The research, published in Neurology, used data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial to investigate whether people who had variants in the haemochromatosis (HFE) gene, which is critical for regulating iron levels in the body, might be at increased risk of dementia.

Co-author Professor John Olynyk, from the Curtin Medical School, said one in three people carry one copy of the variant, known as H63D, while one in 36 carry two copies.

“Having just one copy of this gene variant does not impact someone’s health or increase their risk of dementia. However, having two copies of the variant more than doubled the risk of dementia in men, but not women,” Professor Olynyk said.

“While the genetic variant itself cannot be changed, the brain pathways which it affects — leading to the damage that causes dementia — could potentially be treated if we understood more about it.”

Professor Olynyk said further research was needed to investigate why this genetic variant increased the risk of dementia for males but not females.

“The HFE gene is routinely tested for in most Western countries including Australia when assessing people for haemochromatosis — a disorder that causes the body to absorb too much iron. Our findings suggest that perhaps this testing could be offered to men more broadly,” Professor Olynyk said.

“While the HFE gene is critical for controlling iron levels in the body, we found no direct link between iron levels in the blood and increased dementia risk in affected men.

“This points to other mechanisms at play, possibly involving the increased risk of brain injury from inflammation and cell damage in the body.”

Co-author Professor Paul Lacaze, from Monash University, said the findings could help improve outcomes for people at risk of developing dementia.

“More than 400,000 Australians are currently living with dementia, with around a third of those being men. Understanding why men with the double H63D variant are at higher risk could pave the way for more personalised approaches to prevention and treatment,” Professor Lacaze said.

“This study is a great example of how diverse Australian research groups and universities can collaborate effectively to learn more about these progressive diseases and ultimately improve health outcomes for people around the world.”

The ASPREE trial was a double-blind, randomised, placebo-controlled trial of daily low-aspirin in 19,114 healthy older people in Australia and the USA. Primarily undertaken to evaluate the risks versus benefits of daily low-dose aspirin in this cohort, it created a treasure trove of healthy ageing data that has underpinned a wealth of research studies.

The research was a collaboration between Curtin University, Monash University, The University of Melbourne, The Royal Children’s Hospital, Murdoch Children’s Research Institute and Fiona Stanley Hospital.

Around the world and across cultures, singing to babies seems to come instinctively to caregivers. Now, new findings support that singing is an easy, safe, and free way to help improve the mental well-being of infants. Because improved mood in infancy is associated with a greater quality of life for both parents and babies, this in turn has benefits for the health of the entire family, the researchers say. The study also helps explain why musical behaviors may have evolved in parents.

“Singing is something that anyone can do, and most families are already doing,” said Eun Cho, postdoctoral researcher at the Yale Child Study Center, and co-first author of the study. “We show that this simple practice can lead to real health benefits for babies.”

“We don’t always need to be focusing on expensive, complicated interventions when there are others that are just as effective and easy to adopt,” added Lidya Yurdum, a PhD student in psychology at the University of Amsterdam, affiliated with the Child Study Center, and co-first author.

Increased singing improves infants’ moods

The new study included 110 parents and their babies, most of whom were under the age of four months. The researchers randomly assigned the parents into two groups, encouraging one group to sing to their infants more frequently by teaching the parents new songs, providing karaoke-style instructional videos and infant-friendly songbooks, and sending weekly newsletters offering ideas for incorporating music into daily routines.

For four weeks, these parents received surveys on their smartphones at random times throughout the day. Parents answered questions related to infant mood, fussiness, time spent soothing, caregiver mood, and frequency of musical behavior. For instance, parents were asked to rate how positive or negative their baby’s mood was within the last two to three hours before receiving the survey. The 56 parents in the control group also received an identical intervention in the four weeks following the initial experiment.

The researchers found that parents were successfully able to increase the amount of time they spent singing to their babies. “When you ask parents to sing more and provide them with very basic tools to help them in that journey, it’s something that comes very naturally to them,” said Yurdum.

Not only did the parents sing more frequently, but they also chose to use music especially in one context in particular: calming their infants when they were fussy. “We didn’t say to parents, ‘We think you should sing to your baby when she’s fussy,’ but that’s what they did,” said Samuel Mehr, an adjunct associate professor at the Child Study Center, and director of The Music Lab. Mehr is also the study’s principal investigator. “Parents intuitively gravitate toward music as a tool for managing infants’ emotions, because they quickly learn how effective singing is at calming a fussy baby.”

Most surprisingly, the responses to the survey showed that increased singing led to a measurable improvement in infants’ moods overall, compared to those in the control group — in other words, parents who sang more rated their babies’ moods as significantly higher. Importantly, improved mood was found in general, not just as an immediate response to music.

While singing did not significantly impact caregivers’ moods in this study, Mehr believes that there could be follow-on effects on health in young families. “Every parent knows that the mood of an infant affects everyone around that infant,” said Mehr. “If improvements to infant mood persist over time, they may well generalize to other health outcomes.”

Follow-up study to further explore singing’s benefits

The team believes that the benefits of singing may be even stronger than the current study shows. “Even before our intervention, these participating families were particularly musical,” Yurdum explained. “Despite that, and despite only four weeks of the intervention, we saw benefits. That suggests that the strength of singing to your babies would likely be even stronger in a family that does not already rely on music as a way of soothing their infants.”

The Child Study Center researchers are currently enrolling parents and babies under four months old in a follow-up study, “Together We Grow,” which will investigate the impact of infant-directed singing over an eight-month period.

Although the researchers did not see an improvement in caregiver mood within four weeks, they are intrigued to see if singing can help alleviate stress or conditions such as postpartum depression in the long term. They are also interested in exploring whether singing might have benefits beyond mood in infants, such as improved sleep.

Previous work from The Music Lab has shown that infant-directed music is universal in humans, and that humans can even infer context of songs — such as whether it is for dancing or a lullaby — in foreign languages and from other cultures. For Mehr, the new findings make sense in light of these basic science results. “Our understanding of the evolutionary functions of music points to a role of music in communication,” said Mehr. “Parents send babies a clear signal in their lullabies: I’m close by, I hear you, I’m looking out for you — so things can’t be all that bad.”

The babies, apparently, are listening.

Study participants were randomized into two groups, one following the Mediterranean diet and the other following the low FODMAP diet, a common restrictive diet for IBS.

In the Mediterranean diet group, 73% of the patients met the primary endpoint for symptom improvement, versus 81.8% in the low FODMAP group.

Irritable bowel syndrome affects an estimated 4-11% of all people, and a majority of patients prefer dietary interventions to medication.

The low FODMAP diet leads to symptom improvement in more than half of patients, but is restrictive and hard to follow.

Previous investigations from Michigan Medicine researchers into more accessible alternative diets led to a proposed “FODMAP simple,” which attempted to only restrict the food groups in the FODMAP acronym that are most likely to cause symptoms.

“Restrictive diets, such as low FODMAP, can be difficult for patients to adopt,” said Prashant Singh, MBBS, Michigan Medicine gastroenterologist and lead author on the paper.

“In addition to the issue of being costly and time-consuming, there are concerns about nutrient deficiencies and disordered eating when trying a low FODMAP diet. The Mediterranean diet interested us as an alternative that is not an elimination diet and overcomes several of these limitations related to a low FODMAP diet.”

The Mediterranean diet is already popular among physicians for its benefits to cardiovascular, cognitive, and general health. Previous research on the effect of the Mediterranean diet on IBS, however, had yielded conflicting results.

In this pilot study, two groups of patients were provided with either a Mediterranean diet or the restriction phase of a low FODMAP diet for four weeks.

The primary endpoint was an FDA-standard 30% reduction in abdominal pain intensity after four weeks.

All the patients included in the study were diagnosed with either IBS-D (diarrhea) or IBS-M (mixed symptoms of constipation or diarrhea).

This study was the first randomized controlled trial to compare the Mediterranean diet to another potential diet. (Previous studies had compared the Mediterranean diet to the individuals’ typical diets or were not randomized controlled trials.)

While the Mediterranean diet did provide symptom relief, the low FODMAP group experienced a greater improvement measured by both abdominal pain intensity and IBS symptom severity score.

Researchers found the results of this pilot study — which 20 patients completed — sufficiently encouraging to warrant future, larger controlled trials to investigate the potential of the Mediterranean diet as an effective intervention for patients with IBS.

“This study adds to a growing body of evidence which suggests that a Mediterranean diet might be a useful addition to the menu of evidence-based dietary interventions for patients with IBS,” said William Chey, M.D., chief of Gastroenterology at the University of Michigan, president-elect of the American College of Gastroenterology, and senior author on the paper.

The researchers believe studies comparing long-term efficacy of the Mediterranean diet with long-term outcomes following the reintroduction and personalization phases of low FODMAP are needed.

Neuroscientists and psychiatrists, despite their best efforts, don’t understand nearly enough about the brain activity underlying our emotions, how they make us tick and how they can make us sick.

Now, in a study scheduled to publish May 29 in Science, Stanford Medicine investigators have mapped the brainwide neuronal processing that underlies the emotional response triggered by a mildly unpleasant sensory experience. Features of this brain activity turn out to be shared by humans and mice — and, by extension, every mammal in between. (Perhaps your pet has already explained this to you.)

The findings could help unveil some of the driving forces behind numerous neuropsychiatric disorders, which are characterized in large part by troublesome emotional manifestations.

“Emotional states are fundamental to psychiatry,” said Karl Deisseroth, MD, PhD, professor of bioengineering and of psychiatry and behavioral sciences, who led a collaborative team effort spanning Stanford Medicine’s hospital and laboratory facilities. Sharing senior co-authorship of the study with Deisseroth are Carolyn Rodriguez, MD, PhD, professor of psychiatry and behavioral sciences; Vivek Buch, MD, assistant professor of neurosurgery; and Paul Nuyujukian, MD, PhD, assistant professor of bioengineering and of neurosurgery. The lead co-authors of the study are postdoctoral scholars Isaac Kauvar, PhD, and Ethan Richman, PhD, and MD/PhD student Tony Liu.

The study was a project of Stanford Medicine’s Human Neural Circuitry research program, a multidisciplinary collaboration founded and led by Deisseroth, designed to understand the principles underlying the inner workings of the human brain in health and disease. The HNC program develops and brings together, in an inpatient medical setting, state-of-the-art methods for synchronous and ultraprecise measurement and perturbation of both human behavior and brain activity.

In this study, Deisseroth and his colleagues focused primarily on responses to negative sensory experiences. But he suspects that the brainwide activity pattern his team observed also generalizes to positive experiences. (His group is exploring those, too.)

Pulling it all together

“The mammalian lineage has made a huge evolutionary commitment to large brain size, with all its attendant costs and benefits,” said Deisseroth, who is the D. H. Chen Professor and a Howard Hughes Medical Institute investigator. Even a mouse’s brain (which is large compared with same-sized non-mammals) contains nearly 100 million neurons; a human brain, almost 90 billion — about 1,000 times as many.

“A bigger brain means a richer, more complex mental life,” Deisseroth said. “But there are real constraints once you scale up. The human brain is so big, it takes some time for those rich and complex signals to fully propagate throughout the brain, converge and be properly integrated. Yet, to make accurate decisions, your brain has to pull together your multiple streams of sensory data, your goals, your position in space, your physiological needs and more — all at the same time. If that doesn’t happen, wrong decisions will be made and wrong actions taken.”

Emotions may represent states that integrate a great deal of information to guide lasting patterns of behavior, but may need a window of time with persistent communication among widely separated brain structures to accomplish that integration, Deisseroth said.

“Tuning the time scale of this communication could be an important aspect of typical brain function,” Richman added. “This would be akin to the action of a piano’s sustain pedal, which extends the duration of briefly played notes.” Either overly shortened or overly prolonged stability of such brainwide communication patterns could contribute to neuropsychiatric disorders characterized by emotional dysfunction.

What might those emotion-enabling patterns of activity be? Because human brain activity is so complex, figuring out which observed signals are the important ones is a challenge.

Deisseroth is renowned for developing optogenetics, a sophisticated and now widespread method using a targeted light-activated protein together with pulses of light to induce select nerve cells, or groups of them, to fire or go silent at the flip of a switch. But the new study (relying on briefly hospitalized human patients) did not use optogenetics at all.

Instead, the Stanford team used a clever evolutionary trick. To determine how emotion emerges in response to experience, the researchers carried out brainwide screens of neural activity in both mice and humans — two species that emerged from the same ancestor some 70 million years ago — to search for activity patterns present in both species that could be induced by the same emotion-generating stimulus, measurable in the same way, synchronized with the same high-speed behaviors and blocked by the same interventions.

“This approach allowed us to focus our study on the key principles that were shared between mice and humans,” Kauvar said.

If, over that vast amount of evolutionary time, a particular brain-activity pattern (ultimately determined by genes governing brain structure and function) doesn’t help survival and reproduction, it will be lost, Deisseroth said, while “if a brain dynamical principle is conserved over that time, you’d better believe it could be important.”

Puff, blink, squint

First the reflex, then the emotional response: You burn your hand on a stove, reflexively pull it away, then feel the pain spreading and curse. The sound of a gunshot — or a similar noise — on a dark street in a strange neighborhood late at night elicits a reflexive ducking response, then a sense of fear and caution.

Examples of emotion emerging from an unpleasant sensory input are too numerous to list. But those instances are typically tough to measure and often both difficult and dangerous to stage. For experiments, the triggering stimulus needs to be safe, reproducible and easy to deliver — and, in this case, applicable to mice and people.

For this study, the method of choice was a tool employed in every eye doctor’s office. Deisseroth’s team took advantage of the device an ophthalmologist uses to deliver little puffs of air to check the pressure in their patients’ eyes. While not a painful experience, it certainly can be a touch unpleasant. Here, employing this aversive but medically safe stimulus permitted precision in timing, duration and intensity of the stimulus. The researchers knew exactly when each puff started and when it stopped — critical for tracking each subject’s brainwide response to it.

The scientists administered multiple series of precisely timed “eye puffs” to participants, who, asked how they felt about the puffs, described them as “annoying,” “unpleasant” and “uncomfortable,” though certainly not painful. Repeated rapid-fire eye puffs produced an increasing feeling of annoyance that outlasted the eye puff series.

That bummed-out state of mind can be adaptive, Deisseroth noted. “Any repeated series of negative events is important to the brain, to be considered in guiding future behavior.”

To record brainwide activity at high resolution, Deisseroth and his associates recruited a cohort of patients at Stanford Hospital who, because they were experiencing frequent seizures that were inadequately responsive to medications, had had electrodes surgically inserted deep into their brains so that teams of neurologists and neurosurgeons, to achieve more targeted treatment, could locate each patient’s unique focus — the hyperexcitable point of origin from which seizures would spread across otherwise healthy brain tissue.

While all those electrodes had been implanted in patients’ brains for purely clinical reasons, it provided a serendipitous avenue for experiments that would otherwise be difficult or impossible to perform.

“These patients typically spend about a week in a hospital bed with limited mobility, during recording from these implanted intracranial electrodes, while the treatment team waits for spontaneous seizures to occur,” Liu said. During this long stretch of time, these patients were more than willing to volunteer for and participate in the investigators’ innovative study.

Subjects’ visible responses to randomly timed eye puffs were found to be quite consistent. Immediately in response to each puff, the subjects briefly blinked reflexively. In the seconds following each puff, subjects also exhibited additional eye squinting or rapid additional blinks. This additional post-puff eye closure was a natural response to an unpleasant stimulus (since they could not predict the timing of the next puff). It was also precisely quantifiable, offering insight into emotion-triggered behaviors immediately following a sensory stimulus.

All the while, the experimenters tracked subjects’ brainwide activity. They picked up a distinctive two-phase pattern: In the first roughly 200 milliseconds after the eye puff they observed a strong but short-lived spike of activity broadcasting “news” of the eye puff throughout the brain. This was followed over the next 700 milliseconds or so by a separate, longer-lasting phase of puff-triggered brain activity more specifically localized to a subset of specific circuits across the brain associated with emotion. This pattern — which, Deisseroth noted, was discoverable thanks to the simultaneous electrical recording and behavioral technology of the team — displayed the interesting property of yielding an extended window of time for brainwide communication, which could be related to emotion.

Since the core idea of the study was to search for shared principles among humans and mice, the scientists carried out the same experiment in parallel in mice. Remarkably, the team observed a very similar two-phase pattern of brain activity in mice. Moreover, delivering a series of eight eye puffs in rapid succession to mice induced accumulating second-phase brain activity and put the mice into a generalized negative emotional state, as further evidenced by their persistently reduced willingness to engage in reward-seeking behavior. (Such persistence and generalizability are classic hallmarks of emotion.)

Gone with the squint

The researchers then used a medication, chosen to be suitable for use in both humans and mice, to further test for the importance of this persistent activity pattern. Ketamine, widely used at high doses in anesthesia, is FDA-approved at lower doses as an antidepressant. Even at these lower doses, ketamine is known to cause a phenomenon called dissociation, in which typical emotional responses to stimuli are reduced or absent.

“Ketamine recipients are fully aware of sensory experience, but they often don’t have typical emotions about that experience, even if the sensation would normally be unpleasant,” Deisseroth said. “It’s as if it’s happening to someone or something else.” This dissociative effect of ketamine wears off within an hour or so, he said.

After carefully setting up their research protocol so they could safely administer a single dose of ketamine to electrode-implanted human subjects in the hospital, and with fully informed consent, the scientists found that indeed the negative emotion caused by the repeated puffs of air (as described by the patients) was greatly inhibited.

An important part of the clinical study was the ability to directly ask participants about their experiences, Liu said.

“The air puff . . . felt entertaining,” one participant said. “It felt like little whispers on my eyeballs,” said another.

Consistent with this loss of their subjective sense of annoyance, the human subjects also did not show self-protective behavior — they kept their eyes open between puffs even though they were fully aware of the puffs and continued to have robust reflexive blinks. Remarkably, the same selective effect on behavior (preserving the reflexive blink while blocking self-protection with prolonged eye closure) was observed in the mice.

The team carried out a final set of definitive measurements to test their core hypothesis. If the persistent second phase of brain activity were important in the emotional response, this slower phase would be predicted to be selectively reduced by ketamine in both species, thereby effectively speeding up the brain’s response. In humans and mice alike, the team found that the initial fast burst of brainwide activity was completely unaffected by ketamine. But when the scientists measured the speed at which the slower, second phase of post-eye-puff brain activity subsided, they found that ketamine sped up this decay, effectively sharpening the brain’s response and restricting the puff-induced activity to a brief window of time (analogous to releasing a piano’s sustain pedal to terminate the note).

“This all points to that persistent second phase of brain activity as being strongly linked to emotional state,” Kauvar said.

If speeding-up of brain activity prevents formation of emotional states, this acceleration due to ketamine should also be detectable even in the eye puff’s absence. As predicted, the team found that the “intrinsic time scale” — a measure of the time over which brain-activity patterns were correlated — was accelerated by ketamine even without the eye puff. In both species, intrinsic time scale rapidly recovered to its normal duration after the ketamine wore off.

Finally, the team found that ketamine also reversibly reduced synchrony across the brain in both species. “Dissociative medication may render the stabilizing phase of brain activity so ephemeral that information can’t be properly integrated across the brain, including to build an emotional state,” Deisseroth said.

A science of emotion based on timing?

These tunable, measurable timing properties, when pushed beyond a typical range — either in the slowed or sped-up direction — could offer clues about categorizing, quantifying and perhaps even treating neuropsychiatric disorders.

“Far too-brisk decay of that integrative brain activity (as ketamine causes) could generally prevent coordination of information flowing in from diverse regions of the brain,” Deisseroth said. This could give rise to a situation in which the right hand quite literally doesn’t know what the left hand is doing. “People with schizophrenia report perceptions of alien, as opposed to self-generated, control over their actions,” Deisseroth said.

On the other hand, if a brain disorder causes the second wave of brain activity to decay too slowly or to accumulate excessive strength (perhaps due to differences in brain wiring or gene expression, or even related to personal experiences), this could result in hyperstabilized brain states and, consequently, persistent or untimely emotions or intrusive thoughts like those experienced by people with post-traumatic stress disorder, obsessive-compulsive disorder, depression or eating disorders. Different symptoms (and different disorders) would be expected to arise depending on the specific circuits representing this altered persistence.

Distinct from emotion in health and disease, this same quality of signal persistence could powerfully influence the fundamental speed of information processing, another property that varies substantially in the human population. “People with autism spectrum disorder are often known to have trouble keeping up with high-speed bursts of information, an ability required for language and social-information processing,” Deisseroth said. Could a hyperstabilized brain state be responsible for difficulty in following rapidly changing input?

“These are fascinating possibilities, which we are now exploring,” Deisseroth said. “It’s amazing what an unbiased brainwide screen can reveal, especially with the right technology and across millions of years of evolution.”

Stanford University’s Office of Technology Licensing has filed a patent for intellectual property associated with the study.

Researchers from the Veterans Affairs Palo Alto Health Care System and Weill Cornell Medicine contributed to the work.

The study was funded by National Institutes of Health (grants P50DA042012, R01MH105461, R01MH133553 and R01NS095985), the AE Foundation and anonymous donors.

Leprosy is a neglected disease, mainly caused by the bacterium Mycobacterium leprae, affecting thousands of people worldwide: approximately 200,000 new cases of leprosy are reported each year. Although M. leprae remains the primary cause, this study focused on another species, Mycobacterium lepromatosis, discovered in the United States in 2008 in a Mexican patient, and later in 2016 in red squirrels in the British Isles. Led by scientists from the Laboratory of Microbial Paleogenomics at the Institut Pasteur, also associated with the CNRS, and the University of Colorado, in collaboration with Indigenous communities and over 40 scientists from international institutions including archaeologists, this study analyzed DNA from nearly 800 samples, including ancient human remains (from archaeological excavations) and recent clinical cases presenting symptoms of leprosy. The results confirm that M. lepromatosis was already widespread in North and South America long before European colonization and provide insights into the current genetic diversity of pathogenic Mycobacteria.

“This discovery transforms our understanding of the history of leprosy in America,” said Dr. Maria Lopopolo, the first author of the study and researcher at the Laboratory of Microbial Paleogenomics at the Institut Pasteur. “It shows that a form of the disease was already endemic among Indigenous populations well before the Europeans arrived.”

The team used advanced genetic techniques to reconstruct the genomes of M. lepromatosis from ancient individuals found in Canada and Argentina. Despite the geographic distance of several thousand kilometers, these ancient strains dating from similar periods (approximately 1,000 years ago) were found to be surprisingly genetically close. Although they belong to two distinct branches in the evolutionary tree of the genus Mycobacterium, these branches are genetically closer to each other than to any other known branch. This genetic proximity, combined with their geographical distance, necessarily implies a rapid spread of the pathogen across the continent, likely within just a few centuries.

The scientists also identified several new lineages, including an ancestral branch that despite having diverged from the rest of the known species’ diversity over 9,000 years ago, it continues to infect humans today in North America — a discovery suggesting an ancient and long-lasting diversification on the continent, as well as a largely unexplored diversity that likely remains to be found.

Notably, the analyses also suggest that the strains found in red squirrels in the UK in 2016 are part of an American lineage that was introduced to the British Isles in the 19th century, where it subsequently spread. This discovery highlights the recent ability of the pathogen to cross continents, likely through human or commercial exchanges.

“We are just beginning to uncover the diversity and global movements of this recently identified pathogen. The study allows us to hypothesize that there might be unknown animal reservoirs,” said Nicolás Rascovan, the lead author of the study and head of the Laboratory of Microbial Paleogenomics at the Institut Pasteur. “This study clearly illustrates how ancient and modern DNA can rewrite the history of a human pathogen and help us better understand the epidemiology of contemporary infectious diseases.”

The project was conducted in close collaboration with Indigenous communities, which were involved in decisions regarding the use of ancestral remains and the interpretation of results. Ancient DNA and remaining materials were returned when requested, and the generated data was shared via ethical and adaptable platforms designed to allow data sharing that meets the specific expectations of Indigenous communities.

Published today in Conservation Biology, the study analyzed online seizure records from 2010 to 2021 and found smuggling incidents in 62 countries, with dried seahorses, widely used in traditional medicine, most commonly intercepted at airports in passenger baggage or shipped in sea cargo.

“The nearly 300 seizures we analyzed were based only on online records and voluntary disclosures including government notices and news stories. This means that what we’re seeing is just the tip of the iceberg,“ said first author Dr. Sarah Foster, research associate at UBC’s Project Seahorse and focal point for trade in the International Union for Conservation of Nature global expert group on seahorses and their relatives.

Seahorses were often seized alongside other illegally traded products such as elephant ivory and pangolin scales, showing marine life is smuggled just like terrestrial wildlife in global networks.

The team also found emerging trade routes for dried seahorses involving Europe and Latin America, in addition to major destinations like China and Hong Kong. “Trade routes appear to be diversifying, and so must enforcement efforts,“ said co-author Syd Ascione, an undergraduate research biologist at Project Seahorse.

Legal trade of seahorses

International seahorse trade is allowed with permits certifying it does not harm wild populations under the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), an agreement among 184 countries, including Canada and the European Union. But barriers like proving the trade is sustainable make permits difficult to obtain, moving the trade underground.

The researchers also noted that data about seizures is scarce, particularly for marine life, and enforcement efforts often focus on larger, more charismatic animals like elephants or tigers.

“All countries must step up with strong deterrents — good detective work, determined enforcement, and meaningful penalties — to shut down the illegal seahorse trade,” said senior author Dr. Teale Phelps Bondaroff, director of research at OceansAsia.”At the same time, we must continue using innovative research and investigation methods to uncover hidden networks and outpace traffickers.”

Stepping up enforcement

The study found that most seizures of seahorses occurred in transit or destination countries, highlighting the potential efficacy of enforcement efforts at those points.

Airports were the most common places where seahorses were seized, with passenger baggage accounting for the highest number of cases. However, the largest seizures by volume were found in sea cargo, highlighting the need for countries to keep a close eye on illegal wildlife moving by sea.

Customs and other enforcement agencies made the vast majority of reported seizures, but only seven per cent of these had information on legal penalties, leaving it unclear as to how often seizures lead to punishment.

Values for seized seahorses were provided in 34 records. Using these, the researchers estimated the average value per seahorse was about CAD$7, for a total of CAD$29 million over 10 years.

Seahorses are used in traditional medicine and can be a valuable income source for fishers, so efforts to reduce illegal trade need both a carrot and a stick, said Dr. Foster. “We need to make sustainable, legal trade viable enough that people obey the laws, and ensure that we also have sufficient deterrents to stop illegal activity.”

Seahorses are a symbol of ocean biodiversity and protecting them helps everyone involved, she added. “We’ve done work with traditional medicine traders in Hong Kong, and when we ask them, ‘How long do you want seahorses around?’, they say ‘Forever, they’re really important!’ And we agree.”

Not so for the unadventurous bed bugs that stayed with the bats — their populations have continued to decline since the Last Glacial Maximum, also known as the ice age, which was about 20,000 years ago.

A team led by two Virginia Tech researchers recently compared the whole genome sequence of these two genetically distinct lineages of bed bugs. Published in Biology Letters on Tuesday, May 28, their findings indicate the human-associated lineage followed a similar demographic pattern as humans and may well be the first true urban pest.

“We wanted to look at changes in effective population size, which is the number of breeding individuals that are contributing to the next generation, because that can tell you what’s been happening in their past,” said Lindsay Miles, lead author and postdoctoral fellow in the Department of Entomology.

According to the researchers, the historical and evolutionary symbiotic relationship between humans and bed bugs will inform models that predict the spread of pests and diseases under urban population expansion.

By directly tying human global expansion to the emergence and evolution of urban pests like bed bugs, researchers may identify the traits that co-evolved in both humans and pests during urban expansion.

A stairway graph (at left) shows that the genome-wide patterns of bed bug demography mirrors global human expansion, courtesy of Biology Letters 21: 20250061. The image of bed bugs is courtesy of Warren Booth.

“Initially with both populations, we saw a general decline that is consistent with the Last Glacial Maximum; the bat-associated lineage never bounced back, and it is still decreasing in size,” said Miles, an affiliate with the Fralin Life Sciences Institute. “The really exciting part is that the human-associated lineage did recover and their effective population increased.”

Miles points to the early establishment of large human settlements that expanded into cities such as Mesopotamia about 12,000 years ago.

“That makes sense because modern humans moved out of caves about 60,000 years ago,” said Warren Booth, the Joseph R. and Mary W. Wilson Urban Entomology Associate Professor. “There were bed bugs living in the caves with these humans, and when they moved out they took a subset of the population with them so there’s less genetic diversity in that human-associated lineage.”

As humans increased their population size and continued living in communities and cities expanded, the human-associated lineage of the bed bugs saw an exponential growth in their effective population size.

By using the whole genome data, the researchers now have a foundation for further study of this 245,000 year old lineage split. Since the two lineages have genetic differences yet not enough to have evolved into two distinct species, the researchers are interested in focusing on the evolutionary alterations of the human-associated lineage compared with the bat-associated lineage that have taken place more recently.

“What will be interesting is to look at what’s happening in the last 100 to 120 years,” said Booth. “Bed bugs were pretty common in the old world, but once DDT [dichloro-diphenyl-trichloroethane] was introduced for pest control, populations crashed. They were thought to have been essentially eradicated, but within five years they started reappearing and were resisting the pesticide.”

Booth, Miles, and graduate student Camille Block have already discovered a gene mutation that could contribute to that insecticide resistance in a previous study, and they are looking further into the genomic evolution of the bed bugs and relevance to the pest’s insecticide resistance.

Booth said the project is a good example of what happens when researchers “follow the science,” which he is afforded the space to do thanks in part to the Joseph R. and Mary W. Wilson endowment that supports his faculty position.

“It’s a great resource to have,” said Booth. “We are using it for work investigating the evolution of insecticide resistance and species spread using museum specimens collected from 120 years ago to our present-day samples. “I’m very lucky to have that freedom to explore.”

The Waterloo team analyzed a range of YouTube videos that focused on learning music by ear and identified four simple ways music learning technology can better aid prospective musicians — helping people improve recall while listening, limiting playback to small chunks, identifying musical subsequences to memorize, and replaying notes indefinitely.

“There are a lot of apps and electronic tools out there to help learn by ear from recorded music,” said Christopher Liscio, a recent Waterloo master’s graduate in computer science and the study’s lead author.

“But we see evidence that musicians don’t appear to use them very much, which makes us question whether these tools are truly well-suited to the task. By studying how people teach and learn how to play music by ear in YouTube videos, we can try to understand what might actually help these ear-learning musicians.”

The team studied 28 YouTube ear-learning lessons, breaking each down to examine how the instructors structured their teaching and how students would likely retain what they heard. Surprisingly, they found that very few creators or viewers were using existing digital learning tools to loop playback or manipulate playback speed despite their availability for over two decades.

“We started this research planning to build a specific tool for ear learners, but then we realized we might be reinforcing a negative pattern of building tools without knowing what users actually want,” said Dan Brown, professor of Computer Science at Waterloo. “Then we got excited when we realized YouTube could be a helpful resource for that research process.”

While these cell surface proteins are valuable for viral entry, they also have roles in producing an antiviral response. Before that can happen, the virus manipulates a process cells use to keep themselves healthy to lower the proteins’ activity, clearing the way for unfettered viral infection.

Though other viruses, such as HIV, are known to silence host receptors that let them into cells, Zika is unusual for having at least three of its own proteins that can get the job done, said Shan-Lu Liu, senior author the study and a virology professor in the Department of Veterinary Biosciences at The Ohio State University.

“That’s the most interesting part: It’s amazing that not only one, but several Zika proteins can do this,” said Liu, also a professor in the Department of Microbial Infection and Immunity. “We looked at two Zika virus strains and examined three physiologically relevant cell types. With both strains, we could see the downregulation in all three cell types. It looks like this is an important mechanism.”

The study was published May 23 in Proceedings of the National Academy of Sciences.

The Zika virus, transmitted to humans primarily by Aedes aegypti mosquitoes, has caused infectious outbreaks in Africa, the Americas, Asia and the Pacific since 2007, according to the World Health Organization. Though cases have declined globally since 2017, virus transmission continues at low levels in the Americas and other endemic regions.

A large epidemic in Brazil in 2015 led to confirmation of a link between Zika infection during pregnancy and babies born with congenital problems including microcephaly, or smaller than normal head size. While most infected people develop no or only mild symptoms, the virus is also associated with Guillain-Barré syndrome, neuropathy and myelitis (spinal cord inflammation) in adults and older children.

Previous research has shown that specific cell surface proteins known as PS receptors are important entry points for many viruses, including Zika. This study focused on two of these proteins, known as AXL and TIM-1, that had previously been linked to Zika infection. In this work, Liu and colleagues set out to explain how Zika sustains infection after gaining entry through AXL and TIM-1.

The team completed cell culture experiments using African and Asian strains of Zika virus in three types of cells related to respiratory, reproductive and neurological systems targeted by the pathogen: human cells that line the lungs, embryo-supporting cells called trophoblasts and glioblastoma brain cancer cells.

Experiments showed that both AXL and TIM-1 were downregulated on the three types of cells after infection by Zika. The researchers expected to find this suppression occurred through two common protein degradation processes, but found instead that the Zika virus makes use of a cellular self-preservation routine: autophagy.

“Autophagy is a fundamental physiological mechanism to conserve cellular processes by degrading host components. It’s also called self-eating — the host needs to remove their own damaged organelles or misfolded proteins because they’re not good for the host,” said Liu, also associate director of Ohio State’s Center for Retrovirus Research and a program co-director of the Viruses and Emerging Pathogens Program in Ohio State’s Infectious Diseases Institute.

In this case, the virus’s infectious process manipulated the host cells into suppressing their own protective proteins — a viral adaptive tactic that allows Zika to control its own destiny.

Without this suppression, AXL and TIM-1 would begin producing inflammatory molecules as part of an antiviral response. Their normal level of facilitating viral entry could also enable more Zika particles to access already-infected cells, setting up a competitive scenario called a superinfection — something viruses want to avoid because the overcrowding threatens to kill cells, which kills infecting pathogens.

Further experiments identified three Zika proteins that prompt host cell autophagy, all of which are located on the virus’s membrane.

“Normally those proteins mediate viral entry or are involved in viral replication, but they’re also responsible for this downregulation — kind of a new function, which is not so surprising because viruses encode something that’s important for them, either for their own replication or to modulate the host,” Liu said.

Though further research is needed to know for sure, there is a chance this mechanism is relevant to the Ebola virus, which uses the TIM-1 protein to access host cells, or to other pathogens in the same flavivirus family as Zika, including West Nile, yellow fever and dengue viruses.

“The bottom line is this speaks to the co-evolution of viral-host interactions. The more important a host factor is to a virus, the more a virus is going to do to take control of it,” Liu said. “Understanding these mechanisms is an important part of being prepared for emerging or reemerging viruses that cause infectious diseases.”

This work was primarily conducted by Jingyou Yu, a former graduate student in the Liu lab and now a principal investigator at the Guangzhou National Laboratory in China. Additional contributions were made by Yi-Min Zheng, a senior scientist, and Pei Li, a postdoctoral fellow in the Liu lab. This work was primarily supported by an Ohio State fund and the National Institutes of Health.

Additional co-authors are Megan Sheridan, Toshihiko Ezashi and R. Michael Roberts of the University of Missouri.

A breakthrough study, led by scientists at Waipapa Taumata Rau, University of Auckland, has uncovered how daylight can boost the immune system’s ability to fight infections.

The team focused on the most abundant immune cells in our bodies, called ‘neutrophils’, which are a type of white blood cell. These cells move quickly to the site of an infection and kill invading bacteria.

The researchers used zebrafish, a small freshwater fish, as a model organism, because its genetic make-up is similar to ours and they can be bred to have transparent bodies, making it easy to observe biological processes in real time.

“In earlier studies, we had observed that immune responses peaked in the morning, during the fish’s early active phase,” says lead researcher Associate Professor Christopher Hall, from the Department of Molecular Medicine and Pathology.

“We think this represents an evolutionary response such that during daylight hours the host is more active so more likely to encounter bacterial infections,” says Hall.

However, the scientists wanted to find out how the immune response was being synchronised with daylight.

With this new study, published in Science Immunology, and led by two doctoral researchers, neutrophils were found to possess a circadian clock that alerted them to daytime, and boosted their ability to kill bacteria.

Most of our cells have circadian clocks to tell them what time of day it is in the outside world, in order to regulate the body’s activities. Light has the biggest influence on resetting these circadian clocks.

“Given that neutrophils are the first immune cells to be recruited to sites of inflammation, our discovery has very broad implications for therapeutic benefit in many inflammatory diseases,” Hall says.

“This finding paves the way for development of drugs that target the circadian clock in neutrophils to boost their ability to fight infections.”

The research was funded through the Royal Society of NZ’s Marsden Fund.

Current research is now focussed on understanding the specific mechanisms by which light influences the neutrophil circadian clock.

Now a Tufts interdisciplinary engineer and his team have devised a simple device using specially designed floss that can easily and accurately measure cortisol, a stress hormone, in real time.

“It started in a collaboration with several departments across Tufts, examining how stress and other cognitive states affect problem solving and learning,” said Sameer Sonkusale, professor of electrical and computer engineering. “We didn’t want measurement to create an additional source of stress, so we thought, can we make a sensing device that becomes part of your day-to-day routine? Cortisol is a stress marker found in saliva, so flossing seemed like a natural fit to take a daily sample.”

Their design of a saliva-sensing dental floss looks just like a common floss pick, with the string stretched across two prongs extending from a flat plastic handle, all about the size of your index finger. The saliva is picked up by capillary action through a very narrow channel in the floss. The fluid is drawn into the pick handle and an attached tab, where it spreads across electrodes that detect the cortisol.

Cortisol recognition on the electrodes is accomplished with a remarkable technology developed almost 30 years ago called electropolymerized molecularly imprinted polymers (eMIPs). They work similarly to the way you might make a plaster cast of your hand. A polymer is formed around a template molecule, in this case cortisol, which is later removed to leave behind binding sites. These sites have a physical and chemical shape “memory” of the target molecule so they can bind free-floating molecules that are coming in.

The eMIP molds are versatile, so one can create dental floss sensors that detect other molecules that can be found in saliva, such as estrogen for fertility tracking, glucose for diabetes monitoring, or markers for cancer. There is also potential for detecting multiple biomarkers in saliva at the same time, for more accurate monitoring of stress, cardiovascular disease, cancer, and other conditions.

“The eMIP approach is a game changer,” said Sonkusale. “Biosensors have typically been developed using antibodies or other receptors that pick up the molecule of interest. Once a marker is found, a lot of work has to go into bioengineering the receiving molecule attached to the sensor. eMIP does not rely on a lot of investment in making antibodies or receptors. If you discover a new marker for stress or any other disease or condition, you can just create a polymer cast in a very short period of time.”

Accuracy of the cortisol sensors is comparable to the best-performing sensors on the market or in development. Bringing this device into the home and in the hands of individuals without need for training will make it possible to fold stress monitoring into many aspects of health care. Currently Sonkusale and his colleagues are creating a startup to try and bring the product to market.

He points out that while the dental floss sensor is quantitatively highly accurate, the practice of tracking markers in saliva is best for monitoring, not for the initial diagnosis of a condition. That’s in part because saliva markers can still have variations between individuals.

“For diagnostics, blood is still the gold standard, but once you are diagnosed and put on medication, if you need to track, say, a cardiovascular condition over time to see if your heart health is improving, then monitoring with the sensor can be easy and allows for timely interventions when needed,” he says.

The new research, published in the journal ACS Applied Materials and Interfaces, adds to a number of thread-based sensor innovations by Sonkusale and his research team including sensors that can detect gases, metabolites in sweat, or movement when embedded in clothing and transistors that can be woven into flexible electronic devices.

Scientists at the University’s Sensory Evaluation Center examined how increasing “oral burn” — the spicy taste from ingredients like chili pepper — affects how much food people consume during a meal. The findings, available online now and slated to publish in the October issue of the journal Food Quality and Preference, suggest that making the meal slightly spicier led participants to eat less, consuming fewer calories.

“We know from previous studies that when people slow down, they eat significantly less,” said Paige Cunningham, a postdoctoral researcher and lead author on the study who earned her doctorate in nutritional sciences from Penn State in 2023. “We suspected that making a meal spicier might slow people down. We thought, let’s test, under controlled experimental conditions in the lab, if adding a small amount of spice, but not so much that the meal is inedible, will make people eat slower and therefore eat less.”

The researchers found that increasing spiciness slightly using dried chili pepper slowed down eating and reduced the amount of food and energy consumed at a meal, all without negatively affecting the palatability of the dish.

“This points to added chilies as a potential strategy for reducing the risk of energy overconsumption,” said John Hayes, Penn State professor of food science and corresponding author on the paper. “While portion control wasn’t the explicit goal of this study, our results suggest this might work. Next time you’re looking to eat a little less, try adding a blast of chilies, as it may slow you down and help you eat less.”

The team conducted three related experiments in a total of 130 adults who were served one of two lunch meals — beef chili or chicken tikka masala — in one of two versions: mild or spicy. The spiciness level was controlled by carefully varying the ratio of hot versus sweet paprika added to the dishes to vary the heat while keeping chili flavor constant.

The researchers then recorded participants on high-definition video while they ate their meals to monitor their eating behaviors. From the videos, Hayes’ team measured the amount of food and water consumed, meal duration, eating speed of grams per minute, bite rate, bite size, and collected ratings on appetite, liking and spiciness before and after the meal.

“Formulating the recipes took a long time for the chicken tikka,” Cunningham said. “It took so many rounds of testing that my lab mates were sick of it. But science is about trial and error. I’d make a recipe, see how far I could push the spiciness, and we’d taste it. We did that until we reached a level where palatability was matched even when spiciness increased.”

The study suggests the reduction in intake is driven by changes in oral processing behaviors, she explained. Specifically, participants ate the spicier meals more slowly. She explained that a slower eating rate often means food is in the mouth longer, which can help signal fullness and lead to eating less. Other studies that slow eating rate by manipulating texture have shown similar effects, she said.

“What’s critical here is that the reduction in intake occurred without negatively impacting how much participants liked the food,” Hayes said.

He added that water intake didn’t differ significantly between spicy and mild meals, suggesting that one seemingly obvious explanation, that people drank more water and filled up faster, was not the primary reason people ate less.

“This is why we need to do empirical studies of behavior, because what you might intuitively expect is often not the case,” he said.

Hayes also noted that appetite ratings made before and after the meals were similar, suggesting participants still felt full after the spicy meal, despite eating less of it. Looking ahead, the team is now focused on understanding how oral burn can impact other eating behaviors, like snacking.

Isaiah Smith, a Penn State undergraduate from West Chester, also contributed to this work as part of an Undergraduate Research Internship Program from the NASA Pennsylvania Space Grant Consortium. This work was supported by a gift from the McCormick Science Institute and federal appropriations under the Hatch Act from the U.S. Department of Agriculture’s National Institute of Food and Agriculture.

