In the Literature

Blogs about published peer-reviewed scientific studies.

Measles and Immunosuppression—When Getting Well Means You Can Still Get Sick

Posted on by Kelly Grooms
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In 2000 measles was officially declared eliminated in the United States (1), meaning there had been no disease transmission for over 12 months. Unfortunately it was not gone for good. So far in 2024 there have been 8 outbreaks and 131 cases. Ninety of these case (69%) are associated with an outbreak and seventy (53%) have resulted in hospitalization (as of May 2, 2024; 2).  

Help in Limiting a Dangerous Childhood Disease

Before the development of a vaccine in the 1960s, measles was practically a childhood rite of passage. This common childhood disease is not without teeth however. One out of every 20 children with measles develops pneumonia, 1 out of every 1,000 develops encephalitis (swelling of the brain), and 1 to 3 of every 1,000 dies from respiratory and neurological complications (3). Between the years of 1958 and 1962, the US averaged 503,282 reported cases of measles (4). The first measles vaccine was licensed in the U.S. by John Enders in 1963, and not surprisingly, after the measles vaccine became widely used, the number of cases of measles plummeted. By 1970, there were under 1,000 cases (2).

Decreased Childhood Mortality from Other Infectious Diseases—An Unexpected Benefit

What was surprising was that with the disappearance of this childhood disease, the number of childhood deaths from all infectious diseases dropped dramatically. As vaccination programs were instituted in England and parts of Europe, the same phenomenon was observed. Reduction or elimination of measles-related illness and death alone can’t explain the size of the decrease in childhood mortality. Although measles infection is associated with suppression of the immune system that will make the host vulnerable to other infections, these side effects were assumed to be short lived. In reality, the drop in mortality from infectious diseases following vaccination for measles lasted for years, not months (5).

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Can AI Replace High-Throughput Screens for Drug Discovery?

Posted on by Johanna Lee
This image was created with the assistance of AI

For decades, pharmaceutical companies have relied on high-throughput screening (HTS) as the first step in the drug discovery process. After an initial screening of thousands of compounds, scientists select a smaller list of candidate drugs that is then used for further downstream testing. A major limitation to HTS, however, is the need to synthesize all compounds used in the screen—the compounds need to physically exist to be tested. This significantly limits the number of compounds that can be tested, hindering the discovery of new drugs.

What if we could test compounds even before they are synthesized?

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Silencing the Immunogenicity of AAV Vectors 

Posted on by Jordan Nutting

Recombinant adeno-associated viral (AAV) vectors are an appealing delivery strategy for in vivo gene therapy but face a formidable challenge: avoiding detection by an ever-watchful immune system (1,2). Efforts to compensate for the immune response to these virus particles have included immunosuppressive drugs and engineering the AAV vector to be especially potent to minimize its effective dosage. These methods, however, come with their own challenges and do not directly solve for the propensity of AAV vectors to induce immune responses.  

A recent study introduced a new approach to reduce the inherent immunogenicity of AAV vectors (2). Researchers strategically swapped out amino acids in the AAV capsid to remove the specific sequences recognized by T-cells that elicit the most pronounced immune response. As a result, they significantly reduced T-cell mediated immunogenicity and toxicity of the AAV vector without compromising its performance.  

Read on to get more of the study details, which include the use of NanoLuc® luciferase and Nano-Glo® Fluorofurimazine In Vivo Substrate for in vivo bioluminescent imaging of the AAV variants’ distribution and transduction efficiency in mice. 

A teal colored ribbon model of a AAV virus capsid floats against a black background.
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Connecting Synaptic Gene Polymorphisms to Parkinson’s Disease

Posted on by Kendra Hanslik
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Neurodegenerative disorders represent a significant and growing concern in the realm of public health, particularly as global populations age. Among these, Parkinson’s disease (PD) stands out due to its increasing prevalence and profound impact on individuals. Characterized by the progressive degeneration of motor functions, PD is not just a health challenge but also poses substantial socio-economic burdens. While the etiology of Parkinson’s disease is far from simple, current research efforts elucidating its causes, mechanisms, and potential treatments illustrate the critical nature of this neurodegenerative disorder in today’s healthcare landscape.

In the clinic, Parkinson’s disease is often diagnosed as either sporadic or familial. Familial PD has a clear genetic basis, typically passed down through families, while sporadic PD, comprising about 90% of cases, occurs in individuals without a known family history of the disease. The exact cause of sporadic PD is not fully understood but is believed to be due to a combination of genetic predispositions and environmental factors. In contrast, the factors involved in familial PD are more thoroughly understood, offering insights into the molecular mechanisms underlying PD pathogenesis.

Polymorphisms and Parkinson’s Disease Susceptibility

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How Avian Influenza Crosses Species

Posted on by Johanna Lee

Avian influenza, commonly known as bird flu, has become an increasingly severe public health issue. According to the CDC, the frequency of avian influenza outbreaks and diversity of virus subtypes have increased significantly in the past decade. In 2022, there were reports of sporadic H5 virus infections in mammals across several U.S. states, Canada, and other countries. Affected animals included fox kits, bobcats, coyote pups, raccoons, skunks, mink, and even seals. Human cases of H5N6 and other subtypes following poultry exposures were reported in China, with several cases resulting in severe or critical illness and death.

