Persistence of the Antibacterial and Antiviral Effects after Skin Cleansing ~A New Approach to Suppress the Contact Infection~.

Handwashing represents an important personal hygiene measure for preventing infection. Herein, we report the persistence of antibacterial and antiviral effects after handwashing with fatty acid salt-based hand soap. To this end, we developed a new in vitro test method to measure persistence, utilizing coacervation formed by anionic surfactants and cationic polymers to retain highly effective soap components against each bacterium and virus on the skin. Coacervation with fatty acid salts and poly diallyldimethylammonium chloride (PDADMAC) as a cationic polymer allowed the persistence of antibacterial and antiviral effects against E. coli, S. aureus, and influenza virus even 4 h after handwashing. Furthermore, we confirmed an increase in the number of residual components effective against each bacterium and virus on the skin. In summary, the current findings describe an effective approach for enhancing the protective effects of handwashing.

Policy frameworks and regulations for the research and development of cell-based meats: Systematic literature review.

Cell-based meats have been discussed in terms of improving sensory factors for consumer acceptance and remedying the environmental problems of conventional livestock production. The improvement accompanies the modification of the production process and the consumption habit regarding cell-based meats. This review analyzed the current status of policies that promote cell-based meats, the related literature, and policy frameworks for the regulation and promotion of cell-based meats in the European Union, Singapore, the United States, Israel, and Japan. Sample selection was based on language, that is, English and Japanese. Further selection was exploratory to analyze the diverse degree of the integration of cell-based meats in policies. The region and countries were selected as leading cases, thereby enabling a policy comparison because they host global corporations that produce cell-based meat. The literature review examined peer-reviewed social science articles from 2013 to early 2022 on policies that promote cell-based meats. The results of the policy surveys revealed that regulations focused on the safety of and measures to display these novel foods by conducting a premarket assessment. These regulations are the basis for developing cell-based meats. Furthermore, some countries and the region being studied justified their support for cell-based meats by implementing action plans for decarbonization and food security. However, unclear communication regarding the nomenclature of cell-based meats is likely to slow down the development of cell-based meats. Moreover, religious beliefs and other cultural perceptions, including animal welfare, leave much room to research such promotion. Similarly, environmental impact assessments of cell-based meats demand further considerations and discussions to accompany evidence-based policymaking for cell-based meats.

Divergence and convergence in international regulatory policies regarding genome-edited food: How to find a middle ground.

Regulations for organisms and products to which genome-editing technologies are applied are increasing in diversity, with the path-dependent effect of previous regulations for genetically modified organisms. Regulations for genome-editing technologies are a patchwork of international regulations that are difficult to harmonize. However, if the approaches are arranged in chronological order and the overall trend is examined, the regulation of genome-edited organisms and GM food products has recently been trending toward a middle ground which can be characterized as "limited convergence." There is a trend toward the adoption of two approaches: one that considers GMOs but tries to apply simplified regulations and another that excludes them from the scope of regulations as non-GMOs but requires confirmation. In this paper, we discuss why there is a tendency toward convergence of these two approaches and examine the challenges and implications of these two approaches for the governance of the agricultural and food sectors.

Theoretical approaches for understanding the self-organized formation of the Golgi apparatus.

Eukaryotic cells fold their membranes into highly organized structures called membrane-bound organelles. Organelles display characteristic structures and perform specialized functions related to their structures. Focusing on the Golgi apparatus, we provide an overview of recent theoretical studies to explain the mechanism of the architecture of the Golgi apparatus. These studies are classified into two categories: those that use equilibrium models to describe the robust Golgi morphology and those that use non-equilibrium models to explain the stationarity of the Golgi structures and the constant streaming of membrane traffic. A combinational model of both categories was used for computational reconstruction of the de novo Golgi formation process, which might provide an insight into the integrated understanding of the Golgi structure.

Implications and Lessons From the Introduction of Genome-Edited Food Products in Japan.

Japan clarified its regulatory approaches for products derived from genome editing technologies in 2019. Consequently, Japan has become a pioneer in the social implementation of such technologies, as to date, the notification process for three products, GABA-enriched tomato, fleshier red sea bream, and high-growth tiger puffer, has been completed. However, this has led to questions about how this was achieved, given the poor consumer acceptance and low public support for genetically modified (GM) foods in the past. This paper describes Japan's regulatory approaches and their implementation guidelines for products created using genome editing technologies. It explains the governance of genome editing technologies and how the derived products have been introduced into society. The three factors that made this possible include: 1) improved R&D environments as a result of government-led innovation policy and regulations which have sought a balance between science and social demand 2) changes in the players (i.e. university startups), that engage in R&D and the strategies used for social introduction, and 3) social value changes-the recent rise in momentum for sustainable development goals (SDGs) and environmental, social, and governance (ESG) investing. The lessons and challenges in terms of R&D policy development and regulation from these analyses are presented. As the market size and social impact of genome-edited food products is limited, it is too early to fully assess this topic for Japan and thus, the analysis in this study is preliminary and must be revisited in the coming years.

