551 research outputs found

    Transport in holographic superfluids

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    We construct a slowly varying space-time dependent holographic superfluid and compute its transport coefficients. Our solution is presented as a series expansion in inverse powers of the charge of the order parameter. We find that the shear viscosity associated with the motion of the condensate vanishes. The diffusion coefficient of the superfluid is continuous across the phase transition while its third bulk viscosity is found to diverge at the critical temperature. As was previously shown, the ratio of the shear viscosity of the normal component to the entropy density is 1/(4 pi). As a consequence of our analysis we obtain an analytic expression for the backreacted metric near the phase transition for a particular type of holographic superfluid.Comment: 45 pages + appendice

    Cryo-electron microscopy of viruses

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    Thin vitrified layers of unfixed, unstained and unsupported virus suspensions can be prepared for observation by cryo-electron microscopy in easily controlled conditions. The viral particles appear free from the kind of damage caused by dehydration, freezing or adsorption to a support that is encountered in preparing biological samples for conventional electron microscopy. Cryo-electron microscopy of vitrified specimens offers possibilities for high resolution observations that compare favourably with any other electron microscopical method

    Free energy of binding of coiled-coil complexes with different electrostatic environments: the influence of force field polarisation and capping

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    Coiled-coils are well known protein–protein interaction motifs, with the leucine zipper region of activator protein-1 (AP-1) consisting of the c-Jun and c-Fos proteins being a typical example. Molecular dynamics (MD) simulations using the MM/GBSA method have been used to predict the free energy of interaction of these proteins. The influence of force field polarisation and capping on the predicted free energy of binding of complexes with different electrostatic environments (net charge) were investigated. Although both force field polarisation and peptide capping are important for the prediction of the absolute free energy of binding, peptide capping has the largest influence on the predicted free energy of binding. Polarisable simulations appear better suited to determine structural properties of the complexes of these proteins while non-polarisable simulations seem to give better predictions of the associated free energies of bindin

    Fluvial sediment supply to a mega-delta reduced by shifting tropical-cyclone activity

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    © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. The world's rivers deliver 19 billion tonnes of sediment to the coastal zone annually, with a considerable fraction being sequestered in large deltas, home to over 500 million people. Most (more than 70 per cent) large deltas are under threat from a combination of rising sea levels, ground surface subsidence and anthropogenic sediment trapping, and a sustainable supply of fluvial sediment is therefore critical to prevent deltas being 'drowned' by rising relative sea levels. Here we combine suspended sediment load data from the Mekong River with hydrological model simulations to isolate the role of tropical cyclones in transmitting suspended sediment to one of the world's great deltas. We demonstrate that spatial variations in the Mekong's suspended sediment load are correlated (r = 0.765, P < 0.1) with observed variations in tropical-cyclone climatology, and that a substantial portion (32 per cent) of the suspended sediment load reaching the delta is delivered by runoff generated by rainfall associated with tropical cyclones. Furthermore, we estimate that the suspended load to the delta has declined by 52.6 ± 10.2 megatonnes over recent years (1981-2005), of which 33.0 ± 7.1 megatonnes is due to a shift in tropical-cyclone climatology. Consequently, tropical cyclones have a key role in controlling the magnitude of, and variability in, transmission of suspended sediment to the coast. It is likely that anthropogenic sediment trapping in upstream reservoirs is a dominant factor in explaining past, and anticipating future, declines in suspended sediment loads reaching the world's major deltas. However, our study shows that changes in tropical-cyclone climatology affect trends in fluvial suspended sediment loads and thus are also key to fully assessing the risk posed to vulnerable coastal systems

    Ex Vivo Treatment with a Novel Synthetic Aminoglycoside NB54 in Primary Fibroblasts from Rett Syndrome Patients Suppresses MECP2 Nonsense Mutations

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    BACKGROUND: Nonsense mutations in the X-linked methyl CpG-binding protein 2 (MECP2) comprise a significant proportion of causative MECP2 mutations in Rett syndrome (RTT). Naturally occurring aminoglycosides, such as gentamicin, have been shown to enable partial suppression of nonsense mutations related to several human genetic disorders, however, their clinical applicability has been compromised by parallel findings of severe toxic effects. Recently developed synthetic NB aminoglycosides have demonstrated significantly improved effects compared to gentamicin evident in substantially higher suppression and reduced acute toxicity in vitro. RESULTS: We performed comparative study of suppression effects of the novel NB54 and gentamicin on three MECP2 nonsense mutations (R294X, R270X and R168X) common in RTT, using ex vivo treatment of primary fibroblasts from RTT patients harboring these mutations and testing for the C-terminal containing full-length MeCP2. We observed that NB54 induces dose-dependent suppression of MECP2 nonsense mutations more efficiently than gentamicin, which was evident at concentrations as low as 50 µg/ml. NB54 read-through activity was mutation specific, with maximal full-length MeCP2 recovery in R168X (38%), R270X (27%) and R294X (18%). In addition, the recovered MeCP2 was translocated to the cell nucleus and moreover led to parallel increase in one of the most important MeCP2 downstream effectors, the brain derived neurotrophic factor (BDNF). CONCLUSION: Our findings suggest that NB54 may induce restoration of the potentially functional MeCP2 in primary RTT fibroblasts and encourage further studies of NB54 and other rationally designed aminoglycoside derivatives as potential therapeutic agents for nonsense MECP2 mutations in RTT

