Artificial Intelligence
Wistar Scientists Discover Innate Tumor Suppression Mechanism
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PHILADELPHIA, PA, May 04, 2023 (GLOBE NEWSWIRE) — The p53 gene is one of the most important in the human genome: the only role of the p53 protein that this gene encodes is to sense when a tumor is forming and to kill it. While the gene was discovered more than four decades ago, researchers have so far been unsuccessful at determining exactly how it works. Now, in a recent study published in Cancer Discovery, a journal of the American Association for Cancer Research, researchers at The Wistar Institute have uncovered a key mechanism as to how p53 suppresses tumors. By using a genetic variant of p53 and comparing what that variant failed to accomplish with what the healthy “wild type” p53 gene could do, the researchers discovered the mechanism by which p53 triggers immune function that, in turn, kills the tumor.
“The paradigm shift is that, instead of asking ‘What does p53 do’ we were able to use a lesser-functioning but cancer-predisposing genetic variant in African Americans to tell us ‘What does p53 not do when it doesn’t suppress cancer?’” said Maureen E. Murphy, Ph.D., senior author on the paper and deputy director of the Ellen and Ronald Caplan Cancer Center and Ira Brind Professor and program leader of the Molecular & Cellular Oncogenesis Program at The Wistar Institute.
Four and a half million people in the United States possess inherited, or germline, mutations in p53, which increases their risk of cancer. A small subset of these individuals have a mutation that leads to Li Fraumeni Syndrome, which results in their developing multiple tumors every few years, starting in childhood. Others with different p53 mutations possess what are called hypomorphs: a gene variant having a similar but weaker effect than the corresponding normal, or wild-type, gene. These people also develop cancer, but theirs is less aggressive, and they develop it later in life.
Murphy and her team decided to learn how p53 suppresses tumors by exploring how one particular hypomorph fails to suppress them. The researchers chose an African-specific variant called Y107H due to the fact that African Americans have the largest cancer burden of any ethnic group in the world. Their first hypothesis was that they could use the hypomorph to find which “downstream” genes—which p53 would ordinarily turn on—are critical for suppressing tumors. Their second hypothesis was that they could then screen for drugs that would kill the hypomorph tumors: Murphy’s group was able to accomplish both goals.
The researchers began by using CRISPR engineering to make a mouse model of their African-specific hypomorph Y107H. As expected, the mice with Y107H developed many forms of cancer and, as with humans who possess this variant, they started developing cancer in “middle age” (i.e., after 12-14 months of an average two-year lifespan).
Next, the researchers created tumor cell lines with their Y107H hypomorph, as well as cell lines with a hypomorph found in Ashkenazi Jewish populations, called G334R. They then compared which genes were turned on by normal, or wild type, p53 (to suppress the tumor) but not turned on by the two hypomorphs (which failed to suppress the tumor). The gene that met these conditions was PADI4. To confirm, they checked ten other hypomorphs—none of those variants turned on PADI4, either.
“It’s as though this was the key p53 target gene that, every time you have a genetic variant that predisposes you to cancer, it cannot turn on this gene,” said Murphy. She added that it makes sense that PADI4 would be implicated, because this gene helps the immune system recognize tumors. It does this by modifying components of tumor proteins so that they become citrulline, which is a non-natural amino acid. When the immune system recognizes citrulline as a foreign body, it attacks.
“Essentially, when a tumor cell goes from one cell to two and it’s not supposed to, p53 is alarmed, it turns on PADI4, and PADI4 says, ‘Immune system, you better come get me,’” said Murphy.
The final stages of Murphy’s research went beyond foundational research and looked toward helping cancer patients. First, the researchers used Wistar’s Molecular Screening and Protein Expression facility to identify drugs that would be effective against tumors with the Y107H hypomorph while sparing tumors with wild-type p53. Then, they looked for a way to predict which patients would respond to immunotherapy and which would not. Ordinarily, in order to do this, they would need many more human tissue samples from African Americans than they had. So instead, they turned to machine learning.
“Enter Noam Auslander, Ph.D., who is a brilliant machine learning artificial intelligence person here at Wistar,” said Murphy. “She said, ‘Let me find the genes that p53 and PADI4 control together using bioinformatic approaches and create a gene signature.’”
To do this, Auslander analyzed 60,000 tumors in the TCGA database and identified five genes that were coregulated together by wild type p53 and PADI4 and that the Y107H hypomorph couldn’t turn on. Upon further analysis, she found that this five-gene signature predicted cancer survival, immune infiltration into the tumor, and who would respond to immunotherapy.
Murphy believes that identifying this gene signature through machine learning was what pushed her team’s paper from a scientific breakthrough to a medical game-changer. “We’ve not only said we have an important p53 target gene, but we also have an important five-gene signature that will actually tell us who will respond to immunotherapy and who won’t, and p53 is at the core of this signature.”