Large Language Models (LLMs) are artificial intelligence (AI) systems capable of processing, interpreting and generating human language. The ChatGPT generative AI, for example, is based on this type of model. LLMs can answer questions and solve complex problems. But can they also suggest emotionally intelligent behaviour?

These results pave the way for AI to be used in contexts thought to be reserved for humans.

Emotionally charged scenarios

To find out, a team from UniBE, Institute of Psychology, and UNIGE’s Swiss Center for Affective Sciences (CISA) subjected six LLMs (ChatGPT-4, ChatGPT-o1, Gemini 1.5 Flash, Copilot 365, Claude 3.5 Haiku and DeepSeek V3) to emotional intelligence tests. ”We chose five tests commonly used in both research and corporate settings. They involved emotionally charged scenarios designed to assess the ability to understand, regulate, and manage emotions,” says Katja Schlegel, lecturer and principal investigator at the Division of Personality Psychology, Differential Psychology, and Assessment at the Institute of Psychology at UniBE, and lead author of the study.

For example: One of Michael’s colleagues has stolen his idea and is being unfairly congratulated. What would be Michael’s most effective reaction?

a) Argue with the colleague involved

b) Talk to his superior about the situation

c) Silently resent his colleague

d) Steal an idea back

Here, option b) was considered the most appropriate.

In parallel, the same five tests were administered to human participants. “In the end, the LLMs achieved significantly higher scores — 82% correct answers versus 56% for humans. This suggests that these AIs not only understand emotions, but also grasp what it means to behave with emotional intelligence,” explains Marcello Mortillaro, senior scientist at the UNIGE’s Swiss Center for Affective Sciences (CISA), who was involved in the research.

New tests in record time

In a second stage, the scientists asked ChatGPT-4 to create new emotional intelligence tests, with new scenarios. These automatically generated tests were then taken by over 400 participants. ”They proved to be as reliable, clear and realistic as the original tests, which had taken years to develop,” explains Katja Schlegel. ”LLMs are therefore not only capable of finding the best answer among the various available options, but also of generating new scenarios adapted to a desired context. This reinforces the idea that LLMs, such as ChatGPT, have emotional knowledge and can reason about emotions,” adds Marcello Mortillaro.

These results pave the way for AI to be used in contexts thought to be reserved for humans, such as education, coaching or conflict management, provided it is used and supervised by experts.

The research helps explain differences in chili pepper pungency, or spiciness, by identifying three compounds in a range of pepper samples that chemical analysis predicted, and study participants on a tasting panel confirmed, are linked to lower heat intensity.

The findings have multiple potential applications: customized chili pepper breeding, a pain-relief alternative to capsaicin and, in homes with a range of culinary spice sensitivities, a new condiment to put in the pantry.

“If you’re at home and you’ve ordered cuisine that has spice to it that’s a little too hot for some tastes, you can just sprinkle on a form of chili pepper that has got these suppressant agents in them that will dial it down,” said senior study author Devin Peterson, professor of food science and technology at The Ohio State University.

“I think the idea of using a natural material as an anti-spice, especially for somebody with kids, would have value as a household ingredient.”

The research was published online May 14 in the Journal of Agricultural and Food Chemistry.

Chili pepper heat intensity has long been attributed to two members of a class of compounds called capsaicinoids: capsaicin and dihydrocapsaicin. Scoville Heat Units, a scale used for over a century to determine the pungency of chili peppers, are calculated based on each pepper’s concentration of these two compounds.

For this study, Peterson and colleagues obtained 10 cultivars of chili peppers, determined their Scoville units based on their capsaicinoid content, and normalized the group so all samples, prepared in dried powder form, had the same number of Scoville units. The researchers then added the standardized powders to tomato juice and asked a trained tasting panel to gauge their pungency.

“They’re all in the same base and all normalized, so they should have had a similar heat perception, but they didn’t,” said Peterson, also faculty director of Ohio State’s Foods for Health Research Initiative. “That is a pretty clear indication that other things were at play and impacting the perception.”

With this sensory perception data in hand, the researchers created statistical models and consulted molecular structures in existing libraries of chemicals to arrive at five candidate compounds predicted to be lowering the peppers’ perceived spiciness.

A second trained panel of tasters then compared the pungency of a range of capsaicinoid samples mixed with varying levels of these candidate compounds during tests in which different samples were placed on each side of the tongue simultaneously.

The second round of sensory results combined with high-resolution mass spectrometry and nuclear magnetic resonance experiments led the team to narrow down the heat suppression effects to three compounds: capsianoside I, roseoside and gingerglycolipid A. These results describe an overall mechanism that affects chili pepper heat levels, but are not exclusive to any specific chili pepper varieties.

Peterson’s lab studies the complex relationships between oral cavity receptors and food compounds that influence human perception of flavor. The broad goal: applying findings to improving the taste of healthful foods without adding sugar, salt and fats.

“What is maybe underappreciated from a science perspective is how important food flavor is to your dietary patterns and your enjoyment in life,” he said. “So part of what we focus on is, how do we make healthy eating less difficult?”

When it comes to capsaicinoids, however, there is also a pain management implication from this study’s results.

The TRPV1 receptors in the oral cavity that perceive chili pepper spiciness are triggered by molecules — including capsaicin — that cause sensations of pain and heat. These same receptors are present throughout the body, meaning that capsaicin in supplement and topical form eases pain by initially exposing receptors to the irritation signal and eventually desensitizing them to that stimulus so the pain goes away.

The newly identified heat-suppressing compounds may have the same desensitization effect — without the initial burn, Peterson said.

This work was supported by the Flavor Research and Education Center, which Peterson founded and directs, in Ohio State’s College of Food, Agricultural, and Environmental Sciences. Joel Borcherding, former graduate student, and Edisson Tello, research professor, both in Ohio State’s Department of Food Science and Technology, co-authored the study.

Social connection is now a legitimate health factor, but Holt-Lunstad and doctoral student, Andrew Proctor, recently published two studies showing that most of us — the general population and medical providers — still don’t think social connection affects physical health. And even the professionals who recognize the importance report that they don’t have time or tools to help patients address social concerns.

Proctor, who authored a study recently published in Springer Nature, explained that before the study, they had been watching how the pandemic was influencing internet searches around the topics of isolation and loneliness.

“I have a marketing background, so I thought that maybe the public perception had changed since COVID. Social distancing, isolation and loneliness were huge buzzwords on the internet as seen through Google Trends and BuzzSumo (an online trend analyzer). Everything around these search terms was super viral during that time, and so we wondered if perceptions about social connection had changed,” said Proctor.

With loneliness and isolation trending on the internet, the researchers set up a study. In a nationally representative sample of US adults, as well as samples from the UK and Australia, they surveyed 2,392 people about their perceptions of health risks associated with isolation and loneliness. The data showed that, despite the pandemic and other campaigns, people still underestimate the importance of social connection for physical health. And the underestimation exists equally among the lonely and the socially connected.

“The study identified blind spots in medical care,” said Proctor. “Social connection is like a vital sign. What if we didn’t care about high blood pressure? Or what if we never knew smoking was bad for us? Social connection is like a key vital sign. We just don’t tend to recognize it.”

In a closely connected study, Holt-Lunstad and Proctor, along with coauthors from top research medical centers, surveyed 681 healthcare providers (primarily doctors) about perceptions of health risks associated with poor social connection. Similar to the general population from the first study, healthcare providers underestimated social connection as a medically relevant health factor.

The researchers gleaned some unexpected insights due to an unintentional time lag in data collection in the second study.

“We completed the data collection at two different time points because we were waiting for institutional approvals. Our first cohort was healthcare providers through the University of Utah Health System. Slightly later, we had a second major cohort of University of California San Francisco (UCSF) physicians,” said Holt-Lunstad. “What was interesting is that the perceived importance of social factors was a bit higher among the UCSF group.”

The authors attribute the higher awareness at UCSF to the University’s Social Interventions Research and Evaluation Network as well as the publication of the 2023 Surgeon General’s Advisory, which came out just before the second cohort was surveyed. This suggests that social initiatives as well as institutional support make a difference in the perceived importance of social connection.

“What I hope is that these studies can spur recognition that there is a body of evidence showing social connection as medically relevant,” said Holt-Lunstad. “Together these papers make a really compelling case that not only does the general public underestimate this, but so do healthcare providers who should know this information.”

“Awareness can make a difference,” says Holt-Lunstad. “It’s the first step, but awareness isn’t enough.”

The research brings to light the need for education and strategies for healthcare providers as well as the need for a revised K-12 healthcare curriculum and public health campaigns. Future research includes how to address perceived barriers to integrated medical treatment and actionable strategies such as “social prescribing.”

An international team of researchers led by Max Delbrück Center Scientific Director Professor Maike Sander has for the first time developed an organoid model of human pluripotent stem cell-derived pancreatic islets (SC-islets) with integrated vasculature. Islets are cell clusters in the pancreas that house several different types of hormone-secreting cells, including insulin-producing beta cells. Researchers in the Sander lab at the University of California, San Diego, found that SC-islet organoids with blood vessels contained greater numbers of mature beta cells and secreted more insulin than their non-vascularized counterparts. The vascularized organoids more closely mimicked islet cells found in the body. The study was published in “Developmental Cell.”

“Our results highlight the importance of a vascular network in supporting pancreatic islet cell function,” says Sander. “This model brings us closer to replicating the natural environment of the pancreas, which is essential for studying diabetes and developing new treatments.”

Engineering vascularized stem cell islets

SC-islet cell organoids — mini-organs that mirror the insulin producing cell clusters outside the body — are widely used to study diabetes and other pancreatic endocrine diseases. But beta cells in these organoids are typically immature, making them suboptimal models for the in-vivo environment, says Sander. Although several approaches have been developed to promote beta cell maturation, their effects have been modest, she adds.

To better mimic the in-vivo environment, the researchers added human endothelial cells, which line blood vessels, and fibroblasts, cells that help form connective tissue, to islet organoids grown from stem cells. The team experimented with different cell culture media until they found a cocktail that worked. The cells not only survived, but matured and grew a network of tube-like blood vessels that engulfed and penetrated the SC-islets.

“Our breakthrough was devising the recipe,” Sander says. “It took five years of experimenting with various conditions, involving a dedicated team of stem cell biologists and bioengineers.”

Vascularized stem cell islet organoids are more mature

When the researchers compared vascularized organoids to non-vascularized organoids, they found the former secreted more insulin when exposed to high levels of glucose. “Immature beta cells don’t respond well to glucose. This told us that the vascularized model contained more mature cells,” says Sander.

The researchers next wanted to explore how specifically vasculature helps organoids to mature. They found two key mechanisms: Endothelial cells and fibroblasts help build the extracellular matrix — a web of proteins and carbohydrates at cell surfaces. The formation of the matrix itself is a cue that signals cells to mature. Secondly, endothelial cells secrete Bone Morphogenetic Protein (BMP), which in turn stimulates beta cells to mature.

Recognizing that mechanical forces also stimulate insulin secretion, the team then integrated the organoids into microfluidic devices, allowing nutrient medium to be pumped directly through their vascular networks. They found that the proportion of mature beta cells increased even further.

“We found a gradient,” says Sander. “Non-vascularized organoids had the most immature cells, a greater proportion matured with vascularization, and even more matured by adding nutrient flow through blood vessels. A human cell model of pancreatic islets that closely replicates in-vivo physiology opens up novel avenues for investigating the underlying mechanisms of diabetes,” she adds.

In a final step, the researchers showed that vascularized SC-islets also secrete more insulin in-vivo. Diabetic mice grafted with non-vascularized SC-islets fared poorly compared to those grafted with vascularized SC-islet cells, with some mice showing no signs of the disease at 19-weeks post-transplant. The research supports other studies that have shown that pre-vascularization improves the function of transplanted SC-islets.

A better model to study Type 1 diabetes

Sander now plans to use vascularized SC-islet organoid models to study Type-1 diabetes, which is caused by immune cells attacking and destroying beta cells in the pancreas — in contrast to Type-2 in which the pancreas produces less insulin over time and the body’s cells become resistant to the effects of insulin.

She and her team at the Max Delbrück Center are growing vascularized organoids from the cells of patients with Type-1 diabetes. They are transferring the organoids onto microfluidic chips and adding patients’ immune cells. “We want to understand how the immune cells destroy beta cells,” Sander explains. “Our approach provides a more realistic model of islet cell function and could help develop better treatments in the future.”

First, the interface of both enzyme and molecule should be located at their respective smaller end. This way, a strong coupling between both of them can be achieved. For the same reason, the conformational change in the enzyme should not be smaller than in the reaction. Finally, the conformational change of the enzyme has to take place fast enough to maximize the chemical driving force of the reaction.

“We built our research on two main pillars,” Ramin Golestanian, director of MPI-DS describes the approach. “Conservation of momentum and coupling between the reaction coordinates,” he continues. Thus, the researchers expanded the view of a classical 2-dimensional reaction coordinate. Typically, models for enzymatic reactions define an energy barrier that has to be overcome in order for the reaction to take place.

“As in our model we also consider the enzyme dynamics and coupling, we go beyond this existing concept, considering two reaction coordinates,” say Michalis Chatzittofi, first author of the study. “Instead of overcoming an energy barrier, one can now imagine alternative ways to bypass it by taking alternative routes,” he concludes.

These results provide a new basis for the design of molecular machines, avoiding the tedious and technically challenging approach to simulate the dynamics of each atom individually.

Published in Science, the paper reveals high-skilled emigration from developing countries may actually boost economic development, human capital and innovation in migrants’ countries of origin.

With the U.S. undergoing sweeping immigration policy shifts — which include tighter work visa rules, student visa restrictions and return migration barriers — the new research highlights how these changes will reverberate through the U.S. labor market and economies around the world.

“Global prosperity rises when countries have access to U.S. labor markets,” said Gaurav Khanna, study coauthor and associate professor at the UC San Diego School of Global Policy and Strategy. “And the U.S. benefits when it continues to attract the best global talent — whether it’s tech innovators or trained nurses. But if we shut the door, we risk losing those global gains.”

Migration creates shared prosperity across borders

The research offers compelling evidence that the opportunity to migrate to countries like the United States encourages people in lower-income countries to invest in education and training, creating downstream effects that strengthen both home and host countries.

The researchers also found that high-skilled migrants often maintain professional ties across borders, facilitating trade, investment and innovation. Migrants returning from the U.S. to their home countries, for example, have helped connect domestic firms to international supply chains and research partnerships.

“A lot of trade works through human networks,” said Khanna. “If you’ve worked in the U.S. and return home, you know the people, the standards, the markets — and you can help build business relationships. That creates lasting value.”

A global chain reaction

The paper documented how expanded migration opportunities can trigger a positive chain reaction. When the U.S. increased nursing visa access for Filipinos, for example, enrollment in nursing schools surged — creating nine new nurses in the Philippines for every one who migrated. Similar trends were observed in India, where increased access to H-1B visas increased the earnings of Indians in the U.S. by 10% and raised IT employment in India by 5.8%.

Khanna and coauthors from Yale, Cornell, the World Bank, and other institutions, argue that recent changes in U.S. immigration risk undercutting both U.S. innovation and global progress.

“Earning a U.S. salary is incredibly lucrative,” said Khanna, who is a faculty affiliate at the 21st Century India Center, explained. “That motivates many people to acquire skills even if they never leave. Some eventually return home and work in their local economy; others send money back that helps educate children or launch businesses. All of this contributes to development. And for the U.S., by staying open to global talent, the country strengthens both its economy and the broader world.”

To understand whether high-skilled emigration helps or harms the countries people leave behind, the authors reviewed dozens of recent studies that took advantage of natural experiments. These include sudden changes in visa policies, international lotteries and other real-world events. The authors then analyzed how people and economies changed in response to these events — and compared them to similar groups that weren’t affected.

Yet despite its prevalence, methods to treat MDD often fall short for a not-insignificant portion of the population. Antidepressants — the standard of treatment — don’t work for 30 percent with MDD.

When infused at a low dose ketamine shows remarkable efficacy as a rapidly acting antidepressant, with effects observed within hours even in patients who have been resistant to other antidepressant treatments. However, consistent infusions of ketamine are needed to maintain symptoms at bay, which could result in side effects, such as dissociative behaviors and the possibility of addiction, and stopping treatment can result in relapse.

In a new study published in Science, Lisa Monteggia’s and Ege Kavalali’s labs show that it is feasible to substantially extend the efficacy of a single dose of ketamine from its current duration of up to a week to a longer period of up to two months.

“The premise of this study, which was led by Zhenzhong Ma, a fantastic research assistant professor, was based on a testable mechanistic model that we developed that accounts for ketamine’s rapid antidepressant action,” Monteggia said. Monteggia holds the Lee E. Limbird Chair in Pharmacology and is the Barlow Family Director of the Vanderbilt Brain Institute.

Previously, researchers in the field had determined that ketamine’s antidepressant effect requires the activation of a key signaling pathway called ERK, but only ketamine’s long-term effects — not its rapid effects — are abolished when ERK is inhibited. As a fast-acting antidepressant, ketamine relies on ERK-dependent synaptic plasticity to produce its rapid behavioral effects. Ma and colleagues hypothesized that they could maintain ketamine’s effects for longer periods by enhancing ERK activity.

In the recent paper, Ma discovered that ketamine’s antidepressant effects could be sustained for up to two months by using a drug called BCI, which inhibits a protein phosphatase and results in increased ERK activity. By inhibiting the phosphatase, the authors retained ERK’s activity and augmented the synaptic plasticity that drives ketamine’s prolonged antidepressant effects.

Although the use of BCI make the application of these results to the clinic difficult, Monteggia said that the results provide a proof of principle that ketamine’s antidepressant action can be sustained by targeting intracellular signaling. She and Kavalali, the William Stokes Professor of Experimental Therapeutics and the chair of the Department of Pharmacology, have worked on the project since its inception and hope that it fosters other studies looking to identify specific molecules that will enhance and sustain the action of a single dose of ketamine.

Ultimately, this work will be a steppingstone toward improving MDD patients’ lives by reducing the burden of treatment.

Graduate student Natalie Guzikowski and postdoctoral fellow Ji-Woon Kim were coauthors on the study.

“If an infected mosquito hits or lands on either type of netting, it’s essentially disinfected,” said Institute Scientist Dr. Mike Rubal, a contributor to the Nature article. “The best defense against malaria has been insecticide-treated bed nets or those coated with larvicides, but mosquitoes are developing an immunity to those prevention methods. This novel approach targets the source of the disease.”

In 2023, the World Health Organization reported 263 million cases of malaria and nearly 600,000 deaths worldwide. The disease remains pervasive even with preventative measures and available treatments. Resistance to larvicides and pesticides is a growing concern among malaria researchers.

Rubal’s team coated a commercially available polyester bed net with an ELQ solution synthesized at OHSU/PVAMC. SwRI also blended a second formulation of ELQ into a hot-melt extrusion of high-density polyethylene filaments, which can be woven to make yarn for netting. The team at the Catteruccia lab at Harvard evaluated both netting systems for efficacy.

“We desperately need innovation in malaria control. This study offers a new, effective way to stop the transmission of malaria parasites, which we hope will reduce the burden of this devastating disease in Africa and beyond,” said corresponding author Dr. Flaminia Catteruccia, the Irene Heinz Given Professor of Immunology and Infectious Diseases at Harvard and Howard Hughes Medical Institute Investigator.

Native to tropical and subtropical regions around the world, female Anopheles mosquitoes pass parasites to humans through saliva shared when they bite. Parasites attack and reproduce within the liver and red blood cells causing a variety of symptoms ranging from mild to severe. If left untreated, malaria can lead to brain damage, organ failure and even death, especially among children and other vulnerable populations.

“Our research shows that the two drugs, which are absorbed through the legs of the insect, kill parasites developing within the mosquito. By using two different ELQs, the likelihood of resistance is greatly diminished and possibly eliminated,” said Dr. Michael Riscoe, a professor of molecular microbiology and immunology at OHSU. “This emerging technology has great potential to impact efforts to control and eradicate malaria around the world.”

A National Institute of Health (NIH) R01 grant and funding from Open Philanthropy supported the research.

• People indoors generate an oxidation field consisting of hydroxyl radicals (OH). The oxidation field is generated by the reaction of ozone with oils and fats on our skin
• Researchers now have found that the application of personal care products, such as fragrances and body lotions, suppresses the human oxidation field.
• Body lotion hinders the generation of a key OH precursor by acting as a physical barrier between air ozone and skin squalene.
• A large amount of ethanol solvent in fragrances acts as a OH sink which leads to a reduction of the human generated OH field.
• Used methods: a multiphase chemical kinetic model and a computational fluid dynamics model to demonstrate how the concentrations of the reactive components develop in the indoor environment.

The indoor environment contains multiple sources of chemical compounds. These include continuous emissions from housing materials such as furniture, floors and furnishings, but also periodic intense emissions from human activities such as cooking, smoking, and cleaning. Outdoor air chemicals can also enter indoor environments through infiltration and ventilation. Ozone (O₃) from outdoors can react with compounds indoors to create a complex chemical cocktail within the indoor living space. Since people spend up to 90 percent of their time indoors, exposure to this diverse array of chemical compounds over extended periods is cause for concern, particularly as the human-health impacts of many such chemicals remain poorly understood.

On the basis of their findings in 2022, Jonathan Williams’ research group from the Max Planck Institute for Chemistry had a closer look on how the human oxidation field might be influenced by personal care products. “Given that the human oxidation field influences the chemical composition of air in the breathing zone and close to the skin, it affects our intake of chemicals, which in turn impacts human health. It is therefore of interest to examine how personal care products can influence the strength and spatial extent of the self-generated OH-field,” explains Jonathan Williams.

The experimental measurements made by the Max Planck team were supported by Manabu Shiraiwa and his team at the University of California (Irvine, USA) and Donghyun Rim’s group from the Pennsylvania State University.

“Our team took a unique approach to simulate concentrations of chemical compounds near humans in the indoor environment,” said Shiraiwa. “We developed a state-of-the-art chemical model that can simulate reactions of ozone with human skin and clothing that can lead to the formation of semi-volatile organic compounds.”

“We applied a three-dimensional computational fluid dynamics model to simulate the evolution of the oxidation field around human occupants,” said Rim. “This integrated modeling approach highlights the impact of personal care products on the human oxidation field.”

Personal care products affect the human oxidation field

First, the researchers examined how the application of body lotion impacts the chemistry in the periphery of the persons tested. Then they investigated, how perfume applied to the skin affects the chemical composition of the indoor air. For both cases Williams and his team saw that the OH concentration around the volunteers decreased. This means: It decreased compared to the standard case without cosmetics, where ozone reacts on human skin to form gas phase products that react again in the air with ozone to make OH.

Concerning the perfume, the researchers explain the OH decrease with the primary perfume component ethanol: it reacts with OH, using it up, as ethanol does not produce OH when reacting with ozone.

“Regarding body lotion, we can explain the decline in two ways. One is that phenoxyethanol — a chemical in the body lotion — reacts with OH but does not generate OH with ozone. This is the same as the perfume with ethanol. The second explanation is simply that the body lotion gets in the way of ozone reacting with squalene on the skin,” states atmospheric chemist Jonathan Williams.

“The application of a fragrance and a lotion together showed that fragrances impact the OH reactivity and concentration over shorter time periods, whereas lotions show more persistent effects, consistent with the rate of emissions of organic compounds from these personal care products,” sums up Nora Zannoni, first author of the study published in the research magazine Science Advances. She is currently employed at the Institute of Atmospheric Sciences and Climate in Bologna, Italy.

Implications for indoor chemistry

While thousands of different fragrances and lotions exist on the market, there are some general conclusions valid for any product that the international research team draws based on their tests:

Following the new findings of this study, an applied fragrance indoors would be expected to suppress the personal human oxidation field. In contrast with fragrances, lotions have more variable compositions. Despite their variable composition, they expect most lotions to suppress the human oxidation field due to a combination of dilution of skin oil constituents and reduced interaction between O₃ and the skin. Additionally, marketed lotions contain preservatives acting as antimicrobial agents. Widely used is phenoxyethanol which further contributes to suppressing the human oxidation field by reacting with the OH radicals as experimentally demonstrated in this study.

“If we buy a sofa from major furniture company, it is tested for harmful emissions before being put on sale. However, when we sit on the sofa, we naturally transform some of these emissions because of the oxidation field we generate. This can create many additional compounds in our breathing zone whose properties are not well known or studied. Interestingly body lotion and perfume both seem to dampen down this effect,” says Jonathan Williams.

These findings are part of the project ICHEAR (Indoor Chemical Human Emissions and Reactivity Project) which brought together a group of collaborating international scientists from Denmark (DTU), USA (Rutgers University), and Germany (MPI). The modelling was part of the MOCCIE project based in University of California Irvine and the Pennsylvania State University. Both projects were funded by grants from the A. P. Sloan foundation.

Additional information

Experimental setup in a climate chamber

The experiments were conducted at the Technical University of Denmark (DTU) in Copenhagen in 2021. Four test subjects stayed in a special climate-controlled chamber under standardized conditions. Ozone was added to the chamber air inflow in a quantity that was not harmful for humans but representative of the higher range of indoor levels. The team determined the OH concentrations indirectly by quantifying the individual OH sources and the overall loss rate of OH. The OH field was only generated when ozone was present.

By combining air measurements from within the chamber with model simulations, they calculated the effect of the lotion and fragrance on the human oxidation field.

The landmark report, by experts in adolescent health including from Murdoch Children’s Research Institute (MCRI), has revealed how supporting young people’s health and wellbeing could improve economic, social and public health for generations to come.

The 2025 Lancet Commission on Adolescent Health and Wellbeing found investment in adolescents’ health and wellbeing doesn’t match the scale of the problems faced by young people. Bringing together 44 Commissioners and 10 Youth Commissioners, the Commission stated while adolescents make up 24 per cent of the population (about two billion people), they receive just 2.4 per cent of global development and health funding.

By 2030, more than half of adolescents will be living in countries where their demographic experiences an excess burden of complex disease.

The report found the ongoing challenges faced by this age group included:

• High cases of poor mental health and limited support services
• Increasing rates of obesity due to complex environmental and commercial factors
• Lack of digital safety and exposure to cyberbullying and misinformation
• Experiencing violence in conflict-affected areas and within the home
• Ongoing fallout from the COVID-19 pandemic and related public health measures
• Widening gaps in reproductive rights, particularly for young women
• Environmental challenges and climate change impacts

Published in The Lancet, the report predicted that by 2050, 70 per cent of the world’s adolescents will be living in urban areas. While this potentially brings benefits, rapid unplanned urbanisation may also accelerate poverty, isolation and insecure housing, it found.

The report stated that urban, public spaces should be more amenable and tailored to young people, such as safe and engaging spaces to congregate, which would have a powerful effect on health outcomes.

It also found urgent action was required to better protect young people from violence and ensure equitable access to education and reproductive rights. Almost half of adolescents have experienced violence, profoundly impacting their social and emotional development and wellbeing. Whilst global efforts have largely closed the gender gap in high school education, by 2030, almost a third of young women will not be in post-secondary education, employment or training.

MCRI Professor Peter Azzopardi said there was a great need for targeted actions that focused on early intervention.

“Meaningful, evidence-based, multi-sector partnerships with young people will be the key to improving health and wellbeing,” he said. But we must remain accountable by ensuring that any progress is monitored closely and reported on regularly. As our population ages and fertility rates decline, the health of our adolescents becomes even more crucuial.”

Potential solutions and actions outlined included:

• Advocating for change and amplifying the needs and voices of young people
• Developing goal-centred approaches through the Office of the UN Secretary with a focus on measuring and improving adolescent health and wellbeing
• Involving young people in community-based environmental programs
• Scaling up public health programs that improve sexual and reproductive health outcomes and reduce gender-based violence
• Strengthening actions within health and education sectors while reinforcing collaborations
• Limiting the exposure of advertising targeting adolescents
• Promoting and encouraging the healthy use of social media and online spaces

MCRI Professor Susan Sawyer said partnerships with young people were a cornerstone of the report, which aimed to draw on their capability and leadership to help shape the world they wanted to live in.

“This report represents a wealth of current information about the state of our young people’s health,” she said. The findings are alarming and they demand urgent action and accountability, in collaboration with adolescents, to create safer spaces and meaningful change.”

But Professor Sawyer said lack of national leadership around adolescent health remained a major barrier to overcoming the challenges.

“A common myth is that adolescents are healthy and therefore don’t need health services,” she said. Yet our findings show that in every country, adolescents need access to responsive health services that can confidentially identify and respond to their emerging health needs.”

The report will be launched at the World Health Organization’s 78^th Health Assembly in Geneva.

Ultra-processed foods (UPFs) account for more than half of calories consumed in the average American diet, yet their impact on human health remains unclear, in part because it is so difficult to accurately track exactly how many UPFs people eat.

In the new study, researchers analyzed blood and urine samples from 718 older adults, alongside detailed dietary recalls, to identify chemical fingerprints, called poly-metabolite scores, linked to UPF intake.

The study found that hundreds of blood and urine metabolites were associated with the percentage of energy someone consumes from UPFs. A poly-metabolite score corresponding with UPF intake could be created using 28 of the blood metabolites or 33 urine metabolites. This score was predictive of UPF intake among participants using self-reported dietary data. The researchers then validated the scores in a controlled feeding study, confirming the scores could distinguish, within subjects, between high-UPF and no-UPF diets among 20 inpatients at the NIH Clinical Center with high-controlled diets. The scores also significantly differed between a UPF-heavy diet and one without UPFs.

“The identified poly-metabolite scores could serve as objective measures of UPF intake in large population studies to complement or reduce reliance on self-reported dietary data,” the authors say. “Poly-metabolite scores should be evaluated and iteratively improved in populations with diverse diets and a wide range of UPF intake.”

The authors add, “We developed and tested poly-metabolite scores in blood and urine that were predictive of diets high in energy from UPF intake in an observational study of free-living adults and in a highly controlled feeding trial, respectively. These poly-metabolite scores could serve as objective measures of UPF intake in large population studies to complement or reduce reliance on self-reported dietary data. Additionally, these findings could provide novel insight into the role of UPF in human health.”

Published in Nature on May 19, 2025, the study notes that mpox transmitted among humans in Nigeria for eight years before sparking the international outbreak in 2022. Using genomic tracing, the researchers estimate that the virus’ ancestor first emerged in southern Nigeria in August 2014 and spread to 11 states before human infections were detected in 2017. The findings highlight the need for improved global surveillance and medicines, given the threat of impending pandemics.

“We could have very easily prevented the 2022 multi-country outbreak if countries in Africa were given better access to therapeutics, vaccines and surveillance technologies,” says Edyth Parker, a professional collaborator in the Kristian Andersen Lab at Scripps Research and one of the paper’s first authors. “In a vulnerably connected world, we cannot neglect epidemics until they get exported to the Global North.”

Because the virus involved in the 2022 outbreak had an unexpected number of genetic mutations, scientists thought that mpox might have been circulating in Nigeria for much longer than expected. However, due to a lack of genomic data, it was unclear when and where the virus had first emerged, and what had driven its emergence.

To solve this problem, the study’s senior author, Christian Happi, director of the Institute of Genomics and Global Health at Redeemer’s University in Nigeria, organized a Pan-African consortium to share and generate mpox genomic data. The consortium involved researchers and public health agencies in West and Central Africa, with support from international collaborators including Scripps Research. By pooling samples and laboratory methods, the group generated a genomic dataset that is around three times larger than any previous mpox dataset.

Altogether, the team analyzed 118 viral genomes from human mpox cases that occurred in Nigeria and Cameroon between 2018 and 2023. All of the sequences were identified as Clade IIb — the mpox strain endemic to West Africa. By comparing the genomes’ sequences, the researchers created something called a phylogenetic tree, which estimates how related the different viruses are, and how recently they evolved.

They found that most of the viral samples from Nigeria were the result of human-to-human transmission (105/109), while the remaining four were caused by zoonotic spillover. In contrast, all nine mpox samples from Cameroon were derived from isolated zoonotic spillover events.

“Mpox is no longer just a zoonotic virus in Nigeria; this is very much a human virus,” says Parker. “But the fact that there’s ongoing zoonotic transmission means there’s also a continual risk of re-emergence.”

Using the phylogenetic tree, the team estimated that the ancestor of the human-transmitting mpox virus emerged in animals in November 2013 and first entered the human population in southern Nigeria in August 2014. They also showed that southern Nigeria was the main source of subsequent cases of human mpox: though the virus spread throughout Nigeria, continual human-to-human transmission only occurred in the country’s south.

The team also showed that two of the zoonotically transmitted viral samples from southern Nigeria were related to the Cameroonian viruses, suggesting that viruses are traveling across the border.

“There’s likely a lot more bi-directional viral movement happening between these countries, but we just don’t have the wildlife sampling to detect it,” says Parker. “Our study highlights the need for better wildlife surveillance, as well as better surveillance in the human populations that interface with animals in that forested border region.”

Overall, the study shows the importance of better access to diagnostics, vaccines and therapeutics in Africa, the researchers say.

“Global health inequities really impede our ability to control both zoonotic and sustained human transmission,” says Parker. “We cannot continue to neglect either the human epidemics in Africa or the risk of re-emergence — not only does it perpetuate suffering in these regions, it means that inevitably there will be another pandemic.”

“Other studies have evaluated the interaction of nanoplastics and bacteria, but so far, ours is the first to look at the impacts of microplastics and nanoplastics on human pathogenic bacteria. We focused on one of the key pathogens implicated in outbreaks of foodborne illness — E. coli O157:H7,” said senior study author Pratik Banerjee, associate professor in the Department of Food Science and Human Nutrition and an Illinois Extension Specialist; both units are part of the College of Agricultural, Consumer and Environmental Sciences at Illinois.

Banerjee’s team found that nanoplastics with positively charged surfaces were more likely to cause physiological stress in E. coli O157:H7. Just as a stressed dog is more likely to bite, the stressed bacteria became more virulent, pumping out more Shiga-like toxin, the chemical that causes illness in humans.

The researchers expected positively charged nanoplastics to impact E. coli because the bacteria’s surface carries a negative charge. To test their opposites-attract hypothesis, they created nanoplastics from polystyrene — the material in those ubiquitous white clamshell-style takeout boxes — and applied positive, neutral, or negative charges before introducing the particles to E. coli either free-floating in solution or in biofilms.

“We started with the surface charge. Plastics have an enormous ability to adsorb chemicals. Each chemical has a different effect on surface charge, based on how much chemical is adsorbed and on what kind of plastic,” Banerjee said. “We didn’t look at the effects of the chemicals themselves in this paper — that’s our next study — but this is the first step in understanding how the surface charge of plastics impacts pathogenic E. coli response.”

The bacteria exposed to positively charged nanoplastics showed stress in multiple ways, not just by producing more Shiga-like toxin. They also took longer to multiply when free-floating and congregated into biofilms more slowly. However, growth eventually rebounded.

Biofilms give bacterial cells a measure of protection thanks to an extracellular coating they develop. To test whether this coating protected against nanoplastic-induced stress, the team dunked comparatively large microplastic particles into the bacterial soup and gave E. coli a week or two to colonize. Then, they introduced the same charged nanoplastics.

The positively charged particles still caused stress — and enhanced Shiga-like toxin production — in biofilm-bound E. coli.

“Biofilms are a very robust bacterial structure and are hard to eradicate. They’re a big problem in the medical industry, forming on inserts like catheters or implants, and in the food industry,” Banerjee said. “One of our goals was to see what happens when this human pathogen, which is commonly transmitted via food, encounters these nanoplastics from the vantage point of a biofilm.”

Interactions with plastic particles may be doing more than increasing E. coli‘stoxicity; other studies have shown biofilms on microplastics may serve as hotspots for the transfer of antibiotic resistance genes, making the bacteria harder to manage. Banerjee’s group has studies underway to look at resistance gene transfer and changes in virulence and transmission patterns of major foodborne pathogens in food products and other environments such as soil.

Banerjee is also affiliated with the Carl R. Woese Institute for Genomic Biology and the Center for South Asian and Middle Eastern Studies at U. of I.

Stem cells can produce any other cell type, it is just a matter of telling them in the right way. From a biological perspective, this means activating the proper genetic programme by pressing the right keys, this is, the right genes, at the right moment. Quite often, blood cancer patients require the replacement of their blood stem cells in the bone marrow, the tissue producing blood cells where their cancer grows. Unfortunately, finding a compatible donor happens to be too challenging sometimes. What if we could produce the cells that make blood in the lab, right from basic stem cells, and use them to regenerate a new and healthy bone marrow?

To do this, you would need to know what genes to activate in a stem cell. In a tour de force, the team led by Dr. Anna Bigas screened thousands of genes in the mice genome to see which were able to transform an embryonic stem cell into a blood precursor or, more technically, a Haematopoietic Stem Cell (HPSC). The screening identified a group of seven genes apparently able to accomplish the task.

In subsequent experiments, the team confirmed that the timely activation of the seven genes was sufficient to transform mouse embryonic stem cells into HSPC, and that these newly produced cells were able to regenerate and sustain a functional blood system, producing all kinds of blood cells, including the immune lineages, in adult mice.

The research has been recently published at the journal Blood, official outlet of the American Society of Hematology, first-authored by Dr. Luis Galan Palma, researcher from the Bigas Lab, in a collaboration with other researchers including Dr. Clara Bueno and Dr. Pablo Menéndez, experts in developmental and paediatric leukaemia, also at the Josep Carreras Institute.

Dr. Bigas is confident that the results obtained in mice can be translated into the human system since, despite the differences, the mechanisms driving stem cells differentiation are so fundamental that are shared between species. As Dr. Bigas points out “we know that those genes are also present in the human genome, and they are highly conserved, this is, their genetic sequences are almost identical.” Research is on the way, but chances are they really play the same role in humans as in mice.

This research is a proof-of-concept for the Bigas Lab’s ERC synergy-funded project Making Blood, a highly ambitious endeavour to develop a technological platform aimed at the production of human HSPC off the shelf. If successful, we are just a few years away of a new era in the treatment of leukaemia and other blood disorders, based on the long-awaited regenerative medicine.

This research has been partly funded by the Spanish Ministry of Science, Innovation and Universities, Generalitat de Catalunya, and personal grants by “la Caixa” Foundation, Instituto de Salud Carlos III and the Ramón Areces Foundation.

The study covers nearly 350,000 people of different ages, from 14 cohorts in seven European countries. Information on home addresses of each individual made it possible to link data on various environmental risks in the urban environment to individual people. The environmental exposures included were air pollution, outdoor temperatures, and the level of urban density. The assessment was partly based on satellite images showing grey, green, or blue areas, i.e., where there were buildings, green spaces, or water.

“Previous studies have typically calculated the risk of one environmental factor at a time. We have combined several environmental factors and described how they together affect the risk of developing asthma. This provides a better picture of environmental risks, as life in a city usually involves exposure to several environmental risk factors at the same time,” says first author Zhebin Yu, researcher and assistant professor at the Institute of Environmental Medicine at Karolinska Institutet.

During the study period, nearly 7,500 of the study participants developed asthma as children or adults. The researchers found that 11.6 per cent of asthma cases could be explained by the combination of environmental factors. Or, to put it another way, in a favourable environment, approximately one in ten people with asthma would not have developed the disease. The combination of air pollution, lack of green spaces, and dense urban development was most relevant for the development of asthma.

“This is useful for politicians and others involved in urban planning. The method makes it possible to identify risk areas in existing urban areas, but it can also be used when planning future urban environments,” says Erik Melén, professor at the Department of Clinical Research and Education, Södersjukhuset, and last author of the study.

The next step for the researchers is to examine blood samples from some of the study participants. The aim is to identify their metabolome, i.e., a composite picture of the body’s metabolism and breakdown products. The purpose is to understand how external environmental factors affect the body, which could provide a better understanding of how asthma develops.

The study was conducted in collaboration between various research groups within the framework of the EU project EXPANSE. The researchers involved in the project are also investigating how the risk of other diseases such as stroke, heart attack, COPD and diabetes, is affected by individual exposomes, i.e., the total exposure to many environmental factors.

The study was funded by the EU’s Horizon 2020 programme (EXPANSE, No 874627), the Swedish Research Council, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Heart-Lung Foundation and Region Stockholm, among others.

A new study co-authored by Chapman University professor and founding dean of the Fowler School of Engineering, Dr. L. Andrew Lyon, unveils a major advancement in noninvasive health technology: a smartphone app that uses artificial intelligence and a photo of a user’s fingernail to detect anemia..

Published in the journal Proceedings of the National Academy of Sciences (PNAS), the study demonstrates that this noninvasive, AI-augmented app provides hemoglobin estimates that rival traditional lab testing. With more than 1.4 million tests performed by over 200,000 users, the app represents a scalable, low-cost solution that broadens access to anemia screening, especially in underserved and remote communities.

With increased access, this app brings reliable screening directly into the hands of consumers, enabling real-time health monitoring and earlier intervention, empowering users to make informed decisions without waiting for lab results. While not intended for self-diagnosis, the app helps users understand when to consult a healthcare provider.

The app is particularly valuable for those with chronic anemia, such as people with kidney disease or cancer, who often require frequent monitoring. The study showed that personalized app use in these patients improved accuracy by nearly 50%, enabling safer, easier at-home management.

“This research, more than eight years in the making, represents a meaningful step toward improving accessibility in healthcare,” said Dr. Lyon. “It’s a testament to long-term collaboration and a commitment to empowering patients through innovation.”

Key findings:

• 4 M+ tests performed using smartphone cameras and AI-powered fingernail analysis.
• Hemoglobin (Hgb) estimates showed a mean absolute error of ±0.72 g/dL, improving to ±0.50 g/dL in users with Hgb >10 g/dL.
• Geolocation data enabled the first county-level anemia prevalence map in the U.S.
• App personalization for chronic anemia patients improved accuracy (from ±1.36 to ±0.74 g/dL).
• Users can now track their hemoglobin levels at home, reducing the need for frequent clinic visits.
• Traditional blood testing is time-consuming, expensive, and requires clinical infrastructure. This tool offers a low-cost, noninvasive alternative with massive scalability.

The research team found that when the PPP1R3B gene is more active, the liver tends to store more energy as glycogen. The liver stores more energy as fat when the gene is less active. This shift between glycogen and fat storage is crucial because it affects how the body manages blood sugar and fat levels.

Large scale genomics studies in humans have reported that mutations in the PPP1R3B gene are associated with several metabolic conditions, including type 2 diabetes and fatty liver disease. However, it was unclear how the gene was involved in these conditions.

“Our research shows that PPP1R3B is like a control switch in the liver,” said Creasy. “It directs whether the liver stores energy for quick use in the form of glycogen or for longer-term storage as fat. We also saw changes in how efficiently mice and cells with genetic manipulations of PPP1R3B could use either glucose or fat for energy. This discovery could help us find new ways to help people with metabolic diseases with precision nutrition approaches, based on their genetics.”

