1,335 research outputs found

    Determining the probability of cyanobacterial blooms: the application of Bayesian networks in multiple lake systems

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    A Bayesian network model was developed to assess the combined influence of nutrient conditions and climate on the occurrence of cyanobacterial blooms within lakes of diverse hydrology and nutrient supply. Physicochemical, biological, and meteorological observations were collated from 20 lakes located at different latitudes and characterized by a range of sizes and trophic states. Using these data, we built a Bayesian network to (1) analyze the sensitivity of cyanobacterial bloom development to different environmental factors and (2) determine the probability that cyanobacterial blooms would occur. Blooms were classified in three categories of hazard (low, moderate, and high) based on cell abundances. The most important factors determining cyanobacterial bloom occurrence were water temperature, nutrient availability, and the ratio of mixing depth to euphotic depth. The probability of cyanobacterial blooms was evaluated under different combinations of total phosphorus and water temperature. The Bayesian network was then applied to quantify the probability of blooms under a future climate warming scenario. The probability of the "high hazardous" category of cyanobacterial blooms increased 5% in response to either an increase in water temperature of 0.8°C (initial water temperature above 24°C) or an increase in total phosphorus from 0.01 mg/L to 0.02 mg/L. Mesotrophic lakes were particularly vulnerable to warming. Reducing nutrient concentrations counteracts the increased cyanobacterial risk associated with higher temperatures

    Site-selective Probe of Magnetic Excitations in Rare-earth Nickelates using Resonant Inelastic X-ray Scattering

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    We have used high-resolution resonant inelastic x-ray scattering (RIXS) to study a thin film of NdNiO3_3, a compound whose unusual spin- and bond-ordered electronic ground state has been of long-standing interest. Below the magnetic ordering temperature, we observe well-defined collective magnon excitations along different high-symmetry directions in momentum space. The magnetic spectra depend strongly on the incident photon energy, which we attribute to RIXS coupling to different local electronic configurations of the expanded and compressed NiO6_6 octahedra in the bond-ordered state. Both the noncollinear magnetic ground state and the observed site-dependent magnon excitations are well described by a model that assumes strong competition between the antiferromagnetic superexchange and ferromagnetic double-exchange interactions. Our study provides direct insight into the magnetic dynamics and exchange interactions of the rare-earth nickelates, and demonstrates that RIXS can serve as a site-selective probe of magnetism in these and other materials.Comment: Phys. Rev. X, in pres

    Two-dimensional grid optimization for sedimentation velocity analysis in the analytical ultracentrifuge

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    Accepted author manuscriptSedimentation velocity experiments performed in the analytical ultracentrifuge are modeled using finite-element solutions of the Lamm equation. During modeling, three fundamental parameters are optimized: the sedimentation coefficients, the diffusion coefficients, and the partial concentrations of all solutes present in a mixture. A general modeling approach consists of fitting the partial concentrations of solutes defined in a two-dimensional grid of sedimentation and diffusion coefficient combinations that cover the range of possible solutes for a given mixture. An increasing number of grid points increase the resolution of the model produced by the subsequent analysis, with denser grids giving rise to a very large system of equations. Here, we evaluate the efficiency and resolution of several regular grids and show that traditionally defined grids tend to provide inadequate coverage in one region of the grid, while at the same time being computationally wasteful in other sections of the grid. We describe a rapid and systematic approach for generating efficient two-dimensional analysis grids that balance optimal information content and model resolution for a given signal-to-noise ratio with improved calculation efficiency. These findings are general and apply to one- and two-dimensional grids, although they no longer represent regular grids. We provide a recipe for an improved grid-point spacing in both directions which eliminates unnecessary points, while at the same time providing a more uniform resolution that can be scaled based on the stochastic noise in the experimental data.Ye

    Preparative SDS PAGE as an Alternative to His–Tag Purification of Recombinant Amelogenin

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    Recombinant protein technology provides an invaluable source of proteins for use in structure-function studies, as immunogens and in the development of therapeutics. Recombinant proteins are typically engineered with “tags” that allow the protein to be purified from crude host cell extracts using affinity based chromatography techniques. Amelogenin is the principal component of the developing enamel matrix and a frequent focus for biomineralisation researchers. Several groups have reported the successful production of recombinant amelogenins but the production of recombinant amelogenin free of any tags, and at single band purity on silver stained SDS PAGE is technically challenging. This is important, as rigorous structure-function research frequently demands a high degree of protein purity and fidelity of protein sequence. Our aim was to generate His-tagged recombinant amelogenin at single band purity on silver stained SDS PAGE for use in functionality studies after His-tag cleavage. An acetic acid extraction technique (previously reported to produce recombinant amelogenin at 95% purity directly from E. coli) followed by repeated rounds of nickel column affinity chromatography, failed to generate recombinant amelogenin at single band purity. This was because following an initial round of nickel column affinity chromatography, subsequent cleavage of the His-tag was not 100% efficient. A second round of nickel column affinity chromatography, used in attempts to separate the cleaved His-tag free recombinant from uncleaved His-tagged contaminants, was still unsatisfactory as cleaved recombinant amelogenin exhibited significant affinity for the nickel column. To solve this problem, we used preparative SDS PAGE to successfully purify cleaved recombinant amelogenins to single band purity on silver stained SDS PAGE. The resolving power of preparative SDS PAGE was such that His-tag based purification of recombinant amelogenin becomes redundant. We suggest that acetic acid extraction of recombinant amelogenin and subsequent purification using preparative SDS PAGE provides a simple route to highly purified His-tag free amelogenin for use in structure-function experiments and beyond

    A review and analysis of the relationship between neuropsychological measures and DAT1 in ADHD

