Startle disease mutations reduce the agonist sensitivity of the human inhibitory glycine receptor

The receptor for the inhibitory neurotransmitter glycine is a member of the ligand gated ion channel recep tor superfamily. Point mutations in the gene encoding the alpha 1 subunit of the glycine receptor channel complex (GlyR) have recently been identified in pedigrees with the autosomal dominant neurological disorder, startle disease (hyperekplexia). These mutations result in the substitution of leucine or glutamine for arginine 271. This charged residue is located near the ion channel region and is predicted to affect chloride permeation through the GlyR. We found little evidence for this role from the anion/cation selectivity and lack of pronounced rectification of currents flowing through recombinant human alpha 1 subunit GlyRs containing the startle disease mutations. We reveal, however, that the startle disease mutations profoundly disrupt GlyR func tion by causing 230-410-fold decreases in the sensitivity of receptor currents activated by the agonist glycine. Additionally, we report corresponding 56- and 120-fold reductions in the apparent binding affinity (K-i) of glycine to the mutant GlyRs, but no change in the binding affinity of the competitive antagonist, strychnine. Thus, startle disease reduces the efficacy of glycinergic inhibitory neurotransmission by producing GlyRs with diminished agonist responsiveness. Our results show that startle disease mutations define a novel receptor activation site

Testing in the incremental design and development of complex products

Testing is an important aspect of design and development which consumes significant time and resource in many companies. However, it has received less research attention than many other activities in product development, and especially, very few publications report empirical studies of engineering testing. Such studies are needed to establish the importance of testing and inform the development of pragmatic support methods. This paper combines insights from literature study with findings from three empirical studies of testing. The case studies concern incrementally developed complex products in the automotive domain. A description of testing practice as observed in these studies is provided, confirming that testing activities are used for multiple purposes depending on the context, and are intertwined with design from start to finish of the development process, not done after it as many models depict. Descriptive process models are developed to indicate some of the key insights, and opportunities for further research are suggested

Crop Updates 2000 - Lupins

This session covers nineteen papers from different authors: 1.1999 Lupin Highlights, Bill O’Neill, LUPIN PRODUCTIVITY IMPROVEMENTS AND INDUSTRY DEVELOPMENT LUPIN ANTHRACNOSE 2. Anthracnose – 1999/2000, Geoff Thomas and Mark Sweetingham, Agriculture Western Australia LUPIN BREEDING AND AGRONOMY 3. The genetic control of mildly restricted branching in narrow-leafed lupin (Lupinus augustifolius L), Kedar Adhikari1,3, Nick Galwey1,3 and Miles Dracup2,3 1Plant Sciences, University of Western Australia 2Agriculture Western Australia 3Cooperative Research Centre for Legumes in Mediterranean Agriculture, University of Western Australia 4. Genotype x time of sowing interaction in lupins – Mingenew, Bob French, Agriculture Western Australia 5. Genotype x time of sowing interaction in lupins – Wongan Hills, Bob French, Agriculture Western Australia 6. Genetic variation in lupin tolerance to Brown Leaf Spot, Bob French, Agriculture Western Australia 7. Yellow lupin management in Western Australia, Bob French, Agriculture Western Australia APHIDS AND VIRUS CONTROL 8. Forecasting aphid and virus risk in lupins, Debbie Thackray, Jenny Hawkes and Roger Jones, Centre for Legumes in Mediterranean Agriculture and Agriculture Western Australia 9. When should lupin crops be sprayed for aphids to achieve maximum yield response? Françoise Berlandier, Agriculture Western Australia 10. Yield limiting potential of the new, non-necrotic strain of bean yellow mosaic virus in narrow-leafed lupin, Roger Jones, Yvonne Cheng and Lisa Smith, Crop Improvement Institute, Agriculture Western Australia, and Centre for Legumes in Mediterranean Agriculture LUPIN NUTRITION 11. Increasing the value of a rotation by applying lime, Chris Gazey and Michael O’Connell, Agriculture Western Australia HERBICIDE TOLERANCE AND WEED CONTROL 12. Herbicide damage does not mean lower yield in Lupins, Peter Carlton, Trials Coordinator, Elders Limited 13. Effect of herbicides Tordonä 75D and Lontrelä, used for eradication of Skeleton Weed, on production of Lupins in following seasons, John R. Peirce and Brad J. Rayner, Agriculture Western Australia 14. Herbicide tolerance of lupins, Terry Piper, Agriculture Western Australia 15. Tanjil lupins will tolerate metribuzin under the right conditions, Peter Newman, Agronomist Elders Limited and Cameron Weeks, Mingenew/Irwin Group LUPIN ESTABLISHMENT 16. A new seed pressing system for ryegrass suppression and healthy lupin establishment, Mohammad Amjad and Glen Riethmuller,Agriculture Western Australia 17. Banded surfactant for better lupin yield on non-wetting sand, Dr Paul Blackwell, Agriculture Western Australia DROUGHT TOLERANCE 18. Drought tolerance of lupin genotypes in Western Australia, Jairo A. Palta1,2,, Neil C. Turner1,2, Robert J. French2,3 ,1CSIRO Plant Industry, Centre for Mediterranean Agricultural Research, 2Centre for Legumes in Mediterranean Agriculture, University of Western Australia, 3Agriculture Western Australia, 19. Stem carbohydrate in lupins: a possible buffer to maintain seed growth under adverse conditions, Bob French1, Tim Setter2, Jairo Palta3 , 1Agriculture Western Australia, and CLIMA, 2Agriculture Western Australia, 3CSIRO, Floreat Park, and CLIM

