Researchers at Kanazawa University have studied the structure of one of the virulence factors – haemagglutinin (HA) – of avian influenza virus, H5N1. They did this using high-speed atomic force microscopy (HS-AFM) and the findings are essential for developing therapeutic approaches against influenza A viruses in the future.

Understanding the structure and properties of HA when it is initially synthesised by host cells in its precursor form (HA0) is paramount to deciphering HA. So Dr Richard Wong, senior author of the study, and his research team visually analysed the recombinant HA0 protein of H5N1 with the HS-AFM system developed by Kanazawa University.

Both HA0 and HA exist in homotrimeric forms and conversion of HA0 to HA does not significantly modify the homotrimeric structure. Therefore, it is sensible to use HA as a template to generate HA0 HS-AFM simulation images. Acidic endosomal environment is the critical factor for HA to induce fusion between the viral membrane and endosomal membrane in order to release viral materials into host cells.

To elucidate the acidic effect on HA0, it was first exposed to an acidic environment. The trimer of HA0 turned out to be very sensitive to the acidic solution and expanded considerably. When conformational changes of haemagglutinin were measured in real-time using HS-AFM, the team found that its area was larger, and its height shorter. Acidic environment essentially made the molecule flatter and more circular, as compared to its original counterpart. This change in conformation was, however, reversible as the structure reverted back to its original form upon neutralisation.

HS-AFM setup for direct visualisation of HA0 trimer. Schematic diagram of the HS-AFM setup for scanning the HA0 trimer (credit: Kanazawa University).

“Our pilot work establishes HS-AFM as an inimitable tool to directly study viral protein dynamics, which are difficult to capture with low signal-to-noise techniques relying on ensemble averaging, such as cyro-EM and X-ray crystallography,” said lead author of the study Dr Kee Siang Lim. “With high scanning speed and a minimally invasive cantilever, we predict that HS-AFM is feasible to reveal the flow of irreversible conformational changes of HA2 induced by low pH, which is mimicking the true biological events that occur when HA enters a host endosome, in future study.”

This study paved the way for investigating biological events within viruses in real-time. “Our work establishes HS-AFM as an inimitable tool to directly study viral protein dynamics, which are difficult to capture with low signal-to-noise techniques relying on ensemble averaging, such as cyro-EM and X-ray crystallography,” added Dr Richard Wong.

The research can be found on Science Direct.

 

 

 

A study published on 26 April in Science saw that researchers have discovered an acid-activated protein which could prevent tissue damage from stroke, heart attack, cancer and inflammation.

The researchers at John Hopkins University School of Medicine named the newly found protein the proton-activated chloride channel (PAC). The team believes the discovery of this protein could provide a new drug target for potential therapies for stroke and other health issues.

Damage or disease, leading to oxygen deprivation, causes a raised level of acid in tissues. If acidity increases enough the cells become damaged and potentially die. When the build-up of acid reaches a certain level, it opens specialised channels in the cell membrane causing a build-up of ions in the cell, eventually causing it to swell and die. The opening channel has been unidentified until now.

The researchers discovered the channel protein by engineering human cell lines to produce a fluorescent molecule which ceased to glow when the channels in the cell membrane opened in response to acid. In all, 2,725 genes were tested to see which one would open the channels and the gene TMEM206 was found to influence channel activity. When the gene was inactive, it prevented channel activity in response to the acid. This gene matched with a single protein, which the researchers named PAC.

“Knowing the identity of this acid-stimulated protein opens up a broad new avenue of both basic research and drug discovery,” says Zhaozhu Qiu, Ph.D., the study’s principal investigator.

Artificial Intelligence (AI) has been at the top of many boardroom agendas for the last several years, as execs try to integrate the technology. Recent RELX research found that, across all industries, 88 percent of senior executives believe AI will help their businesses be more competitive. In the life sciences, AI has the potential to scale the benefits of precision medicine or automated disease prediction to more patients across the world, and could generate more than $150 billion in savings for the healthcare industry by 2025. 

3d rendering robot hand working with security laptop

Artificial Intelligence (AI) has been at the top of many boardroom agendas for the last several years, as execs try to integrate the technology. Recent RELX research found that, across all industries, 88 percent of senior executives believe AI will help their businesses be more competitive. In the life sciences, AI has the potential to scale the benefits of precision medicine or automated disease prediction to more patients across the world, and could generate more than $150 billion in savings for the healthcare industry by 2025. 

