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Kanazawa University research: Ion channel block unraveled

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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/s41467-023-39987-0URL: https://www.nature.com/articles/s41467-023-39987-0 
Related fingerhttps://nanolsi.kanazawa-u.ac.jp/wp/wp-content/uploads/Figure1-2.png
©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 OutreachNanoLSI Administrative OfficeWPI Nano Life Science Institute (WPI-NanoLSI)Kanazawa UniversityWPI Nano Life Science Institute (WPI-NanoLSI)Kanazawa UniversityKakuma-machi, Kanazawa 920-1192, JapanEmail: [email protected]: +81 (76) 234-4550
About Nano Life Science Institute (WPI-NanoLSI) https://nanolsi.kanazawa-u.ac.jp/en/  
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 http://www.kanazawa-u.ac.jp/e/
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.
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Thundercomm Launches RUBIK Pi on Qualcomm Platforms

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Making Application Development with AI Inference More Accessible
AUSTIN, Texas, Oct. 8, 2024 /PRNewswire/ — Embedded World — At an industry event in Austin today, Thundercomm announces RUBIK Pi, the first Pi built on Qualcomm® SoC platforms for developers. RUBIK Pi is an innovative tool that aims to lower the barriers application development with AI inference, allowing developers to access high-performance, easy-to-deploy AI R&D tools

The Pi product is a must-have for electronics enthusiasts and developers. It can be seen as a microcomputer, integrating a processor, memory, storage, and various interfaces on a credit card-sized board. Thundercomm, a world-leading IoT product and solution provider, building on its expertise in ICT technologies and developer workflows, launched RUBIK Pi, aiming to create the most user-friendly AI R&D tools.
RUBIK Pi utilizes the Qualcomm® QCS6490 processor, delivering 12.5 TOPS of AI inference performance and support for a 1.8 billion-parameter LLM. With Qualcomm® AI Hub, developers can explore cutting-edge tools that allow developer to download pre-optimized AI models or optimize their custom model to get the best performance from the SoC
RUBIK Pi supports Qualcomm® Linux®, Android, and Windows, ensuring broad operating system compatibility. It also features upward compatibility with Thundercomm’s C8550 SOM and downward compatibility with the C5430P SOM, providing robust scalability for developers.
“We’re excited to see Thundercomm launch RUBIK Pi. It’s the first Pi product built on the Qualcomm® SoC platform, supporting Qualcomm® Linux® and  Android, Windows, and Ubuntu,” said Manvinder Singh, VP, Product Management, Partner Solutions, Developer Experience, Industrial and Embedded IoT, Qualcomm Technologies, Inc. “It has a rich set of IO interfaces and delivers unrivaled compute and AI performance to unleash developer creativity. With the support of Qualcomm® Al Hub, developers will be able to quickly deploy optimized AI models on RUBIK Pi.”
“RUBIK Pi is a lightweight development board that is not only easy to use and is low cost but also holds significant ESG value. By making AI application development accessible to beginners, it promotes AI education, enhances technological literacy, and fosters social equity,” said Pier Zhang, Vice President of Thundercomm.
Preliminary orders of RUBIK Pi will be available at the beginning of November. For more information on RUBIK Pi, please visit the webpage.
About Thundercomm
Thundercomm, headquartered in San Diego, is a joint venture with Qualcomm®. Thundercomm was established to accelerate innovation in the Internet of Things and automotive industry, providing one-stop solutions powered by Qualcomm Technologies. Learn more at www.thundercomm.com
The registered trademark Linux® is used pursuant to a sublicense from the Linux Foundation, the exclusive licensee of Linus Torvalds, owner of the mark on a worldwide basis.
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Precisely Announces Breakthrough in Data Enrichment with New Data Graph API

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Unified access to a connected network of trusted datasets empowers users with enhanced query capabilities to gain valuable insights  
BURLINGTON, Mass., Oct. 8, 2024 /PRNewswire/ — Precisely, the global leader in data integrity, today announced the Data Graph API, a new addition to the Data Enrichment service within the Precisely Data Integrity Suite, during its Trust ’24 Data Integrity Summit in Philadelphia. For the first time, a single API offers simplified access to the Precisely data portfolio for flexible queries, data enrichment, and enhanced data discovery. Supported by the PreciselyID, the company’s unique and persistent identifier for any addressable location, the Data Graph API reduces complexity, ensures consistency, and speeds up the data enrichment process, accelerating time-to-value.

