326 research outputs found

    Blueprint for an intestinal villus: Species‐specific assembly required

    Full text link
    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144650/1/wdev317_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144650/2/wdev317.pd

    Suppression of basophil histamine release and other IgE-dependent responses in childhood Schistosoma mansoni/hookworm coinfection.

    Get PDF
    BACKGROUND: The poor correlation between allergen-specific immunoglobulin E (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm. METHODS: Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Nonspecific (anti-IgE), helminth-specific, and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment. RESULTS: Nonspecific- and helminth-specific-HR, and associations between helminth-specific IgE and helminth-specific HR increased post-treatment. Hookworm infection appeared to modify the relationship between circulating levels of HDM-IgE and HR: a significant positive association was observed among children without detectable hookworm infection, but no association was observed among infected children. In addition, hookworm infection was associated with a significantly reduced risk of wheeze, and IgG4 to somatic adult hookworm antigen with a reduced risk of HDM-SPT sensitivity. There was no evidence for S. mansoni infection having a similar suppressive effect on HDM-HR or symptoms of allergy. CONCLUSIONS: Basophil responsiveness appears suppressed during chronic helminth infection; at least in hookworm infection, this suppression may protect against allergy

    Suppression of basophil histamine-release and other IgE-dependent responses in childhood Schistosoma mansoni hookworm co-infection

    Get PDF
    Background. The poor correlation between allergen-specific-IgE (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm. Methods. Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Non-specific (anti-IgE), helminth-specific and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment. Results. Non-specific- and helminth-specific-HR, and associations between helminth-specific-IgE and helminth-specific-HR increased post-treatment. Hookworm infection appeared to modify the relationship between circulating levels of HDM-IgE and HR: a significant positive association was observed among children without detectable hookworm infection but no association was observed among infected children. In addition, hookworm infection was associated with a significantly reduced risk of wheeze, and IgG4 to somatic adult hookworm antigen with a reduced risk of HDM-SPT sensitivity. There was no evidence for S. mansoniinfection having a similar suppressive effect on HDM-HR or symptoms of allergy. Conclusions. Basophil responsiveness appears suppressed during chronic helminth infection; at least in hookworm infection, this suppression may protect against allergy

    The Arabidopsis cytochrome P450 CYP86A1 encodes a fatty acid ω-hydroxylase involved in suberin monomer biosynthesis

    Get PDF
    The lipophilic biopolyester suberin forms important boundaries to protect the plant from its surrounding environment or to separate different tissues within the plant. In roots, suberin can be found in the cell walls of the endodermis and the hypodermis or periderm. Apoplastic barriers composed of suberin accomplish the challenge to restrict water and nutrient loss and prevent the invasion of pathogens. Despite the physiological importance of suberin and the knowledge of the suberin composition of many plants, very little is known about its biosynthesis and the genes involved. Here, a detailed analysis of the Arabidopsis aliphatic suberin in roots at different developmental stages is presented. This study demonstrates some variability in suberin amount and composition along the root axis and indicates the importance of ω-hydroxylation for suberin biosynthesis. Using reverse genetics, the cytochrome P450 fatty acid ω-hydroxylase CYP86A1 (At5g58860) has been identified as a key enzyme for aliphatic root suberin biosynthesis in Arabidopsis. The corresponding horst mutants show a substantial reduction in ω-hydroxyacids with a chain length <C20, demonstrating that CYP86A1 functions as a hydroxylase of root suberized tissue. Detailed expression studies revealed a strong root specificity and a localized expression in the root endodermis. Transgenic expression of CYP86A1 fused to GFP distributed CYP86A1 to the endoplasmic reticulum, indicating that suberin monomer biosynthesis takes place in this sub-cellular compartment before intermediates are exported in the apoplast

    Relationship of device measured physical activity type and posture with cardiometabolic health markers: pooled dose–response associations from the Prospective Physical Activity, Sitting and Sleep Consortium

