pH Dependence of Amyloid-β Fibril Assembly Kinetics: Unravelling the Microscopic Molecular Processes.

Central to Alzheimer's disease (AD) is the assembly of the amyloid-beta peptide (Aβ) into fibrils. A reduction in pH accompanying inflammation or subcellular compartments, may accelerate fibril formation as the pH approaches Aβ's isoelectric point (pI). Using global fitting of thioflavin-T to monitor fibril formation kinetics over a range of pHs, we identify the impact net charge has on individual microscopic rate constants which are associated with fibril assembly. We show that the primary nucleation has a strong pH dependence. The titration behaviour exhibits a mid-point or pKa of 7.0, close to the pKa of Aβ histidine imidazoles. Surprisingly, both the secondary nucleation and elongation rate constants are pH independent. This indicates the charge of Aβ, in particular histidine protonation, has little impact on this stage of Aβ assembly. These fundamental processes are key to understanding the forces that drive the assembly of Aβ into toxic oligomers and fibrils

Copper(II) Can Kinetically Trap Arctic and Italian Amyloid‑β40 as Toxic Oligomers, Mimicking Cu(II) Binding to Wild-Type Amyloid‑β42: Implications for Familial Alzheimer’s Disease

The self-association of amyloid-β (Aβ) peptide into neurotoxic oligomers is believed to be central to Alzheimer’s disease (AD). Copper is known to impact Aβ assembly, while disrupted copper homeostasis impacts phenotype in Alzheimer’s models. Here we show the presence of substoichiometric Cu(II) has very different impacts on the assembly of Aβ40 and Aβ42 isoforms. Globally fitting microscopic rate constants for fibril assembly indicates copper will accelerate fibril formation of Aβ40 by increasing primary nucleation, while seeding experiments confirm that elongation and secondary nucleation rates are unaffected by Cu(II). In marked contrast, Cu(II) traps Aβ42 as prefibrillar oligomers and curvilinear protofibrils. Remarkably, the Cu(II) addition to preformed Aβ42 fibrils causes the disassembly of fibrils back to protofibrils and oligomers. The very different behaviors of the two Aβ isoforms are centered around differences in their fibril structures, as highlighted by studies of C-terminally amidated Aβ42. Arctic and Italian familiar mutations also support a key role for fibril structure in the interplay of Cu(II) with Aβ40/42 isoforms. The Cu(II) dependent switch in behavior between nonpathogenic Aβ40 wild-type and Aβ40 Arctic or Italian mutants suggests heightened neurotoxicity may be linked to the impact of physiological Cu(II), which traps these familial mutants as oligomers and curvilinear protofibrils, which cause membrane permeability and Ca(II) cellular influx

Soot volume fraction measurements over laminar pool flames of biofuels, diesel and blends

© 2018 The Combustion Institute. Biodiesel and blends with petroleum diesel have shown their potential as renewable alternative fuels for engines, with additional benefits of low particulate matter and low sulfate emissions. In this paper we measure the soot volume fraction produced by three different methyl esters processed biodiesels (extracted from palm (PME), soy (SME) and coconut (CME)), and their blends with petroleum diesel, in a series of co-flow stabilized laminar pool flames, using laser induced-incandescence (LII) and laser extinction optical methods. The soot volume fraction measurement results show that all neat biodiesels produce only up to 33% of the total soot volume compared to pure diesel, and that the total soot volume correlates directly with the degree of unsaturation of the biodiesels. Blending leads to approximately linear behaviour of total soot volume, with a shift in slope with smaller sensitivity towards neat diesel

Quantification of carbon particulates produced under open liquid pool and prevaporised flame conditions: Waste cooking oil biodiesel and diesel blends

