46 research outputs found

    A quantitative map of nuclear pore assembly reveals two distinct mechanisms

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    Understanding how the nuclear pore complex (NPC) assembles is of fundamental importance to grasp the mechanisms behind its essential function and understand its role during evolution of eukaryotes1–4. While we know that at least two NPC assembly pathways exist, one during exit from mitosis and one during nuclear growth in interphase, we currently lack a quantitative map of their molecular events. Here, we use fluorescence correlation spectroscopy (FCS) calibrated live imaging of endogenously fluorescently-tagged nucleoporins to map the changes in composition and stoichiometry of seven major modules of the human NPC during its assembly in single dividing cells. This systematic quantitative map reveals that the two assembly pathways employ strikingly different molecular mechanisms, inverting the order of addition of two large structural components, the central ring complex and nuclear filaments. Our dynamic stoichiometry data allows us to perform the first computational simulation that predicts the structure of postmitotic NPC assembly intermediates

    Social Patterning of Screening Uptake and the Impact of Facilitating Informed Choices: Psychological and Ethical Analyses

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    Screening for unsuspected disease has both possible benefits and harms for those who participate. Historically the benefits of participation have been emphasized to maximize uptake reflecting a public health approach to policy; currently policy is moving towards an informed choice approach involving giving information about both benefits and harms of participation. However, no research has been conducted to evaluate the impact on health of an informed choice policy. Using psychological models, the first aim of this study was to describe an explanatory framework for variation in screening uptake and to apply this framework to assess the impact of informed choices in screening. The second aim was to evaluate ethically that impact. Data from a general population survey (n = 300) of beliefs and attitudes towards participation in diabetes screening indicated that greater orientation to the present is associated with greater social deprivation and lower expectation of participation in screening. The results inform an explanatory framework of social patterning of screening in which greater orientation to the present focuses attention on the disadvantages of screening, which tend to be immediate, thereby reducing participation. This framework suggests that an informed choice policy, by increasing the salience of possible harms of screening, might reduce uptake of screening more in those who are more deprived and orientated to the present. This possibility gives rise to an apparent dilemma where an ethical decision must be made between greater choice and avoiding health inequality. Philosophical perspectives on choice and inequality are used to point to some of the complexities in assessing whether there really is such a dilemma and if so how it should be resolved. The paper concludes with a discussion of the ethics of paternalism

    Refining Disordered Peptide Ensembles with Computational Amide I Spectroscopy: Application to Elastin-Like Peptides

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    The characterization of intrinsically disordered protein (IDP) ensembles is complicated both by inherent heterogeneity and by the fact that many common experimental techniques function poorly when applied to IDPs. For this reason, the development of alternative structural tools for probing IDP ensembles has attracted considerable attention. Here we describe our recent work in developing experimental and computational tools for characterizing IDP ensembles using Amide I (backbone carbonyl stretch) vibrational spectroscopy. In this approach, the infrared (IR) absorption frequencies of isotope-labeled amide bonds probe their local electrostatic environments and structures. Empirical frequency maps allow us to use this spectroscopic data as a direct experimental test of atomistic structural models. We apply these methods to a family of short elastin-like peptides (ELPs), fragments of the elastin protein based around the Pro-Gly turn motif characteristic of the elastomeric segments of the full protein. Using a maximum entropy analysis that applies constraints from experimental spectra to weighting predicted spectra from molecular dynamics (MD) ensembles, we find that peptides with Ala or Val side chains preceding the Pro-Gly turn unit exhibit a stronger tendency toward extended structures than do Gly-Pro-Gly motifs, suggesting an important role for steric interactions in tuning the molecular properties of elastin

    Adsorptive removal of methylene blue using magnetic biochar derived from agricultural waste biomass: Equilibrium, isotherm, kinetic study

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    © 2018 World Scientific Publishing Company. Wastewater discharge from textile industries contribute much to water pollution and threaten the aqua ecosystem balance. Synthesis of agriculture waste based adsorbent is a smart move toward overcoming the critical environmental issues as well as a good waste management process implied. This research work describes the adsorption of methylene blue dye from aqueous solution on nickel oxide attached magnetic biochar derived from mangosteen peel. A series of characterization methods was employed such as FTIR, FESEM analysis and BET surface area analyzer to understand the adsorbent behavior produced at a heating temperature of 800âC for 20min duration. The adsorbate pH value was varied to investigate the adsorption kinetic trend and the isotherm models were developed by determining the equilibrium adsorption capacity at varied adsorbate initial concentration. Equilibrium adsorption isotherm models were measured for single component system and the calculated data were analyzed by using Langmuir, Freundlich, Tempkin and Dubinin-Radushkevich isotherm equations. The Langmuir, Freundlich and Tempkin isotherm model exhibit a promising R2-correlation value of more than 0.95 for all three isotherm models. The Langmuir isotherm model reflectsan equilibrium adsorption capacity of 22.883mg.g-1
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