Wakayama Medical University

Fujifilm and Juntendo Hospital in Japan have developed an AI that can accurately predict the risk of falls among outpatients using hospital data. Their research team collated over 500 features associated with falls, including age and prescription history, from hospital data collected in Fujifilm's CITA Clinical Finder. The data platform is used to centrally manage data across various hospital departments, including EMRs, radiology, and endoscopy. An AI model was then trained on these features to predict an individual's fall risk. The technology displays predicted fall risk in percentage and those features that are potential risk factors. The researchers later tested the effectiveness of their AI on data from approximately 70,000 outpatients at Juntendo Hospital. Based on findings from their latest study, the AI scored 96% accuracy in predicting and generating fall risks. According to a media release, Fujifilm and Juntendo will continue testing their AI and seeking its early clinical application. WHY IT MATTERS Hospitals in Japan are said to be challenged in identifying outpatients susceptible to falls given their limited time in their facilities. They also realised that there are more outpatients to assess for fall risks than inpatients. An efficient and accurate solution to prevent falls in medical settings has been increasingly raised and demanded. MARKET SNAPSHOT There are existing studies in Japan that have also utilised AI to help prevent falls in hospitals and nursing homes. Fujitsu and Wakayama Medical University, for one, had worked on trials of a combined sensor and AI technology to detect falls while preserving patient privacy. Meanwhile, Fujifilm's latest AI innovation adds to its growing elderly care technology portfolio. In 2022, it revealed its AI for predicting Alzheimer's disease progression among patients with mild cognitive impairment.

KANAZAWA, Japan, Dec. 19, 2023 /PRNewswire/ -- Researchers at Kanazawa University report in Nature Communications a high-speed atomic force microscopy study of the structural dynamics of sodium ion channels in cell membranes. The findings provide insights into the mechanism behind the generation of cell-membrane action potentials. The transport of ions to and from a cell is controlled by pore-forming proteins embedded in the cell membrane. In particular, so-called voltage-gated sodium channels (VGSCs) govern the transfer of sodium (Na+) ions and play an important role in the regulation of the membrane potential - the voltage difference between the cell's exterior and interior. In electrically excitable cells such as neurons and muscle cells, VGSCs participate in the generation of action potentials; these are rapid changes in the membrane potential enabling the transmission of e.g. neural signals. The precise structural changes occurring in VGSCs are not completely understood, however. Now, Ayumi Sumino and Takashi Sumikama from Kanazawa University in collaboration with Katsumasa Irie from Wakayama Medical University and colleagues have succeeded in observing the structural dynamics of VGSC by means of high-speed atomic force microscopy (HS-AFM), a method capable of imaging the nanostructure and subsecond dynamics of biomolecules. VGSCs can be in three different states: resting, inactive and active. In the latter state, Na+ ions can pass through the channel; in the resting and inactive states, which are structurally different, ions cannot pass. The basic structure of a VGSC consists of two modules: voltage sensor domains and pore domains. These domains form a square arrangement, with the ion pore at its center. An important open question is whether the voltage sensor domains dissociate from the pore domains when the channel closes. Sumino and colleagues performed experiments on three VGSCs. One is the sodium channel of a particular bacterium (Arcobacter butzleri), the other two are mutants thereof. These three VGSCs have different voltage dependencies, with activation voltages starting at -120 mV, -50 mV and 0 mV, so that at the experimental conditions (0 mV), the VGSCs are in different states. In order to provide insights into the structural dynamics of these three VGSCs, the researchers applied HS-AFM, a powerful technique for producing image sequences of biochemical compounds. A single AFM image is generated by laterally moving a tip just above the sample's surface; during this xy-scanning motion, the tip's position in the direction perpendicular to the xy-plane (the z-coordinate) will follow the sample's height profile. The variation of the z-coordinate of the tip then produces a height map - the image of the sample. The generation of such AFM images in rapid succession then produces a video recording of the sample. The HS-AFM results revealed that for the mutant VGSC in the resting state, the voltage sensor domains are indeed dissociated from the pore domains. Furthermore, the researchers found that the dissociated voltage sensor domains of neighboring channels connect to form pairs - this is referred to as dimerization. The observation of the dissociation of voltage sensor domains, as well as the dimerization between pore channels, are findings that will lead to a better understanding