1,791 research outputs found

    Molecular cloning and functional expression of the human glycine transporter GlyT2 and chromosomal localisation of the gene in the human genome1The nucleotide sequence presented here has been submitted to the GenBank database under accession number AF085412.1

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    AbstractNeurotransmitter transport systems are major targets for therapeutic alterations in synaptic function. We have cloned and sequenced a cDNA encoding the human type 2 glycine transporter GlyT2 from human brain and spinal cord. An open reading frame of 2391 nucleotides encodes a 797 amino acid protein that transports glycine in a Na+/Cl−-dependent manner. When stably expressed in CHO cells, human GlyT2 displays a dose-dependent uptake of glycine with an apparent Km of 108 μM. This uptake is not affected by sarcosine at concentrations up to 1 mM. Radiation hybrid analysis mapped the GlyT2 gene to D11S1308 (LOD=8.988) on human chromosome 11p15.1–15.2

    The Epitheliome: agent-based modelling of the social behaviour of cells

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    We have developed a new computational modelling paradigm for predicting the emergent behaviour resulting from the interaction of cells in epithelial tissue. As proof-of-concept, an agent-based model, in which there is a one-to-one correspondence between biological cells and software agents, has been coupled to a simple physical model. Behaviour of the computational model is compared with the growth characteristics of epithelial cells in monolayer culture, using growth media with low and physiological calcium concentrations. Results show a qualitative fit between the growth characteristics produced by the simulation and the in vitro cell models

    Tracing Nitrogen in Volcanic and Geothermal Volatiles from the Nicaraguan Volcanic Front

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    We report new chemical and isotopic data from 26 volcanic and geothermal gases, vapor condensates, and thermal water samples, collected along the Nicaraguan volcanic front. The samples were analyzed for chemical abundances and stable isotope compositions, with a focus on nitrogen abundances and isotope ratios. These data are used to evaluate samples for volatile contributions from magma, air, air-saturated water, and the crust. Samples devoid of crustal contamination (based upon He isotope composition) but slightly contaminated by air or air-saturated water are corrected using N2/Ar ratios in order to obtain primary magmatic values, composed of contributions from upper mantle and subducted hemipelagic sediment on the down-going plate. Using a mantle endmember with d15N= 5&and N2/He = 100 and a subducted sediment component with d15N=+7& and N2/He = 10,500, the average sediment contribution to Nicaraguan volcanic and geothermal gases was determined to be 71%. Most of the gases were dominated by sediment-derived nitrogen, but gas from Volca´n Mombacho, the southernmost sampling location, had a mantle signature (46% from subducted sediment, or 54% from the mantle) and an affinity with mantle-dominated gases discharging from Costa Rica localities to the south. High CO2/N2 exc. ratios (N2 exc. is the N2 abundance corrected for contributions from air) in the south are similar to those in Costa Rica, and reflect the predominant mantle wedge input, whereas low ratios in the north indicate contribution by altered oceanic crust and/or preferential release of nitrogen over carbon from the subducting slab. Sediment-derived nitrogen fluxes at the Nicaraguan volcanic front, estimated by three methods, are 7.8 · 108 mol N/a from 3He flux, 6.9 · 108 mol/a from SO2 flux, and 2.1 · 108 and 1.3 · 109 mol/a from CO2 fluxes calculated from 3He and SO2, respectively. These flux results are higher than previous estimates for Central America, reflecting the high sediment-derived volatile contribution and the high nitrogen content of geothermal and volcanic gases in Nicaragua. The fluxes are also similar to but higher than estimated hemipelagic nitrogen inputs at the trench, suggesting addition of N from altered oceanic basement is needed to satisfy these flux estimates. The similarity of the calculated input of N via the trench to our calculated outputs suggests that little or none of the subducted nitrogen is being recycled into the deeper mantle, and that it is, instead, returned to the surface via arc volcanism

    Experimental determination of the dispersion relation of magnetosonic waves

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    Magnetosonic waves are commonly observed in the vicinity of the terrestrial magnetic equator. It has been proposed that within this region they may interact with radiation belt electrons, accelerating some to high energies. These wave-particle interactions depend upon the characteristic properties of the wave mode. Hence, determination of the wave properties is a fundamental part of understanding these interaction processes. Using data collected during the Cluster Inner Magnetosphere Campaign, this paper identifies an occurrence of magnetosonic waves, discusses their generation and propagation properties from a theoretical perspective, and utilizes multispacecraft measurements to experimentally determine their dispersion relation. Their experimental dispersion is found to be in accordance with that based on cold plasma theory

    Receptor activity-modifying protein-dependent effects of mutations in the calcitonin receptor-like receptor:implications for adrenomedullin and calcitonin gene-related peptide pharmacology

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    Background and Purpose Receptor activity-modifying proteins (RAMPs) define the pharmacology of the calcitonin receptor-like receptor (CLR). The interactions of the different RAMPs with this class B GPCR yield high-affinity calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors. However, the mechanism for this is unclear. Experimental Approach Guided by receptor models, we mutated residues in the N-terminal helix of CLR, RAMP2 and RAMP3 hypothesized to be involved in peptide interactions. These were assayed for cAMP production with AM, AM2 and CGRP together with their cell surface expression. Binding studies were also conducted for selected mutants. Key Results An important domain for peptide interactions on CLR from I32 to I52 was defined. Although I41 was universally important for binding and receptor function, the role of other residues depended on both ligand and RAMP. Peptide binding to CLR/RAMP3 involved a more restricted range of residues than that to CLR/RAMP1 or CLR/RAMP2. E101 of RAMP2 had a major role in AM interactions, and F111/W84 of RAMP2/3 was important with each peptide. Conclusions and Implications RAMP-dependent effects of CLR mutations suggest that the different RAMPs control accessibility of peptides to binding residues situated on the CLR N-terminus. RAMP3 appears to alter the role of specific residues at the CLR-RAMP interface compared with RAMP1 and RAMP2

    Human security and social quality: contrasts and complementaries

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    Two authors who have been leaders of the "social quality approach" that emerged in European social policy circles in the 1990s, and two authors who have worked with the "human development" and "human security" approaches that emerged in international development policy circles in the 1980s and 90s, collaborate in this paper in order to outline and compare the two traditions. The "human development" tradition has focused on the quality of individual human lives, understood as influenced by interconnections that transcend conventional disciplinary boundaries; its "human security" branch goes deeper into study of human vulnerability and the textures of daily life. The "social quality" tradition tries to understand individual lives as lived within a societal fabric, to identify and measure key elements of that fabric, and to develop a correspondingly grounded public policy approach. The paper is a first step in a project to assess the possible complementarity, in theorising and practical application, of these two streams of work

    Connecting ‘Human’ and ‘Social’ Discourses: The Human Development, Human Security, and Social Quality Approaches

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    __Abstract__ The human development approach emerged in the late 1980s in response to the negative effects of structural adjustment programmes applied to countries in the South. Led originally by two South Asian scholars, Mahbub ul Haq and Amartya Sen, in cooperation with a large international network, the approach is comparative in perspective and global in reach and has been incorporated into parts of the United Nations (UN) system, including the United Nations Development Programme. Over the years this approach has integrated three dimensions – human development, human rights and human security –, and looks at people’s well-being or ill-being, security and insecurity, in the context of issues arising from global interconnectedness and inequities. It has had significant influence, but one constraint has been that its focus on the ‘human’ is accompanied by a widely recognised gap in respect of ‘the social’ (Apthorpe 1997, Gasper 2011, Phillips 2011)
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