Dynein Light Chain Roadblock 1 Regulates FMRP Axonal Transport and Degradation

Okinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyThe fragile X messenger ribonucleoprotein 1 (FMRP) is a multifunctional RNA binding protein (RBP) implicated in human neurodevelopmental and neurodegenerative disorders. FMRP mediates the localization and activitydependent translation of its associated mRNAs through the formation of phase separated condensates that are trafficked by microtubule-based motors in axons. Axonal transport and localized mRNA translation are critical processes for longterm neuronal survival and are closely linked to the pathogenesis of neurological diseases. FMRP dynein-mediated axonal trafficking is still largely unexplored, but likely to constitute a key process underlying FMRP spatiotemporal translational regulation. Here, we show that roadblock 1 (Dynlrb1), a subunit of the dynein complex, is a critical regulator of FMRP function in sensory neurons. In axons, FMRP associates with the dynein complex and is retrogradely trafficked in a Dynlrb1-dependent manner. Moreover, Dynlrb1 silencing induced FMRP granules accumulation and repressed the translation of Map1b, one of its primary mRNA targets. Our findings suggest that Dynlrb1 regulates FMRP function through the control of its transport and degradation.doctoral thesi

Fabrication and Spectroscopic Investigation of a Tunable Magnetic Material and its Heterostructures

Okinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyThe interplay between magnetism and the spin polarized surface states of topological insulators (TIs) can open a gap and give rise to the emergence of exotic states. Such states can be realized by the selective engineering of a magnetic material (MM)/TI heterostructure, inducing magnetic ordering via proximity effects. For this purpose, a tunable layered MM, Cr1+δTe2, is fabricated and investigated in this thesis. A method to systematically control the δ content in molecular beam epitaxy grown thin films is developed. The effect of the δ content on the band structure is visualized by angle-resolved photoemission spectroscopy, revealing a rigid-band-like shift and the resulting tunable Hall properties. The magnetic properties are characterized, revealing the switch of the magnetic anisotropy with δ, explained by the increasing interlayer exchange interactions. To conclude, Cr1.33Te2/Bi2Te3 heterostructures are fabricated and local variations on the magnetic proximity effect are investigated in real space, combining scanning tunneling microscopy/spectroscopy and cross-sectional transmission electron microscopy experiments. A correlation between a spatially inhomogeneous gap opening and distinct Bi2Te3 thicknesses is hypothesized. This thesis provides a universal insight into the direct exploration of quantum phenomena in magnetic TI heterostructures.doctoral thesi

Alarm communication predates eusociality in termites

Termites (Blattodea: Isoptera) have evolved specialized defensive strategies for colony protection. Alarm communication enables workers to escape threats while soldiers are recruited to the source of disturbance. Here, we study the vibroacoustic and chemical alarm communication in the wood roach Cryptocercus and in 20 termite species including seven of the nine termite families, all life-types, and all feeding and nesting habits. Our multidisciplinary approach shows that vibratory alarm signals represent an ethological synapomorphy of termites and Cryptocercus. In contrast, chemical alarms have evolved independently in several cockroach groups and at least twice in termites. Vibroacoustic alarm signaling patterns are the most complex in Neoisoptera, in which they are often combined with chemical signals. The alarm characters correlate to phylogenetic position, food type and hardness, foraging area size, and nesting habits. Overall, species of Neoisoptera have developed the most sophisticated communication system amongst termites, potentially contributing to their ecological success.journal articl

BioNAR: an integrated biological network analysis package in bioconductor

Motivation Biological function in protein complexes emerges from more than just the sum of their parts: molecules interact in a range of different sub-complexes and transfer signals/information around internal pathways. Modern proteomic techniques are excellent at producing a parts-list for such complexes, but more detailed analysis demands a network approach linking the molecules together and analysing the emergent architectural properties. Methods developed for the analysis of networks in social sciences have proven very useful for splitting biological networks into communities leading to the discovery of sub-complexes enriched with molecules associated with specific diseases or molecular functions that are not apparent from the constituent components alone. Results Here, we present the Bioconductor package BioNAR, which supports step-by-step analysis of biological/biomedical networks with the aim of quantifying and ranking each of the network’s vertices based on network topology and clustering. Examples demonstrate that while BioNAR is not restricted to proteomic networks, it can predict a protein’s impact within multiple complexes, and enables estimation of the co-occurrence of metadata, i.e. diseases and functions across the network, identifying the clusters whose components are likely to share common function and mechanisms. Availability and implementation The package is available from Bioconductor release 3.17: https://bioconductor.org/packages/release/bioc/html/BioNAR.html.journal articl

