147,580 research outputs found

    Pathological changes are associated with shifts in the employment of synonymous codons at the transcriptome level

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    The usage of different synonymous codons reflects the genome organization and has been connected to parameters such as mRNA abundance and protein folding. It is also been established that mutations targeting specific synonymous codons can trigger disease. We performed a systematic meta-analysis of transcriptome results from 75 datasets representing 40 pathologies. We found that a subset of codons was preferentially employed in abundant transcripts, while other codons were preferentially found in low-abundance transcripts. By comparing control and pathological transcriptomes, we observed a shift in the employment of synonymous codons for every analyzed disease. For example, cancerous tissue employed preferentially A- or U-ending codons, shifting from G- or C-ending codons, which were preferred by control tissues. This analysis was able to discriminate patients and controls with high specificity and sensitivity. Here we show that the employment of specific synonymous codons, quantified at the whole transcriptome level, changes profoundly in many diseases. We propose that the changes in codon employment offer a novel perspective for disease studies, and could be used to design new diagnostic tools

    Synaptic vesicle pools: an update

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    During the last few decades synaptic vesicles have been assigned to a variety of functional and morphological classes or pools. We have argued in the past (Rizzoli SO and Betz WJ, 2005, Synaptic vesicle pools, Nat. Rev. Neurosci. 6, 57-69) that synaptic activity in several preparations is accounted for by the function of three vesicle pools: the readily releasable pool (docked at active zones and ready to go upon stimulation), the recycling pool (scattered throughout the nerve terminals and recycling upon moderate stimulation), and finally the reserve pool (occupying most of the vesicle clusters and only recycling upon strong stimulation). We discuss here the advancements in the vesicle pool field which took place in the ensuing years, focusing on the behavior of different pools under both strong stimulation and physiological activity. Several new findings have enhanced the three-pool model, with, for example, the disparity between recycling and reserve vesicles being underlined by the observation that the former are mobile, while the latter are fixed. Finally, a number of altogether new concepts have also evolved such as the current controversy on the identity of the spontaneously recycling vesicle pool

    Newly produced synaptic vesicle proteins are preferentially used in synaptic transmission

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    Aged proteins can become hazardous to cellular function, by accumulating molecular damage. This implies that cells should preferentially rely on newly produced ones. We tested this hypothesis in cultured hippocampal neurons, focusing on synaptic transmission. We found that newly synthesized vesicle proteins were incorporated in the actively recycling pool of vesicles responsible for all neurotransmitter release during physiological activity. We observed this for the calcium sensor Synaptotagmin 1, for the neurotransmitter transporter VGAT, and for the fusion protein VAMP2 (Synaptobrevin 2). Metabolic labeling of proteins and visualization by secondary ion mass spectrometry enabled us to query the entire protein makeup of the actively recycling vesicles, which we found to be younger than that of non-recycling vesicles. The young vesicle proteins remained in use for up to similar to 24 h, during which they participated in recycling a few hundred times. They were afterward reluctant to release and were degraded after an additional similar to 24-48 h. We suggest that the recycling pool of synaptic vesicles relies on newly synthesized proteins, while the inactive reserve pool contains older proteins

    A mass spectrometry workflow for measuring protein turnover rates in vivo

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    Proteins are continually produced and degraded, to avoid the accumulation of old or damaged molecules and to maintain the efficiency of physiological processes. Despite its importance, protein turnover has been difficult to measure in vivo. Previous approaches to evaluating turnover in vivo have required custom labeling approaches, involved complex mass spectrometry (MS) analyses, or used comparative strategies that do not allow direct quantitative measurements. Here, we describe a robust protocol for quantitative proteome turnover analysis in mice that is based on a commercially available diet for stable isotope labeling of amino acids in mammals (SILAM). We start by discussing fundamental concepts of protein turnover, including different methodological approaches. We then cover in detail the practical aspects of metabolic labeling and explain both the experimental and computational steps that must be taken to obtain accurate in vivo results. Finally, we present a simple experimental workflow that enables measurement of precise turnover rates in a time frame of similar to 4-5 weeks, including the labeling time. We also provide all the scripts needed for the interpretation of the MS results and for comparing turnover across different conditions. Overall, the workflow presented here comprises several improvements in the determination of protein lifetimes with respect to other available methods, including a minimally invasive labeling strategy and a robust interpretation of MS results, thus enhancing reproducibility across laboratories

    Mapping the Discipline of the Olympic Games An Author-Cocitation Analysis

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    The authors conducted an author cocitation analysis on prominent authors writing about the Olympics during the 1990s. Author cocitation is an established bibliometric technique that can be used to measure the relative similarities of topics written about by the cited authors. This enables a visual representation of the “intellectual space” of the discipline, in this case the Olympics, to be created for the period under review. So core and peripheral research areas are identified, along with their major contributors. The representation appears as a two-dimensional cluster-enhanced map. Subject expertise was then applied to the results to place labels on the generated clusters of authors and their topics