3d rendering robot hand working with security laptop

However, the news wasn’t all good. Only 56 percent of organizations are currently using AI or Machine Learning (ML) and of those, under half (39 percent) believe they are getting the most value out of it. This shows there is still a way to go before the technology’s potential is realized, so businesses looking to get value from AI and ML must consider the following: 

  1. Improved collaboration: Deploying AI successfully requires far greater collaboration across different disciplines and geographies. As Michael Kratsios, deputy CTO of the White House’s Office of Science and Technology Policy stated,“to realize the full potential of AI for the American people, it will require the combined efforts of industry, academia, and government.” Through collaboration, industries will benefit from shared insight and be able to further AI development far quicker than going it alone.  
  • Commit to spending: The research found only 18 percent have concrete plans to increase their AI investments. But investment is crucial in overcoming barriers such as the growing skills shortage – by next year it’s estimated there will be 2.7m unfilled data science jobs. This is particularly worrying for pharma as tech-savvy workers are already opting for better remunerated jobs in other sectors like banking, leaving them even more exposed. 
  • A platform for success: We’ve seen several generalist AI platforms suffer notable set-backs when it comes to life sciences, because they are not designed to handle scientific data. Because of the difficulties involved in processing different types of data, one tool which provides a singular experience cannot meet the needs of multiple different researchers. Businesses must look to specialized AI platforms to make the most out of the technology. 

AI offers industries a chance to find solutions to some of their most difficult challenges, but without careful consideration of the next steps, AI will fail to reach its full potential. Get in touch to find out how Elsevier can help you overcome the barriers to successful AI implementation.

Researchers from King’s College London have shown how skin vaccination can generate protective CD8 T-cells that are recruited to the genital tissues and could be used as a vaccination strategy for STIs.

Before this study, it was thought that vaccines ideally needed to be delivered directly to the body surface where the infection might start, so that the immune system can generate these CD8 T-cells, travel back to the vaccination site and eliminate any future virus that is encountered. However, delivering vaccines directly to the female genital tissue is neither patient-friendly nor efficient.

Now the team from King’s have found that their vaccination strategy marshals a platoon of immune cells, called innate lymphoid cells (ILC1) and monocytes, in the genital tissues to work together and release chemicals (chemokines) to send out a call to the CD8 T-cells generated by the vaccine to troop into the genital tissue.

This research builds on the team’s earlier work to develop skin vaccination techniques using a dissolvable ‘microneedle’ vaccine patch that once placed against the skin dissolves and releases the vaccine without requiring a hypodermic needle injection and generates immune responses.

“This study highlights how specialised groups of ‘innate’ immune cells in distant tissues can be harnessed to attract protective CD8 T-cells, arming the body’s frontline tissues from infection,” said lead author, Professor Linda Klavinskis from King’s. “We now need to confirm these results with other types of vaccines from the one used in the study to see if a common pathway is triggered by skin vaccination.

“If proven, this could have a significant impact in improving the effectiveness of vaccines against sexually transmitted infections.”

The study was published in Nature Communication.

Global Point, LLC

Managed IT Services company in Chicago, IL.

Global Point LLC is the leading provider of computer network services and technology solutions for businesses in the Chicagoland area. Our Mission is to provide the infrastructure and technology tools your business needs allowing you to succeed at the highest levels. We have delivered excellent, cost-effective IT service to many satisfied customers. Global Point has been helping businesses like yours for over 10 years. Global Point LLC is the leading provider of computer network services and technology solutions for businesses in the Chicagoland area.

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Global Point Offers Chicago IT Managed Services
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Istanbul, Turkey – September 6, 2015: A woman wearing 42mm stainless steel Apple Watch with white sports band. The Apple Watch became available April 24, 2015, bringing a new way to receive information at a glance, using apps designed specifically for the wrist.

Apple is a company that has long been thought of us an innovator that has brought consumers an array of enticing gadgets, from home computers to iPods to smartphones. This technology has been transformative for its users, but mostly it has been associated with work and play. Increasingly, though, Apple appears to be interested in getting involved in another critical part of our lives: our health.

