188 research outputs found

    Accuracy and the influence of marrow fat on quantitative CT and dual-energy X-ray absorptiometry measurements of the femoral neck in vitro

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    Abstract Bone mineral measurements with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) were compared with chemical analysis (ChA) to determine (1) the accuracy and (2) the influence of bone marrow fat. Total bone mass of 19 human femoral necks in vitro was determined with QCT and DXA before and after defatting. ChA consisted of defatting and decalcification of the femoral neck samples for determination of bone mineral mass (BmM) and amount of fat. The mean BmM was 4.49 g. Mean fat percentage was 37.2% (23.3%–48.5%). QCT, DXA and ChA before and after defatting were all highly correlated (r>0.96,p<0.0001). Before defatting the QCT values were on average 0.35 g less than BmM and the DXA values were on average 0.65 g less than BmM. After defatting, all bone mass values increased; QCT values were on average 0.30 g more than BmM and DXA values were 0.29 g less than BmM. It is concluded that bone mineral measurements of the femoral neck with QCT and DXA are highly correlated with the chemically determined bone mineral mass and that both techniques are influenced by the femoral fat content

    Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection

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    Streptococcus pneumoniaeinfections lead to high morbidity and mortality rates worldwide.Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but havea limited range of protection, which encourages the development of a broadly protective protein-basedalternative. We and others have shown that immunization with pneumococcal lipoproteins that lackthe lipid anchor protects against colonization. Since immunity againstS. pneumoniaeis mediatedthrough Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects ofa lipid modification on the induced immune responses in either intranasally or subcutaneouslyvaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrAstrongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhancedantibody concentrations and different induction kinetics. The induced humoral immune responsewas modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-typeimmunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderatebut consistent reduction of pneumococcal colonization as compared to the non-lipidated proteins,indicating that protein lipidation can improve the protective capacity of the coupled antigen. Thus,protein lipidation represents a promising approach for the development of a serotype-independentpneumococcal vaccine

    Групповая эргатическая совместимость авиационных операторов в процессе эксплуатации авионики

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    Рассмотрены проблемы групповой эргатической совместимости авиационных операторов (пилотов, авиадиспетчеров, технического персонала) и использования технических средств для оценки групповой эргатической совместимости операторов как средства повышения авиационной безопасности за счет более тщательного отбора кандидатов для совместной работы в составе лeтных и космических экипажей.Розглянуто питання проблеми групової ергатичної сумісності авіаційних операторів (пілотів, авіадиспетчерів, технічного персоналу) і використання технічних пристроїв для оцінки групової ергатичної сумісності операторів як засобу підвищення авіаційної безпеки за рахунок більш кращого відбору кандидатів для спільної роботи у складі льотних і космічних екіпажів.We issued the problems of group ergatic aircraft operators (pilots, air traffic controllers, technicians) and the use of technical devices to assess the compatibility of the group ergatic operators as means of improving aviation safety through a better selection of candidates to work together as part of flight and space crews. In this research article to better selection of candidates for collaboration in the space flight crews and the authors propose to use modern computers with appropriate software. This computer complex will answer a number of important issues related to ensuring: compatibility Soames, rational distribution of functions between components ergatic systems, proper interaction with the machine operators as well as each other in normal and special situations professional selection, preparation and training of aviation operators

