Artificial Intelligence

Kanazawa University research: Researchers identify the dynamic behavior of a key SARS-CoV-2 accessory protein

Published

9 months ago

September 26, 2023

KANAZAWA, Japan, Sept. 26, 2023 /PRNewswire/ — Researchers at Kanazawa University report in the Journal of Physical Chemistry Letters high-speed atomic force microscopy studies that shed light on the possible role of the open reading frame 6 (ORF6) protein COVID19 symptoms.

While many countries across the world are experiencing a reprieve from the intense spread of SARS-CoV-2 infections that led to tragic levels of sickness and multiple national lockdowns at the start of the decade, cases of infection persist. A better understanding of the mechanisms that sustain the virus in the body could help find more effective treatments against sickness caused by the disease, as well as arming against future outbreaks of similar infections. With this in mind there has been a lot of interest in the accessory proteins that the virus produces to help it thrive in the body.
“Similar to other viruses, SARS-CoV-2 expresses an array of accessory proteins to re-program the host environment to favor its replication and survival,” explain Richard Wong at Kanazawa University and Noritaka Nishida at Chiba University and their colleagues in this latest report. Among those accessory proteins is ORF6. Previous studies have suggested that ORF6 potently interferes with the function of interferon 1 (IFN-I), a particular type of small protein used in the immune system, which may explain the instances of asymptomatic infection with SARS-CoV2. There is also evidence that ORF6 causes the retention of certain proteins in the cytoplasm while disrupting mRNA transport from the cell, which may be means for inhibiting IFN-I signalling. However, the mechanism for this protein retention and transport disruption was not clear.
To shed light on these mechanisms the researchers first looked into what clues various software programs might give as to the structure of ORF6. These indicated the likely presence of several intrinsically disordered regions. Nuclear magnetic resonance measurements also confirmed the presence of a very flexible disordered segment. Although the machine learning algorithm AlphaFold2 has proved very useful for determining how proteins fold, the presence of these intrinsically disordered regions limits its use for establishing the structure of ORF6 so the researchers used high-speed atomic force microscopy (HS-AFM), which is able to identify structures by “feeling” the topography of samples like a record player needle feels the grooves in vinyl.
Using HS-AFM the researchers established that ORF 6 is primarily in the form of ellipsoidal filaments of oligomers – strings of repeating molecular units but shorter than polymers. The length and circumference of these filaments was greatest at 37 °C and least at 4 °C, so the presence of fever could be beneficial for producing larger filaments. Substrates made of lipids – fatty compounds – also encouraged the formation of larger oligomers. Because HS-AFM captures images so quickly it was possible to grasp not just the structures but also some of the dynamics of the ORF6 behavior, including circular motion, protein assembly and flipping. In addition, further computer analysis also revealed that the filaments were prone to aggregate into amyloids as found in some neurodegenerative diseases, and which can lead to complications in COVID19 symptoms. As the researchers point out this aggregation works “to effectively sequester a vast numbers of host proteins, particularly transcription factors involved in IFN-I signaling.”
Since these filaments break up in the presence of certain alcohols, urea, or sodium dodecyl sulfate Wong, Nishida and their colleagues conclude that the protein is largely held together by hydrophobic interactions. “Potential druggable candidates that dissociate ORF6 aggregates by disrupting hydrophobic interactions should be considered and tested in the near future to evaluate their therapeutic value in COVID19 management and treatment.”
Related image
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Caption: Observation of aggregation dynamics by COVID-19 severity factor ORF6 protein (licensed as, CC-BY-NC-ND 4.0.)
Glossary
High-speed atomic force microscopy
Atomic force microscopy (AFM) “feels” the topography of surfaces by the increase and decrease of surface forces tugging on a nanoscale tip as changes in surface height change the distance between the tip and the surface. The tip is mounted on a cantilever so that the tiny changes in the force can be read out by the resulting deflection in the cantilever.
AFM can resolve structures with subnanometre scale resolution. It has particular advantages for biological studies because it does not require conducting substrates or a current, which are requirements for other primary microscopes with comparable resolutions, such as the scanning tunnelling microscope.
For a long time AFM was limited by the time it takes to capture an image of the surface, but this changed when Toshio Ando at Kanazawa University revealed how the tool could be upgraded to high-speed AFM using various modifications to the scanning, deflection detection and other electronic devices, as well as specifications for the cantilever. With high-speed AFM it became possible to capture dynamics at the nanoscale for the first time.
Reference
Goro Nishide, Keesiang Lim, Maiki Tamura, Akiko Kobayashi, Qingci Zhao, Masaharu Hazawa, Toshio Ando, Noritaka Nishida, Richard W. Wong Nanoscopic Elucidation of Spontaneous Self-Assembly of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Open Reading Frame 6 (ORF6) Protein Journal of Physical Chemistry Letters, 14, XXX, 8385–8396, (2023)
Online Sept 14, 2023
DOI: 10.1021/acs.jpclett.3c01440
URL: https://pubs.acs.org/doi/10.1021/acs.jpclett.3c01440
Contact
Hiroe YonedaSenior Specialist in Project Planning and OutreachNanoLSI Administrative OfficeWPI Nano Life Science Institute (WPI-NanoLSI)Kanazawa UniversityKakuma-machi, Kanazawa 920-1192, JapanEmail: [email protected] Tel: +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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Artificial Intelligence

