190 research outputs found

    Oat-enriched diet reduces inflammatory status assessed by circulating cell-derived microparticle concentrations in type 2 diabetes

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    This work was funded by the Chief Scientists Office of the Scottish Government by a joint grant to the University of the Highland and Islands, Grampian Health Board, Biomathematics and Statistics Scotland and the Rowett Institute of Nutrition and Health, University of Aberdeen. Additional support was provided by Provexis plc.Peer reviewedPublisher PD

    Activated but functionally impaired memory Tregs are expanded in slow progressors to type 1 diabetes

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    This is the final version. Available on open access from Springer via the DOI in this recordData availability: The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.Aims/hypothesis Slow progressors to type 1 diabetes are individuals positive for multiple pancreatic islet autoantibodies who have remained diabetes-free for at least 10 years; regulation of the autoimmune response is understudied in this group. Here, we profile CD4+ regulatory T cells (Tregs) in a small but well-characterised cohort of extreme slow progressors with a median age 43 (range 31–72 years), followed up for 18–32 years. Methods Peripheral blood samples were obtained from slow progressors (n = 8), age- and sex-matched to healthy donors. One participant in this study was identified with a raised HbA1c at the time of assessment and subsequently diagnosed with diabetes; this donor was individually evaluated in the analysis of the data. Peripheral blood mononuclear cells (PBMCs) were isolated, and to assess frequency, phenotype and function of Tregs in donors, multi-parameter flow cytometry and T cell suppression assays were performed. Unsupervised clustering analysis, using FlowSOM and CITRUS (cluster identification, characterization, and regression), was used to evaluate Treg phenotypes. Results Unsupervised clustering on memory CD4+ T cells from slow progressors showed an increased frequency of activated memory CD4+ Tregs, associated with increased expression of glucocorticoid-induced TNFR-related protein (GITR), compared with matched healthy donors. One participant with a raised HbA1c at the time of assessment had a different Treg profile compared with both slow progressors and matched controls. Functional assays demonstrated that Treg-mediated suppression of CD4+ effector T cells from slow progressors was significantly impaired, compared with healthy donors. However, effector CD4+ T cells from slow progressors were more responsive to Treg suppression compared with healthy donors, demonstrated by increased suppression of CD25 and CD134 expression on effector CD4+ T cells. Conclusions/interpretations We conclude that activated memory CD4+ Tregs from slow progressors are expanded and enriched for GITR expression, highlighting the need for further study of Treg heterogeneity in individuals at risk of developing type 1 diabetes.Diabetes UKJDR

    Characterization of an alpha-L-fucosidase from the periodontal pathogen Tannerella forsythia

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    The periodontal pathogen Tannerella forsythia expresses several glycosidases which are linked to specific growth requirements and are involved in the invasion of host tissues. α-l-Fucosyl residues are exposed on various host glycoconjugates and, thus, the α-l-fucosidases predicted in the T. forsythia ATCC 43037 genome could potentially serve roles in host-pathogen interactions. We describe the molecular cloning and characterization of the putative fucosidase TfFuc1 (encoded by the bfo_2737 = Tffuc1 gene), previously reported to be present in an outer membrane preparation. In terms of sequence, this 51-kDa protein is a member of the glycosyl hydrolase family GH29. Using an artificial substrate, p-nitrophenyl-α-fucose (KM 670 μM), the enzyme was determined to have a pH optimum of 9.0 and to be competitively inhibited by fucose and deoxyfuconojirimycin. TfFuc1 was shown here to be a unique α(1,2)-fucosidase that also possesses α(1,6) specificity on small unbranched substrates. It is active on mucin after sialidase-catalyzed removal of terminal sialic acid residues and also removes fucose from blood group H. Following knock-out of the Tffuc1 gene and analyzing biofilm formation and cell invasion/adhesion of the mutant in comparison to the wild-type, it is most likely that the enzyme does not act extracellularly. Biochemically interesting as the first fucosidase in T. forsythia to be characterized, the biological role of TfFuc1 may well be in the metabolism of short oligosaccharides in the periplasm, thereby indirectly contributing to the virulence of this organism. TfFuc1 is the first glycosyl hydrolase in the GH29 family reported to be a specific α(1,2)-fucosidase

    What’s in a name? Wildlife traders evade authorities using code words

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    Where rare species are concerned, including those with restricted range, their use for traditional medicine can have disastrous impacts on local populations already under pressure. Difficulty in monitoring such illegal activity has been illustrated by enforcement raids across India since June 2017, with authorities seizing supposedly rare Himalayan plant roots referred to as hatha jodi

    Food Intake and Dietary Glycaemic Index in Free-Living Adults with and without Type 2 Diabetes Mellitus

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    A recent Cochrane review concluded that low glycaemic index (GI) diets are beneficial in glycaemic control for patients with type 2 diabetes mellitus (T2DM). There are limited UK data regarding the dietary GI in free-living adults with and without T2DM. We measured the energy and macronutrient intake and the dietary GI in a group (n = 19) of individuals with diet controlled T2DM and a group (n = 19) without diabetes, matched for age, BMI and gender. Subjects completed a three-day weighed dietary record. Patients with T2DM consumed more daily portions of wholegrains (2.3 vs. 1.1, P = 0.003), more dietary fibre (32.1 vs. 20.9 g, P < 0.001) and had a lower diet GI (53.5 vs. 57.7, P = 0.009) than subjects without T2DM. Both groups had elevated fat and salt intake and low fruit and vegetable intake, relative to current UK recommendations. Conclusions: Patients with T2DM may already consume a lower GI diet than the general population but further efforts are needed to reduce dietary GI and achieve other nutrient targets