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    Contains fulltext : 69105.pdf (publisher's version ) (Closed access)Meta-analyses indicate that the gene coding for the dopamine transporter (DAT1 or SLC6A3) is associated with an increased risk for ADHD. The mechanisms of this gene for ADHD are unclear. We systematically reviewed studies linking the VNTR in the 3' UTR of the DAT1 to neurophysiological and neuropsychological measures. In addition, a broad set of executive/cognitive and motor tests was administered to 350 children (5-11 years) and adolescents (11-19 years) with ADHD and 195 non-affected siblings. Two VNTRs (in intron 8 and the 3' UTR) and four SNPs (two 5' and two 3') in DAT1 were genotyped. The effect of the polymorphisms on neuropsychological functioning was studied. The review indicated that the majority of studies did not find a relation between DAT1 and neurophysiological or neuropsychological measures. In our sample, several of the polymorphisms of DAT1 were associated with ADHD and ADHD was associated with impaired neuropsychological functioning. However, none of the DAT1 polymorphisms was convincingly associated with neuropsychological dysfunctioning. This suggests that the effect of DAT1 on ADHD was not mediated by neuropsychological performance. However, since DAT1 is mainly expressed in the striatum and not the prefrontal cortex, it may influence striatum-related functions (such as delay aversion) more heavily than prefrontal related functions (such as executive functions). Associations of DAT1 with ADHD were only found in adolescents, which may suggest that DAT1 mainly exerts its effect in adolescence, and/or that having a more persistent form of ADHD may mark a more severe or homogeneous genetic form of the disorder

    Amelogenesis Imperfecta caused by N-Terminal Enamelin Point Mutations in Mice and Men is driven by Endoplasmic Reticulum Stress

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    ‘Amelogenesis imperfecta’ (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans. Our data indicate that the mutation inhibits the ameloblast secretory pathway leading to ER stress and an activated unfolded protein response (UPR). Initially, with the support of the UPR acting in pro-survival mode, Enam(p.S55I) heterozygous mice secreted structurally normal enamel. However, enamel secreted thereafter was structurally abnormal; presumably due to the UPR modulating ameloblast behaviour and function in an attempt to relieve ER stress. Homozygous mutant mice failed to produce enamel. We also identified a novel heterozygous ENAM(p.L31R) mutation causing AI in humans. We hypothesize that ER stress is the aetiological factor in this case of human AI as it shared the characteristic phenotype described above for the Enam(p.S55I) mouse. We previously demonstrated that AI in mice carrying the Amelx(p.Y64H) mutation is a proteinopathy. The current data indicate that AI in Enam(p.S55I) mice is also a proteinopathy, and based on comparative phenotypic analysis, we suggest that human AI resulting from the ENAM(p.L31R) mutation is another proteinopathic disease. Identifying a common aetiology for AI resulting from mutations in two different genes opens the way for developing pharmaceutical interventions designed to relieve ER stress or modulate the UPR during enamel development to ameliorate the clinical phenotype

    Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation

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    Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating – a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility

    New Parameters for Left Ventricular Function in Atrial Fibrillation: Based on the Relationship between RR Interval and Performance

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    This study was designed to obtain new parameters representing left ventricular (LV) function independent of irregular RR intervals in atrial fibrillation (AF). AF patients were divided into Normal (n=9) and LV Dysfunction (n=9) groups. The relations between LV outflow peak ejection velocity (Vpe) and preceding (RR-1) or pre-preceding RR intervals (RR-2) were obtained using logarithmic equations, from which the squared correlation coefficient (r2), slope, Vpe at RR-1 or RR-2=1 sec (Vpe-1), and the ratio of slope to Vpe-1 (Slope/Vpe-1) were calculated. Among the parameters between RR-1 and Vpe, Slope/Vpe-1 was higher in LV Dysfunction group than in Normal group (p=0.05). When only coordinates with RR-1 from 0.6 to 1 sec were included, Slope/Vpe-1 (p=0.001) was higher in LV Dysfunction group than in Normal group. Among the parameters between RR-2 and Vpe, Slope/Vpe-1, slope, and r2 were different between the two groups. In multivariate analysis, Slope/Vpe-1 between RR-2 and Vpe was only independent parameter. However, Slope/Vpe-1 between RR-1 and Vpe in the coordinates with RR-1 from 0.6 to 1 sec had the highest discriminating power. New parameters derived from the relations between RR intervals and LV performance might be useful to evaluate LV function quantitatively in AF

    Distinct Linkage Disequilibrium (LD) Runs of Single Nucleotide Polymorphisms and Microsatellite Markers; Implications for Use of Mixed Marker Haplotypes in LD-based Mapping

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    It has been suggested that the haplotypic relationship between microsatellite markers and single nucleotide polymorphisms (SNPs) is of considerable importance, as microsatellite markers can potentially be incorporated into haplotypes containing SNPs to increase marker density across a region of interest. However, SNPs and microsatellite markers have different mutation rates and durations, and it is conceivable that the linkage disequilibrium (LD) patterns between the genetic markers may considerably differ. We assessed the LD patterns using 1,661 SNPs and 65 microsatellite markers along chromosome 22 and investigated whether common patterns of LD between the two genetic markers are deduced from the results. The results demonstrated that the patterns of LD among microsatellite markers varied considerably and the LD runs of SNPs and microsatellite markers showed distinct patterns. Microsatellite markers have a much higher mutation rate and the evolution of microsatellite markers is a more complex process which has distinct mutation properties from those of SNPs. We consider that these might contribute to the different LD patterns between the two genetic markers. Therefore, it would seem inadvisable to make assumptions about persistence of LD across even a relatively small genetic distance among microsatellite markers and to construct mixed marker haplotypes/LD maps employing microsatellite markers
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