Co-authors from the Perelman School of Medicine include: Minal B. Mehta, Joseph Park, David Zhang, and Swapnil V. Shewale (all based in the Department of Genetics), Carolin V. Schneider (Division of Translational Medicine and Human Genetics), John S. Millar (Institute for Diabetes, Obesity, and Metabolism), Marijana Vujkovic (Division of Translational Medicine and Human Genetics and the Institute for Diabetes, Obesity, and Metabolism), Nicholas J. Hand (Department of Physiology), Paul M. Titchenell (Institute for Diabetes, Obesity, and Metabolism and the Department of Physiology), Joseph A. Baur (Institute for Diabetes, Obesity, and Metabolism and the Department of Physiology), and Daniel J. Rader (Division of Translational Medicine and Human Genetics in the Department of Genetics, and the Institute for Diabetes, Obesity, and Metabolism). The National Institutes of Health supported this research.

A new University of Arizona study, published in Nature Communications, describes a longer-lasting, 3D-printed, adhesive-free wearable capable of providing a more comprehensive picture of a user’s physiological state.

The device, which measures water vapor and skin emissions of gases, continuously tracks and logs physiological data associated with dehydration, metabolic shifts and stress levels.

“Wearable health monitoring traditionally depends on sensors that directly attach to the skin, but the skin itself constantly renews,” said Philipp Gutruf, an associate professor of biomedical engineering and member of the BIO5 Institute at the U of A who co-authored the study with lead author David Clausen, a doctoral student and researcher in the Gutruf Lab.

“This limits how long you can collect reliable data. With our sensor that tracks gaseous emissions from the skin, we overcome this constraint entirely,” Gutruf said.

Skin shedding weakens adhesives and clogs sensors, so wearables applied with adhesives must be reapplied every few days. Researchers in the Gutruf Lab at the U of A designed a device, worn on the forearm, that resembles a small 3D-printed cuff and can be worn continuously. The device sensors constantly measure gases emitted by the user, comparing their concentrations against normal outside air.

Unlike adhesive-based sports science and health monitoring wearables, which historically only record snapshots, the device developed by Gutruf and his colleagues delivers continuous, real-time data viewable on a smartphone or computer via secure Bluetooth.

“This opens an entirely new space of biomarkers,” said Gutruf. “For example, you can capture the metabolic signatures of exercise or stress without interrupting the subject’s normal routine. Previously, measurements of this kind required an entire room of equipment.”

Practical applications, proven results

With a device such as this, athletes can monitor hydration and exertion during training. The wearable could also record mental health and chronic disease symptoms to aid in prevention and treatment. In fact, tracking and monitoring physiological signs of stress in gas emissions can even help identify early metabolic disturbances, Gutruf said.

“Our design is stable even when exposed to everyday movement and environmental changes,” said Clausen. “We’re able to record data continuously over many days without recharge, all while capturing rich physiological data that isn’t typically possible in a wearable format or requires visible sweat.”

The researchers plan to expand the range of detectable biomarkers and integrate advanced data analytics to provide personalized health insights over even longer periods.

The research was funded by Arizona’s Technology and Research Initiative Fund, the Moore Foundation and with a discretionary award provided to Gutruf as the College of Engineering’s 2024 da Vinci Fellow.

The discovery, published in Science May 15, fundamentally changes current understanding about the determinants of brain network communication and activity. It also calls for greater focus on astrocytes as therapeutic targets in the treatment of attention, memory and emotional disorders.

“Textbooks tell us that neuromodulators like norepinephrine fine-tune neurons directly — in fact, textbooks tell us that everything in the brain is about neurons,” said Thomas Papouin, PhD, assistant professor of neuroscience at WashU Medicine and the senior author of the study. “It seems that a lot of brain wiring and activity is probably orchestrated by astrocytes, on slower timescales. This is the type of discovery that profoundly reshapes our understanding of how the brain works.”

From the brain’s wallflower to center stage

For the brain to dedicate itself to tasks that need attention, or to respond to unexpected stimuli like a fire alarm, it needs to be able to rewire itself by changing how brain cells communicate. This process is driven by the release of chemicals known as neuromodulators, including norepinephrine, in the brain. How these neuromodulators reorganize communication in the brain is poorly understood. The assumption for the past 80 years has been that neuromodulator chemicals act on neurons.

Meanwhile, for at least 30 years astrocytes have been shown to contact and interact with synapses, which are the specialized structures where neurons communicate with one another. Researchers have long suspected that astrocytes had the potential to rearrange communication between neurons and, therefore, the flow of information in the brain.

Because of their very fine and sprawling shape, these cells are ideally positioned to monitor and detect neuromodulators like norepinephrine. “We wanted to test the idea that perhaps neuromodulation of synapses by norepinephrine is an astrocyte business,” Papouin said.

To do so, Papouin and his team stimulated norepinephrine secretion from mouse brain cells or exposed mouse brain slices to norepinephrine and found that norepinephrine weakened connections between neurons, as known for decades. However, researchers found that norepinephrine also triggered activity among surrounding astrocytes. Once triggered by norepinephrine, astrocytes produced a second chemical that they released onto synapses, which caused the dampening of synapse activity. Even when neurons’ ability to directly sense norepinephrine was removed, norepinephrine was still able to rearrange neuronal connections. When astrocytes’ ability to sense or respond to norepinephrine were taken offline, on the other hand, norepinephrine was unable to reorganize neuronal connectivity.

Their findings indicate that neuromodulators such as norepinephrine rearrange neuronal connections in the brain by signaling through astrocytes rather than directly onto neurons.

The results also suggest that targeting astrocytes could be an effective way to reshape brain activity to potentially treat brain disorders. Papouin’s team has started looking at existing drugs that are believed to act on neurons, to see if they require astrocytes to be effective. If so, perhaps astrocytes could be targeted directly for therapeutic purposes.

“There are so many drugs out there that interfere with norepinephrine signaling in the brain, in particular in the treatment of ADHD or depression. I wonder how many of them require astrocytes to modify brain activity,” said Papouin.

Until now, most research has used either generalized cell samples or organoids made from just one type of tropical fruit bat, and only from a single organ. But a breakthrough has arrived: a research team led by the Institute for Basic Science (IBS) in Korea, along with international collaborators, has created the world’s most comprehensive bat organoid platform. These “mini-organs” are grown from five common bat species found across Asia and Europe and represent four different organs — airway, lungs, kidneys, and small intestine.

“Reconstructing bat organ physiology in the lab lets us explore how zoonotic viruses — those that jump from animals to humans — work, in unprecedented detail,” said KOO Bon-Kyoung, Director of the IBS Center for Genome Engineering.

Testing Viruses Where They Live

Armed with these new tools, the researchers were able to directly test how key viruses — including SARS-CoV-2, MERS-CoV, influenza A, and hantavirus — infect different bat species and organs. They found that each virus behaves uniquely, sometimes infecting only certain organs or bat species. For example, a virus that grew easily in one bat’s lung might fail to grow in another’s kidney. This helps explain why some viruses can jump to humans, while others remain confined to bats.

Senior Researcher KIM Hyunjoon emphasized, “This platform lets us isolate viruses, study infections, and test drugs all within one system — something you can’t do with ordinary lab cell models. By mimicking the bat’s natural environment, it boosts the accuracy and real-world value of infectious disease research.”

The team also uncovered another mystery: bats’ immune systems respond differently to the same virus depending on the organ and the species. This could help explain why bats are able to carry so many viruses without becoming sick themselves.

Another big achievement was the discovery of two previously unknown bat viruses — a mammalian orthoreovirus and a paramyxovirus — directly from wild bat feces. Notably, one of these viruses could not be grown in standard cell cultures but thrived in the new bat organoids, proving just how valuable this technology is for future virus isolation.

And, by converting the organoids into a two-dimensional version, the scientists made it possible to quickly test potential antiviral drugs, like Remdesivir. These tests gave more reliable results than traditional lab methods.

A Global Biobank for Future Pandemic Preparedness

This bat organoid platform marks a new era for infectious disease research, making it possible to safely and effectively study dangerous viruses in a setting that closely mirrors real life. For the first time, scientists can screen for new viruses, assess their risk, and test drugs using bat tissues from multiple species and organs.

“With these standardized and scalable bat organoids, we aim to systematically identify novel bat-origin viruses and screen antiviral candidates targeting pathogens with pandemic potential,” said Dr. CHOI Young Ki, Director of the Korea Virus Research Institute, Institute for Basic Science (IBS).

The research team envisions expanding this work into a global biobank resource that will serve as a cornerstone for both national and international biosecurity efforts. This initiative will enable deeper investigation into the viral features that drive cross-species transmission, support the development of comprehensive genetic maps of key bat species, and facilitate global preparedness. Ultimately, this platform will support efforts by health organizations, including the World Health Organization (WHO), to predict and prevent future pandemics.

The study, published today in the journal Science, provides direct evidence for the real-time action of a star-shaped type of glial cell, known as astrocytes, in the live brains of fruit flies. The abundant cell type — roughly 35% of all cells in the human brain — appears to be a key part of orchestrating a complex network governing brain function.

“We hope this begins to fundamentally change how the field thinks about astrocytes and their role in mediating neurophysiology and behavior,” said senior author Marc Freeman, Ph.D., director of the OHSU Vollum Institute. “Over the long run, it should change how people think about developing therapies for regulation of attention, anxiety and mood.”

The discovery was replicated in the astrocytes of rodents, suggesting it’s an ancient feature of evolution likely to be conserved in other mammals including people.

“I think it’s evolutionarily relevant to survival,” said lead author Kevin Guttenplan, Ph.D., a postdoctoral scientist in Freeman’s lab. “If a tiger’s behind you, you need to rapidly change how whole brain regions are thinking — it’s time to shut out everything else on your mind and entirely focus the brain on escaping. It’s not the time to think about anything else.”

Building on discoveries

At one time, astrocytes were thought to serve only a supporting role by providing food and removing waste for neurons, the cells that form the brain’s “hardwiring” by transmitting signals enabling us to think, act and feel sensations.

In 2016, Freeman and collaborators documented for the first time that astrocytes also transmit signals between neurons.

Building on that discovery, researchers show some of the specific mechanisms revealing how those cells transmit signals. It turns out to be a highly complex interplay in which astrocytes can turn on and off their ability to respond to chemical neurotransmitters in the brain, such as dopamine and glutamate.

“Astrocytes are really big, and a single cell can have 100,000 synapses capable of sending signals to other cells,” Guttenplan said. “This mechanism allows them to choose which neurons to listen to. Being able to turn off some of those circuits allows astrocytes to make sense of the cacophony of activity occurring in in the brain from moment to moment.”

Researchers found that by manipulating this gating pathway within astrocytes, they were able to disrupt the behavior of the fruit flies — highlighting the fact that these small changes can have a potent impact.

‘Astrocytes may be the key’

Neuroscientists have previously assumed astrocytes to be a much more passive player in brain physiology.

“This study shows the importance of astrocytes in neuronal activity and behavior,” said Miriam Leenders, Ph.D., program director at the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, which funded the study. “It also demonstrates how fundamental neuroscience studies in model systems like the fruit fly can provide pivotal new insights into brain physiology.”

The new research reveals that astrocytes can directly respond to messages from all types of neurons. In this way, they play a role in the complex network of neuronal signaling that drives cognition and controls physical behavior. In addition, they found these responses change dynamically with brain state, allowing astrocytes to orchestrate the complex network of neurons enabling the brain to attend to the tasks at hand.

“These cells do actively control neuronal activity, really powerfully,” Guttenplan said.

However, scientists caution that the discovery complicates scientific understanding of how the brain functions. Imagine a single astrocyte bristling with thousands of synapses whose gating mechanisms may be alternately activated or silenced by myriad cues swirling around it. And then multiply it by millions of astrocytes throughout the entire human brain.

“It’s overwhelmingly complicated,” Guttenplan said.

At the same time, researchers are increasingly finding evidence that glial cells play a role in brain injuries and in neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases. Improving scientific understanding about how these cells function could help to prevent disease or develop treatments.

“In some of these conditions, things like focus and attention get disrupted,” Guttenplan said. “Astrocytes may be the key.”

In addition to Freeman and Guttenplan, co-authors include Isa Maxwell, B.A., Erin Santos, B.A., Luke A. Borchardt, B.S,, Ernesto Manzo, Ph.D., and Leire Abalde-Atristain, Ph.D., of OHSU; and Rachel D. Kim, Ph.D., of the New York University Grossman School of Medicine.

University of Oklahoma researcher Matthew Potthoff, Ph.D., is the lead author of the study, which provides valuable insight about the mechanism of action of the hormone, which is a target for a new class of highly anticipated drugs that are in Phase 3 clinical trials.

“Fatty liver disease, or MASLD (metabolic dysfunction-associated steatotic liver disease), is a buildup of fat in the liver. It can progress to MASH (metabolic dysfunction-associated steatohepatitis) during which fibrosis and, ultimately, cirrhosis can occur. MASLD is becoming a very big problem in the United States, affecting 40% of people worldwide, and there is currently only one treatment approved by the Food and Drug Administration to treat MASH. A new class of drugs, based on FGF21 signaling, is showing good therapeutic benefits in clinical trials, but until now, the mechanism for how they work has been unclear,” said Potthoff, a professor of biochemistry and physiology at the University of Oklahoma College of Medicine and deputy director of OU Health Harold Hamm Diabetes Center.

The study’s results demonstrated that FGF21 was effective at causing signaling in the model species that changed the liver’s metabolism. In doing so, the liver’s fat was lowered and the fibrosis was reversed. The hormone also sent a separate signal directly to the liver, specifically to lower cholesterol.

“It’s a feedback loop where the hormone sends a signal to the brain, and the brain changes nerve activity to the liver to protect it,” Potthoff said. “The majority of the effect comes from the signal to the brain as opposed to signaling the liver directly, but together, the two signals are powerful in their ability to regulate the different types of lipids in the liver.”

Similar to the family of weight loss drugs known as GLP-1s (glucagon-like peptide 1), which help regulate blood sugar levels and appetite, FGF21 acts on the brain to regulate metabolism. In addition, both are hormones produced from peripheral tissues — GLP-1 from the intestine and FGF21 from the liver — and both work by sending a signal to the brain.

“It is interesting that this metabolic hormone/drug works primarily by signaling to the brain instead of to the liver directly, in this case,” he said. “FGF21 is quite powerful because it not only led to a reduction of fat, but it also mediated the reversal of fibrosis, which is the pathological part of the disease, and it did so while the mice were still eating a diet that would cause the disease. Now, we not only understand how the hormone works, but it may guide us in creating even more targeted therapies in the future.”

“People with a transient ischemic attack can have symptoms such as face drooping, arm weakness or slurred speech and these resolve within a day,” said study author Boris Modrau, MD, PhD, of Aalborg University Hospital in Denmark. “However, some have reported continued challenges including reduced quality of life, thinking problems, depression, anxiety and fatigue. Our study found that for some people, fatigue was a common symptom that lasted up to one year after the transient ischemic attack.”

The study involved 354 people with an average age of 70 who had a mini-stroke. They were followed for a year.

Participants completed questionnaires about their level of fatigue within the first two weeks of the mini-stroke and again at three, six, and 12 months later.

One questionnaire looked at five different types of fatigue, including overall tiredness, physical tiredness, reduced activity, reduced motivation and mental fatigue. Scores ranged from four to 20 with higher scores indicating more fatigue. Participants had an average score of 12.3 at the start of the study. At three months, the average score decreased slightly to 11.9, at six months to 11.4 and at twelve months to 11.1.

Researchers looked at how many participants experienced fatigue as defined as a score of 12 or higher. Of the participants, 61% experienced fatigue two weeks after the mini-stroke and 54% experienced fatigue at each of the three other testing time periods at three, six and 12 months.

Participants also had brain scans. Researchers found that the presence of a blot clot on a scan was equal between people with long term fatigue and those without it, so this did not explain the reason for the level of fatigue.

Researchers did find that previous anxiety or depression was twice as common in those participants who reported lasting fatigue.

“Long-term fatigue was common in our group of study participants, and we found if people experience fatigue within two weeks after leaving the hospital, it is likely they will continue to have fatigue for up to a year,” said Modrau. “For future studies, people diagnosed with a transient ischemic attack should be followed in the weeks and months that follow to be assessed for lingering fatigue. This could help us better understand who might struggle with fatigue long-term and require further care.”

A limitation of the study was that while participants were asked to complete the questionnaires themselves, it is possible some responses may have been completed with assistance from relatives or caretakers and this may have influenced responses, including those around fatigue.

The study was supported by the Danish Physiotherapy Association.

Scientists have long sought to understand how the brain retrieves words during speech. A new study by researchers at New York University sheds light on this mystery, revealing a left-lateralized network in the dorsolateral prefrontal cortex that plays a crucial role in naming. The findings, published in Cell Reports, provide new insights into the neural architecture of language, offering potential applications for both neuroscience and clinical interventions.

Mapping the Brain’s Naming Network

Word retrieval is a fundamental aspect of human communication, allowing us to link concepts to language. Despite decades of research, the exact neural dynamics underlying this process — particularly in natural auditory contexts — remain poorly understood.

NYU researchers — led by Biomedical Engineering Graduate Student Leyao Yu and Associate Professor of Biomedical Engineering at NYU Tandon and Neurology at NYU Grossman School of Medicine Adeen Flinker — recorded electrocorticographic (ECoG) data from 48 neurosurgical patients to examine the spatial and temporal organization of language processing in the brain. By using unsupervised clustering techniques, the researchers identified two distinct but overlapping networks responsible for word retrieval. The first, a semantic processing network, was located in the middle and inferior frontal gyri. This network was engaged in integrating meaning and was sensitive to how surprising a word was within a given sentence. The second, an articulatory planning network, was situated in the inferior frontal and precentral gyri, which played a crucial role in speech production, regardless of whether words were presented visually or auditorily.

Auditory Naming and the Prefrontal Cortex

The study builds upon decades of work in language neuroscience. Previous research suggested that different regions of the brain were responsible for retrieving words depending on whether they were seen or heard. However, earlier studies relied on methods with limited temporal resolution, leaving many unanswered questions about how these networks interact in real time.

By leveraging the high spatial and temporal resolution of ECoG, the researchers uncovered a striking ventral-dorsal gradient in the prefrontal cortex. They found that while articulatory planning was localized ventrally, semantic processing was uniquely represented in a dorsal region of the inferior frontal gyrus and middle frontal gyrus — a previously underappreciated hub for language processing.

“These findings suggest that a missing piece in our understanding of language processing lies in this dorsal prefrontal region,” explains lead author Leyao Yu. “Our study provides the first direct evidence that this area is involved in mapping sounds to meaning in an auditory context.”

Implications for Neuroscience and Medicine

The study has far-reaching implications, not only for theoretical neuroscience but also for clinical applications. Language deficits, such as anomia — the inability to retrieve words — are common in stroke, brain injury, and neurodegenerative disorders. Understanding the precise neural networks involved in word retrieval could lead to better diagnostics and targeted rehabilitation therapies for patients suffering from these conditions.

Additionally, the study provides a roadmap for future research in brain-computer interfaces (BCIs) and neuroprosthetics. By decoding the neural signals associated with naming, scientists could potentially develop assistive devices for individuals with speech impairments, allowing them to communicate more effectively through direct brain-computer communication.

For now, one thing is clear: our ability to name the world around us is not just a simple act of recall, but the result of a sophisticated and finely tuned neural system — one that is now being revealed in greater detail than ever before.

To help address the eldercare challenge, a team of MIT engineers is looking to robotics. They have built and tested the Elderly Bodily Assistance Robot, or E-BAR, a mobile robot designed to physically support the elderly and prevent them from falling as they move around their homes.

E-BAR acts as a set of robotic handlebars that follows a person from behind. A user can walk independently or lean on the robot’s arms for support. The robot can support the person’s full weight, lifting them from sitting to standing and vice versa along a natural trajectory. And the arms of the robot can them by rapidly inflating side airbags if they begin to fall.

With their design, the researchers hope to prevent falls, which today are the leading cause of injury in adults who are 65 and older.

“Many older adults underestimate the risk of fall and refuse to use physical aids, which are cumbersome, while others overestimate the risk and may not to exercise, leading to declining mobility,” says Harry Asada, the Ford Professor of Engineering at MIT. “Our design concept is to provide older adults having balance impairment with robotic handlebars for stabilizing their body. The handlebars go anywhere and provide support anytime, whenever they need.”

In its current version, the robot is operated via remote control. In future iterations, the team plans to automate much of the bot’s functionality, enabling it to autonomously follow and physically assist a user. The researchers are also working on streamlining the device to make it slimmer and more maneuverable in small spaces.

“I think eldercare is the next great challenge,” says E-BAR designer Roberto Bolli, a graduate student in the MIT Department of Mechanical Engineering. “All the demographic trends point to a shortage of caregivers, a surplus of elderly persons, and a strong desire for elderly persons to age in place. We see it as an unexplored frontier in America, but also an intrinsically interesting challenge for robotics.”

Bolli and Asada will present a paper detailing the design of E-BAR at the IEEE Conference on Robotics and Automation (ICRA) later this month.

Home support

Asada’s group at MIT develops a variety of technologies and robotic aides to assist the elderly. In recent years, others have developed fall prediction algorithms, designed robots and automated devices including robotic walkers, wearable, self-inflating airbags, and robotic frames that secure a person with a harness and move with them as they walk.

In designing E-BAR, Asada and Bolli aimed for a robot that essentially does three tasks: providing physical support, preventing falls, and safely and unobtrusively moving with a person. What’s more, they looked to do away with any harness, to give a user more independence and mobility.

“Elderly people overwhelmingly do not like to wear harnesses or assistive devices,” Bolli says. “The idea behind the E-BAR structure is, it provides body weight support, active assistance with gait, and fall catching while also being completely unobstructed in the front. You can just get out anytime.”

The team looked to design a robot specifically for aging in place at home or helping in care facilities. Based on their interviews with older adults and their caregivers, they came up with several design requirements, including that the robot must fit through home doors, allow the user to take a full stride, and support their full weight to help with balance, posture, and transitions from sitting to standing.

The robot consists of a heavy, 220-pound base whose dimensions and structure were optimized to support the weight of an average human without tipping or slipping. Underneath the base is a set of omnidirectional wheels that allows the robot to move in any direction without pivoting, if needed. (Imagine a car’s wheels shifting to slide into a space between two other cars, without parallel parking.)

Extending out from the robot’s base is an articulated body made from 18 interconnected bars, or linkages, that can reconfigure like a foldable crane to lift a person from a sitting to standing position, and vice versa. Two arms with handlebars stretch out from the robot in a U-shape, which a person can stand between and lean against if they need additional support. Finally, each arm of the robot is embedded with airbags made from a soft yet grippable material that can inflate instantly to catch a person if they fall, without causing bruising on impact. The researchers believe that E-BAR is the first robot able to catch a falling person without wearable devices or use of a harness.

They tested the robot in the lab with an older adult who volunteered to use the robot in various household scenarios. The team found that E-BAR could actively support the person as they bent down to pick something up from the ground and stretched up to reach an object off a shelf — tasks that can be challenging to do while maintaining balance. The robot also was able to lift the person up and over the lip of a tub, simulating the task of getting out of a bathtub.

Bolli envisions a design like E-BAR would be ideal for use in the home by elderly people who still have a moderate degree of muscle strength but require assistive devices for activities of daily living.

“Seeing the technology used in real-life scenarios is really exciting,” says Bolli.

In their current paper, the researchers did not incorporate any fall-prediction capabilities in E-BAR’s airbag system. But another project in Asada’s lab, led by graduate student Emily Kamienski, has focused on developing algorithms with machine learning to control a new robot in response to the user’s real-time fall risk level.

Alongside E-BAR, Asada sees different technologies in his lab as providing different levels of assistance for people at certain phases of life or mobility.

“Eldercare conditions can change every few weeks or months,” Asada says. “We’d like to provide continuous and seamless support as a person’s disability or mobility changes with age.”

This work was supported, in part, by the National Robotics Initiative and the National Science Foundation.

Changes to the tackle height law in women’s community rugby in Scotland is linked to reductions in head-to-head and head-to shoulder contacts, the study found.

A study compared more than 11,000 tackles between the 2022/23 season, before the reduced tackle height law was trialed and the 2023/24 season when it was introduced.

Experts found 21 per cent fewer upright tackles and a 34 per cent increase in tacklers entering the tackle bent at the waist, the recommended technique to reduce contact to the high-risk areas of the head and shoulders.

In collaboration with Scottish Rugby and World Rugby, researchers at the University of Edinburgh used video analysis to study the impact of the lowered tackle height law which World Rugby, the sport’s governing body introduced for community rugby in an attempt to improve safety for players.

The research found a 64 per cent reduction in tacklers making initial contact with the ball carriers head and neck — one of the primary causes of sports related concussion.

Lowering the tackle height was also associated with a 17 per cent reduction in the rate of head-to-head and a 35 per cent reduction in head-to-shoulder contacts for the tackler, the study found.

The study, which is the first to evaluate the lowered tackle height law in women’s community rugby, shows a positive change in player behaviour, researchers say.

The findings can inform future injury prevention initiatives in women’s community rugby in Scotland and beyond, they add.

World Rugby recommended an opt-in international trial of lowering the tackle height from the shoulder to below the sternum as part of a drive to reduce the risk of head-on-head contact and concussion in rugby union games.

The trial was adopted by Scottish Rugby for the 2023/2024 season alongside other nations including Australia, England, France, Ireland, Italy, Japan New Zealand, South Africa and Wales.

Researchers at Moray House School of Education and Sport analysed video footage and injury data from 34 Scottish community women’s rugby matches from the top-level Premiership to the third-tier regional leagues.

The analysis used footage from Scottish Rugby which recorded players’ activity including tackle type, body position, contact point and head contact.

Points of contact between players alongside match events and tackle characteristics were coded according to guidelines developed in collaboration with World Rugby and the University of Cape Town.

They also discovered a 19 per cent reduction in contacts above the sternum — known as the red zone — between the tackler and the ball-carrier. There was a 29 per cent reduction in head-to-head proximity for the tackler, alongside a 33 per cent reduction in head-to-head proximity and a 48 per cent reduction in head-to-shoulder contact for the ball-carrier.

Positively, there were no increases in the rate of the tacklers head making contact with the ball carriers’ knee or hip, which has previously been associated with an increased risk of concussion.

Sanctions — including penalties, advantages and yellow cards related to high tackles increased significantly from 3 to 8 in the 2023/2024 season. The number of tackles decreased significantly, but there was no significant change to the rate of other game player metrics.

The rate of concussions and injuries when comparing the 2022/23 (pre-trial) and 2023/24 (trial) seasons did not change significantly but the number of reported injuries overall was very low and may have impacted these findings.

Lead author, Hannah Walton, of the University of Edinburgh’s Moray House School of Education and Sport, said: “Our findings show reducing the maximum legal tackle height in Scottish women’s community rugby has resulted in a positive change in player behaviour, alongside reductions in tackler and ball-carrier head contact and head proximity to the oppositions head and shoulder. Continued collection of robust tackle and injury data is key to further understanding the effect of the law change “

Researchers say the study provides valuable data on the impact of the tackle height change in women’s rugby and further studies could help understand the effect of the change on injury and concussion prevention.

Dr Debbie Palmer, of the Institute for Sport, Physical Education and Health Sciences at the Moray House School of Education and Sport, and co-Director for the UK Collaborating Centre on Injury and Illness Prevention in Sport IOC Research Centre, said: “This is the first study evaluating the impact of a lowered tackle height in community women’s rugby and it is good to see, similar to the men’s community study, that initial results are encouraging.

“While injury and concussion numbers were low gathering robust community wide injury surveillance data may help us make more meaningful conclusions. Overall, reductions in head proximity and contact between players is likely to have been beneficial in potentially reducing these concussive events.”

The study builds on the findings of a recent study to assess the impact of the tackle height law change on Scottish men’s community rugby. Evaluations are underway to assess the change on youth community rugby in Scotland.

Scottish Rugby Head of Regional Pathways and Game Development, Neil Graham said: “We look forward to continuing this partnership with University of Edinburgh as we continue to look at ways to evolve the game, keeping player welfare at the centre of the conversation.

“We also look forward to the third and final study on the youth game being released in the near future.”

The study is published in BMJ Open Sport and Exercise Medicine.

The study is part of an international project led by World Rugby to assess the effects of lowering the tackle height in 11 countries including Australia, England, France, Ireland, Italy, Japan, New Zealand, Scotland, South Africa and Wales.

An international team of experts contributed to the study including researchers from the universities of Cape Town and Stellenbosch in South Africa, Calgary in Canada and Leeds Beckett.

The work was funded by World Rugby and Scottish Rugby.

The researchers detected the virus in wastewater using a sequencing-based approach, a highly sensitive and specific method that analyzes genetic material. This strategy might have broad implications for public health, particularly as a sentinel surveillance system to detect viruses before widespread outbreaks occur. The findings are relevant and timely as measles cases are increasing in Texas and the rest of the country and the study offers a promising strategy to get ahead of potential outbreaks.

“In 2023, we showed that systematically sequencing the genetic material in wastewater reveals dynamic changes in human viruses circulating in a community. Importantly, analyzing these viral changes in wastewater can improve our understanding of outbreaks and transmission and inform public health preparedness, just as one uses meteorological data to better understand and predict weather patterns to anticipate potentially dangerous conditions,” said co-corresponding author Dr. Anthony Maresso, Joseph Melnick Endowed Chair and Professor in Molecular Virology and Microbiology at Baylor.

In the current study, the researchers reported that their wastewater surveillance program detected the measles virus in samples collected on Jan. 7 in two Houston water treatment facilities serving more than 218,000 residents. A parallel investigation confirmed on Jan. 17 the measles virus in two travelers residing in the same area serviced by the sampled water treatment plants.

“In such cases our next step is always validating the signal with a second method, and we were able to do so through a collaboration with the Houston Health Department and Rice University,” said co-first author Dr. Sara Javornik Cregeen, assistant professor in the Alkek Center for Metagenomics and Microbiome Research at Baylor. “They tested for the virus presence in samples from the same date and collection site and confirmed the signal using another technique, PCR.”

“As a reference, the 821 Houston wastewater samples we sequenced from the same area were negative for measles virus in the previous 31 months,” she added.

“Because no other cases have been reported and the detections occurred in the same area where the travelers resided, it is reasonable to assume that the measles signal detected in wastewater is from the two infected cases, which underscores the high sensitivity of the method,” Maresso said.

“With lessons learned from the Houston measles detection event, we are now working with our public health partners to gather data on the current measles outbreak in West Texas. Although not reported here, our program has been monitoring measles in wastewater from those sites as well, hoping the information can help officials get ahead of this virus,” said co-first author Dr. Michael Tisza, assistant professor of molecular virology and microbiology at Baylor.

Currently, the researchers are not detecting measles viruses in wastewater in Houston but are detecting it in West Texas cities. The team continues to record the weekly activity of possible concerning viruses and report the results in the first of its kind sequencing-based health dashboard that is publicly available at https://tephi.texas.gov/early-detection.

Dr. Eric Boerwinkle, dean of the UTHealth Houston School of Public Health and co-corresponding author, said that “This work underscores the ability of sophisticated wastewater analyses to serve as an early detection system benefitting public health, healthcare and communities in preventing a measles outbreak in Houston.”

He goes on to remind us that “The best protection from contracting the measles virus is the MMR vaccine, which has been shown to be safe and effective.”

What do a millennia-old human from the Black Sea region and modern HIV medicine have in common?

Quite a lot, it turns out, according to new research from the University of Copenhagen.

18-25 percent of the Danish population carries a genetic mutation that can make them resistant or even immune to HIV. This knowledge is used to develop modern treatments for the virus.

Until now, it was unknown where, when, or why the mutation occurred. But by using advanced DNA technology, researchers have now solved this genetic mystery.

“It turns out that the variant arose in one individual who lived in an area near the Black Sea between 6,700 and 9,000 years ago,” says Professor Simon Rasmussen from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen, corresponding author of a new study mapping the mutation. He adds:

“HIV is a relatively new disease — less than 100 years old — so it’s almost coincidental and very fascinating that a genetic variation that arose thousands of years ago also protects against a modern virus like HIV.”

Analyzed 900 skeletons

To determine where and when the mutation arose, researchers first mapped it by analyzing the genetic material of 2,000 living people worldwide. They then developed a new AI-based method to identify the mutation in ancient DNA from old bones.

The researchers examined data from over 900 skeletons dating from the early Stone Age to the Viking Age.

“By looking at this large dataset, we can determine where and when the mutation arose. For a period, the mutation is completely absent, but then it suddenly appears and spreads incredibly quickly. When we combine this with our knowledge of human migration at the time, we can also pinpoint the region where the mutation originated,” explains first author Kirstine Ravn, senior researcher at CBMR.

Thus, the researchers were able to locate the mutation in a person from the Black Sea region up to 9,000 years ago — an individual from whom all carriers of the mutation descend.

Was an advantage back then

But why do so many Danes carry a millennia-old genetic mutation that protects against a disease that didn’t exist back then?

The researchers believe the mutation arose and spread rapidly because it gave our ancestors an advantage:

“People with this mutation were better at surviving, likely because it dampened the immune system during a time when humans were exposed to new pathogens,” explains Leonardo Cobuccio, co-first author and postdoc at CBMR. He and Kirstine Ravn elaborate:

“What’s fascinating is that the variation disrupts an immune gene. It sounds negative, but it was likely beneficial. An overly aggressive immune system can be deadly — think of allergic reactions or severe cases of viral infections like COVID-19, where the immune system often causes the damage that kills patients. As humans transitioned from hunter-gatherers to living closely together in agricultural societies, the pressure from infectious diseases increased, and a more balanced immune system may have been advantageous.”

Read the study “Tracing the evolutionary history of the CCR5delta32 deletion via ancient and modern genomes.”

Influenza remains a major respiratory disease, which places a heavy burden on healthcare systems worldwide. Vaccination is the most efficient way to prevent and control influenza. Current seasonal influenza vaccines, however, protect primarily against three selected strains and require annual updates. Their efficacy can significantly decline if the circulating viruses do not match the strains chosen each year for each hemisphere. Moreover, these vaccines fail to guard against human infections caused by animal influenza viruses, such as avian strains, which pose a potential global pandemic threat. The World Health Organization (WHO) has underscored the urgent need for a new generation of universal influenza vaccines.

The research team developed two innovative approaches to create next-generation LAIVs. The first strategy involved inserting a human α-1,3-galactosyltransferase gene into the genome of a human influenza virus. This modification prompts infected host cells to express the α-Gal epitopes on their surface. Since humans naturally produce anti-α-Gal antibodies, this can allow preexisting antibody to recognise cells infected by the vaccine, thereby enhancing vaccine induced immune responses, including antibody-mediated cytotoxicity, opsonisation and phagocytosis. The research data showed that the vaccine is attenuated and is not pathogenic in mouse models. In experiments, vaccinated mice showed strong innate and adaptive immune responses, including antibody and T-cell responses. These immune responses conferred broad protection against various influenza A virus subtypes, including human H1N1 and H3N2, and avian H5N1 strains.

The second approach to developing next-generation LAIVs involved introducing hundreds of silent mutations to a human influenza virus, shifting its codon usage from that of a human influenza virus to that of an avian influenza virus-like pattern. This shift resulted in the attenuation of the virus in mammalian cells, making it safe for use as an LAIV. Additionally, the mutant virus replicated perfectly in chicken eggs, which is crucial for current effective vaccine manufacturing processes. With this approach, the viral protein expression of the LAIV remained identical to the original wildtype virus, providing a robust immune response against the viruses. The research team successfully generated several attenuated viruses with different human influenza virus backbones, including H1N1 and H3N2. The results of in vitro and in vivo experiments confirmed that these viruses were attenuated in mammalian hosts. They can thus be used as LAIVs to protect vaccinated mice from different subtypes of influenza A virus infection, including the human H1N1 and H3N2 viruses, as well as the avian H5N1 and H7N9 influenza viruses.

The development of these two award-winning LAIVs represents a significant advancement in the quest for broadly protective and efficient influenza vaccines. This new generation of LAIVs can both protect humans from seasonal influenza viruses and address the threat posed by emerging viruses, like avian influenza viruses. ‘The advantages of LAIVs lie in their intranasal administration, which has been shown to induce mucosal immune responses along the respiratory tract, providing additional protection against infection,’ highlighted Professor Leo Poon Lit-man, Chair Professor of Public Health Virology and Head of the Division of Public Health Laboratory Sciences, School of Public Health, HKUMed. ‘This needle-free delivery method alleviates the fear of vaccination, particularly in young children, so it will help mitigate vaccine hesitancy.’

These scientific breakthroughs represent a promising step towards a future in which influenza vaccines can offer comprehensive protection against a wide array of viral threats. Moving forward, the research team will leverage the international platform of the Hong Kong Jockey Club Global Health Institute (HKJCGHI) for further development, ensuring continued progress and making a global impact in this vital area.

‘Both HKUMed and the International Vaccine Institute (IVI), one of the collaborators of the HKJCGHI, have initiated discussions and contributed intellectual input towards the vaccine development’, remarked Professor Leo Poon Lit-man, who is also the Co-Director of HKJCGHI. ‘It is anticipated that in the near future, further studies, including research work adhering to Good Laboratory Practice (GLP) standards, will be conducted through the resources of the Institute.’

The research projects were led by Professor Leo Poon Lit-man, Daniel C K Yu Professor in Virology, Chair Professor of Public Health Virology and Head of the Division of Public Health Laboratory Sciences, School of Public Health, HKUMed; the Managing Director and Lead Scientist of the Centre for Immunology & Infection (C2i); the Co-Director of the Hong Kong Jockey Club Global Health Institute (HKJCGHI); and the Co-Director of the HKU-Pasteur Research Pole, HKUMed. Other members included Dr Alex Chin Wing-hong, School of Public Health, HKUMed; and the Centre for Immunology & Infection (C2i).

Most biochemistry labs that study DNA isolate it within a water-based solution that allows scientists to manipulate DNA without interacting with other molecules. They also tend to use heat to separate strands, heating the DNA to over 150 degrees Fahrenheit, a temperature a cell would never naturally reach. By contrast, in a living cell DNA lives in a very crowded environment, and special proteins attach to DNA to mechanically unwind the double helix and then pry it apart.

“The interior of the cell is super crowded with molecules, and most biochemistry experiments are super uncrowded,” said Northwestern professor John Marko. “You can think of extra molecules as billiard balls. They’re pounding against the DNA double helix and keeping it from opening.”

Marko, a professor of molecular biosciences as well as physics in Northwestern’s Weinberg College of Arts and Sciences, led the research along with Northwestern post-doctoral researcher Parth Desai. In Marko’s lab, for their experiments, he and Desai use microscopic magnetic tweezers to separate DNA and then carefully attach strands of it to surfaces on one end, and tiny magnetic particles on the other, then conduct high-tech imaging. The technology has been around for 25 years, and Marko was one of the first researchers theorizing about and then using it.

Marko and Desai wrote the paper that not only identifies but quantifies the amount of stress imposed by crowding, that will be published on June 17 in the Biophysical Journal.

Desai introduced three types of molecules to the solution holding DNA to mimic proteins and investigated interactions among glycerol, ethylene glycol and polyethylene glycol (each approximately the size of one DNA double helix, two or three nanometers).

“We wanted to have a wide variety of molecules where some cause dehydration, destabilizing DNA mechanically, and then others that stabilize DNA,” Desai said. “It’s not exactly analogous to things found in cells, but you could imagine that other competing proteins in cells will have a similar effect. If they’re competing for water, for instance, they would dehydrate DNA, and if they’re not competing for water, they would crowd the DNA and have this entropic effect.”

While fundamental, research like this has “been the basis for many, many, many medical advances,” Marko said, such as deep sequencing of DNA, where scientists can now sequence an entire human genome in under a day. He also thinks their findings may be broadly applicable to other elements of fundamental biochemical processes.

“If this affects DNA strand separation, all protein interactions with DNA are also going to be affected,” Marko said. “For example, the tendency for proteins to stick to specific sites on DNA and to control specific processes — this is also going to be altered by crowding.”

In addition to running more experiments that incorporate multiple crowding agents, the team hopes to move closer to a true representation of a cell, and from there, study how interactions between enzymes and DNA are impacted by crowding.

This work was supported by the National Institutes of Health (grant R01-GM105847) and by subcontract to the University of Massachusetts Center for 3D Structure and Physics of the Genome (under NIH grant UM1-HG011536).

Over 70% of patients with ovarian cancer are diagnosed at an advanced stage, often presenting with large volumes of ascites. This ascites fluid not only supports the spread of cancer throughout the abdominal cavity but also significantly impairs the body’s immune defences. Understanding how ascites affects the immune system is important for developing better treatments that use the immune system to fight cancer.

In this recent study, researchers from Trinity College Dublin and University College Dublin explored how ascites disrupts immune cell function, with a particular focus on natural killer (NK) cells and T cells, which are key players in the body’s ability to eliminate tumours.

By analysing the contents of ascites fluid from ovarian cancer patients, the team identified a group of fat molecules called phospholipids as key drivers of this immune dysfunction.

Dr Karen Slattery, Research Fellow in the Trinity Translational Medicine Institute, is the first author of the research article just published in leading international journal Science Immunology. She said: “We found that these lipids interfere with NK cell metabolism and suppress their ability to kill cancer cells. Crucially, we also discovered that blocking the uptake of these phospholipids into NK cells using a specific receptor blocker can restore their anti-tumour activity, which offers a compelling new target for therapeutic intervention.”

“This work adds a critical piece to the puzzle of why ovarian cancer is so aggressive and has such poor outcomes. While the immune system is naturally equipped to detect and destroy cancer cells, this function is switched off in many individuals with ovarian cancer, and we now know that this is in part due to the fat-rich environment created by ascites.”

Prof. Lydia Lynch, formerly based in Trinity and now in Princeton University, is the senior author of the research article. She said: “This study marks a significant advancement in ovarian cancer research, identifying a new mechanism underpinning immune failure and laying the foundation for new therapies that could restore immune function in these patients. By targeting the fat-induced suppression of immune cells, future treatments could empower the body’s own immune defences to fight back and in doing so, improve outcomes for ovarian cancer patients.”

Published in PNAS Nexus, the study is the first to estimate the scale of global river contamination from human antibiotics use. Researchers calculated that about 8,500 tonnes of antibiotics — nearly one-third of what people consume annually — end up in river systems around the world each year even after in many cases passing through wastewater systems.

“While the amounts of residues from individual antibiotics translate into only very small concentrations in most rivers, which makes them very difficult to detect, the chronic and cumulative environmental exposure to these substances can still pose a risk to human health and aquatic ecosystems,” said Heloisa Ehalt Macedo, a postdoctoral fellow in geography at McGill and lead author of the study.

The research team used a global model validated by field data from nearly 900 river locations. They found that amoxicillin, the world’s most-used antibiotic, is the most likely to be present at risky levels, especially in Southeast Asia, where rising use and limited wastewater treatment amplify the problem.

