. Scientific Frontline

Monday, March 18, 2024

UC Irvine-led research team discovers role of key enzymes that drive cancer mutations

“Both APOBEC3A and APOBEC3B were known to generate mutations in many kinds of tumors, but until now we did not know how to identify the specific type caused by each,” says the study’s corresponding author, Rémi Buisson (center), UCI assistant professor of biological chemistry. He’s flanked by postdoctoral fellow Pedro Ortega (left) and graduate student Ambrocio Sanchez, UCI researchers who developed a new method to characterize the particular kind of DNA modified by the enzymes.
Photo Credit: UCI School of Medicine

A research team led by the University of California, Irvine has discovered the key role that the APOBEC3A and APOBEC3B enzymes play in driving cancer mutations by modifying the DNA in tumor genomes, offering potential new targets for intervention strategies.

The study, published today online in the journal Nature Communications, describes how the researchers identified the process by which APOBEC3A and APOBEC3B detect specific DNA structures, resulting in mutations at distinct positions within the tumor genome.

“It’s critical to understand how cancer cells accumulate mutations leading to hot spots that contribute to disease progression, drug resistance and metastasis,” said corresponding author Rémi Buisson, UCI assistant professor of biological chemistry. “Both APOBEC3A and APOBEC3B were known to generate mutations in many kinds of tumors, but until now we did not know how to identify the specific type caused by each. This finding will allow us to develop novel therapies to suppress mutation formation by directly targeting each enzyme accordingly.”

Bridge in a box: Unlocking origami’s power to produce load-bearing structures

From left, Yi Zhu, a Research Fellow in Mechanical Engineering, and Evgueni Filipov, an associate professor in both Civil and Environmental Engineering and Mechanical Engineering, working in his lab in the George G. Brown Laboratories Building.
Image Credit: Brenda Ahearn/University of Michigan, College of Engineering, Communications and Marketing

For the first time, load-bearing structures like bridges and shelters can be made with origami modules—versatile components that can fold compactly and adapt into different shapes—University of Michigan engineers have demonstrated.

It’s an advance that could enable communities to quickly rebuild facilities and systems damaged or destroyed during natural disasters, or allow for construction in places that were previously considered impractical, including outer space. The technology could also be used for structures that need to be built and then disassembled quickly, such as concert venues and event stages.

“With both the adaptability and load-carrying capability, our system can build structures that can be used in modern construction,” said Evgueni Filipov, an associate professor of civil and environmental engineering and of mechanical engineering, and a corresponding author of the study in Nature Communications.

Principles of the origami art form allow for larger materials to be folded and collapsed into small spaces. And with modular building systems gaining wider acceptance, the applications for components that can be stored and transported with ease have grown.

New strategy to facilitate muscle regeneration after injury

From left to right, Ginés Viscor, Joan Ramon Torrella and Garoa Santocildes.
Photo Credit: Courtesy of University of Barcelona

Muscle injuries are common in the active population, and they cause the majority of player leaves in the world of sport. Depending on the severity, recovery of muscle function is quite slow and may require surgery, medication and rehabilitation. Now, a study led by the University of Barcelona reveals a strategy to improve and accelerate recovery from muscle injuries that has potential application in the sports and health sector in general.

This is the first study to provide scientific evidence for faster and more effective recovery from muscle injuries through intermittent exposure to low oxygen availability (hypoxia) in a low-barometric pressure (hypobaric) chamber that simulates high-altitude geographic conditions.

The new approach is important for the recovery of athletes — especially in the competitive elite — but also to mitigate the socio-economic impact of the loss of work productivity caused by these injuries on the active population.

The study, carried out with animal models, has been published in the Journal of Physiology. The authors of the study are the experts Garoa Santoildes, Teresa Pagès, Joan Ramon Torrella and Ginés Viscor, from the Department of Cell Biology, Physiology and Immunology of the UB’s Faculty of Biology.

All creatures great and small: Sequencing the blue whale and Etruscan shrew genomes

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Image Credit: AI Generated by Copilot / Designer / DALL-E 3

The blue whale genome was published in the journal Molecular Biology and Evolution, and the Etruscan shrew genome was published in the journal Scientific Data.

Research models using animal cell cultures can help navigate big biological questions, but these tools are only useful when following the right map.