She also believes that this research could only have been performed at an institution like Wistar, because collaboration was so crucial. “If you look at the authors on this, I have immunologists who did the immunology; I have machine learning people who did the bioinformatics; and I have drug screening people who did the compound screens,” said Murphy.
“Wistar is just a thrilling place where everyone here is saying, ‘Here’s how I can help your research.’ It makes all the difference.”
Co-authors: Alexandra Indeglia, Jessica C. Leung, James F. Dougherty, Nicole Clarke, Nicole A. Kirven, Chunlei Shao, Thibaut Barnoud, David Y. Lu, Isabela Batista Oliva, Qin Liu, Joel Cassel, Noam Auslander, Cindy Lin, Tyler Yang, Daniel Claiborne, Yulia Nefedova, Toshitha Kannan, and Andrew V. Kossenkov from The Wistar Institute; Sven A. Miller, Lei Ke, and John Karanicolas from Fox Chase Cancer Center; Julia I-Ju Leu from the Perelman School of Medicine at the University of Pennsylvania; Scott Lovell and Lijun Liu from the Del Shankel Structural Biology Center at The University of Kansas; Kevin P. Battaile from the New York Structural Biology Center; and Peter Vogel from St. Jude Children’s Research Hospital.
Work supported by: National Health Institutes (NIH) grants CA102184 to M.M., CA238611 to M.M., R00CA241367 to T.B., and P30CA006927 to J.K.
Publication information: An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression, Cancer Discovery, 2023. Online publication.
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The Wistar Institute, the first independent, nonprofit biomedical research institute in the United States, marshals the talents of an international team of outstanding scientists through a culture of biomedical collaboration and innovation. Wistar scientists are focused on solving some of the world’s most challenging and important problems in the field of cancer, infectious disease, and immunology. Wistar has been producing groundbreaking advances in world health for more than a century. Consistent with its legacy of leadership in biomedical research and a track record of life-saving contributions in immunology and cell biology, Wistar scientists’ early-stage discoveries shorten the path from bench to bedside. wistar.org.
HONG KONG, May 27, 2024 /PRNewswire/ — Computime Group, a leading innovator in manufacturing, branded products and technology solutions, is proud to announce the upcoming launch of one of the first true Matter thermostats. This milestone highlights our commitment to pioneering smart home technology and providing our OEM and ODM customers with state-of-the-art solutions.
Matter is set to revolutionize the Internet of Things (IoT) landscape as the next-generation standard for connected devices. Developed by the Connectivity Standards Alliance, Matter offers an open, universal protocol that is not bound to any single ecosystem, providing consumers with unparalleled freedom and flexibility. It ensures privacy-sensitive, secure, and reliable local controls without the need for cloud dependency, addressing the growing demand for enhanced privacy and security in smart home devices.
The key principles driving Matter’s development include simplicity, reliability, interoperability, and security. By ensuring that all Matter-certified devices work seamlessly together, Matter eliminates the complexities often associated with smart home technology. This leads to greater compatibility, easier setup, and more robust user experiences across various device types, including thermostats.
Computime’s Matter thermostat represents a significant advancement in smart home technology, providing our customers with cutting-edge solutions and a short lead time to market, to meet the growing demand for interconnected and efficient home environments. We invite our customers to explore the capabilities of our new thermostat solutions. Computime’s extensive expertise in developing and manufacturing smart home devices ensures that our customers receive high-quality, reliable products with a short lead-time that stand out in the competitive market.
CONTACT: Computime Group, [email protected]
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MADRID, May 27, 2024 /PRNewswire/ — Global Voice Group (GVG) now features as one of the top 100 Africa-focused innovative RegTech organizations that are set to power Africa to a $1 billion market size by 2025.
This acknowledgment bears witness to GVG’s compliance monitoring capabilities within the Mobile Money (MM) ecosystem. GVG developed the Mobile Money Monitoring (M3) solution, an intelligent data platform that supports East African regulatory authorities in monitoring the fast-expanding MM market. Through M3, the authorities can ensure the security and integrity of the related financial transactions, as well as transparency and compliance, for enhanced revenue assurance. M3 currently monitors approximately 25% of the financial flows passing through MM platforms in East Africa, verifying over 90 billion USD worth of transactions annually.
Moreover, the platform is also in use in Central and West Africa, in the Republic of Congo and in Ghana. In Congo, M3 has brought the local telecommunications regulator, the ARPCE, 100% visibility and control over all utility payments made via Mobile Money to the government. In Ghana, it has contributed to an average annual growth of 20% in revenue since its deployment. Overall, M3 has captured, verified and analyzed 1 trillion USD in MM transaction value since 2014.
