3,023 research outputs found

    Subcellular compartmentalisation of copper, iron, manganese, and zinc in the Parkinson's disease brain

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    © 2017 The Royal Society of Chemistry. Elevated iron and decreased copper levels are cardinal features of the degenerating substantia nigra pars compacta in the Parkinson's disease brain. Both of these redox-active metals, and fellow transition metals manganese and zinc, are found at high concentrations within the midbrain and participate in a range of unique biological reactions. We examined the total metal content and cellular compartmentalisation of manganese, iron, copper and zinc in the degenerating substantia nigra, disease-affected but non-degenerating fusiform gyrus, and unaffected occipital cortex in the post mortem Parkinson's disease brain compared with age-matched controls. An expected increase in iron and a decrease in copper concentration was isolated to the soluble cellular fraction, encompassing both interstitial and cytosolic metals and metal-binding proteins, rather than the membrane-associated or insoluble fractions. Manganese and zinc levels did not differ between experimental groups. Altered Fe and Cu levels were unrelated to Braak pathological staging in our cases of late-stage (Braak stage V and VI) disease. The data supports our hypothesis that regional alterations in Fe and Cu, and in proteins that utilise these metals, contribute to the regional selectively of neuronal vulnerability in this disorder

    Live to cheat another day: bacterial dormancy facilitates the social exploitation of beta-lactamases

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    The breakdown of antibiotics by ÎČ-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of ÎČ-lactamases from cells. Here, we investigated whether a broad-spectrum ÎČ-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours

    Observation of completely destructive quantum interference between interacting resonances in molecular predissociation

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    Predissociating resonances were observed for destructive interference in a region between the resonances. Multiphoton ionization spectroscopy which was enhanced by resonance was used for probing single rotational levels of O2 in case of double resonance technique. Double resonance technique resulted in the elimination of overlapping rotational structure

    The d 1Πg(v=1) Rydberg state of O2: Optical-optical double-resonance and Huggins-band ozone-photolysis, resonance-enhanced multiphoton-ionization studies with a b 1Σ+g(v=0)-state platform

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    The d←←b(1,0) band of O2 following Huggins-band photolysis of O3 was explored. Analyses of these REMPI spectra yield, not only the first information on d(v=1) rotational levels with J>29, but also the first estimate of an O2(b-state fragment rotation

    Super-resolution far-field ghost imaging via compressive sampling

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    Much more image details can be resolved by improving the system's imaging resolution and enhancing the resolution beyond the system's Rayleigh diffraction limit is generally called super-resolution. By combining the sparse prior property of images with the ghost imaging method, we demonstrated experimentally that super-resolution imaging can be nonlocally achieved in the far field even without looking at the object. Physical explanation of super-resolution ghost imaging via compressive sampling and its potential applications are also discussed.Comment: 4pages,4figure

    Generalized Uncertainty Principle, Modified Dispersion Relation and Barrier penetration by a Dirac particle

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    We have studied the energy band structure of a Dirac particle in presence of a generalised uncertainty principle (GUP). We start from defining a modified momentum operator and derive corresponding modified dispersion relation (MDR) and GUP. Apart from the forbidden band within the range ±m\pm m, mm being the mass of the particle, we find the existence of additional forbidden bands at the both ends of the spectrum. Such band structure forbids a Dirac particle to penetrate a potential step of sufficient height (∌EP\sim E_P, EPE_P being Planck energy). This is also true for massless particle. Unlike the relativistic case, a massless particle also can reflect from a barrier of sufficient height. Finally we discuss about the Klein's paradox in presence of the GUP.Comment: 10 pages, 7 figures, LaTe

    The Phyre2 web portal for protein modeling, prediction and analysis

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    Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission

    Evidence that a Panel of Neurodegeneration Biomarkers Predicts Vasospasm, Infarction, and Outcome in Aneurysmal Subarachnoid Hemorrhage

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    Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH) with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6–9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf), hypophosphorylated neurofilament H
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