Fractal Announces Merger of Eugenie.ai to Bolster AI-Powered Climate Solutions

Published

17 mins ago

June 26, 2024

CISION (PR Newswire)

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MUMBAI, India, June 26, 2024 /PRNewswire/ — Fractal (www.fractal.ai), a global provider of artificial intelligence and advanced analytics solutions to Fortune 500® companies, today announced the merger of Eugenie AI (Eugenie.ai), an AI company dedicated to providing AI-driven products for climate change and industrial sustainability.

Founded in 2021, Eugenie has established itself as one of the pioneering forces in AI-driven climate solutions. Their clientele includes some of the world’s largest industrial corporations across energy, metals & mining, and other hard-to-abate sectors. Eugenie’s achievements include being featured at the prestigious 2024 Google I/O, being an alum of the Google for Startups: Climate Change accelerator and winning multiple global accolades such as the NASSCOM Emerge 50, Tech30 recognition by YourStory, and the Vedanta Spark Corporate Innovation Challenge. Eugenie has been featured as a key provider by Gartner in its 2023 Market Guide for Energy Management and Optimization Systems & Market Guide for Commercial and Industrial Energy Management and Optimization Systems.
Srikanth Velamakanni, Co-founder, Group Chief Executive & Vice Chairman, Fractal, said, “We are excited to welcome Eugenie back into the Fractal family. Eugenie’s cutting-edge AI technologies and their commitment to combating climate change align perfectly with our vision to leverage AI for social good. Together, we aim to accelerate the development and deployment of innovative solutions that address some of the most pressing environmental challenges of our time. Eugenie’s expertise in serving major industrial clients complements our goal of creating significant value for client in Fortune 100 organizations.”
Dr. Soudip Roy Chowdhury, Founder and CEO, Eugenie AI, said, “Joining forces with Fractal marks a significant milestone for Eugenie. Our shared values and complementary expertise will enable us to scale our impact and continue our mission to drive sustainable industrial transformations. We look forward to working together to create a future where technology and nature coexist harmoniously. By integrating our AI-driven solutions with Fractal’s extensive capabilities, we can offer even greater value to our clients, helping them achieve their sustainability goals.”
The merger of Eugenie reinforces Fractal’s commitment to harnessing the power of artificial intelligence to address global challenges and underscores its dedication to sustainability and innovation. By integrating Eugenie’s expertise in climate-focused AI solutions, Fractal aims to expand its portfolio and deliver even greater value to its clients and communities worldwide.
Eugenie’s focus on providing AI solutions to some of the hardest-to-abate sectors aligns perfectly with Fractal’s vision of driving significant value for large enterprises. This strategic merger will enhance Fractal’s ability to offer comprehensive AI solutions that not only optimize business operations but also contribute to a more sustainable and resilient industrial ecosystem.
For more information, please visit www.fractal.ai and www.eugenie.ai.
About Fractal
Fractal is one of the most prominent providers of Artificial Intelligence to Fortune 500® companies. Fractal’s vision is to power every human decision in the enterprise, and bring AI, engineering, and design to help the world’s most admired companies.
Fractal’s businesses include Crux Intelligence (AI driven business intelligence), Eugenie.ai (AI for sustainability), Asper.ai (AI for revenue growth management), Senseforth.ai (conversational AI for customer service) & Flyfish (generative AI for Sales). Fractal incubated Qure.ai, a leading player in healthcare AI for detecting Tuberculosis and Lung cancer.
Fractal currently has 4500+ employees across 17 global locations, including the United States, UK, Ukraine, India, Singapore, Middle East and Australia. Fractal has been recognized as ‘Great Workplace’ and ‘India’s Best Workplaces for Women’ in the top 100 (large) category by The Great Place to Work® Institute; featured as a leader in Data Engineering services 2024 & Data Science Services 2024 by Information Services Group, Leader in AI and Analytics Services Specialists Peak Matrix Assessment 2021 by Everest Group, Leader in Customer Analytics Service Providers Wave™ 2023 by Forrester Research, Inc.
About Eugenie AI:
Eugenie is a forward-thinking AI company, headquartered in NY, USA dedicated to creating solutions that address climate change and promote industrial sustainability. Leveraging advanced AI technologies, Eugenie empowers organizations to achieve their sustainability goals and contribute to a healthier planet.

