Human IFIT1 inhibits mRNA translation of rubulaviruses but not other members of the Paramyxoviridae family

This work was supported by The Welcome Trust (101788/Z/13/Z, 101792/Z/13/Z) and Medical research council grant (G1100110/1, MR/K024213/1).We have previously shown that IFIT1 is primarily responsible for the antiviral action of interferon (IFN) alpha/beta against parainfluenza virus (PIV) type 5, selectively inhibiting the translation of PIV5 mRNAs. Here we report that whilst PIV2, PIV5 and mumps virus (MuV) are sensitive to IFIT1, non-rubulavirus members of the paramyxoviridae such as PIV3, Sendai virus (SeV) and canine distemper virus (CDV) are resistant. The IFIT1-sensitivity of PIV5 was not rescued by co-infection with an IFIT1-resistant virus (PIV3), demonstrating that PIV3 does not specifically inhibit the antiviral activity of IFIT1 and that the inhibition of PIV5 mRNAs is regulated by cis-acting elements. We developed an in vitro translation system using purified human IFIT1 to further investigate the mechanism of action of IFIT1. Whilst the translation of PIV2, PIV5 and MuV mRNAs were directly inhibited by IFIT1, the translation of PIV3, SeV and CDV mRNAs were not. Using purified human mRNA capping enzymes we show biochemically that efficient inhibition by IFIT1 is dependent upon a 5’ guanosine nucleoside cap (which need not be N7-methylated) and that this sensitivity is partly abrogated by 2’ O methylation of the cap 1 ribose. Intriguingly, PIV5 M mRNA, in contrast to NP mRNA, remained sensitive to inhibition by IFIT1 following in vitro 2’ O methylation, suggesting that other structural features of mRNAs may influence their sensitivity to IFIT1. Thus, surprisingly, the viral polymerases (which have 2’ -O-methyltransferase activity) of rubulaviruses do not protect these viruses from inhibition by IFIT1. Possible biological consequences of this are discussed. Importance Paramyxoviruses cause a wide variety of diseases and yet most of their genes encode for structural proteins and proteins involved in their replication cycle. Thus the amount of genetic information that determines the type of disease paramyxoviruses cause is relatively small. One factor that will influence disease outcomes is how they interact with innate host cell defences, including the interferon (IFN) system. Here we show that different paramyxoviruses interact in distinct ways with cells in a pre-existing IFN-induced antiviral state. Strikingly, all the rubulaviruses tested were sensitive to the antiviral action of ISG56/IFIT1, whilst all the other paramyxoviruses tested were resistant. We developed novel in vitro biochemical assays to investigate the mechanism of action of IFIT1, demonstrating that the mRNAs of rubulaviruses can be directly inhibited by IFIT1 and that this is at least partially because their mRNAs are not correctly methylated.Publisher PDFPeer reviewe

Orthonormal sequences in L2(Rd)L^2(R^d) and time frequency localization

We study uncertainty principles for orthonormal bases and sequences in $L^2(\R^d)$. As in the classical Heisenberg inequality we focus on the product of the dispersions of a function and its Fourier transform. In particular we prove that there is no orthonormal basis for $L^2(\R)$ for which the time and frequency means as well as the product of dispersions are uniformly bounded. The problem is related to recent results of J. Benedetto, A. Powell, and Ph. Jaming. Our main tool is a time frequency localization inequality for orthonormal sequences in $L^2(\R^d)$. It has various other applications.Comment: 18 page

Stellar Pulsations excited by a scattered mass

We compute the energy spectra of the gravitational signals emitted when a mass m is scattered by the gravitational field of a star of mass M >> m. We show that, unlike black holes in similar processes, the quasi-normal modes of the star are excited, and that the amount of energy emitted in these modes depends on how close the exciting mass can get to the star.Comment: 23 pages, 6 figures, RevTe

Tidally-Induced Apsidal Precession in Double White Dwarfs: a new mass measurement tool with LISA

Galactic interacting double white dwarfs (DWD) are guaranteed gravitational wave (GW) sources for the GW detector LISA, with more than 10^4 binaries expected to be detected over the mission's lifetime. Part of this population is expected to be eccentric, and here we investigate the potential for constraining the white dwarf (WD) properties through apsidal precession in these binaries. We analyze the tidal, rotational, and general relativistic contributions to apsidal precession by using detailed He WD models, where the evolution of the star's interior is followed throughout the cooling phase. In agreement with previous studies of zero-temperature WDs, we find that apsidal precession in eccentric DWDs can lead to a detectable shift in the emitted GW signal when binaries with cool (old) components are considered. This shift increases significantly for hot (young) WDs. We find that apsidal motion in hot (cool) DWDs is dominated by tides at orbital frequencies above ~10^{-4}Hz (10^{- 3}$Hz). The analysis of apsidal precession in these sources while ignoring the tidal component would lead to an extreme bias in the mass determination, and could lead us to misidentify WDs as neutron stars or black holes. We use the detailed WD models to show that for older, cold WDs, there is a unique relationship that ties the radius and apsidal precession constant to the WD masses, therefore allowing tides to be used as a tool to constrain the source masses.Comment: 23 pages, 7 figures, revised to match accepted ApJ versio

A Magnetically-Switched, Rotating Black Hole Model For the Production of Extragalactic Radio Jets and the Fanaroff and Riley Class Division