Apple is a company that has long been thought of us an innovator that has brought consumers an array of enticing gadgets, from home computers to iPods to smartphones. This technology has been transformative for its users, but mostly it has been associated with work and play. Increasingly, though, Apple appears to be interested in getting involved in another critical part of our lives: our health.

Istanbul, Turkey – September 6, 2015: A woman wearing 42mm stainless steel Apple Watch with white sports band. The Apple Watch became available April 24, 2015, bringing a new way to receive information at a glance, using apps designed specifically for the wrist.

The Apple Watch, which initially seemed like little more than a way to check text messages at a glance, has been one of the main ways that the company has insinuated itself into the healthcare space. As a part of the vanguard of “wearables,” the Apple Watch initially addressed personal health by measuring the wearer’s steps and providing heart rate information. But the newest, 4thseries of the device boasts an EKG app and a fall detection feature, making a stronger case for its genuine usefulness in health monitoring.

In further evidence that Apple is serious about its future in the healthcare business, CNBC recently revealed that Apple has actually been talking to multiple private Medicare plans about the possibility of subsidizing the Watch for senior citizens to use as a health tracker. “The talks have not resulted in any official deals just yet,” reported Christina Farr. “Apple has paid a visit to several of the largest insurers in the market, as well as some smaller, venture-backed Medicare Advantage plans.” 

Medicare Advantage plans are offered by private insurance companies, with Medicare paying the company to cover the patient’s benefits. “Medicare Advantage has been a lucrative space for potential experimentation in lowering healthcare costs due to its capitated model which allows for more flexibility in approach in providing care,” writes Kevin Truong of MedCity News. “Around 19 million people are enrolled in Medicare Advantage plans currently, but that number is continuing to grow with major insurers like Aetna and UnitedHealth announcing major expansion plans.”

That’s a lot of potential Apple Watch customers.

So, would it actually be advantageous for Medicare Advantage providers to subsidize the hefty $399 price tag for all those Apple Watches? Business Insider contributor Nicky Lineaweaver makes an argument in the affirmative. “The annual medical costs from hospital admissions for an AFib patient are nearly $5,000 higher than a non-AFib patient,” Lineaweaver writes. “Skirting just one admission through the Watch’s AFib detection or expediting care for a recently fallen patient would likely create a large return on investment from reduced medical costs.”

Apple has been pretty quiet about its courting of Medicare Advantage providers so far, but it will be interesting to see what steps the tech giant takes next as it further explores its future role in the healthcare industry.

AI in Drug Discovery Has Great Potential – But Also Significant Barriers

It’s an exciting new time for drug discovery and development as whole new worlds of data have opened up. Wearable devices that collect personal health readings and services such as consumer genetic testing are making loads of potentially insightful data available. But all that potential comes with new challenges – namely, how do we process and analyze all this new data?

Artificial intelligence presents a timely answer to this problem. AI has an array of useful applications in pharma, whether it’s identifying candidates for drug repurposing or assessing safety issues in early-stage discovery. Once deployed to help in these capacities, AI and machine learning can speed up costly, time-consuming processes – freeing up researchers’ time to focus on the actual science.

But there are many real barriers to making all of these possibilities into realities. The recent announcement that IBM is stopping development and sales of Watson for Drug Discovery, a product that was using IBM’s Watson AI software, points to this fact.

What are the challenges to implementing AI? Tim Miller, Vice President of Life Sciences Platform Solutions at Elsevier, addresses these questions in the World Pharma Today article Why AI in Drug Discovery Has Yet to Live Up to Its Promise.

Read here

Nicki Catchpole

As a professional with over 14 years of experience in strategy development and partnership management across a variety of industries, Nicki’s latest role as a Senior Manager, Segment Marketing at Elsevier applies her skills to the area of drug discovery and development in the Pharma and Biotech industry.
In this capacity she is focused on understanding biopharmaceutical R&D challenges and turning them into opportunity to further Elsevier’s ability to serve industry executives and the professionals who innovate in the drug discovery and development space. 
Nicki resides in New York City and holds a BA in English Literature and Mandarin Chinese from Carleton College in Northfield, MN.

