The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents

<p>Abstract</p> <p>Background</p> <p>The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs) is one of the largest gene families in most mammals and the most exploited in terms of drug discovery. An accurate comparison of the GPCR repertoires in dog and human is valuable for the prediction of functional similarities and differences between the species.</p> <p>Results</p> <p>We searched the dog genome for non-olfactory GPCRs and obtained 353 full-length GPCR gene sequences, 18 incomplete sequences and 13 pseudogenes. We established relationships between human, dog, rat and mouse GPCRs resolving orthologous pairs and species-specific duplicates. We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire. There is a higher number of orthologous pairs between dog and human that are conserved as compared with either mouse or rat. In almost all cases the differences observed between the dog and human genomes coincide with other variations in the rodent species. Several GPCR gene expansions characteristic for rodents are not found in dog.</p> <p>Conclusion</p> <p>The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents. The comparison of the dog, human and rodent repertoires revealed several examples of species-specific gene duplications and deletions. This information is useful in the selection of model organisms for pharmacological experiments.</p

Anomalous material-dependent transport of focused, laser-driven proton beams.

Intense lasers can accelerate protons in sufficient numbers and energy that the resulting beam can heat materials to exotic warm (10 s of eV temperature) states. Here we show with experimental data that a laser-driven proton beam focused onto a target heated it in a localized spot with size strongly dependent upon material and as small as 35 μm radius. Simulations indicate that cold stopping power values cannot model the intense proton beam transport in solid targets well enough to match the large differences observed. In the experiment a 74 J, 670 fs laser drove a focusing proton beam that transported through different thicknesses of solid Mylar, Al, Cu or Au, eventually heating a rear, thin, Au witness layer. The XUV emission seen from the rear of the Au indicated a clear dependence of proton beam transport upon atomic number, Z, of the transport layer: a larger and brighter emission spot was measured after proton transport through the lower Z foils even with equal mass density for supposed equivalent proton stopping range. Beam transport dynamics pertaining to the observed heated spot were investigated numerically with a particle-in-cell (PIC) code. In simulations protons moving through an Al transport layer result in higher Au temperature responsible for higher Au radiant emittance compared to a Cu transport case. The inferred finding that proton stopping varies with temperature in different materials, considerably changing the beam heating profile, can guide applications seeking to controllably heat targets with intense proton beams

Impurity generation during intense lower hybrid heating experiments on the Alcator C tokamak

and disposal, in whole or in part by or for the United States govern-ment is permitted. By acceptance of this article, the publisher and/or recipient ac-knowledges the U.S. Government&apos;s right to retain a non-exclusive, royalty-free license in and to any copyright covering this paper. Experiments are underway on the Alcator C Tokamak with over 1 MW of RF power injected into the plasma at a frequency of 4.6 GHz to study both heating and current drive effects. During these studies, impurity genera-tion from limiter structures has been observed. The RF induced impurity influx is a strongly nonlinear function of net injected power. For Prf &lt; 500 kW, only small effects are seen. As Prf approaches 1 MW, however, sharp increases in impurity influxes and Zeff are observed. Three different lim-iter materials have been used during these studies: molybdenum, graphite, and silicon-carbide coated graphite. In each case, the materials of the limiter structure are seen to dominate the increased impurity influx. In a typical case, with Prf = 1.0 MW e = 1.3 x 1014 cm- 3, and the SiC coated limiters, Zeff is seen to increase from 1.5 before the RF pulse to about 4 during the heating. At the same time, central Te increases from 2000 eV to 3000 eV and central Ti from 1200 eV to 1800 eV. Similar effects are seen in both H2 and D2 working gas discharges. The contribution to impurity genera-tion of nonthermal electrons, which are produced by the RF, is under investi-gation. Changes in edge plasma temperature and density, as well as the possibility that the particle transport is affected by the RF, are also being examined. Results of the experiments with the three different limiter materials are compared, and contributions of impurity radiation to the overall power balance are estimated