“The genome is a blueprint of an organism,” says Yury Bukhman, first author of the published research and a computational biologist in the Ron Stewart Computational Group at the Morgridge Institute, an independent research organization that works in affiliation with the University of Wisconsin–Madison in emerging fields such as regenerative biology, metabolism, virology and biomedical imaging. “In order to manipulate cell cultures or measure things like gene expression, you need to know the genome of the species — it makes more research possible.”

The Morgridge team’s interest in the blue whale and the Etruscan shrew began with research on the biological mechanisms behind the “developmental clock” from James Thomson, emeritus director of regenerative biology at Morgridge and longtime professor of cell and regenerative bBiology in the UW School of Medicine and Public Health.  It’s generally understood that larger organisms take longer to develop from a fertilized egg to a full-grown adult than smaller creatures, but the reason why remains unknown.

“It’s important just for fundamental biological knowledge from that perspective. How do you build such a large animal? How can it function?” says Bukhman.

Attacking metastatic prostate cancer early with combination treatment approach improves outcomes in preliminary study

Photo Credit: Accuray

A team of UCLA Health Jonsson Comprehensive Cancer Center investigators has shown the combination of a short course of powerful and intense hormonal therapy with targeted radiation is safe and effective in treating people with prostate cancer that has come back and has spread to other parts of the body.

In the small study, researchers found that 50% of the patients who were treated with the combination therapy had no signs of the cancer and remained free of recurrence six months after their treatment, with less than a quarter experiencing severe side effects from the treatment. 

“In contrast, without this combined treatment approach, we would expect approximately 1% of patients to have no evidence of disease at the six-month stage,” said Dr. Amar Kishan, professor of radiation oncology at the David Geffen School of Medicine at UCLA and senior author of the study. “These results suggest a substantial improvement and strongly suggest there can be a meaningful impact —namely, delaying the need for hormonal therapy and thus without the significant side effects of it— by attacking metastatic prostate cancer early.”

The results were published in the journal of European Urology.

Nearly all men who are diagnosed with metastatic hormone-sensitive prostate cancer are treated with androgen deprivation therapy, a type of hormonal therapy that aims to lower the levels of male hormones called androgens that can stimulate the growth of prostate cancer cells. 

Bioengineers manage a first: measuring pH in cell condensates

Researchers were able to measure pH in a type of condensate called the nucleolus, the site of ribosome production. They report that the distinct protein compositions of nucleoli give them an acidic character.
 Image Credit: Matthew King

Scientists trying to understand the physical and chemical properties that govern biomolecular condensates now have a crucial way to measure pH and other emergent properties of these enigmatic, albeit important cellular compartments.

Condensates are communities of proteins and nucleic acids. They lack a membrane and come together and fall apart as needed. The nucleolus is a prominent condensate in cells. It serves vital roles in cellular physiology and is the site of ribosome production.

Ribosomes are the multi-protein and RNA assemblies where the genetic code is translated to synthesize proteins. Impairment of ribosome production and other nucleolar dysfunctions lie at the heart of cancers, neurodegeneration and developmental disorders.

In a first for the condensate field, researchers from the lab of Rohit Pappu, the Gene K. Beare Distinguished Professor of biomedical engineering, and colleagues in the Center for Biomolecular Condensates in the McKelvey School of Engineering at Washington University in St. Louis, figured out how nucleolar substructures are assembled. This organization gives rise to unique pH profiles within nucleoli, which they measured and compared with the pH of nearby non-nucleolar condensates including nuclear speckles and Cajal bodies.

Rice research could advance soft robotics manufacturing, design

Te Faye Yap (left) and Daniel Preston
Photo Credit: Jeff Fitlow/Rice University

Soft robots use pliant materials such as elastomers to interact safely with the human body and other challenging, delicate objects and environments. A team of Rice University researchers has developed an analytical model that can predict the curing time of platinum-catalyzed silicone elastomers as a function of temperature. The model could help reduce energy waste and improve throughput for elastomer-based components manufacturing.

“In our study, we looked at elastomers as a class of materials that enables soft robotics, a field that has seen a huge surge in growth over the past decade,” said Daniel Preston, a Rice assistant professor of mechanical engineering and corresponding author on a study published in Cell Reports Physical Science. “While there is some related research on materials like epoxies and even on several specific silicone elastomers, until now there was no detailed quantitative account of the curing reaction for many of the commercially available silicone elastomers that people are actually using to make soft robots. Our work fills that gap.”

