Papers please: Predictive factors of national and international attitudes toward immunity and vaccination passports. Online representative surveys

BACKGROUND: In response to the COVID-19 pandemic, countries are introducing digital passports that allow citizens to return to normal activities if they were previously infected with (immunity passport) or vaccinated against (vaccination passport) SARS-CoV-2. To be effective, policy decision-makers must know whether these passports will be widely accepted by the public and under what conditions. This study focuses attention on immunity passports, as these may prove useful in countries both with and without an existing COVID-19 vaccination program; however, our general findings also extend to vaccination passports. OBJECTIVE: We aimed to assess attitudes toward the introduction of immunity passports in six countries, and determine what social, personal, and contextual factors predicted their support. METHODS: We collected 13,678 participants through online representative sampling across six countries—Australia, Japan, Taiwan, Germany, Spain, and the United Kingdom—during April to May of the 2020 COVID-19 pandemic, and assessed attitudes and support for the introduction of immunity passports. RESULTS: Immunity passport support was moderate to low, being the highest in Germany (775/1507 participants, 51.43%) and the United Kingdom (759/1484, 51.15%); followed by Taiwan (2841/5989, 47.44%), Australia (963/2086, 46.16%), and Spain (693/1491, 46.48%); and was the lowest in Japan (241/1081, 22.94%). Bayesian generalized linear mixed effects modeling was used to assess predictive factors for immunity passport support across countries. International results showed neoliberal worldviews (odds ratio [OR] 1.17, 95% CI 1.13-1.22), personal concern (OR 1.07, 95% CI 1.00-1.16), perceived virus severity (OR 1.07, 95% CI 1.01-1.14), the fairness of immunity passports (OR 2.51, 95% CI 2.36-2.66), liking immunity passports (OR 2.77, 95% CI 2.61-2.94), and a willingness to become infected to gain an immunity passport (OR 1.6, 95% CI 1.51-1.68) were all predictive factors of immunity passport support. By contrast, gender (woman; OR 0.9, 95% CI 0.82-0.98), immunity passport concern (OR 0.61, 95% CI 0.57-0.65), and risk of harm to society (OR 0.71, 95% CI 0.67-0.76) predicted a decrease in support for immunity passports. Minor differences in predictive factors were found between countries and results were modeled separately to provide national accounts of these data. CONCLUSIONS: Our research suggests that support for immunity passports is predicted by the personal benefits and societal risks they confer. These findings generalized across six countries and may also prove informative for the introduction of vaccination passports, helping policymakers to introduce effective COVID-19 passport policies in these six countries and around the world

Particle simulation approach for subcellular dynamics and interactions of biological molecules

BACKGROUND: Spatio-temporal dynamics within cells can now be visualized at appropriate resolution, due to the advances in molecular imaging technologies. Even single-particle tracking (SPT) and single fluorophore video imaging (SFVI) are now being applied to observation of molecular-level dynamics. However, little is known concerning how molecular-level dynamics affect properties at the cellular level. RESULTS: We propose an algorithm designed for three-dimensional simulation of the reaction-diffusion dynamics of molecules, based on a particle model. Chemical reactions proceed through the interactions of particles in space, with activation energies determining the rates of these chemical reactions at each interaction. This energy-based model can include the cellular membrane, membranes of other organelles, and cytoskeleton. The simulation algorithm was tested for a reversible enzyme reaction model and its validity was confirmed. Snapshot images taken from simulated molecular interactions on the cell-surface revealed clustering domains (size ~0.2 μm) associated with rafts. Sample trajectories of raft constructs exhibited "hop diffusion". These domains corralled the diffusive motion of membrane proteins. CONCLUSION: These findings demonstrate that our approach is promising for modelling the localization properties of biological phenomena

