. Scientific Frontline

Monday, March 18, 2024

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

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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.

Sandia collaboration produces improved microneedle technology

Adam Bolotsky demonstrates how Sandia National Laboratories, in collaboration with SRI, has enhanced the extraction of interstitial fluid. The improved extraction method gets more fluid in less time.
Photo Credit: Craig Fritz

Microneedles measure only two to three times the diameter of human hair and are about a millimeter long. But their impact is significant, from helping U.S. service members in the field diagnose infections earlier, to helping individuals monitor their own health.

Sandia National Laboratories is at the forefront of microneedle research and is partnering with others to expand the technology.

A microneedle is a minimally invasive way to sample interstitial fluid from under the skin. Interstitial fluid shares many similarities with blood, but there is still much to learn about it.

“When we started work in this field in 2011, our goal was to develop microneedles as a wearable sensor, as an alternate to blood samples,” said Ronen Polsky, who has led Sandia’s work in microneedles. Microneedles can access interstitial fluid for real-time and continuous measurements of circulating biomarkers.

“People wear continuous glucose monitors for blood sugar measurements,” Polsky said. “We want to expand this to a whole range of other conditions to take advantage of this minimally invasive sampling using microneedles.”

Using light to produce medication and plastics more efficiently

Radicals generated by light can only unfold their reactivity as soon as they break out of a kind of "cage" that the solvent forms around them. Researchers in Basel show how to make this "cage escape" more successful and how it leads to more efficient photochemistry.
Illustration Credit: University of Basel, Jo Richers

Anyone who wants to produce medication, plastics or fertilizer using conventional methods needs heat for chemical reactions – but not so with photochemistry, where light provides the energy. The process to achieve the desired product also often takes fewer intermediate steps. Researchers from the University of Basel are now going one step further and are demonstrating how the energy efficiency of photochemical reactions can be increased tenfold. More sustainable and cost-effective applications are now tantalizingly close.

Industrial chemical reactions usually occur in several stages across various interim products. Photochemistry enables shortcuts, meaning fewer intermediate steps are required. Photochemistry also allows you to work with less hazardous substances than in conventional chemistry, as light produces a reaction in substances which do not react well under heat. However, to this point there have not been many industrial applications for photochemistry, partly because supplying energy with light is often inefficient or creates unwanted by-products.

The research group led by Professor Oliver Wenger at the University of Basel now describes a fundamental principle which has an unexpectedly strong impact on the energy efficiency of photochemistry and can increase the speed of photochemical reactions. Their results are published in Nature Chemistry.

Two artificial intelligences talk to each other

A UNIGE team has developed an AI capable of learning a task solely on the basis of verbal instructions. And to do the same with a «sister» AI.
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Performing a new task based solely on verbal or written instructions, and then describing it to others so that they can reproduce it, is a cornerstone of human communication that still resists artificial intelligence (AI). A team from the University of Geneva (UNIGE) has succeeded in modelling an artificial neural network capable of this cognitive prowess. After learning and performing a series of basic tasks, this AI was able to provide a linguistic description of them to a ‘‘sister’’ AI, which in turn performed them. These promising results, especially for robotics, are published in Nature Neuroscience.

Performing a new task without prior training, on the sole basis of verbal or written instructions, is a unique human ability. What’s more, once we have learned the task, we are able to describe it so that another person can reproduce it. This dual capacity distinguishes us from other species which, to learn a new task, need numerous trials accompanied by positive or negative reinforcement signals, without being able to communicate it to their congeners.

A sub-field of artificial intelligence (AI) - Natural language processing - seeks to recreate this human faculty, with machines that understand and respond to vocal or textual data. This technique is based on artificial neural networks, inspired by our biological neurons and by the way they transmit electrical signals to each other in the brain. However, the neural calculations that would make it possible to achieve the cognitive feat described above are still poorly understood.

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