Kobe University

An analysis of how synaptic proteins change during early development reveals differences between mice and marmosets but also what's different in individuals with autism spectrum disorders. The findings offer first insights into the mechanism behind synaptic development and open up routes for research on possible treatments. The first analysis of how synaptic proteins change during early development reveals differences between mice and marmosets but also what's different in individuals with autism spectrum disorders. The Kobe University findings offer first insights into the mechanism behind synaptic development and open up routes for research on possible treatments. Given that synapses are the connections between our brain cells, one might think that having as many of these as possible is a good thing. However, primate brains do something unexpected: After early childhood, the connections between brain cells start to decrease in a process called "synaptic pruning." Surprisingly, we know very little about the molecular mechanism behind how synapses change as brains mature and this is also a hurdle for the development of cures to neuropsychological disorders such as the autism spectrum disorder. Both recent developments in the ability to analyze complex protein assemblies and the recent availability of marmosets as non-human primate model organisms for studies on the brain enabled Kobe University neuroscientist TAKUMI Toru to tackle this knowledge gap. He explains, "The Collaboration with experts in proteomics and non-human primate brain has been a critical factor for enabling this study. Also, we have established an analytical pipeline to compare multiple biological data sets using the latest statistical and bioinformatics tools, which was another crucial element." With this, they focused their studies on the analysis of a protein agglomeration found on the signal-receiving side of synapses, the so-called "postsynaptic density," as it has become clear in previous studies that its constituents are key to the development of small mushroom-shaped protrusions on the signal-receiving cells where synapses are formed. Their results, published in the journal Nature Communications, are science's first look at what is happening at the protein level in synapses during brain development in the first weeks, months and years after birth. The Kobe University-led research team identified a group of proteins that are produced more and others that are produced less as time passes and could confirm that this is due to changes in gene regulation. They also found that the timing of this regulation is different in mice and marmosets: What happens in mice two weeks after birth happens before or around birth in marmosets. In addition, marmosets have a second phase of protein changes that mice don't have. "This may be related to the evolutionary differences between rodent and primate brains," comments KAIZUKA Takeshi, the first author of the paper, also in respect to the process of synaptic pruning. Takumi's interest didn't stop there. Knowing that the development of autism spectrum disorder is connected to developmental immaturities of synapses, they investigated what this means on the level of the proteins his group had identified to be connected to synapse development. And indeed, they found that the genes reported to be expressed differentially in autism patients also feature prominently in their data. "These data suggest that the postsynaptic density in autism spectrum disorder patients is relatively similar to that in the prenatal or neonatal period compared to healthy subjects," the researchers write in the study. Being thus able to construct hypotheses on the molecular mechanism behind the emergence of the disorder, this might open up the path for the development of treatments. Takumi sums up the implications of this study. "Synapse development is a crucial issue to consider in the maturation of brains. Its abnormalities are related to neuropsychiatric disorders, including autism spectrum disorders and schizophrenia. The proteome datasets we provided are important for considering molecular mechanisms of synapse development and the difference between rodents and primates." This research was funded by the Japan Society for the Promotion of Science (grants 16H06316, 16H06463, 18K14830, 21H04813, 23H04233, 23KK0132 and 16J04376), the Japan Agency for Medical Research and Development (grants JP21wm0425011 and JP20dm0207001), the Japan Science and Technology Agency (grants JPMJMS2299 and JPMJMS229B), the National Center of Neurology and Psychiatry (grant 30-9), the Takeda Science Foundation, and the Taiju Life Social Welfare Foundation. It was conducted in collaboration with researchers from the RIKEN Center for Brain Science, the RIKEN Center for Sustainable Resource Science, the Max Planck Institute for Experimental Medicine, Hokkaido University and Keio University.

