Social Return on Investment Report (SROI) final report on a type 2 diabetes prevention and management programme delivered by Westbank CHC

Final SROI report on Living Well Taking Control, diabetes prevention and management programme delivered by Westbank CHC, Devon. This is part of a Big Lottery Funded evaluation of South west Wellbeing programme. This led to a total of nine SROI analyses with community health projects in the South west of England

Structural Basis for Copper-Oxygen Mediated C-H Bond Activation by the Formylglycine-Generating Enzyme

The formylglycine-generating enzyme (FGE) is a unique copper protein that catalyzes oxygen-dependent C-H activation. We describe 1.66 Å- and 1.28 Å-resolution crystal structures of FGE from Thermomonospora curvata in complex with either AgI or CdII providing definitive evidence for a high-affinity metal-binding site in this enzyme. The structures reveal a bis-cysteine linear coordination of the monovalent metal, and tetrahedral coordination of the bivalent metal. Similar coordination changes may occur in the active enzyme as a result of CuI/II redox cycling. Complexation of copper atoms by two cysteine residues is common among copper-trafficking proteins, but is unprecedented for redox-active copper enzymes or synthetic copper catalysts

The age and hydrological history of Blue Lake, South Australia

Three sediment cores from the Blue Lake, a groundwater fed lake of volcanic origin in South Australia, have been investigated using a range of chemical and isotopic parameters. The C-14 activity of both the inorganic and organic carbon fractions of the sediment decreases monotonically with depth. The rate of change with depth is greater for near-surface samples with an apparent hiatus in sedimentation rate at about 7000 yr B.P. Estimates of age for the precipitated authigenic carbonate, after correction for dilution with dead carbon from the groundwater, agree well with calculated ages from the organic carbon fraction of the sediment. We suggest the lake is much older than previously proposed using other dating techniques. Variations in the delta(13)C and delta(18)O composition of the authigenic carbonate reflect different residence times of dissolved inorganic carbon and water in the lake caused by changes in the lake level. During periods of hydrologic steady-state, it is suggested that relative changes in the temperature of the lake can be seen in delta(18)O changes in authigenic carbonate. Blue Lake has been undergoing sedimentation for at least 28,000 years, including two lengthy periods of hydrologic steady state. The lake, for a large proportion of its existence, was much shallower while for the last 7000 years has maintained a level close to the present one. The influence of pumping from the lake for urban water supply during this century is reflected in the isotopic composition of carbonate in the sediment

Terminating Tableaux for Graded Hybrid Logic with Global Modalities and Role Hierarchies

We present a terminating tableau calculus for graded hybrid logic with global modalities, reflexivity, transitivity and role hierarchies. Termination of the system is achieved through pattern-based blocking. Previous approaches to related logics all rely on chain-based blocking. Besides being conceptually simple and suitable for efficient implementation, the pattern-based approach gives us a NExpTime complexity bound for the decision procedure

Potato late blight field resistance from QTL dPI09c is conferred by the NB-LRR gene R8

Following the often short-lived protection that major nucleotide binding, leucine-rich-repeat (NB-LRR) resistance genes offer against the potato pathogen Phytophthora infestans, field resistance was thought to provide a more durable alternative to prevent late blight disease. We previously identified the QTL dPI09c on potato chromosome 9 as a more durable field resistance source against late blight. Here, the resistance QTL was fine-mapped to a 186 kb region. The interval corresponds to a larger, 389 kb, genomic region in the potato reference genome of Solanum tuberosum Group Phureja doubled monoploid clone DM1-3 (DM) and from which functional NB-LRRs R8, R9a, Rpi-moc1, and Rpi-vnt1 have arisen independently in wild species. dRenSeq analysis of parental clones alongside resistant and susceptible bulks of the segregating population B3C1HP showed full sequence representation of R8. This was independently validated using long-range PCR and screening of a bespoke bacterial artificial chromosome library. The latter enabled a comparative analysis of the sequence variation in this locus in diverse Solanaceae. We reveal for the first time that broad spectrum and durable field resistance against P. infestans is conferred by the NB-LRR gene R8, which is thought to provide narrow spectrum race-specific resistance

Circulating Soluble RAGE Isoforms are Attenuated in Obese, Impaired Glucose Tolerant Individuals and are Associated with the Development of Type 2 Diabetes