Modeling Membrane Morphological Change during Autophagosome Formation.

Autophagy is an intracellular degradation process that is mediated by de novo formation of autophagosomes. Autophagosome formation involves dynamic morphological changes; a disk-shaped membrane cisterna grows, bends to become a cup-shaped structure, and finally develops into a spherical autophagosome. We have constructed a theoretical model that integrates the membrane morphological change and entropic partitioning of putative curvature generators, which we have used to investigate the autophagosome formation process quantitatively. We show that the membrane curvature and the distribution of the curvature generators stabilize disk- and cup-shaped intermediate structures during autophagosome formation, which is quantitatively consistent with in vivo observations. These results suggest that various autophagy proteins with membrane curvature-sensing properties control morphological change by stabilizing these intermediate structures. Our model provides a framework for understanding autophagosome formation.

Discovery of a Potent Anticancer Agent PVHD303 with in Vivo Activity.

As a part of our continuous structure-activity relationship (SAR) studies on 1-(quinazolin-4-yl)-1-(4-methoxyphenyl)ethan-1-ols, the synthesis of derivatives and their cytotoxicity against the human lung cancer cell line A549 were explored. This led to the discovery of 1-(2-(furan-3-yl)quinazolin-4-yl)-1-(4-methoxyphenyl)ethan-1-ol (PVHD303) with potent antiproliferative activity. PVHD303 disturbed microtubule formation at the centrosomes and inhibited the growth of tumors dose-dependently in the HCT116 human colon cancer xenograft model in vivo.

Phagocytosis is mediated by two-dimensional assemblies of the F-BAR protein GAS7.

Phagocytosis is a cellular process for internalization of micron-sized large particles including pathogens. The Bin-Amphiphysin-Rvs167 (BAR) domain proteins, including the FCH-BAR (F-BAR) domain proteins, impose specific morphologies on lipid membranes. Most BAR domain proteins are thought to form membrane invaginations or protrusions by assembling into helical submicron-diameter filaments, such as on clathrin-coated pits, caveolae, and filopodia. However, the mechanism by which BAR domain proteins assemble into micron-scale phagocytic cups was unclear. Here, we show that the two-dimensional sheet-like assembly of Growth Arrest-Specific 7 (GAS7) plays a critical role in phagocytic cup formation in macrophages. GAS7 has the F-BAR domain that possesses unique hydrophilic loops for two-dimensional sheet formation on flat membranes. Super-resolution microscopy reveals the similar assemblies of GAS7 on phagocytic cups and liposomes. The mutations of the loops abolishes both the membrane localization of GAS7 and phagocytosis. Thus, the sheet-like assembly of GAS7 plays a significant role in phagocytosis.

Molecular Dynamics Simulations of Condensin-Mediated Mitotic Chromosome Assembly.

Molecular dynamics simulation is a powerful tool used in modern molecular modeling, which enables a deeper comprehension of the physical behavior of atoms and molecules at a micro level. In this study, we simulated mitotic chromosome assembly mediated by condensins, a class of large protein complexes containing a pair of structural maintenance of chromosomes (SMC) subunits that are central to this process. In this chapter, we present the construction of a coarse-grained physical model of chromosomal DNA fibers and condensin molecules, and monitoring of the function of condensins in mitotic chromosome assembly, using computer-based molecular dynamics simulation. We explain how our model of chromosomes and condensins may be simulated using a package of molecular dynamics simulation. Procedures involved in calculating the observables of dynamics are described, together with an example of the simulation results.

Modeling the functions of condensin in chromosome shaping and segregation.

The mechanistic details underlying the assembly of rod-shaped chromosomes during mitosis and how they segregate from each other to act as individually mobile units remain largely unknown. Here, we construct a coarse-grained physical model of chromosomal DNA and condensins, a class of large protein complexes that plays key roles in these processes. We assume that condensins have two molecular activities: consecutive loop formation in DNA and inter-condensin attractions. Our simulation demonstrates that both of these activities and their balancing acts are essential for the efficient shaping and segregation of mitotic chromosomes. Our results also demonstrate that the shaping and segregation processes are strongly correlated, implying their mechanistic coupling during mitotic chromosome assembly. Our results highlight the functional importance of inter-condensin attractions in chromosome shaping and segregation.

