Thursday, January 04, 2024

Study reveals clues to how Eastern equine encephalitis virus invades brain cells

Structural biology research also enables scientists to design decoy molecule that blocks deadly infection

WASHINGTON UNIVERSITY SCHOOL OF MEDICINE

EEEV — IMAGE:
RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE DETERMINED HOW EASTERN EQUINE ENCEPHALITIS VIRUS ATTACHES TO A RECEPTOR IT USES TO ENTER AND INFECT CELLS. THE WHOLE VIRUS IS SHOWN ON THE LEFT AND A MAGNIFIED VIEW OF THE VIRAL STRUCTURAL PROTEINS ON THE RIGHT. THE FINDINGS LAID THE GROUNDWORK FOR A RECEPTOR DECOY MOLECULE THAT PROTECTS MICE FROM ENCEPHALITIS CAUSED BY THE VIRUS.
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CREDIT: LUCAS ADAMS/WASHINGTON UNIVERSITY

An atomic-level investigation of how Eastern equine encephalitis virus binds to a key receptor and gets inside of cells also has enabled the discovery of a decoy molecule that protects against the potentially deadly brain infection, in mice.

The study, from researchers at Washington University School of Medicine in St. Louis, is published Jan. 3 in the journal Cell. By advancing understanding of the complex molecular interactions between viral proteins and their receptors on animal cells, the findings lay a foundation for treatments and vaccines for viral infections.

“Understanding how viruses engage with the cells they infect is a critical part of preventing and treating viral disease,” said co-senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor at Washington University. “Once you understand that, you have the foundation for developing vaccines and drugs to block it. In this study, it took us a long time to sort out the complexity associated with the particular receptor-virus interaction, but once we acquired this knowledge, we were able to design a decoy molecule that turned out to be very effective at neutralizing the virus and protecting mice from disease.”

Though infections of Eastern equine encephalitis virus in people are rare — with only a few cases reported worldwide each year — about one-third of those with the infection die, and many survivors suffer lasting neurological problems. Further, scientists predict that as the planet warms and climate change lengthens mosquito populations’ seasons and geographical reach, risk of infection will grow. At present, there are no approved vaccines against the virus or specific medications to treat it.

As a first step to finding ways to treat or prevent the deadly virus, Diamond and co-senior author Daved H. Fremont, PhD, a professor of pathology & immunology, set about investigating how the virus attaches to one of its key receptors — a molecule called VLDLR, or very low density lipoprotein receptor. The molecule is found on the surface of cells in the brain and other parts of the body. Co-first author Lucas Adams, an MD/PhD student in the Fremont and Diamond laboratories, used cryo-electron microscopy to reconstruct the virus binding to the receptor in atomic-level detail.

The results turned out to be unexpectedly complex. The molecule is composed of eight repeated segments, called domains, strung together like beads on a chain. Usually, a viral protein and its receptor fit together in one very specific way. In this case, however, two or three different spots on the viral surface proteins were capable of attaching to any of five of the molecule’s eight domains.

“What’s really striking is that we find multiple binding sites, but the chemistry of each of the binding sites is very similar and also similar to the chemistry of binding sites for other viruses that interact with related receptors,” said Fremont, who is also a professor of biochemistry & molecular biophysics and of molecular microbiology. “The chemistry just works out well for the way viruses want to attach to cell membranes.”

The domains that make up this molecule also are found in several related cell-surface proteins. Similar domains are found in proteins from across the animal kingdom.

“Since they’re using a molecule that naturally has repetitive domains, some of the alphaviruses have evolved to use the same strategy of attachment with multiple different domains in the same receptor,” said Diamond, who is also a professor of medicine, of molecular microbiology, and of pathology & immunology. Alphaviruses include Eastern equine encephalitis virus and several other viruses that cause brain or joint disease. “There are sequence differences in the VLDLR receptor over evolution in different species, but since the virus has this flexibility in binding, it is able to infect a wide variety of species including mosquitoes, birds, rodents and humans.”

To block attachment, the researchers created a panel of decoy receptors by combining subsets of the eight domains. The idea was that the virus mistakenly would bind to the decoy instead of the receptor on cells, and the decoy with the virus attached could then be cleared away by immune cells.

Co-first author Saravanan Raju, MD, PhD, a postdoctoral researcher in the Diamond lab, evaluated the panel of decoys. First, he tested them on cells in dishes. Many neutralized the virus. Then, he turned to mice. Raju pretreated mice with a decoy or saline solution, as a control, six hours before injecting the virus under their skin, a mode of infection that mimics natural infection via mosquito bite. Three decoys were tested: one known to be unable to neutralize the virus; one made from the full-length molecule; and one made from just the first two domains.