of what causes pores to close in the resting state, and how the development of action potentials is regulated. Quoting the scientists, dimerization offers "a potential explanation for the facilitation of positive cooperativity of channel activity in the rising phase of the action potential". Background High-speed atomic force microscopy The principle behind atomic force microscopy (AFM) is to scan the surface of a sample with a very small tip. During this horizontal (xy) scanning, the tip, which is attached to a small cantilever, follows the sample's vertical (z) profile, which induces a force on the cantilever that can be measured. The magnitude of the force at the xy position can be related to the z value. The xyz data generated during a scan then result in a height map providing structural information about the investigated sample. In high-speed-AFM (HS-AFM), the working principle is slightly more involved: the cantilever is made to oscillate near its resonance frequency. When the tip is moved around a surface, the variations in the amplitude (or the frequency) of the cantilever's oscillation - resulting from the tip's interaction with the sample's surface - are recorded, as these provide a measure for the local z value. HS-AFM produces a sequence of AFM images recorded in rapid succession - a video, where the time interval between frames depends on the speed with which a single image can be generated (by xy-scanning the sample). In recent years, researchers at Kanazawa University have further developed HS-AFM so that it can be applied for studying biochemical molecules and biomolecular processes in real-time. Ayumi Sumino and colleagues have now applied the method to study the structural dynamics of Na+ ion channels, revealing the dissociation of channel components and the formation of inter-channel dimers when the channel is in the resting (blocking) state. Reference Ayumi Sumino, Takashi Sumikama, Mikihiro Shibata, and Katsumasa Irie. Voltage sensors of a Na+ channel dissociate from the pore domain and form inter-channel dimers in the resting state, Nature Communications 14, article number 7835 (2023). DOI: 10.1038/s41467-023-43347-3 URL: Figure Figure 1. Caption HS-AFM of the Nav channels. (a and e) Snapshots of HS-AFM movies of WT (open) and E32Q/N49K (closed) channels. (b and f) Time-averaged images of (a) and (e). (c and g) Localization AFM images of (a) and (e). (d and h) Schematic illustration of results. Contact Hiroe Yoneda Senior Specialist in Project Planning and Outreach NanoLSI Administrative Office WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University Kakuma-machi, Kanazawa 920-1192, Japan Email: [email protected] Tel: +81 (76) 234-4550 About Nano Life Science Institute (WPI-NanoLSI) WPI Nano Life Science Institute, Kanazawa University – blogdescription The Nano Life Science Institute of Kanazawa University is unique in the world with the goal of exploring unexplored nano-domains remaining inside and outside cells and understanding the mechanisms of life phenomena at the atomic and molecular level (≒nano-level). A one-of-a-kind research base. Nano Life Science Institute (WPI-NanoLSI), Kanazawa University is a research center established in 2017 as part of the World Premier International Research Center Initiative of the Ministry of Education, Culture, Sports, Science and Technology. The objective of this initiative is to form world-tier research centers. NanoLSI combines the foremost knowledge of bio-scanning probe microscopy to establish 'nano-endoscopic techniques' to directly image, analyze, and manipulate biomolecules for insights into mechanisms governing life phenomena such as diseases. About Kanazawa University Kanazawa University This is an informational site of Kanazawa University As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities. The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas. SOURCE Kanazawa University

KANAZAWA, Japan, Aug. 1, 2023 /PRNewswire/ -- Researchers at Kanazawa University report in Nature Communications how calcium ions can block sodium ion channels located in cell membranes. Structural analysis and computer simulations made it possible to identify where and why calcium ions get stuck. Ion channels are structures within cell membranes that enable specific ions to travel to and from the cell. Such transfer is essential for a variety of physiological processes like muscle cell contraction and nerve excitation. In so-called tetrameric cation channels, the ion selectivity results from the unique structural and chemical environment of the part referred to as the selectivity filter, which is located between two intertwined helical structures. Tetrameric ion channels are prone to 'divalent cation block', the blocking of the channel by ions like calcium (Ca2+). Such blocking disrupts the channel's functioning, which in turn can cause cellular malfunction. How exactly divalent cation block happens is still unclear at the moment — particularly, a direct observation of the cation actually blocking the ion pathway has not been reported yet. Now, Takashi Sumikama from Kanazawa University in collaboration with Katsumasa Irie from Wakayama Medical University and colleagues has discovered the mechanism behind