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排序方式: 共有898条查询结果,搜索用时 15 毫秒
891.
Winnie Chua Jonathan P. Law Victor R. Cardoso Yanish Purmah Georgiana Neculau Muhammad Jawad-Ul-Qamar Kalisha Russell Ashley Turner Samantha P. Tull Frantisek Nehaj Paul Brady Peter Kastner Andr Ziegler Georgios V. Gkoutos Davor Pavlovic Charles J. Ferro Paulus Kirchhof Larissa Fabritz 《PLoS medicine》2021,18(2)
BackgroundLarge-scale screening for atrial fibrillation (AF) requires reliable methods to identify at-risk populations. Using an experimental semi-quantitative biomarker assay, B-type natriuretic peptide (BNP) and fibroblast growth factor 23 (FGF23) were recently identified as the most suitable biomarkers for detecting AF in combination with simple morphometric parameters (age, sex, and body mass index [BMI]). In this study, we validated the AF model using standardised, high-throughput, high-sensitivity biomarker assays.Methods and findingsFor this study, 1,625 consecutive patients with either (1) diagnosed AF or (2) sinus rhythm with CHA2DS2-VASc score of 2 or more were recruited from a large teaching hospital in Birmingham, West Midlands, UK, between September 2014 and February 2018. Seven-day ambulatory ECG monitoring excluded silent AF. Patients with tachyarrhythmias apart from AF and incomplete cases were excluded. AF was diagnosed according to current clinical guidelines and confirmed by ECG. We developed a high-throughput, high-sensitivity assay for FGF23, quantified plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and FGF23, and compared results to the previously used multibiomarker research assay. Data were fitted to the previously derived model, adjusting for differences in measurement platforms and known confounders (heart failure and chronic kidney disease). In 1,084 patients (46% with AF; median [Q1, Q3] age 70 [60, 78] years, median [Q1, Q3] BMI 28.8 [25.1, 32.8] kg/m2, 59% males), patients with AF had higher concentrations of NT-proBNP (median [Q1, Q3] per 100 pg/ml: with AF 12.00 [4.19, 30.15], without AF 4.25 [1.17, 15.70]; p < 0.001) and FGF23 (median [Q1, Q3] per 100 pg/ml: with AF 1.93 [1.30, 4.16], without AF 1.55 [1.04, 2.62]; p < 0.001). Univariate associations remained after adjusting for heart failure and estimated glomerular filtration rate, known confounders of NT-proBNP and FGF23. The fitted model yielded a C-statistic of 0.688 (95% CI 0.656, 0.719), almost identical to that of the derived model (C-statistic 0.691; 95% CI 0.638, 0.744). The key limitation is that this validation was performed in a cohort that is very similar demographically to the one used in model development, calling for further external validation.ConclusionsAge, sex, and BMI combined with elevated NT-proBNP and elevated FGF23, quantified on a high-throughput platform, reliably identify patients with AF.Trial registrationRegistry IRAS ID 97753 Health Research Authority (HRA), United KingdomWinnie Chua and colleagues identify and validate biomarkers for atrial fibrillation 相似文献
892.