“This study is not intended to warn about the use of antibiotics — we need antibiotics for global health treatments — but our results indicate that there may be unintended effects on aquatic environments and antibiotic resistance, which calls for mitigation and management strategies to avoid or reduce their implications,” said Bernhard Lehner, a professor in global hydrology in McGill’s Department of Geography and co-author of the study.

The findings are especially notable because the study did not consider antibiotics from livestock or pharmaceutical factories, both of which are major contributors to environmental contamination.

“Our results show that antibiotic pollution in rivers arising from human consumption alone is a critical issue, which would likely be exacerbated by veterinarian or industry sources of related compounds” said Jim Nicell, an environmental engineering professor at McGill and co-author of the study. “Monitoring programs to detect antibiotic or other chemical contamination of waterways are therefore needed, especially in areas that our model predicts to be at risk.”

Humans are the only species on earth known to use language. They do this by combining sounds into words and words into sentences, creating infinite meanings. This process is based on linguistic rules that define how the meaning of calls is understood in different sentence structures. For example, the word “ape” can be combined with other words to form compositional sentences that add meaning: “the ape eats” or append meaning: “big ape,” and non-compositional idiomatic sentences that create a completely new meaning: “go ape.” A key component of language is syntax, which determines how the order of words affects meaning, for instance how “go ape” and “ape goes” convey different meanings.

One fundamental question in science is to understand where this extraordinary capacity for language originates from. Researchers often use the comparative approach to trace the evolutionary origins of human language by comparing the vocal production of other animals, particularly primates, with that of humans. Unlike humans, other primates typically rely on single calls (referred to as call types), and while some species combine calls, these combinations are only a few per species and mostly serve to alert others to the presence of predators. This suggests that their communication systems may be too restricted to be a precursor to the complex, open-ended combinatorial system that is human language. However, we may not have a full picture of the linguistic capacities of our closest living relatives, particularly how they might use call combinations to significantly expand their meaning.

Studying the meaning of chimpanzee vocalisations

Researchers from the Max Planck Institutes for Evolutionary Anthropology and for Cognitive and Brain Sciences in Leipzig, Germany, and from the Cognitive Neuroscience Center Marc Jeannerod (CNRS/Université Claude Bernard Lyon 1) and Neuroscience Research Center (CNRS/Inserm/Université Claude Bernard Lyon 1) in Lyon, France recorded thousands of vocalisations from three groups of wild chimpanzees in the Taï National Park in Ivory Coast. They examined how the meanings of 12 different chimpanzee calls changed when they were combined into two-call combinations. “Generating new or combined meanings by combining words is a hallmark of human language, and it is crucial to investigate whether a similar capacity exists in our closest living relatives, chimpanzees and bonobos, in order to decipher the origins of human language,” says Catherine Crockford, senior author of the study. “Recording chimpanzee vocalisations over several years in their natural environment is essential in order to document their full communicative capabilities, a task that is becoming increasingly challenging due to growing human threats to wild chimpanzee populations,” says Roman Wittig, co-author of the study and director of the Taï Chimpanzee Project.

Chimpanzees’ complex communication system

The study reveals four ways in which chimpanzees alter meanings when combining single calls into 16 different two-call combinations, analogous to the key linguistic principles in human language. Chimpanzees used compositional combinations that added meaning (e.g., A = feeding, B = resting, AB = feeding + resting) and clarified meaning (e.g., A = feeding or travelling, B = aggression, AB = travelling). They also used non-compositional idiomatic combinations that created entirely new meanings (e.g., A = resting, B = affiliation, AB = nesting). Crucially, unlike previous studies which have mostly reported call combinations in limited situations such as predator encounters, the chimpanzees in this study expanded their meanings through the versatile combination of most of their single calls into a large diversity of call combinations used in a wide range of contexts.

“Our findings suggest a highly generative vocal communication system, unprecedented in the animal kingdom, which echoes recent findings in bonobos suggesting that complex combinatorial capacities were already present in the common ancestor of humans and these two great ape species,” says Cédric Girard-Buttoz, first author on the study. He adds: “This changes the views of the last century which considered communication in the great apes to be fixed and linked to emotional states, and therefore unable to tell us anything about the evolution of language. Instead, we see clear indications here that most call types in the repertoire can shift or combine their meaning when combined with other call types. The complexity of this system suggests either that there is indeed something special about hominid communication — that complex communication was already emerging in our last common ancestor, shared with our closest living relatives — or that we have underestimated the complexity of communication in other animals as well, which requires further study.”

“This study provides a starting point for understanding which cancers are increasing among individuals under age 50,” said lead investigator Meredith Shiels, Ph.D., of NIH’s National Cancer Institute. “The causes of these increases are likely to be cancer specific, including cancer risk factors becoming more common at younger ages, changes in cancer screening or detection, and updates to clinical diagnosis or coding of cancers.”

The study appeared May 8, 2025, in Cancer Discovery.

Researchers examined incidence and mortality trends for 33 cancer types, including incidence data for 2010-2019 from CDC’s United States Cancer Statistics database, which includes cancer registry data that represent the entire U.S. population, and mortality data for 2010-2022 from national death certificate data. Data were analyzed in six age groups: three early-onset (15-29 years, 20-39 years, and 40-49 years) and three older-onset (50-59 years, 60-69 years, and 70-79 years).

Incidence of 14 of the 33 cancer types increased in at least one of the younger age groups. Incidence of nine of these 14 types also increased in at least one of the older age groups: female breast, colorectal, kidney, testicular, uterine, pancreatic, and three types of lymphoma. Although death rates did not increase in early-onset age groups for most of these cancers, researchers did observe concerning increases in rates of colorectal and uterine cancers deaths at younger ages.

Only five cancer types increased in incidence among one of the younger age groups but not among any of the older age groups: melanoma, cervical cancer, stomach cancer, myeloma, and cancers of the bones and joints.

To understand the magnitude of the increases in terms of absolute numbers, the researchers estimated how many additional people were diagnosed with early-onset cancers in 2019 compared with expected diagnoses based on rates in 2010. The largest absolute increases were seen for female breast cancer, with about 4,800 additional cases in 2019, followed by colorectal (2,100), kidney (1,800), uterine (1,200), and pancreatic cancers (500). Female breast, colorectal, kidney, and uterine cancers contributed to more than 80% of the additional early onset cancers in 2019.

The researchers speculated that risk factors such as increasing obesity may have contributed to some of the increases in early-onset cancer incidence in recent years. Changes in cancer screening guidelines, advances in imaging technologies, and increased surveillance of high-risk individuals may also have led to earlier cancer diagnoses, potentially contributing to rising rates among younger age groups.

To more fully understand and address these increasing rates, the authors said that future studies should examine trends in early-onset cancers across demographics and geography in the U.S. and internationally. Additional research is also needed to better understand the risk factors that are particularly relevant to younger people.

Previously, scientists have used infrared light to trigger polymerization, the linking of the basic units, or monomers, of polymers within living animals. “But infrared penetration is very limited. It only reaches right below the skin,” says Wei Gao, professor of medical engineering at Caltech and a Heritage Medical Research Institute Investigator. “Our new technique reaches the deep tissue and can print a variety of materials for a broad range of applications, all while maintaining excellent biocompatibility.”

Gao and his colleagues report their new in vivo 3D-printing technique in the journal Science. Along with bioadhesive gels and polymers for drug and cell delivery, the paper also describes the use of the technique for printing bioelectric hydrogels, which are polymers with embedded conductive materials for use in the internal monitoring of physiological vital signs as in electrocardiograms (ECGs). The lead author of the study is Elham Davoodi, an assistant professor of mechanical engineering at the University of Utah, who completed the work while a postdoctoral scholar at Caltech.

The Origin of a Novel Idea

Wanting to figure out a way to realize deep tissue in vivo printing, Gao and his colleagues turned to ultrasound, a platform that is widely used in biomedicine for deep tissue penetration. But they needed a way to trigger crosslinking, or binding of monomers, at a specific location and only when desired.

They came up with a novel approach: Combine ultrasound with low-temperature-sensitive liposomes. Such liposomes, spherical cell-like vesicles with protective fat layers, are often used for drug delivery. In the new work, the scientists loaded the liposomes with a crosslinking agent and embedded them in a polymer solution containing the monomers of the polymer they wanted to print, an imaging contrast agent that would reveal when the crosslinking had occurred, and the cargo they hoped to deliver — a therapeutic drug, for example. Additional components can be included, such as cells and conductive materials like carbon nanotubes or silver. The composite bioink was then injected directly into the body.

Raise the Temperature Just a Touch to Trigger Printing

The liposome particles are low-temperature sensitive, which means that by using focused ultrasound to raise the temperature of a small targeted region by about 5 degrees Celsius, the scientists can trigger the release of their payload and initiate the printing of polymers.

“Increasing the temperature by a few degrees Celsius is enough for the liposome particle to release our crosslinking agents,” says Gao. “Where the agents are released, that’s where localized polymerization or printing will happen.”

The team uses gas vesicles derived from bacteria as an imaging contrast agent. The vesicles, air-filled capsules of protein, show up strongly in ultrasound imaging and are sensitive to chemical changes that take place when the liquid monomer solution crosslinks to form a gel network. The vesicles actually change contrast, detected by ultrasound imaging, when the transformation takes place, allowing scientists to easily identify when and precisely where polymerization crosslinking has occurred, enabling them to customize the patterns printed in live animals.

The team calls the new technique the deep tissue in vivo sound printing (DISP) platform.

When the team used the DISP platform to print polymers loaded with doxorubicin, a chemotherapeutic drug, near a bladder tumor in mice, they found substantially more tumor cell death for several days as compared to animals that received the drug through direct injection of drug solutions.

“We have already shown in a small animal that we can print drug-loaded hydrogels for tumor treatment,” Gao says. “Our next stage is to try to print in a larger animal model, and hopefully, in the near future, we can evaluate this in humans.”

The team also believes that machine learning can enhance the DISP platform’s ability to precisely locate and apply focused ultrasound. “In the future, with the help of AI, we would like to be able to autonomously trigger high-precision printing within a moving organ such as a beating heart,” Gao says.

The work was supported by funding from the National Institutes of Health, the American Cancer Society, the Heritage Medical Research Institute, and the Challenge Initiative at UCLA. Fluorescence microscopy was performed at the Advanced Light Microscopy/Spectroscopy Laboratory and Leica Center of Excellence at the California NanoSystems Institute at UCLA.

In a new study, researchers from Mass General Brigham identified a natural “brake” within the innate immune system: the inhibitory receptor Siglec-E (SigE) and its human counterparts, Siglec-7 and Siglec-9. This receptor helps prevent overactivation of immune cells that drive rejection. When this brake is missing, inflammation worsens, leading to faster rejection in preclinical models. Importantly, transplant patients with higher levels of Siglec-7 and Siglec-9 showed better graft survival, highlighting this pathway as a promising target for new therapies. Results are published in Science Translational Medicine.

“For decades, we’ve focused almost exclusively on controlling T cells to prevent rejection,” said Leonardo Riella, MD, PhD, medical director of Kidney Transplantation at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. Riella is also the Harold and Ellen Danser Endowed Chair in Transplantation at Harvard Medical School. “Our research shows that the innate immune system plays a pivotal role. By harnessing natural inhibitory pathways like Siglec-E, we can develop safer, more precise therapies that protect transplanted organs without compromising overall immune health.”

To conduct their studies, the researchers, led by first author Thiago J. Borges, PhD, of the Center for Transplantation Sciences at MGH, used mouse models of heart, kidney, and skin transplantation to study the roles of SigE, the murine equivalent of Siglec-7 and Siglec-9. Recipients deficient in SigE had accelerated acute rejection and increased inflammation. The researchers also looked at the levels of the receptors in samples from human transplant biopsies, finding that higher levels of the receptors were associated with improved allograft survival, suggesting that the findings in mice will be translatable to organ transplants in humans.

“This discovery paves the way for next-generation treatments that address both arms of the immune system, offering hope for longer-lasting transplant success and reducing the need for lifelong immunosuppression,” said Riella.

The team characterized the function of D1 and D2 dopamine receptors in the ventral hippocampus of mice, a region involved in the regulation of emotions and stress responses. Their work expands the field’s knowledge of dopamine signaling beyond its well-known actions in other brain regions that influence reward and motivation, and sets the stage for future research into dopamine dysregulation in a range of anxiety and depressive disorders. The results of the study appeared in the May 7 issue of Nature.

“Healthy and dysregulated emotional processing related to an individual’s ability to resolve conflict between approach and avoidance when making decisions on a moment-by-moment basis have long implicated the hippocampus,” says senior author Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience and Director of The Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai, and Chief Scientific Officer of the Mount Sinai Health System. “Ours is the first comprehensive, functional study of newly discovered D1 and D2 expressing cells in the ventral hippocampus. We demonstrate that dopamine is more important in that area of the brain than previously believed and, moreover, that it conveys information related to decision-making under stressful conditions.”

The hippocampus coordinates decision-making in anxiety-inducing situations, like when an individual has to choose whether to obtain food or drink under threatening situations. Such approach/avoidance dilemmas, where a particular goal has both desirable and potentially undesirable consequences, can cause excessive fear, confusion, and anxiety in humans.

The Mount Sinai team investigated the influence of dopamine signaling within the ventral hippocampus on approach/avoidance behavior in male mice. Researchers learned that D1 and D2 dopamine receptors expressed in different neuronal populations are called into play to help execute approach/avoidance decisions. These receptors and the cells that express them mediate opposite approach/avoidance responses, and are differentially impacted by dopamine transmission in that region of the brain.

The team was surprised to learn that the neuronal cells that express D1 and D2 receptors, which are most highly enriched in the striatum — a critical part of the motor and reward system — are also relevant in the hippocampus. Another unexpected behavioral observation was that mice whose D2 cells were artificially activated became much less fearful.

“These discoveries underscored for us that dopamine is an important component of the hippocampal circuitry and that dopamine signaling should be reconsidered in many brain regions where it was previously overlooked, especially those associated with learning, memory, and emotional behavior,” notes Dr. Nestler, whose considerable research over the years has been designed to better understand the molecular mechanisms of drug addiction and depression. “Our work further implicates dopamine dysregulation in anxiety and mood disorders.”

Dr. Nestler credits the study’s two co-first authors, Arthur Godino, PhD, a graduate student and later postdoctoral fellow, and Marine Salery, PhD, a postdoctoral fellow, and the rest of the large research team for the creative advances made in this investigation.

The next step for Dr. Nestler and his team is to show precisely how the dopamine-hippocampus circuit that modulates approach/avoidance is dysregulated in several stress-related conditions, such as anxiety disorders and major depressive disorders (which involve increased avoidance) and in drug addiction (where individuals seek drug rewards despite harmful consequences).

“By helping to delineate the neuromodulatory circuits that govern these disorders,” says Dr. Nestler, “we’re taking an essential step toward addressing a leading cause of disability in humans worldwide.”

This work was funded by grants from the National Institute on Drug Abuse, National Institute of Mental Health, and Hope for Depression Research Foundation.

Nitrogen atoms and nitrogen-containing rings, known as heterocycles, play crucial roles in the development of medicines. A research team led by OU Presidential Professor Indrajeet Sharma has found a way to change these rings by adding just one carbon atom using a fast-reacting chemical called sulfenylcarbene. This method, called skeletal editing, transforms existing molecules into new drug candidates.

“By selectively adding one carbon atom to these existing drug heterocycles in the later stages of development, we can change the molecule’s biological and pharmacological properties without changing its functionalities,” he said. “This could open uncharted regions of chemical space in drug discovery.”

Previous studies have demonstrated a similar concept but relied on potentially explosive reagents, exhibited limited functional group compatibility, and posed significant safety concerns for industrial-scale applications.

Sharma’s team has developed a bench-stable reagent that generates sulfenylcarbenes under metal-free conditions at room temperature, achieving yields as high as 98%. Avoiding metal-based carbenes helps reduce environmental and health risks because many metals are known to have some level of human toxicity.

The researchers are also exploring how this chemistry could revolutionize a fast-growing area in pharmaceutical science known as DNA-encoded library (DEL) technology. DEL platforms allow researchers to rapidly screen billions of small molecules for their potential to bind to disease-relevant proteins.

The metal-free, room-temperature conditions of the team’s new carbon insertion strategy make it a compelling candidate for use in DNA-encoded libraries. Unlike other reactions that need harsh chemicals or high heat, this new method works in water-friendly liquids and is gentle enough to use with molecules attached to DNA.

By enabling precise skeletal editing in collaboration with the Damian Young group at the Baylor College of Medicine, Sharma’s approach could significantly enhance the chemical diversity and biological relevance of DEL libraries. Importantly, these are two key bottlenecks in drug discovery.

“The cost of many drugs depends on the number of steps involved in making them, and drug companies are interested in finding ways to reduce these steps. Adding a carbon atom in the late stages of development can make new drugs cheaper. It’s like renovating a building rather than building it from scratch,” Sharma said. “By making these drugs easier to produce at large scale, we could reduce the cost of healthcare for populations around the world.”

NRT maintains that rather than relying on learned expectations or prediction, musical experiences arise from the brain’s natural oscillations that sync with rhythm, melody and harmony. This resonance shapes our sense of timing, musical pleasure and the instinct to move with the beat.

“This theory suggests that music is powerful not just because we hear it, but because our brains and bodies become it,” said Palmer, Professor in the Department of Psychology at McGill and Director of the Sequence Production Lab. “That has big implications for therapy, education and technology.” The study’s publication in Nature Reviews Neuroscience marks the first time the entire NRT is being published in a single paper, she said.

The theory suggests that structures like pulse and harmony reflect stable resonant patterns in the brain, shared across people independent of their musical background. According to NRT, how we hear and produce music can be explained by fundamental dynamical principles of human brain mechanisms that apply from the ear all the way to the spinal cord and limb movements.

Researchers say potential applications of the theory include:

The study was led by Edward Large (University of Connecticut) and co-authored by Caroline Palmer.

The study was funded in part by a Canada Research Chair and a NSERC Discovery Grant.

Scientists examined over 20 years of data on 164 wild mountain gorillas, to see how their social lives affected their health.

Costs and benefits changed depending on the size of gorilla groups, and differed for males and females.

For example, friendly females in small groups didn’t get ill very often but had fewer offspring — while those in large groups got ill more but had higher birth rates.

Meanwhile, males with strong social bonds tended to get ill more — but were less likely to be injured in fights.

The study — by the Dian Fossey Gorilla Fund and the universities of Exeter and Zurich — may help to explain why such a wide range of traits have evolved in social animals, including humans.

“Having a lot of strong social relationships is often really good — but sometimes it isn’t,” said Dr Robin Morrison, lead author on the paper and Senior Researcher at the University of Zurich.

“For example, our study found that strong and stable social bonds are generally linked to less illness in female gorillas — but more illness in males.

“We can’t be certain why this happens, but it appears it’s not a simple matter of social contact leading to more disease risk.

“It’s possible that males expend more energy by having close social ties, as they have to defend females and offspring, and the stress of this may reduce their immune function.”

The study focussed on the strength of each gorilla’s key social bonds, and its integration in the group — along with wider context such as group size, stability and conflict with other groups.

The findings highlight the forces that affect the evolution of social behaviour.

“With these forces pushing in different directions, the ‘optimal’ social type will depend on an individual’s sex, age, offspring and wider social group,” said Dr Sam Ellis, from the University of Exeter.

“In humans and other social mammals, the social environment is one of the strongest predictors of health and lifespan.

“But our study shows this isn’t a straightforward case of more and stronger social ties always being better. In some situations social traits that we’ve previously thought of as maladaptive can have important benefits.”

The study is based on long-term observations of mountain gorillas in Volcanoes National Park, Rwanda, which usually live in groups of about 12 with a single dominant male.

“This paper highlights the incredible value of long-term studies to furthering our understanding of the evolution of sociality and how the benefits or costs of sociality can vary considerably across different environments,” said Dr Tara Stoinski, CEO and Chief Scientific Officer of the Dian Fossey Gorilla Fund and one of the study co-authors.

The research was funded by the Swiss National Science Foundation and the Dian Fossey Gorilla Fund.

The paper, published in the journal Proceedings of the National Academy of Sciences, is entitled: “Group traits moderate the relationship between individual social traits and fitness in gorillas.”

Case studies: the varied social lives of mountain gorillas

Gutangara — an adult female — lives in one of the largest gorilla groups. She has good relationships with many gorillas but spends most of her time with her offspring — some that are still young and others that are already adults. She is the most successful gorilla mother the researchers have seen, with eight surviving offspring.

Maggie was the highest-ranking female gorilla in the Bwenge group. She was one of the most frequently aggressive group members but was also quick to provide friendly support such as grooming. Maggie often led group interactions and acted as a protector, a role usually taken by males. When the dominant male died unexpectedly, Maggie took charge, guiding the group until they merged with a neighbouring group. But Maggie struggled to fit into this new group and eventually chose to leave. She travelled alone for a month until she crossed into Congo, where her trail was lost.

Titus — a “silverback” adult male mountain gorilla — had a difficult childhood. He lost his father and many other group members to poachers, and his mother died when he was only four. He became the dominant male of his group at the early age of 15. Titus had an unusual leadership style, being exceptionally gentle and calm. His closest relationships were with the females in his group, who often stayed in physical contact with him, something rarely observed to this extent in other groups. His gentle nature made him very attractive to females and contributed to his 20-year tenure as dominant male until his death in 2009.

Cantsbee, also a silverback, led his group for 22 years — the longest dominance tenure ever recorded — and fathered at least 28 offspring. He was known for his authoritative but peaceful nature, rarely initiating or entering fights, but was quick to protect others and resolve conflicts in the group. He had a particularly close relationship with his son Gicurasi, whose mother left when he was young, and who eventually took over leadership of the group in Cantsbee’s final years. When Cantsbee later became ill, he chose to leave the group, spending his final months alone, except for one brief visit to the group shortly before his death.

This month, researchers participating in the Cilento Initiative on Aging Outcomes or CIAO study will gather in Acciaroli (Pollica-Cilento) Salerno, Italy to review a decade of work and plan their next steps. Launched in 2016, the CIAO study seeks to identify key factors (biological, psychological and social) that promote healthy aging and extreme longevity.

The Natural Park of Cilento region in southern Italy is home to roughly 300 residents who are more than 100 years old and in robust health. The broader region is notable for the long lives of its residents. It was the original source of research for Ancel Keys, the American physiologist who studied the influence of diet on health and first promoted the benefits of the Mediterranean diet.

Scientists hope to reveal the longevity secrets of the Cilento region using an array of tools to measure metabolomics, biomes, cognitive dysfunction and protein biomarkers for risk of heart disease, Alzheimer’s, kidney disease and cancer, along with psychological, social and lifestyle surveys.

“There is no single secret to living a long, healthy life,” said Salvatore Di Somma, MD, the study’s lead Italian investigator, founder of Great Health Science and symposium co-chair. “It is many secrets, most of which we are only beginning to understand and more importantly, learn how they might be applied to the well-being of everybody. The remarkable centenarians in our study are leading the way.”

The CIAO study is a multi-institution collaboration that includes Sanford Burnham Prebys, an independent, nonprofit biomedical research institute in San Diego, the Sanford Stem Cell Institute at University of California San Diego, University La Sapienza in Rome and Great Health Science, a network of public and private research organizations based in Rome, Italy.

The May 22-23 symposium, officially called the “CIAO Study: A decade of science on healthy aging, stem cells and the revealed secrets of longevity,” will feature a series of scientists and physicians describing their work and findings, from general demographic and epidemiological aspects to deeper dives into brain cell aging, the regenerative powers of stem cells and RNA biology.

“Understanding how we age and how we might age better is a timeless pursuit,” said David Brenner, MD, president and CEO of Sanford Burnham Prebys and co-chair of the symposium. “Ten years in, with the benefit of new and emerging technologies and global collaborations, we’ve come a long way. It’s important to look at where we are now and what our key questions and steps will be in the next 10 years.”

One current CIAO project leverages genetic, epigenetic, transcriptomic, metabolic, proteomic and environmental analyses to identify key contributors to extreme longevity. Supported by the Sanford Stem Cell Institute at UC San Diego, researchers are using induced pluripotent stem cell (iPSC) derived from the centenarians to model age-related and metabolic stresses in human 3D organoids.

“This study will provide new insights into the development of regenerative medicine strategies for promoting healthy aging and treating age-related conditions,” said Tatiana Kisseleva, MD, PhD, professor of surgery at UC San Diego School of Medicine and director of the Sanford Stem Cell Fitness and Space Medicine Center. Preliminary findings are expected to be presented at the symposium.

The CIAO study has already generated multiple published papers and intriguing findings. Among them:

1. In a 2016 presentation, researchers reported that the oldest residents participating in the CIAO study exhibited robust microcirculation of blood comparable in efficiency to people 30 years younger. They also noted that low blood levels of the peptide hormone adrenomedullin were an indicator for good microcirculation.
2. In 2018, using a mix of scales to measure mental and physical well-being, resilience, optimism, anxiety, depression and perceived stress, researchers assessed 29 nonagenarians and 51 family members between the ages of 51 and 75. They found the study participants aged 90 and older had worse physical health but better mental well-being than their younger counterparts. Exceptional longevity was characterized by a balance between acceptance of and grit to overcome adversities, along with a positive attitude and close ties to family, religion and the land, providing purpose in life.
3. In 2020, a cross-sectional sampling of nonagenarians and centenarians, along with younger co-inhabitants from Cilento, evaluated key lifestyle, medical, echocardiographic and electrocardiographic features to identify the cardiovascular profile and lifetstyle factors associated with longevity. In contrast to their younger co-inhabitants, the older group did not smoke, had lower fasting glucose levels and lower LDL cholesterol despite being half as likely to be taking statins. They were physically active and enjoyed comparatively low levels of cardiovascular disease — even persons with structural heart abnormalities experienced fewer symptoms.
4. Also in 2020, researchers sought to define the neurocognitive profiles of 29 residents of the Cilento region at least 90 years old and 49 younger residents ages 50 to 75 years. They found that the older cohort appeared to enjoy cognitive status comparable to their younger cohabitants without significant differences in oxidative stress markers or the APOE genotype — a genetic variation that determines a person’s risk for developing certain diseases, particularly Alzheimer’s. The authors concluded that the results might be related to the older group’s optimal adherence to the Mediterranean diet, though other lifestyle factors and positive personality traits might be contributing to their healthy aging.
5. Researchers investigating the relationship between loneliness and wisdom compared different age cohorts in San Diego and Cilento, using two validated loneliness scales. They found no significant differences in levels of loneliness among the groups, but a strong inverse correlation between loneliness and wisdom in all groups. Loneliness worsened general health, sleep quality and feelings of happiness, while wisdom improved these measures.

EEG is critical for diagnosing and assessing neurological conditions like epilepsy and brain injuries. In some cases, clinicians need to monitor brain waves for longer periods of time, for example, to evaluate seizures, sleep disorders and conditions that affect the blood vessels and blood flow in the brain.

The researchers described the new electrodes, which were shown to maintain stable performance for over 24 hours of continuous wear, in a study published in the journal npc biomedical innovations. This technology holds promise for use in consumer health and wellness products, in addition to clinical health care application, according to the researchers.

“This electrode allows for more consistent and reliable monitoring of EEG signals and can be worn without being noticeable, which enhances both functionality and patient comfort,” said Tao Zhou, Wormley Family Early Career Professor of engineering science and mechanics and senior author on the paper.

EEG monitoring is a widely used method to measure the brain’s electrical activity, Zhou explained. Small metal electrodes are placed on the scalp and pick up the faint electrical impulses generated by cells in the brain. The electrodes are attached to wires that are then connected to a machine that displays the brain’s activity as patterns that look like waves.

The traditional EEG monitoring process, however, can be a cumbersome — and sometimes messy — affair. Its limitations make it difficult to use for continuous, long-term monitoring.

To get a good recording of the brain’s activity, the electrodes need to conform to the scalp. Any gaps between the electrode and the skin or dense hair can diminish the quality of the recorded signal. Researchers and clinicians must apply gels to the scalp to maintain good surface-to-surface contact between the electrodes and skin and signal quality. For some people, though, the gels can cause skin irritation.

It’s a time-consuming process that must be repeated when the gels dry out, especially for someone needs to be monitored continuously or over the course of multiple sessions. The application and re-application process is imprecise, too, and can result in different amounts of gel used on the electrodes.

“This will change the impedance — or interface — between the electrodes and the scalp and it can affect the brain signal that’s recorded,” Zhou said. “We also don’t always apply the electrodes in the exact same position either because we’re human. But if you change the position, even a little bit, the brain signals you’re monitoring can be different.”

The conventional EEG electrodes are rigid, too, and can shift when someone moves their head, even slightly, which can compromise the data uniformity.

To address these limitations, the research team designed a small monitoring device that looks like a strand of hair and is made from 3D-printed hydrogel material. One end is the electrode. It looks like a small dot and captures the brain’s electrical signals from the scalp. There’s a long, thin wire-like component that extends from the electrode, which connects to the monitoring system.

The device also uses a 3D-printable bioadhesive ink that allows the electrode to stick directly onto the scalp without the need for any gloopy gels or other skin preparation. This minimizes the gap between the electrode and scalp, improving the signal quality. The lightweight, flexible and stretchable nature of the device also means that the device stays put — even when combing hair and donning and removing a baseball cap — and can be worn for longer periods of time, making it suitable for chronic monitoring.

The team found that the new device performed comparably to gold electrodes, the current standard electrodes used for EEG. However, the hairlike electrode maintained better contact between the electrode and skin and performed reliably for over 24 hours of continuous wear without any degradation in signal quality. Because the electrodes don’t have to be removed and replaced like traditional EEG monitoring systems, they eliminate the risk of inconsistent data, even across different monitoring sessions.

“You don’t have to worry if the position of the electrode has changed or if the impedance has changed because the electrodes haven’t moved,” Zhou said.

Unlike the traditional metal electrodes, the new electrodes mimic human hair and are inconspicuous on the head. Since the device is 3D-printed, Zhou explained that they can print the electrode in different colors to match a person’s hair, too.

“This makes it discreet, and people may be more comfortable wearing this, especially if they require continuous EEG monitoring and need to wear the electrodes for an extended period of time,” Zhou said.

Currently, the EEG is still wired; patients need to be connected to a machine while their brain activity is recorded. In the future, the researchers hope to make the system wireless so that people can move around more freely during recording sessions.

Other Penn State authors on the paper include lead authors Salahuddin Ahmed and Marzia Momin, both doctoral students in the Department of Engineering Science and Mechanics. Jiashu Ren, doctoral student in the Department of Engineering Science and Mechanics; Hyunjin Lee, doctoral student in the Department of Biomedical Engineering; Li-Pang Huang, research assistant; and Basma AlMahmood, undergraduate student in the Department of Physics also contributed to the paper.

Other authors include Chi-Ching Kuo, Archana Pandiyan and Loganathan Veeramuthu from the Department of Molecular Science and Engineering, National Taipei University of Technology.

Funding from the National Institutes of Health; Oak Ridge Associated Universities; the National Taipei University of Technology-Penn State Collaborative Seed Grant Program; and the Department of Engineering Science and Mechanics, the Materials Research Institute and the Huck Institutes of Life Sciences at Penn State supported this work.

The research team, led by Pennington Biomedical Executive Director Dr. John Kirwan, focused on the significance of deubiquitinating enzymes, or DUBs, in regulating mitochondrial dynamics within skeletal muscle. Findings suggest that mitochondrial fragmentation can bypass defects in mitophagy, the process by which cells remove damaged mitochondria, to sustain skeletal muscle quality control in patients with T2D. This adaptation may help maintain mitochondrial function despite impaired mitophagy.​

In other words, the study shows that people with T2D have fewer healthy mitochondria, the parts of the cell that produce energy, because a certain protein – dynamin-related protein 1, or DRP1 – is working too much. In addition, another group of proteins – DUBs – are shown to interfere with a process that helps the body clean up damaged mitochondria. This interference makes it harder for muscles to use insulin properly, which is a key issue in diabetes.

The research findings advance the understanding of how impaired mitochondrial dynamics and quality control may contribute to skeletal muscle insulin resistance and the manifestation of T2D, and also provides key evidence that DUB antagonists may play an important role in preventing or treating T2D.

“Our research team examined how certain enzymes affect mitochondria in muscle cells of people with diabetes,” said Dr. Kirwan Dr. Kirwan, Executive Director and George A. Bray, Jr. Endowed Super Chair in Nutrition at Pennington Biomedical. “We found that when the normal cleanup process for damaged mitochondria isn’t working well, the cells adapt by breaking mitochondria into smaller pieces. This alternative approach helps maintain muscle function despite the metabolic challenges of Type 2 diabetes. Our study highlights the complex interplay between mitochondria and insulin, paving the way for future interventions aimed at improving metabolic health.”

How we make antivenom has not changed much over the past century. Typically, it involves immunizing horses or sheep with venom from single snake species and collecting the antibodies produced. While effective, this process could result in adverse reactions to the non-human antibodies, and treatments tend to be species and region-specific.

While exploring ways to improve this process, scientists stumbled upon someone hyper-immune to the effects of snake neurotoxins. “The donor, for a period of nearly 18 years, had undertaken hundreds of bites and self-immunizations with escalating doses from 16 species of very lethal snakes that would normally a kill a horse,” says first author Jacob Glanville, CEO of Centivax, Inc.

After the donor, Tim Friede, agreed to participate in the study, researchers found that by exposing himself to the venom of various snakes over several years, he had generated antibodies that were effective against several snake neurotoxins at once.

“What was exciting about the donor was his once-in-a-lifetime unique immune history,” says Glanville. “Not only did he potentially create these broadly neutralizing antibodies, in this case, it could give rise to a broad-spectrum or universal antivenom.”

To build the antivenom, the team first created a testing panel with 19 of the World Health Organization’s category 1 and 2 deadliest snakes across the elapid family, a group which contains roughly half of all venomous species, including coral snakes, mambas, cobras, taipans, and kraits. Next, researchers isolated target antibodies from the donor’s blood that reacted with neurotoxins found within the snake species tested. One by one, the antibodies were tested in mice envenomated from each species included in the panel. In this way, scientists could systematically build a cocktail comprising a minimum but sufficient number of components to render all the venoms ineffective.

The team formulated a mixture comprising three major components: two antibodies isolated from the donor and a small molecule. The first donor antibody, called LNX-D09, protected mice from a lethal dose of whole venom from six of the snake species present in the panel. To strengthen the antiserum further, the team added the small molecule varespladib, a known toxin inhibitor, which granted protection against an additional three species. Finally, they added a second antibody isolated from the donor, called SNX-B03, which extended protection across the full panel.

“By the time we reached 3 components, we had a dramatically unparalleled breadth of full protection for 13 of the 19 species and then partial protection for the remaining that we looked at,” says Glanville. “We were looking down at our list and thought, ‘what’s that fourth agent’? And if we could neutralize that, do we get further protection?” Even without a fourth agent, their results suggest that the three-part cocktail could be effective against many other, if not most, elapid snakes not tested in this study.

With the antivenom cocktail proving effective in mouse models, the team now looks to test its efficacy out in the field, beginning by providing the antivenom to dogs brought into veterinary clinics for snake bites in Australia. Further, they wish to develop an antivenom targeting the other major snake family, the vipers.

“We’re turning the crank now, setting up reagents to go through this iterative process of saying what’s the minimum sufficient cocktail to provide broad protection against venom from the viperids,” says lead author Peter Kwong, Richard J. Stock professor of medical sciences at Columbia University Vagelos College of Physicians and Surgeons and formerly of the National Institutes of Health. “The final contemplated product would be a single, pan-antivenom cocktail or we potentially would make two: one that is for the elapids and another that is for the viperids because some areas of the world only have one or the other.”

The other major goal is to approach philanthropic foundations, governments, and pharmaceutical companies to support the manufacturing and clinical development of the broad-spectrum antivenom. “This is critical, because although there are millions of snake envenomations per year, the majority of those are in the developing world, disproportionately affecting rural communities,” Glanville says.

This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, the National Institutes of Health Small Business Innovation Research program, and the US Department of Energy.

“The Haenyeo are amazing, and their incredible ability is written in their genes,” says geneticist Melissa Ilardo of the University of Utah. “The fact that women are diving through their pregnancy, which is a really tough thing to do, has actually influenced an entire island’s people.”

The Haenyeo, or “women of the sea,” dive year-round in social collectives to harvest food for their communities. They begin training at around age ten and continue for their whole lives. Inspired by the Haenyeo’s remarkable diving abilities, the researchers wanted to know whether they have distinguishable physiological traits that help them cope with the strain of diving, and if so, whether these traits are due to genetic adaptation or training.

To find out, the team compared the physiological traits and genomes of 30 Haenyeo divers to 30 non-Haenyeo people from Jeju, as well as 31 people from mainland Korea. To match the age of the divers, the average age of all participants was 65. The researchers compared the participants’ heart rate and blood pressure at rest and during “simulated dives” where the participants held their breath while submerging their faces in cold water.

“If you hold your breath and put your face in a bowl full of cold water, your body responds as if you’re diving,” says Ilardo. “A lot of the same processes happen in your body that would happen if you were to jump in the ocean, but it’s done in a way that’s safe for people with no diving experience.”

The team’s genomic analysis showed that Jeju residents — both Haenyeo and non-Haenyeo — were distinct from individuals from mainland Korea, suggesting that all Jeju residents are descended from the same ancestral population.

“We can essentially think of everyone from Jeju as either ‘diving Haenyeo’ or ‘non-diving Haenyeo,’ because their genetics are the same,” says Ilardo.

The genomic analysis also revealed two gene variants in the Haenyeo that may help them cope with the pressures of diving, making the Haenyeo the second known population of traditional breath-hold divers that has evolved for diving. One gene is associated with cold tolerance, which could make the divers less vulnerable to hypothermia. The other gene is associated with decreased diastolic blood pressure (i.e., blood pressure in between heart contractions). The variant was found in 33% of participants from Jeju but only 7% of mainland participants.

“This association may reflect natural selection to mitigate the complications of diastolic hypertension experienced by female divers while diving through pregnancy,” says Ilardo. “Since Bajau women also dive while they’re pregnant, we wonder whether pregnancy is actually driving a lot of the genetic changes in these diving populations.”

During the simulated dives, all of the participants showed decreased heart rates, but the Haenyeo’s heart rates dropped significantly more than those of either control group. On average, the divers’ heart rates decreased by 18.8 beats per minute (bpm) compared to a decrease of 12.6 bpm in the Jeju non-divers. A lowered heart rate during diving is beneficial because it saves energy and conserves oxygen. Since their genomic analysis indicated that Haenyeo and non-diving Jeju are genetically members of the same population, the researchers concluded that this feature is likely due to the divers’ training.

“Because the Haenyeo have been diving for a very long time, their heart rate has been trained to drop more,” says Ilardo. “This was something we could actually visually see — we had one diver whose heart rate dropped by over 40 beats per minute in less than 15 seconds.”

The researchers say that these findings highlight the potential of studying traditional diving populations to better understand human genetic and physiological adaptation.

“We’re really excited to learn more about how these genetic changes may be affecting the health of the broader population of Jeju,” says Ilardo. “If we can more deeply characterize how those changes affect physiology, it could inspire the development of therapeutics to treat different conditions, such as hypertensive disorders of pregnancy and stroke.”

This research was supported by the Office of Naval Research, the National Institutes of Health, and the National Science Foundation.

“Despite many advances in understanding the genomic drivers and other factors causing cancer, with few exceptions, stage IV colorectal cancer remains a largely incurable disease,” said Emil Lou, MD, PhD, a gastrointestinal oncologist with the University of Minnesota Medical School, Masonic Cancer Center and M Health Fairview, and clinical principal investigator for the trial. “This trial brings a new approach from our research labs into the clinic and shows potential for improving outcomes in patients with late-stage disease.”

In the study, researchers used CRISPR/Cas9 gene-editing to modify a type of immune cell called tumor-infiltrating lymphocytes (TILs). By deactivating a gene called CISH, the researchers found that modified TILs were better able to recognize and attack cancer cells.

The treatment was tested in 12 highly metastatic, end-stage patients and found to be generally safe, with no serious side effects from the gene editing. Several patients in the trial saw the growth of their cancer halt, and one patient had a complete response, meaning that in this patient, the metastatic tumors disappeared over the course of several months and have not returned in over two years.

“We believe that CISH is a key factor preventing T cells from recognizing and eliminating tumors,” said Branden Moriarity, PhD, associate professor at the University of Minnesota Medical School, Masonic Cancer Center researcher and co-director of the Center for Genome Engineering. “Because it acts inside the cell, it couldn’t be blocked using traditional methods, so we turned to CRISPR-based genetic engineering.”

Unlike other cancer therapies that require ongoing doses, this gene edit is permanent and built into the T cells from the start.

“With our gene-editing approach, the checkpoint inhibition is accomplished in one step and is permanently hardwired into the T cells,” said Beau Webber, PhD, associate professor at the University of Minnesota Medical School and Masonic Cancer Center researcher.

The research team delivered more than 10 billion engineered TIL without adverse side effects, demonstrating the feasibility of genetically engineering TIL without sacrificing the ability to grow them to large numbers in the lab in a clinically compliant environment, which has never been done before.

While the results are promising, the process remains costly and complex. Efforts are underway to streamline production and better understand why the therapy worked so effectively in the patient with a complete response in order to improve the approach in future trials.

This research was funded by Intima Bioscience.

Nearly all these inserted elements have been silenced by our cells’ defense mechanisms over time, but a few, nicknamed “jumping genes,” can still move around the human genome like viruses. Just one, called long interspersed nuclear element 1 (LINE-1), can still move by itself.

As an element type that behaves like the retrovirus HIV, the LINE-1 “retrotransposon” is first copied into a molecule of RNA, the genetic material that partners with DNA, and then the RNA LINE-1 copy is converted back into DNA in a new place in the genome. In this way, retrotransposons add code to the human genome every time they move, which explains why 500,000 LINE-1 repeats now represent a “staggering” 20 percent of the human genome. These repeats drive genome evolution, but can also cause neurological diseases, cancer, and aging when LINE-1 randomly jumps into essential genes, or triggers an immune response like a virus to cause inflammation.

To copy itself, however, LINE-1 must enter each cell’s nucleus, the inner barrier that houses DNA. Now a new study, published online May 2 in the journal Science Advances, reveals that LINE-1 binds to cellular DNA during the brief periods when nuclei break open as cells continually divide in two, creating replacements to keep tissues viable as we age. The research team found that LINE-1 RNA takes advantage of these moments, assembling into clusters with one of the two proteins it encodes, ORF1p, to hold tightly to DNA until the nucleus reforms after cell division.

Led by researchers at NYU Langone Health and the Munich Gene Center at Ludwig-Maximilians-Universität (LMU) München in Germany, the work revealed specifically that LINE-1 can only bind to DNA when ORF1p — which can bind to RNA, DNA, and itself in linked copies called multimers — accumulates into clusters of hundreds of molecules called condensates. As more ORF1p molecules build up, they eventually envelop the LINE-1 RNA, which makes more binding sites available for the entire cluster to attach to DNA.

