Carrageenan induced phosphorylation of Akt is dependent on neurokinin-1 expressing neurons in the superficial dorsal horn

<p>Abstract</p> <p>Background</p> <p>Paw carrageenan induces activation of phosphatidylinositol 3-kinase (PI-3K) and Akt in dorsal horn neurons in addition to induction of pain behavior. Spinal PI-3K activation is also thought to be required for inflammation-induced trafficking of GluA1, AMPA receptor subunits, into plasma membranes from cytosol. Phosphorylation of Akt has a unique time course. It occurs first in the superficial dorsal horn (0.75 h), then soon dissipates and is followed an hour later by Akt phosphorylation in deeper dorsal horn laminae, primarily lamina V. Initially, we wished to determine if Akt phosphorylation in the deeper laminae were dependent on the presence of lamina I, neurokinin receptor bearing projection neurons. As the study progressed, our aims grew to include the question, whether carrageenan-induced GluA1 subunit trafficking was downstream of Akt phosphorylation.</p> <p>Results</p> <p>Rats pretreated with spinal saporin conjugated to a stabilized form of substance P had substantial loss of neurons with neurokinin 1 receptors throughout their superficial, but not deep dorsal horns. Animals pre-treated with substance P-saporin exhibited no change in locomotor ability and a small, but significant decrease in carrageenan-induced mechanical allodynia when compared to animals pre-treated with spinal saporin alone. Importantly, carrageenan-induced phosphorylation of Akt was blocked, in the substance P-saporin treated group, throughout the spinal cord grey matter. In marked contrast, carrageenan induced-trafficking of the GluA1 receptor subunit increased equivalently in both treatment groups.</p> <p>Conclusions</p> <p>We infer from these data that 1) phosphorylation of Akt in the deep dorsal horn is dependent on prior activation of NK1 receptor bearing cells in superficial dorsal horn, and 2) there are parallel spinal intracellular cascades initiated by the carrageenan injection downstream of PI-3K activation, including one containing Akt and another involving GluA1 trafficking into neuronal plasma membranes that separately lead to enhanced pain behavior. These results imply that the two pathways downstream of PI-3K can be activated separately and therefore should be able to be inhibited independently.</p

Binary black hole late inspiral: Simulations for gravitational wave observations

Coalescing binary black hole mergers are expected to be the strongest gravitational wave sources for ground-based interferometers, such as the LIGO, VIRGO, and GEO600, as well as the space-based interferometer LISA. Until recently it has been impossible to reliably derive the predictions of General Relativity for the final merger stage, which takes place in the strong-field regime. Recent progress in numerical relativity simulations is, however, revolutionizing our understanding of these systems. We examine here the specific case of merging equal-mass Schwarzschild black holes in detail, presenting new simulations in which the black holes start in the late inspiral stage on orbits with very low eccentricity and evolve for ~1200M through ~7 orbits before merging. We study the accuracy and consistency of our simulations and the resulting gravitational waveforms, which encompass ~14 cycles before merger, and highlight the importance of using frequency (rather than time) to set the physical reference when comparing models. Matching our results to PN calculations for the earlier parts of the inspiral provides a combined waveform with less than half a cycle of accumulated phase error through the entire coalescence. Using this waveform, we calculate signal-to-noise ratios (SNRs) for iLIGO, adLIGO, and LISA, highlighting the contributions from the late-inspiral and merger-ringdown parts of the waveform which can now be simulated numerically. Contour plots of SNR as a function of z and M show that adLIGO can achieve SNR >~ 10 for some intermediate-mass binary black holes (IMBBHs) out to z ~ 1, and that LISA can see massive binary black holes (MBBHs) in the range 3x10^4 100 out to the earliest epochs of structure formation at z > 15.Comment: 17 pages, 20 figures. Final published versio

Violacein: Properties and Production of a Versatile Bacterial Pigment

Violacein-producing bacteria, with their striking purple hues, have undoubtedly piqued the curiosity of scientists since their first discovery. The bisindole violacein is formed by the condensation of two tryptophan molecules through the action of five proteins. The genes required for its production, vio ABCDE, and the regulatory mechanisms employed have been studied within a small number of violacein-producing strains. As a compound, violacein is known to have diverse biological activities, including being an anticancer agent and being an antibiotic against Staphylococcus aureus and other Gram-positive pathogens. Identifying the biological roles of this pigmented molecule is of particular interest, and understanding violacein&apos;s function and mechanism of action has relevance to those unmasking any of its commercial or therapeutic benefits. Unfortunately, the production of violacein and its related derivatives is not easy and so various groups are also seeking to improve the fermentative yields of violacein through genetic engineering and synthetic biology. This review discusses the recent trends in the research and production of violacein by both natural and genetically modified bacterial strains.open0

