Postprandial apoE isoform and conformational changes associated with VLDL lipolysis products modulate monocyte inflammation.

ObjectivePostprandial hyperlipemia, characterized by increased circulating very low-density lipoproteins (VLDL) and circulating lipopolysaccharide (LPS), has been proposed as a mechanism of vascular injury. Our goal was to examine the interactions between postprandial lipoproteins, LPS, and apoE3 and apoE4 on monocyte activation.Methods and resultsWe showed that apoE3 complexed to phospholipid vesicles attenuates LPS-induced THP-1 monocyte cytokine expression, while apoE4 increases expression. ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4. Electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels placed on specific amino acids of apoE3 showed that LPS interferes with conformational changes normally associated with lipid binding. Specifically, compared to apoE4, apoE bearing the E3-like R112→Ser mutation displays increased self association when exposed to LPS, consistent with a stronger apoE3-LPS interaction. Additionally, lipolysis of fasting VLDL from normal human donors attenuated LPS-induced TNFα secretion from monocytes to a greater extent than postprandial VLDL, an effect partially reversed by blocking apoE. This effect was reproduced using fasting VLDL lipolysis products from e3/e3 donors, but not from e4/e4 subjects, suggesting that apoE3 on fasting VLDL prevents LPS-induced inflammation more readily than apoE4.ConclusionPostprandial apoE isoform and conformational changes associated with VLDL dramatically modulate vascular inflammation

Geochemistry and geochronology of the Paleozoic sedimentary rocks in the Shar Khutul area, Central Mongolia

The study area is located in the central part of Tsetserleg terrane in the southwestern margin of the Khangai-Khentey orogenic system. The paper presents new data on geochemistry and geochronology of sedimentary rocks from the Shar Khutul area, where the Tsetserleg terrane consists of Silurian-Devonian oceanic plate stratigraphic unit and Carboniferous shallow water sediment. The Upper Silurian to Middle Devonian Erdenetsogt Formation (S3-D2er), which is an oceanic plate stratigraphic unit, is mainly composed of siliceous siltstone, volcanites, tuffs, quartzite, and cherts. The shallow water sediments are divided into Upper Devonian to Lower Carboniferous Tsetserleg Formation (D3-C1cc) and Lower–Middle Carboniferous Dzargalant Formation (C1-2dz). The Tsetserleg Formation (D3-C1cc) consists of only sedimentary rocks such as bluish-grey sandstones and siltstones, and Lower–Middle Carboniferous Dzargalant Formation (C1-2dz) is principally composed of medium- to coarse-grained, brown-greenish grey sandstones with thin-layers of dark siltstones and gravelites. The SiO2 content of the Shar Khutul area sandstones ranges from 63.85 to 67.95 wt.% and the average content of TiO2 is 0.72 wt.% and Al2O3 content is 14.38 wt.%. The Chemical Index of Alteration (CIA) value ranges from 48.71 to 56.94 and the range of Index of compositional variations (ICV) is from 0.98 to 1.24. Moreover, the samples studied show that most of the sandstones are generally immature and were derived from weakly weathered source rocks. The ratios of Eu/Eu* (0.83), La/Sc (3.81), La/Co (5.30), and Cr/Th (13.81) indicate that the derivation of the Shar Khutul area sandstones from felsic rock sources and confirm the signatures of a felsic igneous provenance and suggest an active continental margin tectonic setting of the source area. The clastic zircons from the medium grained sandstone (Erdenetsogt formation) yield ages between 2.5 Ga and 236 Ma and the detrital zircons exhibit four peak ages at 1.7-2.5 Ga (n = 13), 455-499 Ma (n = 6), 337-382 Ma (n = 13) and 236–250 Ma (n = 5)