Data enrichment, the process of augmenting company data with carefully curated third-party data to improve its overall value, accuracy, and usability, is fast becoming a critical priority for organizations. This is especially true for companies looking to ensure that initiatives, such as AI and machine learning, are driven by contextually relevant data. In fact, research indicates a 22% increase in use of data enrichment as a key strategy for improving data integrity year over year. Despite this, many organizations continue to struggle with the time-consuming and often manual process of accurately integrating third-party data.
Powered by GraphQL technology, the Data Graph API dramatically simplifies data enrichment by enabling users to specify their data needs in a single query. The API filters and organizes the data before delivery, ensuring that businesses receive only the most relevant information according to their needs.  
Korem, a leading expert in geospatial technologies, and design partner for the Data Graph API, are looking forward to implementing the new functionality into their solutions to support a wide range of industry use cases. “We are excited about the launch of the new Data Graph API from Precisely,” said Jonathan Houde, CTO at Korem. “Instead of licensing entire datasets or making multiple web service calls, our customers can now access all the necessary information through one efficient and cost-effective service.”
At the heart of the Data Graph API is the PreciselyID, which allows customers to connect addresses to a wealth of trusted data for additional insight, such as relationships between buildings, parcels, property attributes, addresses, demographics, natural perils, and more. The Data Graph API simplifies queries to the rich portfolio of Precisely connected data and can facilitate the same easy access to data from industry partners. One such partner is GeoX, an aerial image processing company that provides property intelligence data to the insurance industry. As an industry partner, GeoX integrates their property intelligence into the Data Graph API, enabling insurers to enhance risk assessments, accurately underwrite policies, and predict and prevent losses by establishing a complete, 360-degree view of residential and commercial properties.
“The launch of the Data Graph API fundamentally transforms how companies bring together data to enhance the contextual relevance of AI and advanced analytics,” said Dan Adams, Senior Vice President and General Manager for Data Enrichment at Precisely. “Our data enrichment portfolio is designed to work together seamlessly, using unique identifiers to create a network of connected data where all feature relationships are mapped across datasets. As we extend this by pre-linking data from our trusted partners, the possibilities become limitless. We know this will save our customers time, allowing them to focus more on innovation rather than data preparation.”
The Data Graph API and a broad range of other market-leading tools are available in the company’s recently announced Precisely Data Integrity Suite Developer Portal, providing developer-friendly tools and resources to shorten the time it takes to build applications.
Learn more about the Data Graph API and how it helps customers to unlock a new world of data enrichment or register for the virtual Trust ’24 event taking place October 15 – 16 to hear about the latest data integrity innovations.
About PreciselyAs a global leader in data integrity, Precisely ensures that your data is accurate, consistent, and contextual. Our portfolio, including the Precisely Data Integrity Suite, helps integrate your data, improve data quality, govern data usage, geocode and analyze location data, and enrich with complementary datasets for confident business decisions. Over 12,000 organizations in more than 100 countries, including 93 of the Fortune 100, trust Precisely software, data, and strategy services to power AI, automation, and analytics initiatives. Learn more at www.precisely.com.
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Precisely Advances Data Integrity Foundation to Power Data Management at Scale

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Common foundation enables interoperability of Precisely Data Integrity Suite services to accelerate delivery of trusted data for analytics and AI initiatives
BURLINGTON, Mass., Oct. 8, 2024 /PRNewswire/ — Precisely, the global leader in data integrity, today announced significant enhancements to its Precisely Data Integrity Suite during its Trust ’24 Data Integrity Summit in Philadelphia. The Data Integrity Foundation that drives the Data Integrity Suite is now expanded to include a new connector framework, advanced data catalog, hybrid execution agents, workflow orchestration, AI-driven intelligence, and more. In addition, Precisely improves the performance of the Data Integrity Suite’s user experience and introduces a new Developer Portal to deliver tools and resources that enable developers to build data integrity into their applications.

