Mortality associated with avian reovirus infection in a free-living magpie (Pica pica) in Great Britain

Avian reoviruses (ARVs) cause a range of disease presentations in domestic, captive and free-living bird species. ARVs have been reported as a cause of significant disease and mortality in free-living corvid species in North America and continental Europe. Until this report, there have been no confirmed cases of ARV-associated disease in British wild birds

A cross-sectional survey on the seroprevalence of dengue fever in febrile patients attending health facilities in Cross River State, Nigeria

Background In Nigeria, recent reports suggest that dengue viruses could be a major cause of acute fevers. We sought to make a cross-sectional estimate of the prevalence of current and previous dengue infections in patients presenting with fever to healthcare centres in Cross River State Nigeria. Methodology/Principal findings This cross-sectional health facility survey recruited persons with temperature ≥38°C. Dengue virus immunoglobulin M (IgM)/immunoglobulin G (IgG) antibody testing using Onsite Duo dengue Ag-IgG/IgM lateral flow immunoassay cassettes was done. Samples which tested positive were further confirmed using the RecombiLISA dengue IgM and IgG enzyme linked immunosorbent assay kits and classified into primary and secondary dengue infection. Malaria testing was carried out using microscopy. Between 4 January 2017 and 24 August 2017 a total of 420 participants were sampled across 11 health centres. The mean age was 34 (range = 1–99), 63% were female, 49% reported sleeping under a treated mosquito net in the past week and 44% reported taking an antimalarial prior to seeking care. The mean number of days fever was present prior to seeking care was 8, and many of the participants presented with symptoms indicative of respiratory or urinary tract infections. Testing indicated that 6% (95% CI: 2, 13; n = 24) had either a primary or secondary dengue infection with or without co-existing malaria, while 4% (95% CI: 2, 9; n = 16) had either a primary or secondary dengue infection without co-existing malaria. 52% (95% CI: 46, 58; n = 218) had a malaria infection with or without any dengue infection, and 50% (95% CI: 44, 57; n = 210) had a malaria infection without any dengue infection. Conclusion Our study confirms the presence of dengue at not insignificant levels in patients attending health centres with fever in this south eastern province of Nigeria. These data highlight the danger of the common presumption in this setting that fever is due to malaria. Surveillance for dengue is vital in this setting

Cavity formation on the surface of a body entering water with deceleration

The two-dimensional water entry of a rigid symmetric body with account for cavity formation on the body surface is studied. Initially the liquid is at rest and occupies the lower half plane. The rigid symmetric body touches the liquid free surface at a single point and then starts suddenly to penetrate the liquid vertically with a time-varying speed. We study the effect of the body deceleration on the pressure distribution in the flow region. It is shown that, in addition to the high pressures expected from the theory of impact, the pressure on the body surface can later decrease to sub-atmospheric levels. The creation of a cavity due to such low pressures is considered. The cavity starts at the lowest point of the body and spreads along the body surface forming a thin space between a new free surface and the body. Within the linearised hydrodynamic problem, the positions of the two turnover points at the periphery of the wetted area are determined by Wagner’s condition. The ends of the cavity’s free surface are modelled by the Brillouin–Villat condition. The pressure in the cavity is assumed to be a prescribed constant, which is a parameter of the model. The hydrodynamic problem is reduced to a system of integral and differential equations with respect to several functions of time. Results are presented for constant deceleration of two body shapes: a parabola and a wedge. The general formulation made also embraces conditions where the body is free to decelerate under the total fluid force. Contrasts are drawn between results from the present model and a simpler model in which the cavity formation is suppressed. It is shown that the expansion of the cavity can be significantly slower than the expansion of the corresponding zone of sub-atmospheric pressure in the simpler model. For forced motion and cavity pressure close to atmospheric, the cavity grows until almost complete detachment of the fluid from the body. In the problem of free motion of the body, cavitation with vapour pressure in the cavity is achievable only for extremely large impact velocities