The platinum-catalyzed silicone elastomers that Preston and his team studied typically start out as two viscoelastic liquids that, when mixed together, transform over time into a rubbery solid. As a liquid mixture, they can be poured into intricate molds and thus used for casting complex components. The curing process can occur at room temperature, but it can also be sped up using heat.

Manufacturing processes involving elastomers have typically relied on empirical estimates for temperature and duration to control the curing process. However, this ballpark approach makes it difficult to predict how elastomers will behave under varying curing conditions. Having a quantitative framework to determine exactly how temperature impacts curing speed will enable manufacturers to maximize efficiency and reduce waste.

Even small amounts of licorice raise blood pressure

Researchers have studied how licorice affects blood pressure, among other things.
Photo Credit: Marion Wellmann

It is known that large amounts of licorice cause high blood pressure. A study by researchers at Linköping University now shows that even small amounts of licorice raise blood pressure. The individuals who react most strongly also show signs of strain on the heart.

Licorice is produced from the root of plants of the Glycyrrhiza species and has long been used as an herbal remedy and flavoring. However, it is known that eating licorice can also raise blood pressure. This is mainly due to a substance called glycyrrhizic acid that affects the body’s fluid balance through effects on an enzyme in the kidney. High blood pressure, in turn, increases the risk of cardiovascular disease.

Both the European Union and the World Health Organization have concluded that 100 mg of glycyrrhizic acid per day is probably safe to eat for most individuals. But some people eat more licorice than that. The Swedish Food Agency has estimated that 5 per cent of Swedes have an intake higher than this level.

Alzheimer’s Drug Fermented with Help from AI and Bacteria Moves Closer to Reality

Photo-Illustration Credit: Martha Morales/The University of Texas at Austin

Galantamine is a common medication used by people with Alzheimer’s disease and other forms of dementia around the world to treat their symptoms. Unfortunately, synthesizing the active compounds in a lab at the scale needed isn’t commercially viable. The active ingredient is extracted from daffodils through a time-consuming process, and unpredictable factors, such as weather and crop yields, can affect supply and price of the drug. 

Now, researchers at The University of Texas at Austin have developed tools — including an artificial intelligence system and glowing biosensors — to harness microbes one day to do all the work instead. 

In a paper in Nature Communications, researchers outline a process using genetically modified bacteria to create a chemical precursor of galantamine as a byproduct of the microbe’s normal cellular metabolism.  Essentially, the bacteria are programmed to convert food into medicinal compounds.

“The goal is to eventually ferment medicines like this in large quantities,” said Andrew Ellington, a professor of molecular biosciences and author of the study. “This method creates a reliable supply that is much less expensive to produce. It doesn’t have a growing season, and it can’t be impacted by drought or floods.” 

Keeping score: novel method might help differentiate 2 serious skin diseases

Close-up of skin symptoms   
A scoring system has been developed to help distinguish between the two diseases. Left: generalized pustular psoriasis (GPP). Right: acute generalized exanthematous pustulosis (AGEP).   
Image Credit: Osaka Metropolitan Universit

Two rare skin conditions with similar symptoms can be mistaken for each other, so a scoring system has been formulated to aid physicians in distinguishing two diseases

Your skin becomes red and spots filled with pus appear, so you visit a dermatologist. When these symptoms spread to the skin throughout the body, it is difficult for the physician to distinguish whether it is generalized pustular psoriasis (GPP) or acute generalized exanthematous pustulosis (AGEP), as both have similar symptoms. The two diseases run different courses and require different treatments. Without proper treatment, the symptoms can worsen severely and cause complications, so it is essential to distinguish between them.

Researchers from Osaka Metropolitan University and the Mayo Clinic in the United States have developed a scoring system as a novel tool to distinguish between the two diseases. Led by Dr. Mika Yamanaka-Takaichi and Professor Daisuke Tsuruta, both from the Department of Dermatology at OMU’s Graduate School of Medicine, and Professor Afsaneh Alavi from the Department of Dermatology at the Mayo Clinic in Rochester, Minnesota, the team studied data on clinical symptoms and laboratory findings of the diseases to create the system.

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