Domain Growth Kinetics in a Cell-sized Liposome

We investigated the kinetics of domain growth on liposomes consisting of a ternary mixture (unsaturated phospholipid, saturated phospholipid, and cholesterol) by temperature jump. The domain growth process was monitored by fluorescence microscopy, where the growth was mediated by the fusion of domains through the collision. It was found that an average domain size r develops with time t as r ~ t^0.15, indicating that the power is around a half of the theoretical expectation deduced from a model of Brownian motion on a 2-dimensional membrane. We discuss the mechanism of the experimental scaling behavior by considering the elasticity of the membrane

Influences of Excluded Volume of Molecules on Signaling Processes on Biomembrane

We investigate the influences of the excluded volume of molecules on biochemical reaction processes on 2-dimensional surfaces using a model of signal transduction processes on biomembranes. We perform simulations of the 2-dimensional cell-based model, which describes the reactions and diffusion of the receptors, signaling proteins, target proteins, and crowders on the cell membrane. The signaling proteins are activated by receptors, and these activated signaling proteins activate target proteins that bind autonomously from the cytoplasm to the membrane, and unbind from the membrane if activated. If the target proteins bind frequently, the volume fraction of molecules on the membrane becomes so large that the excluded volume of the molecules for the reaction and diffusion dynamics cannot be negligible. We find that such excluded volume effects of the molecules induce non-trivial variations of the signal flow, defined as the activation frequency of target proteins, as follows. With an increase in the binding rate of target proteins, the signal flow varies by i) monotonically increasing; ii) increasing then decreasing in a bell-shaped curve; or iii) increasing, decreasing, then increasing in an S-shaped curve. We further demonstrate that the excluded volume of molecules influences the hierarchical molecular distributions throughout the reaction processes. In particular, when the system exhibits a large signal flow, the signaling proteins tend to surround the receptors to form receptor-signaling protein clusters, and the target proteins tend to become distributed around such clusters. To explain these phenomena, we analyze the stochastic model of the local motions of molecules around the receptor.Comment: 31 pages, 10 figure

Random walk with barriers: Diffusion restricted by permeable membranes

Restrictions to molecular motion by barriers (membranes) are ubiquitous in biological tissues, porous media and composite materials. A major challenge is to characterize the microstructure of a material or an organism nondestructively using a bulk transport measurement. Here we demonstrate how the long-range structural correlations introduced by permeable membranes give rise to distinct features of transport. We consider Brownian motion restricted by randomly placed and oriented permeable membranes and focus on the disorder-averaged diffusion propagator using a scattering approach. The renormalization group solution reveals a scaling behavior of the diffusion coefficient for large times, with a characteristically slow inverse square root time dependence. The predicted time dependence of the diffusion coefficient agrees well with Monte Carlo simulations in two dimensions. Our results can be used to identify permeable membranes as restrictions to transport in disordered materials and in biological tissues, and to quantify their permeability and surface area.Comment: 8 pages, 3 figures; origin of dispersion clarified, refs adde

Curvature-coupling dependence of membrane protein diffusion coefficients

We consider the lateral diffusion of a protein interacting with the curvature of the membrane. The interaction energy is minimized if the particle is at a membrane position with a certain curvature that agrees with the spontaneous curvature of the particle. We employ stochastic simulations that take into account both the thermal fluctuations of the membrane and the diffusive behavior of the particle. In this study we neglect the influence of the particle on the membrane dynamics, thus the membrane dynamics agrees with that of a freely fluctuating membrane. Overall, we find that this curvature-coupling substantially enhances the diffusion coefficient. We compare the ratio of the projected or measured diffusion coefficient and the free intramembrane diffusion coefficient, which is a parameter of the simulations, with analytical results that rely on several approximations. We find that the simulations always lead to a somewhat smaller diffusion coefficient than our analytical approach. A detailed study of the correlations of the forces acting on the particle indicates that the diffusing inclusion tries to follow favorable positions on the membrane, such that forces along the trajectory are on average smaller than they would be for random particle positions.Comment: 16 pages, 8 figure