    Crystal Structure of the YBa2Cu3O7 Superconductor by Single Crystal X-Ray Diffraction

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    Just after Wu et al.1 reported superconductivity above 90 K in barium, yttrium and copper ternary oxides, the formula (YBa2Cu 3O7-x) and the structural arrangement (oxygen-deficient tripled-perovskite-type structure) of the superconducting phase was proposed by different groups. As theoretical proposals depend crucially on the details of the atomic arrangement reducing the dimensionality of the system, a number of structural determinations were carried out by X-ray, neutron and electron diffraction. Although these studies established the structure of the metal framework (the ordering of Ba and Y in the sequence Y-Ba-Ba being responsible for tripling the crystallographic c axis), discrepancies persist regarding the position of the oxygen vacancies. X-ray experiments on single crystals 2-3 have reported that the oxygen vacancies are distributed in an ordered way in the plane containing Y atoms (z = 1/2) and statistically in the plane at z = 0. High-resolution neutron-powder diffraction4,5 showed, on the other hand, a reduction in the structure dimensionality. The oxygen vacancies in the plane at z = 0 are ordered along the a-axis, so that one-dimensional chains of square-coordinated copper ions parallel to the b-c plane are formed. These results, confirmed by electron diffraction6, justify the reduction of crystal symmetry from tetragonal to orthorhombic observed in several studies. Structural differences between X-ray and neutron diffraction studies were attributed4 to the fact that single crystals used in X-ray measurements were probably highly twinned. But neutron experiments need large amounts of material, increasing the possibility of the samples being inhomogeneous. Here we report X-ray structure determination on a YBa2Cu3O7 single crystal showing a T c above 90 K. The results, in agreement with neutron-powder diffraction, confirm the complete ordering of the oxygen vacancies leading to the one-dimensional chains

    The benefit of textile design research to the textile designer.

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    If Textile Designers do not embark on and utilise textile research we will be left in a ‘sole less’ vacuum. The following article aims to show the benefit of textile design research to the textile designer. Textile design is increasingly complex, and influenced by a number of factors such as ethical textiles, sustainability, fast versus slow fashion, new digital technology and science. It is therefore necessary for increased research by the textile designer into these areas in order to understand and gain knowledge that can be incorporated into the vast textile industry so that we produce the most relevant cloth and fabrics, that satisfy both consumer and ethical requirements. “Work on good prose has three steps: a musical stage when its composed, an architectonic stage when its built and textile stage when its woven” Walter Benjamin 1892-1940. [1

    Mosses new to Hong Kong (1)

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    Ten moss species - Garkea flexuosa (Griffith) Marg. & Nork., Campylopus laxitextus Lac., Fissidens dubius P. Beauv., Fissidens ceylonensis Dozy & Molk, Fissidens maceratus Mitt., Philonotis thwaitesii Mitt., Isopterygium minutirameum (C. Muell.)Jaeg., Homalia trichomanoides (Hedw.) B.S.G., Pogonatum neesii (C. Muell.) Dozyand Polytrichum formosum Hedw. are reported new to Hong Kong. Among them, five are new to Guangdong Province of China

    Not So Quiet . . . A Novel

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    This story offers a rare, funny, bitter, feminist look at war from women actively engaged in it. Published in London in 1930, Not So Quiet...(on the Western Front) is a novel in autobiographical guise that describes a group of British women ambulance drivers on the French front lines during World War 1. As Voluntary Aid Detachment workers, the women pay for the privilege of driving the wounded through shell fire in the freezing cold, on no sleep and an inedible diet, under the watchful eye of their punishing commandant, nicknamed Mrs. Bitch.Front Cover -- Title Page -- Copyright Page -- Table of Contents -- Epigraph -- Chapter 1 -- Chapter 2 -- Chapter 3 -- Chapter 4 -- Chapter 5 -- Chapter 6 -- Chapter 7 -- Chapter 8 -- Chapter 9 -- Chapter 10 -- Chapter 11 -- Chapter 12 -- Afterword -- Notes -- About the Author -- About the Feminist Press -- Also Available from the Feminist PressThis story offers a rare, funny, bitter, feminist look at war from women actively engaged in it. Published in London in 1930, Not So Quiet...(on the Western Front) is a novel in autobiographical guise that describes a group of British women ambulance drivers on the French front lines during World War 1. As Voluntary Aid Detachment workers, the women pay for the privilege of driving the wounded through shell fire in the freezing cold, on no sleep and an inedible diet, under the watchful eye of their punishing commandant, nicknamed Mrs. Bitch.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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