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Dynein Motor Proteins Could Be the Moving Power Behind Cancer Metastasis

Posted on by Kelly Grooms
3D Cancer Cell

“The cancer has spread.” are perhaps some of the most frightening words for anyone touched by cancer. It means that cancer cells have migrated away from the primary tumor, invaded health tissues and firmed secondary tumors. Called metastasis, this event is the deadliest feature of any type of cancer (1). The cellular mechanisms that play a role in metastasis could serve as powerful therapeutic targets. Unfortunately, understanding of these mechanisms is limited. However, some studies have suggested a link between the dysregulation of microtubule motors and cancer progression. A new study by a team from Penn State has revealed that the motor protein dynein plays a pivotal role in the movement of metastatic breast cancer cells through two model systems simulating soft tissues (1).

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The Tiniest Test Tube: Studying Cell-Specific Protein Secretion

Posted on by AnnaKay Kruger
Free floating single cells, blue
Researchers explore an innovative method for single-cell analysis

Cells produce proteins that serve different purposes in maintaining human health. These bioactive secretions range from growth factors to antibodies to cytokines and vary between different types of cells. Even within a certain cell type, however, there are individual cells that produce more secretions than others, a phenomenon that especially interests scientists studying cell-based therapies. In contrast to molecular therapies, which typically involve specific genes or proteins, a primary challenge to crafting cell therapies is the wide range of functional outputs seen in cells that have the same genetic template. This leads to the question of what molecular properties, from a genomic and transcriptomic perspective, would lead one cell to produce more of a protein than its companions. 

There have been few investigative strategies put forth that allow scientists to connect a cell’s characteristics and genetic coding with its secretions. In July 2023 a team of scientists published a paper in Nature Communications outlining an innovative solution: little hydrogel particles, or “nanovials”, that essentially serve as tiny test tubes and can be used to measure protein secretion, track transcriptome data, and identify relevant surface markers in a single cell.

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Will Artificial Intelligence (AI) Transform the Future of Life Science Research?

Posted on by Ken Doyle

Artificial intelligence (AI) is not a new technological development. The idea of intelligent machines has been popular for several centuries. The term “artificial intelligence” was coined by John McCarthy for a workshop at Dartmouth College in 1955 (1), and this workshop is considered the birthplace of AI research. Modern AI owes much of its existence to an earlier paper by Alan Turing (2), in which he proposed the famous Turing Test to determine whether a machine could exhibit intelligent behavior equivalent to—or indistinguishable from—that of a human.

The explosive growth in all things AI over the past few years has evoked strong reactions from the general public. At one end of the spectrum, some people fear AI and refuse to use it—even though they may have unwittingly been using a form of AI in their work for years. At the other extreme, advocates embrace all aspects of AI, regardless of potential ethical implications. Finding a middle ground is not always easy, but it’s the best path forward to take advantage of the improvements in efficiency that AI can bring, while still being cautious about widespread adoption. It’s worth noting that AI is a broad, general term that covers a wide range of technologies (see sidebar).

AI personified looking at a dna double helix against an abstract cosmic background
Image generated with Adobe Firefly v.2.

For life science researchers, AI has the potential to address many common challenges; a previous post on this blog discussed how AI can help develop a research proposal. AI can help with everyday tasks like literature searches, lab notebook management, and data analysis. It is already making strides on a larger scale in applications for lab automation, drug discovery and personalized medicine (reviewed in 3–5). Significant medical breakthroughs have resulted from AI-powered research, such as the discovery of novel antibiotic classes (6) and assessment of atherosclerotic plaques (7). A few examples of AI-driven tools and platforms covering various aspects of life science research are listed here.

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Cell-Based Target Engagement and Functional Assays for NLRP3 Inhibitor Profiling Help Identify Successes and Failures

Posted on by Kari Kenefick

Identifying Inflammasome Inhibitors: What’s Missing
The NLRP3 inflammasome is implicated in a wide range of diseases. The ability to inhibit this protein complex could provide more precise, targeted relief to inflammatory disease sufferers than current broad-spectrum anti-inflammatory compounds, potentially without side effects.

Studies of NLRP3 inflammasome inhibitors have relied on cell-free assays using purified NLRP3. But cell-free assays cannot assess physical engagement of the inhibitor and target in the cellular micro-environment. Cell-free assays cannot show if an NLRP3 inhibitor enters the cell, binds the target and how long the inhibitor binding lasts.

Cell-based assays that interrogate the physical interaction of the NLRP3 target and inhibitor inside cells are needed.

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Addressing the Problem of Dosing in Gene Therapy

Posted on by AnnaKay Kruger

One key obstacle to crafting effective gene therapies is the ability to tailor dosing according to a patient’s needs. This can be tricky because even if protein production is successful, staying within the therapeutic window is paramount—too much of a protein could be toxic, and too little will not produce the desired effect. This balance is difficult to achieve with current technologies. In a study recently published in Nature Biotechnology, researchers at Baylor College of Medicine investigated a possible solution to this problem, engineering a molecular “on/off” switch that could regulate gene expression and maintain protein production at dose-dependent, therapeutic levels.

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