56 research outputs found

    Signatures of anthocyanin metabolites identified in humans inhibit biomarkers of vascular inflammation in human endothelial cells

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    Scope The physiological relevance of contemporary cell culture studies is often perplexing, given the use of unmetabolized phytochemicals at supraphysiological concentrations. We investigated the activity of physiologically relevant anthocyanin metabolite signatures, derived from a previous pharmacokinetics study of 500 mg 13C5-cyanidin-3-glucoside in 8 healthy participants, on soluble vascular adhesion molecule-1 (VCAM-1) and interleukin-6 (IL-6) in human endothelial cells. Methods and results Signatures of peak metabolites (previously identified at 1, 6 and 24 h post-bolus) were reproduced using pure standards and effects were investigated across concentrations ten-fold lower and higher than observed mean (<5 μM) serum levels. Tumor necrosis factor-α (TNF-α)-stimulated VCAM-1 was reduced in response to all treatments, with maximal effects observed for the 6 h and 24 h profiles. Profiles tested at ten-fold below mean serum concentrations (0.19-0.44 μM) remained active. IL-6 was reduced in response to 1, 6 and 24 h profiles, with maximal effects observed for 6 h and 24 h profiles at concentrations above 2 μM. Protein responses were reflected by reductions in VCAM-1 and IL-6 mRNA, however there was no effect on phosphorylated NFκB-p65 expression. Conclusion Signatures of anthocyanin metabolites following dietary consumption reduce VCAM-1 and IL-6 production, providing evidence of physiologically relevant biological activity

    Inertial imaging with nanomechanical systems

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    Mass sensing with nanoelectromechanical systems has advanced significantly during the last decade. With nanoelectromechanical systems sensors it is now possible to carry out ultrasensitive detection of gaseous analytes, to achieve atomic-scale mass resolution and to perform mass spectrometry on single proteins. Here, we demonstrate that the spatial distribution of mass within an individual analyte can be imaged - in real time and at the molecular scale - when it adsorbs onto a nanomechanical resonator. Each single-molecule adsorption event induces discrete, time-correlated perturbations to all modal frequencies of the device. We show that by continuously monitoring a multiplicity of vibrational modes, the spatial moments of mass distribution can be deduced for individual analytes, one-by-one, as they adsorb. We validate this method for inertial imaging, using both experimental measurements of multimode frequency shifts and numerical simulations, to analyse the inertial mass, position of adsorption and the size and shape of individual analytes. Unlike conventional imaging, the minimum analyte size detectable through nanomechanical inertial imaging is not limited by wavelength-dependent diffraction phenomena. Instead, frequency fluctuation processes determine the ultimate attainable resolution. Advanced nanoelectromechanical devices appear capable of resolving molecular-scale analytes. © 2015 Macmillan Publishers Limited. All rights reserved

    Tomato: a crop species amenable to improvement by cellular and molecular methods

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    Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

    Dyson-Schwinger Equations: Density, Temperature and Continuum Strong QCD

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    Continuum strong QCD is the application of models and continuum quantum field theory to the study of phenomena in hadronic physics, which includes; e.g., the spectrum of QCD bound states and their interactions; and the transition to, and properties of, a quark gluon plasma. We provide a contemporary perspective, couched primarily in terms of the Dyson-Schwinger equations but also making comparisons with other approaches and models. Our discourse provides a practitioners' guide to features of the Dyson-Schwinger equations [such as confinement and dynamical chiral symmetry breaking] and canvasses phenomenological applications to light meson and baryon properties in cold, sparse QCD. These provide the foundation for an extension to hot, dense QCD, which is probed via the introduction of the intensive thermodynamic variables: chemical potential and temperature. We describe order parameters whose evolution signals deconfinement and chiral symmetry restoration, and chronicle their use in demarcating the quark gluon plasma phase boundary and characterising the plasma's properties. Hadron traits change in an equilibrated plasma. We exemplify this and discuss putative signals of the effects. Finally, since plasma formation is not an equilibrium process, we discuss recent developments in kinetic theory and its application to describing the evolution from a relativistic heavy ion collision to an equilibrated quark gluon plasma.Comment: 103 Pages, LaTeX, epsfig. To appear in Progress in Particle and Nuclear Physics, Vol. 4

    New insights into the genetic etiology of Alzheimer's disease and related dementias

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    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

    Beam-target helicity asymmetry e in K0 Λ and K0 Σ0 photoproduction on the neutron

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    We report the first measurements of the E beam-target helicity asymmetry for the γ - n - →K0Λ and K0Σ0 channels in the energy range 1.70≤W≤2.34 GeV. The CLAS system at Jefferson Lab uses a circularly polarized photon beam and a target consisting of longitudinally polarized solid molecular hydrogen deuteride with low background contamination for the measurements. The multivariate analysis method boosted decision trees is used to isolate the reactions of interest. Comparisons with predictions from the KaonMAID, SAID, and Bonn-Gatchina models are presented. These results will help separate the isospin I=0 and I=1 photocoupling transition amplitudes in pseudoscalar meson photoproduction
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