‘Social glands’ in parasitoids? – convergent evolution of metapleural glands in Hymenoptera

For over a century, the metapleural gland, an exocrine gland above the hind coxa, has been thought to be a unique structure for ants (Hymenoptera: Formicidae), and regarded as a catalyst for the ecological and evolutionary success of the family. This gland is one of the most researched exocrine glands in arthropods and its anatomy, ultrastructure, and chemistry are well documented. Herein, we describe an exocrine gland from the proctotrupoid wasp Pelecinus polyturator (Hymenoptera: Pelecinidae) with a similar position, structure, and chemistry to the ant metapleural gland: it is located just above the hind coxa, corresponds to an externally concave and fenestrated atrium, is composed of class 3 gland cells, and its extract contains relatively strong acids. We discover that the pelecinid gland is associated with the dilator muscle of the first abdominal spiracle, a trait that is shared with ants, but remained overlooked, possibly due to its small diameter, or obfuscation by the extensive metapleural gland. We also provide a biomechanical argument for passive emptying of the gland in both taxa. Pelecinids and ants with metapleural glands share a close association with soil. The pelecinid metapleural gland might therefore also have an antiseptic function as suggested for ants. We examined 44 other Hymenoptera families and found no glands associated with the oclusor apodeme or any signs of external modification. Our results strongly indicate that this complex trait (anatomical & chemical) evolved independently in ants and pelecinid wasps providing an exceptional system to better understand exocrine gland evolution in Hymenoptera.journal articl

A tool to promote experimental zoology at the end of the 19th century: the creation of the “Archives de Zoologie Expérimentale et Générale”

1872, France. An eminent zoologist of the time, Henri de Lacaze-Duthiers, realises one of his most important goals: he creates a new journal, focused on zoological discoveries, which he calls “Archives de Zoologie Expérimentale et Générale”. His motivations were threefold. the first was to participate in the intellectual reconstruction of France, humiliated by the defeat against Prussia in 1871. the second was to promote a new way of conceiving and doing zoology: zoology should be approached through experience (and not just observation), and it should be general, including everything related to animal life (embryology, physiology, histology, ecology). the third was to acquire freedom and autonomy by liberating himself from the conservative journal that had a quasi-monopoly on zoology at the time, “les Annales de sciences naturelles”. the Archives, which had a difficult start, had an impressive success, revealing young talents from all over Europe and reporting on major discoveries, until their last issue in 1981. this article recounts their adventure.journal articl

Functional dissection of two amino acid substitutions unique to the human FOXP2 protein

The transcription factor forkhead box P2 (FOXP2) is involved in the development of language and speech in humans. Two amino acid substitutions (T303N, N325S) occurred in the human FOXP2 after the divergence from the chimpanzee lineage. It has previously been shown that when they are introduced into the FOXP2 protein of mice they alter striatal synaptic plasticity by increasing long-term depression in medium spiny neurons. Here we introduce each of these amino acid substitutions individually into mice and analyze their effects in the striatum. We find that long-term depression in medium spiny neurons is increased in mice carrying only the T303N substitution to the same extent as in mice carrying both amino acid substitutions. In contrast, the N325S substitution has no discernable effects.journal articl