“Our study provides crucial insight into how a genetic element that has come to make up a large part of human DNA can successfully invade the nucleus to copy itself, said Liam J. Holt, PhD., associate professor in the Department of Biochemistry and Molecular Pharmacology, and the Institute for Systems Genetics, at NYU Grossman School of Medicine.”These findings on the precise mechanisms behind LINE-1 insertion lay the foundations for the design of future therapies to prevent LINE-1 replication.”

The work also suggests that the LINE-1 condensate acts as a delivery vehicle to bring its RNA into proximity of the right sequences (rich in the DNA bases adenine and thymine) on DNA where the retrotransposon tends to insert, say the study authors. Packaged in its condensates, LINE-1 is thought to evade mechanisms that exclude large particles from the nucleus during mitosis as a cellular defense against viruses.

“LINE-1 condensates have a remarkable feature in that their DNA binding ability emerges only when the ratio of ORF1p copies to RNA is high enough in the condensates,” added Dr. Holt. “Moving forward we will be looking to see if other condensates undergo functional changes as the ratios between their components change.”

Along with Dr. Holt, the first study authors were graduate student Farida Ettefa at NYU Grossman School of Medicine and its Institutes for Systems Genetics; and Sarah Zernia of Gene Center Munich at Ludwig-Maximilians-Universität (LMU) München in Germany. Also study authors were Cas Koeman, Joëlle Deplazes-Lauber, Marvin Freitag, and co-senior author Johannes Stigler from Ludwig-Maximilians-Universität München. The study was supported by the LMU-NYU Research Cooperation Program.

While exploring a digitally represented object through their artificially created sense of touch, users described the warm fur of a purring cat, the smooth rigid surface of a door key and cool roundness of an apple. This research, a collaboration between Pitt and the University of Chicago, was published today in Nature Communications.

In contrast to earlier experiments where artificial touch often felt like indistinct buzzing or tingling and didn’t vary from object to object, scientists gave BCI users control over the details of the electrical stimulation that creates tactile sensations, rather than making those decisions themselves. This key innovation allowed participants to recreate a sense of touch that felt intuitive to them.

“Touch is an important part of non-verbal social communication; it is a sensation that is personal and that carries a lot of meaning,” said lead author Ceci Verbaarschot, Ph.D., assistant professor of neurological surgery and biomedical engineering at the University of Texas-Southwestern and a former postdoctoral fellow at Pitt Rehab Neural Engineering Labs. “Designing their own sensations allows BCI users to make interactions with objects feel more realistic and meaningful, which gets us closer to creating a neuroprosthetic that feels pleasant and intuitive to use.”

A brain-computer interface is a system that converts brain activity into signals that could replace, restore or improve body functions that are typically controlled by the brain, such as muscle movement. A BCI can also be used to repair damaged feedback from the body and restore lost sensations by directly stimulating the brain.

Over the last decade of research, Pitt scientists helped a paralyzed man to experience the sensation of touch through a mind-controlled robotic arm and showed that this artificial sense of touch made moving the robotic arm more efficient. Still, those tactile sensations were imperfect and stayed similar between objects that had different texture or temperature: shaking someone’s hand felt the same as lifting a solid, hard rock.

Now, researchers are closer to their goal of creating an intuitive sense of touch.

In the new study, BCI users were able to design distinct tactile experiences for different objects displayed on a computer screen, and could guess the object just by sensation alone, though imperfectly.

Searching for the perfect touch resembled a game of “hot and cold” in a dark room of infinite tactile sensations. Scientists asked study participants, all of whom lost sensation in their hands because of a spinal cord injury, to find a combination of stimulation parameters that felt like petting a cat or touching an apple, key, towel or toast — while exploring an object presented to them digitally.

All three study participants described objects in rich and vivid terms that made logical sense but were also unique and subjective: to one participant, a cat felt warm and “tappy;” to another — smooth and silky.

When the image was taken away and participants had to rely on stimulation alone, they were able to correctly identify one of five objects 35% of the time: better than chance but far from perfect.

“We designed this study to shoot for the moon and made it into orbit,” said senior author of the study Robert Gaunt, Ph.D., associate professor of physical medicine and rehabilitation at Pitt. “Participants had a really hard task of distinguishing between objects by tactile sensation alone and they were quite successful at it. Even when they made mistakes, those mistakes were predictable: it’s harder to tell apart a cat and a towel since both are soft, but they were less likely to confuse a cat for a key.”

The study represents an important step towards invoking accurate sensation of touch on a person’s paralyzed hand and creating an artificial limb that seamlessly integrates into a person’s unique sensory world.

Other authors of this research are Vahagn Karapetyan, M.D., Ph.D., and Michael Boninger, M.D., both of Pitt; Charles Greenspon, Ph.D., and Sliman Bensmaia, Ph.D., both of the University of Chicago; and Bettina Sorger, Ph.D., of Maastricht University.

That is the message of a new peer-reviewed study, published in the Annals of Medicine (Elevate), that found smoking and other vices are associated with declines in health in people as young as 36.

The impact is even greater when these bad habits are indulged in over the long-term, state experts whose study tracked the mental and physical health of hundreds of people for more than 30 years.

Previous research has followed people from middle-age, typically for around 20 years. Studies to-date have shown that smoking and other aspects of a healthy lifestyle are adapted before the age of 30. However, in this new study a research team from Finland wanted to track people from a younger age — and to unpick, at the same time, the effect of unhealthy habits on mental health.

Using a long-running longitudinal study, in which hundreds of children who were born in the Finnish city of Jyväskylä in 1959 were followed from childhood until their early 60s, the team analyzed participants’ mental and physical health via data that was collected from surveys and medicals when they were 27 years old (326 participants) and again at age 36, 42, 50 and 61 (206 participants).

Mental health was assessed via surveys on symptoms of depression and on psychological wellbeing. Physical health was assessed by creating a metabolic risk score based on blood pressure, waist size and levels of blood sugar, cholesterol and other blood fats.

Self-health was assessed by asking the participants to rate the state of their health over the past year.

Three risky behaviours were also assessed at each point in time: smoking, heavy drinking (defined as consuming at least 7,000g/875 units of alcohol a year for women and 10,000g/1,250 units a year for men) and physical inactivity (exercising less than once a week).

Analysis of the results showed that if an individual had all three unhealthy habits — they smoked, drank heavily and were inactive — at a given point in time, their mental and physical health were poorer than if they didn’t have any of these risky behaviours.

Depressive symptoms rose by 0.1 points, metabolic risk score rose by 0.53 points, psychological wellbeing fell by 0.1 point and self-rated health fell by 0.45 points. Depressive symptoms and psychological wellbeing was measured on a scale of 1-4; self-rated health was measured on a scale of 1-5; and metabolic risk was scored from 0-5.

Having all three unhealthy behaviours long-term was even more strongly associated with poor health. Depressive symptoms rose by 0.38 points, metabolic risk score rose by 1.49 points, psychological wellbeing fell by 0.14 points and self-rated health fell by 0.45 points.

Lack of exercise was particularly linked to poor physical health, smoking was mainly linked to poor mental health and heavy alcohol consumption was associated with declines in both mental and physical health.

Crucially, the effects were apparent by the time the participants were in their mid-30s.

“Non-communicable diseases such as heart disease and cancer cause almost three-quarters of deaths worldwide,” says lead author Dr Tiia Kekäläinen, a health scientist who has a particular interest in aging. “But by following a healthy lifestyle, an individual can cut their risk of developing these illnesses and reduce their odds of an early death.

“Our findings highlight the importance of tackling risky health behaviours, such as smoking, heavy drinking and physical inactivity, as early as possible to prevent the damage they do to from building up over the years, culminating in poor mental and physical health later in later life.

“However, it is never too late to change to healthier habits. Adopting healthier habits in midlife also has benefits for older age.”

The authors note that the study was observational and so couldn’t establish that the risky behaviours were fuelling ill health, rather than vice versa.

They say that the relationship is likely two-way. For example, someone who is stressed may drink heavily to help them cope. This could then cause problems with family and friends that lead to poorer mental well-being.

They add that the results are likely to apply to people born in Finland and other Western countries in late 1950s and in the 1960s. However, they may not be as relevant to younger generations, owing to cultural and societal changes, and partly different risky behaviors occurring nowadays.

The study’s limitations include rating each of the three habits as being equally damaging to health, instead of weighting them.

The authors also acknowledge that they only looked at three types of behaviour and say that other factors, such as diet, should be included in future studies.

In a study published in Intelligent Systems, Blockchain and Communication Technologies, electrical and computer engineering assistant professor Kasem Khalil shows that a new technology developed at his lab could improve heart attack detection methods without sacrificing accuracy.

“For this issue, a few minutes or even a few extra seconds is going to give this person the care they need before it becomes worse,” Khalil said. “Compared to traditional methods, our technology is up to two times faster, while still highly accurate.

“Our target was not only to increase performance for classifying heart attacks. We are also focusing on the design. If we want to make this device a usable machine for any person, that means it has to be something lightweight and economic.”

In the United States, someone dies from a heart attack every 40 seconds. Heart disease — a collection of underlying conditions that can lead to a heart attack — is the leading cause of death in the United States.

Khalil and his team used artificial intelligence and advanced mathematics to design a chip that can analyze electrocardiograms, known as ECGs — graphs of the heart’s electrical signals — and detect a heart attack in real-time.

The resulting technology is lightweight and energy efficient enough to be embedded in wearable devices while still being 92.4% accurate — higher than many current methods.

“We wanted to be able to implement this in a way that is real,” said Tamador Mohaidat, a doctoral student in Khalil’s lab and co-author of the publication. “This is portable hardware that can be in wearable or monitoring devices.

“This method will save lives because we can monitor the heart in real time.”

Mohaidat, from Irbid, Jordan, focused on creating the artificial neural network, while Md. Rahat Kader Khan focused on building the software for the device. Khan, a second-year computer engineering graduate student from Dhaka, Bangladesh, said the Khalil lab is unique in that it focuses on all aspects of the technology they hope to create.

“Some labs only focus on the software part, and they don’t think about the hardware that’s needed,” Khan said. “But in our lab, we focus on the whole product. Each of us has a responsibility, but we work together.

“That’s how we optimize the whole system, by focusing on the overall architecture.”

Current methods of heart attack detection often must happen in a medical facility. A patient experiencing chest pain or who suspects they’re having a heart attack must first go through an electrocardiogram or blood tests to diagnose their condition.

All of that takes time that a patient might not have, the researchers said. If a wearable device such as a watch or a phone can cut down on diagnosis time, patients could get faster treatment.

“When a patient is having a heart attack, the sooner you can treat them, the less likely they are to have permanent damage,” Khalil said. “There’s a huge time-sensitive element to heart attacks.”

While Khalil and his team continue developing the technology, he said he sees other health care applications for these devices.

“We want to be able to predict or identify many problems using technology like this,” he said. “Whether that’s heart attacks or seizures or dementia. The detection of a disease or condition depends on the disease itself, but we’re working to find faster, more efficient ways of doing that.”

Breast cancer incidence rates in women aged 20 to 49 years have been increasing over the past 20 years across most racial and ethnic groups, but few studies have examined mortality data for patients in this age group, according to Adetunji Toriola, MD, PhD, MPH, professor in the Department of Surgery and Division of Public Health Sciences and Siteman Cancer Center at Washington University School of Medicine.

“Understanding recent trends in mortality will enable us to assess progress over the years and inform where to direct resources to reduce cancer burden in this age group,” explained Toriola, who presented the study.

Toriola and colleagues analyzed data from the SEER Program 17 registry, which included data on 11,661 breast cancer deaths among women ages 20-49 between 2010 and 2020. They evaluated breast cancer incidence-based mortality by race and molecular subtypes — including luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer — and identified differences in trends using annual percent changes (APC). Additionally, they performed relative survival analyses by examining the 10-year survival rate for each group and subtype.

Across all subtypes and racial/ethnic groups, incidence-based mortality declined from 9.70 per 100,000 women in 2010 to 1.47/100,000 in 2020. Luminal A had the most pronounced decline among the four subtypes, with a decline throughout the time period and the largest drop in 2017 (-32.88% APC). Triple-negative breast cancer followed a similar trend, with 2018 marking its largest decline (-32.82% APC).

Even though the decline in incidence-based mortality was the largest for luminal A overall, the 10-year relative survival for women with this breast cancer subtype varied depending on age. Among women ages 40-49, luminal A had the highest 10-year survival while among women ages 20-39, luminal A (78.3%) had lower 10-year survival than luminal B (84.2%).

“This was unexpected as luminal A is generally the least aggressive subtype with the most favorable prognosis,” Toriola said. “This requires confirmation in other studies but may suggest that luminal A tumors in women ages 20-39 may represent a more biologically heterogeneous and potentially aggressive subgroup.”

While incidence-based mortality declined for each of the racial/ethnic groups, non-Hispanic Black women had the highest incidence-based mortality in both 2010 (16.56/100,000) and 2020 (3.41/100,000) and non-Hispanic white women had the lowest incidence-based mortality in 2010 (9.18/100,000) and 2020 (1.16/100,000). Declines became most pronounced for non-Hispanic Black women in 2016 (-24.15% APC), for non-Hispanic Asian/Pacific Islander women in 2013 (-18.46% APC), for Hispanic women in 2017 (-30.15% APC), and for non-Hispanic American Indian and Alaska Native women in 2018 (-47.97% APC).

The 10-year relative survival analysis found that non-Hispanic Black women had the worst survival outcomes, while non-Hispanic white women and non-Hispanic Asian/Pacific Islander women had the best.

“We have made tremendous advances in reducing mortality from breast cancer in young women but there are still opportunities for improvements, especially in relation to eliminating disparities,” Toriola said.

Toriola explained that the more drastic declines seen after 2016 likely reflect advancements in treatment options, greater uptake of precision medicine, and expanded access to care and screening in women ages 40-49. For example, he mentioned how the broader adoption of CDK4/6 inhibitors and optimization of endocrine therapy, which began receiving FDA approval and clinical adoption between 2015 and 2016, likely played key roles in improving mortality rates for hormone receptor-positive, HER2-negative cancers — including luminal A.

“We must continue to perform impactful research to ensure further reduction in breast cancer mortality, including research into understanding the tumor biology and molecular mechanisms driving carcinogenesis and treatment response in younger women,” Toriola said. “Additionally, we must encourage and provide access to population-based screening in women ages 40-49 and targeted screening in younger high-risk women, and advocate for access to high-quality treatment and care for all women.”

Key limitations of this study include a follow-up time limited to 10 years and a relatively smaller number of breast cancer deaths in some racial/ethnic groups.

Funding for this study was provided by the Washington University School of Medicine. Toriola declares no conflicts of interest.

While the chemicals, called phthalates, are in widespread use globally, the Middle East, South Asia, East Asia, and the Pacific bore a much larger share of the death toll than others — about three-fourths of the total.

For decades, experts have connected health problems to exposure to certain phthalates found in cosmetics, detergents, solvents, plastic pipes, bug repellants, and other products. When these chemicals break down into microscopic particles and are ingested, studies have linked them to an increased risk of conditions ranging from obesity and diabetes to fertility issues and cancer.

Led by researchers at NYU Langone Health, the current study focused on a kind of phthalate called di-2-ethylhexyl phthalate (DEHP), which is used to make food containers, medical equipment, and other plastic softer and more flexible. Exposure has been shown in other studies to prompt an overactive immune response (inflammation) in the heart’s arteries, which, over time, is associated with increased risk of heart attack or stroke. In their new analysis, the authors estimated that DEHP exposure contributed to 356,238 deaths, or more than 13% of all global mortality from heart disease in 2018 among men and women ages 55 through 64.

“By highlighting the connection between phthalates and a leading cause of death across the world, our findings add to the vast body of evidence that these chemicals present a tremendous danger to human health,” said study lead author Sara Hyman, BS, an associate research scientist at NYU Grossman School of Medicine.

According to the authors, the resulting economic burden from the deaths identified in their study was estimated to be around $510 billion and may have reached as high as $3.74 trillion.

In a past study from 2021, the research team tied phthalates to more than 50,000 premature deaths each year, mostly from heart disease, among older Americans. Their latest investigation is believed to be the first global estimate to date of cardiovascular mortality — or indeed any health outcome — resulting from exposure to the chemicals, says Hyman, who is also a graduate student at NYU School of Public Global Health.

A report on the findings is publishing online April 29 in the journal Lancet eBiomedicine.

For the research, the team used health and environmental data from dozens of population surveys to estimate DEHP exposure across 200 countries and territories. The information included urine samples containing chemical breakdown products left by the plastic additive. Mortality data was obtained from the Institute for Health Metrics and Evaluation, a research group in the US that collects medical information worldwide to identify trends in public health.

Among the key findings, the study showed that losses in the combined region of East Asia and the Middle East and the combined region of East Asia and the Pacific accounted, respectively, for about 42% and 32% of the mortality from heart disease linked to DEHP. Specifically, India had the highest death count at 103,587 deaths, followed by China and Indonesia. The larger heart death risks in these populations held true even after the researchers adjusted their statistical analysis to take into account population size within the studied age group.

A possible explanation, the authors say, is that these countries face higher rates of exposure to the chemicals, possibly because they are undergoing a boom in plastic production but with fewer manufacturing restrictions than other regions.

“There is a clear disparity in which parts of the world bear the brunt of heightened heart risks from phthalates,” said study senior author Leonardo Trasande, MD, MPP. “Our results underscore the urgent need for global regulations to reduce exposure to these toxins, especially in areas most affected by rapid industrialization and plastic consumption,” added Trasande, the Jim G. Hendrick, MD, Professor of Pediatrics at NYU Grossman School of Medicine.

Trasande, who is also a professor in the Department of Population Health, cautions that the analysis was not designed to establish that DEHP directly or alone caused heart disease and that higher death risks did not take into account other types of phthalates. Nor did it include mortality among those in other age groups. As a result, the overall death toll from heart disease connected to these chemicals is likely much higher, he says.

Trasande says that the researchers next plan to track how reductions in phthalate exposure may, over time, affect global mortality rates, as well as to expand the study to other health concerns posed by the chemicals, such as preterm birth. Trasande also serves as director of NYU Grossman School of Medicine’s Division of Environmental Pediatrics and the Center for the Investigation of Environmental Hazards.

Funding for the study was provided by National Institutes of Health grant P2CES033423. Further study funding was provided by Beyond Petrochemicals.

Trasande has received support for travel or meetings from the Endocrine Society, World Health Organization, the United Nations Environment Programme, Japan’s Environment and Health Ministries, and the American Academy of Pediatrics. He has also received royalties and licenses from Houghton Mifflin Harcourt, Audible, Paidós, and Kobunsha, and has served in leadership or fiduciary roles at Beautycounter, Ahimsa, Grassroots Environmental Education, and Footprint. None of these activities were related to the current study. The terms and conditions of all of these relationships are being managed by NYU Langone Health.

In addition to Hyman and Trasande, other NYU Langone researchers involved in the study are Jonathan Acevedo, MPH, and Chiara Gianarelli, MD, PhD.

When applying the algorithm to vertebral fracture assessment (VFA) images taken in older women during routine bone density testing, often as part of treatment plans for osteoporosis, the patient’s presence and extent of abdominal aortic calcification (AAC) was assessed.

The algorithm shortens the timeframe to screen for AAC significantly, taking less than a minute to predict AAC scores for thousands of images, compared with the five to six minutes it would take for an experienced reader to obtain the AAC score from one image.

During her research, ECU research fellow Dr Cassandra Smith found that 58% of older individuals screened during routine bone density testing presented with moderate to high levels of AAC, with one in four walking through the door unaware that they had high AAC, placing them at the highest risk of heart attack and stroke.

“Women are recognised as being under screened and under-treated for cardiovascular disease. This study shows that we can use widely available, low radiation bone density machines to identify women at high risk of cardiovascular disease, which would allow them to seek treatment.

“People who have AAC don’t present any symptoms, and without doing specific screening for AAC, this prognosis would often go unnoticed. By applying this algorithm during bone density scans, women have a much better chance of a diagnosis,” Dr Smith said.

Using the same algorithm, ECU senior research fellow Dr Marc Sim found that these patients with moderate to high AAC scores also had a greater chance of fall-associated hospitalisation and fractures, compared with those with low AAC scores.

“The higher the calcification in your arteries, the higher the risk of falls and fracture,” Dr Sim said.

“When we look at traditional falls and fracture risk factors, things like have you fallen in the past year and bone mineral density are generally very good indicators of how likely someone is to fall and fracture. Some medications are also associated with higher falls risks. Rarely do we consider vascular health when considering falls and fractures.

“Our analysis uncovered that AAC was a very strong contributor to falls risks and was actually more significant than other factors that are clinically identified as falls risk factors.”

Dr Sim said that the new machine algorithm, when applied to bone density scans, could give clinicians more information around the vascular health of patients, which is an under-recognised risk factor for falls and fractures.

Combining virtual reality with force feedback, VR-haptic technology is becoming more and more common in dental education where it complements traditional preclinical hand skill training methods. The aim of the present study was to understand dental educators’ perceptions and needs regarding the acceptability and application of VR-haptics in dental education, as well as to gather suggestions for system improvements.

Over a third of 387 respondents (35%) cited technical limitations in current systems, such as insufficient haptic precision and restricted procedural options, which undermine skill transfer to real patient care. Financial constraints were another major hurdle, with 28% of institutions struggling to afford devices, leading to shortages and limited student access.

Resistance to change also persists: 24% noted low acceptance among educators and students, driven by disruptions to traditional teaching methods. Additionally, 13% highlighted time-intensive curriculum adaptations and training requirements as critical obstacles.

To address these challenges, the authors recommend further hardware and software development, seeking cost-reduction innovations, and providing targeted faculty training to demonstrate VR-haptics’ educational benefits. They point out that future success hinges on multidisciplinary collaboration — particularly among restorative dentistry, prosthodontics, and endodontics — to develop realistic, discipline-specific training scenarios.

Dry eye disease occurs when the eyes do not make enough tears, or make poor-quality tears without sufficient lipid or mucus levels which leads to poor tear film stability and rapid evaporation. Sufferers may have gritty feeling eyes, itching or stinging in the eyes, red eyes, sensitivity to light and blurry vision. There are several risk factors for dry eye disease, including stress and wearing contact lenses. It is also more prevalent in females. In the 18-25 age group, a major risk factor is screen use.

The research, following 50 18-25-year-olds over time, was led by Dr Rachel Casemore at Aston University School of Optometry and is the first of its kind. The researchers looked for symptoms of dry eye disease in the participants, studied lifestyle factors, and followed up with participants one year on to find out if there had been any progression of the condition.

The initial study showed that 56% of participants had dry eye disease, while 90% had at least one symptom of the condition. Around half of the participants in the study had lost at least 25% of a type of gland in the eye called the meibomian gland. These glands produce the outer lipid layer of the eye’s tear film, which is responsible for preventing evaporation of tears, and therefore keeps the tear film stable and the eye moist. One year on, the researchers found that there had been significant progression of dry eye disease in the study participants.

Additionally, the researchers found correlation found between how long the study group used screens and signs of dryness on the eye surface. The average screen use of participants was eight hours per day.

The researchers concluded that the evidence of dry eye disease symptoms and progression in the young adults in their study shows the need for early detection of potential signs, and the identification of those who may go on to develop dry eye disease. These individuals can then be advised on managing the condition before progression.

The progression and development of dry eye disease can be slowed by various methods. Dr Casemore says that the simplest ways are to take regular screen breaks, to carry out blink exercises to ensure the release of oils from the meibomian glands and to keep hydrated. A healthy, balanced diet, including sources of omega-3 fatty acids, such as oily fish, is also important, as is regular sleep patterns.

Dr Casemore suggests that those with irregular sleep patterns, such as those caused by sleep disorders or anxiety, should seek advice. People who wear contact lenses need to ensure they get regular check-ups to ensure optimum fitting, and that they adhere to their replacement schedule, wearing time schedule, cleaning regimes and safety advice, such as no sleeping, showering or swimming in contact lenses.

Dr Casemore said:

“It is concerning to note the increasing prevalence of dry eye disease signs and symptoms in young adults, which has been referred to as a ‘lifestyle epidemic’ by some researchers. Eye care practitioners are well placed to identify the clinical indicators of dry eye disease and counsel young adults around modifiable risk factors, such as screen use habits, sleeping habits, contact lens use, diet, blinking patterns, and management of stress levels.

“Our future research aims to continue investigation of the potential tear and meibomian gland oil biomarkers which were identified during the study and further explore the effect of diet on dry eye disease development.”

They are the building blocks of life, serving as essential components in nearly all cellular processes. They facilitate communication between cells and ensure that biological systems function properly.

Put simply, life wouldn’t exist without proteins. That’s why researchers around the world are dedicated to understanding them.

Now, a new study from the University of Copenhagen highlights how protein research could revolutionize multiple areas within biology and medicine. The study, published in the journal Cell, was led by scientists at the University of Copenhagen’s Novo Nordisk Foundation Center for Protein Research.

“We hope our findings will help explore how drugs influence protein turnover and contribute to the development of better medicines. Our research could also reveal how protein stability changes with age and how we might promote healthy aging,” says Professor Jesper Velgaard Olsen.

“In short, we have developed a cutting-edge technology that allows us to analyse and quantify proteins in individual cells with unprecedented depth. We can now identify exactly which proteins are present and in what quantities.”

With this new approach, researchers can measure how individual cells produce and break down proteins — a process known as ‘protein turnover’. The technique, called SC-pSILAC, enables scientists to track both the abundance of proteins and the rate at which they are turned over in single cells. These insights could have significant implications for cancer research, drug development, and personalized medicine.

Mapping the impact of cancer treatments

Despite their fundamental importance, there is still much we don’t know about proteins — including how many exist in a human cell.

SC-pSILAC is a breakthrough since it can distinguish between dividing and non-dividing cells. A prime example is cancer cells, which divide rapidly and are typically targeted by chemotherapy.

However, some cancer cells do not divide, allowing them to evade chemotherapy. The new method helps identify these treatment-resistant cells, leading to better therapies.

“We can now observe that non-dividing cells remain metabolically active and continue to affect their surroundings — something previous methods couldn’t detect,” explains Olsen.

The researchers have also used this technique to examine how specific drugs impact protein turnover in individual cells, including the cancer medication bortezomib. Their findings uncovered specific proteins and previously unknown biological processes influenced by the treatment.

“This method represents a significant leap in protein research,” Olsen states.

“In my field, we have worked for years to analyze proteins within cells. Only recently has technological progress enabled us to do so at the single-cell level.”

Thanks to this innovation, scientists now have a far more detailed understanding of how proteins operate at the molecular level. The hope is that this knowledge will drive advancements in disease diagnostics and treatment strategies.

The phase 3b, double-blind, randomised, placebo-controlled trial enrolled 1,457 influenza-positive index patients and 2,681 household contacts across 15 countries from 2019 to 2024. The index patients, aged 5 to 64, were assigned to receive either baloxavir or a placebo within 48 hours of symptom onset. The primary endpoint was laboratory-confirmed influenza transmission to household contacts by day 5.

Key Findings:

• Treatment with baloxavir reduced the odds of untreated household members contracting the virus by 32%.
• Transmission resulting in symptomatic influenza was lower with baloxavir (5.8% vs. 7.6%), though the difference was not statistically significant (P=0.16).
• Baloxavir led to a faster reduction in viral titers, with a mean reduction of 2.22 log₁₀ TCID₅₀/mL by day 3 compared to 1.85 log₁₀ TCID₅₀/mL for placebo.
• Drug-resistant viruses emerged in 7.2% of baloxavir-treated index patients but were not detected in household contacts, suggesting limited transmission risk.
• No new safety concerns were identified, with adverse events reported in 4.6% of baloxavir-treated patients compared to 7.0% in the placebo group.

‘These results highlight baloxavir’s potential not only to treat influenza but also to reduce its spread within communities,’ said Professor Benjamin Cowling, co-author of the study and Helen and Francis Zimmern Professor in Population Health, Chair Professor of Epidemiology, and Head of the Division of Epidemiology and Biostatistics, School of Public Health, HKUMed. ‘This dual effect could transform how we manage seasonal influenza and prepare for future pandemics.’

The study underscores the complementary role of antiviral drugs alongside vaccination, particularly in unvaccinated populations or during pandemics when vaccines may not be immediately available.

Thyroid cancer is among the most prevalent cancers in Hong Kong and globally. Precision management of the disease often rely on two systems: (1) the 8th edition of the American Joint Committee on Cancer (AJCC) or Tumour-Node-Metastasis (TNM) cancer staging system to determine the cancer stage; and (2) the American Thyroid Association (ATA) risk classification system to categorise cancer risk. These systems are crucial for predicting patient survival and guiding treatment decisions. However, the manual integration of complex clinical information into these systems can be time-consuming and lack efficiency.

The research team developed an AI assistant that leverages large language models (LLMs), like ChatGPT and DeepSeek, which are designed to understand and process human language, to analyse clinical documents and enhance the accuracy and efficiency of thyroid cancer staging and risk classification.

The model leverages four offline open-source LLMs — Mistral (Mistral AI), Llama (Meta), Gemma (Google), and Qwen (Alibaba) — to analyse free-text clinical documents. The AI model was trained with a United States based open-access data with pathology reports of 50 thyroid cancer patients from The Cancer Genome Atlas Programme (TCGA), with subsequent validation against pathology reports from 289 TCGA patients and 35 pseudo cases created by endocrine surgeons.

By combining the output of all four LLMs, the team improved the overall performance of the AI model, achieving overall accuracy of 88.5% to 100% in ATA risk classification and 92.9% to 98.1% in AJCC cancer staging. Compared to traditional manual document reviews, this advancement is expected to halve the time clinicians spend on pre-consultation preparation.

Professor Joseph T Wu, Sir Kotewall Professor in Public Health and Managing Director of InnoHK D24H at HKUMed, emphasised the model’s remarkable performance. ‘Our model achieves more than 90% accuracy in classifying AJCC cancer stages and ATA risk category’, he said. ‘A significant advantage of this model is its offline capability, which would allow local deployment without the need to share or upload sensitive patient information, thereby providing maximum patient privacy.’

‘In view of the recent debut of DeepSeek, we conducted further comparative tests with a “zero-shot approach” against the latest versions of DeepSeek — R1 and V3 — as well as GPT-4o. We were pleased to find that our model performed on par with these powerful online LLMs,’ added Professor Wu.

Dr Matrix Fung Man-him, Clinical Assistant Professor and Chief of Endocrine Surgery, Department of Surgery, School of Clinical Medicine, HKUMed, stated, ‘In addition to providing high accuracy in extracting and analysing information from complex pathology reports, operation records and clinical notes, our AI model also dramatically reduces doctors’ preparation time by almost half compared to human interpretation. It could simultaneously provide cancer staging and clinical risk stratification based on two internationally recognised clinical systems.’

‘The AI model is versatile and could be readily integrated into various settings in the public and private sectors, and both local and international healthcare and research institutes,’ said Dr Fung. ‘We are optimistic that the real-world implementation of this AI model could enhance the efficiency of frontline clinicians and improve the quality of care. In addition, doctors will have more time to counsel with their patients.’

‘In line with government’s strong advocacy of AI adoption in healthcare, as exemplified by the recent launch of LLM-based medical report writing system in the Hospital Authority, our next step is to evaluate the performance of this AI assistant with a large amount of real-world patient data. Once validated, the AI model can be readily deployed in real clinical settings and hospitals to help clinicians improve operational and treatment efficiency,’ explained Dr Carlos Wong, Honorary Associate Professor in the Department of Family Medicine and Primary Care, School of Clinical Medicine, HKUMed.

The study was led by Professor Joseph Wu Tsz-kei, Sir Robert Kotewall Professor in Public Health in the School of Public Health, and Managing Director & Lead Scientist of InnoHK D24H; Dr Matrix Fung Man-him, Clinical Assistant Professor and Chief of Endocrine Surgery in the Department of Surgery, School of Clinical Medicine; and Dr Carlos Wong King-ho, Honorary Associate Professor in the Department of Family Medicine and Primary Care, School of Clinical Medicine, and Senior Research Director in InnoHK D24H; all under HKUMed. The first authors were Dr Eric Tang Ho-man and Dr Tingting Wu from InnoHK D24H.

In their study, published in the American Journal of Preventive Medicine, the researchers found that when simple but strategic digital features, such as colour-coded nutritional quality signals and a healthier alternative prompt, were added to an online grocery shopping platform, the nutritional quality of shoppers’ carts improved significantly.

The team’s findings verified the effectiveness of deploying front-of-package (FOP) labels — which only marginally improve diet quality when used alone — alongside other interventions.

In a randomised trial conducted on NUSMart, an online grocery store designed by the Duke-NUS team, study participants were randomly divided into two groups and asked to make a total of three orders over a period of three to six weeks. While those assigned to the control group used a standard version of the store, those assigned to the experimental group used a version of the store with additional digital features, including:

Signalling nutritional quality with a traffic light: FOP labels resembling traffic light signals alerted shoppers to food products’ nutritional quality using three colour bands — green (best), amber and red with an “X” mark — for easy identification of foods to avoid.

Items were sorted into the colour bands based on their Nutri-Score (NS)[1] points, which were assigned according to energy, sugar, sodium, saturated fat, fruit/vegetable, protein, and dietary fibre levels per 100g/ml. The points were then converted into grades on a five-letter grading system, with A being the healthiest and E being the least healthy.

Sorting groceries by nutritional value: Using food products’ NS points, the researchers presented the items by order of nutritional value, with the healthiest options appearing first. Items in the control version of NUSMart appeared in alphabetical order.

Showing real-time cart feedback: Participants could track the nutritional quality of their grocery carts via a pie chart that indicated the proportion of items in each colour band. They could also compare their carts with a reference cart for health grocery shopping, which the researchers had curated using past data.

Suggesting healthier options: Shoppers could also view up to four healthier alternatives with similar prices and characteristics to each selected food product and replace their chosen product with the healthier alternative at the click of a button.

With these interventions, the nutritional quality of participants’ grocery carts improved from NS grade C to NS grade B, which was more significant than results from previous studies involving standalone FOP labels. The interventions also reduced the amount of calories (12.86 kcal), total fat (1.21g), saturated fat (0.85g), sugar (0.82g) and sodium (156.64mg) purchased.

Notably, the researchers found that shopping with the four digital features led to healthier food choices across all three orders.

Assistant Professor Soye Shin from Duke-NUS’ Health Services and Systems Research Programme, the study’s first author, said of the findings: “As online grocery shopping is rapidly gaining ground, we wanted to see if we could design low cost, scalable online tools that could be used to nudge consumers toward healthier choices at the point of purchase. These results show the potential of these tools to improve diet and health outcomes.”

These findings underscore the advantages of introducing diet quality labels, such as Singapore’s Nutri-Grade labelling initiative, which currently only includes beverages but is planned to expand to other food categories.

Senior author Professor Eric Finkelstein, from Duke-NUS’ Health Services and Systems Research Programme, said: “These results are encouraging but the next step is to work with retailers to incorporate these features into existing online stores. Only then will the full value of this approach be realised.”

Next, the researchers will expand the study to include consumers of low socio-economic status and little nutritional knowledge. They will also investigate if the multi-pronged intervention strategy has the potential to positively impact consumers’ health in the long term.

Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, commented on the study’s impact: “This study reflects how smart, evidence-based interventions — when applied at the right moment — can empower people to make better everyday choices for their health. It also shows how research can lead to practical tools that improve not just individual choices, but population health outcomes.”

Duke-NUS is at the forefront of biomedical research and translational innovations. This new study is part of the School’s ongoing efforts to improve global health through systems research and scientific breakthroughs.

New findings may explain why: Not all senescent skin cells are the same.

Researchers from Johns Hopkins University have identified three subtypes of senescent skin cells with distinct shapes, biomarkers, and functions — an advance that could equip scientists with the ability to target and kill the harmful types while leaving the helpful ones intact.

The findings were published today in the journal Science Advances.

“We’ve known that senescent skin cells are different from senescent immune cells or senescent muscle cells. But within a cell type, senescent cells are often considered the same — in essence, skin cells are either senescent or not, for example,” said Jude Phillip, an assistant professor of biomedical engineering at Johns Hopkins University. “But we’re finding that when a skin cell goes into senescence, or a zombie-like state, the cell could go down one of three different paths, each leading to a slightly different subtype.”

Leveraging new advances in machine learning and imaging technology, the researchers compared skin cell samples from 50 healthy donors between the ages of 20 and 90 who participated in the Baltimore Longitudinal Study, an NIH-funded project that is the longest ongoing study of aging in the United States.

Researchers extracted fibroblasts — cells that produce the scaffolding to give tissues their structure — associated with skin tissue and pushed them toward senescence by damaging their DNA, something that happens with aging. Because senescent cells build up naturally as people grow older, the aged samples contained a mix of healthy/nonsenescent and senescent fibroblasts.

Using specialized dyes, the researchers were able to capture images of the cells’ shapes and stained elements that are known to indicate senescent cells. Algorithms developed for this study analyzed the images, measured 87 different physical characteristics for each cell, and sorted the fibroblasts into groups.

Fibroblasts come in 11 different shapes and sizes, three of which are distinct to senescent skin cells, the researchers found. Only one subtype of senescent fibroblast, which the researchers named C10, was more prevalent in older donors.

In the petri dishes, each subtype responded differently when exposed to existing drug regimens designed to target and kill zombie cells. Dasatinib + Quercetin, a drug being tested in clinical trials, for example, most effectively killed C7 senescent fibroblasts but was limited in killing the age-associated C10 senescent fibroblasts.

Though further research is needed to verify which fibroblast subtype is harmful and which is helpful, the findings show that drugs can target one subtype and not the others.

“With our new findings, we have the tools ready to develop new drugs or therapies that preferentially target the senescence subtype that drives inflammation and disease as soon as it is identified,” Phillip said.

More precise targeting of senescence could benefit cancer treatments, the researchers said.

Certain therapies are being designed to trigger senescence in cancer cells, converting uncontrollably replicating cancer cells into dead-in-the-water zombie cells. While these therapies could stop tumor growth, they leave senescent cells in their wake. Conventional chemotherapies also push cells like fibroblasts toward senescence as a side effect. The buildup of senescent cells during treatment can be problematic as those cells may promote inflammation at a time when a patient’s immune system is at its most vulnerable.

Patients may benefit from a drug administered after chemotherapy that can sweep up the mess, removing harmful senescent cells while leaving behind the helpful senescent cells. These types of drugs are called senotherapies.

Next, the researchers plan to look at senescence subtypes in tissue samples, not just in flasks and petri dishes, to see how those subtypes might be associated with various skin diseases and age-associated diseases.

“We hope, with some more development, our technology will be used to help predict which drugs might work well for targeting senescent cells that contribute to specific diseases,” Phillip said. “Eventually, the dream is to be able to provide more information in a clinical setting to help with individual diagnoses and boost health outcomes.”

In a phase 1 trial involving 40 patients, the research group investigated the use of T cell receptor (TCR)-engineered T cells. Using genetic engineering techniques, the researchers incorporated a kind of target identification into the T cells to enable them to recognize tumor-specific proteins. The newly tested IMA203 therapy targets the PRAME peptide, which is produced almost exclusively by tumors and not by healthy tissue. This enables the T cells to attack tumor cells in a targeted manner without damaging normal cells. PRAME is produced by many tumors, such as melanoma, ovarian cancer, sarcomas, and lung cancer.

A good half of the people treated who had not responded to standard therapies previously responded to the therapy. The majority of them even responded over a period of eight months or several years. Compared to chemotherapy, which usually lasts three to six months, this is a significant advancement in treatment. The cell therapy was also well tolerated. Side effects such as fever or skin rash were mostly mild to moderate and only temporary.

“Based on these results, we can speak of a breakthrough,” says Prof. Martin Wermke, head and first author of the trail: “For the first time, we have achieved a lasting response in truly common solid tumors. The efficacy of IMA203 goes far beyond what we can achieve with our current chemotherapy and immunotherapy treatments. Not only do we have significantly more patients responding to treatment, but the effect is also lasting much longer. We now have patients who have not had a relapse of their tumor disease more than two years after receiving IMA203. Some of these patients may even have been permanently cured of their cancer.”

In a next step, IMA203 could be used in a larger trial in patients with melanoma who have not responded to conventional immune and targeted therapies. The NCT/UCC Dresden is testing other cell therapies for other types of skin cancer and lung cancer.

In a recent study published in Food Chemistry: Molecular Sciences, researchers at the University of Mississippi center found that cinnamaldehyde — a primary component of cinnamon — activates receptors that control the metabolic clearance of medication from the body, meaning consuming large amounts of cinnamon could reduce the effects of drugs.

“Health concerns could arise if excessive amounts of supplements are consumed without the knowledge of health care provider or prescriber of the medications,” said Shabana Khan, a principal scientist in the center. “Overconsumption of supplements could lead to a rapid clearance of the prescription medicine from the body, and that could result in making the medicine less effective.”

Aside from its culinary uses, cinnamon has a long history of being used in traditional medicine and can help manage blood sugar and heart health and reduce inflammation. But how the product actually functions in the body remains unclear.

Sprinkling cinnamon on your morning coffee is unlikely to cause an issue, but using highly concentrated cinnamon as a dietary supplement might.

“Despite its vast uses, very few reports were available to describe the fate of its major component — cinnamaldehyde,” Khan said. “Understanding its bioaccessibility, metabolism and interaction with xenobiotic receptors was important to evaluate how excess intake of cinnamon would affect the prescription drugs if taken at the same time.”

Not all cinnamon is equal. Cinnamon oil — which is commonly used topically as an antifungal or antibacterial and as a flavoring agent in food and drinks — presents almost no risk of herb-drug interactions, said Amar Chittiboyina, the center’s associate director.

But cinnamon bark — especially Cassia cinnamon, a cheaper variety of cinnamon that originates in southern China — contains high levels of coumarin, a blood thinner, compared to other cinnamon varieties. Ground Cassia cinnamon bark is what is normally found in grocery stores.

“In contrast, true cinnamon from Sri Lanka carries a lower risk due to its reduced coumarin content,” he said. “Coumarin’s anticoagulant properties can be hazardous for individuals on blood thinners.”

More research is needed to fully understand the role that cinnamon plays in the body and what potential herb-drug interactions may occur, said Bill Gurley, a principal scientist in the center and co-author of the study.

“We know there’s a potential for cinnamaldehyde to activate these receptors that can pose a risk for drug interactions,” he said. “That’s what could happen, but we won’t know exactly what will happen until we do a clinical study.”

Until those studies are complete, the researchers recommend anyone interested in using cinnamon as a dietary supplement to check with their doctor first.

“People who suffer from chronic diseases — like hypertension, diabetes, cancer, arthritis, asthma, obesity, HIV, AIDS or depression — should be cautious when using cinnamon or any other supplements,” Khan said. “Our best advice is to talk to a health care provider before using any supplements along with the prescription medicine.

“By definition, supplements are not meant to treat, cure or mitigate any disease.”