Syndecans Reside in Sphingomyelin-Enriched Low-Density Fractions of the Plasma Membrane Isolated from a Parathyroid Cell Line

BACKGROUND: Heparan sulfate proteoglycans (HSPGs) are one of the basic constituents of plasma membranes. Specific molecular interactions between HSPGs and a number of extracellular ligands have been reported. Mechanisms involved in controlling the localization and abundance of HSPG on specific domains on the cell surface, such as membrane rafts, could play important regulatory roles in signal transduction. METHODOLOGY/PRINCIPAL FINDINGS: Using metabolic radiolabeling and sucrose-density gradient ultracentrifugation techniques, we identified [(35)S]sulfate-labeled macromolecules associated with detergent-resistant membranes (DRMs) isolated from a rat parathyroid cell line. DRM fractions showed high specific radioactivity ([(35)S]sulfate/mg protein), implying the specific recruitment of HSPGs to the membrane rafts. Identity of DRM-associated [(35)S]sulfate-labeled molecules as HSPGs was confirmed by Western blotting with antibodies that recognize heparan sulfate (HS)-derived epitope. Analyses of core proteins by SDS-PAGE revealed bands with an apparent MW of syndecan-4 (30-33 kDa) and syndecan-1 (70 kDa) suggesting the presence of rafts with various HSPG species. DRM fractions enriched with HSPGs were characterized by high sphingomyelin content and found to only partially overlap with the fractions enriched in ganglioside GM1. HSPGs could be also detected in DRMs even after prior treatment of cells with heparitinase. CONCLUSIONS/SIGNIFICANCE: Both syndecan-1 and syndecan-4 have been found to specifically associate with membrane rafts and their association seemed independent of intact HS chains. Membrane rafts in which HSPGs reside were also enriched with sphingomyelin, suggesting their possible involvement in FGF signaling. Further studies, involving proteomic characterization of membrane domains containing HSPGs might improve our knowledge on the nature of HSPG-ligand interactions and their role in different signaling platforms

Monte Carlo Investigation of Diffusion of Receptors and Ligands that Bind Across Opposing Surfaces

Studies of receptor diffusion on a cell surface show a variety of behaviors, such as diffusive, sub-diffusive, or super-diffusive motion. However, most studies to date focus on receptor molecules diffusing on a single cell surface. We have previously studied receptor diffusion to probe the molecular mechanism of receptor clustering at the cell–cell junction between two opposing cell surfaces. Here, we characterize the diffusion of receptors and ligands that bind to each other across two opposing cell surfaces, as in cell–cell and cell–bilayer interactions. We use a Monte Carlo method, where receptors and ligands are simulated as independent agents that bind and diffuse probabilistically. We vary receptor–ligand binding affinity and plot the molecule-averaged mean square displacement (MSD) of ligand molecules as a function of time. Our results show that MSD plots are qualitatively different for flat and curved interfaces, as well as between the cases of presence and absence of directed transport of receptor–ligand complexes toward a specific location on the interface. Receptor–ligand binding across two opposing surfaces leads to transient sub-diffusive motion at early times provided the interface is flat. This effect is entirely absent if the interface is curved, however, in this instance we observe sub-diffusive motion. In addition, a decrease in the equilibrium value of the MSD occurs as affinity increases, something which is absent for a flat interface. In the presence of directed transport of receptor–ligand complexes, we observe super-diffusive motion at early times for a flat interface. Super-diffusive motion is absent for a curved interface, however, in this case we observe a transient decrease in MSD with time prior to equilibration for high-affinity values

GWAS of bipolar disorder

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10−9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (P best=5.8 × 10−10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (P best=1.9 × 10−9), TRANK1 (P best=2.1 × 10−9) and ODZ4 (P best=3.3 × 10−9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for ‘within Japanese comparisons’, Pbest~10−29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for ‘trans-European-Japanese comparison,’ Pbest~10−13, R2~0.27%). This ‘trans population’ effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD ‘risk’ effect are shared between Japanese and European populations