The First Hour of Extra-galactic Data of the Sloan Digital Sky Survey Spectroscopic Commissioning: The Coma Cluster

On 26 May 1999, one of the Sloan Digital Sky Survey (SDSS) fiber-fed spectrographs saw astronomical first light. This was followed by the first spectroscopic commissioning run during the dark period of June 1999. We present here the first hour of extra-galactic spectroscopy taken during these early commissioning stages: an observation of the Coma cluster of galaxies. Our data samples the Southern part of this cluster, out to a radius of 1.5degrees and thus fully covers the NGC 4839 group. We outline in this paper the main characteristics of the SDSS spectroscopic systems and provide redshifts and spectral classifications for 196 Coma galaxies, of which 45 redshifts are new. For the 151 galaxies in common with the literature, we find excellent agreement between our redshift determinations and the published values. As part of our analysis, we have investigated four different spectral classification algorithms: spectral line strengths, a principal component decomposition, a wavelet analysis and the fitting of spectral synthesis models to the data. We find that a significant fraction (25%) of our observed Coma galaxies show signs of recent star-formation activity and that the velocity dispersion of these active galaxies (emission-line and post-starburst galaxies) is 30% larger than the absorption-line galaxies. We also find no active galaxies within the central (projected) 200 h-1 Kpc of the cluster. The spatial distribution of our Coma active galaxies is consistent with that found at higher redshift for the CNOC1 cluster survey. Beyond the core region, the fraction of bright active galaxies appears to rise slowly out to the virial radius and are randomly distributed within the cluster with no apparent correlation with the potential merger of the NGC 4839 group. [ABRIDGED]Comment: Accepted in AJ, 65 pages, 20 figures, 5 table

Colors of 2625 Quasars at 0<z<5 Measured in the Sloan Digital Sky Survey Photometric System

We present an empirical investigation of the colors of quasars in the Sloan Digital Sky Survey (SDSS) photometric system. The sample studied includes 2625 quasars with SDSS photometry. The quasars are distributed in a 2.5 degree wide stripe centered on the Celestial Equator covering $\sim529$ square degrees. Positions and SDSS magnitudes are given for the 898 quasars known prior to SDSS spectroscopic commissioning. New SDSS quasars represent an increase of over 200% in the number of known quasars in this area of the sky. The ensemble average of the observed colors of quasars in the SDSS passbands are well represented by a power-law continuum with $\alpha_{\nu} = -0.5$ ($f_{\nu} \propto \nu^{\alpha}$). However, the contributions of the $3000 {\rm \AA}$ bump and other strong emission lines have a significant effect upon the colors. The color-redshift relation exhibits considerable structure, which may be of use in determining photometric redshifts for quasars. The range of colors can be accounted for by a range in the optical spectral index with a distribution $\alpha_{\nu}=-0.5\pm0.65$ (95% confidence), but there is a red tail in the distribution. This tail may be a sign of internal reddening. Finally, we show that there is a continuum of properties between quasars and Seyfert galaxies and we test the validity of the traditional division between the two classes of AGN.Comment: 66 pages, 15 figures (3 color), accepted by A

Assessing the Safety of Stem Cell Therapeutics

Unprecedented developments in stem cell research herald a new era of hope and expectation for novel therapies. However, they also present a major challenge for regulators since safety assessment criteria, designed for conventional agents, are largely inappropriate for cell-based therapies. This article aims to set out the safety issues pertaining to novel stem cell-derived treatments, to identify knowledge gaps that require further research, and to suggest a roadmap for developing safety assessment criteria. It is essential that regulators, pharmaceutical providers, and safety scientists work together to frame new safety guidelines, based on “acceptable risk,” so that patients are adequately protected but the safety “bar” is not set so high that exciting new treatments are lost

The Fifth Data Release of the Sloan Digital Sky Survey

This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and represents the completion of the SDSS-I project (whose successor, SDSS-II will continue through mid-2008). It includes five-band photometric data for 217 million objects selected over 8000 square degrees, and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 square degrees of that imaging data. These numbers represent a roughly 20% increment over those of the Fourth Data Release; all the data from previous data releases are included in the present release. In addition to "standard" SDSS observations, DR5 includes repeat scans of the southern equatorial stripe, imaging scans across M31 and the core of the Perseus cluster of galaxies, and the first spectroscopic data from SEGUE, a survey to explore the kinematics and chemical evolution of the Galaxy. The catalog database incorporates several new features, including photometric redshifts of galaxies, tables of matched objects in overlap regions of the imaging survey, and tools that allow precise computations of survey geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS Sixth Data Release (DR6) is now public, available from http://www.sdss.or