86 research outputs found

    7-Azido-N,N-diethyl-4,5-O-isopropyl­idene-4-C-methyl-3,6-anhydro-7-de­oxy-d-glycero-d-manno-heptonamide

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    The reaction of 5-azido-5-de­oxy-2,3-O-isopropyl­idene-2-C-methyl-d-ribose with N,N-diethyl-2-(dimethyl­sulfuranyl­idene)acetamide gave the title compound, C15H26N4O5, as the major product arising from initial formation of an epoxide which was subsequently opened by intra­molecular attack of the free 4-hydroxyl group. X-ray crystallography confirmed the relative stereochemistry of the title compound and the absolute configuration was determined by the use of d-ribose as the starting material. The crystal structure contains chains of mol­ecules running parallel to the a axis, being linked by weak bifurcated O—H⋯(N,N) hydrogen bonds

    The intrinsically disordered distal face of nucleoplasmin recognizes distinct oligomerization states of histones

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    The role of Nucleoplasmin (NP) as a H2A-H2B histone chaperone has been extensively characterized. To understand its putative interaction with other histone ligands, we have characterized its ability to bind H3-H4 and histone octamers. We find that the chaperone forms distinct complexes with histones, which differ in the number of molecules that build the assembly and in their spatial distribution. When complexed with H3-H4 tetramers or histone octamers, two NP pentamers form an ellipsoidal particle with the histones located at the center of the assembly, in stark contrast with the NP/H2A-H2B complex that contains up to five histone dimers bound to one chaperone pentamer. This particular assembly relies on the ability of H3-H4 to form tetramers either in solution or as part of the octamer, and it is not observed when a variant of H3 (H3C110E), unable to form stable tetramers, is used instead of the wild-type protein. Our data also suggest that the distal face of the chaperone is involved in the interaction with distinct types of histones, as supported by electron microscopy analysis of the different NP/histone complexes. The use of the same structural region to accommodate all type of histones could favor histone exchange and nucleosome dynamics

    A Health Sector Online Toolkit for Implementing Learning into Practice from Violence Against Women Trainings (TILPVAWT)

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    Violence against women (VAW) is a major public health and human rights concern. Intimate partner violence and sexual violence are among the most pervasive forms of violence against women. Training health professionals in VAW is essential to raise awareness and improve the care for victims with a comprehensive approach. One of the objectives of this project was the development of a set of 28 tools to facilitate VAW training of health professionals, using certain common content, and the transfer of this knowledge into their clinical practice. This toolkit has been presented on the website http://www.toolner.com/en/. This website has been designed in an easy to use and friendly way, and is oriented to trainers, organisations and individuals interested in improving their teaching skills in VAW, but with the potential to be adapted and used independently by different organisations. The toolkit is divided into five phases of training: preparation, development, implementation, post-training, and assessment; each containing different tools and examples. Training in VAW is the first step to change attitudes but it is necessary to motivate professionals, adapt content, methodology and assess the impact of the training. This website is a tool by which to achieve this

    Truncation-Driven Lateral Association of α-Synuclein Hinders Amyloid Clearance by the Hsp70-Based Disaggregase

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    The aggregation of α-synuclein is the hallmark of a collective of neurodegenerative disorders known as synucleinopathies. The tendency to aggregate of this protein, the toxicity of its aggregation intermediates and the ability of the cellular protein quality control system to clear these intermediates seems to be regulated, among other factors, by post-translational modifications (PTMs). Among these modifications, we consider herein proteolysis at both the N- and C-terminal regions of α-synuclein as a factor that could modulate disassembly of toxic amyloids by the human disaggregase, a combination of the chaperones Hsc70, DnaJB1 and Apg2. We find that, in contrast to aggregates of the protein lacking the N-terminus, which can be solubilized as efficiently as those of the WT protein, the deletion of the C-terminal domain, either in a recombinant context or as a consequence of calpain treatment, impaired Hsc70-mediated amyloid disassembly. Progressive removal of the negative charges at the C-terminal region induces lateral association of fibrils and type B* oligomers, precluding chaperone action. We propose that truncation-driven aggregate clumping impairs the mechanical action of chaperones, which includes fast protofilament unzipping coupled to depolymerization. Inhibition of the chaperone-mediated clearance of C-truncated species could explain their exacerbated toxicity and higher propensity to deposit found in vivo.This work was supported by grants PID2019-111068GB-I00 (to A.M.) (AEI/FEDER, UE) and PID2019-105872GB-I00 (to J.M.V.) (AEI/FEDER, UE) from the Ministry of Science and Innovation and by the Basque Government (grant IT1201-19 to AM). The Centro Nacional de Biotecnología (CNB) is a Severo Ochoa Center of Excellence (MINECO award SEV 2017-0712). N.O. holds a contract funded by Fundacion Biofisika Bizkaia. Acknowledgment

    Modelling the inner disc of the Milky Way with manifolds. I - A first step

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    We study the bar-driven dynamics in the inner part of the Milky Way by using invariant manifolds. This theory has been successfully applied to describe the morphology and kinematics of rings and spirals in external galaxies, and now, for the first time, we apply it to the Milky Way. We compute the orbits confined by the invariant manifolds of the unstable periodic orbits located at the ends of the bar. We discuss whether the COBE/DIRBE bar and the Long bar compose a single bar or two independent bars and perform a number of comparisons which, taken together, argue strongly in favour of the former. More specifically, we favour the possibility that the so-called COBE/DIRBE bar is the boxy/peanut bulge of a bar whose outer thin parts are the so-called Long bar. This possibility is in good agreement both with observations of external galaxies, with orbital structure theory and with simulations. We then analyse in detail the morphology and kinematics given by five representative Galactic potentials. Two have a Ferrers bar, two have a quadrupole bar and the last one a composite bar. We first consider only the COBE/DIRBE bar and then extend it to include the effect of the Long bar. We find that the large-scale structure given by the manifolds describes an inner ring, whose size is similar to the near and far 3-kpc arm, and an outer ring, whose properties resemble those of the Galactic Molecular Ring. We also analyse the kinematics of these two structures, under the different galactic potentials, and find they reproduce the main over-densities found in the galactic longitude-velocity CO diagram. Finally, we consider for what model parameters, the global morphology of the manifolds may reproduce the two outer spiral arms. We conclude that this would necessitate either more massive and more rapidly rotating bars, or including in the potential an extra component describing the spiral arms.Comment: 18 pages, 11 figures, accepted in MNRA

    Stellar populations of bulges at low redshift

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    This chapter summarizes our current understanding of the stellar population properties of bulges and outlines important future research directions.Comment: Review article to appear in "Galactic Bulges", Editors: Laurikainen E., Peletier R., Gadotti D., Springer Publishing. 34 pages, 12 figure

    Sloan Digital Sky Survey IV: mapping the Milky Way, nearby galaxies, and the distant universe

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    We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median ). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July
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