Okazaki National Research Institutes

From bird flocks and fish schools to migrating cell sheets, collective motion is a ubiquitous biological phenomenon that inspires quantitative modeling through self-propelled particle (SPP) frameworks. Conventional SPP models prescribe either distance-based (metric) or rank-based (topological) interactions; however, empirical studies indicate that real groups may blend both types of interaction. Motivated by this graded perception, we introduce an extended three-dimensional SPP model in which metric and topological alignments act simultaneously and are weighted by a single tunable blending parameter called the interaction parameter. Large-scale simulations spanning a wide range of interaction parameters, densities, and neighborhood sizes revealed rich dynamics. Even when the global order parameter is low, cluster-level analysis with HDBSCAN shows that particles self-organize into several spatially distinct but internally well-aligned sub-flocks, exposing a hidden layer of order. Most importantly, an intermediate balance in which metric and topological cues contribute almost equally maximizes the global order parameter and markedly improves robustness to density variations. Numerical experiments supported by linear stability analysis demonstrate that activating metric and topological interactions in concert bridges the traditional modeling dichotomy and furnishes a more adaptive and resilient framework for collective motion. Therefore, the proposed model provides a versatile platform for exploring mixed-interaction effects in biological and engineered multi-agent systems. • Developed 3D SPP model that applies two interaction types in tunable proportions. • Introduced quantitative indicator for to evaluate local clusters in SPP simulations. • Increasing complexity of interactions enhances robustness of single-flock formation.

We investigate the impact of glycoform alterations on the dynamic structure of the human immunoglobulin G1 (IgG1) Fc region using integrated computational and experimental approaches. Four distinct IgG1-Fc glycoforms, varying in core fucosylation and nonreducing terminal galactosylation, were generated through a combination of cell engineering and in vitro enzymatic reactions. Stable-isotope-assisted NMR spectroscopy, incorporating both glycan and protein signals, revealed that galactosylation induces chemical shift perturbations extending from the glycan-protein interface to the CH2-CH3 domain boundary. Molecular dynamics simulations demonstrated that the absence of galactose enhances the mobility of both the glycan and the CH2 domain, broadening the conformational landscape of the Fc quaternary structure. This increased flexibility likely contributes to a greater entropic penalty upon binding to effector molecules, which constrain the Fc in an asymmetric conformation. Conversely, the effects of fucosylation are more localized, primarily influencing the dynamics of residues involved in Fcγ receptor IIIa binding. These findings provide atomic-level insights into the distinct yet synergistic mechanisms by which galactosylation and fucosylation modulate IgG1-Fc dynamics and effector functions, offering crucial information for the optimization of therapeutic antibodies.

The characteristics of a gas-temperature-controllable atmospheric-pressure helium plasma jet and the development of an experimental system for cell viability assays of yeasts (fission yeast Schizosaccharomyces pombe and budding yeast Saccharomyces cerevisiae) are reported. The physicochemical properties of the plasma plume, which can maintain the temperature of the irradiated object at a temperature suitable for yeast, were not significantly different from those of a typical helium plasma jet. Furthermore, good reproducibility of cell viability was observed when gas temperature, gas flow rate, applied high voltage, and irradiation distance remained fixed, and only irradiation time was used as a parameter. This experimental system allows us to carry out various experiments, such as the search for plasma-resistant mutants that will contribute to the identification of genes involved in resistance to direct plasma irradiation.

Wnt2022 was held on November 15th-19th, 2022, in Awaji Yumebutai International Conference Center, Hyogo Prefecture, Japan, as an in-person meeting for the first time in last 3 years. Wnt signaling is a highly conserved pathway among various species. Since Wnt1 was discovered in 1982, a number of studies using many model animals and human samples have revealed that Wnt signaling plays crucial roles in embryonic development, tissue morphogenesis, and regeneration, as well as many other physiological and pathological processes. Since the year 2022 marks the 40th anniversary of Wnt research, we aimed to look back at our research progress and discuss the future direction of this field. The scientific program consisted of plenary lectures, invited talks, short talks selected from abstracts, and poster sessions. Whereas several different Wnt meetings have been held almost every year in Europe and the United States, this was the first Wnt meeting convened in Asia. Therefore, Wnt2022 was highly anticipated to bring together leaders and young scientists from Europe, the United States, and especially Asia and Oceania. In fact, 148 researchers from 21 countries attended this meeting. Although there were travel and administrative restrictions due to COVID-19, the meeting was highly successful in enabling face-to-face discussions.

Abstract Protein complexes exert various functions through allosterically controlled cooperative work. De novo design of allosteric control into protein complexes provides understanding of their working principles and potential tools for synthetic biology. Here, we hypothesized that an allosteric control can be created by restoring lost functions of pseudo-enzymes contained as subunits in protein complexes. This was demonstrated by computationally de novo designing ATP binding ability of the pseudo-enzyme subunits in a rotary molecular motor, V1-ATPase. Single molecule experiments with solved crystal structures revealed that the designed V1is allosterically accelerated than the wild-type by the ATP binding to the created allosteric site and the rate is tunable by modulating the binding affinity. This work opened up an avenue for programming allosteric control into proteins exhibiting concerted functions.

Although DNA can form triplex and quadruplex structures through hydrogen bonds, design and preparation of structures with more than five strands is difficult even when artificial nucleic acids are used. Herein we report a hexaplex formed by oligomers of artificial nucleic acids bearing bifacial molecules on d-threoninol. Aminopyrimidine and cyanuric acid derivatives were selected as bases because they have complementary hydrogen bonding patterns. The complex formed by aminopyrimidine and cyanuric acid decamers melted with large hysteresis. Hexaplex formation was indicated by gel electrophoresis, size exclusion chromatography and atomic force microscopy imaging, and proven directly through native mass spectrometry. CD measurements and molecular dynamics simulations indicated that the hexaplex adopts a helical structure. The hexaplex formation was highly dependent on pH and the presence of divalent cations. The hexaplex was stable in aqueous solution, and its unique structure and properties may lead to novel nanostructures, molecular assemblies, metal sensors, and ion channels.

Abstract Review: [114 refs.]

In Daphnia pulex, juveniles form "neckteeth" a defensive structure on their heads, in response to predatory kairomones released by Chaoborus larvae. This phenomenon provides a model experimental system for the study of developmental mechanisms and evolutionary processes in predator-induced polyphenisms. Although it is thought that kairomone signals are sensed and converted into physiological signals resulting in morphological changes, little is known about the endocrine and physiological mechanisms of this process. Juvenile hormones and related chemicals, that is, juvenoids, are key hormones responsible for various physiological events in insects, including polyphenisms. In some crustaceans, methyl farnesoate (MF) is known to act as a juvenoid. In order to investigate the functions of juvenoids in defense morph formation, we treated daphnids with MF as well as JHIII (Juvenile Hormone III, an insect juvenoid) and fenoxycarb (a synthetic juvenile hormone analog) during their developmental stages. Strikingly, in the first-instar juveniles, all examined juvenoids stimulated the formation of neckteeth only in the presence of kairomones, not by themselves. This juvenoid effect on the neckteeth formation might be due to disturbance of the JH pathway. Juvenoid treatments reduced tail-spine length, whereas predatory kairomones are known to elongate tail spine. These results suggest that other physiological factors are responsible for the tail-spine elongation.