All of the mice that received saline solution, the non-neutralizing decoy or the full-length decoy died within eight days of infection. All of the mice that received the decoy made from the first two domains survived without signs of illness.

Certain aspects of its biology give Eastern equine encephalitis virus the potential to be weaponized, making it particularly important to find a way to protect against it. In a subsequent experiment in which the mice were infected by inhalation — as would happen if the virus were aerosolized and used as a bioweapon — the decoy made from the first two domains was still effective, reducing the mice’s chance of death by 70%.

“Through a combination of the structural work and the domain deletion work, we were able to figure out which domains are the most critical and create a quite effective decoy receptor that can neutralize viral infection,” Fremont said. “This study broadens what we know about virus-receptor interactions and could lead to new approaches to preventing viral infections.”

JOURNAL

Cell

DOI

10.1016/j.cell.2023.11.031

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Structural and functional basis of VLDLR usage by Eastern equine encephalitis virus

ARTICLE PUBLICATION DATE

3-Jan-2024

COI STATEMENT

Diamond is a consultant or adviser for Inbios, Ocugen, Vir Biotechnology, Topspin Therapeutics, Moderna, Merck, and Immunome. The Diamond laboratory has received funding support from Emergent BioSolutions, Moderna, and Vir Biotechnology. Fremont is a founder of Courier Therapeutics and has received funding support from Emergent BioSolutions and Mallinckrodt Pharmaceuticals.

Computational method discovers hundreds of new ceramics for extreme environments

A new computational method unveils hundreds of new ceramic materials with a wide range of potentially industry-disrupting properties like electronics that could function in a lava bath

Peer-Reviewed Publication

DUKE UNIVERSITY

Molecular Boxes — IMAGE:
AN ARTISTIC REPRESENTATION OF THE MOLECULAR STRUCTURE OF THE NEWLY DISCOVERED CERAMIC MATERIALS THAT COULD POTENTIALLY DISRUPT SEVERAL INDUSTRIES THANKS TO THEIR ABILITY TO CREATE FUNCTIONAL ELECTRONICS AT THOUSANDS OF DEGREES.
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CREDIT: HAGEN ECKERT, DUKE UNIVERSITY

DURHAM, N.C. – If you have a deep-seated, nagging worry over dropping your phone in molten lava, you’re in luck.

A research team led by materials scientists at Duke University has developed a method for rapidly discovering a new class of materials with heat and electronic tolerances so rugged that they that could enable devices to function at lava-like temperatures above several thousands of degrees Fahrenheit.

Harder than steel and stable in chemically corrosive environments, these materials could also form the basis of new wear- and corrosion-resistant coatings, thermoelectrics, batteries, catalysts and radiation-resistant devices.

The recipes for these materials — ceramics made using transition metals carbonitrides or borides — were discovered through a new computational method called Disordered Enthalpy-Entropy Descriptor (DEED). In its first demonstration, the program predicted the synthesizability of 900 new formulations of high-performance materials, 17 of which were then tested and successfully produced in laboratories.

The results appear online January 3 in the journal Nature and include contributions from collaborators at Penn State University, Missouri University of Science and Technology, North Carolina State University, and State University of New York at Buffalo.

“The capability of rapidly discovering synthesizable compositions will allow researchers to focus on optimizing their industry-disrupting properties,” said Stefano Curtarolo, the Edmund T. Pratt Jr. School Distinguished Professor of Mechanical Engineering and Materials Science at Duke.

The Curtarolo group maintains the Duke Automatic-FLOW for Materials Database (AFLOW)—an enormous reservoir of material properties data connected to many online tools for materials optimization. This wealth of information allows algorithms to accurately predict the properties of unexplored mixtures without having to attempt to simulate the complexities of atomic dynamics or make them in the laboratory.

For the past several years, the Curtarolo group has been working to develop predictive powers for “high-entropy” materials that derive enhanced stability from a chaotic mixture of atoms rather than relying solely on the orderly atomic structure of conventional materials. In 2018, they discovered high-entropy carbides, which were a simpler, special-case scenario.

“The high-entropy carbides all had a relatively uniform amount of enthalpy, so we could ignore part of the equation,” Curtarolo said. “But to predict new ceramic recipes with other transition metals, we had to address the enthalpy.”

To better understand the concepts of entropy and enthalpy in this application, think of a 10-year-old trying to construct a doghouse out of a giant pile of Legos. Even with limited types of building blocks, there would be many possible design outcomes.