This work is based on material supported in part by the United States Department of Agriculture Specific Cooperative Agreement No. 58-6060-6-015.

Exposomics explores how the complex interplay of environmental factors — from pollutants in our water and food to social and psychological stressors — shapes our biology. By studying these combined exposures, researchers can uncover how they collectively influence health, from metabolism and heart function to brain health and disease risk.

The Perspectives article is led by the Banbury Exposomics Consortium — an interdisciplinary group of scientists who gathered at Cold Spring Harbor’s Banbury Center in 2023 to define the core principles of this rapidly evolving field. Gary Miller, PhD, a foremost expert in exposomics and faculty member at Columbia University Mailman School of Public Health, was the lead organizer of the Consortium.

Miller, Vice Dean of Research and Innovation and Professor of Environmental Health Sciences at Columbia Mailman School, co-leads the NIH-funded national coordinating center for exposomics, NEXUS. He also leads IndiPHARM, an ARPA-H-funded initiative using exposomics to predict drug interactions and enhance medication effectiveness.

Exposomics in Action

The young field is already proving its transformative potential. Researchers analyzing molecular evidence identified a specific industrial solvent as the culprit behind kidney disease clusters among factory workers. In another study, scientists merged satellite pollution mapping with residential location information to reveal how airborne particulates prematurely age the brain. Scientists analyzing thousands of circulating molecules pinpointed TMAO, a gut microbiome metabolite produced when eating red meat and dairy, as a previously overlooked major contributor to heart attack risk.

These discoveries are made possible by cutting-edge technologies and tools such as wearable sensors that track chemical exposures in real-time, satellite imagery that maps pollution down to city blocks, and ultra-sensitive mass spectrometers that detect compounds present at just one part per trillion.

A Wider Lens on Our Health

While genetics provides our biological blueprint, it explains only a fraction of chronic disease risk. The exposome captures everything that happens to us, from industrial chemicals to social stressors. Unlike traditional studies examining single exposures in isolation, exposomics integrates advanced tools to understand how environmental, social, and psychological factors collectively interact with our biology.

This approach synergizes powerfully with other “omics” sciences. When combined with genomics, proteomics, and metabolomics, exposomics creates the first complete picture of health determinants. The authors envision a future where all major disease studies incorporate exposome analysis as standard practice.

Systematically analyzing these complex interactions can improve drug development, uncover hidden drivers of disease, and address health disparities. The approach bridges precision medicine and population health.

The Way Forward

Miller and colleagues outline critical priorities for advancing exposomics. These include the development of more sensitive technologies, such as wearable or minimally invasive tools that measure an individual’s exposome; the creation of a human exposome reference to enable analysis and contextualization at the population scale; and the implementation of standardized protocols to enable AI-driven analysis of complex datasets. The field must also address ethical considerations around data privacy and the need for greater focus on the social determinants of health, the authors write.

Newly launched U.S. and European exposomics hubs now provide the infrastructure for worldwide collaboration, standardizing methods, harmonizing data, and training researchers in the cross-disciplinary skills needed to advance this field. These centers form the critical backbone for the future progress of exposomics.

“We’re now building the first systematic framework to measure how all exposures — from chemical to social — interact with biology across the lifespan. Our goal is to create actionable strategies for healthier lives,” says Miller.

The study, recently published in The Journal of Clinical Ophthalmology, highlights the trust patients place in their physicians and the critical role of doctor-patient communication in making medical decisions.

The research was led by Lisa Kelly, MD, a Taylor Asbury-endowed professor-educator and director of medical student education in the Department of Ophthalmology at the University of Cincinnati College of Medicine. Kelly also serves as medical director of UC eye clinics. The study’s corresponding author was Samantha Hu, a fourth-year medical student. Stephanie Wey, MD, a former UC resident, and Rainier Yono, a third-year medical student, also contributed.

The research team surveyed 42 patients at Hoxworth Eye Clinic, the training site for UC’s ophthalmology residents located near UC Medical Center. The study explored a possible link between health literacy and fear surrounding cataract surgery.

“We hypothesized that patients with lower health literacy would fear surgery more, especially the risk of vision loss,” said Hu. “But our findings didn’t support that.”

Cataracts develop when proteins in the eye’s natural lens break down and clump together, leading to blurry or dimmed vision. Because the condition is most commonly age-related, those surveyed were all 50 and older. Sixty percent reported a yearly income below $50,000.

Study findings

Among those surveyed, 36% reported fear of cataract surgery, and more than half of those specifically feared it would lead to vision loss. However, researchers found no correlation between this fear and a patient’s health literacy level.

“We found patients who would benefit from surgery reasonably understood the procedure after we educated them,” Kelly said. “But even with clear explanations, sometimes their fear persisted.”

Hu noted that simply providing more information wasn’t always helpful. “Overloading patients with data doesn’t necessarily ease their concerns,” she said.

Instead, the study pointed to the importance of open communication.

“Yes, patient education matters, but it’s not always sufficient,” said Kelly. “What’s equally important is building relationships and trust to help patients overcome fear.”

Hu said the findings emphasize how much patients rely on their physicians to guide them to medical decisions based on their individual needs.

“It underscores the trust patients place in their doctors — and the need for physicians to truly understand their patient population,” said Hu.

Kelly added, “It’s a reminder that our patients are people with real fears. Our role is to partner with them in their health care.”

Moving forward, researchers are likely to delve deeper into patients’ fear around cataract surgery and how physicians can further strengthen doctor-patient relationships.

Path to residency

Hu is part of the UC College of Medicine’s Class of 2025. She is originally from Greenwood Village, Colorado, a suburb of Denver.

As Hu became more focused on pursuing the ophthalmology specialty, she said she reached out to Kelly about taking part in research and joined the study in her second year of medical school for the data gathering process.

Hu said she was intrigued by this study because of her interest in the social determinants of health, the economic and social conditions that influence differences in people’s health. “Sam and I spent a lot of one-on-one time together as she worked on this research project,” said Kelly. “I got to know her well.”

The results of the study were first presented at a medical conference last year and likely helped Hu stand out in the competitive residency matching process.

“Engaging with a scholarly question in research like this better positions medical students to take a critical look at the literature,” Kelly said.

After she graduates this spring, Hu will begin her ophthalmology residency at Loyola University Chicago.

The glasses are one of the wizard’s many deceits; the city viewed through green-tinted glasses would, of course, only look more green.

But using a new technique called “Oz,” scientists at the University of California, Berkeley, have found a way to manipulate the human eye into seeing a brand-new color — a blue-green color of unparalleled saturation that the research team has named “olo.”

“It was like a profoundly saturated teal … the most saturated natural color was just pale by comparison,” said Austin Roorda, a professor of optometry and vision science at UC Berkeley’s Herbert Wertheim School of Optometry & Vision Science, and one of the creators of Oz.

Oz works by using tiny doses of laser light to individually control up to 1,000 photoreceptors in the eye at one time. Using Oz, the team is able to show people not only a green more stunning than anything in nature, but also other colors, lines, moving dots and images of babies and fish.

The platform could also be used to answer basic questions about human sight and vision loss.

“We chose Oz to be the name because it was like we were going on a journey to the land of Oz to see this brilliant color that we’d never seen before,” said James Carl Fong, a doctoral student in electrical engineering and computer sciences (EECS) at UC Berkeley.

“We’ve created a system that can track, target and stimulate photoreceptor cells with such high precision that we can now answer very basic, but also very thought-provoking, questions about the nature of human color vision,” Fong said. “It gives us a way to study the human retina at a new scale that has never been possible in practice.”

The Oz technique is described in a new study published last week in the journal Science Advances. The work was funded in part by federal grants from the National Institutes of Health and the Air Force Office of Scientific Research.

Untapped photoreceptors

Humans are able to see in color thanks to three different types of photoreceptor “cone” cells embedded in the retina. Each type of cone is sensitive to different wavelengths of light: S cones detect shorter, bluer wavelengths;, M cones detect medium, greenish wavelengths; and L cones detect longer, reddish wavelengths.

However, due to an evolutionary quirk, the light wavelengths that activate the M and L cones are almost entirely overlapping. This means that 85% of the light that activates M cones also activates L cones.

“There’s no wavelength in the world that can stimulate only the M cone,” said study senior author Ren Ng, a professor of EECS at UC Berkeley, “I began wondering what it would look like if you could just stimulate all the M cone cells. Would it be like the greenest green you’ve ever seen?”

To find out, Ng teamed up with Roorda, who had created a technology that used tiny microdoses of laser light to target and activate individual photoreceptors. Roorda calls the technology “a microscope for looking at the retina,” and it is already being used by ophthalmologists to study eye disease.

But for a human to actually perceive a whole new color, Ng and Roorda would need to find a way to activate not just one cone cell, but thousands of them.

A movie screen the size of a fingernail

Fong first started working on the Oz project in 2018 as an undergraduate engineering student, and has created much of the complex software needed to translate images and colors into thousands of tiny laser pulses directed at the human retina.

“I joined after meeting this other student who was working with Ren, who told me that they were shooting lasers into people’s eyes to make them see impossible colors,'” Fong said.

For Oz to work, first you need a map of the unique arrangement of the S, M and L cone cells on an individual’s retina. To get these maps, the researchers collaborated with Ramkumar Sabesan and Vimal Prahbhu Pandiyan at the University of Washington, who have developed an optical system that can image the human retina and identify each cone cell.

With an individual’s cone map in hand, the Oz system can be programmed to rapidly scan a laser beam over a small patch of the retina, delivering tiny pulses of energy when the beam reaches a cone that it wants to activate, and otherwise staying off.

The laser beam is just one color — the same hue as a green laser pointer — but by activating a combination of S, M and L cone cells, it can trick the eye into seeing images in full technicolor. Or, by primarily activating the M cone cells, Oz can show people the color olo.

“If you look at your index fingernail at arm’s length, that’s about the size of the display,” said Roorda. “But if we could, we would have filled the entire visual space like an IMAX.”

The ‘wow’ experience

Hannah Doyle, a doctoral student in EECS and co-lead author of the paper, designed and ran the human experiments with Oz. Five human subjects got the chance to see the color olo, including Roorda and Ng, who were aware of the purpose of the study, but not the specifics of what they would see.

In one experiment, Doyle asked the participants to compare olo to other colors. They described it as blue-green or peacock green, and reported that it was much more saturated than the nearest monochromatic color.

“The most saturated colors you can experience in nature are the monochromatic ones. Light from a green laser pointer is one example,” Roorda said. “When I pinned olo up against other monochromatic light, I really had that ‘wow’ experience.”

Doyle also tried “jittering” the Oz laser, directing it ever-so-slightly off target so the light pulses hit random cones rather than only M cones. The participants immediately stopped seeing olo and started seeing the regular green of the laser.

“I wasn’t a subject for this paper, but I’ve seen olo since, and it’s very striking. You know you’re looking at something very blue-green,” Doyle said. “When the laser gets jittered, the normal color of the laser almost looks like yellow because the difference is so stark.”

Probing the nature of color vision

Oz isn’t just useful for projecting tiny movies into the eye. The research team is already finding ways to use the technique to study eye disease and vision loss.

“Many diseases that cause visual impairment involve lost cone cells,” Doyle said. “One application that I’m exploring now is to use this cone by cone activation to simulate cone loss in healthy subjects.”

They are also exploring whether Oz could help people with color blindness to see all the colors of the rainbow, or if the technique could be used to allow humans to see in tetrachromatic color, as if they had four sets of cone cells.

It may also help answer more fundamental questions about how the brain makes sense of the complex world around us.

“We found that we can recreate a normal visual experience just by manipulating the cells — not by casting an image, but just by stimulating the photoreceptors. And we found that we can also expand that visual experience, which we did with olo,” Roorda said. “It’s still a mystery whether, if you expand the signals or generate new sensory inputs, will the brain be able to make sense of them and appreciate them? And, you know, I like to believe that it can. I think that the human brain is this really remarkable organ that does a great job of making sense of inputs, existing or even new.”

Additional authors of the study include Congli Wang, Alexandra E. Boehm, Sophie R. Herbeck, Brian P. Schmidt, Pavan Tiruveedhula, John E. Vanston and William S. Tuten of UC Berkeley. This work was supported by a Hellman Fellowship, FHL Vive Center Seed Grant, Air Force Office of Scientific Research grants (FA9550-20-1-0195, FA9550-21-1-0230), National Institutes of Health grant (R01EY023591, R01EY029710, U01EY032055) and a Burroughs Wellcome Fund Career Award at the Scientific Interface.

“Our results add another chapter to the emerging field of skyrmion research,” proclaims Prof. Harald Giessen, head of the Fourth Physics Institute at the University of Stuttgart, whose group achieved this breakthrough. The team demonstrated the existence of “skyrmion bags” of light on the surface of a metal layer.

A better understanding of physical phenomena

Skyrmions are a mathematical description of vortex-like structures that help researchers better understand fundamental physical relationships. In recent years, this theoretical concept has been confirmed experimentally across a wide range of areas, including magnetic solids and material surfaces. Giessen’s group has now investigated whether light impinging on the structured surface of a thin gold layer can be made to behave like skyrmion bags that follow specific symmetries. These bags consist of skyrmions contained within a larger skyrmion. For their experiment, the researchers etched fine grooves in the shape of two twisted hexagons into the gold surface with each hexagon generating a skyrmion light field.

Targeted manipulation of light fields

“We then observed a superposition of two skyrmion light fields, from which the skyrmion bags formed,” explains Julian Schwab, lead author of the publication and doctoral student in Giessen’s research group. Even more strikingly, the researchers were able to vary the number of skyrmions gathered within the skyrmion bags by adjusting the degree to which the light fields were twisted relative to one another. In other words, the researchers can manipulate light fields in a targeted manner, thereby giving them shapes that usually do not occur. For the experimental verification, Giessen’s team collaborated with a research group at the University of Duisburg-Essen, and for the theoretical description of the phenomenon, with a group at the Technion in Haifa.

Fundamental research with application potential

So far, this is still fundamental physics. However, these light-field skyrmions exhibit extraordinary properties, thereby sparking researchers’ imagination in terms of potential technical applications. Whether the gold surface used by Giessen’s team is suitable for this purpose remains to be seen. “If someone finds a suitable material, our concept could be applied in microscopy,” states Giessen. We could achieve resolutions with specialized microscopes that would otherwise be impossible because of the limits set by the wavelength of the light.

One particularly vexing challenge is seeing all the molecules in an intact tissue sample, down to the level of single cells, simultaneously. Detecting the location of hundreds or thousands of biomolecules — from lipids to metabolites to proteins — in their native environment allows researchers to better understand their functions and interactions. Unfortunately, scientists don’t have great tools to accomplish this task.

Imaging methods, including most types of microscopy, provide a view of molecules inside cells. But they can track only a select handful of molecules at one time, and they can’t detect all types of biomolecules, including some lipids. Other methods, like regular mass spectrometry, can detect hundreds of molecules but don’t work on intact samples, so researchers can’t see how the biomolecules are oriented.

One promising technique — mass spectrometry imaging — overcomes some of these challenges. It allows researchers to see hundreds of molecules at one time in intact tissues. However, it doesn’t have high enough resolution to allow detection at the single cell level.

This was the problem Janelia Senior Group Leader Meng Wang faced. Wang and her team study the fundamental mechanisms behind aging and longevity, and they wanted to detect many different biomolecules in intact tissues to understand how the components change as tissues age.

“Knowing at each specific location what molecules are there and what is in the neighboring cells is very important for any kind of biological question,” Wang says.

Luckily, Wang’s lab is down the hall from Janelia Principal Scientist Paul Tillberg. Tillberg co-invented a technique called expansion microscopy as a graduate student at MIT. The method uses a swellable hydrogel material to expand samples uniformly in all directions to a point where fine details, like sub-organelle structure, can be detected with a conventional microscope.

Now a decade old, the expansion process is being applied to other methods outside traditional microscopy. Wang, Tillberg, and their collaborators at Janelia and the University of Wisconsin-Madison wanted to see if they could use expansion to overcome mass spectrometry imaging’s spatial resolution problem.

The result is a new method that expands tissue samples gradually without having to degrade them at the molecular level, as happens in the original expansion process. By expanding the intact samples in all directions, researchers can use mass spectrometry imaging to simultaneously detect hundreds of molecules at the single cell level in their native locations.

“This lets you have an untargeted look in the molecular space, and we are trying to bring it closer to what microscopy can do in terms of spatial resolution,” Tillberg says.

The team used the new technique to delineate the specific spatial patterns of small molecules in different layers of the cerebellum. They found that these molecules — including lipids, peptides, proteins, metabolites, and glycans — are not uniformly distributed, as previously thought. Moreover, they found that each specific layer of the cerebellum has its own signature of lipids, metabolites, and proteins.

The team was also able to detect biomolecules in kidney, pancreas, and tumor tissues, demonstrating that the method can be adapted for many different tissue types. In tumor tissues, they were able to visualize large variations in biomolecules, which could be useful for understanding the molecular mechanisms of tumors and potentially aid in drug development.

“When you can see these biomolecules, then you can start to understand why they have such patterns and how that is related to function,” says Wang. She believes the new technology will allow researchers to track these patterns during development, aging, and disease to understand how different molecules contribute to these processes.

Because the new method doesn’t require adding hardware to an existing mass spec imaging system, and the expansion technique is relatively easy to learn, the team hopes it will be used by many labs around the world. They also hope the new technique will make mass spec imaging a more useful tool for biologists and have laid out a detailed description of the new method and a roadmap for adapting it to other tissue types.

“We wanted to develop something that did not require specialized instruments or procedures, but can be broadly adopted,” Wang says.

University of Arizona neuroscientists have come up with a new treatment approach for PPA that combines traditional speech therapy with noninvasive electrical stimulation of the brain. The technique — called transcranial direct current stimulation — uses a low electrical current applied through electrodes on the scalp.

A new study published in the Journal of Speech, Language, and Hearing Research describes the treatment approach, which the researchers found to be more effective at managing PPA compared to speech therapy alone.

“Primary progressive aphasia is a condition that causes worsening of communication skills over time. It was identified in the literature only in the last three to four decades, so it is considered pretty new in the health care world — it’s still an understudied area,” said Katlyn Nickels, the study’s lead researcher and a postdoctoral researcher in the U of A Department of Speech, Language and Hearing Sciences.

While writing and speaking words, people don’t just retrieve their meaning. They also retrieve the sound of a word while it is being spoken or written, said Aneta Kielar, the study’s senior author and an associate professor in the Department of Speech, Language and Hearing Sciences.

If there is a problem with associating words with the way they sound, it is difficult to put letters together and speak or write a word, Kielar said. This affects people’s communication in their day-to-day life and their ability to work. For their study, the researchers focused on a type of PPA called the logopenic PPA, in which people have trouble finding the right words and repeating phrases or sentences.

The researchers did neuroimaging analysis of the brain to determine the area of the brain that needs to be stimulated, as people with PPA have brain atrophy or a loss of brain cells.

“We wanted to stimulate the area that is most responsive to language and were careful not to stimulate an area that would have been atrophied already,” Kielar said.

Twelve individuals with written language deficits each received two phases of treatment: in one phase, they got speech therapy paired with active transcranial direct current stimulation. In another phase, they received the same speech therapy with placebo transcranial direct current stimulation. The order of the phases was randomized and separated by a two-month break in between.

Although all participants improved after both treatments, they showed greater and more lasting improvement following the phase with active transcranial direct current stimulation compared to placebo transcranial direct current stimulation.

“People who made numerous spelling errors and struggled to frame complete sentences before the treatment were able to form sentences that were grammatically correct, had fewer spelling errors and were more meaningful after treatment,” Kielar said.

The researchers say brain stimulation helped induce neuroplasticity, the brain’s capacity to continue to reorganize and learn. And it boosted the effects of speech therapy.

“What that means is that brain stimulation can induce the formation of synapses, the connections between neurons. These connections are important for people’s ability to learn and maintain new skills,” Kielar said.

In the future, the research group is planning to look at the genetic, cognitive and neural markers that influence the recovery from PPA. The researchers’ long-term goal is to translate their research findings to a clinical setting.

Because transcranial direct current stimulation is inexpensive, safe and easy to perform, the barriers to implementing it in clinical practice are less significant, Nickels said.

“There’s a misconception sometimes with neurodegenerative diseases, that once you get a diagnosis, there is nothing that can be done,” Nickels said. “But we have learned through our research that even when there’s a progressive brain disease, we can help restore lost function and even slow down the progression.”

This work was supported by the following grants to the senior author, Aneta Kielar: Arizona Alzheimer’s Consortium Grant, Arizona Department of Health Services (018676-00001); Innovations in Healthy Aging: Grand Challenges of Aging Seed Grant, The University of Arizona Health Sciences (2259304); and Data Science Academy-Transdisciplinary Research in Principles of Data Science at The University of Arizona (2259910). Research reported in the publication was supported by the Arizona Department of Health Services and the state of Arizona (ADHS Grant No. CTR057001) to Aneta Kielar.

Published on Friday in the International Journal of Obesity, the research is the first to test in humans the relationship between HFHS diets, particularly those high in refined sugar and saturated fat, and first-person spatial navigation. Spatial navigation is the ability to learn and remember a path from one location to another, a process that can approximate the health of the brain’s hippocampus.

Dr Dominic Tran from the Faculty of Science’s School of Psychology led the research, which found HFHS diets have a detrimental effect on some aspects of cognitive function. It is likely those effects centre on the hippocampus, the brain structure important for spatial navigation and memory formation, rather than acting across the entire brain.

“The good news is we think this is an easily reversible situation,” Dr Tran said. “Dietary changes can improve the health of the hippocampus, and therefore our ability to navigate our environment, such as when we’re exploring a new city or learning a new route home.”

The research team recruited 55 university students aged between 18 and 38. Each participant completed questionnaires capturing their intake of sugary and fatty foods. They also had their working memory tested in a number recall exercise, and their body mass index (BMI) recorded.

The experiment itself required participants to navigate a virtual reality maze and locate a treasure chest six times. The maze was surrounded by landmarks that participants could use to remember their route. Their starting point and the location of the treasure chest remained constant in each trial.

If participants found the treasure in less than four minutes, they continued to the next trial. If they failed to find the treasure in this time, they were teleported to its location and given 10 seconds to familiarise themselves with that location before the next trial.

A seventh trial removed the treasure chest from the virtual maze but asked participants to find and mark its former location based purely on memory. Those with lower levels of fat and sugar in their diets were able to pinpoint the location with a higher degree of accuracy than those who consumed these foods multiple times a week.

“After controlling for working memory and BMI, measured separately to the experiment, participants’ sugar and fat intake was a reliable predictor of performance in that final, seventh, test,” Dr Tran said.

Dr Tran said the results highlight the importance of making good dietary choices to maintain healthy brain function.

“We’ve long known eating too much refined sugar and saturated fat brings the risk of obesity, metabolic and cardiovascular disease, and certain cancers. We also know these unhealthy eating habits hasten the onset of age-related cognitive decline in middle age and older adults.

“This research gives us evidence that diet is important for brain health in early adulthood, a period when cognitive function is usually intact,” Dr Tran said.

Dr Tran said the sample group used in this research was not representative of the wider population, but the findings still apply more broadly.

“It’s likely our participants were a little healthier than the general population and we think, if our sample better represented the public, the impact of diet on spatial navigation would likely be even more pronounced.”

Dr Tran is a recipient of an Australian Research Council Discovery Early Career Research Award (DECRA).

The researchers integrated computational and functional approaches that enabled them to identify not only specific genes whose alterations predicted increased AD risk in humans and behavioral impairments in AD fruit fly models but also showed that reversing the gene changes has a neuroprotective effect in living organisms.

“Alzheimer’s disease affects more than 50 million people worldwide and although researchers have learned a great deal about it over the years, its causes are still not fully understood and effective therapies are not yet available,” said corresponding author Dr. Juan Botas, professor of molecular and human genetics and molecular and cellular biology at Baylor. Botas also is the director of the High-Throughput Behavioral Screening Core at the Duncan NRI.

Although extensive genome-wide studies have uncovered hundreds of genes potentially associated with the disease, assessing the roles these genes play in AD is necessary to distinguish those that confer risk for the condition from uninvolved bystanders.

“We addressed this issue by first integrating published genome-wide association data with multiple computational approaches to identify genes likely involved in AD,” said co-first author Morgan C. Stephens, a graduate student in the Botas lab. “We then tested those computational predictions experimentally in the lab.”

The researchers systematically perturbed AD candidate genes identified from their computational analyses and assessed their potential to modulate neuronal dysfunction and hallmark AD-related cellular alterations, such as neuropathology or accumulation of tau protein, in living organisms.

“We worked with fruit fly models of the condition to assess whether these altered genes drove neuronal dysfunction leading to motor impairments. Importantly, we also investigated whether reversing the activity of those altered genes would also reverse the motor alterations in flies and tau or beta-amyloid protein accumulation in cells,” Botas said.

The computational analyses revealed 123 candidate genes for AD risk and the team confirmed that the expression of many of them is altered in human AD and correlates with the accumulation of tau or beta-amyloid protein in brain cells affected by the condition. Evaluation of 60 of these gene candidates available in fruit fly models pointed at 46 that modulated neuronal dysfunction in one or both fly models. The altered expression of 18 of these genes predicted the increase of AD risk in humans.

Importantly, reversing the alterations in 11 of these genes protected fruit flies from damage to their nervous system.

“In the list of final candidates, MTCH2 turned up to be at the top on the functional studies,” Stephens said. “MTCH2 expression is downregulated in human AD brain samples, and reducing its function in flies aggravates motor dysfunction. It was very exciting to find that restoring MTCH2 expression in flies reversed motor dysfunction and reduced tau accumulation in human neural progenitor cells in the lab.”

“Our findings support further exploration of MTCH2 for therapeutic purposes and highlight the value of a combined computational and experimental approach to uncover main genetic players in Alzheimer’s disease and other neurodegenerative conditions,” Botas said.

Other contributors to this work include co-first author Jiayang Li, as well as Megan Mair, Justin Moore, Katy Zhu, Akash Tarkunde, Bismark Amoh, Alma M. Perez, Arya Bhakare, Fangfei Guo, Joshua M. Shulman and Ismael Al-Ramahi. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and Baylor’s Center for Alzheimer’s and Neurodegenerative Disease.

This work was supported by NIH grants U01AG072439, R01AG074009 and F31NS129062.

The earthquake, which killed more than 23,000 people and left about 1.5 million people homeless, took place along the Motagua Fault, at the boundary between the North American and Caribbean tectonic plate boundary.

Severe ground shaking from the 1976 earthquake caused landslides and sediment-laden turbidity currents that can be seen clearly in cores taken from the lakebeds. Normally, researchers might expect that this shaking would produce the thinnest sediment deposits in lakes furthest away from an earthquake, since seismic waves weaken as they travel away from an earthquake epicenter.

But in the Guatemalan lakes, the cores with the thickest sediment traces of the earthquake occur at the end of the fault rupture, said Jonathan Obrist-Farner, a geologist at Missouri University of Science and Technology. “What we see is lakes that are actually the closest to the epicenter but just away from the rupture path have very thin deposits.”

Jeremy Maurer, a geophysicist also at Missouri University, suggested that the unusual pattern had in this case recorded the directivity of the 1976 shaking.

It’s not unusual for scientists to find evidence of past earthquakes in lake sediment cores, Maurer added, noting examples from New Zealand to Turkey that offer a glimpse at how far away a particular earthquake could have an impact.

“What hasn’t been done as much is looking at where these lakes are located in relationship to the fault,” said Maurer. “Are they off-axis or on-axis? Does the direction of the rupture have an effect on sediment deposits?”

When the U.S. Geological Survey collected field data after the 1976 earthquake, “they found, for example, adobe houses that were 10 kilometers south of the main rupture path that were still standing, yet those that were actually on the fault trace and towards the propagation direction all collapsed,” said Maurer. “I think there’s a lot of evidence that points to the directivity of the rupture and now we’re just looking at it sedimentologically from the lakes.”

The researchers began recovering and analyzing cores from the lakes in 2022. “We thought it would be a very interesting opportunity to not just look at the 1976 earthquake, but actually learn a little bit more about the paleoseismic history of the plate boundary, which we know very little of,” said Obrist-Farner, who is originally from Guatemala.

Although there was a brief rush of seismologists to the region after the 1976 earthquake, the impacts of a 36-year civil war and sparse instrumentation have left the plate boundary poorly monitored. Paleoseismic data like the lake records are important for building a more complete picture of the country’s seismic risk.

Last year Obrist-Farner’s team retrieved their largest cores yet from the lakes, with lengths of sediment that may represent up to four thousand years of lake history. Their initial analysis shows evidence of the 1816 earthquake of at least magnitude 7.5 that is known mostly from historical documents.

It depends, of course, on whether you’re making a hearty winter stew or getting ready to watch the Super Bowl.

Most scientists agree that categorizing an object — like thinking of a carrot as either a root vegetable or a party snack — is the job of the prefrontal cortex, the brain region responsible for reasoning and other high-level functions that make us smart and social. In that account, the eyes and visual regions of the brain are kind of like a security camera collecting data and processing it in a standardized way before passing it off for analysis.

However, a new study led by biomedical engineer and neuroscientist Nuttida Rungratsameetaweemana, an assistant professor at Columbia Engineering, shows that the brain’s visual regions play an active role in making sense of information. Crucially, the way it interprets the information depends on what the rest of the brain is working on.

If it’s Super Bowl Sunday, the visual system sees those carrots on a veggie tray before the prefrontal cortex knows they exist.

Published April 11 in Nature Communications, the study provides some of the clearest evidence yet that early sensory systems play a role in decision-making — and that they adapt in real-time. It also points to new approaches for designing AI systems that can adapt to new or unexpected situations.

Scientists at the Medical Research Council (MRC) Mitochondrial Biology Unit, University of Cambridge, have worked out the structure of this machine and shown how it operates like the lock on a canal to transport pyruvate — a molecule generated in the body from the breakdown of sugars — into our mitochondria.

Known as the mitochondrial pyruvate carrier, this molecular machine was first proposed to exist in 1971, but it has taken until now for scientists to visualise its structure at the atomic scale using cryo-electron microscopy, a technique used to magnify an image of an object to around 165,000 times its real size. Details are published today in Science Advances.

Dr Sotiria Tavoulari, a Senior Research Associate from the University of Cambridge, who first determined the composition of this molecular machine, said: “Sugars in our diet provide energy for our bodies to function. When they are broken down inside our cells they produce pyruvate, but to get the most out of this molecule it needs to be transferred inside the cell’s powerhouses, the mitochondria. There, it helps increase 15-fold the energy produced in the form of the cellular fuel ATP.”

Maximilian Sichrovsky, a PhD student at Hughes Hall and joint first author of the study, said: “Getting pyruvate into our mitochondria sounds straightforward, but until now we haven’t been able to understand the mechanism of how this process occurs. Using state-of-the-art cryo-electron microscopy, we’ve been able to show not only what this transporter looks like, but exactly how it works. It’s an extremely important process, and understanding it could lead to new treatments for a range of different conditions.”

Mitochondria are surrounded by two membranes. The outer one is porous, and pyruvate can easily pass through, but the inner membrane is impermeable to pyruvate. To transport pyruvate into the mitochondrion, first an outer ‘gate’ of the carrier opens, allowing pyruvate to enter the carrier. This gate then closes, and the inner gate opens, allowing the molecule to pass through into the mitochondrion.

“It works like the locks on a canal but on the molecular scale,” said Professor Edmund Kunji from the MRC Mitochondrial Biology Unit, and a Fellow at Trinity Hall, Cambridge. “There, a gate opens at one end, allowing the boat to enter. It then closes and the gate at the opposite end opens to allow the boat smooth transit through.”

Because of its central role in controlling the way mitochondria operate to produce energy, this carrier is now recognised as a promising drug target for a range of conditions, including diabetes, fatty liver disease, Parkinson’s disease, specific cancers, and even hair loss.

Pyruvate is not the only energy source available to us. Our cells can also take their energy from fats stored in the body or from amino acids in proteins. Blocking the pyruvate carrier would force the body to look elsewhere for its fuel — creating opportunities to treat a number of diseases. In fatty liver disease, for example, blocking access to pyruvate entry into mitochondria could encourage the body to use potentially dangerous fat that has been stored in liver cells.

Likewise, there are certain tumour cells that rely on pyruvate metabolism, such as in some types of prostate cancer. These cancers tend to be very ‘hungry’, producing excess pyruvate transport carriers to ensure they can feed more. Blocking the carrier could then starve these cancer cells of the energy they need to survive, killing them.

Previous studies have also suggested that inhibiting the mitochondrial pyruvate carrier may reverse hair loss. Activation of human follicle cells, which are responsible for hair growth, relies on metabolism and, in particular, the generation of lactate. When the mitochondrial pyruvate carrier is blocked from entering the mitochondria in these cells, it is instead converted to lactate.

Professor Kunji said: “Drugs inhibiting the function of the carrier can remodel how mitochondria work, which can be beneficial in certain conditions. Electron microscopy allows us to visualise exactly how these drugs bind inside the carrier to jam it — a spanner in the works, you could say. This creates new opportunities for structure-based drug design in order to develop better, more targeted drugs. This will be a real game changer.”

The research was supported by the Medical Research Council and was a collaboration with the groups of Professors Vanessa Leone at the Medical College of Wisconsin, Lucy Forrest at the National Institutes of Health, and Jan Steyaert at the Free University of Brussels.

Previous research indicates the rate of ischemic (clot-caused) stroke among adults 18-49 years old is increasing and propelled by a corresponding rise in cryptogenic strokes (strokes of unknown cause) in adults without traditional risk factors, including high blood pressure, smoking, obesity, high cholesterol and Type 2 diabetes.

“Up to half of all ischemic strokes in younger adults are of unknown causes, and they are more common in women. For effective prevention, careful and routine assessment of both traditional and nontraditional risk factors in younger people is critical,” said lead study author Jukka Putaala, M.D., Ph.D., M.Sc., head of the stroke unit at the Neurocenter, Helsinki University Hospital in Helsinki, Finland. “We should also carefully screen people after they have a stroke to prevent future strokes.”

Researchers analyzed data for more than 1,000 adults aged 18-49 in Europe, with a median age of 41 years. Half of the participants had experienced a cryptogenic ischemic stroke, while half had no history of stroke. The study examined the associations of 12 traditional risk factors, 10 nontraditional risk factors and five risk factors specific to women (such as gestational diabetes or pregnancy complications). Researchers also closely reviewed participants with a heart defect called patent foramen ovale (PFO), a hole between the heart’s upper chambers. A PFO is usually harmless yet is known to increase the odds of stroke. The study aimed to determine which risk factors contribute the most to unexplained strokes.

The analysis found:

• Traditional risk factors were more strongly associated with stroke in men and women without a PFO.
• In contrast, nontraditional risk factors, such as blood clots in the veins, migraine with aura, chronic kidney disease, chronic liver disease or cancer, were more strongly associated with stroke among study participants with a PFO.
• In those without a PFO, each additional traditional risk factor increased stroke risk by 41%, while each nontraditional risk factor increased stroke risk by 70%.
• Risk factors related to women also increased stroke risk by 70% independent of traditional and nontraditional risk factors.
• Among participants with a PFO, each traditional risk factor increased the risk of stroke by 18%. However, after considering individual demographic factors, such as age, sex and level of education, nontraditional risk factors more than doubled the odds of having an ischemic stroke.

Researchers also analyzed the study population’s attributable risk (determining how a disease would be impacted if a certain risk factor were eliminated). To calculate population-attributable risk, researchers analyzed each risk factor and their contribution to the increased risk separately and found:

• For strokes that occur without a PFO, traditional risk factors accounted for about 65% of the cases, nontraditional risk factors contributed 27% and risk factors specific to women made up nearly 19% of the cases.
• In contrast, for strokes associated with a PFO, traditional risk factors contributed about 34%, nontraditional risk factors accounted for 49% and female-specific risk factors represented about 22%.
• Notably, migraine with aura was the leading nontraditional risk factor associated with strokes of unknown origin, with a population-attributable risk of about 46% for strokes among people with a PFO and about 23% for those without a PFO, indicating a higher risk for people with PFO.

“We were surprised by the role of non-traditional risk factors, especially migraine headaches, which seems to be one of the leading risk factors in the development of strokes in younger adults,” Putaala said. “Our results should inform the health professional community to develop a more tailored approach to risk factor assessment and management. We should be asking young women if they have a history of migraine headaches and about other nontraditional risk factors.”

American Heart Association chair of the Clinical Cardiology (CLCD)/Stroke Women’s Health Science Committee, Tracy E. Madsen, M.D., Ph.D., FAHA, said, “This study is helpful because the authors present data by sex and age group. We know that stroke risk changes based on sex and age. For instance, recent data shows that younger women may have a higher risk of stroke than younger men. However, during middle age, men usually have a higher risk. Recognizing specific risks that affect women and those not commonly seen, such as migraine with aura and pregnancy complications as significant contributors to stroke risk in younger women, could change our approach to screening for these risks and educating our patients throughout their lives.” Madsen, who was not involved in the study, is also an associate professor, vice chair of research in emergency medicine and director of the EpiCenter at the Robert Larner, M.D. College of Medicine at the University of Vermont in Burlington, Vermont.

The study’s limitations include being an observational study, meaning that it was a review and analysis of existing health data on patients enrolled in another trial or database; therefore, this study’s findings cannot prove cause and effect. The study also relied on patient-reported risk factors, which may impact accuracy. In addition, 95% of participants were self-reported to be white adults of European descent, which limits the applicability of the findings to other populations.

Study details, background and design:

• The study included 523 adults aged 18-49 (median age 41 years; 47.3% female; 37.5% with PFO) who had suffered a cryptogenic ischemic stroke and 523 peers of similar age with no history of stroke.
• The purpose of the review was to evaluate traditional and nontraditional risk factors associated with an increased risk of cryptogenic ischemic stroke.
• Participants were enrolled in Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO) study at 19 centers in 13 European nations (Estonia, Finland, Germany, Greece, Italy, Lithuania, Netherlands, Norway, Portugal, Spain, Sweden, Turkey and the United Kingdom) between November 2013 and January 2022.

Constructed using 22 small pressure sensors and fueled by small solar panels on the tops of shoes, the system offers real-time health tracking based on how a person walks, a biomechanical process that is as unique as a human fingerprint.

This complex personal health data can then be transmitted via Bluetooth to a smartphone for quick and detailed analysis, said Jinghua Li, co-author of the study and an assistant professor of materials science and engineering at The Ohio State University.

“Our bodies carry lots of useful information that we’re not even aware of,” said Li. “These statuses also change over time, so it’s our goal to use electronics to extract and decode those signals to encourage better self health care checks.”

It’s estimated that at least 7% of Americans suffer from ambulatory difficulties, activities that include walking, running or climbing stairs. While efforts to manufacture a wearable insole-based pressure system have risen in popularity in recent years, many previous prototypes were met with low energy limitations and unstable performances.

To overcome the challenges of their precursors, Li and Qi Wang, the lead author of the study and a current PhD student in materials science and engineering at Ohio State, sought to ensure that their wearable is durable, has a high degree of precision when collecting and analyzing data, and can provide consistent and reliable power, said Li.

“Our device is innovative in terms of high resolution, spatial sensing, self-powering capability, and its ability to combine with machine learning algorithms,” she said. “So we feel like this research can go further based on the pioneering successes of this field.”

The study was recently published in the journal Science Advances.

This team’s system is also made unique through its use of AI. Using an advanced machine learning model, the wearable can recognize eight different motion states, including static ones like sitting and standing to more dynamic movements such as running and squatting.

Additionally, since the materials the insoles are made of are flexible and safe, the device, much like a smartwatch, is low-risk and safe for continuous use. For instance, after the solar cells convert sunlight to energy, that power is stored in tiny lithium batteries that don’t harm the user or affect daily activities.

Because of the distribution of sensors from toe to heel, the researchers could see how the pressure on parts of the foot is different in activities such as walking versus running.

During walking, pressure is applied sequentially from the heel to the toes, whereas during running, almost all sensors are subjected to pressure simultaneously. In addition, during walking, the pressure application time accounts for about half of the total time, while during running, it accounts for only about a quarter.

In health care, the smart insoles could support gait analysis to detect early abnormalities associated with foot pressure-related conditions (such as diabetic foot ulcers), musculoskeletal disorders (such as plantar fasciitis) and neurological conditions (such as Parkinson’s disease).

The new system also used machine learning to learn and classify different types of motion. That offers opportunities for personalized health management, including real-time posture correction, injury prevention and rehabilitation monitoring. Customized fitness training may also be a future use, the researchers said.

According to the study, these smart insoles showed no notable deterioration in performance after 180,000 cycles of compression and decompression, showing their long-term durability.

“The interface is flexible and quite thin, so even during repetitive deformation, it can remain functional,” said Li. “The combination of the software and hardware means it isn’t as limited.”

Researchers expect the technology will likely be available commercially within the next three to five years. Next steps to advance the work will be aimed at improving the system’s gesture recognition abilities, which, according to Li, will likely be helped with further testing on more diverse populations.

“We have so many variations among individuals, so demonstrating and training these fantastic capabilities on different populations is something we need to give further attention to,” said Li.

Other co-authors include Hui Guan, Chen Wang, Peiming Lei, Hongwei Sheng, Huasheng Bi, Jinkun Hu, Chenhui Guo, Yichuan Mao, Jiao Yuan, Mingjiao Shao, Zhiwen Jin and Wei Lan from Lanzhou University in China.

Urinary incontinence — the loss of bladder control — is a common condition, especially in older adults. Previous studies have stated that it can affect between 38% and 60% of women. The researchers aimed to find out whether urinary incontinence was linked to a decline in physical activity, which can lead to a host of health issues, including greater risk for cardiovascular disease.

In the study, the researchers — led by Lisa VanWiel, assistant professor at the University of Wisconsin-La Crosse who in April earned her doctorate in health and human physiology from Iowa — analyzed medical records over two years from more than 20,000 female patients in the Hartford Healthcare system in Connecticut. Of those patients, 5.4% reported through a questionnaire to have urinary incontinence. All patients were asked to rate their level of physical activity in the questionnaire.

The researchers found that the respondents with urinary incontinence did not report engaging in less physical activity than those who did not have the condition. But the team did find an association between patients with urinary incontinence and cardiovascular disease risk factors or events, such as dyslipidemia, type 2 diabetes, and stroke.

“There is an association between incontinence and cardiovascular disease (CVD) risk,” the study authors write. “Women should be screened for incontinence regularly as it may contribute to CVD risk, and women with CVD risk factors should be screened for undiagnosed incontinence.”

VanWiel is the study’s corresponding author. Co-authors from Iowa are Kara Whitaker, associate professor in the Department of Health and Human Physiology, who is VanWiel’s mentor; and Lucas Carr, associate professor in the Department of Health and Human Physiology. Other co-authors are Dale Bond, Yin Wu, Elena Tunitsky-Bitton, Paul Tulikangas, and Adam Steinberg, all from Hartford Hospital.

