161 research outputs found

    Vortex interaction, chaos and quantum probabilities

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    The motion of a single vortex is able to originate chaos in the quantum trajectories defined in Bohm's interpretation of quantum mechanics. In this Letter, we show that this is also the case in the general situation, in which many interacting vortices exist. This result gives support to recent attempts in which Born's probability rule is derived in terms of an irreversible time evolution to equilibrium, rather than being postulated.Comment: 4 pages, 4 figure

    Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population

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    Acknowledgements Generation Scotland has received core funding from the Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 and the Scottish Funding Council HR03006. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants and nurses. We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. For the Lothian Birth Cohorts (LBC1921 and LBC1936), we thank Paul Redmond for database management assistance; Alan Gow, Martha Whiteman, Alison Pattie, Michelle Taylor, Janie Corley, Caroline Brett and Caroline Cameron for data collection and data entry; nurses and staff at the Wellcome Trust Clinical Research Facility, where blood extraction and genotyping was performed; staff at the Lothian Health Board; and the staff at the SCRE Centre, University of Glasgow. The research was supported by a program grant from Age UK (Disconnected Mind) and by grants from the Biotechnology and Biological Sciences Research Council (BBSRC). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Medical Research Council (MRC) and BBSRC is gratefully acknowledged. DJM is an NRS Career Research Fellow funded by the CSO. BATS were funded by the Australian Research Council (A79600334, A79906588, A79801419, DP0212016, DP0664638, and DP1093900) and the National Health and Medical Research Council (389875) Australia. MKL is supported by a Perpetual Foundation Wilson Fellowship. SEM is supported by a Future Fellowship (FT110100548) from the Australian Research Council. GWM is supported by a National Health and Medical Research Council (NHMRC), Australia, Fellowship (619667). We thank the twins and siblings for their participation, Marlene Grace, Ann Eldridge and Natalie Garden for cognitive assessments, Kerrie McAloney, Daniel Park, David Smyth and Harry Beeby for research support, Anjali Henders and staff in the Molecular Epidemiology Laboratory for DNA sample processing and preparation and Scott Gordon for quality control and management of the genotypes. This work is supported by a Stragetic Award from the Wellcome Trust, reference 104036/Z/14/Z.Peer reviewedPublisher PD

    The ESCRT-III machinery participates in the production of extracellular vesicles and protein export during Plasmodium falciparum infection

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    Malaria is a disease caused by Plasmodium parasites that is still a leading cause of death in many low-income countries, and for which currently available therapeutic strategies are not succeeding in its control, let alone eradication. An interesting feature observed after Plasmodium invasion is the increase of extracellular vesicles (EVs) generated by parasitized red blood cells (pRBCs), which lack a vesicular trafficking that would explain EV production. Here, by combining different approaches, we demonstrated the participation of the endosomal sorting complex required for transport (ESCRT) machinery from Plasmodium falciparum in the production of EVs in pRBCs. Moreover, we were able to detect ESCRT-III proteins adjacent to the membrane of the host and in EVs purified from a pRBC culture, which shows the export of these proteins and their participation in EV production. Finally, the disruption of an ESCRT-III associated gene, Pfvps60, led to a significant reduction in the amount of EVs. Altogether, these results confirm ESCRT-III participation in EV production and provide novel information on the P. falciparum protein export mechanisms, which can be used for the development of new therapeutic strategies against malaria, based on the disruption of EV formation and trafficking

    Synthesis and reactivity of 4-oxo-5-trimethylsilanyl derived α-amino acids

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    A Lewis-acid promoted one-carbon homologation of an aspartic acid semialdehyde with trimethylsilyldiazomethane has led to the efficient synthesis of two silicon-containing α-amino acids. The use of trimethylaluminium or catalytic tin(II) chloride gave novel 4-oxo-5-trimethylsilanyl derived amino acids in yields of 71–88%. An investigation into the reactivity of these highly functional α-amino acids showed that selective cleavage of the C–Si bond could be achieved under mild basic conditions to give a protected derivative of the naturally occurring amino acid, 4-oxo-l-norvaline. Alternatively, Peterson olefination with aryl or alkyl aldehydes resulted in the formation of E-enone derived α-amino acids

    A striking correspondence between the dynamics generated by the vector fields and by the scalar parabolic equations