Two-way coupled long-wave isentropic ocean-atmosphere dynamics

The events following the 15 January 2022 explosions of the Hunga Tonga-Hunga Ha'apai volcano highlighted the need for a better understanding of ocean-atmosphere interactions when large amounts of energy are locally injected into one (or both). Starting from the compressible Euler equations, a two-way coupled (TWC) system is derived governing the long-wave behaviour of the ocean and atmosphere under isentropic constraint. Bathymetry and topography are accounted for along with three-dimensional atmospheric non-uniformities through their depth average over a spherical shell. A linear analysis, yielding two pairs of gravito-acoustic waves, offers explanations for phenomena observed during the Tonga event. A continuous transcritical regime (in terms of water depth) is identified as the source of large wave generation in deep water bodies, removing the singularity-driven Proudman-type resonance observed in one-way coupled models. The refractive properties, governing the interaction of the atmospheric wave with step changes in water depth, are derived to comment on mode-to-mode energy transfer. Two-dimensional global simulations modelling the propagation of the atmospheric wave (under realistic conditions on the day) and its worldwide effect on oceans are presented. Local maxima of water-height disturbance in the farfield from the volcano, linked to the atmospheric wave deformation (in agreement with observations), are identified, emphasising the importance of the TWC model for any daylong predictions. The proposed framework can be extended to include additional layers and physics, e.g. ocean and atmosphere stratification. With the aim of contributing to warning system improvement, the code necessary to simulate the event with the proposed model is made available.journal articl

Multi-Agent Reinforcement Learning for Distributed Solar-Battery Energy Systems

Okinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyEfficient utilization of renewable energy sources, such as solar energy, is crucial for achieving sustainable development goals. As solar energy production varies in time and space depending on weather conditions, how to combine it with distributed energy storage and exchange systems with intelligent control is an important research issue. In this thesis, I explore the use of reinforcement learning (RL) for adaptive control of energy storage in local batteries and energy sharing through energy grids. I first test multiple RL algorithms for energy storage control of single houses. I then extend the Autonomous Power Interchange System (APIS) from SONY to combine it with reinforcement learning algorithms in each house. I consider different design decisions in applying RL: whether to use centralized or distributed control, at what level of detail actions should be learned, what information is used by each agent, and how much information is shared across agents. Based on these considerations, I implemented deep Q-network (DQN) and prioritized DQN to set the parameters of real-time energy exchange protocol of APIS and tested it using the actual data collected from OIST DC-based Open Energy System (DCOES). The simulation results showed that DQN agents outperform rule-based control on energy sharing and that prioritized experience replay further improves the performance of DQN. Simulation results also suggest that sharing average energy production, storage and usage within the community helps the performance. The results contribute to future designs of distributed intelligent agents and effective operations of energy grid systems.doctoral thesi

Protein Sequence, Structure, and Dynamics Reveal Insights in the Divergence of Protein Functions

Okinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyProteins participate in every important aspect of known living. The amino acid sequence of which a protein is composed contains information about the physicochemical properties, the three-dimensional structure, and its function. However, connecting protein sequence to function is still an open challenge, particularly for protein families with complex inter-relationships, i.e., heteromeric interactions. Such is the case of the Epidermal Growth Factor (EGF) receptor system, comprising four or more paralogs of the EGF receptor interacting with seven or more paralogs of the peptide ligand. In this thesis, I use the evolutionary history of the EGF receptor system to show how phylogenetic patterns of evolution relate to functional divergence at the protein sequence level. By combining measures of residue conservation and residue co-evolution I developed a method to identify residues responsible of a specific protein function. Mutations on the residues highlighted by this method altered the auto-phosphorylation level of the EGF receptor and affected cellular growth. Next, I studied a fish-specific gene duplication of the EGF receptor and used it to describe and model a rare pattern of sequence evolution. I showed that this pattern could be related to functional divergence, thus providing a way to identify the occurrence of the event and the residues responsible of it. Ultimately, I analyzed whole protein families using protein similarity networks. My results showed how the networks made from structural similarity of predicted 3D-models give a better representation of the protein functions compared to sequence similarity networks, thus supporting a paradigm shift from sequence-based to predicted-structure-based bioinformatics software. Overall, my thesis shows a deep interconnection between functional divergence and protein sequence evolution that can be exploited for prediction of function or identification of evolutionary events. The conceptual foundations of this study could be used in other fields where gene duplication and functional residues play an important part, as for example protein engineering and the study of copy number variation in cancer biology.doctoral thesi