213 research outputs found

    Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

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    Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal (GI) dysfunction, and altered gut microbiome compositions. Methods: We sought to better understand non-behavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (LC/MS and DMS-MS) with broad panels of identified metabolites. Herein, we present the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing (TD) controls. Results: Differences in amino acid, lipid, and xenobiotic metabolism discriminate ASD and TD samples. Our results implicate oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also reveal correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with GI dysfunction in ASD are provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice were identified. Conclusions: These findings support a connection between metabolism, GI physiology, and complex behavioral traits, and may advance discovery and development of molecular biomarkers for ASD

    Artists on the edge of the world : an integrated approach to the study of Magdalenian engraved stone plaquettes from Jersey (Channel Islands)

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    Excavations at Les Varines were funded by Jersey Heritage through the States of Jersey Tourism Development Fund (https://www.gov.je/Leisure/Events/TourismDevelopmentFundTDF/pages/abouttdf.aspx) in 2013-15 and in 2017 (BS received the funding), by the British Museum research fund in 2016-18 (https://www.britishmuseum.org/research) (Grant nos EC164/EC208) (BS received the funding), in 2016 by British Academy (https://www.thebritishacademy.ac.uk) small grant SG152868 (CC received the funding) and Society of Antiquaries (https://www.sal.org.uk/) Research Grants R121086 in 2017 and BH181355 in 2018 (CC received the funding). Funding from the Universities of Manchester, Southampton and UCL supported student training at the excavation. Silvia Bello’s work was part of the ‘Human Behaviour in 3D’ Project funded by the Calleva Foundation. Beccy Scott’s work was also supported by the Calleva foundation (Pathways to Ancient Britain project).The Upper Palaeolithic is characterised by the appearance of iconographic expressions most often depicting animals, including anthropomorphic forms, and geometric signs. The Late Upper Palaeolithic Magdalenian saw a flourishing of such depictions, encompassing cave art, engraving of stone, bone and antler blanks and decoration of tools and weapons. Though Magdalenian settlement exists as far northwest as Britain, there is a limited range of art known from this region, possibly associated with only fleeting occupation of Britain during this period. Stone plaquettes, flat fragments of stone engraved on at least one surface, have been found in large quantities at numerous sites spanning the temporal and geographical spread of the Magdalenian, but they have been absent so far from the archaeological record of the British Isles. Between 2015 and 2018, ten fragments of stone plaquettes extensively engraved with abstract designs were uncovered at the Magdalenian site of Les Varines, Jersey, Channel Islands. In this paper, we report detailed analyses of these finds, which provide new evidence for technologies of abstract mark-making, and their significance within the lives of people on the edge of the Magdalenian world. These engraved stone fragments represent important, rare evidence of artistic expression in what is the far northern and western range of the Magdalenian and add new insight to the wider significance of dynamic practices of artistic expression during the Upper Palaeolithic.Publisher PDFPeer reviewe

    Information sources and knowledge about chronic wasting disease in Colorado and Wisconsin

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    This research note examines hunters' and non-hunters' information sources and knowledge about chronic wasting disease (CWD). Data were obtained from surveys of and Wisconsin (n = 360

    Prediagnostic Serum Concentrations of Organochlorine Compounds and Risk of Testicular Germ Cell Tumors

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    BACKGROUND: Recent findings suggest that exposure to organochlorine (OC) compounds, chlordanes and p,pâ€Č-dichlorodiphenyldichloroethylene (p,pâ€Č-DDE) in particular, may increase the risk of developing testicular germ cell tumors (TGCTs). OBJECTIVE: To further investigate this question, we conducted a nested case-control study of TGCTs within the Norwegian Janus Serum Bank cohort. METHODS: The study was conducted among individuals with serum collected between 1972 and 1978. TGCT cases diagnosed through 1999 (n = 49; 27-62 years of age at diagnosis) were identified through linkage to the Norwegian Cancer Registry. Controls (n =51) were matched to cases on region, blood draw year, and age at blood draw. Measurements of 11 OC insecticide compounds and 34 polychlorinated biphenyl (PCB) congeners were performed using gas chromatography/high-resolution mass spectrometry. Case-control comparisons of lipid-adjusted analyte concentrations were performed using the Wilcoxon signed-rank test. Odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles of analyte concentration were calculated using conditional logistic regression. RESULTS: TGCT cases had elevated concentrations of p,pâ€Č-DDE (tertile 3 vs. tertile 1 OR (ORT3) 2.2; 95% CI, 0.7-6.5; p Wilcoxon = 0.07), oxychlordane (ORT3 3.2; 95% CI, 0.6-16.8; pWilcoxon = 0.05), trans-nonachlor (ORT3 2.6; 95% CI, 0.7-8.9; pWilcoxon = 0.07), and total chlordanes (OR T3 2.0; 95% CI, 0.6-7.2; pWilcoxon = 0.048) compared with controls, although no ORs were statistically significant. Seminoma cases had significantly lower concentrations of PCB congeners 44, 49, and 52 and significantly higher concentrations of PCBs 99, 138, 153, 167, 183, and 195. CONCLUSIONS: Our study provides additional but qualified evidence supporting an association between exposures to p,pâ€Č-DDE and chlordane compounds, and possibly some PCB congeners, and TGCT risk

    Sarcoidosis following alemtuzumab treatment for multiple sclerosis

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    Despite proven efficacy of alemtuzumab in multiple sclerosis (MS), approximately 50% of individuals will develop a new autoimmune disease following treatment. To date, these have largely been antibody mediated and organ specific (primarily affecting the thyroid gland). In a retrospective case series of 187 patients from two UK specialist centres (Cardiff and Cambridge) followed up for a median of 10 years, we report three (1.6%) cases of sarcoidosis following alemtuzumab treatment of MS. This report increases the spectrum of auto-inflammatory disease following alemtuzumab and should be considered by clinicians when using this therapeutic agent for MS

    Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

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    Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria
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