Recoiling from a kick in the head-on collision of spinning black holes

Recoil ``kicks'' induced by gravitational radiation are expected in the inspiral and merger of black holes. Recently the numerical relativity community has begun to measure the significant kicks found when both unequal masses and spins are considered. Because understanding the cause and magnitude of each component of this kick may be complicated in inspiral simulations, we consider these effects in the context of a simple test problem. We study recoils from collisions of binaries with initially head-on trajectories, starting with the simplest case of equal masses with no spin and then adding spin and varying the mass ratio, both separately and jointly. We find spin-induced recoils to be significant relative to unequal-mass recoils even in head-on configurations. Additionally, it appears that the scaling of transverse kicks with spins is consistent with post-Newtonian theory, even though the kick is generated in the nonlinear merger interaction, where post-Newtonian theory should not apply. This suggests that a simple heuristic description might be effective in the estimation of spin-kicks.Comment: 12 pages, 10 figures. Replaced with published version, including more discussion of convergence and properties of final hol

The Spitzer C2D Survey of Nearby Dense Cores: Jet and Molecular Outflow Associated With A Young Stellar Object in Core A of L1251

A long infrared jet has been discovered by the Spitzer c2d Legacy Program in core A of L1251. It is associated with a very embedded Class 0 object with an accretion luminosity of about 0.9 L(circle dot) derived by radiative transfer model fitting to the observed spectral energy distribution. Comparing the observed Infrared Array Camera colors along the infrared jet with those calculated from a model of an admixture of gas with a power-law temperature distribution indicates that the jet is possibly created by a paraboloidal bow shock propagating into the ambient medium of n(H(2)) = 10(5) cm(-3). In addition, the variation of the power-law index along the jet suggests that the portion of hot gas decreases with distance from the jet engine. The molecular outflow in this region has been mapped for the first time using CO data. From the calculated outflow momentum flux, a very strong lower limit to the average accretion luminosity is 3.6 sin i/cos(3) i L(circle dot), indicative of a decrease in the accretion rate with time.Korean government (MEST) 2009-0062865NRF R01-2007-000-20336-0NASA 1407, 1224608Astronom

Full-length genomic analysis of korean porcine sapelovirus strains.

Porcine sapelovirus (PSV), a species of the genus Sapelovirus within the family Picornaviridae, is associated with diarrhea, pneumonia, severe neurological disorders, and reproductive failure in pigs. However, the structural features of the complete PSV genome remain largely unknown. To analyze the structural features of PSV genomes, the full-length nucleotide sequences of three Korean PSV strains were determined and analyzed using bioinformatic techniques in comparison with other known PSV strains. The Korean PSV genomes ranged from 7,542 to 7,566 nucleotides excluding the 3' poly(A) tail, and showed the typical picornavirus genome organization; 5'untranslated region (UTR)-L-VP4-VP2-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3'UTR. Three distinct cis-active RNA elements, the internal ribosome entry site (IRES) in the 5'UTR, a cis-replication element (CRE) in the 2C coding region and 3'UTR were identified and their structures were predicted. Interestingly, the structural features of the CRE and 3'UTR were different between PSV strains. The availability of these first complete genome sequences for PSV strains will facilitate future investigations of the molecular pathogenesis and evolutionary characteristics of PSV

Evolving a puncture black hole with fixed mesh refinement

We present an algorithm for treating mesh refinement interfaces in numerical relativity. We detail the behavior of the solution near such interfaces located in the strong field regions of dynamical black hole spacetimes, with particular attention to the convergence properties of the simulations. In our applications of this technique to the evolution of puncture initial data with vanishing shift, we demonstrate that it is possible to simultaneously maintain second order convergence near the puncture and extend the outer boundary beyond 100M, thereby approaching the asymptotically flat region in which boundary condition problems are less difficult and wave extraction is meaningful.Comment: 18 pages, 12 figures. Minor changes, final PRD versio

Recoiling from a Kick in the Head-On Case

Recoil "kicks" induced by gravitational radiation are expected in the inspiral and merger of black holes. Recently the numerical relativity community has begun to measure the significant kicks found when both unequal masses and spins are considered. Because understanding the cause and magnitude of each component of this kick may be complicated in inspiral simulations, we consider these effects in the context of a simple test problem. We study recoils from collisions of binaries with initially head-on trajectories, starting with the simplest case of equal masses with no spin; adding spin and varying the mass ratio, both separately and jointly. We find spin-induced recoils to be significant even in head-on configurations. Additionally, it appears that the scaling of transverse kicks with spins is consistent with post-Newtonian (PN) theory, even though the kick is generated in the nonlinear merger interaction, where PN theory should not apply. This suggests that a simple heuristic description might be effective in the estimation of spin-kicks

Analysis of ``Gauge Modes'' in Linearized Relativity

By writing the complete set of $3 + 1$ (ADM) equations for linearized waves, we are able to demonstrate the properties of the initial data and of the evolution of a wave problem set by Alcubierre and Schutz. We show that the gauge modes and constraint error modes arise in a straightforward way in the analysis, and are of a form which will be controlled in any well specified convergent computational discretization of the differential equations.Comment: 11pages LaTe

Intense field stabilization in circular polarization: 3D time-dependent dynamics

We investigate the stabilization of a hydrogen atom in circularly polarized laser fields. We use a time-dependent, fully three dimensional approach to study the quantum dynamics of the hydrogen atom subject to high intensity, short wavelength laser pulses. We find enhanced survival probability as the field is increased under fixed envelope conditions. We also confirm wavepacket dynamics seen in prior time-dependent computations restricted to two dimensions.Comment: 4 pages, 3 figures, submitte