Low carbon housing: lessons from Elm Tree Mews

This report sets out the findings from a low carbon housing trial at Elm Tree Mews, York, and discusses the technical and policy issues that arise from it. The Government has set an ambitious target for all new housing to be zero carbon by 2016. With the application of good insulation, improved efficiencies and renewable energy, this is theoretically possible. However, there is growing concern that, in practice, even existing carbon standards are not being achieved and that this performance gap has the potential to undermine zero carbon housing policy. The report seeks to address these concerns through the detailed evaluation of a low carbon development at Elm Tree Mews. The report: * evaluates the energy/carbon performance of the dwellings prior to occupation and in use; * analyses the procurement, design and construction processes that give rise to the performance achieved; * explores the resident experience; * draws out lessons for the development of zero carbon housing and the implications for government policy; and * proposes a programme for change, designed to close the performance gap

Crystallization and preliminary X-ray analysis of the sporulation factor SpoIIAA in its native and phosphorylated forms

Sporulation in Bacillus begins with an asymmetric cell division producing two progeny with identical chromosomes but different developmental fates. As such, it is a simple example of cellular differentiation. The establishment of cell type is controlled by a series of alternate RNA polymerase sigma subunits. The first compartment-specific sigma factor is sigma (F), whose activity is controlled by SpoIIAB, an anti-sigma factor, and SpoIIAA, an anti-sigma factor antagonist which is phosphorylated by the kinase activity of SpoIIAB. Here, the preliminary crystallographic analysis of SpoIIAA and phosphorylated SpoIIAA from B. sphaericus in forms suitable for high-resolution structure determination are reported

Pharmacological and genetic characterisation of the canine P2X4 receptor

Background and Purpose: P2X4 receptors are emerging therapeutic targets for treating chronic pain and cardiovascular disease. Dogs are well-recognised natural models of human disease, but information regarding P2X4 receptors in dogs is lacking. To aid the development and validation of P2X4 receptor ligands, we have characterised and compared canine and human P2X4 receptors. Experimental Approach: Genomic DNA was extracted from whole blood samples from 101 randomly selected dogs and sequenced across the P2RX4 gene to identify potential missense variants. Recombinant canine and human P2X4 receptors tagged with Emerald GFP were expressed in 1321N1 and HEK293 cells and analysed by immunoblotting and confocal microscopy. In these cells, receptor pharmacology was characterised using nucleotide-induced Fura-2 AM measurements of intracellular Ca 2+ and known P2X4 receptor antagonists. P2X4 receptor-mediated inward currents in HEK293 cells were assessed by automated patch clamp. Key Results: No P2RX4 missense variants were identified in any canine samples. Canine and human P2X4 receptors were localised primarily to lysosomal compartments. ATP was the primary agonist of canine P2X4 receptors with near identical efficacy and potency at human receptors. 2′(3′)-O-(4-benzoylbenzoyl)-ATP, but not ADP, was a partial agonist with reduced potency for canine P2X4 receptors compared to the human orthologues. Five antagonists inhibited canine P2X4 receptors, with 1-(2,6-dibromo-4-isopropyl-phenyl)-3-(3-pyridyl)urea displaying reduced sensitivity and potency at canine P2X4 receptors. Conclusion and Implications: P2X4 receptors are highly conserved across dog pedigrees and display expression patterns and pharmacological profiles similar to human receptors, supporting validation and use of therapeutic agents for P2X4 receptor-related disease onset and management in dogs and humans

Housing associations and rent arrears Attitudes, beliefs and behaviour

A report prepared for the Joseph Rowntree Foundation and published by the Chartered Inst. of HousingSIGLEAvailable from British Library Document Supply Centre-DSC:f99/2343 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Dynamic thyroid testing, thyroid histology and thyroxine replacement therapy in Basenji dogs