The soot volume fraction (SVF) of waste cooking oil (WCO) biodiesel and blends was quantified and compared under the same total carbon flow rate via two experimental setups, namely prevaporised diffusion jet flames and pool flames using extinction calibrated laser induced-incandescence (LII). The spatial SVF distribution shows that for diesel-rich fuels, soot formation peaks near the flame and is convected downstream, whereas biodiesel flames show a more evenly distributed SVF at the flame center region. An increase in biodiesel fraction in diesel results in a reduced propensity for soot, as evident in both pool and vapour flames. Comparison of the radial profiles of SVF along the centerline shows broader SVF profiles for pool flames, reflecting the longer residence times for soot diffusion and growth compared to vapour flames, which reflected the lower mass flux for the pool burner. The total soot produced from pool flames was found to be higher than vapour flame by a factor of two for the same fuel mass consumption rate. WCO biodiesel exhibited the lowest total SVF value regardless of flame type owing to the combined effects of lack of aromatic compounds and fuel chemistry. The soot primary particle sizes produced by WCO biodiesel show lower mean diameter values by a factor of approximately 1.5 compared to diesel-produced soot. The pool flames produced carbon particulates of larger mean diameter by around 22% and 8% for diesel and WCO biodiesel, respectively, relative to the counterpart vapour flames, as a result of extended soot surface growth period.Royal Society-Newton Advanced Fellow (NA160115) Academy of Sciences Malaysia (ASM) Malaysian Industry-Government Group for High Technology (MIGHT

Biodiesel sustainability: The global impact of potential biodiesel production on the energy–water–food (EWF) nexus

A data-driven model is used to analyse the global effects of biodiesel on the energy–water–food (EWF) nexus, and to understand the complex environmental correlation. Several criteria to measure the sustainability of biodiesel and four main limiting factors for biodiesel production are discussed in this paper. The limiting factors includes water stress, food stress, feedstock quantity and crude oil price. The 155-country model covers crude oil prices ranging from USD10/bbl to USD160/bbl, biodiesel refinery costs ranging from -USD0.30/L to USD0.30/L and 45 multi-generation biodiesel feedstocks. The model is capable of ascertaining changes arising from biodiesel adoption in terms of light-duty diesel engine emissions (NO, CO, UHC and smoke opacity), water stress index (WSI), dietary energy supply (DES), Herfindahl–Hirschman index (HHI) and short-term energy security. With the addition of potential biodiesel production, the renewable energy sector of global primary energy profile can increase by 0.43%, with maximum increment up to 10.97% for Malaysia. At current crude oil price of USD75/bbl and refinery cost of USD0.1/L, only Benin, Ireland and Togo can produce biodiesel profitably. The model also shows that water requirement varies non-linearly with multi-feedstock biodiesel production as blending ratio increases. Out of the 155 countries, biodiesel production is limited by feedstock quantity for 82 countries, 47 are limited by crude oil price, 20 by water stress and 6 by food stress. The results provide insights for governments to set up environmental policy guidelines, in implementing biodiesel technology as a cleaner alternative to diesel

Experimental and numerical study on soot formation in laminar diffusion flames of biodiesels and methyl esters

Biodiesel and blends with petroleum diesel are promising renewable alternative fuels for engines. In the present study, the soot concentration generated from four biodiesels, two pure methyl esters, and their blends with petroleum diesel are measured in a series of fully pre-vapourised co-flow diffusion flames. The experimental measurements are conducted using planar laser induced-incandescence (LII) and laser extinction optical methods. The results show that the maximum local soot volume fractions of neat biodiesels are 24.4% - 41.2% of pure diesel, whereas the mean soot volume fraction of neat biodiesel cases was measured as 11.3% - 21.3% of pure diesel. The addition of biodiesel to diesel not only reduces the number of inception particles, but also inhibits their surface growth. The discretised population balance modelling of a complete set of soot processes is employed to compute the 2D soot volume fraction and size distribution across the tested flames. The results show that the model also demonstrates a reduction of both soot volume fraction and primary particle size by adding biodiesel fuels. However, it is not possible to clearly determine which factors are responsible for the reduction from the comparison alone. Moreover, analysis of the discrepancies between numerical and experimental results for diesel and low-blending cases offers an insight for the refinement of soot formation modelling of combustion with large-molecule fuels.Bo Tian is supported by the fellowship provided by ZEPI. C. T. Chong is supported by the Newton Advanced Fellowship of the Royal Society (NA160115). Anxiong Liu gratefully acknowledges the financial support of the Chinese Scholarship Council (CSC) and the EPSRC grant No. EP/S012559/1