A model is presented in which both Fanaroff and Riley class I and II extragalactic jets are produced by magnetized accretion disk coronae in the ergospheres of rotating black holes. While the jets are produced in the accretion disk itself, the output power still is an increasing function of the black hole angular momentum. For high enough spin, the black hole triggers the magnetic switch, producing highly-relativistic, kinetic-energy-dominated jets instead of Poynting-flux-dominated ones for lower spin. The coronal mass densities needed to trigger the switch at the observed FR break power are quite small ($\sim 10^{-15} g cm^{-3}$), implying that the source of the jet material may be either a pair plasma or very tenuous electron-proton corona, not the main accretion disk itself. The model explains the differences in morphology and Mach number between FR I and II sources and the observed trend for massive galaxies to undergo the FR I/II transition at higher radio power. It also is consistent with the energy content of extended radio lobes and explains why, because of black hole spindown, the space density of FR II sources should evolve more rapidly than that of FR I sources. If the present model is correct, then the ensemble average speed of parsec-scale jets in sources distinguished by their FR I morphology (not luminosity) should be distinctly slower than that for sources with FR II morphology. The model also suggests the existence of a population of high-redshift, sub-mJy FR I and II radio sources associated with spiral or pre-spiral galaxies that flared once when their black holes were formed but were never again re-kindled by mergers.Comment: 14 pages, 2 figures, final version to appear in Sept Ap

Surgical Mask to Prevent Influenza Transmission in Households: A Cluster Randomized Trial

Facemasks and respirators have been stockpiled during pandemic preparedness. However, data on their effectiveness for limiting transmission are scarce. We evaluated the effectiveness of facemask use by index cases for limiting influenza transmission by large droplets produced during coughing in households.A cluster randomized intervention trial was conducted in France during the 2008-2009 influenza season. Households were recruited during a medical visit of a household member with a positive rapid influenza A test and symptoms lasting less than 48 hours. Households were randomized either to the mask or control group for 7 days. In the intervention arm, the index case had to wear a surgical mask from the medical visit and for a period of 5 days. The trial was initially intended to include 372 households but was prematurely interrupted after the inclusion of 105 households (306 contacts) following the advice of an independent steering committee. We used generalized estimating equations to test the association between the intervention and the proportion of household contacts who developed an influenza-like illness during the 7 days following the inclusion. Influenza-like illness was reported in 24/148 (16.2%) of the contacts in the intervention arm and in 25/158 (15.8%) of the contacts in the control arm and the difference between arms was 0.40% (95%CI: -10% to 11%, P = 1.00). We observed a good adherence to the intervention. In various sensitivity analyses, we did not identify any trend in the results suggesting effectiveness of facemasks.This study should be interpreted with caution since the lack of statistical power prevents us to draw formal conclusion regarding effectiveness of facemasks in the context of a seasonal epidemic.clinicaltrials.gov NCT00774774

Resonant origin for density fluctuations deep within the Sun: helioseismology and magneto-gravity waves

We analyze helioseismic waves near the solar equator in the presence of magnetic fields deep within the solar radiative zone. We find that reasonable magnetic fields can significantly alter the shapes of the wave profiles for helioseismic g-modes. They can do so because the existence of density gradients allows g-modes to resonantly excite Alfven waves, causing mode energy to be funnelled along magnetic field lines, away from the solar equatorial plane. The resulting wave forms show comparatively sharp spikes in the density profile at radii where these resonances take place. We estimate how big these waves might be in the Sun, and perform a first search for observable consequences. We find the density excursions at the resonances to be too narrow to be ruled out by present-day analyses of p-wave helioseismic spectra, even if their amplitudes were to be larger than a few percent. (In contrast it has been shown in (Burgess et al. 2002) that such density excursions could affect solar neutrino fluxes in an important way.) Because solar p-waves are not strongly influenced by radiative-zone magnetic fields, standard analyses of helioseismic data should not be significantly altered. The influence of the magnetic field on the g-mode frequency spectrum could be used to probe sufficiently large radiative-zone magnetic fields should solar g-modes ever be definitively observed. Our results would have stronger implications if overstable solar g-modes should prove to have very large amplitudes, as has sometimes been argued.Comment: 18 pages, 6 figures; misprints correcte

Quantum Symmetries and Strong Haagerup Inequalities

In this paper, we consider families of operators $\{x_r\}_{r \in \Lambda}$ in a tracial C$^\ast$-probability space $(\mathcal A, \phi)$, whose joint $\ast$-distribution is invariant under free complexification and the action of the hyperoctahedral quantum groups $\{H_n^+\}_{n \in \N}$. We prove a strong form of Haagerup's inequality for the non-self-adjoint operator algebra $\mathcal B$ generated by $\{x_r\}_{r \in \Lambda}$, which generalizes the strong Haagerup inequalities for $\ast$-free R-diagonal families obtained by Kemp-Speicher \cite{KeSp}. As an application of our result, we show that $\mathcal B$ always has the metric approximation property (MAP). We also apply our techniques to study the reduced C$^\ast$-algebra of the free unitary quantum group $U_n^+$. We show that the non-self-adjoint subalgebra $\mathcal B_n$ generated by the matrix elements of the fundamental corepresentation of $U_n^+$ has the MAP. Additionally, we prove a strong Haagerup inequality for $\mathcal B_n$, which improves on the estimates given by Vergnioux's property RD \cite{Ve}

On twisted Fourier analysis and convergence of Fourier series on discrete groups

We study norm convergence and summability of Fourier series in the setting of reduced twisted group $C^*$-algebras of discrete groups. For amenable groups, F{\o}lner nets give the key to Fej\'er summation. We show that Abel-Poisson summation holds for a large class of groups, including e.g. all Coxeter groups and all Gromov hyperbolic groups. As a tool in our presentation, we introduce notions of polynomial and subexponential H-growth for countable groups w.r.t. proper scale functions, usually chosen as length functions. These coincide with the classical notions of growth in the case of amenable groups.Comment: 35 pages; abridged, revised and update