Maze solvers demystified and some other thoughts

There is a growing interest towards implementation of maze solving in spatially-extended physical, chemical and living systems. Several reports of prototypes attracted great publicity, e.g. maze solving with slime mould and epithelial cells, maze navigating droplets. We show that most prototypes utilise one of two phenomena: a shortest path in a maze is a path of the least resistance for fluid and current flow, and a shortest path is a path of the steepest gradient of chemoattractants. We discuss that substrates with so-called maze-solving capabilities simply trace flow currents or chemical diffusion gradients. We illustrate our thoughts with a model of flow and experiments with slime mould. The chapter ends with a discussion of experiments on maze solving with plant roots and leeches which show limitations of the chemical diffusion maze-solving approach.Comment: This is a preliminary version of the chapter to be published in Adamatzky A. (Ed.) Shortest path solvers. From software to wetware. Springer, 201

Quantifying the performance of a hybrid anion exchanger/adsorbent for phosphorus removal using mass spectrometry coupled with batch kinetic trials

Increasingly stricter phosphorus discharge limits represent a significant challenge for the wastewater industry. Hybrid media comprising anionic exchange resins with dispersions of hydrated ferric oxide nanoparticles have been shown to selectively remove phosphorus from wastewaters, and display greater capacity and operational capability than both conventional treatment techniques and other ferric-based adsorbent materials. Spectrographic analyses of the internal surfaces of a hybrid media during kinetic experiments show that the adsorption of phosphorus is very rapid, utilising 54% of the total capacity of the media within the first 15 min and 95% within the first 60 min. These analyses demonstrate the importance of intraparticle diffusion on the overall rate in relation to the penetration of phosphorus. Operational capacity is a function of the target effluent phosphorus concentration and for 0.1 mg P L−1, this is , which is 8–13% of the exhaustive capacity. The adsorbed phosphorus can be selectively recovered, offering a potential route to recycle this important nutrient. The main implication of the work is that the ferric nanoparticle adsorbent can provide a highly effective means of achieving a final effluent phosphorus concentration of 0.1 mg P L−1, even when treating sewage effluent at 5 mg P L−1

Role for the flagellum attachment zone in Leishmania anterior cell tip morphogenesis

The shape and form of the flagellated eukaryotic parasite Leishmania is sculpted to its ecological niches and needs to be transmitted to each generation with great fidelity. The shape of the Leishmania cell is defined by the sub-pellicular microtubule array and the positioning of the nucleus, kinetoplast and the flagellum within this array. The flagellum emerges from the anterior end of the cell body through an invagination of the cell body membrane called the flagellar pocket. Within the flagellar pocket the flagellum is laterally attached to the side of the flagellar pocket by a cytoskeletal structure called the flagellum attachment zone (FAZ). During the cell cycle single copy organelles duplicate with a new flagellum assembling alongside the old flagellum. These are then segregated between the two daughter cells by cytokinesis, which initiates at the anterior cell tip. Here, we have investigated the role of the FAZ in the morphogenesis of the anterior cell tip. We have deleted the FAZ filament protein, FAZ2 and investigated its function using light and electron microscopy and infection studies. The loss of FAZ2 caused a disruption to the membrane organisation at the anterior cell tip, resulting in cells that were connected to each other by a membranous bridge structure between their flagella. Moreover, the FAZ2 null mutant was unable to develop and proliferate in sand flies and had a reduced parasite burden in mice. Our study provides a deeper understanding of membrane-cytoskeletal interactions that define the shape and form of an individual cell and the remodelling of that form during cell division

Renal trematode infection due to Paratanaisia bragai in zoo housed Columbiformes and a Red Bird-of-Paradise (Paradisaea rubra)