Ergothioneine supplementation in people with metabolic syndrome (ErgMS): protocol for a randomised, double-blind, placebo-controlled pilot study

Background Ergothioneine is a naturally occurring metabolite of histidine found in many foods and in high amounts in mushrooms. In vivo, ergothioneine acts as an antioxidant and is widely distributed in most mammalian tissues. While ergothioneine is sold as a dietary supplement for its antioxidant and anti-inflammatory properties, to date there are no published intervention trials examining its health benefits in humans. The aim of this work was to develop a study protocol for a pilot interventional trial that will establish the primary and secondary outcomes, and the power required, for a definitive randomised controlled trial to test the hypothesis that ergothioneine supplementation is beneficial for people with metabolic syndrome. Methods We have designed the ErgMS study as a single-centre, randomised, double-blind, placebo-controlled, 3-arm parallel, pilot intervention trial, which aims to supplement participants with either placebo, 5 or 30 mg/day ergothioneine for 12 weeks. Measurements of metabolic syndrome risk factors, serum markers of oxidative stress (lipid peroxidation), inflammation, blood platelet function and liver function will take place at baseline, and after 6 weeks and 12 weeks of supplementation. In addition, we will examine if there are any changes in the serum metabolome in response to ergothioneine supplementation. Linear regression and two-way ANOVA will be utilised to analyse the association between ergothioneine and measured variables. Discussion The ErgMS study will be the first study to address the question does ergothioneine supplementation have health benefits for people with metabolic syndrome. Study results will provide preliminary data as to which dose may improve inflammatory markers in adults with metabolic syndrome and will inform dose and primary outcome selection for a definitive randomised controlled trial. Trial registration ISRCTN, ISRCTN25890011 Registered February 10th, 202

Semidiurnal temperature changes caused by tidal front movements in the warm season in seabed habitats on the Georges Bank northern margin and their ecological implications

This article is distributed under the terms of the Creative Commons Public Domain. The definitive version was published in PLoS ONE 8 (2013): e55273, doi:10.1371/journal.pone.0055273.Georges Bank is a large, shallow feature separating the Gulf of Maine from the Atlantic Ocean. Previous studies demonstrated a strong tidal-mixing front during the warm season on the northern bank margin between thermally stratified water in the Gulf of Maine and mixed water on the bank. Tides transport warm water off the bank during flood tide and cool gulf water onto the bank during ebb tide. During 10 days in August 2009, we mapped frontal temperatures in five study areas along ~100 km of the bank margin. The seabed “frontal zone”, where temperature changed with frontal movment, experienced semidiurnal temperature maxima and minima. The tidal excursion of the frontal boundary between stratified and mixed water ranged 6 to 10 km. This “frontal boundary zone” was narrower than the frontal zone. Along transects perpendicular to the bank margin, seabed temperature change at individual sites ranged from 7.0°C in the frontal zone to 0.0°C in mixed bank water. At time series in frontal zone stations, changes during tidal cycles ranged from 1.2 to 6.1°C. The greatest rate of change (−2.48°C hr−1) occurred at mid-ebb. Geographic plots of seabed temperature change allowed the mapping of up to 8 subareas in each study area. The magnitude of temperature change in a subarea depended on its location in the frontal zone. Frontal movement had the greatest effect on seabed temperature in the 40 to 80 m depth interval. Subareas experiencing maximum temperature change in the frontal zone were not in the frontal boundary zone, but rather several km gulfward (off-bank) of the frontal boundary zone. These results provide a new ecological framework for examining the effect of tidally-driven temperature variability on the distribution, food resources, and reproductive success of benthic invertebrate and demersal fish species living in tidal front habitats.This study was supported by salary funds from the regular annual salary budget from Northeast Fisheries Science Center (NEFSC) and United States Geological Survey Woods Hole Coastal and Marine Science Center (USGS WH C&MSC), respectively; ship time funds from the NEFSC annual budget for days-at-sea ship operations; equipment from the NEFSC and USGS WH C&MSC annual equipment budgets