Measurement of L-shell emission from mid-Z targets under non-LTE conditions using Transmission Grating Spectrometer and DANTE power diagnostics

Producción CientíficaIn this work, we present the measurement of L-band emission from buried Sc/V targets in experiments performed at the OMEGA laser facility. The goal of these experiments was to study non-local thermodynamic equilibrium plasmas and benchmark atomic physics codes. The L-band emission was measured simultaneously by the time resolved DANTE power diagnostic and the recently fielded time integrated Soreq-Transmission Grating Spectrometer (TGS) diagnostic. The TGS measurement was used to support the spectral reconstruction process needed for the unfolding of the DANTE data. The Soreq-TGS diagnostic allows for broadband spectral measurement in the 120 eV–2000 eV spectral band, covering L- and M-shell emission of mid- and high-Z elements, with spectral resolution λ/Δλ = 8–30 and accuracy better than 25%. The Soreq-TGS diagnostic is compatible with ten-inch-manipulator platforms and can be used for a wide variety of high energy density physics, laboratory astrophysics, and inertial confinement fusion experiments

X-ray Astronomy in the Laboratory with a Miniature Compact Object Produced by Laser-Driven Implosion

Laboratory spectroscopy of non-thermal equilibrium plasmas photoionized by intense radiation is a key to understanding compact objects, such as black holes, based on astronomical observations. This paper describes an experiment to study photoionizing plasmas in laboratory under well-defined and genuine conditions. Photoionized plasma is here generated using a 0.5-keV Planckian x-ray source created by means of a laser-driven implosion. The measured x-ray spectrum from the photoionized silicon plasma resembles those observed from the binary stars Cygnus X-3 and Vela X-1 with the Chandra x-ray satellite. This demonstrates that an extreme radiation field was produced in the laboratory, however, the theoretical interpretation of the laboratory spectrum significantly contradicts the generally accepted explanations in x-ray astronomy. This model experiment offers a novel test bed for validation and verification of computational codes used in x-ray astronomy.Comment: 5 pages, 4 figures are included. This is the original submitted version of the manuscript to be published in Nature Physic

Observation and control of shock waves in individual nanoplasmas

In a novel experiment that images the momentum distribution of individual, isolated 100-nm-scale plasmas, we make the first experimental observation of shock waves in nanoplasmas. We demonstrate that the introduction of a heating pulse prior to the main laser pulse increases the intensity of the shock wave, producing a strong burst of quasi-monochromatic ions with an energy spread of less than 15%. Numerical hydrodynamic calculations confirm the appearance of accelerating shock waves, and provide a mechanism for the generation and control of these shock waves. This observation of distinct shock waves in dense plasmas enables the control, study, and exploitation of nanoscale shock phenomena with tabletop-scale lasers.Comment: 8 pages of manuscript, 9 pages of supplemental information, total 17 page

The systematic annotation of the three main GPCR families in Reactome

Reactome is an open-source, freely available database of human biological pathways and processes. A major goal of our work is to provide an integrated view of cellular signalling processes that spans from ligand–receptor interactions to molecular readouts at the level of metabolic and transcriptional events. To this end, we have built the first catalogue of all human G protein-coupled receptors (GPCRs) known to bind endogenous or natural ligands. The UniProt database has records for 797 proteins classified as GPCRs and sorted into families A/1, B/2 and C/3 on the basis of amino accid sequence. To these records we have added details from the IUPHAR database and our own manual curation of relevant literature to create reactions in which 563 GPCRs bind ligands and also interact with specific G-proteins to initiate signalling cascades. We believe the remaining 234 GPCRs are true orphans. The Reactome GPCR pathway can be viewed as a detailed interactive diagram and can be exported in many forms. It provides a template for the orthology-based inference of GPCR reactions for diverse model organism species, and can be overlaid with protein–protein interaction and gene expression datasets to facilitate overrepresentation studies and other forms of pathway analysis