Objective: To monitor the long-term health status of a cohort of client-owned Basenji dogs over several years; to compare the accuracy of various laboratory methods to assess thyroid status; and to document any adverse effects of routinely recommended doses of thyroxine for confirmed or presumptive hypothyroidism. Methods: Health outcomes were followed by 1-8 years of clinical surveillance using serum total thyroid hormone (TT4) and canine thyroid-stimulating hormone (cTSH) concentrations, and either dynamic thyroid testing using recombinant human (rh) TSH, and/or thyroid histopathology at necropsy. The long-term accuracy of the various diagnostic interpretative criteria for rhTSH stimulation was analysed. The clinical history and serial concentrations of TT4 and cTSH in dogs suspected of exhibiting adverse clinical responses to standard thyroxine supplementation were reviewed. Results: When rhTSH interpretative criteria were compared with thyroid histology at necropsy, Larsson's equation correctly identified normal Basenji dogs from dogs with hypothyroidism and extensive thyroid pathology, yet provided an equivocal result for dogs that were not hypothyroid. Despite sequential low TT4 concentration measurements over several years of clinical surveillance, these 'equivocal' dogs had unremarkable thyroid histology (consistent with breed and age) at necropsy. Thyroxine supplementation at recommended dose rates resulted in clinical signs of thyrotoxicosis in six elderly Basenji dogs. Conclusion: Age and breed may account for dose-related adverse responses in Basenji dogs dosed with thyroxine at recommended doses. We recommend that when conducting therapeutic thyroid supplementation trials in this breed, the drug be administered in gradually increasing doses to avoid dose-related side effects. In a breed with a lower than 'normal' reference interval for serum TT4 concentration, attempts to achieve the post-pill TT4 concentration achieved in normal dogs may induce signs of thyrotoxicosis. Serial cTSH concentration measurements are helpful when adjusting thyroxine supplementation in Basenji dogs. Larsson's equation can be of assistance in interpreting dynamic thyroid testing using rhTSH in this breed. The overall prevalence of hypothyroidism in the Basenji breed appears to be low.9 page(s

Young people, money and risk in early adult life

Period of award Jun 1999 - Mar 2001SIGLEAvailable from British Library Document Supply Centre-DSC:3739.0605(000237993) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Structure of the Bacillus cell fate determinant SpoIIAA in phosphorylated and unphosphorylated forms

Background: The asymmetric cell division during sporulation in Bacillus subtilis gives rise to two compartments: the mother cell and the forespore. Each follow different programs of gene expression coordinated by a succession of alternate RNA polymerase σ factors. The activity of the first of these σ factors, σF, is restricted to the forespore although σF is present in the predivisional cell and partitions into both compartments following the asymmetric septation. For σF to become active, it must escape from a complex with its cognate anti-σ factor, SpoIIAB. This relief from SpoIIAB inhibition requires the dephosphorylation of the anti-σ factor antagonist, SpoIIAA. The phosphorylation state of SpoIIAA is thus a key determinant of σF activity and cell fate. Results: We have solved the crystal structures of SpoIIAA from Bacillus sphaericus in its phosphorylated and unphosphorylated forms. The overall structure consists of a central β-pleated sheet, one face of which is buried by a pair of α helices, while the other is largely exposed to solvent. The site of phosphorylation, Ser57, is located at the N terminus of helix α2. The phosphoserine is exceptionally well defined in the 1.2 Å electron density maps, revealing that the structural changes accompanying phosphorylation are slight. Conclusions: Comparison of unphosphorylated and phosphorylated SpoIIAA shows that covalent modification has no significant effect on the global structure of the protein. The phosphoryl group has a passive role as a negatively charged flag rather than the active role it plays as a nucleus of structural reorganization in many eukaryotic signaling systems

Association of a P2RX7 gene missense variant with brachycephalic dog breeds

Missense variants are associated with various phenotypic traits and disorders in dogs. The canine P2RX7 gene, coding the ATP-gated P2X7 receptor ion channel, contains four known missense variants. The current study aimed to examine the presence of these variants in a random sample of pedigree and mixed-pedigree dogs. Exons 3, 8, 11 and 13 of the P2RX7 gene, encoding these four respective variants, in 65 dogs were assessed by Sanger sequencing and combined with existing sequencing data from another 69 dogs. The distribution of these variants was then evaluated in all 134 dogs combined and separately within individual breeds including 35 different pure breeds. The rs23314713 (p.Phe103Leu) and rs23315462 (p.Pro452Ser) variants were present in 47 and 40% of all dogs studied respectively, with the rs23314713 variant associated with brachycephalic breeds. Among pedigree dogs, the rs23314713 and rs23315462 variants were associated with brachycephalic and non-brachycephalic breeds respectively. The rs851148233 (p.Arg270Cys) and rs850760787 (p.Arg365Gln) variants were present only in dogs of Cocker Spaniel and Labrador Retriever pedigrees respectively. No other missense variants were found in exons 3, 8, 11 and 13 of the P2RX7 gene within the dogs. In conclusion, the rs23314713 and rs23315462 missense variants of the P2RX7 gene are present in a large proportion of dogs, with the rs23314713 variant associated with a number of brachycephalic breeds. However, the association of this variant with dogs of bulldog ancestry, not brachycephaly per se, cannot be excluded