Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes

Aims/hypothesis: An abnormal urinary albumin excretion rate (AER) is often the first clinically detectable manifestation of diabetic nephropathy. Our aim was to estimate the heritability and to detect genetic variation associated with elevated AER in patients with type 1 diabetes. 
 Methods: The discovery phase genome-wide association study (GWAS) included 1,925 patients with type 1 diabetes and with data on 24 h AER. AER was analysed as a continuous trait and the analysis was stratified by the use of antihypertensive medication. Signals with a p value <10^{−4 were followed up in 3,750 additional patients with type 1 diabetes from seven studies.} 
 Results: The narrow-sense heritability, captured with our genotyping platform, was estimated to explain 27.3% of the total AER variability, and 37.6% after adjustment for covariates. In the discovery stage, five single nucleotide polymorphisms in the GLRA3 gene were strongly associated with albuminuria (p < 5 × 10^{−8). In the replication group, a nominally significant association (p = 0.035) was observed between albuminuria and rs1564939 in GLRA3, but this was in the opposite direction. Sequencing of the surrounding genetic region in 48 Finnish and 48 UK individuals supported the possibility that population-specific rare variants contribute to the synthetic association observed at the common variants in GLRA3. The strongest replication (p = 0.026) was obtained for rs2410601 between the PSD3 and SH2D4A genes. Pathway analysis highlighted natural killer cell mediated immunity processes.} 
 Conclusions/interpretation: This study suggests novel pathways and molecular mechanisms for the pathogenesis of albuminuria in type 1 diabetes.

Three-dimensional pure deflagration models with nucleosynthesis and synthetic observables for type ia supernovae

We investigate whether pure deflagration models ofChandrasekhar-mass carbon-oxygen white dwarf stars can account for one or more subclass of the observed population of Type Ia supernova (SN Ia) explosions. We compute a set of 3D full-star hydrodynamic explosion models, in which the deflagration strength is parametrized using the multispot ignition approach. For each model, we calculate detailed nucleosynthesis yields in a post-processing step with a 384 nuclide nuclear network. We also compute synthetic observables with our 3D Monte Carlo radiative transfer code for comparison with observations. For weak and intermediate deflagration strengths (energy release E {less-than or approximate} 1.1 × 10 erg), we find that the explosion leaves behind a bound remnant enriched with 3 to 10 per cent (by mass) of deflagration ashes. However, we do not obtain the large kick velocities recently reported in the literature. We find that weak deflagrations with E ~ 0.5 × 10 erg fit well both the light curves and spectra of 2002cx-like SNe Ia, and models with even lower explosion energies could explain some of the fainter members of this subclass. By comparing our synthetic observables with the properties of SNe Ia, we can exclude the brightest, most vigorously ignited models as candidates for any observed class of SN Ia: their B-V colours deviate significantly from both normal and 2002cx-like SNe Ia and they are too bright to be candidates for other subclasses.

Synthetic light curves and spectra for three-dimensional delayed-detonation models of type ia supernovae

In a companion paper, Seitenzahl et al. have presented a set of three-dimensional delayed detonation models for thermonuclear explosions of near-Chandrasekhar-mass white dwarfs (WDs). Here,we present multidimensional radiative transfer simulations that provide synthetic light curves and spectra for those models. The model sequence explores both changes in the strength of the deflagration phase (which is controlled by the ignition configuration in our models) and the WD central density. In agreement with previous studies, we find that the strength of the deflagration significantly affects the explosion and the observables. Variations in the central density also have an influence on both brightness and colour, but overall it is a secondary parameter in our set of models. In many respects, the models yield a good match to the observed properties of normal Type Ia supernovae (SNe Ia): peak brightness, rise/decline time-scales and synthetic spectra are all in reasonable agreement. There are, however, several differences. In particular, the models are systematically too red around maximum light, manifest spectral line velocities that are a little too high and yield I-band light curves that do not match observations. Although some of these discrepancies may simply relate to approximations made in the modelling, some pose real challenges to the models. If viewed as a complete sequence, our models do not reproduce the observed light-curve width- luminosity relation (WLR) of SNe Ia: all our models show rather similar B-band decline rates, irrespective of peak brightness. This suggests that simple variations in the strength of the deflagration phase in Chandrasekhar-mass deflagration-to-detonation models do not readily explain the observed diversity of normal SNe Ia. This may imply that some other parameter within the Chandrasekhar-mass paradigm is key to the WLR, or that a substantial fraction of normal SNe Ia arise from an alternative explosion scenario.