The scientists, funded by the National Institute of Allergy and Infectious Diseases (NIAID), discovered and characterised the structure of a naturally occurring human antibody that recognises and disrupts a portion of the hemagglutinin (HA) protein that the influenza virus uses to enter and infect cells.

The investigators determined that the antibody, FluA-20, binds tightly to an area on the globular head of the HA protein that is only very briefly accessible to antibody attack. 

The team, led by James E. Crowe, Jr, MD, of Vanderbilt University Medical Centre, Nashville, Tennessee, and Ian A Wilson, DPhil., of The Scripps Research Institute, San Diego, California, then isolated FluA-20 antibody from a person who had received many influenza immunisations. Then, in a series of experiments, showed that FluA-20 can ‘reach into’ an otherwise inaccessible part of the three-part HA trimer molecule and cause it to fall apart, thus preventing the spread of virus from cell to cell.

This region of trimeric HA was thought to be stable and inaccessible to antibodies and (unlike the rest of HA’s head) varies little from strain to strain. In theory, antibody-based therapeutics directed at that precise region would be effective against many strains of influenza A virus.

Similarly, vaccines designed to elicit antibodies against this target might provide long-lasting protection against any influenza strain, potentially eliminating the need for annual seasonal influenza vaccination.

In mouse studies, FluA-20 prevented infection or illness when the animals were exposed to four different influenza A viral subtypes that cause disease in humans.

Two viruses used in the experiments, H1N1 and H5N1, are Group 1 influenza subtypes, while the two others, H3N2 and H7N9, are members of Group 2. Current influenza vaccines must contain viral components from both subtypes to elicit matching antibodies. A single vaccine able to generate potent antibodies against members of both groups could provide broad multi-year protection against influenza.

This study, ‘A site of vulnerability on the influenza virus hemagglutinin head domain trimer interface’ by S Bangaru et al. was published in Cell. 

 

 

New Legal Site Launches ChrisCoffman.Rocks

We had a little fun with the name I will admit that.  Honestly I wasn’t even aware that .rocks was a valid domain, it feels more like an 80s throwback which predates the internet.  With that said it is memorable and I’ve gone with it.

Hall of Justice in Louisville, KY

Hall of Justice in Louisville, KY

Chris Coffman is in fact an attorney in Louisville, KY whom I’ve known for twenty years.  Which is likely the only reason why he agreed to allow me to toss up a site in his name and SEO it.  Chris has been told over and over by the established attorneys in Louisville that a web site yields little result and that referrals are the means to gain clients.

I do not believe that is accurate.  Today, people find their spouse, music, work, pets and news online.  I do believe that if you fail to maintain a web site then sure, referrals are the only way a lawyer will attract clients.  If you only leave people with one avenue to reach you then that will be the way most people find you.  But it’s important to realize that people can not find you in ways that you neglect.  No profession or business is beyond the internet and even people looking for legal representation likely begin their search online.

Site To Serve As Case Study

So for that reason I’ve picked up a side project to build ChrisCoffman.rocks into a legal site that brings relevant clients and traffic.

Legal Practices 

Criminal Defense

Drug Charges both Possession and Trafficking 

Real Estate Contracts including Commercial Contracts and Business Law

Family Law

Divorce Law

Louisville Attorney Chris Coffman is now represented on chriscoffman.rocks if you’ve received a DUI or a traffic ticket you do need an attorney.  The justice system in Louisville, KY can either send you into a downhill tumble or you can be guided out of the trip falls.  The Jefferson County Attorney and his prosecutors don’t get elected for how much justice they seek, it is all about convictions.  You are just another notch in their crusade to keep Louisville’s jails overcrowded and to squeeze as much money out of anyone’s pocket that has the misfortune of finding themselves needing a defense.

If you’ve been hurt and are seeking damages from an insurance company you need a lawyer.  They have a lawyer and it is in their best interest to pay you as little as they have too.  Personal injury law is complicated and often they will take advantage of the situation if you lack an attorney.

Jefferson County Judicial Center, Louisville KY

Jefferson County Judicial Center, Louisville KY

Through this new site Louisville residents can book consultations with Chris, read about his work and even submit a question that Chris can answer on the site.  Check it out, Chris practices law in Kentucky and is often in Lexington, Frankfort and many other KY cities.

