Infrared Magnitude-Redshift Relations for Luminous Radio Galaxies

Infrared magnitude-redshift relations for the 3CR and 6C samples of radio galaxies are presented for a wide range of plausible cosmological models, including those with non-zero cosmological constant OmegaLambda. Variations in the galaxy formation redshift, metallicity and star formation history are also considered. The results of the modelling are displayed in terms of magnitude differences between the models and no-evolution tracks, illustrating the amount of K-band evolution necessary to account for the observational data. Given a number of plausible assumptions, the results of these analyses suggest that: (i) cosmologies which predict T_0xH_0>1 (where T_0 denotes the current age of the universe) can be excluded; (ii) the star formation redshift should lie in the redshift interval 5<z<20, values towards the lower end of the range being preferred in cosmologies with larger values of T_0xH_0; (iii) the Einstein-de Sitter model provides a reasonable fit to the data; (iv) models with finite values of OmegaLambda can provide good agreement with the observations only if appropriate adjustments of other parameters such as the galaxy metallicities and star-formation histories are made. Without such modifications, even after accounting for stellar evolution, the high redshift radio galaxies are more luminous (ie. more massive) than those nearby in models with finite OmegaLambda, including the favoured model with Omega=0.3, OmegaLambda=0.7. For cosmological models with larger values of T_0xH_0, the conclusions are the same regardless of whether any adjustments are made or not. The implications of these results for cosmology and models of galaxy formation are discussed.Comment: 14 pages, LaTeX, 9 figures, accepted for publication in MNRAS. Replacement corrects some annoying typo

G.P.7.10 Investigation of the patho-biology of MYH7 myopathy mutations

The β-cardiac myosin (β-MyHC) protein is a molecular motor fundamental to both the contractile and structural properties of the muscle sarcomere. Mutations in the gene encoding β-MyHC (MYH7) cause multiple disease phenotypes: early-onset distal myopathy (MPD1), myosin storage myopathy (MSM), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Mutations causing HCM and DCM are spread across almost the entire gene, while those causing MPD1 and MSM are confined to exons encoding the C-terminal light-meromyosin (LMM) region of β-MyHC. How mutations located in the same region of MYH7 cause such a wide phenotypic range is as yet unknown. To investigate structural and functional effects of different β-MyHC mutants, full-length MYH7 and rod/LMM domain regions of interest were cloned for expression in mammalian cells or for recombinant protein expression. Fusion to enhanced green fluorescent protein (EGFP) allowed visualisation of the location of wildtype (WT) or mutant β-cardiac myosin in C2C12 myoblast and myotube cultures and in COS7 cells. Both WT and mutant proteins were able to arrange into ordered, striated structures in differentiated C2C12 myotubes. Analysis in COS7 cells however, suggested mutant β-MyHC showed reduced ability to form higher order structures compared to the WT protein. Secondary-structure analysis of recombinant expressed myosin tail fragments by circular dichroism (CD) revealed that both WT and mutant proteins are almost entirely α-helical. Mutant myosin tails however, tend to show a slight reduction in α-helical content. This reduction is amplified when temperature is increased to replicate physiological conditions. CD melt curve analysis indicated mutant β-MyHC proteins have decreased thermostability. Overall, the effects of the MYH7 LMM mutations on measured properties are less marked than might have been expected from missense mutations to proline or deletion or insertion of an amino-acid in a coiled coil

Production of human skeletal α-actin proteins by the baculovirus expression system

Mutations within the human skeletal muscle α-actin gene cause three different skeletal muscle diseases. Functional studies of the mutant proteins are necessary to better understand the pathogenesis of these diseases, however, no satisfactory system for the expression of mutant muscle actin proteins has been available. We investigated the baculovirus expression vector system (BEVS) for the abundant production of both normal and mutant skeletal muscle α-actin. We show that non-mutated actin produced in the BEVS behaves similarly to native actin, as shown by DNase I affinity purification, Western blotting, and consecutive cycles of polymerisation and depolymerisation. Additionally, we demonstrate the production of mutant actin proteins in the BEVS, without detriment to the insect cells in which they are expressed. The BEVS therefore is the method of choice for studying mutant actin proteins causing human diseases

Clinical Utility Gene Card for: Becker muscular dystrophy

No abstract availabl

T-cell immunity to human alphaherpesviruses

Human alphaherpesviruses (aHHV) - herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (V

Clinical Utility Gene Card for: Autosomal dominant myotonia congenita (Thomsen Disease)

No abstract availabl

CUGC for Duchenne muscular dystrophy (DMD)

No abstract availabl