Adsorption Study using Optimised 3D Organised Mesoporous Silica Coated with Fe and Al Oxides for Specific As(III) and As(V) Removal from Contaminated Synthetic Groundwater

This work presents the possibility of optimising 3D Organised Mesoporous Silica (OMS) coated with both iron and aluminium oxides for the optimal removal of As(III) and As(V) from synthetic contaminated water. The materials developed were fully characterised and were tested for removing arsenic in batch experiments. The effect of total Al to Fe oxides coating on the selective removal of As(III) and As(V) was studied. It was shown that 8% metal coating was the optimal configuration for the coated OMS materials in removing arsenic. The effect of arsenic initial concentration and pH, kinetics and diffusion mechanisms was studied, modelled and discussed. It was shown that the advantage of an organised material over an un-structured sorbent was very limited in terms of kinetic and diffusion under the experimental conditions. It was shown that physisorption was the main adsorption process involved in As removal by the coated OMS. Maximum adsorption capacity of 55 mg As(V).g-1 was noticed at pH 5 for material coated with 8% Al oxides while 35 mg As(V).g-1 was removed at pH 4 for equivalent material coated with Fe oxides.

Feleucin-BO1: A Novel Antimicrobial Non-Apeptide Amide from the Skin Secretion of the Toad, Bombina orientalis, and Design of a Potent Broad-Spectrum Synthetic Analogue, Feleucin-K3

Feleucins-BV1 and -BV2 are recently-described prototypes of a novel antimicrobial nonapeptide (AMP) family identified in the skin secretion of the bombinid toad, Bombina variegata. They are encoded on different precursors that also encode a novel bombinin. Here we describe the identification of feleucin-BO1 (FLGLLGSLLamide) which is co-encoded with a different novel bombinin, named feleucin precursor-associated bombinin (FPA-bombinin-BO), from the skin secretion of Bombina orientalis. Synthetic feleucin-BO1 displayed activity against a reference Gram-positive bacterium. Staphylococcus aureus (MIC 34 μM) but was inactive (> 250 μM) against the Gram-negative bacterium, Escherichia coli, and the yeast, Candida albicans. This pattern of activity was similar to that of the prototypes. Design and synthesis of a cationicity-enhanced analogue, feleucin-K3 (F-K3), in which the amino acid residues at positions 3 (G), 6 (G) and 7 (S) of feleucin-BO1 were substituted with Lys (K) residues, resulted in a peptide with significantly-enhanced potency and spectrum of activity. The MICs of F-K3 against the reference microorganisms were 7 μM (S. aureus), 14 μM (E. coli) and 7 μM (C. albicans). These data indicate that the skin secretions of amphibians can continue to provide novel peptide templates for the rational design of analogues with possible therapeutic utility.

Manual mapping of drumlins in synthetic landscapes to assess operator effectiveness

Mapped topographic features are important for understanding processes that sculpt the Earth’s surface. This paper presents maps that are the primary product of an exercise that brought together 27 researchers with an interest in landform mapping wherein the efficacy and causes of variation in mapping were tested using novel synthetic DEMs containing drumlins. The variation between interpreters (e.g. mapping philosophy, experience) and across the study region (e.g. woodland prevalence) opens these factors up to assessment. A priori known answers in the synthetics increase the number and strength of conclusions that may be drawn with respect to a traditional comparative study. Initial results suggest that overall detection rates are relatively low (34–40%), but reliability of mapping is higher (72–86%). The maps form a reference dataset.

Molecular surveillance for carbapenemase genes in carbapenem-resistant Pseudomonas aeruginosa in Australian patients with cystic fibrosis.

Summary: The aim of this study was to assess the prevalence of acquired carbapenemase genes amongst carbapenem non-susceptible Pseudomonas aeruginosa isolates in Australian patients with cystic fibrosis (CF). Cross-sectional molecular surveillance for acquired carbapenemase genes was performed on CF P. aeruginosa isolates from two isolate banks comprising: (i) 662 carbapenem resistant P. aeruginosa isolates from 227 patients attending 10 geographically diverse Australian CF centres (2007-2009), and (ii) 519 P. aeruginosa isolates from a cohort of 173 adult patients attending one Queensland CF clinic in 2011. All 1189 P. aeruginosa isolates were tested by polymerase chain reaction (PCR) protocols targeting ten common carbapenemase genes, as well the Class 1 integron intI1 gene and the aadB aminoglycoside resistance gene. No carbapenemase genes were identified among all isolates tested. The intI1 and aadB genes were frequently detected and were significantly associated with the AUST-02 strain (OR 24.6, 95% CI 9.3-65.6; p < 0.0001) predominantly from Queensland patients. Despite the high prevalence of carbapenem resistance in P. aeruginosa in Australian patients with CF, no acquired carbapenemase genes were detected in the study, suggesting chromosomal mutations remain the key resistance mechanism in CF isolates. Systematic surveillance for carbapenemase-producing P. aeruginosa in CF by molecular surveillance is ongoing.