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

Application of CRISPR/Cas9 editing and digital droplet PCR in human iPSCs to generate novel knock-in reporter lines to visualize dopaminergic neurons

Human induced pluripotent stem cells (hiPSCs) have become indispensable for disease modelling. They are an important resource to access patient cells harbouring disease-causing mutations. Derivation of midbrain dopaminergic (DAergic) neurons from hiPSCs of PD patients represents the only option to model physiological processes in a cell type that is not otherwise accessible from human patients. However, differentiation does not produce a homogenous population of DA neurons and contaminant cell types may interfere with the readout of the in vitro system. Here, we use CRISPR/Cas9 to generate novel knock-in reporter lines for DA neurons, engineered with an endogenous fluorescent tyrosine hydroxylase \u2013 enhanced green fluorescent protein (TH-eGFP) reporter. We present a reproducible knock-in strategy combined with a highly specific homologous directed repair (HDR) screening approach using digital droplet PCR (ddPCR). The knock-in cell lines that we created show a functioning fluorescent reporter system for DA neurons that are identifiable by flow cytometry

Identification of a tyrosine residue responsible for N-acetylimidazole-induced increase of activity of ecto-nucleoside triphosphate diphosphohydrolase 3

Chemical modification in combination with site-directed mutagenesis was used to identify a tyrosine residue responsible for the increase in ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) nucleotidase activity after acetylation with a tyrosine-selective reagent, N-acetylimidazole. The NTPDase3 ATPase activity is increased more than the ADPase activity by this reagent. Several fairly well conserved tyrosine residues (252, 255, and 262) that are located in or very near apyrase conserved region 4a (ACR4a) were mutated. These mutants were all active, but mutation of tyrosine 252 to either alanine or phenylalanine eliminated the activity increase observed after N-acetylimidazole treatment of the wild-type enzyme. This suggests that the acetylation of tyrosine 252 is responsible for the increased activity. Stabilization of quaternary structure has resulted in increased enzyme activities for the NTPDases. However, mutation of these three tyrosine residues did not result in global changes of tertiary or quaternary structure, as measured by Cibacron blue binding, chemical cross linking, and native gel electrophoretic analysis. Nevertheless, disruption of the oligomeric structure with the detergent Triton X-100 abolished the increase in activity induced by this reagent. In addition, mutations that abolished the N-acetylimidazole effect also attenuated the increases of enzyme activity observed after lectin and chemical cross-linking treatments, which were previously attributed to stabilization of the quaternary structure. Thus, we speculate that the acetylation of tyrosine 252 might induce a subtle conformational change in NTPDase3, resulting in the observed increase in activity

Synthesis and Thermoelectric Properties of Bi2Se3 Nanostructures

Bismuth selenide (Bi2Se3) nanostructures were synthesized via solvothermal method. The crystallinity of the as-synthesized sample has been analyzed by X-ray diffraction, which shows the formation of rhombohedral Bi2Se3. Electron microscopy examination indicates that the Bi2Se3 nanoparticles have hexagonal flake-like shape. The effect of the synthesis temperature on the morphology of the Bi2Se3 nanostructures has also been investigated. It is found that the particle size increases with the synthesis temperature. Thermoelectric properties of the Bi2Se3 nanostructures were also measured, and the maximum value of dimensionless figure of merit (ZT) of 0.096 was obtained at 523 K

The AFLOW Fleet for Materials Discovery

The traditional paradigm for materials discovery has been recently expanded to incorporate substantial data driven research. With the intent to accelerate the development and the deployment of new technologies, the AFLOW Fleet for computational materials design automates high-throughput first principles calculations, and provides tools for data verification and dissemination for a broad community of users. AFLOW incorporates different computational modules to robustly determine thermodynamic stability, electronic band structures, vibrational dispersions, thermo-mechanical properties and more. The AFLOW data repository is publicly accessible online at aflow.org, with more than 1.7 million materials entries and a panoply of queryable computed properties. Tools to programmatically search and process the data, as well as to perform online machine learning predictions, are also available.Comment: 14 pages, 8 figure