Trematode infections affect a diverse range of avian species and the organs that are parasitised are also very varied. The family Eucotylidae contains seven genera of renal flukes that parasitise various birds. In birds, mild to severe lesions have been reported for species of the genus Paratanaisia, which was originally described from columbiform and galliform specimens collected in South America and has been identified in a number of wild avian species. This paper investigates eight cases of renal trematode infection at Chester Zoo in the UK due to Paratanaisia bragai in five previously unreported species: red bird-of-paradise, Socorro dove, Mindanao bleeding heart dove, laughing dove and emerald dove. Pathological changes, which varied between species, are discussed. A known intermediate snail host Allopeas clavulinum was present in the enclosures but there was no direct evidence of trematode infection. The size of the snails, possible low prevalence and the difficulty of visualising sporocysts contributed to this. Thus the development and application of further molecular diagnostic markers that can be applied to snail tissues is warranted. Parasite identification was confirmed utilizing DNA amplification from formalin-fixed paraffin-embedded tissues using PCR and trematode specific primers. Sequencing full ssrDNA and D1-D3 lsrDNA confirmed the identity in all cases as P. bragai. However, the short 310 bp fragment used provides insufficient variation or sequence length for wider application. The epidemiology, pathology and consequences for the management of these endangered species are discussed. Preliminary work on developing an effective ante mortem diagnostic PCR test kit is also highlighted

Nitrifying Microorganisms Linked to Biotransformation of Perfluoroalkyl Sulfonamido Precursors from Legacy Aqueous Film-Forming Foams

Drinking water supplies across the United States have been contaminated by firefighting and fire-training activities that use aqueous film-forming foams (AFFF) containing per- and polyfluoroalkyl substances (PFAS). Much of the AFFF is manufactured using electrochemical fluorination by 3M. Precursors with six perfluorinated carbons (C6) and non-fluorinated amine substituents make up approximately one-third of the PFAS in 3M AFFF. C6 precursors can be transformed through nitrification (microbial oxidation) of amine moieties into perfluorohexane sulfonate (PFHxS), a compound of regulatory concern. Here, we report biotransformation of the most abundant C6 sulfonamido precursors in 3M AFFF with available commercial standards (FHxSA, PFHxSAm, and PFHxSAmS) in microcosms representative of the groundwater/surface water boundary. Results show rapid (\u3c1 day) biosorption to living cells by precursors but slow biotransformation into PFHxS (1–100 pM day–1). The transformation pathway includes one or two nitrification steps and is supported by the detection of key intermediates using high-resolution mass spectrometry. Increasing nitrate concentrations and total abundance of nitrifying taxa occur in parallel with precursor biotransformation. Together, these data provide multiple lines of evidence supporting microbially limited biotransformation of C6 sulfonamido precursors involving ammonia-oxidizing archaea (Nitrososphaeria) and nitrite-oxidizing bacteria (Nitrospina). Further elucidation of interrelationships between precursor biotransformation and nitrogen cycling in ecosystems would help inform site remediation efforts

Does owning a pet protect older people against loneliness?

This article has been made available through the Brunel Open Access Publishing Fund.Pet ownership is thought to make a positive contribution to health, health behaviours and the general well-being of older people. More specifically pet ownership is often proposed as a solution to the problem of loneliness in later life and specific 'pet based' interventions have been developed to combat loneliness. However the evidence to support this relationship is slim and it is assumed that pet ownership is a protection against loneliness rather than a response to loneliness. The aim of this paper is to examine the association between pet ownership and loneliness by exploring if pet ownership is a response to, or protection against, loneliness using Waves 0-5 from the English Longitudinal Study of Ageing (ELSA)

SUpporting well-being through PEeR-Befriending (SUPERB) trial: an exploration of fidelity in peer-befriending for people with aphasia

Assessing the evolution of severely brain-injured patients with disorders of consciousness (DOC) with current tools like the Glasgow Outcome Scale-Extended (GOS-E) remains a challenge. At the bedside, the most reliable diagnostic tool is currently the Coma Recovery Scale-Revised. The CRS-R distinguishes patients with unresponsive wakefulness syndrome (UWS) from patients in minimally conscious state (MCS) and patients who have emerged from MCS (EMCS). This international multi-centric study aims to validate a phone outcome questionnaire (POQ) based on the CRS-R and compare it to the CRS-R performed at the bedside and to the GOS-E which evaluates the level of disability and assigns patient’s in outcomes categories. The POQ will allow clinicians to probe the evolution of patient’s state of consciousness based on caregivers feedback. This research project is part of the International Brain Injury Association, Disorders of Consciousness-Special Interest Group (DOCSIG) and DOCMA consortium