Vitamin K antagonists predispose to calciphylaxis in patients with end-stage renal disease.

BACKGROUND/AIMS: Calciphylaxis is associated with a poor prognosis in dialysis patients, and its pathogenesis remains incompletely understood. Although the use of vitamin K antagonists (VKA) has been implicated, previous reports are conflicting. We aimed to determine if vitamin K antagonists conferred an increased risk of calciphylaxis in patients on dialysis. METHODS: We performed a single-centre, retrospective cohort study of 2,234 patients receiving dialysis, and compared the characteristics of those with and without calciphylaxis. RESULTS: We identified 5 cases of calciphylaxis (all female) between January 2009 and December 2013. Overall, 142 patients (6.4%) were treated with VKA during the study period. Calciphylaxis was more common in the VKA group (4 of 142 patients, OR = 61, 95% CI 6.7-546, p = 0.0001). VKA was withdrawn in all cases and treatment instituted with sodium thiosulphate, cinacalcet and supportive measures. All patients recovered, although there was one sudden cerebrovascular death during follow-up. CONCLUSION: Treatment with VKA predisposes to the development of calciphylaxis.TFH is funded by the Cambridge BRC and NIHR.This is the accepted manuscript for a paper published in Nephron Clinical Practice, Vol. 129, No. 3, 2015, DOI:10.1159/00037144

Xyloglucan is released by plants and promotes soil particle aggregation

Soil is a crucial component of the biosphere and is a major sink for organic carbon. Plant roots are known to release a wide range of carbon-based compounds into soils, including polysaccharides, but the functions of these are not known in detail. Using a monoclonal antibody to plant cell wall xyloglucan, we show that this polysaccharide is secreted by a wide range of angiosperm roots, and relatively abundantly by grasses. It is also released from the rhizoids of liverworts, the earliest diverging lineage of land plants. Using analysis of water-stable aggregate size, dry dispersion particle analysis and scanning electron microscopy, we show that xyloglucan is effective in increasing soil particle aggregation, a key factor in the formation and function of healthy soils. To study the possible roles of xyloglucan in the formation of soils, we analysed the xyloglucan contents of mineral soils of known age exposed upon the retreat of glaciers. These glacial forefield soils had significantly higher xyloglucan contents than detected in a UK grassland soil. We propose that xyloglucan released from plant rhizoids/roots is an effective soil particle aggregator and may, in this role, have been important in the initial colonization of land

Sticky mucilages and exudates of plants: putative microenvironmental design elements with biotechnological value

Plants produce a wide array of secretions both above- and belowground. Known as mucilages or exudates, they are secreted by seeds, roots, leaves and stems and fulfil a variety of functions including adhesion, protection, nutrient acquisition or infection. Mucilages are generally polysaccharide-rich and often occur in the form of viscelastic gels and in many cases have adhesive properties. In some cases, progress is being made in understanding the structure-function relations of mucilages such as for the secretions that allow growing ivy to attach to substrates and the biosynthesis and secretion of the mucilage compounds of the Arabidopsis seed coat. Work is just beginning in understanding root mucilage and the proposed adhesive polymers involved in the formation of rhizosheaths at root surfaces and for the secretions involved in host plant infection by parasitic plants. In this article, we summarize knowledge on plant exudates and mucilages within the concept of their functions in microenvironmental design, focusing especially on their bioadhesive functions and the molecules responsible for them. We draw attention to areas of future knowledge need, including the microstructure of mucilages and their compositional and regulatory dynamics. This article is protected by copyright. All rights reserved

Segmentation of the C57BL/6J mouse cerebellum in magnetic resonance images

The C57BL mouse is the centerpiece of efforts to use gene-targeting technology to understand cerebellar pathology, thus creating a need for a detailed magnetic resonance imaging (MRI) atlas of the cerebellum of this strain. In this study we present a methodology for systematic delineation of the vermal and hemispheric lobules of the C57BL/6J mouse cerebellum in magnetic resonance images. We have successfully delineated 38 cerebellar and cerebellar-related structures. The higher signal-to-noise ratio achieved by group averaging facilitated the identification of anatomical structures. In addition, we have calculated average region volumes and created probabilistic maps for each structure. The segmentation method and the probabilistic maps we have created will provide a foundation for future studies of cerebellar disorders using transgenic mouse models

Possible Resonances in the 12C + 12C Fusion Rate and Superburst Ignition

Observationally inferred superburst ignition depths are shallower than models predict. We address this discrepancy by reexamining the superburst trigger mechanism. We first explore the hypothesis of Kuulkers et al. that exothermic electron captures trigger superbursts. We find that all electron capture reactions are thermally stable in accreting neutron star oceans and thus are not a viable trigger mechanism. Fusion reactions other than 12C + 12C are infeasible as well since the possible reactants either deplete at much shallower depths or have prohibitively large Coulomb barriers. Thus we confirm the proposal of Cumming & Bildsten and Strohmayer & Brown that 12C + 12C triggers superbursts. We then examine the 12C + 12C fusion rate. The reaction cross-section is experimentally unknown at astrophysically relevant energies, but resonances exist in the 12C + 12C system throughout the entire measured energy range. Thus it is likely, and in fact has been predicted, that a resonance exists near the Gamow peak energy ~ 1.5 MeV. For such a hypothetical 1.5 MeV resonance, we derive both a fiducial value and upper limit to the resonance strength and find that such a resonance could decrease the theoretically predicted superburst ignition depth by up to a factor of 4; in this case, observationally inferred superburst ignition depths would accord with model predictions for a range of plausible neutron star parameters. Said differently, such a resonance would decrease the temperature required for unstable 12C ignition at a column depth 10^12 g/cm^2 from 6 x 10^8 K to 5 x 10^8 K. Determining the existence of a strong resonance in the Gamow window requires measurements of the 12C + 12C cross-section down to a center-of-mass energy near 1.5 MeV, which is within reach of the proposed DUSEL facility.Comment: 13 pages, 4 figures; minor improvements, results and conclusions unchanged, accepted to Ap

Efficient ancestry and mutation simulation with msprime 1.0

Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this, a large number of specialized simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and the tskit library. We summarize msprime’s many features, and show that its performance is excellent, often many times faster and more memory efficient than specialized alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement