Circulating Nucleic Acids in Human Biofluids and Liquid Biopsy Research

Several different types of nucleic acids can be found circulating in human biofluids. Fragmented DNA and RNA are now routinely purified from plasma and other bodily fluids. These types of nucleic acids need to be purified from a cell-free fraction of the biofluids to ensure that the isolated nucleic acids are truly circulating and not from intact cells. In this blog post, we will learn a bit more about circulating nucleic acids (CNA) and how they can be used as biomarkers in research.

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“Forever” Chemicals: Forever No More

If you were tasked with destroying something called “forever chemicals”, chances are you’d be leaning towards rather harsh methods. Incineration would probably be on the table.

These so-called “forever chemicals”, or per- and polyfluoroalkyl substances (PFAS), are a family of organic compounds where fluoride replaces hydrogens atoms on carbon chains. They are very water and oil repellent, which makes them ideal for use in non-stick cookware, stain-proof fabrics and fire-suppressing foams. Recent studies, however, show that exposure to PFAS is linked to a range of health issues—from increased cholesterol levels to some cancers. Even levels of PFAS present in drinking water in as low as parts per billion levels can pose risks to human health. These risks are exacerbated by the tendency for PFAS to bioaccumulate, or become concentrated in the tissues of humans and animals.

Methods do exist to filter out PFAS from water. But what do you do when it’s time to replace those filters? Simply throwing out PFAS-contaminated equipment just moves the problem to a landfill.

Person getting a glass of water from a kitchen faucet.

Instead, these “forever chemicals” need to be destroyed. Most existing strategies for breaking down PFAS use harsh conditions, such as incinerating PFAS residues in furnaces or oxidizing them in supercritical water—water that is at more than 37°C and 200atm of pressure. Now, scientists reporting in Science have discovered that such extreme methods may not be needed to destroy “forever chemicals” (1).

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mRNA Vaccine Manufacturing: Responding Effectively to a Global Pandemic

We’ve learned a few important lessons from the COVID-19 pandemic.

Perhaps the most significant one is the importance of an early and rapid global response to the initial outbreak. A coordinated response—including widespread use of masks and other personal protective equipment (PPE), travel restrictions, lockdowns and social distancing—could save lives and reduce long-term health effects (1). Widespread availability of effective vaccines goes hand in hand with these measures.

New Boosters to Fight Omicron

Last month, Pfizer/BioNTech announced the US Food and Drug Administration (FDA) had granted emergency use authorization (EUA) for a new adapted-bivalent COVID-19 booster vaccine for individuals 12 years and older. This vaccine combines mRNA encoding the wild-type Spike protein from the original vaccine with another mRNA encoding the Spike protein of the Omicron BA.4/BA.5 subvariants. Moderna also announced FDA EUA for its new Omicron-targeting COVID-19 booster vaccine. The Omicron variant of SARS-CoV-2 shows multiple mutations across its subvariants, and it is currently the dominant SARS-CoV-2 variant of concern across the world.

Genomic epidemiology of SARS-CoV-2 with subsampling focused globally over the past 6 months. This phylogenetic tree shows evolutionary relationships of SARS-CoV-2 viruses from the ongoing COVID-19 pandemic. Image from Nextstrain.org; generated September 20, 2022

Booster doses of vaccines have become a way of life, both due to declining effectiveness of the original vaccines especially in older adults (2), and the rapid mutation rate of SARS-CoV-2 (3). Clinical data for the new Pfizer/BioNTech booster vaccine showed superior effectiveness in eliciting an immune response against Omicron BA.1 compared to the original vaccine. Previously, Moderna published interim results from an ongoing phase 2-3 clinical trial, showing that the new bivalent booster vaccine elicited a superior neutralizing antibody response against Omicron, compared to its original COVID-19 vaccine (4).

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Onward with Online Learning!

National Online Learning Day is celebrated annually on September 15, and although it was only created in 2016, it’s a growing “day”. This day highlights students of all ages who have the ability to learn anywhere, anytime, and thrive wherever their technology and imagination take them.

Technology in the past decade has completely transformed and built bridges in education. Even before the pandemic, online learning was growing and being adopted. As we entered the COVID-19 pandemic, educational institutions were forced to think digitally, and our viewpoint of online education shifted from “option” to “necessity”.

Whether you’re enrolled in a virtual course, working from home, or sitting in on a virtual conference, nearly all of us, at some compacity, take part in online learning—and it’s here to stay! The ability to learn online will continue to provide people with new resources and support for many years to come. Let’s dive into some advantages of online learning and discover helpful resources to thrive online.

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A Virus Makes a Comeback: Emerging Poliovirus Transmission in the West

In 1921, at age 39, Franklin D. Roosevelt, the man who would later be elected the 32nd president of the United States, was diagnosed with polio (poliomyelitis). His symptoms included fever, gastrointestinal issues, numbness, and leg and facial paralysis. The disease left him paralyzed from the waist down, relying on a wheelchair and leg braces to walk.

The paralysis from poliovirus infection affected the involuntary muscles that allow breathing, and iron lungs were used to keep patients breathing until they cleared the infection.
The paralysis from poliovirus infection affected the involuntary muscles that allow breathing, and iron lungs were used to keep patients breathing until they cleared the infection.

At the height of the polio epidemic in 1952, more than 3,000 people died of polio in the United States, and 20,000 more people suffered paralysis. Pictures of the era show children in special hospital wards, inside ominous-looking iron lungs, while “recovered” children played on the grounds of hospitals wearing leg braces.

In 1938, Roosevelt founded the March of Dimes, which funded the development of the Salk polio vaccine. Two years after the introduction of the Salk vaccine in 1955, polio cases in the US dropped by 90%. In fact, sustained polio transmission has been absent from the US for nearly 40 years; according to the CDC, the last case of wild poliovirus in the US occurred in 1979.

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The Bell Burnell Observatory: 140 Years of Inspiring Scientific Curiosity

The Bell Burnell Observatory, located at Promega Madison

On a hill at the top of the Promega Madison campus, an old observatory overlooks the city of Fitchburg, Wisconsin. Inside, cutting-edge telescopes are ready to give students and astronomers breathtaking views of the cosmos.

Over the past 140 years, this observatory has served as the first launchpad for storied careers in astronomy. Following a relocation, it gave a passionate community a home for their curiosity. Today, it supports modern research while also welcoming stargazers of all ages. It is now one of the oldest operational observatories in the United States. This is the Bell Burnell Observatory.

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A Different Kind of Sustainable Growth: What’s Happening in the Promega Garden

Tomatoes growing in the Promega garden
Tomato season is ending soon, and Mike has already harvested 2,500 pounds from the Promega garden.

Summer is winding down at Promega Madison. Kids are heading back to school, sunset is creeping earlier, and a new cycle of academic research projects are ramping up. However, in the Promega garden, Master Gardener Mike Daugherty is still hard at work harvesting fresh produce that will soon become delicious meals in our cafeterias. As the seasons begin to change, I stopped by to learn what’s happening on the farm. Here are a few highlights that Mike shared.

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Improved FFPE Tissue Sample Processing with High-Throughput Automated DNA Extraction

In oncology, tissue biopsies are commonly fixed in formalin and embedded in paraffin (FFPE). These FFPE samples can be used with immunohistochemical or molecular analysis for identifying biomarkers that guide the diagnosis and therapeutic management of patients. This fixation technique allows long-term storage of samples but impacts the integrity of nucleic acids. This makes extracting DNA and RNA from FFPE tissues in sufficient quantity and quality for molecular analysis techniques such as NGS analyses challenging for molecular oncology laboratories.

“At Rennes University Hospital, we receive many lung cancer samples with little material available, or samples of poor quality. The nucleic acid extraction step is therefore critical to get good yield. We have seen that it had a direct impact on the success of downstream analysis,” said Dr. Alexandra Lespagnol. Lespagnol is the Technical Manager of the Molecular Genetics of Cancer core lab at the University Hospital of Rennes in France.

In order to accommodate the increasing number of samples that needed to be analyzed, the Molecular Genetics of Cancer core lab of the University Hospital of Rennes initiated an automation project for extracting DNA from FFPE tissues. The lab also wanted to improve sample tracking and reproducibility of their results.

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From Outside the Window to Inside the Cell: How Photography has Broadened Our View of the World

Photography. From the time the first image was captured almost 200 years ago, people have been using photography techniques to record, improve and expand their world.  Joseph Nicéphore Niépce is credited with capturing the very first photograph—a view of outside his window—using a technique called heliography. From that blurry, one-of-a-kind print to the stunning images captured today we can capture using our mobile phones, the advances in personal photography have been phenomenal. But progress has not been limited to capturing images of the world we see, scientists have leveraged these advances into new tools to capture images of the world we can’t see.

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Keeping Cool When It Hurts: An Engineered Alternative to Pharmacological Pain Management

Pain management, particularly long-term pain management, is a difficult problem. Opioids are effective at reducing pain, but they are addictive and carry with them the significant costs of addiction and overdose that affect not only the individual but society as well. 

Saltatory conduction in neurons.  Localized cooling of neurons may provide a non-addictive method for pain management.

Recently, work presented in Science by Reeder and colleagues proposes an engineering solution to pain management: miniature, implantable devices that can deliver localized and reversible neural blocking to reduce pain. While such devices could deliver any kind of stimulus ranging from electrical to pharmacological, the researchers developed a device that temporarily blocks neural signals by cooling.

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