Pumpkin pectin: gel formation at unusually low concentration 总被引:2,自引:0,他引:2
Nataliya M. Ptitchkina Irina A. Danilova Georgios Doxastakis Stefan Kasapis Edwin R. Morris 《Carbohydrate polymers》1994,23(4):265-273
The gel properties of high-methoxy pectin from pumpkins have been investigated to assess the potential of this material as a hard-currency export from the former Soviet Union. Comparison was made with commercial slow-set, medium-set and rapid-set pectins from citrus peel. Gels were formed by cooling pectin solutions (pH 3·0; 60% (w/w) sucrose; 5% (w/w) corn syrup) from 95°C to 25°C, and the time-temperature course of network formation was monitored by small-deformation oscillatory measurements of storage modulus (G′). At concentrations above 1% (w/w) the pumpkin pectin gave weaker gels than the other three samples, but its minimum critical gelling concentration (c0) was found to be much lower (by at least a factor of five). Compression testing gave similar results, with pumpkin pectin giving useful breaking-stress (‘hardness’) at concentrations down to 0·5% (w/w), about a factor of two lower than for the citrus samples. Its gelation was also less rapid, giving G′ values below those of the other three samples at temperatures down to 60°C, but then setting sharply; this behaviour could be useful in avoiding ‘pregelation’ in commercial processing. The commercial slow-set pectin showed typical ‘weak gel’ properties in the solution state at 95°C, with systematic reduction in gel-like character with increasing ester content in the other samples. The rigidity of the final gels also decreased systematically through the series: rapid-set < medium-set < slow-set. These observations are tentatively ascribed to stable association of unesterified galacturonate chain segments at low pH, where electrostatic repulsion is suppressed. 相似文献
893.
Petros Giastas Nikos Pinotsis Georgios Efthymiou Matthias Wilmanns Panayotis Kyritsis Jean-Marc Moulis Irene M. Mavridis 《Journal of biological inorganic chemistry》2006,11(4):445-458
The structure of the 2[4Fe–4S] ferredoxin (PaFd) from Pseudomonas aeruginosa, which belongs to the Allochromatium vinosum (Alvin) subfamily, has been determined by X-ray crystallography at 1.32-Å resolution, which is the highest up to now for a member of this subfamily of Fds. The main structural features of PaFd are similar to those of AlvinFd. However, the significantly higher resolution of the PaFd structure makes possible a reliable comparison with available high-resolution structures of [4Fe–4S]-containing Fds, in an effort to rationalize the unusual electrochemical properties of Alvin-like Fds. Three major factors contributing to the reduction potential values of [4Fe–4S]2+/+ clusters of Fds, namely, the surface accessibility of the clusters, the N–H···S hydrogen-bonding network, and the volume of the cavities hosting the clusters, are extensively discussed. The volume of the cavities is introduced in the present work for the first time, and can in part explain the very negative potential of cluster I of Alvin-like Fds.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
894.
Nik Veldhoen Jared Hobbs Georgios Ikonomou Michael Hii Mary Lesperance Caren C. Helbing 《PloS one》2016,11(11)
Environmental stewardship requires timely, accurate information related to the status of a given ecosystem and the species that occupy it. Recent advances in the application of the highly sensitive real-time quantitative polymerase chain reaction (qPCR) towards identification of constituents within environmental DNA (eDNA) now allow targeted detection of the presence of species-specific biological material within a localized geographic region. However, as with all molecular techniques predicated on the specificity and sensitivity of the PCR assay, careful validation of each eDNA qPCR assay in development must be performed both under controlled laboratory conditions and when challenged with field-derived eDNA samples. Such a step-wise approach forms the basis for incorporation of innovative qPCR design features that strengthen the implementation and interpretation of the eDNA assay. This includes empirical determination that the qPCR assay is refractory to the presence of human DNA and the use of a tripartite assay approach comprised of 1) a primer set targeting plant chloroplast that evaluates the presence of amplifiable DNA from field samples to increase confidence in a negative result, 2) an animal group primer set to increase confidence in the assay result, and 3) a species-specific primer set to assess presence of DNA from the target species. To demonstrate this methodology, we generated eDNA assays specific for the North American bullfrog (Lithobates (Rana) catesbeiana) and the Rocky Mountain tailed frog (Ascaphus montanus) and characterized each with respect to detection sensitivity and specificity with demonstrated performance in a field survey scenario. The qPCR design features presented herein address specific challenges of eDNA assays thereby increasing their interpretative power. 相似文献
895.
