2,994 research outputs found

    Analysis of mutations causing familial hypercholesterolaemia in black South African patients of different ancestry

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    Background. Familial hypercholesterolaemia (FH) is usually caused by mutations in three genes (LDLR, APOB and PCSK9).Objective. To identify the spectrum of FH-causing mutations in black South African (SA) patients.Methods. DNA samples of 16 unrelated South African FH patients with elevated low-density lipoprotein cholesterol levels, tendon xanthomas and corneal arcus (3 clinically homozygous FH and 13 heterozygous FH) of ethnic African origin were screened for mutations in the LDLR (coding region, promoter and intron/exon boundaries), APOB (part of exon 26) and PCSK9 genes (exon 7), using high-resolution melting.Results. Eight LDLR mutations were identified, for an overall detection rate of 8/19 predicted FH-causing alleles (42.1%). The previously reported six base pair deletion p.(D47_G48del) was found in two patients, and two novel variants (c.1187-25T>C and c.1664T>G p.(L555R)) were found, both predicted to be pathogenic using in silico web-based predictive algorithms. No pathogenic variants in APOB or PCSK9 were found.Conclusions. These findings contribute to the knowledge of allelic heterogeneity in the spectrum of FH-causing mutations in black SA patients, signifying their ancestral diversity. The relatively low overall detection rate may reflect locus heterogeneity of the FH phenotype in black SA FH patients

    Organic contaminant content and physico-chemical characteristics of waste materials recycled in agriculture

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    A range of wastes representative of materials currently applied, or with future potential to be applied, to agricultural land in the UK as fertilisers and soil improvers or used as animal bedding in livestock production, were investigated. In addition to full physico-chemical characterization, the materials were analysed for a suite of priority organic contaminants. In general, contaminants were present at relatively low concentrations. For example, polychlorinated dibenzo-p-dioxins/dibenzofurans and polychlorinated biphenyls in biosolids and compost-like-outputs (CLOs) were, in most cases, between 5-50 times lower than proposed and implemented European limit values for biosolids or composts applied to agricultural land. However, the technical basis for these limits may need to be re-evaluated. Polybrominated, and mixed halogenated, dibenzo-p-dioxins/dibenzofurans are not currently considered in risk assessments of dioxins and dioxin-like chemicals, but were detected in the biosolids and compost-like-outputs and their potential contribution to the overall toxic equivalency will be assessed. Other, ‘emerging’ contaminants such as perfluoralkyl compounds (PFCs) and organophosphate flame retardants were detected in several of the waste materials, and their potential significance is discussed. The study is part of a wider research programme that will provide evidence to improve confidence in the use of waste-derived materials in agriculture and establish guidelines to protect the food chain where necessary

    Optimisation of energetic and reproductive gains explains behavioural responses to environmental variation across seasons and years

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    Animals switch between inactive and active states, simultaneously impacting their energy intake, energy expenditure and predation risk, and collectively defining how they engage with environmental variation and trophic interactions. We assess daily activity responses to long‐term variation in temperature, resources and mating opportunities to examine whether individuals choose to be active or inactive according to an optimisation of the relative energetic and reproductive gains each state offers. We show that this simplified behavioural decision approach predicts most activity variation (R2 = 0.83) expressed by free‐ranging red squirrels over 4 years, as quantified through accelerometer recordings (489 deployments; 5066 squirrel‐days). Recognising activity as a determinant of energetic status, the predictability of activity variation aggregated at a daily scale, and the clear signal that behaviour is environmentally forced through optimisation of gain, provides an integrated approach to examine behavioural variation as an intermediary between environmental variation and energetic, life‐history and ecological outcomes.By assessing daily activity responses to long‐term variation in temperature, resources, and mating opportunities, we examine whether individuals choose to be active or inactive according to an optimization of energetic and reproductive gains. This simplified behavioural decision approach predicts most daily activity variation (R2 = 0.83) expressed by free‐ranging red squirrels over four years, as quantified through accelerometer recordings. Here we provide an integrated approach to examine behavioural variation as an intermediary between environmental variation and energetic, life‐history, and ecological outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154889/1/ele13494_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154889/2/ele13494.pd

    Index

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    The interest in relativistic beam-plasma instabilities has been greatly rejuvenated over the past two decades by novel concepts in laboratory and space plasmas. Recent advances in this long-standing field are here reviewed from both theoretical and numerical points of view. The primary focus is on the two-dimensional spectrum of unstable electromagnetic waves growing within relativistic, unmagnetized, and uniform electron beam-plasma systems. Although the goal is to provide a unified picture of all instability classes at play, emphasis is put on the potentially dominant waves propagating obliquely to the beam direction, which have received little attention over the years. First, the basic derivation of the general dielectric function of a kinetic relativistic plasma is recalled. Next, an overview of two-dimensional unstable spectra associated with various beam-plasma distribution functions is given. Both cold-fluid and kinetic linear theory results are reported, the latter being based on waterbag and Maxwell–Jüttner model distributions. The main properties of the competing modes (developing parallel, transverse, and oblique to the beam) are given, and their respective region of dominance in the system parameter space is explained. Later sections address particle-in-cell numerical simulations and the nonlinear evolution of multidimensional beam-plasma systems. The elementary structures generated by the various instability classes are first discussed in the case of reduced-geometry systems. Validation of linear theory is then illustrated in detail for large-scale systems, as is the multistaged character of the nonlinear phase. Finally, a collection of closely related beam-plasma problems involving additional physical effects is presented, and worthwhile directions of future research are outlined.Original Publication: Antoine Bret, Laurent Gremillet and Mark Eric Dieckmann, Multidimensional electron beam-plasma instabilities in the relativistic regime, 2010, Physics of Plasmas, (17), 12, 120501-1-120501-36. http://dx.doi.org/10.1063/1.3514586 Copyright: American Institute of Physics http://www.aip.org/</p

    Neighborhoods of trees in circular orderings

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    In phylogenetics, a common strategy used to construct an evolutionary tree for a set of species X is to search in the space of all such trees for one that optimizes some given score function (such as the minimum evolution, parsimony or likelihood score). As this can be computationally intensive, it was recently proposed to restrict such searches to the set of all those trees that are compatible with some circular ordering of the set X. To inform the design of efficient algorithms to perform such searches, it is therefore of interest to find bounds for the number of trees compatible with a fixed ordering in the neighborhood of a tree that is determined by certain tree operations commonly used to search for trees: the nearest neighbor interchange (nni), the subtree prune and regraft (spr) and the tree bisection and reconnection (tbr) operations. We show that the size of such a neighborhood of a binary tree associated with the nni operation is independent of the tree’s topology, but that this is not the case for the spr and tbr operations. We also give tight upper and lower bounds for the size of the neighborhood of a binary tree for the spr and tbr operations and characterize those trees for which these bounds are attained

    Reconstructing the three-dimensional GABAergic microcircuit of the striatum

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    A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study
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