Native Tertiary Structure and Nucleoside Modifications Suppress tRNA's Intrinsic Ability to Activate the Innate Immune Sensor PKR

Interferon inducible protein kinase PKR is an essential component of innate immunity. It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell. Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation. We have previously demonstrated that a 5′-end triphosphate-a signature of certain viral and bacterial transcripts-confers the ability of relatively unstructured model RNA transcripts to activate PKR to inhibit translation, and that this activation is abrogated by certain modifications present in cellular RNAs. In order to understand the biological implications of native RNA tertiary structure and nucleoside modifications on PKR activation, we study here the heavily modified cellular tRNAs and the unmodified or the lightly modified mitochondrial tRNAs (mt-tRNA). We find that both a T7 transcript of yeast tRNAPhe and natively extracted total bovine liver mt-tRNA activate PKR in vitro, whereas native E. coli, bovine liver, yeast, and wheat tRNAPhe do not, nor do a variety of base- or sugar-modified T7 transcripts. These results are further supported by activation of PKR by a natively folded T7 transcript of tRNAPhe in vivo supporting the importance of tRNA modification in suppressing PKR activation in cells. We also examine PKR activation by a T7 transcript of the A14G pathogenic mutant of mt-tRNALeu, which is known to dimerize, and find that the misfolded dimeric form activates PKR in vitro while the monomeric form does not. Overall, the in vitro and in vivo findings herein indicate that tRNAs have an intrinsic ability to activate PKR and that nucleoside modifications and native RNA tertiary folding may function, at least in part, to suppress such activation, thus serving to distinguish self and non-self tRNA in innate immunity

A Unified Algebraic Approach to Few and Many-Body Correlated Systems

The present article is an extended version of the paper {\it Phys. Rev.} {\bf B 59}, R2490 (1999), where, we have established the equivalence of the Calogero-Sutherland model to decoupled oscillators. Here, we first employ the same approach for finding the eigenstates of a large class of Hamiltonians, dealing with correlated systems. A number of few and many-body interacting models are studied and the relationship between their respective Hilbert spaces, with that of oscillators, is found. This connection is then used to obtain the spectrum generating algebras for these systems and make an algebraic statement about correlated systems. The procedure to generate new solvable interacting models is outlined. We then point out the inadequacies of the present technique and make use of a novel method for solving linear differential equations to diagonalize the Sutherland model and establish a precise connection between this correlated system's wave functions, with those of the free particles on a circle. In the process, we obtain a new expression for the Jack polynomials. In two dimensions, we analyze the Hamiltonian having Laughlin wave function as the ground-state and point out the natural emergence of the underlying linear $W_{1+\infty}$ symmetry in this approach.Comment: 18 pages, Revtex format, To appear in Physical Review

Negative Energy in String Theory and Cosmic Censorship Violation

We find asymptotically anti de Sitter solutions in N=8 supergravity which have negative total energy. This is possible since the boundary conditions required for the positive energy theorem are stronger than those required for finite mass (and allowed by string theory). But stability of the anti de Sitter vacuum is still ensured by the positivity of a modified energy, which includes an extra surface term. Some of the negative energy solutions describe classical evolution of nonsingular initial data to naked singularities. Since there is an open set of such solutions, cosmic censorship is violated generically in supergravity. Using the dual field theory description, we argue that these naked singularities will be resolved in the full string theory.Comment: 23 pages, 2 figures, v2: argument for forming naked singularities clarified, references adde

Gravitational collapse of a Hagedorn fluid in Vaidya geometry

The gravitational collapse of a high-density null charged matter fluid, satisfying the Hagedorn equation of state, is considered in the framework of the Vaidya geometry. The general solution of the gravitational field equations can be obtained in an exact parametric form. The conditions for the formation of a naked singularity, as a result of the collapse of the compact object, are also investigated. For an appropriate choice of the arbitrary integration functions the null radial outgoing geodesic, originating from the shell focussing central singularity, admits one or more positive roots. Hence a collapsing Hagedorn fluid could end either as a black hole, or as a naked singularity. A possible astrophysical application of the model, to describe the energy source of gamma-ray bursts, is also considered.Comment: 14 pages, 2 figures, to appear in Phys. Rev.

Application of information entropy to nuclei

Shannon's information entropies in position- and momentum- space and their sum $S$ are calculated for various $s$-$p$ and $s$-$d$ shell nuclei using a correlated one-body density matrix depending on the harmonic oscillator size $b_0$ and the short range correlation parameter $y$ which originates from a Jastrow correlation function. It is found that the information entropy sum for a nucleus depends only on the correlation parameter $y$ through the simple relation $S= s_{0A} + s_{1A} y^{-\lambda_{sA}}$, where $s_{0A}$, $s_{1A}$ and $\lambda_{sA}$ depend on the mass number $A$. A similar approximate expression is also valid for the root mean square radius of the nucleus as function of $y$ leading to an approximate expression which connects $S$ with the root mean square radius. Finally, we propose a method to determine the correlation parameter from the above property of $S$ as well as the linear dependence of $S$ on the logarithm of the number of nucleons.Comment: 10 pages, 10 EPS figures, RevTeX, Phys.Rev.C accepted for publicatio

Two-Dimensional Unoriented Strings And Matrix Models

We investigate unoriented strings and superstrings in two dimensions and their dual matrix quantum mechanics. Most of the models we study have a tachyon tadpole coming from the RP^2 worldsheet which needs to be cancelled by a renormalization of the worldsheet theory. We find evidence that the dual matrix models describe the renormalized theory. The singlet sector of the matrix models is integrable and can be formulated in terms of fermions moving in an external potential and interacting via the Calogero-Moser potential. We show that in the double-scaling limit the latter system exhibits particle-hole duality and interpret it in terms of the dual string theory. We also show that oriented string theories in two dimensions can be continuously deformed into unoriented ones by turning on non-local interactions on the worldsheet. We find two unoriented superstring models for which only oriented worldsheets contribute to the S-matrix. A simple explanation for this is found in the dual matrix model.Comment: 36 pages, harvmac, 2 eps figure