“People have been using FOXR2 activation as a clinical diagnostic for CNS neuroblastoma,” said corresponding author Jason Cheng-Hsuan Chiang, MD, PhD, St. Jude Department of Pathology. “But we unexpectedly saw it in a patient’s recurrent non-neuroblastoma tumor, which motivated us to look into other brain tumors.”

The researchers searched for and found FOXR2 activation using data from the St. Jude Cloud, which houses whole genome, whole exome and RNA sequencing data from St. Jude patients. In total, they identified 42 tumors with activated FOXR2 in 41 patients. Only 11 of the tumors were the expected CNS neuroblastoma. The other 31 were a mix of high-grade gliomas and other embryonal and rare tumors, indicating a large, previously undiscovered category of disease with implications for diagnosis, prognosis and treatment.

“When we looked at the clinical outcomes of the different types of tumors with FOXR2 activation, there was a pretty stark difference,” said co-first author Emily Hanzlik, MD, St. Jude Department of Pediatric Medicine. “The CNS neuroblastomas had an exceptionally good outcome when they were treated with multimodal therapy, whereas the other types of tumors in the cohort, the high-grade gliomas and the pineoblastomas, had pretty dismal outcomes.”

Those differences indicate that physicians should not use FOXR2 activation as an exclusive marker of CNS neuroblastoma since it can occur in other tumor types. “Hopefully, our findings can help guide patients to the most appropriate clinical care,” Chiang said.

Finding undetected mechanisms of FOXR2 activation in multiple brain tumor types

The underlying mechanisms of FOXR2 activation has gone unnoticed in brain tumors due to the difficulty in identifying them using standard molecular diagnostics. Still, the St. Jude scientists closely examined the clinical genomic data from the St. Jude Cloud to discover and better describe these hard-to-detect alterations.

“Now that we described these genomic events, hopefully, others will be able to detect them in their patients as well,” said co-first author Alexa Siskar, PhD, St. Jude Department of Pathology, who analyzed the genomic data.

“Our study highlights the importance of combining every piece of information we have for classifying a patient’s tumors, including molecular findings like DNA and RNA sequencing, histology and imaging,” Chiang added. “Only with a holistic view can we correctly understand a specific brain tumor and choose the best treatment approach for that patient.”

“Blood tests that detect biomarkers for Alzheimer’s disease and other dementias are emerging and as these tests are further developed, they are becoming important tools for understanding and diagnosing these conditions,” said study author Hannah Stocker, PhD, MPH, of Heidelberg University in Germany. “Our findings provide valuable insights into how age, sex, genetics and hormonal changes during menopause are linked to three biomarkers believed to influence a person’s risk of dementia.”

Researchers analyzed data from a larger 17-year study, comparing 513 people who developed dementia during the study to 513 people who remained free of dementia during that time. The participants had an average age of 64 at the start of the study.

Researchers took blood samples from participants three times during the study to measure levels of three biomarkers: neurofilament light chain proteins, glial acidic proteins and phosphorylated tau 181. Neurofilament light chain proteins are found in the blood when nerve cells are injured or die. Glial acidic proteins are released when cells work to repair injury. Phosphorylated tau 181 is linked to the buildup of amyloid proteins in the body, which occurs in Alzheimer’s disease.

Researchers then compared levels of the biomarkers in people with and without dementia in the following ways: over time as people aged; in male and female participants; in people with and without a gene linked to Alzheimer’s; and in female participants before and after menopause.

After adjusting for age, sex, and APOEe4, a genetic biomarker that indicates a strong risk of Alzheimer’s disease, researchers found that an older age was tied to higher levels of all three markers.

For neurofilament light chain proteins, people age 75 had an average of 25 picograms per milliliter (pg/ml) compared to people age 50 with an average of 10 pg/ml. For glial acidic proteins, people age 75 had an average of 140 pg/ml compared to people age 50 with an average of 45 pg/ml. For phosphorylated tau 181, people age 75 had an average of two to three pg/ml compared to people age 50 with an average of 0.5 to 1.5 pg/ml.

Researchers also found that female participants had higher levels of glial acidic proteins, while male participants had higher levels of neurofilament light chain proteins.

In addition, they found people who had the APOEe4 gene had higher levels of tau and glial acidic proteins.

Lastly, the study found that female participants who had not yet gone through menopause had higher levels of glial acidic proteins, which Stocker noted may be due to having higher levels of sex hormones. Stocker said previous studies have found a link between sex hormones and neuroinflammation.

“Gaining a better understanding of these biomarkers will help improve our ability to test for dementia in the future with simple blood tests,” said Stocker. “Our research underscores the need to further explore these biomarkers, including during menopause, in the development of dementia.”

A limitation of the study was that participants were of European descent, so the results may not be the same for other populations.

The study was supported by the German Alzheimer Forschung Initiative.

In a study published in the journal ACS Nano and supported by the National Institutes of Health, the research team showed that nanoparticles injected into the retina can successfully stimulate the visual system and restore vision in mice with retinal disorders. The findings suggest that a new type of visual prosthesis system in which nanoparticles, used in combination with a small laser device worn in a pair of glasses or goggles, might one day help people with retinal disorders to see again.

“This is a new type of retinal prosthesis that has the potential to restore vision lost to retinal degeneration without requiring any kind of complicated surgery or genetic modification,” said Jiarui Nie, a postdoctoral researcher at the National Institutes of Health who led the research while completing her Ph.D. at Brown. “We believe this technique could potentially transform treatment paradigms for retinal degenerative conditions.”

Nie performed the work while working in the lab of Jonghwan Lee, an associate professor in Brown’s School of Engineering and a faculty affiliate at Brown’s Carney Institute for Brain Science, who oversaw the work and served as the study’s senior author.

Retinal disorders like macular degeneration and retinitis pigmentosa affect millions of people in the U.S. and around the world. These conditions damage light-sensitive cells in the retina called photoreceptors — the “rods” and “cones” that convert light into tiny electric pulses. Those pulses stimulate other types of cells further up the visual chain called bipolar and ganglion cells, which process the photoreceptor signals and send them along to the brain.

This new approach uses nanoparticles injected directly into the retina to bypass damaged photoreceptors. When infrared light is focused on the nanoparticles, they generate a tiny amount of heat that activates bipolar and ganglion cells in much the same way that photoreceptor pulses do. Because disorders like macular degeneration affect mostly photoreceptors while leaving bipolar and ganglion cells intact, the strategy has the potential to restore lost vision.

In this new study, the research team tested the nanoparticle approach in mouse retinas and in living mice with retinal disorders. After injecting a liquid nanoparticle solution, the researchers used patterned near-infrared laser light to project shapes onto the retinas. Using a calcium signal to detect cellular activity, the team confirmed that the nanoparticles were exciting bipolar and ganglion cells in patterns matched the shapes projected by the laser.

The experiments showed that neither the nanoparticle solution nor the laser stimulation caused detectable adverse side effects, as indicated by metabolic markers for inflammation and toxicity. Using probes, the researchers confirmed that laser stimulation of the nanoparticles caused increased activity in the visual cortices of the mice — an indication that previously absent visual signals were being transmitted and processed by the brain. That, the researchers say, is a sign that vision had been at least partially restored, a good sign for potentially translating a similar technology to humans.

For human use, the researchers envision a system that combines the nanoparticles with a laser system mounted in a pair of glasses or goggles. Cameras in the goggles would gather image data from the outside world and use it to drive the patterning of an infrared laser. The laser pulses would then stimulate the nanoparticles in people’s retinas, enabling them to see.

The approach is similar to one that was approved by the Food and Drug Administration for human use a few years ago. The older approach combined a camera system with a small electrode array that was surgically implanted in the eye. The nanoparticle approach has several key advantages, according to Nie.

For starters, it’s far less invasive. As opposed to surgery, “an intravitreal injection is one of the simplest procedures in ophthalmology,” Nie said.

There are functional advantages as well. The resolution of the previous approach was limited by the size of the electrode array — about 60 square pixels. Because the nanoparticle solution covers the whole retina, the new approach could potentially cover someone’s full field of vision. And because the nanoparticles respond to near-infrared light as opposed to visual light, the system doesn’t necessarily interfere with any residual vision a person may retain.

More work needs to be done before the approach can be tried in a clinical setting, Nie said, but this early research suggests that it’s possible.

“We showed that the nanoparticles can stay in the retina for months with no major toxicity,” Nie said of the research. “And we showed that they can successfully stimulate the visual system. That’s very encouraging for future applications.”

The research was funded by the National Institutes of Health’s National Eye Institute (R01EY030569), the China Scholarship Council scholarship, the Saudi Arabian Cultural Mission scholarship, and South Korea’s Alchemist Project Program (RS-2024-00422269). Co-authors also include Professor Kyungsik Eom from Pusan National University, Brown Professor Tao Lui, as well as Brown students Hafithe M. Al Ghosain, Alexander Neifert, Aaron Cherian, Gaia Marie Gerbaka, and Kristine Y. Ma.

“I was very surprised by our findings. As far as I know, no one has previously discovered molecules like these bile acids that can interact with the androgen receptor in this way,” said co-senior author Dr. Chun-Jun Guo, an associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a scientist at the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

Dr. David Artis, director of the Jill Roberts Institute and the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor in Immunology, and Dr. Nicholas Collins, assistant professor of immunology in medicine, both at Weill Cornell Medicine, are co-senior authors of the study. Drs. Wen-Bing Jin, formerly a postdoctoral associate, and Leyi Xiao, a current postdoctoral associate in Dr. Guo’s lab, are the co-first authors of the study.

Primary bile acids are produced by the liver and released into the gut, where diverse groups of bacteria work together to modify their chemical structures. Researchers suspected these gut microbial modifications could affect how bile acids function and interact with human signaling pathways. To test this idea, the investigators set out to explore the full extent of bacterial modifications to bile acids and understand how these changes affect their biological roles.

It turns out that gut bacteria have remarkable potential to transform bile acids. “We discovered more than fifty different bile acid molecules modified by the microbiota — many of which had never been identified before,” said Dr. Guo, who is also the Halvorsen Family Research Scholar in Metabolic Health at Weill Cornell Medicine.

These newly uncovered structures could open the door to new biological insights-particularly in how they interact with human receptors that sense bile acids. Given that bile acids share the same steroid backbone as sex hormones like testosterone and estrogen, the structural resemblance raised an intriguing question for the researchers: could these microbially modified bile acids also interact with sex hormone receptors in the body? “It seemed like a wild idea at the time,” Dr. Guo said.

Surprisingly, the answer appears to be yes. When the investigators tested the 56 altered bile acids that they discovered, they found one that antagonizes the androgen receptor — a molecule that interacts with sex hormones to regulate many aspects of human development. When they tested an additional 44 microbiota-modified bile acids that had previously been characterized, the team found three more that act similarly. This unexpected finding raised exciting new questions for the team: which specific cells were affected by the altered bile acids — and what biological functions these modified molecules might influence.

In addition to its role in development, the androgen receptor is also found in certain immune cells, including CD8 T cells. Previous studies have shown that blocking this receptor can enhance the ability of these immune cells to fight tumors. The investigators wondered whether the bile acids could replicate this effect by binding to and inactivating the androgen receptor. To test the idea, they treated mice with bladder cancer using these compounds — and observed a potent anti-tumor response. Further analysis revealed that the modified bile acids specifically boosted the activity of T cells — the immune cells best equipped to kill cancer.

“Our results suggest that these altered bile acids help shrink tumors by enhancing T cells’ ability to survive within the tumor and destroy cancer cells,” Dr. Collins said.

“This study highlights the profound and evolving partnership between the human host and its gut microbiota, emphasizing the importance of integrating microbial activity into the design of future cancer therapies.” Dr. Artis said. “It also exemplifies the power of multidisciplinary collaboration in driving microbiome science toward deeper molecular understanding of host-microbe interactions.”

This discovery opens up exciting new possibilities for boosting tumor-killing immune response. Potential approaches include introducing targeted gut microbes to cancer patients before therapy, or directly administering the anti-cancer bile acids as part of treatment, the researchers suggested. Although these compounds still need to be tested in humans, the team is optimistic that bile acids could eventually become a key component of effective cancer therapies — especially when combined with existing treatments for a more powerful impact.

However, important questions remain. For example, how might diet — which is known to influence microbiota composition — affect the production of these bile acids? And beyond their anti-cancer properties, what physiological effects might these androgen receptor-blocking bile acids have in healthy individuals? The team is now focused on precisely controlling the synthesis and release of these beneficial molecules using advanced techniques to genetically engineer gut commensal bacteria, aiming to understand the broader physiological impact in the host initiated by these androgen blocking, microbiota-derived bile acids.

It is often thought that the effects of exercise are short-lived, and a break from the gym for just a few weeks can cause stress over muscle loss for some people. However, the research from the University of Jyväskylä has shown that this stress is partly unnecessary, as the effects of resistance training persist in muscles for up to two months and the gains are fast when training is started again after the break. But what mechanisms and changes at the cellular and molecular levels explain muscle memory? This is what the researchers investigated by studying the quantities of thousands of muscle proteins from muscle.

In the study, ten weeks of resistance training was followed by a break of the same length and then followed by another ten weeks of resistance training. Using the proteomics method, it was possible to simultaneously study the quantities of over 3,000 muscle proteins using advanced mass spectrometry equipment.

Training gets encoded into muscle proteins

The study found two types of change profiles in muscle proteins.

Some proteins changed as a result of training, returned to their pre-training state during the break, and changed again during the new training period similarly to the first training period. These included proteins related to aerobic metabolism.

Another group of proteins changed as a result of training and remained changed during the break and after the new training period. Among these proteins were several calcium-binding proteins, such as calpain-2, whose gene has recently been identified to retain a memory trace even after a training break.

“At the level of the number of muscle nuclei and the memory traces of genes, that is, epigenetics, long-term responses that persist even after a break and possibly explain ‘muscle memory’ have previously been observed,” says the lead researcher, Professor Juha Hulmi from the Faculty of Sport and Health Sciences.

“Now, for the first time, we have shown that muscles ‘remember’ previous resistance training at the protein level for at least two and a half months.”

“So, even though muscles eventually shrink back to their original size during a long training break, a memory trace of previous training remains in the muscles. This can make it easier to start training again,” explains Hulmi.

The research is part of a larger TraDeRe research project funded by the Research Council of Finland and led by Associate Professor of Coaching Science Juha Ahtiainen (PI) in collaboration with Juha Hulmi (Co-PI).

The data collection was carried out at the Faculty of Sport and Health Sciences, University of Jyväskylä. The participants were young adult and middle-aged Finnish men and women who were physically quite active but had no previous experience of systematic resistance training. Proteomic analyses were conducted on 116 muscle samples at the University of Helsinki in the laboratory of research director Markku Varjosalo.

The study has been published in the Journal of Physiology. The study was funded by Renaissance Periodization, Rehabilitation Foundation Peurunka, the Research Council of Finland and Suomen Urheilututkimussäätiö.

The consequences of heavy drinking — which is defined as four or more drinks per occasion for women and five or more for men — are felt throughout the college community. These include blackouts, academic underperformance and interpersonal problems. Then there are the secondhand consequences for students who don’t drink, such as interrupted study, aggression, assault and having to care for intoxicated peers.

In a new study, researchers from the Brown University School of Public Health developed and tested an intervention called Counter-Attitudinal Advocacy (CAA). CAA involves advocating for a position that contradicts a personally held attitude or behavior. In this context, CAA targets positive perceptions of heavy drinking and the belief that alcohol is an essential part of college life.

In randomized controlled trials at two sites with 585 college students, researchers compared CAA to the well-established Personalized Normative Feedback (PNF) to evaluate their effectiveness in decreasing drinks per week, peak blood alcohol concentration and alcohol-related consequences relative to a control group. Researchers focused on drinks per week, a standard measure given the irregular drinking patterns of college students, who often veer between heavy drinking and alcohol-free days.

Ultimately, they worked on answering two main questions:

• Does CAA effectively reduce alcohol-related risk compared to our control?
• How does CAA compare to PNF, which has proven to be an effective low-cost way of reducing alcohol consumption among high-risk students?

Here’s what they found: Participants who received PNF reported significantly fewer drinks per week than the control group, while those who received CAA reported significantly fewer consequences. CAA had a harm reduction effect on consequences — its intended focus — but not on consumption of alcohol, which it did not target.

“Both interventions take just 5-10 minutes, making them ideal for broad prevention efforts,” said Kate Carey, co-lead investigator of the study and professor of behavioral and social sciences at Brown. “Our results showed that PNF did reduce alcohol consumption, as expected. But CAA specifically reduced the number of problems participants reported due to drinking. So, while they had different effects, they were complementary — giving us another useful tool for harm reduction.”

Carey explained that PNFs show participants how their drinking habits stack up against those of their peers, often exposing a common misconception that others drink more than they actually do: an insight that can help them adjust their own behavior. In contrast, CAA encourages participants to reflect on why it is a good idea to avoid alcohol-related problems, such as passing out or taking excessive risks, and to identify specific actions they can take to minimize these risks.

“Instead of directly telling students what to do, we prompt them to generate their own strategies,” Carey said. “This makes the intervention personalized and non-confrontational. Unlike some interventions that make people feel defensive about their drinking, CAA frames the discussion more broadly: ‘Why is it good for young people to avoid problems?’ rather than ‘You personally need to change.'”

As participants responded to these prompts, a research assistant or peer asked them to explain their written responses. Carey noted that this act of verbal reinforcement likely strengthened the intervention’s effect, since we tend to feel more committed to our viewpoints when we share them publicly.

It’s important to have a variety of brief interventions, since no single approach works for everyone, Carey stressed. Offering multiple evidence-based options increases the chances of reaching more people who are undergoing a period of heightened risk.

The research team, which includes co-primary investigators Angelo DiBello associate professor of applied and professional psychology at Rutgers University and Clayton Neighbors, professor of social psychology at the University of Houston, are encouraged that CAA provides another effective tool — especially for those who may not respond to PNF.

Authors Maria Marco, professor with the Department of Food Science and Technology, and Lei Wei, a postdoctoral researcher in Marco’s lab, looked at what happens during fermentation — specifically, how the metabolites in sauerkraut compared to those in raw cabbage.

Researchers tested whether sauerkraut’s nutrients could help protect intestinal cells from inflammation-related damage. The study compared raw cabbage, sauerkraut and the liquid brine left behind from the fermentation process. The sauerkraut samples included both store-bought products and fermented cabbage made in the lab.

They found that sauerkraut helped maintain the integrity of intestinal cells, while raw cabbage and brine did not. Marco said that there was also no noticeable difference between grocery store sauerkraut and the lab-made version.

“Some of the metabolites we find in the sauerkraut are the same kind of metabolites we’re finding to be made by the gut microbiome, so that gives us a little more confidence that this connection we found between the metabolites in sauerkraut and good gut health makes sense,” Marco said. “It doesn’t matter, in a way, if we make sauerkraut at home or we buy it from the store; both kinds of sauerkraut seemed to protect gut function.”

Digestive benefits

Chemical analysis shows that fermentation changes cabbage’s nutritional profile, increasing beneficial metabolites such as lactic acid, amino acids and plant-based chemicals linked to gut health. These changes may explain why fermented foods are often associated with digestive benefits.

Marco said she and Wei identified hundreds of different metabolites produced during fermentation and are now working to determine which ones play the biggest role in supporting long-term gut health.

“Along with eating more fiber and fresh fruits and vegetables, even if we have just a regular serving of sauerkraut, maybe putting these things more into our diet, we’ll find that can help us in the long run against inflammation, for example, and make our digestive tract more resilient when we have a disturbance,” Marco said.

Fermented vegetables and foods are already a staple in many diets, but this research suggests they could be more than just a flavorful side dish. Marco said the next step is to conduct human trials to see if the gut-protective metabolites found in sauerkraut can have the same positive effects when included in everyday diets, as was shown in the lab.

“A little bit of sauerkraut could go a long way,” she said. “We should be thinking about including these fermented foods in our regular diets and not just as a side on our hot dogs.”

This research was funded by a grant from the California Department of Food and Agriculture, as well as a Jastro Shields Graduate Research Award from the UC Davis College of Agricultural and Environmental Sciences.

Virginia Tech researchers have gained a better understanding of this insidious virus by studying its rodent hosts in North America. Using National Science Foundation data, they found three hotspots of hantavirus circulation in wildlife — Virginia, Colorado, and Texas — and identified 15 rodent species as carriers, including six species that had not previously been identified as hosts of the virus.

The details of their study was published in Ecosphere.

“This project is timely because hantavirus is considered an emerging disease of pandemic potential with symptoms that resemble severe COVID-19 infections,” said Paanwaris Paansri, a Ph.D. student in the Department of Fish and Wildlife Conservation and co-author of the study.

Hantaviruses are a family of viruses that have been identified in regions all over the globe and can reach mortality rates similar to other diseases of high concern, such as nipah and Ebola. In Asia, hemorrhagic fever with renal syndrome is caused by the Hantaan virus, in Europe that syndrome is caused by the Dobrava-Belgrade virus, and in North and South America, hantavirus pulmonary syndrome is caused by Sin Nombre virus and Andes virus — all hantaviruses. Sin Nombre virus was first discovered in New Mexico in 1993.

Little is known about the ecology of hantaviruses in wildlife except that the pathogen is spread to humans by inhalation of aerosolized excreta, urine, or saliva from asymptomatic rodent hosts, and it can be fatal in humans.

The Virginia Tech team used data from the National Science Foundation’s National Ecological Observatory Network program to gain a better understanding of hantavirus circulation in its sylvatic cycle — the pathogen’s life cycle in wildlife — by examining the environmental influences and geographical distribution of the rodent hosts. The program collected and tested 14,004 blood samples from 49 species at 45 field sites across the United States from 2014-19.

“In North America, Peromyscus maniculatus, the deer mouse, is the most common carrier but our study also revealed that other rodent species have a higher prevalence of hantavirus, which changes the current paradigm in hantavirus circulation in wildlife,” said Paansri, whose mentor Associate Professor Luis E. Escobar, led the study and is an affiliate with the Fralin Life Sciences Institute. “This new information is expected to help us understand where and when hantavirus is most likely to occur, which is crucial for predicting outbreaks and informing public health officials.”

The discovery of six new rodent species of hantavirus hosts is significant. Some of these newly discovered hosts inhabit regions where traditional hosts, such as the deer mouse or the white-footed mouse (Peromyscus leucopus), are absent, meaning they could be potential reservoirs of the virus in new or overlooked areas.

“This expands our understanding of the basic biology of the virus and shows that the virus is more adaptable than previously believed,” Paansri said. “This has direct implications for surveillance strategies and risk assessments and can help explain some cases of hantavirus in humans where the main reservoir is absent or rare.”

In addition to expanding the known host species, the researchers were able to gain a better understanding of seasonal trends and effects of seasonal weather shifts. For example, warmer winters and increased precipitation can increase rodent populations and drier conditions can facilitate the generation of contaminated dust containing particulates from rodent excrement and saliva, increasing the risk of transmission to humans.

“Climate change can cause population increases or distributional shifts of rodents, altering the epidemiology of hantavirus,” Paansri said. “These fluctuations can lead to more frequent rodent-human interactions and increase the chance of spillover. We found some evidence that rodent demography and hantavirus prevalence can be predicted months in advance.”

The actual number of human cases of hantavirus infections is largely unknown, according to Paansri, because many infections remain silent, meaning the infected individual may not develop any symptoms or the symptoms could mirror other diseases, such as the common cold or influenza.

The researchers plan to further explore the extent to which climatic variations influence hantavirus transmission in wildlife and in humans..

“We believe that many lessons learned from this study can be generalized to other wildlife diseases, considering that their distribution is global,” Paansri said.

Abdelghafar Alkishe, a Virginia Tech 2022-23 presidential postdoctoral fellow, also worked on this study.

In the study, published Apr. 11 in Nature Methods, the researchers benchmarked the cancer-detection performance of a new commercial sequencing platform from Ultima Genomics. They demonstrated that a low-cost platform such as this one enables a very high “depth” of coverage — a measure of the sequencing data quality — allowing investigators to detect extremely low concentrations of circulating tumor DNA. Adding an error-correcting method greatly improved the accuracy of the technique.

“We’re now entering an era of low-cost DNA sequencing, and in this study, we took advantage of that to apply whole-genome sequencing techniques that in the past would have been considered wildly impractical,” said senior author Dr. Dan Landau, the Bibliowicz Family Professor of Medicine, and a member of the Englander Institute for Precision Medicine and the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, and a core faculty member of the New York Genome Center.

Blood-test-based “liquid biopsy” technology for early cancer detection and monitoring of cancer burden in patients could revolutionize cancer care. However, sensitively and accurately identifying the mutational signatures of cancer, just from tiny concentrations of tumor DNA in blood samples, has involved major challenges. The Landau laboratory for most of the past decade has been working to overcome these challenges using methods based on whole-genome sequencing — not just targeted sequencing of stretches of DNA where mutations are expected. In a study published last year, they showed that they could reliably detect advanced melanoma and lung cancer from patient blood samples, even without access to sequence data from tumor samples.

In the new study, they took their approach a step further. First, they showed that the low cost of a new sequencing platform enables a depth of whole-genome sequencing that would have been prohibitively expensive with older technology. Using that platform alone, and having the known mutational patterns in patient tumors as a guide, they were able to detect tumor DNA in patient blood samples at concentrations in the part per million range. All samples in the study were collected after obtaining informed consent from the patients.

Next, the team enhanced the accuracy of this approach with an error-correction method that makes use of the redundant information in natural two-stranded DNA. They showed that the combined technique has extremely low error rates, making it feasible in principle to use on blood samples without also needing access to patient tumors.

Collaborating with other research teams, the researchers demonstrated the potential of this high-sensitivity, low-error approach by using it to detect and assess very low cancer levels in patients with bladder cancer and melanoma from blood samples alone.

“This collaboration allowed us to analyze circulating tumor DNA from patients with bladder cancer and identify the distinct mutational signatures that my lab has extensively studied,” said Dr. Bishoy M. Faltas, chief research officer of the Englander Institute for Precision Medicine and associate professor of medicine and of cell and developmental biology at Weill Cornell Medicine. Dr. Faltas is also a urologic oncologist at NewYork-Presbyterian/Weill Cornell Medical Center. “Incorporating these signatures into the analysis significantly increased the sensitivity of circulating tumor DNA detection.”

“We were able, for example, to see increases in circulating tumor DNA levels after treatment in patients with cancers that progressed or recurred, and declines in those levels in patients whose cancers had full or partial responses,” said first author Dr. Alexandre Cheng, a postdoctoral researcher in the Landau laboratory during the study.

“These results allow us to think about a future in which we can detect and track cancer from blood tests alone,” said Dr. Landau, who is also an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.

Autoimmune diseases are often chronic conditions that affect up to ~15 million people in the U.S. and up to 12% of the global population. CAR-T cell therapy has demonstrated curative potential in select autoimmune diseases by creating a system-wide immune ‘reset’, improving a patient’s quality of life, and reducing the need for life-long immune suppressants. However, conventional CAR-T cell therapies require lymphodepletion — a chemotherapy procedure used to eliminate existing immune cells to ensure the CAR-T cells can effectively expand. Further, this procedure can lead to increased risk of infection and severe side effects. CLBR001 + SWI019 was designed to avoid these issues by eliminating the need for lymphodepletion, reducing side effects and potentially making treatment accessible to a broader patient population.

“Patients with chronic autoimmune diseases need curative options that do not require life-long immunosuppressive therapy to manage their condition,” says Travis Young, vice president of biologics at Calibr-Skaggs. “Our CLBR001 + SWI019 cell therapy has the potential to transform the treatment paradigm for patients by eliminating chemotherapy-associated risks.”

Calibr-Skaggs’ Chief Medical Officer Chan Beals says, “Successfully establishing safety and efficacy of CLBR001 + SWI019 for conditions like lupus and rheumatoid arthritis could pave the way for broader therapeutic use in other autoimmune diseases, offering new hope to many more patients in the future.”

Patient enrollment for the clinical trial is anticipated to begin soon.

About CLBR001 + SWI019 Switchable CAR-T

Calibr-Skaggs’ CLBR001 + SWI019 switchable CAR-T cell therapy differs from conventional CAR-T approaches by leveraging two components, a sCAR-T cell (CLBR001) and a protein-based biologic “switch” (SWI019) that targets CD19-positive B cells. CLBR001 + SWI019 has already demonstrated promising results in treating patients with B cell malignancies, with the ability to shorten the duration of adverse effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and preclinical work has demonstrated the unique ability to work without lymphodepletion. In early-stage trials, CLBR001 cells expanded in patients to higher levels in peripheral blood compared to approved CAR-T cell products, with robust persistence.

Researchers from the Wellcome Sanger Institute and their collaborators used whole genome sequencing to study when BCR::ABL1 — an abnormal fusion of the different genes called BCR and ABL1, which is known to cause chronic myeloid leukaemia. The team investigated when BCR::ABL1 first arises in a blood cell and how quickly these cells with this genetic change then multiply and expand to lead to a diagnosis of a type of leukaemia.

The research, published today (9 April) in Nature, contributes to the scientific understanding of how strong this abnormal fusion gene is in its ability to drive cancer.

Chronic myeloid leukaemia (CML) is a cancer of the bone marrow and blood. CML is caused by a rearrangement of genetic material between two chromosomes. In those with CML, part of the ABL1 gene from chromosome 9 is fused with the BCR gene from chromosome 22. This creates an abnormal fusion gene called BCR::ABL1 on chromosome 22, also known as the Philadelphia chromosome.

However, despite its well-understood role in CML, little is known about the evolution of this fusion gene, the rate at which cells with BCR::ABL1 start to multiply, and how this contributes to disease progression.

In a new study, researchers from the Sanger Institute used DNA sequencing to analyse over 1,000 whole genomes of single blood cells from nine people with CML, ranging from 22 to 81 years of age. The researchers then used the genetic changes identified in these genomes to study how the cells were ancestrally related to one another. This is akin to creating family trees of cells — known as phylogenetic trees — which allowed the team to look back in the past to explore how the tumour cells grew over time and exactly when the abnormal fusion of the two genes occurred to start off the cancer growth.

The phylogenetic trees from CML patients showed that the BCR::ABL1 fusion gene typically appeared three to 14 years before diagnosis. Once this fusion occurred, the tumour clones — tumour cells that are genetically identical — grew very quickly, sometimes in excess of 100,000 per cent growth annually, suggesting the fusion gene has a uniquely strong ability to drive the disease. Interestingly, this rapid growth is substantially faster than the growth rates of other blood cancers and solid tumours, which tend to develop more slowly with multiple genetic changes accumulating over many decades. Not only was the rapid growth of the tumour compared to other cancers unusual, but that this growth was driven by just one single genetic variation, whereas most other cancers require multiple genetic changes to accumulate before the cancer arises.

The researchers also discovered that age impacts tumour growth rates, with younger patients showing much higher rates at which cancerous cells with the fusion gene multiply compared to older patients. The study also found that patients with faster-growing CML were less likely to respond well to tyrosine kinase inhibitors (TKIs) — the standard treatment for CML. With one in five patients not responding to TKIs, this study has implications for considering cancer cell growth rates in a clinical setting. However, the researchers note that further studies in larger patient cohorts are needed to validate this.

To investigate whether people could carry BCR::ABL1 without showing symptoms, the researchers also analysed sequencing data and health records from over 200,000 participants from the USA-based “All of Us” cohort. They showed that almost all individuals with BCR::ABL1 were later diagnosed with a blood disorder, and so they suggest that expansion of BCR::ABL1 clones without developing subsequent symptoms is unlikely.

Overall, the results show the uniquely strong ability of the BCR::ABL1 fusion gene to drive growth of cancerous cells in CML, and that variation in these growth rates between patients may be useful in the future clinical setting to better predict patient responses to treatment.

Dr Aleksandra Kamizela, co-first author of the study, resident doctor at the Lister Hospital, Stevenage and soon Addenbrooke’s Hospital, Cambridge, said: “In a clinical setting, healthcare professionals will perform a reverse transcription polymerase chain reaction (RT-PCR) test, a type of blood test, to measure a patient’s response to CML treatment. However, they are not able to routinely see differences in the genetic cause of CML in patients at the DNA level, which we have been able to highlight in our study. Our findings also provide a rationale to look at the rate of cancer growth more closely in future studies in order to understand if we can use such information in a clinical setting.”

Dr Jyoti Nangalia, senior author of the study, haematologist at the University of Cambridge and Group Leader at the Wellcome Sanger Institute, said: “What our study suggests is that chronic myeloid leukaemia is an outlier compared to other cancers — both solid tumours and other blood cancers. We have shown that chronic myeloid leukaemia cells undergo incredibly rapid growth within a few years to a decade before diagnosis, whereas for most cancers, the timeline from start to clinical presentation is several decades. This work paves the way to understanding how we might optimise treatment for those patients that currently respond poorly to treatment.”

The digital twin was trained on large datasets of brain activity collected from the visual cortex of real mice as they watched movie clips. It could then predict the response of tens of thousands of neurons to new videos and images.

Digital twins could make studying the inner workings of the brain easier and more efficient.

“If you build a model of the brain and it’s very accurate, that means you can do a lot more experiments,” said Andreas Tolias, PhD, Stanford Medicine professor of ophthalmology and senior author of the study published April 10 in Nature. “The ones that are the most promising you can then test in the real brain.”

The lead author of the study is Eric Wang, PhD, a medical student at Baylor College of Medicine.

Beyond the training distribution

Unlike previous AI models of the visual cortex, which could simulate the brain’s response to only the type of stimuli they saw in the training data, the new model can predict the brain’s response to a wide range of new visual input. It can even surmise anatomical features of each neuron.

The new model is an example of a foundation model, a relatively new class of AI models capable of learning from large datasets, then applying that knowledge to new tasks and new types of data — or what researchers call “generalizing outside the training distribution.”

(ChatGPT is a familiar example of a foundation model that can learn from vast amounts of text to then understand and generate new text.)

“In many ways, the seed of intelligence is the ability to generalize robustly,” Tolias said. “The ultimate goal — the holy grail — is to generalize to scenarios outside your training distribution.”

Mouse movies

To train the new AI model, the researchers first recorded the brain activity of real mice as they watched movies — made-for-people movies. The films ideally would approximate what the mice might see in natural settings.

“It’s very hard to sample a realistic movie for mice, because nobody makes Hollywood movies for mice,” Tolias said. But action movies came close enough.

Mice have low-resolution vision — similar to our peripheral vision — meaning they mainly see movement rather than details or color. “Mice like movement, which strongly activates their visual system, so we showed them movies that have a lot of action,” Tolias said.

Over many short viewing sessions, the researchers recorded more than 900 minutes of brain activity from eight mice watching clips of action-packed movies, such as Mad Max. Cameras monitored their eye movements and behavior.

The researchers used the aggregated data to train a core model, which could then be customized into a digital twin of any individual mouse with a bit of additional training.

Accurate predictions

These digital twins were able to closely simulate the neural activity of their biological counterparts in response to a variety of new visual stimuli, including videos and static images. The large quantity of aggregated training data was key to the digital twins’ success, Tolias said. “They were impressively accurate because they were trained on such large datasets.”

Though trained only on neural activity, the new models could generalize to other types of data.

The digital twin of one particular mouse was able to predict the anatomical locations and cell type of thousands of neurons in the visual cortex as well as the connections between these neurons.

The researchers verified these predictions against high-resolution, electron microscope imaging of that mouse’s visual cortex, which was part of a larger project to map the structure and function of the mouse visual cortex in unprecedented detail. The results of that project, known as MICrONS, was published simultaneously in Nature.

Opening the black box

Because a digital twin can function long past the lifespan of a mouse, scientists could perform a virtually unlimited number of experiments on essentially the same animal. Experiments that would take years could be completed in hours, and millions of experiments could run simultaneously, speeding up research into how the brain processes information and the principles of intelligence.

“We’re trying to open the black box, so to speak, to understand the brain at the level of individual neurons or populations of neurons and how they work together to encode information,” Tolias said.

In fact, the new models are already yielding new insights. In another related study, also simultaneously published in Nature, researchers used a digital twin to discover how neurons in the visual cortex choose other neurons with which to form connections.

Scientists had known that similar neurons tend to form connections, like people forming friendships. The digital twin revealed which similarities mattered the most. Neurons prefer to connect with neurons that respond to the same stimulus — the color blue, for example — over neurons that respond to the same area of visual space.

“It’s like someone selecting friends based on what they like and not where they are,” Tolias said. “We learned this more precise rule of how the brain is organized.”

The researchers plan to extend their modeling into other brain areas and to animals, including primates, with more advanced cognitive capabilities.

“Eventually, I believe it will be possible to build digital twins of at least parts of the human brain,” Tolias said. “This is just the tip of the iceberg.”

Researchers from the University Göttingen and the Allen Institute for Brain Science contributed to the work.

The study received funding from the Intelligence Advanced Research Projects Activity, a National Science Foundation NeuroNex grant, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke (grant U19MH114830), the National Eye Institute (grant R01 EY026927 and Core Grant for Vision Research T32-EY-002520-37), the European Research Council and the Deutsche Forschungsgemeinschaft.

AML patients are often treated using allogeneic hematopoietic stem cell transplantation (allo-HCT), where they receive stem cells from a donor. Unfortunately, despite advancements with allo-HCT, many AML patients relapse.

In a recent article published in Nature Cancer, a multi-institutional research team led by The University of Osaka describes how a molecule called HLA-DRB1 can be used as a target for chimeric antigen receptor (CAR)-based therapy for AML. In CAR-based therapy, T cells are engineered to target and kill cells that express a specific molecule. CAR T cells have been highly successful in individuals with B cell leukemia/lymphoma and multiple myeloma (MM). However, most of the CAR T cell targets currently in clinical trials for AML are also expressed in normal cell types, leading to potential toxicity.

“In our previous work in MM, we screened monoclonal antibodies (mAbs) to identify any that could react with human MM samples but not with normal blood cells,” says Shunya Ikeda, lead author of the study. “We aimed to use that same strategy to find AML-specific antigens.”

The team began screening thousands of mAbs raised against AML cells, narrowing this list down to 32 that bind specifically to AML cells. One mAb, named KG2032, clearly bound to AML cells in over 50% of patient samples tested. Using a sequencing strategy, the researchers determined that KG2032 bound to HLA-DRB1.

“Interestingly, we found that KG2032 reacted with a specific HLA-DRB1 subset in which the protein has an amino acid other than aspartic acid in the 86^th position,” explains Naoki Hosen, senior author of the article. “KG2032 would therefore only be reactive to AML cells in individuals with mismatched HLA-DRB1, meaning the patient carries this amino acid residue but the allo-HCT donor does not.”

This finding indicates that HLA-DRB1 can be a potential target in treating certain patients with AML who have relapsed after allo-HCT.

The team then engineered KG2032 CAR T cells without the reactive HLA-DRB1 allele to test this finding. The KG2032 CAR T cells displayed strong and specific anti-AML effects in vitro with cell culture experiments, as well as in vivo with a mouse model. The treated mice did not display any overt signs of toxicity. Engineered cord blood-derived CAR natural killer (NK) cells showed similar results.

Overall, these very promising findings indicate that KG2032-derived CAR T or NK cells may be a lifesaving intervention for AML patients who have relapsed following allo-HCT. Clinical trials are currently being planned for both cell types.

Large language models (LLMs) like ChatGPT could streamline this process, but enabling an LLM to understand and reason about the atoms and bonds that form a molecule, the same way it does with words that form sentences, has presented a scientific stumbling block.

Researchers from MIT and the MIT-IBM Watson AI Lab created a promising approach that augments an LLM with other machine-learning models known as graph-based models, which are specifically designed for generating and predicting molecular structures.

Their method employs a base LLM to interpret natural language queries specifying desired molecular properties. It automatically switches between the base LLM and graph-based AI modules to design the molecule, explain the rationale, and generate a step-by-step plan to synthesize it. It interleaves text, graph, and synthesis step generation, combining words, graphs, and reactions into a common vocabulary for the LLM to consume.

When compared to existing LLM-based approaches, this multimodal technique generated molecules that better matched user specifications and were more likely to have a valid synthesis plan, improving the success ratio from 5 percent to 35 percent.

It also outperformed LLMs that are more than 10 times its size and that design molecules and synthesis routes only with text-based representations, suggesting multimodality is key to the new system’s success.

“This could hopefully be an end-to-end solution where, from start to finish, we would automate the entire process of designing and making a molecule. If an LLM could just give you the answer in a few seconds, it would be a huge time-saver for pharmaceutical companies,” says Michael Sun, an MIT graduate student and co-author of a paper on this technique.

Sun’s co-authors include lead author Gang Liu, a graduate student at the University of Notre Dame; Wojciech Matusik, a professor of electrical engineering and computer science at MIT who leads the Computational Design and Fabrication Group within the Computer Science and Artificial Intelligence Laboratory (CSAIL); Meng Jiang, associate professor at the University of Notre Dame; and senior author Jie Chen, a senior research scientist and manager in the MIT-IBM Watson AI Lab. The research will be presented at the International Conference on Learning Representations.

Best of both worlds

Large language models aren’t built to understand the nuances of chemistry, which is one reason they struggle with inverse molecular design, a process of identifying molecular structures that have certain functions or properties.

LLMs convert text into representations called tokens, which they use to sequentially predict the next word in a sentence. But molecules are “graph structures,” composed of atoms and bonds with no particular ordering, making them difficult to encode as sequential text.

On the other hand, powerful graph-based AI models represent atoms and molecular bonds as interconnected nodes and edges in a graph. While these models are popular for inverse molecular design, they require complex inputs, can’t understand natural language, and yield results that can be difficult to interpret.

The MIT researchers combined an LLM with graph-based AI models into a unified framework that gets the best of both worlds.

Llamole, which stands for large language model for molecular discovery, uses a base LLM as a gatekeeper to understand a user’s query — a plain-language request for a molecule with certain properties.

For instance, perhaps a user seeks a molecule that can penetrate the blood-brain barrier and inhibit HIV, given that it has a molecular weight of 209 and certain bond characteristics.

As the LLM predicts text in response to the query, it switches between graph modules.

One module uses a graph diffusion model to generate the molecular structure conditioned on input requirements. A second module uses a graph neural network to encode the generated molecular structure back into tokens for the LLMs to consume. The final graph module is a graph reaction predictor which takes as input an intermediate molecular structure and predicts a reaction step, searching for the exact set of steps to make the molecule from basic building blocks.

The researchers created a new type of trigger token that tells the LLM when to activate each module. When the LLM predicts a “design” trigger token, it switches to the module that sketches a molecular structure, and when it predicts a “retro” trigger token, it switches to the retrosynthetic planning module that predicts the next reaction step.

“The beauty of this is that everything the LLM generates before activating a particular module gets fed into that module itself. The module is learning to operate in a way that is consistent with what came before,” Sun says.

In the same manner, the output of each module is encoded and fed back into the generation process of the LLM, so it understands what each module did and will continue predicting tokens based on those data.