divalent cation block in NavAb, a well-known tetrameric sodium (Na) channel. Through structural analysis and computer simulations, the researchers were able to reveal the relevant structural features and molecular processes at play. NavAb is a sodium channel cloned from a bacterium (Arcobacter butzleri) and has a well-known structure. Sumikama and Irie's colleagues performed experiments with NavAb and three mutants. The structures of the mutants were determined for environments with and without calcium. The scientists focused on the differences in electron densities for the different structures, as these provide insights into the locations of the calcium ions. They found that for the mutants displaying calcium blocking, one or two calcium ions are located at the bottom of the selectivity filter. They also discovered that magnesium (Mg2+) and strontium (Sr2+) ions, two other divalent cations, blocked the calcium-blocking mutant sodium channels. The researchers then performed computer simulations to obtain a detailed understanding of the interaction between the calcium ions and the mutated NavAb channels. The simulations reproduce the dynamics of ions passing — or not passing — the channel. In the absence of calcium ions, sodium ions were observed to penetrate the channel. In the presence of calcium ions, penetration significantly decreased in the calcium-blocking mutants. The simulations also confirmed that the blocking calcium ions are 'stuck' at the bottom of the selectivity filter, and revealed that this 'sticking' is related to the increased hydrophilicity (affinity to water) of relevant structural parts of the mutated channels. The results of Sumikama and Irie's colleagues provide an important step forward towards a full understanding of the mechanism of divalent cation block in NavAb, an important and representative sodium ion channel. Quoting the scientists: "… our results and methods of structural analysis and molecular dynamics simulations are … expected to play an active and meaningful role in the advanced analysis of divalent cation-blocking mechanism." Background Ion channels are proteins embedded in cellular membranes enabling particular ions to pass through the membrane. They are present in the membranes of all types of cells. The regulation of ion transfer across cellular membranes — in particular, the flow of calcium, potassium and sodium ions —is essential for many physiological processes, including insulin release, heart muscle contraction and nerve signaling. Ion channels enable passive ion flow towards equilibrium, which is driven by ion concentration differences across the membrane and the membrane potential (the difference electric potential between the cell interior and exterior). Tetrameric cation channels are the largest and best characterized group of ion channels. For this type of ion channel, the ion pathway lies in a pore domain consisting of two transmembrane helices surrounding the so-called selectivity filter — a unique structural and chemical environment that lets only one species of ion pass. In tetrameric cation channels, a phenomenon known as divalent cation block is known to occur: the blocking of ion transport due to the presence of divalent cations such as calcium (Ca2+) or magnesium (Mg2+). The mechanism underlying cation block is not well understood. But now, by combining structural studies and computer simulations of a bacterium-based tetrameric sodium channel and mutated variants, Takashi Sumikama from Kanazawa University, Katsumasa Irie from Wakayama Medical University and colleagues provide valuable mechanistic insights into the origins of divalent cation block. Reference Katsumasa Irie, Yoshinori Oda, Takashi Sumikama, Atsunori Oshima, and Yoshinori Fujiyoshi. The structural basis of divalent cation block in a tetrameric prokaryotic sodium channel, Nature Communications 14, 4236 (2023). DOI: 10.1038/s41467-023-39987-0 URL: Related finger ©2023 Irie, et al CC BY 4.0 Caption Schematical illustration of the pore domain of a tetrameric cation channel, with the selectivity filter (SF) located between two transmembrane helices (Outer and Inner helix). Contact Hiroe Yoneda Senior Specialist in Project Planning and Outreach NanoLSI Administrative Office WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa UniversityWPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University Kakuma-machi, Kanazawa 920-1192, Japan Email: [email protected] Tel: +81 (76) 234-4550 About Nano Life Science Institute (WPI-NanoLSI) Nano Life Science Institute (NanoLSI), Kanazawa University is a research center established in 2017 as part of the World Premier International Research Center Initiative of the Ministry of Education, Culture, Sports, Science and Technology. The objective of this initiative is to form world-tier research centers. NanoLSI combines the foremost knowledge of bio-scanning probe microscopy to establish 'nano-endoscopic techniques' to directly image, analyze, and manipulate biomolecules for insights into mechanisms governing life phenomena such as diseases. About Kanazawa University As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities. The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas. SOURCE Kanazawa University