Misha Kudryashev Aikaterini Aktoudianaki Dimitrios Dedoglou Henning Stahlberg Georgios Tsiotis 《BBA》2014
Chlorobaculum (Cba) tepidum is a green sulfur bacterium that oxidizes sulfide, elemental sulfur, and thiosulfate for photosynthetic growth. As other anoxygenic green photosynthetic bacteria, Cba tepidum synthesizes bacteriochlorophylls for the assembly of a large light-harvesting antenna structure, the chlorosome. Chlorosomes are sac-like structures that are connected to the reaction centers in the cytoplasmic membrane through the BChl α-containing Fenna–Matthews–Olson protein. Most components of the photosynthetic machinery are known on a biophysical level, however, the structural integration of light harvesting with charge separation is still not fully understood. Despite over two decades of research, gaps in our understanding of cellular architecture exist. Here we present an in-depth analysis of the cellular architecture of the thermophilic photosynthetic green sulfur bacterium of Cba tepidum by cryo-electron tomography. We examined whole hydrated cells grown under different electron donor conditions. Our results reveal the distribution of chlorosomes in 3D in an unperturbed cell, connecting elements between chlorosomes and the cytoplasmic membrane and the distribution of reaction centers in the cytoplasmic membrane. 相似文献
896.
Julia M.C. Busch Minos-Timotheos Matsoukas Maria Musgaard Georgios A. Spyroulias Philip C. Biggin Ioannis Vakonakis 《The Journal of biological chemistry》2020,295(52):17922
Centrioles are key eukaryotic organelles that are responsible for the formation of cilia and flagella, and for organizing the microtubule network and the mitotic spindle in animals. Centriole assembly requires oligomerization of the essential protein spindle assembly abnormal 6 (SAS-6), which forms a structural scaffold templating the organization of further organelle components. A dimerization interaction between SAS-6 N-terminal “head” domains was previously shown to be essential for protein oligomerization in vitro and for function in centriole assembly. Here, we developed a pharmacophore model allowing us to assemble a library of low-molecular-weight ligands predicted to bind the SAS-6 head domain and inhibit protein oligomerization. We demonstrate using NMR spectroscopy that a ligand from this family binds at the head domain dimerization site of algae, nematode, and human SAS-6 variants, but also that another ligand specifically recognizes human SAS-6. Atomistic molecular dynamics simulations starting from SAS-6 head domain crystallographic structures, including that of the human head domain which we now resolve, suggest that ligand specificity derives from favorable Van der Waals interactions with a hydrophobic cavity at the dimerization site. 相似文献
897.
Fraser Aitken Georgios Menelaou Oliver Warrington Rene S. Koolschijn Nadge Corbin Martina F. Callaghan Peter Kok 《PLoS biology》2020,18(12)
The way we perceive the world is strongly influenced by our expectations. In line with this, much recent research has revealed that prior expectations strongly modulate sensory processing. However, the neural circuitry through which the brain integrates external sensory inputs with internal expectation signals remains unknown. In order to understand the computational architecture of the cortex, we need to investigate the way these signals flow through the cortical layers. This is crucial because the different cortical layers have distinct intra- and interregional connectivity patterns, and therefore determining which layers are involved in a cortical computation can inform us on the sources and targets of these signals. Here, we used ultra-high field (7T) functional magnetic resonance imaging (fMRI) to reveal that prior expectations evoke stimulus-specific activity selectively in the deep layers of the primary visual cortex (V1). These findings are in line with predictive processing theories proposing that neurons in the deep cortical layers represent perceptual hypotheses and thereby shed light on the computational architecture of cortex.The way we perceive the world is strongly influenced by our expectations, but the neural circuitry through which the brain achieves this remains unknown. A study using ultra-high field fMRI reveals that prior expectations evoke stimulus-specific signals in the deep layers of the primary visual cortex. 相似文献
898.
Michael E.B. FitzPatrick Nicholas M. Provine Lucy C. Garner Kate Powell Ali Amini Sophie L. Irwin Helen Ferry Tim Ambrose Peter Friend Georgios Vrakas Srikanth Reddy Elizabeth Soilleux Paul Klenerman Philip J. Allan 《Cell reports》2021,34(3):108661
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