In simple terms, enthalpy is a measure of how sturdy each design is, and entropy a measure of the number of possible designs that all have similar strength. The first promotes ordered configurations, like those that might be found in instruction booklets. The latter captures the unavoidable chaos that would occur as the child puts more time and energy into the increasingly confusing construction effort. Both are a measure of the amount of energy and heat that end up being absorbed into the final product.

“To rapidly quantify both enthalpy and entropy, we had to calculate the energy contained within the hundreds of thousands of various combinations of ingredients that we could potentially create instead of the ceramics we’re looking for,” Curtarolo said. “It was a mammoth undertaking.”

Besides predicting new recipes for stable disordered ceramics, DEED also helps direct their further analysis to discover their inherent properties. To find the optimal ceramics for various applications, researchers will need to refine these calculations and physically test them in laboratories.

DEED is specifically tailored to a production method called hot-pressed sintering. This involves taking powdered forms of the constituent compounds and heating them in a vacuum to as high as 4000 degrees Fahrenheit while applying pressure for times that can be as long as a few hours. Between all the preparation, reaction and cooling times, the entire process takes more than eight hours.

“The final step in synthesis, called spark plasma sintering, is an emerging method in materials science that is common in research labs,” said William Fahrenholtz, the Curators’ Distinguished Professor of Ceramic Engineering at Missouri S&T.

The finished ceramics have a metallic appearance and look dark grey or black. They feel like metal alloys such as stainless steel and have a similar density, but they are much darker in appearance. And even though they appear metallic, they are hard and brittle like conventional ceramics.

Moving forward, the group expects other researchers to begin using DEED to synthesize and test the properties of new ceramic materials for various applications. Given the incredible array of potential properties and uses, they believe it’s only a matter of time before some of them enter commercial production.

“Spark plasma sintering or field assisted sintering technology (FAST) is not a common technique in industry yet,” added Doug Wolfe, professor of materials science and engineering and associate vice president for research at Penn State. “However, current ceramic manufacturers could pivot to making these materials by making small adjustments to existing processes and facilities.”

This research was primarily supported by a five-year, $7.5 million grant through the US Department of Defense’s Multidisciplinary University Research Initiative (MURI) competition led by Curtarolo (N00014-21-1-2515, N00014-23-1-2615) and the Department of Defense High Performance Computing Modernization Program (HPC-Frontier).

CITATION: “Disordered Enthalpy-Entropy Descriptor for High-Entropy Ceramics Discovery,” Simon Divilov, Hagen Eckert, David Hicks, Corey Oses, Cormac Toher, Rico Friedrich, Marco Esters, Michael J. Mehl, Adam C. Zettel, Yoav Lederer, Eva Zurek, Jon-Paul Maria, Donald W. Brenner, Xiomara Campilongo, Suzana Filipović, William G. Fahrenholtz, Caillin J. Ryan, Christopher M. DeSalle, Ryan J. Crealese, Douglas E. Wolfe, Arrigo Calzolari and Stefano Curtarolo. Nature, Jan. 3, 2024`. DOI: 10.1038/s41586-023-06786-y

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JOURNAL

Nature

DOI

10.1038/s41586-023-06786-y

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Disordered enthalpy-entropy descriptor for high-entropy ceramics discovery.

ARTICLE PUBLICATION DATE

3-Jan-2024

Beta blocker used to treat heart problems and other medical concerns could be new treatment for sickle cell cardiomyopathy

Grant and Award Announcement

INDIANA UNIVERSITY SCHOOL OF MEDICINE

INDIANAPOLIS—A beta blocker typically used to treat heart problems, hemangioma, migraines and anxiety could be a new therapeutic for patients with sickle cell disease. Researchers led by Ankit A. Desai, MD, associate professor of medicine at the Krannert Cardiovascular Research Center (KCVRC) at Indiana University School of Medicine, have been awarded a $3 million grant by the U.S. Department of Defense to evaluate the efficacy of this drug.

Patients with sickle cell disease, a red blood cell disorder that can cause harm to multiple organs when red blood vessels are blocked or when the cells break down, are at risk of major complications when they also develop heart damage. The median age of death is 43 years old.

“Cardiomyopathy or heart damage can predispose patients to a fatal rhythm disturbance called ventricular tachycardia,” Desai said. “We believe that inflammation plays a key role in both, creating this injurious heart and exacerbating it. We are deeply interested in translating this potential therapeutic to patients, developing a clinical trial and trying to understand the impact R-propranolol, given that propranolol appears to be well tolerated in patients otherwise.”