    Get PDF
    AIMS/HYPOTHESIS: The aim of this study was to examine the dose–response associations of device-measured physical activity types and postures (sitting and standing time) with cardiometabolic health. METHODS: We conducted an individual participant harmonised meta-analysis of 12,095 adults (mean ± SD age 54.5±9.6 years; female participants 54.8%) from six cohorts with thigh-worn accelerometry data from the Prospective Physical Activity, Sitting and Sleep (ProPASS) Consortium. Associations of daily walking, stair climbing, running, standing and sitting time with a composite cardiometabolic health score (based on standardised z scores) and individual cardiometabolic markers (BMI, waist circumference, triglycerides, HDL-cholesterol, HbA1c and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines. RESULTS: We observed more favourable composite cardiometabolic health (i.e. z score <0) with approximately 64 min/day walking (z score [95% CI] −0.14 [−0.25, −0.02]) and 5 min/day stair climbing (−0.14 [−0.24, −0.03]). We observed an equivalent magnitude of association at 2.6 h/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose–response associations for any activity type or standing. There was an inverse dose–response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 h/day. Associations for sitting time were no longer significant after excluding participants with prevalent CVD or medication use. The dose–response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers. CONCLUSIONS/INTERPRETATION: In this first activity type-specific analysis of device-based physical activity, ~64 min/day of walking and ~5.0 min/day of stair climbing were associated with a favourable cardiometabolic risk profile. The deleterious associations of sitting time were fully attenuated after exclusion of participants with prevalent CVD and medication use. Our findings on cardiometabolic health and durations of different activities of daily living and posture may guide future interventions involving lifestyle modification

    DataSHIELD: mitigating disclosure risk in a multi-site federated analysis platform

    Get PDF
    \ua9 The Author(s) 2025. Published by Oxford University Press.Motivation: The validity of epidemiologic findings can be increased using triangulation, i.e. comparison of findings across contexts, and by having sufficiently large amounts of relevant data to analyse. However, access to data is often constrained by practical considerations and by ethico-legal and data governance restrictions. Gaining access to such data can be time-consuming due to the governance requirements associated with data access requests to institutions in different jurisdictions. Results: DataSHIELD is a software solution that enables remote analysis without the need for data transfer (federated analysis). DataSHIELD is a scientifically mature, open-source data access and analysis platform aligned with the \u27Five Safes\u27 framework, the international framework governing safe research access to data. It allows real-time analysis while mitigating disclosure risk through an active multi-layer system of disclosure-preventing mechanisms. This combination of real-time remote statistical analysis, disclosure prevention mechanisms, and federation capabilities makes DataSHIELD a solution for addressing many of the technical and regulatory challenges in performing the large-scale statistical analysis of health and biomedical data. This paper describes the key components that comprise the disclosure protection system of DataSHIELD. These broadly fall into three classes: (i) system protection elements, (ii) analysis protection elements, and (iii) governance protection elements

    Seismic Constraints on the Thickness and Structure of the Martian Crust from InSight

    Get PDF
    NASA¿s InSight mission [1] has for the first time placed a very broad-band seismometer on the surface of Mars. The Seismic Experiment for Interior Structure (SEIS) [2] has been collecting continuous data since early February 2019. The main focus of InSight is to enhance our understanding of the internal structure and dynamics of Mars, which includes the goal to better constrain the crustal thickness of the planet [3]. Knowing the present-day crustal thickness of Mars has important implications for its thermal evolution [4] as well as for the partitioning of silicates and heat-producing elements between the different layers of Mars. Current estimates for the crustal thickness of Mars are based on modeling the relationship between topography and gravity [5,6], but these studies rely on different assumptions, e.g. on the density of the crust and upper mantle, or the bulk silicate composition of the planet and the crust. The resulting values for the average crustal thickness differ by more than 100%, from 30 km to more than 100 km [7]. New independent constraints from InSight will be based on seismically determining the crustal thickness at the landing site. This single firm measurement of crustal thickness at one point on the planet will allow to constrain both the average crustal thickness of Mars as well as thickness variations across the planet when combined with constraints from gravity and topography [8]. Here we describe the determination of the crustal structure and thickness at the InSight landing site based on seismic receiver functions for three marsquakes compared with autocorrelations of InSight data [9].We acknowledge NASA, CNES, partner agencies and institutions (UKSA, SSO,DLR, JPL, IPGP-CNRS, ETHZ, IC, MPS-MPG) and the operators of JPL, SISMOC, MSDS, IRIS-DMC and PDS for providing SEED SEIS data. InSight data is archived in the PDS, and a full list of archives in the Geosciences, Atmospheres, and Imaging nodes is at https://pds-geosciences.wustl.edu/missions/insight/. This work was partially carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. ©2021, California Institute of Technology. Government sponsorship acknowledge
    corecore