After demonstrating the relevance, effectiveness, and innovation of the M3 solution to the jury, composed of recognized leaders of the Regtech industry, GVG was shortlisted and, following the voting phase, earned a place on the prestigious list. The M3 platform uses machine learning to ensure effective oversight of the MM market, ensure regulatory compliance and detect suspicious transactions. Since its first implementation in 2013, GVG’s M3 solution has provided the relevant regulatory authorities with reliable MM ecosystem metrics to support data-driven decision-making, promote compliance within the market, and reduce fraud and revenue leakage.
Responding to the announcement, James Claude, GVG’s CEO, declared: “It is with a great sense of achievement that I see GVG featuring among the 100 top RegTech providers in Africa. On behalf of the whole company, I sincerely thank Africa RegTech Horizon, as well as our voters, for supporting us in what we do best: providing governments and regulatory authorities with the market insights they need to address the challenges related to the fast-expanding financial ecosystem.”
The Africa RegTech Horizon-100 list is a directory of African RegTech companies and solution providers compiled to showcase the products and services of the latter, as well as assist financial institutions, regulators, and governments in identifying high-performing and trustworthy RegTech providers.
About GVG
Founded in 1998 and present in 11 countries, Global Voice Group is a global provider of ICT and RegTech solutions for governments and regulatory bodies. GVG assists governments and authorities, through Big Data analytics, in their digital transformation and the effective promotion of compliant and truly inclusive digital ecosystems. The company monitors, collects and analyses data from crucial economic sectors and turns it into actionable information. We promote data-driven decision-making.
Discover GVG’s website: www.globalvoicegroup.com
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Artificial Intelligence
Unlock an Exclusive Olympic Experience: Celebrating Live4Well’s Sold-Out Genesis NFT
HONG KONG, May 25, 2024 /PRNewswire/ — The buzz surrounding Live4Well’s successful Genesis NFT membership launch on May 23 has captivated both traditional and web3 communities. Combining the power of AI technology and decentralized physical infrastructure (DePin) concept, Live4Well has infused new life into the NFT market. The overwhelming response to their first NFT sales, showcases the project’s immense potential. Renowned web3 community leaders from Azuki, Bored Ape, Pudgy Penguins, WELL3, etc have joined forces with Live4Well, propelling the Genesis NFT membership collection to its resounding success.
Live4Well aims to transform the wellness industry by creating a reward-based infrastructure that connects global fitness data, enhances their AI database, and drives the development of sports and wellness. Backed by a multi-billion family office, which recently invested $20 million in Live4Well, the project has gained support in both web3 and traditional spaces. The team believes that every drop of sweat and effort toward better health should be rewarded, fostering motivation and integrating exercise into daily lives for enhanced well-being.
Live4Well’s announcement of an Olympic-themed raffle for Genesis NFT holders reflects their commitment to connecting wellness between Web2 and Web3 platforms. This testament to Live4Well’s demand and innovative vision solidifies their position as a promising leader in the industry. Their integration of the Olympic signifies their determination to inspire a global audience, leveraging blockchain technology to create an immersive ecosystem that revolutionizes how individuals engage with fitness on a daily basis for better health. Live4Well’s dedication to bridging the gap between traditional practices and the digital landscape sets them apart as pioneers in promoting well-being on a global scale.
What is Genesis NFT membership?
The Genesis NFT unlocks a multitude of benefits for holders, including the opportunity to cash out their sportive income and access a range of exclusive physical products and services. In addition to future airdrops and angel round whitelist privileges, Genesis holders will receive VIP tailor-made product packs from an innovative German sportswear company, elevating their exercise performance to new heights. With over 400 million sweat points farmed by their users, they are eager to redeem through the Genesis NFT membership. These enticing incentives explain why there was a widespread eagerness to participate in this thrilling event.
Unlike typical projects that raise funds before launching products or services, Live4Well has already released its AI-powered app, amassing over 250,000 users as a community base actively engaging in daily exercise. This early success has fostered a promising community within the wellness industry, as users trust Live4Well’s roadmap and collaborative ventures. The growing traction from both ordinary individuals and web3 enthusiasts has intensified the demand for redeeming and cashing out sweat points, the project’s exercise-based rewards. Obtaining the Genesis NFT membership is now seen as an essential step for accessing the highest tier of benefits and cashing out sportive income.
What’s next for Live4Well?
Following the Genesis sales, Live4Well’s team will shift their focus to the upcoming token generation event (TGE) and a series of farming events. They also have exciting plans for partnerships and other collaborations in the global wellness and fitness industries. If you missed the initial launch, be sure to stay updated on Live4Well’s journey and join this extraordinary revolution.
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