Propranolol is a mixture of two chemical formulations – R-prop and S-Propranolol, which are similar in composition. The only difference is that R-prop does not demonstrate as much beta blocker activity. The team also plans to evaluate potential for toxicity before introducing R-prop in a clinical trial.

“Evaluating a therapeutic that has already been consumed by millions for other diseases could help accelerate the potential use in patients with sickle cell more quickly,” said Desai, principal investigator of the study, a cardiologist at IU Health and leader of KCVRC’s Cardiopulmonary Research Program. “This grant will allow us to study heart injury as well as rhythm disturbance impact in preclinical models of sickle cell disease. The study funds a disease that is underrecognized and underrepresented and supports a broader goal at closing health care gaps.”

Desai will collaborate with Bum-Rak Choi, PhD, associate professor of medicine at Rhode Island Hospital and Brown University. He will work closely with Choi on data related to the development of fatal arrhythmias in sickle cell disease.

“While new therapies are being explored, cleverly repurposed drugs that have already had human exposure with strong safety profile, such as R-propranolol, stand to make major headway in solving a long-standing health issue affecting the heart and cardiovascular system in the United States and abroad,” said Rohan Dharmakumar, PhD, executive director of the KCVRC.

About IU School of Medicine

IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability

Researchers improve seed nitrogen content by reducing plant chlorophyll levels

Peer-Reviewed Publication

CARL R. WOESE INSTITUTE FOR GENOMIC BIOLOGY, UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

Researcher image — IMAGE:
YOUNG CHO USED AN ETHANOL SPRAY TO REDUCE THE CHLOROPHYLL LEVELS IN LEAVES. THE SPRAY INDUCED SMALL RNA THAT INTERFERED WITH CHLOROPHYLL SYNTHESIS RESULTING IN PALE YELLOW PLANTS, AND THE UNTREATED PLANTS REMAINED COMPLETELY GREEN.
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CREDIT: CLAIRE BENJAMIN

Chlorophyll plays a pivotal role in photosynthesis, which is why plants have evolved to have high chlorophyll levels in their leaves. However, making this pigment is expensive because plants invest a significant portion of the available nitrogen in both chlorophyll and the special proteins that bind it. As a result, nitrogen is unavailable for other processes. In a new study, researchers reduced the chlorophyll levels in leaves to see if the plant would invest the nitrogen saved into other process that might improve nutritional quality.

Over the past few decades, researchers have been trying to increase crop yield to meet the global food demand. One of their biggest challenges has been to improve the photosynthetic efficiency of agricultural crops.

When light hits a leaf, one of three things can happen: the leaf can absorb the light for photosynthesis, the leaf can reflect it back into the atmosphere, or the light can pass through the leaf. Unfortunately, even though a fully green leaf absorbs over 90% of the light that hits it, the leaf doesn’t use it all for photosynthesis.

“We grow our crop plants at very high densities. As a result, although the leaves at the top of the canopy have more light, they cannot use it all and the layer below is light starved,” said Don Ort (GEGC leader/CABBI/BSD), a professor of integrative biology. “Our rationale was to reduce the amount of chlorophyll at the top of the canopy so more light can penetrate and be used more efficiently lower in the canopy.”

In the current study, the researchers engineered tobacco plants to have lower chlorophyll levels as the crop canopy grows more dense.

“Previous models have shown that if you have lower chlorophyll levels before you have a dense canopy, it is detrimental to plant growth,” Ort said. “We wanted to take plants that have full canopies and ensure that the new leaves that are added on top have lower chlorophyll levels.”

To do so, the researchers used small RNAs that interfere with key steps in chlorophyll synthesis. The production of these small RNAs were put under the control of an inducible promoter—a piece of DNA that responds to a specific signal and directs the cell to produce RNA.

In the study, the researchers used an ethanol-inducible promoter. When they sprayed the leaves with ethanol, the resulting small RNAs interfered with the synthesis of chlorophyll, creating a canopy that had a lighter shade of green.

“We found that even when chlorophyll synthesis decreased 70%, there was no inhibition of growth,” said Young Cho, a postdoctoral researcher in the Ort lab and the study’s lead author. “Although we had theoretically predicted this result, observing these pale green or yellow plants growing normally was astonishing, considering that such discoloration typically indicates plant illness.”

