acids, while the pool of free amino acids remained stable. Seedlings lost the capacity to store lipids in cytosolic lipid droplets, but developed large plastoglobuli. Arabidopsis seedlings arrested in their development because of mineral starvation displayed therefore a remarkable resilience, using their metabolic and physiological plasticity to maintain a steady state for weeks, allowing resumption of development when favourable conditions ensue

Isotopic labelling reveals the efficient adaptation of wheat root TCA cycle flux modes to match carbon demand under ammonium nutrition

Proper carbon (C) supply is essential for nitrogen (N) assimilation especially when plants are grown under ammonium (NH4+) nutrition. However, how C and N metabolic fluxes adapt to achieve so remains uncertain. In this work, roots of wheat (Triticum aestivum L.) plants grown under exclusive NH4+ or nitrate (NO3−) supply were incubated with isotope-labelled substrates (15NH4+, 15NO3−, or [13C]Pyruvate) to follow the incorporation of 15N or 13C into amino acids and organic acids. Roots of plants adapted to ammonium nutrition presented higher capacity to incorporate both 15NH4+ and 15NO3− into amino acids, thanks to the previous induction of the NH4+ assimilative machinery. The 15N label was firstly incorporated into [15N]Gln vía glutamine synthetase; ultimately leading to [15N]Asn accumulation as an optimal NH4+ storage. The provision of [13C]Pyruvate led to [13C]Citrate and [13C]Malate accumulation and to rapid [13C]2-OG consumption for amino acid synthesis and highlighted the importance of the anaplerotic routes associated to tricarboxylic acid (TCA) cycle. Taken together, our results indicate that root adaptation to ammonium nutrition allowed efficient assimilation of N thanks to the promotion of TCA cycle open flux modes in order to sustain C skeleton availability for effective NH4+ detoxification into amino acids

Heating and decoherence suppression using decoupling techniques

We study the application of decoupling techniques to the case of a damped vibrational mode of a chain of trapped ions, which can be used as a quantum bus in linear ion trap quantum computers. We show that vibrational heating could be efficiently suppressed using appropriate ``parity kicks''. We also show that vibrational decoherence can be suppressed by this decoupling procedure, even though this is generally more difficult because the rate at which the parity kicks have to applied increases with the effective bath temperature.Comment: 13 pages, 5 figures. Typos corrected, references adde

Microscopic Derivation of Non-Markovian Thermalization of a Brownian Particle

In this paper, the first microscopic approach to the Brownian motion is developed in the case where the mass density of the suspending bath is of the same order of magnitude as that of the Brownian (B) particle. Starting from an extended Boltzmann equation, which describes correctly the interaction with the fluid, we derive systematicaly via the multiple time-scale analysis a reduced equation controlling the thermalization of the B particle, i.e. the relaxation towards the Maxwell distribution in velocity space. In contradistinction to the Fokker-Planck equation, the derived new evolution equation is non-local both in time and in velocity space, owing to correlated recollision events between the fluid and particle B. In the long-time limit, it describes a non-markovian generalized Ornstein-Uhlenbeck process. However, in spite of this complex dynamical behaviour, the Stokes-Einstein law relating the friction and diffusion coefficients is shown to remain valid. A microscopic expression for the friction coefficient is derived, which acquires the form of the Stokes law in the limit where the mean-free in the gas is small compared to the radius of particle B.Comment: 28 pages, no figure, submitted to Journal of Statistical Physic

Phase diffusion as a model for coherent suppression of tunneling in the presence of noise

We study the stabilization of coherent suppression of tunneling in a driven double-well system subject to random periodic $\delta-$function ``kicks''. We model dissipation due to this stochastic process as a phase diffusion process for an effective two-level system and derive a corresponding set of Bloch equations with phase damping terms that agree with the periodically kicked system at discrete times. We demonstrate that the ability of noise to localize the system on either side of the double-well potenital arises from overdamping of the phase of oscillation and not from any cooperative effect between the noise and the driving field. The model is investigated with a square wave drive, which has qualitatively similar features to the widely studied cosinusoidal drive, but has the additional advantage of allowing one to derive exact analytic expressions.Comment: 17 pages, 4 figures, submitted to Phys. Rev.

Chaos or Noise - Difficulties of a Distinction

In experiments, the dynamical behavior of systems is reflected in time series. Due to the finiteness of the observational data set it is not possible to reconstruct the invariant measure up to arbitrary fine resolution and arbitrary high embedding dimension. These restrictions limit our ability to distinguish between signals generated by different systems, such as regular, chaotic or stochastic ones, when analyzed from a time series point of view. We propose to classify the signal behavior, without referring to any specific model, as stochastic or deterministic on a certain scale of the resolution $\epsilon$, according to the dependence of the $(\epsilon,\tau)$-entropy, $h(\epsilon, \tau)$, and of the finite size Lyapunov exponent, $\lambda(\epsilon)$, on $\epsilon$.Comment: 24 pages RevTeX, 9 eps figures included, two references added, minor corrections, one section has been split in two (submitted to PRE

Molecular basis of FIR-mediated c-myc transcriptional control

The far upstream element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream of the c-myc promoter. Then, FBP recruits its specific repressor (FIR), which acts as an on/off transcriptional switch. Here we describe the molecular basis of FIR recruitment, showing that the tandem RNA recognition motifs of FIR provide a platform for independent FUSE DNA and FBP protein binding and explaining the structural basis of the reversibility of the FBP-FIR interaction. We also show that the physical coupling between FBP and FIR is modulated by a flexible linker positioned sequentially to the recruiting element. Our data explain how the FUSE system precisely regulates c-myc transcription and suggest that a small change in FBP-FIR affinity leads to a substantial effect on c-Myc concentration.MRC Grant-in-aid U11757455