Understanding the public, the visitors, and the participants in science communication activities.

Despite the promotion of public engagement in science, there has been little empirical research on the sociocultural and attitudinal characteristics of participants in science communication activities and the extent to which such individuals are representative of the general population. We statistically investigated the distinctiveness of visitors to a scientific research institution by contrasting samples from visitor surveys and nationally representative surveys. The visitors had more cultural capital (science and technology/art and literature) and believed more in the value of science than the general public, but there was no difference regarding assessment of the levels of national science or of the national economy. A deeper examination of the variations in the visitors' exhibit-viewing behaviors revealed that individuals with more scientific and technical cultural capital viewed more exhibits and stayed longer at the events. This trend in exhibit-viewing behaviors remained consistent among the different questionnaire items and smart-card records.

Measurement of caveolin-1 densities in the cell membrane for quantification of caveolar deformation after exposure to hypotonic membrane tension.

Caveolae are abundant flask-shaped invaginations of plasma membranes that buffer membrane tension through their deformation. Few quantitative studies on the deformation of caveolae have been reported. Each caveola contains approximately 150 caveolin-1 proteins. In this study, we estimated the extent of caveolar deformation by measuring the density of caveolin-1 projected onto a two-dimensional (2D) plane. The caveolin-1 in a flattened caveola is assumed to have approximately one-quarter of the density of the caveolin-1 in a flask-shaped caveola. The proportion of one-quarter-density caveolin-1 increased after increasing the tension of the plasma membrane through hypo-osmotic treatment. The one-quarter-density caveolin-1 was soluble in detergent and formed a continuous population with the caveolin-1 in the caveolae of cells under isotonic culture. The distinct, dispersed lower-density caveolin-1 was soluble in detergent and increased after the application of tension, suggesting that the hypo-osmotic tension induced the dispersion of caveolin-1 from the caveolae, possibly through flattened caveolar intermediates.

Golgi apparatus self-organizes into the characteristic shape via postmitotic reassembly dynamics.

The Golgi apparatus is a membrane-bounded organelle with the characteristic shape of a series of stacked flat cisternae. During mitosis in mammalian cells, the Golgi apparatus is once fragmented into small vesicles and then reassembled to form the characteristic shape again in each daughter cell. The mechanism and details of the reassembly process remain elusive. Here, by the physical simulation of a coarse-grained membrane model, we reconstructed the three-dimensional morphological dynamics of the Golgi reassembly process. Considering the stability of the interphase Golgi shape, we introduce two hypothetical mechanisms-the Golgi rim stabilizer protein and curvature-dependent restriction on membrane fusion-into the general biomembrane model. We show that the characteristic Golgi shape is spontaneously organized from the assembly of vesicles by proper tuning of the two additional mechanisms, i.e., the Golgi reassembly process is modeled as self-organization. We also demonstrate that the fine Golgi shape forms via a balance of three reaction speeds: vesicle aggregation, membrane fusion, and shape relaxation. Moreover, the membrane fusion activity decreases thickness and the number of stacked cisternae of the emerging shapes.

Dynamical pattern selection of growing cellular mosaic in fish retina.

A Markovian lattice model for photoreceptor cells is introduced to describe the growth of mosaic patterns on fish retina. The radial stripe pattern observed in wild-type zebrafish is shown to be selected naturally during retina growth, against the geometrically equivalent circular stripe pattern. The mechanism of such dynamical pattern selection is clarified on the basis of both numerical simulations and theoretical analyses, which find that the successive emergence of local defects plays a critical role in the realization of the wild-type pattern.

Controlling segregation speed of entangled polymers by the shapes: A simple model for eukaryotic chromosome segregation.

We report molecular dynamics simulations of the segregation of two overlapping polymers motivated by chromosome segregation in biological cells. We investigate the relationship between polymer shapes and segregation dynamics and show that elongation and compaction make entangled polymers segregate rapidly. This result suggests that eukaryotic chromosomes take such a characteristic rod-shaped structure, which is induced by condensins, to achieve rapid segregation.

Flat leaf formation realized by cell-division control and mutual recessive gene regulation.