The researchers had also hypothesized that decreasing the amount of chlorophyll would influence other aspects of plant growth because it would free up the nitrogen that was being invested into making the pigment and associated proteins. They were proven right when they saw that the seed nitrogen concentration was 17% higher in the plants in which the ethanol-inducible promoter controlling the interfering small RNAs were activated.

“We had also expected an increase in yield because as you get more light into the canopy, you would expect it to be used more efficiently,” Ort said. “However, we didn’t detect an increase, which probably means that the plants did not invest enough of the extra nitrogen to improve the photosynthetic capacity in the lower parts of the canopy. This result gives us another engineering target.”

In their future work, the researchers will test whether they can get similar results with light-inducible promoters, which farmers will find easier to use. “Ethanol-inducible promoters are very convenient and important research tools. However, farmers will not want to spray an entire field with ethanol, so we need to look at other promoters that respond to the intensity or the color of light,” Ort said.

The study “Reducing chlorophyll levels in seed-filling stages results in higher seed nitrogen without impacting canopy carbon assimilation,” was published in Plant, Cell & Environment and can be found at https://doi.org/10.1111/pce.14737.

This work is supported by the research project Realizing Increased Photosynthetic Efficiency (RIPE) which is funded by the Bill & Melinda Gates Foundation, Foundation for Food and Agriculture Research, and U.K. Foreign, Commonwealth & Development Office.

JOURNAL

Plant Cell & Environment

DOI

10.1111/pce.14737

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Reducing chlorophyll levels in seed-filling stages results in higher seed nitrogen without impacting canopy carbon assimilation

Survival of the fittest: Words like 'Sex' and 'fight' are most likely to stand the test of time

New research from the University of Warwick reveals that words like 'sex' endure in our language in a ‘survival of the fittest’ way, similar to natural selection

Peer-Reviewed Publication

UNIVERSITY OF WARWICK

New research from the University of Warwick reveals that words like 'sex' endure in our language in a ‘survival of the fittest’ way, similar to natural selection.

Whilst the recent announcement of Word of the Year explores new words, like ‘rizz’ or ‘situationship’, Professor Thomas Hills’ research delves into why some words survive in our modern linguistic landscape, while others don’t.

The study concludes that words with the strongest lasting power are:

Words acquired earlier in life
Words associated with things people can see or imagine, termed 'concrete' words. For example, cat' is more concrete than 'animal', which is more concrete than 'organism'.
Words that are more arousing, including words like ‘sex’ and ‘fight’

Academics suggest that these findings shed light on how the human brain processes and filters information—a process known as 'cognitive selection.' This becomes crucial in today's world, where various information forms continually compete for our attention.

Thomas Hills, professor of Psychology at the University of Warwick and an author of the study, said:

“Information is a complex organism, constantly evolving as it undergoes cognitive selection within our minds.

“Languages change due to social, cultural, and cognitive influences. Information environments evolve due to war, disease, population changes, and technological innovations. However, the mind remains relatively stable, capable of exerting lasting impacts on language evolution. This cognitive selection influences what, in an information marketplace, will endure.

“Our study finds that properties like early acquisition, concreteness, and arousal give linguistic information a selective advantage.”

The first study involved a story-retelling experiment where more than 12,000 people were asked to retell a collection of thousands of short stories, each on average 200 words long. For the second part of the study, psychologists analysed millions of words of language from fiction and non-fiction books, newspapers, and magazines, over hundreds of years, from 1800 up to 2000.

The research, How cognitive selection affects language change, is published in the Proceedings of the National Academy of Sciences (PNAS). www.pnas.org/doi/10.1073/pnas.2220898120

New research from the University of Warwick reveals that words like 'sex' endure in our language in a ‘survival of the fittest’ way, similar to natural selection.

The study concludes that words with the strongest lasting power are:

Words acquired earlier in life
Words associated with things people can see or imagine, termed 'concrete' words. For example, cat' is more concrete than 'animal', which is more concrete than 'organism'.
Words that are more arousing, including words like ‘sex’ and ‘fight’

“Our study finds that properties like early acquisition, concreteness, and arousal give linguistic information a selective advantage.”

The research, How cognitive selection affects language change, is published in the Proceedings of the National Academy of Sciences (PNAS). www.pnas.org/doi/10.1073/pnas.2220898120

Older adults with newly diagnosed migraine disorder three times more likely to have motor vehicle crash

Study finds older adult drivers with history of migraines were not at increased risk of motor vehicle crashes, while drivers with new onset of migraines are more than three times as likely to experience a crash

Peer-Reviewed Publication

UNIVERSITY OF COLORADO ANSCHUTZ MEDICAL CAMPUS

A new study from researchers at the University of Colorado Anschutz Medical Campus finds that older adult drivers who are recently diagnosed with migraines are three times as likely to experience a motor vehicle crash. Older adult drivers who reported having ever had migraines in the past were no more likely to have a motor vehicle crash than those without migraines.