Legal Site Launches To Teach A Lesson
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Elsevier is recognized as ‘Best of Show Award Finalist’ and ‘People’s Choice Award Finalist” at Bio-IT World Conference & Expo 2019

For more than a decade, the pharmaceutical and life science community has had an annual opportunity to join the Bio-IT World Conference & Expo, an event where pharmaceutical and life science industry leaders and experts come together to represent their companies, share ideas, domain knowledge, best practices and achievements in R&D and technology areas.

The Bio-IT World Conference & Expo 2019 welcomed 3,400+ life sciences, pharmaceutical, clinical, healthcare and IT professionals from 40+ countries.

To encourage and appreciate the development of novel technology solutions that can enable better research and discovery in the pharmaceutical and life science industries, a dedicated industry awards program is part of the Bio-IT World Conference & Expo 2019 as well. As specified on the event’s website, the respective recognition program includes the:

  • ‘Innovative Practices Award’ – since 2003, it is awarded for highlighting outstanding examples of technology innovation in the life sciences. The respective award is designed to recognize partnerships and projects pushing the industry forward, striving to highlight strategies that can be widely shared and implemented across the industry to improve the quality, pace, and reach of our science.
  • ‘Best of Show 2019 Award’,also including the ‘People’s Choice Award’ – are awarded to distinguish and highlight products ranging from an innovative application, technology, tool, or solution from the competition’s entrants. Judged by a team of leading industry experts, and Bio-IT World editors, this program identifies exceptional innovation in technologies used by life science professionals today. Products considered are new products, or significant product upgrades, introduced between April 2018 and April 2019. Winners are judged based on the products’ technical merit, functionality, innovation, and in-person presentations to the judges at the show.
  • ‘Benjamin Franklin Award’ – is a humanitarian/bioethics award presented annually by the Bioinformatics Organization to an individual who has, in his or her practice, promoted free and open access to the materials and methods used in the life sciences.

Besides traditionally being a platinum sponsor of the event, Elsevier  has marked its presence at the Bio-IT World 2019 as a provider of platform-as-a-service (PaaS) by introducing Entellect – a new platform for research data management in pharmaceutical and life science industries.

In the era of digital disruption and big data and advanced analytics, the R&D and information technology are very much interconnected and terms like AI, machine learning, data science, blockchain, IoT and cloud are becoming increasingly familiar to the companies in the industry. Many pharmaceutical and life science companies today want to get competitive advantage by becoming more efficient and agile, aiming towards a more efficient, data-driven R&D. In this context, understanding all the needs and challenges of the players in the industry, Elsevier created Entellect.

Entellect is a cloud-based platform designed to overcome R&D data challenges in the rapidly evolving world of applied analytics. It helps companies to achieve optimal results by delivering high-quality, enriched content from multiple internal and third-party sources, including Elsevier’s wealth of science research data and information. Entellect also provides search and analytics capabilities along with the workspace to develop custom applications. It is specifically designed to answer questions in pharmaceutical R&D.

While introducing Entellect to the wider audience at the Bio-IT World & Expo 2019, it is also worth mentioning that Entellect was nominated and became a finalist for the ‘Best of Show Award 2019’, as well as the ‘Best of Show – People’s Choice Award’.

In addition to the recognition that Entellect received, Elsevier nominated Bayer Pharmaceuticals for the Innovative Practices award based on Bayer’s Dr. Thomas Steger Hartmann’s contribution to the following study: “A big data approach to the concordance of the toxicity of pharmaceuticals in animals and human” and Bayer was named among the finalists.

We are extremely proud to contribute and to be recognized among the industry for both innovative new offerings and partnerships. 

For more information about Entellect, visit elsevier.com/entellect .

Veaceslav Mamaliga

Veaceslav Mamaliga joined Elsevier as Solutions Marketing Manager taking the lead on marketing and business development activities for Entellect, a new smart platform that empowers research and discovery, delivering AI-ready data to help pharmaceutical and life sciences companies improve the way they extract knowledge from big data. Veaceslav brings over fifteen years of professional experience in marketing, business development, project management and analytics. Prior to Elsevier Veaceslav has worked at IBM, Pierre Audoin Consultants and GE Healthcare.