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Artificial Intelligence

ADOLFO DOMÍNGUEZ PRESENTS HIS NEW FASHION AND FRAGRANCE COLLECTION AT A WORLD FASHION SHOW

Published

17 mins ago

June 26, 2024

CISION (PR Newswire)

adolfo-dominguez-presents-his-new-fashion-and-fragrance-collection-at-a-world-fashion-show

The brand intertwines fashion and perfume to create an immersive experience in the olfactory and creative universe
The fashion show, which will take place in Chile, will be broadcast online in 29 countries. It can be followed live on the brand’s website and social media profiles
MADRID, June 26, 2024 /PRNewswire/ — Adolfo Domínguez keeps moving forward in its commitment to bring fashion closer to society. The brand will showcase Ikigai, its autumn-winter 2024 collection, together with a selection of new perfumes in a global fashion show.

The event, which will mix fashion and fragrances, will be streamed live on 27 June at 6 p.m. (Portuguese time) on the brand’s website, accessible from 29 countries around the world, as well as through Mega, the main television channel in Chile, and Movistar+, in Spain. The event will also be broadcast on the company’s profiles on social media.
Adolfo Dominguez will showcase its fashion and perfume collections from the La Moneda cultural centre in Santiago de Chile, where it will create an immersive experience with artistic performances and music developed exclusively for the occasion. Attendees will have the opportunity to experience first-hand the essence and innovation that define Adolfo Dominguez, consolidating its presence and relevance in the Latin American market.
“Clothes matter. It is our second skin. Perfume is the trace we leave as we walk by. With each new collection, we explore our creativity and out contribution to society as a brand- why should we limit it to a privileged few in a room?” states Patricia Alonso, Corporate Director of Marketing and Communication at Adolfo Domínguez.
Ikigai, a Japanese concept that invites each person to go in search of their vital purpose, is the driving force behind Adolfo Domínguez’s autumn-winter 2024 collection: a selection of garments designed to liberate oneself. The result is a collection designed to be lived, with garments that are born to make people understand that beauty and happiness reside in the little things.
The fashion show will be streamed on www.adolfodominguez.com and on the brand’s profiles on social media (Youtube, Instagram and Facebook). In Latin America, the fashion show can also be seen on Mega, one of the main Chilean television channels.
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Artificial Intelligence

Darwin CX Broadens Global Reach via Strategic Partnership with dsb

Published

17 mins ago

June 26, 2024

CISION (PR Newswire)

darwin-cx-broadens-global-reach-via-strategic-partnership-with-dsb

TORONTO, NECKARSULM, Germany and NORTHAMPTON, UK, June 26, 2024 /PRNewswire/ — Darwin CX and dsb deepen their alliance as Darwin CX becomes a shareholder of dsb. The Canadian company’s investment in dsb expands Darwin CX into the UK and European market and dsb becomes part of the pioneering Darwin CX family. The strategic partnership marks a significant milestone for Darwin CX and dsb, both leading providers of SaaS solutions and services for publishers.