Additionally, study results, published in the Journal of the American Geriatrics Society, explored the relationships medications commonly prescribed for migraine management have with increased crash risk.

“Migraine headaches affect more than 7% of U.S. adults over the age of 60,” says Carolyn DiGuiseppi, MPH, PhD, MD, professor with the Colorado School of Public Health and study lead author. “The US population is aging, which means increasing numbers of older adult drivers could see their driving abilities affected by migraine symptoms previously not experienced. These symptoms include sleepiness, decreased concentration, dizziness, debilitating head pain and more.”

Researchers conducted a five-year longitudinal study of more than 2,500 active drivers aged 65-79 in five sites across the United States. Participants were categorized as having previously been diagnosed with migraine symptoms (12.5%), no previous diagnosis but experienced symptoms during the study timeframe (1.3%) or never migraine respondents. Results indicate those with previous diagnosis did not have a different likelihood of having crashes after baseline, while those with new onset migraines were three times as likely to experience a crash within one year of diagnosis. However, previously diagnosed drivers experienced more hard braking events compared to adults who had never experienced a migraine.

Additionally, researchers examined the role medications commonly prescribed for migraines have in motor vehicle events and found that there was no impact on the relationship between migraines and either crashes or driving habits. However, few participants in the study sample were using acute migraine medications.

“These results have potential implications for the safety of older patients that should be addressed,” says DiGuiseppi. “Patients with a new migraine diagnosis would benefit from talking with their clinicians about driving safety, including being extra careful about other risks, such as distracted driving, alcohol, pain medication and other factors that affect driving.”

This research was sponsored by AAA Foundation for Traffic Safety and was co-authored by Emmy Betz, MD, MPH of the Injury and Violence Prevention Center at the University of Colorado Anschutz Medical Campus

JOURNAL

Journal of the American Geriatrics Society

DOI

10.1111/jgs.18719

ARTICLE TITLE

Migraine headaches are associated with motor vehicle crashes and driving habits among older drivers: Prospective cohort study

Seismic and infrasonic signals used to characterize Nord Stream pipeline events

Peer-Reviewed Publication

SEISMOLOGICAL SOCIETY OF AMERICA

Seismic events that coincided with sudden drops in pressure within the Nord Stream 1 and 2 natural gas pipelines in September 2022 alerted the world to the rupture of pipelines in the western Baltic Sea. The suspected act of sabotage, which reportedly used explosive charges to rupture the pipelines, is still under investigation by multiple countries.

A new study published in The Seismic Record provides further evidence that the Nord Stream seismic signals came from a complex source. The signals lasted longer than would be expected from a single explosive source, the researchers say, and were more like the signals detected from an underwater volcano or a pipeline venting gas.

The initial signals from seismic events detected on 26 September 2022 “may be dominated by energy generated by the rapid venting of high-pressure gas, which means it may be difficult to assess the source size and characteristics of any explosive charges used to rupture the Nord Stream pipelines,” said Ross Heyburn of AWE Blacknest.

The Nord Stream events offer a rare opportunity to study seismic and infrasound signals from the rupture of an underwater gas pipeline, Heyburn and colleagues noted. The researchers had access to data collected by local and regional seismic networks as well as seismic and infrasound data collected by the International Monitoring System (IMS), a global network that detects nuclear and other explosions for the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO).

“To the best of our knowledge, this was the first time that the IMS has recorded signals from an underwater event associated with a gas pipeline rupture,” Heyburn said. “The events therefore provided an opportunity to observe the characteristics of signals, such as the long durations, generated by this type of source.”

Natural seismic activity in the region is low, but the research team was able to analyze the Nord Stream signals with the help of seismic data from a few small earthquakes and explosions detonated during a 2019 NATO operation in the region to clear World War II British ground mines.

One of the methods seismologists use to determine whether a seismic event is caused by an explosion or an earthquake is to measure the ratio of P to S waves for the event. Explosions usually have a higher ratio of P to S waves than earthquakes, and the Nord Stream events are very different to nearby earthquakes in this regard, the researchers concluded.

The spectra of seismic signals from underwater explosions sometimes display a series of modulations caused by interference between the primary pulse generated by the explosion and later pulses generated by the changing size of the gas bubble created by the explosion. Heyburn and colleagues did not observe this series of modulations clearly, which suggests a complex source rather than a simple explosion source for the Nord Stream events.