 
 
“The advancements in the Data Integrity Foundation significantly streamline the services in the Data Integrity Suite,” said Chris Hall, Chief Product Officer, Precisely. “By eliminating the complexities associated with integrating, configuring, and maintaining multiple solutions, the Suite reduces costs and resource requirements, enabling data teams to focus on driving strategic analytics and AI initiatives. The Data Integrity Suite’s unified and accelerated user experience enables our customers to drive deeper engagement with their data and sets the stage for new and innovative approaches to business problems.”
The Data Integrity Foundation powers the interoperable SaaS services of the Data Integrity Suite. Key elements of the newly expanded Foundation include:
Comprehensive Data and Metadata Connectors provide a common framework for centrally managing and reusing any connection across all Data Integrity Suite services, reducing the complexity of managing multiple connections and saving time and resources.Advanced Data Catalog shared by all Data Integrity Suite services provides a high-performance, searchable metadata repository designed to surface insights about data, monitor its health, and visualize data relationships, lineage, and business impact.AI-driven Intelligence has expanded to proactively detect data errors, send alerts, and automate data cleansing, validation, and business rule generation. Intelligence also accelerates data integrity pipeline development by providing smart recommendations for next steps and data enrichment options to reduce the time spent manually managing data.In addition, the Foundation provides the flexibility to run and tune multiple AI models for different use cases while centrally managing those models to ease security and compliance concerns.
Workflow Orchestration enables Data Integrity Suite users to design, manage, and automate tasks from one central place, reducing costs, minimizing human errors, and fostering collaboration between technical and business teams.Hybrid Execution Agents securely run data integrity processes and pipelines wherever data lives, enabling customers to choose between the control of on-premises environments and the elasticity and scalability of the cloud while porting and reusing processes as data environments change.”In our ongoing commitment to make data easy to discover, understand, and use reliably, we are procuring the Precisely Data Integrity Suite,” said Zachary Decent, Data Governance & Quality Manager, Enterprise Data Management at UK Power Networks, providing power to a quarter of the UK’s population. “This move signifies our dedication to fostering Data Best Practice principles, leveraging this platform to offer stakeholders an enriched experience through a comprehensive data catalog, with clearly defined data responsibilities and robust quality monitoring mechanisms.”
Precisely has also implemented significant user experience performance enhancements in the Data Integrity Suite, reducing the time needed to perform basic functions, such as data quality rule reuse, where time was reduced by 77%. Additionally, Precisely has introduced its new Precisely Data Integrity Suite Developer Portal. The portal provides developer-friendly tools and resources that enable the creation of powerful applications with built-in data integrity capabilities like address geocoding and data enrichment. The Developer Portal is a central resource for information on Precisely API products and updates.
Learn more about the Precisely Data Integrity Suite and the enhanced Data Integrity Foundation or register for the virtual Trust ’24 event on October 15 – 16 to hear more from Chris Hall on the latest data integrity innovations.
About Precisely 
As a global leader in data integrity, Precisely ensures that your data is accurate, consistent, and contextual. Our portfolio, including the Precisely Data Integrity Suite, helps integrate your data, improve data quality, govern data usage, geocode and analyze location data, and enrich with complementary datasets for confident business decisions. Over 12,000 organizations in more than 100 countries, including 93 of the Fortune 100, trust Precisely software, data, and strategy services to power AI, automation, and analytics initiatives. Learn more at www.precisely.com. 
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