    N-glycosylation of LRP6 by B3GnT2 promotes Wnt/βcatenin signalling

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    Reception of Wnt signals by cells is predominantly mediated by Frizzled receptors in conjunction with a co-receptor, the latter being LRP6 or LRP5 for the Wnt/β-catenin signalling pathway. It is important that cells maintain precise control of receptor activation events in order to properly regulate Wnt/β-catenin signalling as aberrant signalling can result in disease in humans. Phosphorylation of the intracellular domain (ICD) of LRP6 is well known to regulate Wntβ-catenin signalling; however, less is known for regulatory post-translational modification events within the extracellular domain (ECD). Using a cell culture-based expression screen for functional regulators of LRP6, we identified a glycosyltransferase, B3GnT2-like, from a teleost fish (medaka) cDNA library, that modifies LRP6 and regulates Wnt/β-catenin signalling. We provide both gain-of-function and loss-of-function evidence that the single human homolog, B3GnT2, promotes extension of polylactosamine chains at multiple N-glycans on LRP6, thereby enhancing trafficking of LRP6 to the plasma membrane and promoting Wnt/β-catenin signalling. Our findings further highlight the importance of LRP6 as a regulatory hub in Wnt signalling and provide one of the few examples of how a specific glycosyltransferase appears to selectively target a signalling pathway component to alter cellular signalling events.Proteomic

    Microvascular damage assessed by optical coherence tomography angiography for glaucoma diagnosis: a systematic review of the most discriminative regions

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    A growing number of studies have reported a link between vascular damage and glaucoma based on optical coherence tomography angiography (OCTA) imaging. This multitude of studies focused on different regions of interest (ROIs) which offers the possibility to draw conclusions on the most discriminative locations to diagnose glaucoma. The objective of this work was to review and analyse the discriminative capacity of vascular density, retrieved from different ROIs, on differentiating healthy subjects from glaucoma patients. PubMed was used to perform a systematic review on the analysis of glaucomatous vascular damage using OCTA. All studies up to 21 April 2019 were considered. The ROIs were analysed by region (macula, optic disc and peripapillary region), layer (superficial and deep capillary plexus, avascular, whole retina, choriocapillaris and choroid) and sector (according to the Garway–Heath map). The area under receiver operator characteristic curve (AUROC) and the statistical difference (p-value) were used to report the importance of each ROI for diagnosing glaucoma. From 96 screened studies, 43 were eligible for this review. Overall, the peripapillary region showed to be the most discriminative region with the highest mean AUROC (0.80 ± 0.09). An improvement of the AUROC from this region is observed when a sectorial analysis is performed, with the highest AUROCs obtained at the inferior and superior sectors of the superficial capillary plexus in the peripapillary region (0.86 ± 0.03 and 0.87 ± 0.10, respectively). The presented work shows that glaucomatous vascular damage can be assessed using OCTA, and its added value as a complementary feature for glaucoma diagnosis depends on the region of interest. A sectorial analysis of the superficial layer at the peripapillary region is preferable for assessing glaucomatous vascular damage

    Examining the distribution and impact of single nucleotide polymorphisms in the capsular locus of Streptococcus pneumoniae serotype 19A

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    Streptococcus pneumoniae serotype 19A prevalence has increased after implementation of PCV7 and PCV10 vaccines. In this study, we have provided, with high accuracy, the genetic diversity of the 19A serotype in a cohort of Dutch invasive pneumococcal disease patients and asymptomatic carriers obtained in the period 2004-2016. Whole genomes of the 338 pneumococcal isolates in this cohort were sequenced and their capsule (cps) loci compared to examine the diversity and determine the impact on the production of CPS sugar precursors and CPS shedding. We discovered 79 types with a unique CPS locus sequence. Most variation was observed in the rmlB and rmlD genes of the TDP-Rha synthesis pathway, and in the wzg gene, of unknown function. Interestingly, gene variation in the cps locus was conserved in multiple alleles. Using RmlB and RmlD protein models, we predict that enzymatic function is not affected by the single nucleotide polymorphisms as identified. To determine if RmlB and RmlD function was affected, we analyzed nucleotide sugar levels using UHPLC-MS. CPS precursors differed between 19A cps locus subtypes, including TDP-Rha, but no clear correlation was observed. Also, a significant difference in multiple nucleotide sugar levels was observed between phylogenetically branched groups. Because of indications of a role for Wzg in capsule shedding, we analyzed if this was affected. No clear indication of a direct role in shedding was found. We thus describe genotypic variety in rmlB, rmlD and wzg in serotype 19A the Netherlands, for which we have not discovered an associated phenotype
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