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    The purpose of this paper is to enhance a correspondence between the dynamics of the differential equations y˙(t)=g(y(t))\dot y(t)=g(y(t)) on Rd\mathbb{R}^d and those of the parabolic equations u˙=Δu+f(x,u,u)\dot u=\Delta u +f(x,u,\nabla u) on a bounded domain Ω\Omega. We give details on the similarities of these dynamics in the cases d=1d=1, d=2d=2 and d3d\geq 3 and in the corresponding cases Ω=(0,1)\Omega=(0,1), Ω=T1\Omega=\mathbb{T}^1 and dim(Ω\Omega)2\geq 2 respectively. In addition to the beauty of such a correspondence, this could serve as a guideline for future research on the dynamics of parabolic equations

    Single-molecule imaging of glycan-lectin interactions on cells with Glyco-PAINT

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    Most lectins bind carbohydrate ligands with relatively low affinity, making the identification of optimal ligands challenging. Here we introduce a point accumulation in nanoscale topography (PAINT) super-resolution microscopy method to capture weak glycan-lectin interactions at the single-molecule level in living cells (Glyco-PAINT). Glyco-PAINT exploits weak and reversible sugar binding to directly achieve single-molecule detection and quantification in cells and is used to establish the relative kon and koff rates of a synthesized library of carbohydrate-based probes, as well as the diffusion coefficient of the receptor-sugar complex. Uptake of ligands correlates with their binding affinity and residence time to establish structure-function relations for various synthetic glycans. We reveal how sugar multivalency and presentation geometry can be optimized for binding and internalization. Overall, Glyco-PAINT represents a powerful approach to study weak glycan-lectin interactions on the surface of living cells, one that can be potentially extended to a variety of lectin-sugar interactions.NWOICI-024.002.009Bio-organic Synthesi

    Super-resolution correlative light-electron microscopy using a click-chemistry approach for studying intracellular trafficking

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    Correlative light and electron microscopy (CLEM) entails a group of multimodal imaging techniques that are combined to pinpoint to the location of fluorescently labeled molecules in the context of their ultrastructural cellular environment. Here we describe a detailed workflow for STORM-CLEM, in which STochastic Optical Reconstruction Microscopy (STORM), an optical super-resolution technique, is correlated with transmission electron microscopy (TEM). This protocol has the advantage that both imaging modalities have resolution at the nanoscale, bringing higher synergies on the information obtained. The sample is prepared according to the Tokuyasu method followed by click-chemistry labeling and STORM imaging. Then, after heavy metal staining, electron microscopy imaging is performed followed by correlation of the two images. The case study presented here is on intracellular pathogens, but the protocol is versatile and could potentially be applied to many types of samples.Microscopic imaging and technolog

    Antimicrobial and cell-penetrating peptides induce lipid vesicle fusion by folding and aggregation

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    According to their distinct biological functions, membrane-active peptides are generally classified as antimicrobial (AMP), cell-penetrating (CPP), or fusion peptides (FP). The former two classes are known to have some structural and physicochemical similarities, but fusogenic peptides tend to have rather different features and sequences. Nevertheless, we found that many CPPs and some AMPs exhibit a pronounced fusogenic activity, as measured by a lipid mixing assay with vesicles composed of typical eukaryotic lipids. Compared to the HIV fusion peptide (FP23) as a representative standard, all designer-made peptides showed much higher lipid-mixing activities (MSI-103, MAP, transportan, penetratin, Pep1). Native sequences, on the other hand, were less fusogenic (magainin 2, PGLa, gramicidin S), and pre-aggregated ones were inactive (alamethicin, SAP). The peptide structures were characterized by circular dichroism before and after interacting with the lipid vesicles. A striking correlation between the extent of conformational change and the respective fusion activities was found for the series of peptides investigated here. At the same time, the CD data show that lipid mixing can be triggered by any type of conformation acquired upon binding, whether α-helical, β-stranded, or other. These observations suggest that lipid vesicle fusion can simply be driven by the energy released upon membrane binding, peptide folding, and possibly further aggregation. This comparative study of AMPs, CPPs, and FPs emphasizes the multifunctional aspects of membrane-active peptides, and it suggests that the origin of a peptide (native sequence or designer-made) may be more relevant to define its functional range than any given name
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