    A comparison of fresh and used aircraft oil for the identification of toxic substances linked to aerotoxic syndrome

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    Fresh and used aircraft engine lubricants (Mobil Jet Oil II) were analysed using a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICRMS) and comprehensive two dimensional gas chromatography with high resolution time of flight mass spectrometry (GCxGC-HRTOFMS). The composition of the fresh oil was established, with special focus to its tricresyl phosphate (TCP) content as this has formed the focus for most investigations into aerotoxic syndrome. The results showed that only four TCP isomers were present at detectable levels in the fresh oil: mmm-TCP, mmp-TCP, ppm-TCP and ppp-TCP. The results indicate that the formulation of Mobile Jet Oil II does not contain the more toxic ortho substituted TCP isomers at concentrations above 0.0005%. The temperatures of jet engines during operation are greater than 200 °C which creates the potential to alter the composition of the original oil and create other toxic compounds. The results show there may be a significant risk from alkylated cresyl phosphates, which were identified in the used oils at concentrations calculated in the range of 0.13–0.69%. w/w. Several xylenyl and ethylphenyl phosphates have been shown to exhibit a similar toxicity to ortho substituted TCP isomers which makes there discovery in used oil significant. These compounds should be included in future aircraft air quality studies and when assessing the risks and causes of aerotoxic syndrome

    An advanced analytical assessment of rare earth element concentration, distribution, speciation, crystallography and solid-state chemistry in fly ash

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    This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Data availability: The raw (unprocessed) data that support the findings of this study are available from Mendeley Data: https://data.mendeley.com/datasets/k54hnzxp3j/1.Fly ash represents a promising alternative source of rare earth elements (REE). However, information on REE containing mineral phases and their association with other fly ash components, vital for REE recovery from fly ash, is currently lacking. Herein, the mass fraction, distribution, crystallography and solid-state chemistry of REE, U and Th in Nigerian simulated fly ash samples were characterised using a range of laboratory and synchrotron x-ray based analytical techniques to underpin future extraction methodologies. Inductively coupled plasma mass spectrometry following full-acid digest of forty-five samples revealed recoverable average total REE content which ranged between 442 mgkg−1and 625 mgkg−1, comprising over 30 wt% of the critical REE Nd, Eu, Tb, Dy, Y and Er. These REE within the fly ash samples were found to be most frequently associated with discrete monazite, xenotime and Y-bearing zircon mineral particles, with the former the most detected, which could be beneficiated through gravity separation. Analysis of monazite particles isolated from the composite samples through a complimentary suite of analytical synchrotron radiation techniques revealed a core-shell pattern, with the shell rich in colocalised Ce, Nd and La, and the core enrich in both U and Th. Ce in monazite was found to exist in a mixed trivalent and tetravalent oxidation state, with the monazite structure amorphized due to the high temperature combustion process. Such results demonstrate the strong co-association and physical distribution of REE, U and Th within monazite in fly ash; knowledge of which can subsequently be used to optimise or develop a more selective, cost-effective and environmentally friendly solvent extraction methodology, by targeting the strongly colocalised and surface bound REE in fly ash monazite particles.Engineering and Physical Sciences Research Counci

    Congener specific determination of polychlorinated naphthalenes in sediment and biota by gas chromatography high resolution mass spectrometry

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    © 2016 Elsevier B.V. An isotope dilution congener-specific method for the determination of the most abundant and most toxic polychlorinated naphthalenes (PCNs) was developed using gas chromatography with high resolution mass spectrometry (GC-HRMS). The method was used to determine the concentration of 24 target congeners and total PCN concentrations in fish and sediment samples. Tissue samples were extracted using pressurized liquid extraction (PLE) and sediment samples were extracted using Soxhlet extraction. Sample extracts were cleaned up using either a manual two-stage open column procedure or an automated FMS Power Prep System with multi-analyte and multi-sample capability using a three-column cleanup procedure. Sediment extracts were cleaned up with a dual open column cleanup technique involving the use of both a multi-layered silica (silver nitrate/acid/base/neutral silica) column followed by column containing carbon-activated silica. Fish tissue extracts were cleaned up on the automated system involving the use of a high capacity ABN (acid/base/neutral column), carbon celite column, and a basic alumina column. The method is capable of producing instrument detection limits (IDLs) between 0.06 and 0.13 pg for each PCN (on column), with method detection limits (MDLs) for the fish extracts ranging from 1.3 to 3.4 pg/g (wet weight) and 0.46 to 1.2 pg/g (dry weight) for sediments. The average accuracy of 34 spiked fish samples analysed over a period of several months was 100% with a precision (%RSD) of 12%. Similarly, the average accuracy for 28 spiked sediment samples was 104% with a precision (%RSD) of 12%. The application of the method to environmental samples was demonstrated through the analysis of sediment and fish samples obtained from Lake Ontario, Canada. The method is used both for the determination of 24 PCNs and to perform non-targeted screening for the remaining 51 PCN congeners, which are included in the total PCN quantification result. It is currently one of the most comprehensive and accurate congener-specific methods available and was developed from the existing techniques used for the determination of polychlorinated dioxins and furans to produce high quality data with only minor modifications in the clean-up procedure. It can therefore be readily adopted by other laboratories performing dioxin and POP analyses
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