The soluble receptor for advanced glycation end products (sRAGE) may be protective against inflammation associated with obesity and type 2 diabetes (T2DM). The aim of this study was to determine the distribution of sRAGE isoforms and whether sRAGE isoforms are associated with risk of T2DM development in subjects spanning the glucose tolerance continuum. In this retrospective analysis, circulating total sRAGE and endogenous secretory RAGE (esRAGE) were quantified via ELISA, and cleaved RAGE (cRAGE) was calculated in 274 individuals stratified by glucose tolerance status (GTS) and obesity. Group differences were probed by ANOVA, and multivariate ordinal logistic regression was used to test the association between sRAGE isoform concentrations and the proportional odds of developing diabetes, vs. normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). When stratified by GTS, total sRAGE, cRAGE, and esRAGE were all lower with IGT and T2DM, while the ratio of cRAGE to esRAGE (cRAGE:esRAGE) was only lower ( P &lt; 0.01) with T2DM compared with NGT. When stratified by GTS and obesity, cRAGE:esRAGE was higher with obesity and lower with IGT ( P &lt; 0.0001) compared with lean, NGT. In ordinal logistic regression models, greater total sRAGE (odds ratio, 0.91; P &lt; 0.01) and cRAGE (odds ratio, 0.84; P &lt; 0.01) were associated with lower proportional odds of developing T2DM. Reduced values of sRAGE isoforms observed with both obesity and IGT are independently associated with greater proportional odds of developing T2DM. The mechanisms by which each respective isoform contributes to obesity and insulin resistance may reveal novel treatment strategies for diabetes. </jats:p

The novel gene Ny-1 on potato chromosome IX confers hypersensitive resistance to Potato virus Y and is an alternative to Ry genes in potato breeding for PVY resistance

Hypersensitive resistance (HR) is an efficient defense strategy in plants that restricts pathogen growth and can be activated during host as well as non-host interactions. HR involves programmed cell death and manifests itself in tissue collapse at the site of pathogen attack. A novel hypersensitivity gene, Ny-1, for resistance to Potato virus Y (PVY) was revealed in potato cultivar Rywal. This is the first gene that confers HR in potato plants both to common and necrotic strains of PVY. The locus Ny-1 mapped on the short arm of potato chromosome IX, where various resistance genes are clustered in Solanaceous genomes. Expression of HR was temperature-dependent in cv. Rywal. Strains PVYO and PVYN, including subgroups PVYNW and PVYNTN, were effectively localized when plants were grown at 20°C. At 28°C, plants were systemically infected but no symptoms were observed. In field trials, PVY was restricted to the inoculated leaves and PVY-free tubers were produced. Therefore, the gene Ny-1 can be useful for potato breeding as an alternative donor of PVY resistance, because it is efficacious in practice-like resistance conferred by Ry genes

Depression and Motivation

Among the characteristic features of depression is a diminishment in or lack of action and motivation. In this paper, I consider a dominant philosophical account which purports to explain this lack of action or motivation. This approach comes in different versions but a common theme is, I argue, an over reliance on psychologistic assumptions about action–explanation and the nature of motivation. As a corrective I consider an alternative view that gives a prominent place to the body in motivation. Central to the experience of depression are changes to how a person is motivated to act and, also as central, are changes to bodily feelings and capacities. I argue that broadly characterizing motivation in terms of bodily capacities can, in particular, provide a more compelling account of depressive motivational pathology

Variability in Avian Eggshell Colour: A Comparative Study of Museum Eggshells

Background: The exceptional diversity of coloration found in avian eggshells has long fascinated biologists and inspired a broad range of adaptive hypotheses to explain its evolution. Three main impediments to understanding the variability of eggshell appearance are: (1) the reliable quantification of the variation in eggshell colours; (2) its perception by birds themselves, and (3) its relation to avian phylogeny. Here we use an extensive museum collection to address these problems directly, and to test how diversity in eggshell coloration is distributed among different phylogenetic levels of the class Aves. Methodology and Results: Spectrophotometric data on eggshell coloration were collected from a taxonomically representative sample of 251 bird species to determine the change in reflectance across different wavelengths and the taxonomic level where the variation resides. As many hypotheses for the evolution of eggshell coloration assume that egg colours provide a communication signal for an avian receiver, we also modelled reflectance spectra of shell coloration for the avian visual system. We found that a majority of species have eggs with similar background colour (long wavelengths) but that striking differences are just as likely to occur between congeners as between members of different families. The region of greatest variability in eggshell colour among closely related species coincided with the medium-wavelength sensitive region around 500 nm. Conclusions: The majority of bird species share similar background eggshell colours, while the greatest variability among species aligns with differences along a red-brown to blue axis that most likely corresponds with variation in the presence and concentration of two tetrapyrrole pigments responsible for eggshell coloration. Additionally, our results confirm previous findings of temporal changes in museum collections, and this will be of particular concern for studies testing intraspecific hypotheses relating temporal patterns to adaptation of eggshell colour. We suggest that future studies investigating the phylogenetic association between the composition and concentration of eggshell pigments, and between the evolutionary drivers and functional impacts of eggshell colour variability will be most rewarding.Phillip Cassey, Steven J. Portugal, Golo Maurer, John G. Ewen, Rebecca L. Boulton, Mark E. Hauber and Tim M. Blackbur