Most of the land plants generally have dorsoventrally flat leaves, maximizing the surface area of both upper (adaxial) side and lower (abaxial) side. The former is specialized for light capturing for photosynthesis and the latter is specialized for gas exchange. From findings of molecular genetics, it has been considered that the coupled dynamics between tissue morphogenesis and gene regulation for cell identity is responsible for making flat leaves. The hypothesis claims that a flat leaf is generated under two assumptions, (i) two mutually recessive groups of genes specify adaxial and abaxial sides of a leaf, (ii) cell divisions are induced at the limited region in the leaf margin where both of two groups are expressed. We examined the plausibility and possibility of this hypothesis from the dynamical point of view. We studied a mathematical model where two processes are coupled, tissue morphogenesis induced by cell division and deformation, and dynamics of gene regulations. From the analysis of the model we found that the classically believed hypothesis is not sufficient to generate flat leaves with high probability. We examined several different modifications and revision of the model. Then we found that a simple additional rule of polarized cell division facilitates flat leaf formation. The result of our analysis gives prediction of possible mechanism, which can be easily verified in experiments.

Mathematical study of pattern formation accompanied by heterocyst differentiation in multicellular cyanobacterium.

The filamentous cyanobacterium, Anabaena sp. PCC 7120, is one of the simplest models of a multicellular system showing cellular differentiation. In nitrogen-deprived culture, undifferentiated vegetative cells differentiate into heterocysts at ~10-cell intervals along the cellular filament. As undifferentiated cells divide, the number of cells between heterocysts (segment length) increases, and a new heterocyst appears in the intermediate region. To understand how the heterocyst pattern is formed and maintained, we constructed a one-dimensional cellular automaton (CA) model of the heterocyst pattern formation. The dynamics of vegetative cells is modeled by a stochastic transition process including cell division, differentiation and increase of cell age (maturation). Cell division and differentiation depend on the time elapsed after the last cell division, the "cell age". The model dynamics was mathematically analyzed by a two-step Markov approximation. In the first step, we determined steady state of cell age distribution among vegetative cell population. In the second step, we determined steady state distribution of segment length among segment population. The analytical solution was consistent with the results of numerical simulations. We then compared the analytical solution with the experimental data, and quantitatively estimated the immeasurable intercellular kinetics. We found that differentiation is initially independent of cellular maturation, but becomes dependent on maturation as the pattern formation evolves. Our mathematical model and analysis enabled us to quantify the internal cellular dynamics at various stages of the heterocyst pattern formation.

Nonlinearity in cytoplasm viscosity can generate an essential symmetry breaking in cellular behaviors.

The cytoplasms of ameboid cells are nonlinearly viscous. The cell controls this viscosity by modulating the amount, localization and interactions of bio-polymers. Here we investigated how the nonlinearity infers the cellular behaviors and whether nonlinearity-specific behaviors exist. We modeled the developed plasmodium of the slime mold Physarum polycephalum as a network of branching tubes and examined the linear and nonlinear viscous cytoplasm flows in the tubes. We found that the nonlinearity in the cytoplasm׳s viscosity induces a novel type of symmetry breaking in the protoplasmic flow. We also show that symmetry breaking can play an important role in adaptive behaviors, namely, connection of behavioral modes implemented on different time scales and transportation of molecular signals from the front to the rear of the cell during cellular locomotion.

Mathematical study for the mechanism of vascular and spot patterns by auxin and pin dynamics in plant development.

Inhomogeneous distribution of auxin is essential in various differentiation processes of plant development. Auxin transfer between cells by efflux carrier protein called PINFORMED (PIN) has been considered to be responsible for inhomogeneous distribution of auxin. Two major types of auxin distribution patterns are "spot" patterns and "passage" patterns, which are responsible for determining the position of the primordia of a leaf or flower in shoot apical meristem and formation of leaf veins, respectively. In this study, we studied the pattern formation of auxin distribution mediated by polarization of PIN using mathematical methods. We developed several different models which show possible interaction mechanisms between auxin and PIN on 2-dimentional hexagonal cellular lattice, (1) Basic auxin flux model, (2) auxin-dependent PIN degradation model and (3) auxin self-feedback model. We analyzed these models by numerical calculation and mathematical analysis. From intensive numerical calculations under different conditions, we found that some models show three different types of pattern formations in dynamics, (a) homogeneous, (b) passage and (c) spot pattern depending on parameter condition. We analyzed these models mathematically using approximation of 1-dimensional periodic space. We determined the conditions that passage and spot patterns are generated in each model, respectively. After these analyses, we propose possible mechanisms by which plants switch passage and spot patterns in different organs by small modification.

A mathematical model for period-memorizing behavior in Physarum plasmodium.

Mathematical models to describe period-memorizing behavior in Physarum plasmodium are reported. In constructing the model, we first examine the basic characteristics required for the class of models, then create a minimal linear model to fulfill these requirements. We also propose two modifications of the minimal model, nonlinearization and noise addition, which improve the reproducibility of experimental evidences. Differences in the mechanisms and in the reproducibility of experiments between our models and the previous models are discussed.