    A MAP6-Related Protein Is Present in Protozoa and Is Involved in Flagellum Motility

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    In vertebrates the microtubule-associated proteins MAP6 and MAP6d1 stabilize cold-resistant microtubules. Cilia and flagella have cold-stable microtubules but MAP6 proteins have not been identified in these organelles. Here, we describe TbSAXO as the first MAP6-related protein to be identified in a protozoan, Trypanosoma brucei. Using a heterologous expression system, we show that TbSAXO is a microtubule stabilizing protein. Furthermore we identify the domains of the protein responsible for microtubule binding and stabilizing and show that they share homologies with the microtubule-stabilizing Mn domains of the MAP6 proteins. We demonstrate, in the flagellated parasite, that TbSAXO is an axonemal protein that plays a role in flagellum motility. Lastly we provide evidence that TbSAXO belongs to a group of MAP6-related proteins (SAXO proteins) present only in ciliated or flagellated organisms ranging from protozoa to mammals. We discuss the potential roles of the SAXO proteins in cilia and flagella function

    Genetic linkage analysis in the age of whole-genome sequencing

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    For many years, linkage analysis was the primary tool used for the genetic mapping of Mendelian and complex traits with familial aggregation. Linkage analysis was largely supplanted by the wide adoption of genome-wide association studies (GWASs). However, with the recent increased use of whole-genome sequencing (WGS), linkage analysis is again emerging as an important and powerful analysis method for the identification of genes involved in disease aetiology, often in conjunction with WGS filtering approaches. Here, we review the principles of linkage analysis and provide practical guidelines for carrying out linkage studies using WGS data

    Search for new phenomena in multi-body invariant masses in events with at least one isolated lepton and two jets using √s = 13 TeV proton–proton collision data collected by the ATLAS detector

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    A search for resonances in events with at least one isolated lepton (e or μ) and two jets is performed using 139 fb −1 of s = 13 TeV proton–proton collision data recorded by the ATLAS detector at the LHC. Deviations from a smoothly falling background hypothesis are tested in three- and four-body invariant mass distributions constructed from leptons and jets, including jets identified as originating from bottom quarks. Model-independent limits on generic resonances characterised by cascade decays of particles leading to multiple jets and leptons in the final state are presented. The limits are calculated using Gaussian shapes with different widths for the invariant masses. The multi-body invariant masses are also used to set 95% confidence level upper limits on the cross-section times branching ratios for the production and subsequent decay of resonances predicted by several new physics scenarios. [Figure not available: see fulltext.]

    Production of ϒ(nS) mesons in Pb + Pb and pp collisions at 5.02 TeV

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    A measurement of the production of vector bottomonium states, ϒ(1S), ϒ(2S), and ϒ(3S), in Pb + Pb and pp collisions at a center-of-mass energy per nucleon pair of 5.02 TeV is presented. The data correspond to integrated luminosities of 1.38 nb-1 of Pb + Pb data collected in 2018, 0.44 nb-1 of Pb + Pb data collected in 2015, and 0.26 fb-1 of pp data collected in 2017 by the ATLAS detector at the Large Hadron Collider. The measurements are performed in the dimuon decay channel for transverse momentum pμμT < 30 GeV, absolute rapidity |yμμ| < 1.5, and Pb + Pb event centrality 0-80%. The production rates of the three bottomonium states in Pb + Pb collisions are compared with those in pp collisions to extract the nuclear modification factors as functions of event centrality, pμμT, and |yμμ|. In addition, the suppression of the excited states relative to the ground state is studied. The results are compared with theoretical model calculations

    B-Cyclin/CDKs Regulate Mitotic Spindle Assembly by Phosphorylating Kinesins-5 in Budding Yeast

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    Although it has been known for many years that B-cyclin/CDK complexes regulate the assembly of the mitotic spindle and entry into mitosis, the full complement of relevant CDK targets has not been identified. It has previously been shown in a variety of model systems that B-type cyclin/CDK complexes, kinesin-5 motors, and the SCFCdc4 ubiquitin ligase are required for the separation of spindle poles and assembly of a bipolar spindle. It has been suggested that, in budding yeast, B-type cyclin/CDK (Clb/Cdc28) complexes promote spindle pole separation by inhibiting the degradation of the kinesins-5 Kip1 and Cin8 by the anaphase-promoting complex (APCCdh1). We have determined, however, that the Kip1 and Cin8 proteins are present at wild-type levels in the absence of Clb/Cdc28 kinase activity. Here, we show that Kip1 and Cin8 are in vitro targets of Clb2/Cdc28 and that the mutation of conserved CDK phosphorylation sites on Kip1 inhibits spindle pole separation without affecting the protein's in vivo localization or abundance. Mass spectrometry analysis confirms that two CDK sites in the tail domain of Kip1 are phosphorylated in vivo. In addition, we have determined that Sic1, a Clb/Cdc28-specific inhibitor, is the SCFCdc4 target that inhibits spindle pole separation in cells lacking functional Cdc4. Based on these findings, we propose that Clb/Cdc28 drives spindle pole separation by direct phosphorylation of kinesin-5 motors
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