To combine two low-energy photons into one high-energy photon efficiently, the energy must be able to hop freely, but not too quickly, between randomly oriented molecules of a solid. The discovery provides a much-needed design guideline for developing materials for more efficient PV cells, displays, or even anti-cancer therapies. To combine two low-energy photons into one high-energy photon efficiently, the energy must be able to hop freely, but not too quickly, between randomly oriented molecules of a solid. This Kobe University discovery provides a much-needed design guideline for developing materials for more efficient PV cells, displays, or even anti-cancer therapies. Light of different colors has different energies and is therefore useful for very different things. For the development of more efficient PV cells, OLED displays, or anti-cancer therapies it is desirable to be able to upcycle two low-energy photons into a high-energy photon, and many researchers worldwide are working on materials for this up-conversion. During this process, light is absorbed by the material and its energy is handed around amongst the material's molecules as a so-called "triplet exciton." However, it was unclear what allows two triplet excitons to efficiently combine their energies into a different excited state of a single molecule that then emits a high-energy photon, and this knowledge gap has been a serious bottleneck in the development of such materials. Kobe University photoscientist KOBORI Yasuhiro and his research group have been working on a property called the "electron spin states" of moving and interacting excited states. They realized that their expertise was exactly what was needed to solve the problem of up-conversion and applied it on a material especially suitable for their analysis. Kobori explains, "In solution systems, it is difficult to observe the magnetic properties of the electron spins due to the high-speed rotation of the molecules, and in conventional solid-state systems, the reaction efficiency is too low for electron spin resonance studies. The thin-film solid-state material used in our study, however, was suitable for observing the magnetic properties of electron spins and generating sufficient triplet exciton concentrations." Their results, now published in The Journal of Physical Chemistry Letters, show that for the transfer of energies to one light-emitting molecule, the electron spin states of two triplet excitons have to be aligned, which depends on the relative orientation of the participating molecules. For that to happen with a high likelihood, though, the triplet excitons need to be able to move around between molecules of many different orientations. In addition, this hopping must not be too quick, so there is enough time for the interconversion of different excited states. The Kobe University researcher lists the steps necessary to arrive at this conclusion. "We first directly observed the time evolution of the electron spin state inside up-conversion materials in solid-state systems, then modeled the observed electron spin motion, and finally proposed a new theoretical model for how the electron spin state relates to the up-conversion process." These results finally yield a guideline for how to design highly efficient photon up-conversion materials that is based on the knowledge of the process's microscopic mechanism. Kobori explains why this excited him. "I expect this knowledge to contribute to the development of high-efficiency solar cells to alleviate our energy problems, but also to expand into a wide range of fields such as photodynamic cancer therapy and diagnostics that utilize near-infrared light for optical up-conversion without harming the human body." This work was supported by the Japan Society for the Promotion of Science (grants JP20H05832, JP21H05411, JP22K19008, JP20K21174 and JP22K14648), the Japan Science and Technology Agency (grant JPMJPR2101), and the Yukawa Memorial Foundation. It was conducted in collaboration with a researcher from the Tokyo Institute of Technology.

Quantum bits, or qubits, can revolutionize computing and sensing systems. However, cryogenic temperatures are required to ensure the stability of qubits. In a groundbreaking study, researchers observed stable molecular qubits of four electron spins at room temperature for the first time by suppressing the mobility of a dye molecule within a metal-organic framework. Their innovative molecular design opens doors to materials that could drive the development of quantum technologies capable of functioning in real-world conditions. In a study published in Science Advances, a group of researchers led by Associate Professor Nobuhiro Yanai from Kyushu University's Faculty of Engineering, in collaboration with Associate Professor Kiyoshi Miyata from Kyushu University and Professor Yasuhiro Kobori of Kobe University, reports that they have achieved quantum coherence at room temperature: the ability of a quantum system to maintain a well-defined state over time without getting affected by surrounding disturbances This breakthrough was made possible by embedding a chromophore, a dye molecule that absorbs light and emits color, in a metal-organic framework, or MOF, a nanoporous crystalline material composed of metal ions and organic ligands. Their findings mark a crucial advancement for quantum computing and sensing technologies. While quantum computing is positioned as the next major advancement of computing technology, quantum sensing is a sensing technology that utilizes the quantum mechanical properties of qubits (quantum analogs of bits in classical computing that can exist in a superposition of 0 and 1). Various systems can be employed to implement qubits, with one approach being the utilization of intrinsic spin -- a quantum property related to a particle's magnetic moment -- of an electron. Electrons have two spin states: spin up and spin down. Qubits based on spin can exist in a combination of these states and can be "entangled," allowing the state of one qubit to be inferred from another. By leveraging the extremely sensitive nature of a quantum entangled state to environmental noise, quantum sensing technology is expected to enable sensing with higher resolution and sensitivity compared to traditional techniques. However, so far, it has been challenging to entangle four electrons and make them respond to external molecules, that is, achieve quantum sensing using a nanoporous MOF. Notably, chromophores can be used to excite electrons with desirable electron spins at room temperatures through a process called singlet fission. However, at room temperature causes the quantum information stored in qubits to lose quantum superposition and entanglement. As a result, it is usually only possible to achieve quantum coherence at liquid nitrogen level temperatures. To suppress the molecular motion and achieve room-temperature quantum coherence, the researchers introduced a chromophore based on pentacene (polycyclic aromatic hydrocarbon consisting of five linearly fused benzene rings) in a UiO-type MOF. "The MOF in this work is a unique system that can densely accumulate chromophores. Additionally, the nanopores inside the crystal enable the chromophore to rotate, but at a very restrained angle," says Yanai. The MOF structure facilitated enough motion in the pentacene units to allow the electrons to transition from the triplet state to a quintet state, while also sufficiently suppressing motion at room temperature to maintain quantum coherence of the quintet multiexciton state. Upon photoexciting electrons with microwave pulses, the researchers could observe the quantum coherence of the state for over 100 nanoseconds at room temperature. "This is the first room-temperature quantum coherence of entangled quintets," remarks an excited Kobori. While the coherence was observed only for nanoseconds, the findings will pave the way for designing materials for the generation of multiple qubits at room temperatures. "It will be possible to generate quintet multiexciton state qubits more efficiently in the future by searching for guest molecules that can induce more such suppressed motions and by developing suitable MOF structures," speculates Yanai. "This can open doors to room-temperature molecular quantum computing based on multiple quantum gate control and quantum sensing of various target compounds."