One of the most striking features of the Nord Stream events is its long-lasting seismic and infrasonic signals, the researchers found. These signals decay slowly over thousands of seconds—much longer than would be expected from an impulsive, single explosion event. For instance, the infrasound recorded in Southern Germany from the first Nord Stream event of 26 September lasted about 2000 seconds, while an impulsive event recorded at that distance would normally last no longer than about 600 seconds.

These long-lasting seismic and infrasound signals are likely the result of vibrations caused by high-pressure gas venting rapidly from the pipeline into the water and atmosphere. The lengthy signals are similar to seismic signals caused by roaring flames when pipelines explode on land, Heyburn and colleagues concluded, noting that the duration of the Nord Stream infrasound signals was similar to those detected during venting by underwater volcanoes.

The researchers also compared the magnitude of the first Nord Stream pipeline seismic event to the magnitude of a seismic event on 7 October 2023 caused by the underwater rupture of the Balticconnector gas pipeline connecting Finland and Estonia. The Balticconnector pipeline rupture is thought to have been caused by a ship’s anchor rather than an explosive charge.

The difference in seismic magnitudes between the two events “is consistent with the estimated potential energy ratio of the gas in each of these pipelines,” Heyburn explained, which suggests that seismoacoustic signals from the initial Nord Stream event were dominated by the rapid venting of high-pressure gas.

JOURNAL

The Seismic Record

DOI

10.1785/0320230047

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

The 26 September 2022 Nord Stream Events: Insights from Nearby Seismic Events

ARTICLE PUBLICATION DATE

3-Jan-2024

Surprise! – How the brain learns to deal with the unexpected

Peer-Reviewed Publication

UNIVERSITY OF BASEL

For children, the world is full of surprises. Adults, on the other hand, are much more difficult to surprise. And there are complex processes behind this apparently straightforward state of affairs. Researchers at the University of Basel have been using mice to decode how reactions to the unexpected develop in the growing brain.

Babies love playing peekaboo, continuing to react even on the tenth sudden appearance of their partner in the game. Recognizing the unexpected is an important cognitive ability. After all, new can also mean dangerous.

The exact way in which surprises are processed in the brain changes as we grow, however: unusual stimuli are much more quickly categorized as “important” or “uninteresting”, and are significantly less surprising the second and third time they appear. This increased efficiency makes perfect sense: new stimuli may gain our attention, but do not cause an unnecessarily strong reaction that costs us energy. While this may appear trivial at first, so far there has been very little research into this fact in the context of brain development.

Experiments with young mice conducted by Professor Tania Barkat’s research team have now begun to decode how the developing brain processes surprising sounds and what changes as we grow up. The researchers have reported on their findings in the journal Science Advances.

Strange sounds

In their experiments, the researchers used sequences of sounds in which a different tone was heard at irregular intervals in between a series of identical ones. At the same time, they recorded the animals’ brain waves. This process is known as the “oddball paradigm”, and is used by health professionals for purposes such as the diagnosis of schizophrenia.

Using these measurements, the researchers were able to understand how the reaction of different brain regions to the change of tone developed over time in the young mice. This reaction was initially very strong, but decreased as the relevant brain region matured, to a level comparable to that of measurements in adult animals. This development does not take place simultaneously in the various areas of the brain that process sound, however.

A region known as the inferior colliculus, located at the beginning of the path from the auditory nerve to the auditory cortex, was already fully mature in the animals at the age of 20 days, the earliest point in time studied by the team. A second site, the auditory thalamus, only showed an “adult” reaction to the differing tone at the age of 30 days.

Development in the cerebral cortex itself, the “primary auditory cortex”, took even longer, until day 50. “This development of the surprise reaction thus begins in the periphery and ends in the cerebral cortex,” says study leader Tania Barkat. The cerebral cortex therefore matures much later than expected – in human years, this would equate roughly to the early 20s.

No development without experience

The researchers also observed that experiences play a key role in the development of the surprise response in the cerebral cortex. If the mice were reared in a noise-neutral environment, the processing of unexpected sounds in the auditory cortex was significantly delayed.

One possible explanation for this is that the brain – and the cerebral cortex in particular – forms an internal image of the world during growth, which it then compares with external stimuli. Anything that does not correspond to this “worldview” is a surprise, but may also result in an update. “Without experience with sounds, however, the cerebral cortex in these mice is unable to develop such a model of the world,” says neuroscientist Barkat. As a result, the animal is unable to categorize sounds properly into “familiar” and “unexpected”.