The most remarkable aspect of this union is the parallel trajectories of these formidable companies prior to the partnership. Darwin CX and dsb’s fly ecosystem both launched in 2018 with the common goal of modernizing the publishing industry, which had become heavily reliant on outdated practices and legacy systems. Each company was on an independent mission to create an ecosystem of tools and solutions that would allow publishers to thrive in a fast-paced, data-driven, digital-first marketplace.
Best practices from North America meet European recipes for success
“While Darwin CX developed a platform for the needs of a North American publishing audience, the dsb fly ecosystem offers its European customers a variety of tools to increase acquisition, maximize customer lifetime value and reduce costs and effort,” explains Liam Lynch, CEO of Darwin CX.
Broader range of resources and features
Darwin CX and dsb are process experts in the publishing environment. “We know the industry’s workflows inside out and have the same vision. Now, as subscription professionals, we are joining forces and offering our customers scalable solutions that enable them to tap into new revenue streams in a dynamic market,” emphasizes Olaf Bendt, CEO of the dsb Group. “Our customers benefit from an even broader range of resources and features.”
Next generation sales and marketing solutions
Publishers are battling dwindling attention spans and declining engagement. dsb and Darwin CX offer the publishing industry new, powerful tools for even more accurate content offers, prices and subscription conditions. All of this is based on data-driven, AI-supported personalization, which offers publishers new insights into their customers’ engagement and launches targeted measures to increase loyalty.
Prioritizing business continuity
“To meet the growing needs of our customers, dsb will expand their fly back-end infrastructure while integrating some of Darwin CX’s key marketing and data management tools. Of course, business continuity will be maintained for both our European and North American clients. We will offer our clients the best of both worlds without disrupting their day-to-day business,” emphasizes Alex Münch, COO at dsb Group.
Solutions for digital and printed content
Darwin CX and dsb are united by a focus on maximizing recurring revenue, seamless integration of online and offline solutions, and a fundamental belief in customer centricity. “The DNA of both companies is the publishing industry. That’s why, together with dsb, we are focusing on customized solutions for printed and digital Content”, stresses Michael Smith, Darwin CX Co-Founder and Chief Technology Officer.
About Darwin CX
Darwin CX is a transformative SaaS and services platform at the leading edge of the subscription and membership economies. Founded in Toronto, Canada, Darwin CX assists brands accelerate acquisition and retention—and increase loyalty—through innovative and customized check-out pages, targeted audience offerings, real-time A/B testing and best-in-class analytics, paywall and customer data platform (CDP). The Darwin CX platform enables clients to have complete freedom and control over customer data in order to tailor the best possible customer experiences. Over 140 well-known publishers and more than 300 brands in the USA, Canada and Australia rely on Darwin CX for their data and subscription management needs. Led by CEO, Liam Lynch, CTO, Michael Smith, COO, Cat Kiernan and President, Cary Zel, Darwin CX is backed by a group of growth equity investors with a common theme of disrupting industries and driving digital innovation including First Ascent Ventures, New Era Capital Partners and Felicitas Global Partners.
About dsb
With dsb fly, the dsb group develops and operates Europe’s leading subscription ecosystem for the publishing industry. Key players in the media industry have been relying on dsb’s holistic and customer-centric monetization solutions for over 50 years. Whether lifestyle products, seminars, events, digital or print titles – the dsb fly ecosystem offers media companies a customized 360-degree customer view of print and digital consumption. This all-round view is the basis for highly individualized worlds of experience and high customer loyalty. dsb fly manages customer relationships along the entire customer life cycle and maximizes subscription retention and sales with accurate subscription offers and highly individualized worlds of experience.
TAGGED WITH: Darwin CX, Liam Lynch, Michael Smith, Cary Zel, dsb, dsb.net, Olaf Bendt, Alex Münch
To find out if Darwin CX and dsb are right for your international business, contact [email protected]
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