Understanding diversity of human innate immunity receptors: analysis of surface features of leucine-rich repeat domains in NLRs and TLRs.

BackgroundThe human innate immune system uses a system of extracellular Toll-like receptors (TLRs) and intracellular Nod-like receptors (NLRs) to match the appropriate level of immune response to the level of threat from the current environment. Almost all NLRs and TLRs have a domain consisting of multiple leucine-rich repeats (LRRs), which is believed to be involved in ligand binding. LRRs, found also in thousands of other proteins, form a well-defined "horseshoe"-shaped structural scaffold that can be used for a variety of functions, from binding specific ligands to performing a general structural role. The specific functional roles of LRR domains in NLRs and TLRs are thus defined by their detailed surface features. While experimental crystal structures of four human TLRs have been solved, no structure data are available for NLRs.ResultsWe report a quantitative, comparative analysis of the surface features of LRR domains in human NLRs and TLRs, using predicted three-dimensional structures for NLRs. Specifically, we calculated amino acid hydrophobicity, charge, and glycosylation distributions within LRR domain surfaces and assessed their similarity by clustering. Despite differences in structural and genomic organization, comparison of LRR surface features in NLRs and TLRs allowed us to hypothesize about their possible functional similarities. We find agreement between predicted surface similarities and similar functional roles in NLRs and TLRs with known agonists, and suggest possible binding partners for uncharacterized NLRs.ConclusionDespite its low resolution, our approach permits comparison of molecular surface features in the absence of crystal structure data. Our results illustrate diversity of surface features of innate immunity receptors and provide hints for function of NLRs whose specific role in innate immunity is yet unknown

Stability Properties of Strongly Magnetized Spine Sheath Relativistic Jets

The linearized relativistic magnetohydrodynamic (RMHD) equations describing a uniform axially magnetized cylindrical relativistic jet spine embedded in a uniform axially magnetized relativistically moving sheath are derived. The displacement current is retained in the equations so that effects associated with Alfven wave propagation near light speed can be studied. A dispersion relation for the normal modes is obtained. Analytical solutions for the normal modes in the low and high frequency limits are found and a general stability condition is determined. A trans-Alfvenic and even a super-Alfvenic relativistic jet spine can be stable to velocity shear driven Kelvin-Helmholtz modes. The resonance condition for maximum growth of the normal modes is obtained in the kinetically and magnetically dominated regimes. Numerical solution of the dispersion relation verifies the analytical solutions and is used to study the regime of high sound and Alfven speeds.Comment: 42 pages includes 7 figures, to appear in Ap

Giant molecular clouds as regions of particle acceleration

One of the most interesting results of investigations carried out on the satellites SAS-II and COS-B is the discovery of unidentified discrete gamma sources. Possibly a considerable part of them may well be giant molecular clouds. Gamma emission from clouds is caused by the processes with participation of cosmic rays. The estimation of the cosmic ray density in clouds has shown that for the energy E approx. = I GeV their density can 10 to 1000 times exceed the one in intercloud space. We have made an attempt to determine the mechanism which could lead to the increase in the cosmic ray density in clouds

3D Relativistic Magnetohydrodynamic Simulations of Magnetized Spine-Sheath Relativistic Jets

Numerical simulations of weakly magnetized and strongly magnetized relativistic jets embedded in a weakly magnetized and strongly magnetized stationary or weakly relativistic (v = c/2) sheath have been performed. A magnetic field parallel to the flow is used in these simulations performed by the new GRMHD numerical code RAISHIN used in its RMHD configuration. In the numerical simulations the Lorentz factor $\gamma = 2.5$ jet is precessed to break the initial equilibrium configuration. In the simulations sound speeds are $\lesssim c/\sqrt 3$ in the weakly magnetized simulations and $\lesssim 0.3c$ in the strongly magnetized simulations. The Alfven wave speed is $\lesssim 0.07c$ in the weakly magnetized simulations and $\lesssim 0.56c$ in the strongly magnetized simulations. The results of the numerical simulations are compared to theoretical predictions from a normal mode analysis of the linearized relativistic magnetohydrodynamic (RMHD) equations capable of describing a uniform axially magnetized cylindrical relativistic jet embedded in a uniform axially magnetized relativistically moving sheath. The theoretical dispersion relation allows investigation of effects associated with maximum possible sound speeds, Alfven wave speeds near light speed and relativistic sheath speeds. The prediction of increased stability of the weakly magnetized system resulting from c/2 sheath speeds and the stabilization of the strongly magnetized system resulting from c/2 sheath speeds is verified by the numerical simulation results.Comment: 31 pages, 8 figures, accepted for publicatin in ApJ. A paper with high resolution figures available at http://gammaray.nsstc.nasa.gov/~mizuno/research_new.htm

Circular dichroism at equal energy sharing in photo-double-ionization of He

Interference between dipole and quadrupole transition amplitudes in photo-double-ionization of He by an elliptically polarized vuv photon is shown to induce circular dichroism in the case of equal energy sharing. The magnitude of this retardation-induced dichroic effect is estimated and its impact on the nondipole asymmetries of the triply differential cross section is demonstrated

Does Pulsar B1757--24 Have a Fallback Disk?

Radio pulsars are thought to spin-down primarily due to torque from magnetic dipole radiation (MDR) emitted by the time-varying stellar magnetic field as the star rotates. This assumption yields a `characteristic age' for a pulsar which has generally been assumed to be comparable to the actual age. Recent observational limits on the proper motion of pulsar B1757-24, however, revealed that the actual age (>39 kyr) of this pulsar is much greater than its MDR characteristic age (16 kyr) - calling into question the assumption of pure MDR spin-down for this and other pulsars. To explore the possible cause of this discrepancy, we consider a scenario in which the pulsar acquired an accretion disk from supernova ejecta, and the subsequent spin-down occurred under the combined action of MDR and accretion torques. A simplified model of the accretion torque involving a constant mass inflow rate at the pulsar magnetosphere can explain the age and period derivative of the pulsar for reasonable values of the pulsar magnetic field and inflow rate. We discuss testable predictions of this model.Comment: Accepted by ApJ Letters. 15 pages with 1 figur

Transformation of the Poynting flux into the kinetic energy in relativistic jets

The acceleration of relativistic jets from the Poynting to the matter dominated stage is considered. The are generally two collimation regimes, which we call equilibrium and non-equilibrium, correspondingly. In the first regime, the jet is efficiently accelerated till the equipartition between the kinetic and electro-magnetic energy. We show that after the equilibrium jet ceases to be Poynting dominated, the ratio of the electro-magnetic to the kinetic energy decreases only logarithmically so that such jets become truly matter dominated only at extremely large distances. Non-equilibrium jets remain generally Poynting dominated till the logarithmically large distances. In the only case when a non-equilibrium jet is accelerated till the equipartition level, we found that the flow is not continued to the infinity but is focused towards the axis at a finite distance from the origin.Comment: Submitted to MNRAS Minor changes in the Conclusion