JOURNAL

Science Advances

DOI

10.1126/sciadv.adi7624

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Sequential maturation of stimulus-specific adaptation in the mouse lemniscal auditory system

ARTICLE PUBLICATION DATE

3-Jan-2024

Genetic variants underlying male bisexual behavior, risk-taking linked to more children, study shows

Peer-Reviewed Publication

UNIVERSITY OF MICHIGAN

ANN ARBOR—Because same-sex sexual behavior does not result in offspring, evolutionary biologists have long wondered how the genes associated with this behavior have persisted in the human genome, and whether they will remain in the future.

A new University of Michigan-led study, scheduled for publication Jan. 3 in the journal Science Advances, suggests that part of the explanation—specifically for male bisexuals—has to do with risk-taking behavior.

The U-M researchers analyzed data from more than 450,000 participants of European ancestry in the United Kingdom's Biobank database of genetic and health information. Participants responded to a questionnaire that included the question, "Would you describe yourself as someone who takes risks?"

The U-M analysis revealed that male heterosexuals who carry the genetic variants associated with bisexual behavior, which are known as BSB-associated alleles, father more children than average. Furthermore, men who describe themselves as risk-takers tend to have more children and are more likely to carry BSB-associated alleles.

These and other observations suggest that male BSB-associated alleles confer reproductive benefits because of the shared genetic variants between male bisexual and risk-taking behaviors.

"Our results suggest that male BSB-associated alleles are likely reproductively advantageous, which may explain their past persistence and predict their future maintenance," said U-M evolutionary biologist Jianzhi Zhang, the study's senior author.

"These results also suggest that risk-taking behavior is the underlying cause of BSB-associated alleles' promotion of reproduction in heterosexuals. That is, the reproductive advantage of BSB-associated alleles is a byproduct of the reproductive advantage of risk-taking behavior," said Zhang, the Marshall W. Nirenberg Collegiate Professor in the Department of Ecology and Evolutionary Biology.

The first author of the new study is U-M graduate student Siliang Song.

Risk-taking propensity usually describes a tendency to engage in reward-seeking actions despite the possibility of negative consequences. Although the UK Biobank question on risk-taking did not specify the type of risk, it is likely that self-reported risk-taking includes unprotected sex and promiscuity, which could result in more children, Zhang said.

In their analysis of the genetic underpinnings of same-sex sexual behavior, the U-M researchers looked at both bisexual behavior and exclusive same-sex behavior, which they call eSSB.

When they compared the genetic basis of bisexual behavior to the genetic basis of eSSB, they found them to be significantly different. They found that eSSB-associated genetic variants are correlated with fewer children, which is expected to lead to a gradual decline in their frequency over time.

However, the authors stress that their study looks at the genetic underpinnings of same-sex sexual behavior and not the behaviors themselves, which are affected by both genetic and environmental factors.

In fact, the proportion of UK Biobank participants reporting same-sex sexual behavior has been on the rise in recent decades, likely due to growing societal openness toward it, according to the researchers.

In addition, the authors say their new results "predominantly contribute to the diversity, richness, and better understanding of human sexuality. They are not, in any way, intended to suggest or endorse discrimination on the basis of sexual behavior," they wrote.

The new study is a follow-up to one published in May in Proceedings of the National Academy of Sciences by Song and Zhang. That study also sought to explain the persistence of genetic variants associated with same-sex sexual behavior.

In 2021, Australian biologist Brendan Zietsch and colleagues presented evidence that heterosexuals carrying same-sex-associated alleles have more sexual partners than those not carrying the variants. This could confer a genetic advantage, the authors suggested, because more sexual partners could translate into more children.

In their PNAS study, which also relied on UK Biobank data, Zhang and Song showed that while the mechanism proposed by Zietsch likely worked in pre-modern societies, it is not active today because the widespread use of contraception has decoupled the number of offspring from the number of sexual partners in heterosexuals.

The findings presented in that PNAS paper led Zhang and Song to search for other potential mechanisms for the genetic maintenance of human same-sex behavior. That led to the Science Advances study, which was supported by the U.S. National Institutes of Health.

Study: Genetic variants underlying human bisexual behavior are reproductively advantageous (DOI: 10.1126/sciadv.adj6958)

JOURNAL

Science Advances

DOI

10.1126/sciadv.adj6958

METHOD OF RESEARCH

Survey

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Genetic variants underlying human bisexual behavior are reproductively advantageous

ARTICLE PUBLICATION DATE

3-Jan-2024