Better, simpler molecular structures

In the end, Llamole outputs an image of the molecular structure, a textual description of the molecule, and a step-by-step synthesis plan that provides the details of how to make it, down to individual chemical reactions.

In experiments involving designing molecules that matched user specifications, Llamole outperformed 10 standard LLMs, four fine-tuned LLMs, and a state-of-the-art domain-specific method. At the same time, it boosted the retrosynthetic planning success rate from 5 percent to 35 percent by generating molecules that are higher-quality, which means they had simpler structures and lower-cost building blocks.

“On their own, LLMs struggle to figure out how to synthesize molecules because it requires a lot of multistep planning. Our method can generate better molecular structures that are also easier to synthesize,” Liu says.

To train and evaluate Llamole, the researchers built two datasets from scratch since existing datasets of molecular structures didn’t contain enough details. They augmented hundreds of thousands of patented molecules with AI-generated natural language descriptions and customized description templates.

The dataset they built to fine-tune the LLM includes templates related to 10 molecular properties, so one limitation of Llamole is that it is trained to design molecules considering only those 10 numerical properties.

In future work, the researchers want to generalize Llamole so it can incorporate any molecular property. In addition, they plan to improve the graph modules to boost Llamole’s retrosynthesis success rate.

And in the long run, they hope to use this approach to go beyond molecules, creating multimodal LLMs that can handle other types of graph-based data, such as interconnected sensors in a power grid or transactions in a financial market.

“Llamole demonstrates the feasibility of using large language models as an interface to complex data beyond textual description, and we anticipate them to be a foundation that interacts with other AI algorithms to solve any graph problems,” says Chen.

This research is funded, in part, by the MIT-IBM Watson AI Lab, the National Science Foundation, and the Office of Naval Research.

“We’ve known that the virus SARS-CoV-2 enters the body through the respiratory tract, with the nose being a key entry point. What’s new — and surprising — is that bacteria in our noses can influence the levels of proteins that the virus uses to infect cells,” said Cindy Liu, associate professor of environmental and occupational health at the GW Milken Institute School of Public Health.

Higher Gene Expression of Viral Entry Proteins Increases COVID-19 Infection Risk

In the study, Liu and her team analyzed nasal swab samples from over 450 people, including some who later tested positive for COVID-19. They found that those who became infected had higher levels of gene expression for two key proteins — ACE2 and TMPRSS2. ACE2 allows the virus to enter nasal cells, while TMPRSS2 helps activate the virus by cleaving its spike protein.

Those with high expression for these proteins were more than three times as likely to test positive for COVID-19, while those with moderate levels had double the risk. The study also found that people who became infected had more unstable levels of gene expression, with the sharpest increases just days before testing positive, suggesting rising expression levels may signal increased vulnerability to the virus.

Notably, while women generally had higher gene expression levels of these proteins — consistent with previous studies showing higher COVID-19 infection rates in women — men with higher levels were more likely to get infected, indicating elevated protein levels may present a greater risk for men.

Nasal Bacteria May Play a Role in COVID-19 Risk

To understand what could impact the expression levels of these viral entry proteins, the researchers turned to the nasal microbiome — the diverse community of bacteria that naturally reside in the nose. They found that certain nasal bacteria may affect the expression levels of ACE2 and TMPRSS2, influencing the respiratory tract’s susceptibility to COVID-19.

The study identified three common nasal bacteria — Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis/nonliquefaciens — that were linked to higher expression levels of ACE2 and TMPRSS2 and increased COVID-19 risk. On the other hand, Dolosigranulum pigrum, another common type of nasal bacteria, was connected to lower levels of these key proteins and may offer some protection against the virus.

“Some bacteria in your nose may be setting the stage — or even holding the door open — for viruses like SARS-CoV-2 to get in,” said Daniel. Park, a senior research scientist at GW and the first author of the study.

While some of the high-risk bacteria were less common, 20% of participants carried enough S. aureus to nearly double their risk for having elevated ACE2 and TMPRSS2 expression, making it a major nasal microbiome risk factor for increasing individuals’ risk for COVID-19 infection.

Why This Matters

The findings offer new potential ways to predict and prevent COVID-19 infection. The study suggests that monitoring ACE2 and TMPRSS2 gene expression could help identify individuals at higher risk for infection. The research also highlights the potential of targeting the nasal microbiome to help prevent viral infections.

“We’re only beginning to understand the complex relationship between the nasal microbiome and our health,” said Liu. “This study suggests that the bacteria in our nose — and how they interact with the cells and immune system in our nasal cavity — could play an important role in determining our risk for respiratory infections like COVID-19.”

The team plans to explore whether modifying the nasal microbiome, such as through nasal sprays or live biotherapeutics, could reduce the risk of infection — potentially paving the way for new ways to prevent respiratory viral infections in future pandemics.

The study, “The Nasal Microbiome Modulates Risk for SARS-CoV-2 Infection,” was published April 9 in the journal EBioMedicine. The research was supported by the GW Milken Institute School of Public Health and by the National Institutes of Health.

Hyaline arteriolosclerosis is a condition that causes the small blood vessels to narrow, becoming thick and stiff. This makes it harder for blood to flow, which can damage the brain over time. It appears as lesions, areas of damaged tissue in the brain.

“Heavy alcohol consumption is a major global health concern linked to increased health problems and death,” said study author Alberto Fernando Oliveira Justo, PhD, of University of Sao Paulo Medical School in Brazil. “We looked at how alcohol affects the brain as people get older. Our research shows that heavy alcohol consumption is damaging to the brain, which can lead to memory and thinking problems.”

The study included 1,781 people who had an average age of 75 at death. All had brain autopsies.

Researchers examined brain tissue to look for signs of brain injury including tau tangles and hyaline arteriolosclerosis. They also measured brain weight and the height of each participant.

Family members answered questions about participants’ alcohol consumption.

Researchers then divided the participants into four groups: 965 people who never drank, 319 moderate drinkers who had seven or fewer drinks per week; 129 heavy drinkers who had eight or more drinks per week; and 368 former heavy drinkers. Researchers defined one drink as having 14 grams of alcohol, which is about 350 milliliters (ml) of beer, 150 ml of wine or 45 ml of distilled spirits.

Of those who never drank, 40% had vascular brain lesions. Of the moderate drinkers, 45% had vascular brain lesions. Of the heavy drinkers, 44% had vascular brain lesions. Of the former heavy drinkers, 50% had vascular brain lesions.

After adjusting for factors that could affect brain health such as age at death, smoking and physical activity, heavy drinkers had 133% higher odds of having vascular brain lesions compared to those who never drank, former heavy drinkers had 89% higher odds and moderate drinkers, 60%.

Researchers also found heavy and former heavy drinkers had higher odds of developing tau tangles, a biomarker associated with Alzheimer’s disease, with 41% and 31% higher odds, respectively.

Former heavy drinking was associated with a lower brain mass ratio, a smaller proportion of brain mass compared to body mass, and worse cognitive abilities. No link was found between moderate or heavy drinking and brain mass ratio or cognitive abilities.

Justo noted that, in addition to brain injuries, impaired cognitive abilities were observed only in former drinkers.

Researchers also found that heavy drinkers died an average of 13 years earlier than those who never drank.

“We found heavy drinking is directly linked to signs of injury in the brain, and this can cause long-term effects on brain health, which may impact memory and thinking abilities,” said Justo. “Understanding these effects is crucial for public health awareness and continuing to implement preventive measures to reduce heavy drinking.”

A limitation of the study was that it did not look at participants before death and did not have information on the duration of alcohol consumption and cognitive abilities.

The study was supported by The São Paulo Research Foundation.

“Biodegradable starch-based plastics may not be as safe and health-promoting as originally assumed,” says Yongfeng Deng, the corresponding author of the study.

Microplastics (plastic pieces less than 5 millimeters wide) are entering human bodies through contaminated water supplies, foods and drinks — and even IV infusions. Scientists have linked plastic particles in the bloodstream and tissues to various health risks. For example, a study found that people with inflammatory bowel disease have more microplastics in their feces. Biodegradable plastics have been presented as a safer, more environmentally friendly alternative to traditional petroleum-based plastics. One of the most common types comes from starch, a carbohydrate found in potatoes, rice and wheat. However, there is a lack of information on how starch-based biodegradable plastics affect the body. A team of researchers led by Deng tackled this issue by exploring these effects in animal trials.

The researchers compared three groups of five mice: one group consuming normal chow and two groups consuming food infused with starch-based microplastics. The doses (low and high) were calculated and scaled from what an average human is expected to consume daily. They fed the mice for 3 months and then assessed the animals’ organ tissues, metabolic functions and gut microbiota diversity. Mice exposed to the starch-based plastic particles had:

• Multiple damaged organs, including the liver and ovaries, with more pronounced damage in the high-dose group. However, mice eating normal chow showed normal organ tissue biopsies.
• Altered glucose management, including significant abnormality in triglycerides (a type of fat) and disruption in molecular biomarkers associated with glucose and lipid metabolism, compared to mice fed normal chow.
• Dysregulated genetic pathways and specific gut microbiota imbalances, which the researchers suggest could alter microplastic-consuming animals’ circadian rhythms.

“Prolonged low-dose exposure to starch-based microplastics can lead to a broad spectrum of health impacts, particularly perturbing circadian rhythms and disrupting glucose and lipid metabolism,” says Deng. However, the researchers acknowledge that because this is one of the first studies examining the impacts of consuming starch-based microplastics, further research is needed to understand how these biodegradable particles break down in the body.

The authors acknowledge funding from the Natural Science Foundation of China, the Jiangsu Province Young Science and Technology Talent Support Program, the Joint Fund of Departments and Schools, the Start-up Research Fund, and the Zhishan Young Scholars Fund of Southeast University by the Fundamental Research Funds for the Central Universities.

Given the complexity of human existence, it can be difficult to accurately define which aspects of youth have certain impacts later on in life. Interventions and experiments to explore theories are nearly impossible due to the long times involved. It is possible to compare different populations but depending on the matter investigated, there might often be too many confounding aspects to produce reliable data from which to draw conclusions. So when exploring a matter like the downstream impact of educational interventions, researchers ideally need multiple nearly identical populations different only in the presence of the intervention in question.

“Building upon previous research which found that day care in Japan improves noncognitive skills of very young children around age 3, my colleagues and I wished to investigate whether these benefits persist over time and if early childhood education can genuinely change behavioral outcomes later in life,” said Professor Shintaro Yamaguchi from the University of Tokyo’s Graduate School of Economics. “Our latest study examines Japan’s 1960s preschool expansion and its long-term effects on adolescent risky behaviors. By leveraging regional variations, we found that increased preschool enrollment significantly reduced violent crime arrests and teenage pregnancies, highlighting the lasting impact of early childhood education, even in a society with low baseline rates of such behaviors.”

The team’s findings are particularly significant because they come from a universal program that served all children regardless of socioeconomic background. Most previous evidence on the crime-reducing effects of early childhood education comes from small-scale targeted programs for disadvantaged children in the United States.

“A key challenge was ensuring that the effects we observed were genuinely caused by Japan’s preschool reform and not by other factors. Since different prefectures expanded preschool at different rates, we needed to rule out alternative explanations for changes in juvenile crime and teenage pregnancy,” said Yamaguchi. “To address this, we used a simple but effective approach: We examined adult crime and pregnancy rates before and after the reforms. If preschool had a real impact, the effects should appear only in children who attended, not in older individuals who missed out on the reform.”

What’s also interesting, and possibly counterintuitive in some ways, is that this preschool rollout program did not increase high school or college enrollment rates. Yamaguchi and colleagues suggest the mechanism behind the reduction in risky behaviors was likely improvement in noncognitive skills rather than additional schooling. This insight is important for understanding how early childhood education produces its long-term benefits.

“Our next step is to further investigate the mechanisms through which early childhood education affects adolescent behaviors. While our current research suggests that noncognitive skills play an important role, we would like to gather more direct evidence about which specific skills are most influenced by preschool education and how they develop over time,” said Yamaguchi. “Additionally, we’re planning to investigate even longer-term outcomes into adulthood, including effects on health behaviors, family formation and intergenerational outcomes. Understanding these broader and longer-term impacts would provide a more complete picture of the value of investing in early childhood education.”

Dunedin Multidisciplinary Health and Development Study researchers discovered the blood vessels at the back of the eye — called retinal microvasculature — can show early signs someone is at risk of developing dementia.

Co-lead author Dr Ashleigh Barrett-Young, of the Department of Psychology, says the findings link to previous work by members of the research team, “putting together pieces of a puzzle” when it comes to recognising early signs of dementia.

The findings are too premature to be applied in the real world yet, but research is continuing around the world.

“Treatments for Alzheimer’s and some other forms of dementia may be most effective if they’re started early in the disease course.”

Knowing who would benefit from early treatment is crucial, but difficult to do with current testing methods, which she hopes will improve in the future.

Cognitive tests aren’t sensitive enough in the early stages and a person may not be experiencing any decline yet, while other tests, like MRI and PET scanning, are expensive and not widely available.

“In our study, we looked at the retina which is directly connected to the brain,” she says.

“It’s thought that many of the disease processes in Alzheimer’s are reflected in the retina, making it a good target as a biomarker to identify people at risk of developing dementia.”

The study was co-led by Dr Aaron Reuben, of the University of Virginia, showcasing one of Otago’s many collaborations with universities around the world.

Published in the Journal of Alzheimer’s Disease, researchers used data from eye scans from the Dunedin Study’s age 45 assessment.

It is New Zealand’s longest-running longitudinal study and is considered the world’s most detailed study of human health and development.

The scans reveal narrower arterioles (the small blood vessels that carry blood away from the heart) and wider venules (the smallest veins which receive blood from capillaries), and thinner retinal nerve fibre layers (which carry visual signals from the retina to the brain) were associated with greater dementia risk.

Dr Barrett-Young says this was somewhat unexpected.

“I was surprised that venules were associated with so many different domains of Alzheimer’s disease — that suggests that it might be a particularly useful target for assessing dementia risk.”

Despite the findings, she reminds people not to panic.

“This research is still in an early stage, and we can’t predict your future looking at an eye scan,” she says.

“Hopefully, one day we’ll be able to use AI methods on eye scans to give you an indication of your brain health, but we’re not there yet.”

The good news? A multi-institutional team, led by researchers from the Penn State College of Medicine and the University of Wisconsin-Madison, found that eight weeks of either mindfulness or cognitive behavioral therapy (CBT) training led to meaningful improvements among adults with chronic low back pain that’s currently treated with opioids and had not responded to prior treatments. These behavioral therapies helped improve physical function and quality of life and reduce pain and opioid dose in a randomized clinical trial. The benefits persisted for up to 12 months.

The findings were published in JAMA Network Open. This is the largest trial to date comparing mindfulness with CBT as treatments for opioid-treated chronic pain and the research team followed up with participants over a longer time period than many previous trials of mindfulness.

“Both mindfulness and cognitive behavioral therapy were shown to be safe, effective treatments, providing lasting benefits for people with opioid-treated chronic back pain,” said Aleksandra Zgierska, Jeanne L. and Thomas L. Leaman, MD, endowed professor and vice chair of research of family and community medicine and professor of anesthesiology and perioperative medicine and of public health sciences at the Penn State College of Medicine, who led the study. “These evidence-based behavioral therapies should be standard of care available to our patients.”

Pain is multifaceted, especially chronic pain that can last for months or years. Chronic low back pain is the most common form of chronic non-cancer pain that’s treated with opioids. Previous research has shown that adults with chronic pain may benefit from behavioral therapies, which can help people change their thoughts about and relationship to pain, but it’s been understudied, the researchers explained. Studies on behavioral therapies were generally small in size and evaluated benefits over the short-term.

“People think of chronic pain as a physical condition that requires a physical intervention,” said Eric Garland, endowed professor in health sciences and professor of psychology at the University of California, San Diego and senior author of the study.

The research team set out to evaluate the effectiveness of mindfulness compared to CBT as treatments for chronic opioid-treated low back pain and their long-term effects. CBT is considered the standard psychotherapy for chronic pain, but its long-term benefits haven’t been well studied. To date, only 17 studies have evaluated mindfulness for chronic low-back pain and three studies have compared mindfulness and CBT.

This study was planned in partnership with an advisory panel composed of clinicians and representatives of community and advocacy organizations that work with people with chronic pain as well as adults with opioid-treated chronic low back pain and their caregivers. The panel’s feedback, included throughout the study, helped the researchers design and implement the study and better translate the study’s results to be meaningful and useful to patients and clinicians.

The team enrolled 770 adults to participate in a randomized clinical trial conducted in three sites — Madison, Wisconsin; Boston, Massachusetts; and Salt Lake City, Utah. Participants, on average, experienced moderate-to-severe pain, functional limitations, compromised quality of life and numerous prior treatments for their chronic low-back pain and were treated with daily opioid medications for at least three months.

“The people in this study had quite severe back pain that interfered with their life and was bad enough to need opioid medication. Usually, in that condition, people don’t really get better over time on their own,” said Bruce Barrett, professor of family medicine and community health at the University of Wisconsin-Madison and co-lead of the study.

Participants were then assigned to either receive mindfulness-based therapy or CBT, which were conducted in therapist-led, two-hour group sessions for eight weeks. The mindfulness group learned to notice the sensations they experienced, giving them more control over how they related and respond to the pain and other symptoms. The CBT group learned coping skills and strategies to change their negative thought patterns. Participants were instructed to practice on their own for 30 minutes a day, six days a week during the 12-month study and to continue with their routine care. They were not instructed to reduce their opioid dosage. They reported on their pain level, ability to do daily activities, mental and physical health-related quality of life and daily opioid medication use at the start of the study and after three, six, nine and 12 months.

At the end of the study, participants in both groups reported significant and long-lasting benefits including reductions in pain and daily opioid dose. They also reported increased function and health-related quality of life through 12 months. Both mindfulness and CBT tools were shown that they could be effective and used safely over the long-term, the researchers said.

“The goal of pain management is to improve quality of life, increase function and reduce the sense of suffering. The study’s interventions likely helped reduce the participants’ sense of suffering, which probably allowed them to function a whole lot better,” said Penney Cowan, founder of the American Chronic Pain Association and co-author and advisor on the study. “People can live with pain, but they need to know how to do it. This study provides a sense of hope. It says you can do this and help yourself to a better quality of life.”

The research team explained that people living with chronic pain assemble a toolkit filled with different self-coping and self-care methods to manage their pain. They can use these tools at different times and in different ways.

“Mindfulness and CBT are other tools that you can add to your toolbox to increase your capacity to cope and live a meaningful life,” said Christin Veasley, founder of the Chronic Pain Research Alliance and co-author and advisor on the study. “What’s important about the types of therapies, like the ones evaluated in this study, is that they can be used broadly across all pain conditions and all pain severities.”

For example, while participants were told to continue their usual treatment, including pain medication as advised by their usual clinicians, opioid dosage decreased in both groups through 12 months following the intervention. Zgierska explained that participants learned skills, like taking a mindful breath before taking medication. The improvements, the research team said, were the byproduct of people implementing these tools, learning to better cope with pain and deciding to decrease their opioid use on their own.

“These therapies aren’t a total cure, but they teach people how to develop the inner resources they need to cope with chronic pain and to live a better life,” Garland said. “Mindfulness is a self-regulated tool that comes from within, unlike surgery or medication where something is being done to you from the outside. By learning these techniques, patients continue to experience lasting benefit.”

Other Penn State College of Medicine authors include Vernon Chinchilli, distinguished professor; Chan Shen, professor; Wen-Jan Tuan, assistant professor; Robert Lennon, who was associate professor during the time of the research; and statisticians Yuxin Liu and Huamei Dong.

Other authors include Robert Edwards and Robert Jamison from Harvard Medical School, Brigham and Women’s Hospital; Cindy Burzinski, Mary Henningfield, Alyssa Turnquist, Nalini Sehgal and Anthony Schiefelbein from the University of Wisconsin-Madison; Yoshio Nakamura from the University of Utah School of Medicine; and Elizabeth Jacobs from the University of California, Riverside School of Medicine.

Funding from the Patient-Centered Outcomes Research Institute (PCORI) supported this work. Funding and institutional support from the University of Wisconsin-Madison School of Medicine and Public Health; Brigham and Women’s Hospital, Harvard Medical School; University of Utah College of Social Work; and the Penn State College of Medicine also supported this work.

Therefore, Associate Professor Mitsuko Tanaka at Osaka Metropolitan University’s Graduate School of Sustainable System Sciences examined the impact of a PBL group work environment on student motivation using 154 university students who had taken an English as a second language class. Separated into 50 groups ranging from three to five members, the students were tasked with topic-based projects and presentations. At the end of the semester, a questionnaire that analyzed gender, group size, and individual factors, including learner beliefs and competence, was distributed to assess the group work environment.

The results of the analysis showed that there was no effect due to the size of the group, but there was a significant difference depending on the group work environment and individual factors. In addition, it was also found that if the group work environment is good, motivation tends to increase regardless of such factors.

“This research has shown that appropriate environmental preparation is essential for the success of project-based learning,” stated Professor Tanaka. “I believe these findings can be an important guideline for educational practitioners to recognize the importance of the group work environment in PBL.”

The findings were published in System.

Scientists from University Hospital Düsseldorf and HHU have — in collaboration with the University of Cologne and the Center for Molecular Medicine Cologne (CMMC) — discovered a mechanism, which protects and repairs the mitochondria. The research team, headed by Professor Pla-Martín from the Institute of Biochemistry and Molecular Biology I at HHU, has identified a specialised recycling system, which cells activate when they identify damage to the mtDNA.

According to the authors in Science Advances, this mechanism relies on a protein complex known as retromer and the lysosomes — cell organelles containing digestive enzymes. These special cellular compartments act like recycling centres, eliminating the damaged genetic material. This process is one of the mechanisms, which prevent the accumulation of faulty mtDNA, thus maintaining cellular health and potentially preventing diseases.

“We have identified a previously unknown cellular pathway, which is important for mitochondrial health and thus for the natural defences of our cells,” explains Professor Pla-Martín, continuing: “By understanding this mechanism, we can explain how mitochondrial damage can trigger diseases like Parkinson’s and Alzheimer’s. This could in turn form the basis for developing preventive therapies.”

In collaboration with the cell biologist Dr Parisa Kakanj from the University of Cologne, who is also a member of the CEPLAS Cluster of Excellence, Professor Pla-Martín was able to verify and extend the findings using fruit flies (Drosophila) as a model organism. Dr Kakanj showed that damaged mitochondrial DNA are eliminated much more quickly and that mitochondrial function improves significantly when the activity of the retromer complex — in particular the protein VPS35 — is increased.

Dr Kakanj: “Using Drosophila allowed us to confirm our initial findings in human cells and demonstrate clear improvements in mitochondrial health. This opens up exciting possibilities for therapeutic strategies for treating mitochondrial diseases and age-related conditions.”

Diet contributes significantly to cardiovascular disease mortality, with estimates indicating that across the European region, one in every five premature deaths could be prevented by an optimised diet.

“In 2019, the Planetary Health Diet (PHD) was developed to optimise global dietary quality while keeping the environmental impacts of food production within sustainable planetary boundaries,” said study author Dr. Mercedes Sotos Prieto of the Autonomous University of Madrid, Spain. “However, there was a lack of evidence on how the PHD compares with the Mediterranean Diet, a plant-based diet with established health and environmental benefits, that is well rooted in Mediterranean countries. We evaluated the effects of both diets on all-cause mortality and environmental impact in a large representative Spanish population.”

The PHD involves energy intake of around 2,500 kcal/day and focuses primarily on high consumption of fruits and vegetables, whole grains, legumes, nuts and unsaturated oils; moderate intake of dairy, starchy vegetables, poultry and fish; and low consumption of saturated fats, red meat and added sugars.

The Mediterranean Diet is characterised by a pattern rich in fruits and vegetables (seasonal), legumes, whole grains and nuts, with olive oil as the main dietary fat, greater consumption of white or lean meats than of red or processed meats, and with moderate consumption of dairy products, fish and eggs.

In the analysis, data on food intake were collected from 11,488 participants in the Study on Nutrition and Cardiovascular Risk in Spain (ENRICA), a prospective cohort study of individuals recruited between June 2008 and October 2010. The PHD Index (0-140 points) was calculated for each participant based on their consumption of 15 food groups: whole grains, starchy vegetables, vegetables, whole fruits, dairy foods, red/processed meat, chicken and other poultry, eggs, fish/shellfish, nuts, non-soy legumes, soybean/soy foods, added saturated and trans-fat, added unsaturated oils, and added sugar and fruit juice. Adherence to the Mediterranean Diet was assessed using the 14-item MEDAS score (0-14 points), which is based on components such as using olive oil for cooking and dressings, eating white meat and seafood over red meat, the consumption of fruits, vegetables, legumes and nuts, and low intake of high-fat dairy products, commercial baked goods and sugar-sweetened/carbonated beverages. The environmental impact of each diet was assessed using the SHARP-Indicators Database (SHARP-ID), which includes data on greenhouse gas emissions and land use. Mortality data were obtained from the National Death Index of Spain. Analyses were performed across tertiles of adherence to the diets, with adjustment for confounders.

Study participants had a mean age of 47.5 years (range, 18-96 years) and around a half (52.5%) were women. A total of 1,157 all-cause deaths occurred during a mean follow-up of 14.4 years.

Higher adherence to the PHD and Mediterranean Diet was similarly associated with lower all-cause mortality. Participants in the top third for adherence to the PHD had a 22% lower chance of dying than those in the lowest third (adjusted hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.66-0.91). For the Mediterranean Diet, participants in the top third for adherence had a 21% lower chance of dying than those in the lowest third (adjusted HR 0.79; 95% CI 0.68-0.93). Adherence to some components of the PHD (fruits, dairy and unsaturated oils) and the Mediterranean Diet (nuts, low consumption of soda and pastries) was independently associated with lower mortality.

In terms of environmental impact, both diets had similarly low footprints. For the PHD, the average level of greenhouse gas emissions was 4.15 kg of CO₂ per day and average level of land use was 5.54 m2 per daily food intake. The average level of greenhouse gas emissions for the Mediterranean Diet including dairy was 4.36 kg of CO₂ per day and the average level of land use was 5.43 m2 per daily food intake. Dairy and meat products were the largest footprint contributors.

Dr. Sotos Prieto concluded: “Higher adherence to both diets was similarly associated with lower all-cause mortality and with comparable low environmental impact, highlighting the substantial health and planetary advantages of adopting one of these plant-based diets.”

But more common viral diseases also contribute to global health challenges and economic costs. For example, seasonal influenza epidemics occur annually, causing a substantial global disease burden and economic losses exceeding $11.2 billion each year in the United States alone. Meanwhile, herpes simplex virus-1 (HSV-1), spread primarily through oral contact, infects over two-thirds of the global population and is the leading cause of infectious blindness in Western countries.

Low vaccination rates for influenza viruses and the lack of an HSV vaccine underscore the need for a new approach — one that targets reducing viral loads at the sites where transmission occurs. And for viruses like these, which are transmitted more efficiently through the mouth than the nose, this means focusing on the oral cavity.

Now, in a study published in Molecular Therapy, researchers at the School of Dental Medicine at the University of Pennsylvania and collaborators in Finland, have done just that.

Building on their previous work — now in clinical trial — showing that a similar approach was able to reduce SARS-CoV-2 in COVID-19 patient saliva or swab samples by more than 95%, Henry Daniell, W.D. Miller Professor in Penn’s School of Dental Medicine, and collaborators tested the ability of a chewing gum made from lablab beans, Lablab purpureus — that naturally contain an antiviral trap protein (FRIL) — to neutralize two herpes simplex viruses (HSV-1 and HSV-2) and two influenza A strains (H1N1 and H3N2). The chewing gum formulation allowed for effective and consistent release of FRIL at sites of viral infection.

They demonstrated that 40 milligrams of a two-gram bean gum tablet was adequate to reduce viral loads by more than 95%, a reduction similar to what they saw in their SARS-CoV-2 study.

Importantly, the researchers prepared the gum as a clinical-grade drug product to comply with the FDA specifications for drug products and found the gum to be safe. Daniell notes, “These observations augur well for evaluating bean gum in human clinical studies to minimize virus infection/transmission.”

Daniell and his colleagues are now looking to use lablab bean powder to tackle bird flu, which is currently having a significant impact in North America. In the previous three months, 54 million birds have been affected by H5N1, and several human infections have been reported in the U.S. and Canada.

Previously, bean powder was shown by others to effectively neutralize H5N1 and H7N9 — two strains of influenza A known to cause bird flu in humans as well as in birds. Daniell and colleagues are currently looking to test its use in bird feed to help control bird flu in birds.

“Controlling transmission of viruses continues to be major global challenge. A broad spectrum antiviral protein (FRIL) present in a natural food product (bean powder) to neutralize not only human flu viruses but also avian (bird) flu is a timely innovation to prevent their infection and transmission,” says Daniell.

Henry Daniell is the W.D. Miller Professor in the Department of Basic & Translational Sciences at the School of Dental Medicine at the University of Pennsylvania.

Other authors include Gary H. Cohen, Yuwei Guo, Uddhab Karki, Rachel J. Kulchar, Rahul Singh, and Geetanjali Wakade of Penn Dental Medicine, Hamid Khazaei of the Natural Resources Institute Finland (Luke) and the University of Finland and Juha-Matti Pihlava of the University of Finland.

Research performed in the Daniell lab is supported by NIH grant R01 HL 107904.

But the disease has made a troubling comeback in recent years as vaccine coverage declined after the COVID-19 pandemic. In 2024, several outbreaks left public health officials and hospitals scrambling to accommodate a sudden influx of patients, primarily infants, who are often too young to be vaccinated and suffer the most severe symptoms.

Now, new research from The University of Texas at Austin could aid in improving whooping cough vaccines to once again push this disease toward eradication by targeting two key weaknesses in the infection.

A New Target

Against this backdrop, a team of researchers, including members of UT’s McKetta Department of Chemical Engineering and Department of Molecular Biosciences, has made significant strides in understanding and enhancing pertussis immunity. One of the things that makes pertussis infections dangerous is pertussis toxin (PT), a chemical weapon produced by the bacteria that weakens a patient’s immune response and causes many of the severe symptoms associated with whooping cough.

The new research, described in a new study published in the Proceedings of the National Academy of Sciences, focuses on two powerful antibodies, hu11E6 and hu1B7, which neutralize the PT in different ways.

Using cutting-edge cryo-electron microscopy approaches, the researchers identified the specific epitopes on PT where these antibodies bind. Epitopes are chemical targets the immune system can zero in on to fight pathogens. Hu11E6 blocks the toxin from attaching to human cells by interfering with sugar-binding sites, while hu1B7 prevents the toxin from entering cells and causing harm. These findings are the first to precisely map these critical regions, providing a blueprint to improve vaccines.

“There are currently several promising new pertussis vaccines in the research and clinical trial phases,” said Jennifer Maynard, professor of chemical engineering at the Cockrell School of Engineering and corresponding author of the new study. “Our findings could be incorporated into future versions quite easily, improving overall effectiveness and longevity of protection.”

She pointed to innovations like mRNA technology used in the COVID-19 vaccine, as well as breakthroughs in using genetic engineering on pertussis toxin (PT_gen) to generate safer and more potent new recombinant acellular pertussis vaccines as technologies preserving neutralizing epitopes that can combine with her team’s new findings.

“Training the immune system to target the most vulnerable sites on the toxin is expected to create more effective vaccines,” Maynard said. “And the more effective and longer-lasting a vaccine is, hopefully, the more people will take it.”

In addition to helping guide future vaccine designs, the hu1B7 and hu11E6 antibodies themselves hold promise as therapeutic medicines for infected and high-risk infants. Previous work by Maynard and colleagues show that they can prevent the lethal aspects of pertussis infection. UT researchers are actively seeking partnerships to develop ways to prevent lung damage and death in newborns exposed to the disease.

A Persistent Threat

Caused by the bacterium Bordetella pertussis, whooping cough is infamous for its violent coughing fits, which can lead to complications like pneumonia, seizures, and even death, particularly in infants. One nickname for the disease is the 100-days cough because the painful coughing fits can linger for months, even in mild or moderate cases. The disease kills an estimated 200,000 people each year worldwide, most of them infants and children, and survivors of severe illness can be left with brain damage and lung scarring.

While modern vaccines have reduced the toll, their effectiveness wanes over time, with protection only lasting two to five years. Modern pertussis vaccines are acellular, which means they contain portions of the bacteria that train the immune system to recognize the pathogen, including PT.

Recent outbreaks of whooping cough around the world have stunned public health officials. This fall, New York City saw a 169% increase in whooping cough cases since 2023. Cases have increased 500% since 2019. Australia is currently suffering through the largest outbreak of whooping cough since the introduction of the vaccine in the 1940s, with an estimated 41,000 cases reported this year.

Health officials point to missed initial and booster vaccinations as major contributors to the outbreaks.

Overcoming Hesitancy

While advances in fighting pertussis are exciting, they face a dual challenge: overcoming the biological complexity of pertussis and the societal hurdles of vaccine hesitancy. The most effective way to prevent pertussis in vulnerable newborns is for mothers to be vaccinated during pregnancy, which confers protection to the newborn until it is old enough to be vaccinated. According to the CDC, the full vaccination rate against pertussis in kindergarteners is typically over 90% in the US, but under 60% of mothers receive the vaccine during pregnancy. Skepticism about vaccine safety and slow normalization of routine vaccination after the COVID-19 pandemic has led to pockets of under-vaccinated communities and overall low protection of newborns, providing fertile ground for deadly outbreaks. This environment, coupled with the limitations of current vaccines, makes innovation essential.

Co-author Annalee W. Nguyen, a research professor in chemical engineering, emphasized the importance of prevention over treatment. “It’s always easier to prevent disease in a high-risk person,” she said. “Once someone is extremely ill, their immune system isn’t functioning well, and it’s harder to help them recover. Mothers have an incredible opportunity to shield their babies after they are born by getting a pertussis booster vaccination during pregnancy, and parents can continue to protect their families by working with their pediatrician to ensure children and teens are up-to-date on vaccinations.”

By focusing on neutralizing epitopes — areas where antibodies can effectively block the toxin — new vaccines can potentially provide stronger, longer-lasting immunity. This could help bolster public confidence in pertussis vaccines and curb the disease’s resurgence.

Rebecca E. Wilen of the McKetta Department of Chemical Engineering at UT Austin, Jory A. Goldsmith and Jason McLellan of the Molecular Biosciences Department at UT Austin and Wassana Wijagkanalan of BioNet-Asia were also authors on the paper. The research was financially supported by the Cancer Prevention and Research Institute of Texas, Welch Foundation and the National Institutes of Health.

Scientists and researchers around the globe are investigating a series of mysteries about what happens to our bones over time. In a new study, a team led by The University of Texas at Austin, in collaboration with Mayo Clinic and Cedars-Sinai Medical Center just made a major break in the case. New research found that osteocytes undergo dramatic structural and functional changes with age that impair their ability to keep our bones strong. Their findings, published in Small and Aging Cell, offer new insights that could pave the way for better treatments for osteoporosis and age-related bone loss.

Aging and stress can induce cellular senescence in osteocytes, resulting in cytoskeletal and mechanical changes that impair their ability to sense mechanical signals, ultimately weakening bone.

Osteocytes are the master regulators of bone health, sensing mechanical forces and directing when to build or break down bone. But when exposed to senescent cells — damaged cells that stop dividing but don’t die — osteocytes themselves begin to stiffen. This cytoskeletal stiffening and altered plasma membrane viscoelasticity undermine their ability to respond to mechanical signals, disrupting healthy bone remodeling and leading to bone fragility.

“Imagine the cytoskeleton as the scaffolding inside a building,” said Maryam Tilton, assistant professor in the Cockrell School of Engineering’s Walker Department of Mechanical Engineering and principal investigator of the study. “When this scaffolding becomes rigid and less flexible, the building can’t adapt to changes and stresses, leading to structural problems. Similarly, stiffened osteocytes can’t effectively regulate bone remodeling, contributing to bone loss.”

Senescent cells release a toxic brew of molecules, called senescence-associated secretory phenotype (SASP), which triggers inflammation and damage in surrounding tissues. They’ve been linked to the development of cancer and many other chronic diseases. Until now, most research has focused on detecting senescence through genetic markers, a notoriously challenging task because these markers vary widely across cell types.

Tilton and her collaborators approach the issue from a different perspective, focusing on cell mechanics. Combining genetic and mechanical approaches could lead to improved treatments for aging cells.

“Much like physical therapy helps restore movement when our joints stiffen, we’re exploring how mechanical cues might help reverse or even selectively clear these aging cells,” Tilton said.

“In the future, biomechanical markers could not only help identify senescent cells but also serve as precise targets for eliminating them, complementing or offering alternatives to current drug-based senolytic therapies,” added Dr. James Kirkland, principal investigator of the National Institutes of Health Translational Geroscience Network, director at the Center for Advanced Gerotherapeutics at Cedars-Sinai and a co-leader of the new research.

Improved knowledge about how bones age could improve treatments for osteoporosis. The condition leads to weakened bones and an increased risk of fractures and affects millions of people worldwide, particularly those over the age of 50. As the global population ages, understanding the mechanisms behind bone deterioration becomes increasingly important.

The team plans to expand their research by exploring the effects of different stressors on osteocytes and investigating potential therapeutic interventions.

This project is led by Tilton in collaboration with Kirkland. Other co-authors on the project include Junhan Liao, Domenic J. Cordova, and Hossein Shaygani of the Walker Department of Mechanical Engineering; Chanul Kim of the Department of Biomedical Engineering; Maria Astudillo Potes from Mayo Clinic; and Kyle M. Miller of Emory University.

The researchers then perform single-cell analyses on each cell to measure the effects of the editing, including identifying which genes have been turned on or off and which genes are accessible (based on epigenetic markers). The team applied this tool to immature blood cells to identify the important transcription factors — and DNA regions that code for them — that strongly affect how blood cells develop.

They discovered that many of the DNA regions they identified as important for driving blood cell production are also regions known to harbor mutations linked to blood disorders. The DNA regions they identified as important occupy less than 0.3% of the genome, but they explain a disproportionately large share of the genetic influence on blood cell features and specialization.

In earlier work, investigators from this team and other collaborators used genome-wide association studies to identify the transcription factor responsible for switching off fetal hemoglobin after birth, laying the groundwork for the development of gene therapy for sickle cell disease and beta thalassemia.

This new Perturb-multiome approach enables researchers to systematically reveal how thousands of transcription factor variants influence blood cell production and influence disease risk, creating opportunities for finding many more novel targeted therapies for blood disorders.

Funding: La Caixa Foundation, the Rafael del Pino Foundation, the American Society of Hematology, the Broad Institute, the New York Stem Cell Foundation, the Lodish Family, the Howard Hughes Medical Institute, and the National Institutes of Health.

The aptamers — short single-strand snippets of DNA that can target molecules like larger antibodies do — not only deliver cancer-fighting drugs, but also are themselves toxic to the cancer stem cells, the researchers said.

Led by Xing Wang, a U. of I. professor of bioengineering and of chemistry, the researchers documented their findings in the journal Advanced Functional Materials.

“This work demonstrates a way to get to the root of leukemia,” Wang said. “Targeted cancer treatments often have problems with toxicity or efficacy. Our aptamers seek out these stem cells specifically and kill them effectively.”

Leukemia and other cancers of the blood are more difficult to target than cancers that produce localized tumors because the cancerous cells circulate throughout the body and can’t be surgically removed, said postdoctoral researcher Abhisek Dwivedy, first author of the paper. Leukemia has a high rate of relapse due to its evasive stem cells. Though they make up a tiny fraction of cancerous cells, leukemia stem cells have the ability to evade chemotherapy by retreating to the bone marrow, since they share markers and properties, Dwivedy said. The cancerous cells can lurk, sometimes for years, and later proliferate and migrate.

“It’s important in leukemia, lymphoma or other blood cancers that we actually target and eliminate these stem cells, because as long as any are remaining, they can cause relapse and secondary cancers,” Dwivedy said.

The researchers began by finding DNA aptamers that seek out markers found on the surface of acute myeloid leukemia stem cells. They wanted to target not just the cancer, but the stem cells specifically.

“A big thing we showed in this study is that having two targets is better than one in terms of selectivity,” Wang said. “There are known antibody-drug conjugates for blood cancers that target one marker, but that marker is also found on a lot of healthy cells. So there is a lot of toxicity associated with antibody conjugates. But we used two targets: a combination often found in leukemia cancer cells and leukemia stem cells. The two together give a very specific target.”

The researchers then paired their aptamers with the leukemia-fighting drug daunorubicin. The drug-laden aptamers carry the drug to their target, then release the drug once inside the cell so the drug can act.

“This is especially important for drugs like daunorubicin, because the drug on its own cannot cross the cell membrane easily. But aptamers can carry it in,” Dwivedy said.

The researchers tested the drug-delivering aptamers in leukemia cell cultures as well as in live mice with leukemia.

After 72 hours, the aptamer alone had reduced the cancer cells in culture by 40 percent, demonstrating the aptamer’s toxicity to the cancer, the researchers report. When the aptamers carried the leukemia-fighting drug, the cells were wiped out with a dose 500 times smaller than the standard dosage of the drug. In mice with leukemia, delivering the drug via aptamer yielded the same efficacy at a dose 10 times smaller than the clinical standard, showing that the one-two punch of the aptamer and drug is more effective than either alone.

“This was exciting to us, because in cancer research, what we see in vitro is not always what we see in the body. Yet we saw excellent survivability and tumor reduction in the mice treated with our aptamer-drug conjugates, at one-tenth of the therapeutic dose, and no off-target effects,” Wang said.

The researchers said they hope to expand their suite of drug-delivering aptamers by identifying key marker combinations for other cancers, as well as coupling the aptamers with other drugs.

“Every cancer cell has a signature in its surface biomarkers. If we can find markers that are present uniquely in cancer cells, we can target other cancer types as well. Also, in my experience, it’s much easier to pair a drug with the DNA molecules than proteins, so that opens possibilities for delivering more drugs this way,” Dwivedy said.

The clinical study has now shown that early treatment with fosdenopterin in the first days of life significantly reduces the risk of early death and promotes healthy brain development. The study was published under the title “Treatment of molybdenum cofactor deficiency (MoCD) Type A with cyclic pyranopterin monophosphate (cPMP)” in the Journal of Inherited Metabolic Disease.

Without treatment, MoCD type A results in severe impairments such as seizures and severe developmental and movement disorders, and often leads to early death within the first few months of life. Until recently, the only treatments available for patients with MoCD were symptomatic. They therefore targeted the symptoms and not the actual cause of the disease. The present study now shows that treatment with fosdenopterin/rcPMP combats the underlying cause of MoCD type A by restoring the missing molecule cPMP. The researchers found that early administration of this drug can not only prolong life, but also promote important developmental milestones such as sitting, walking and eating behaviour. The infants treated in the study showed significant improvements compared to untreated patients, with many achieving development equivalent to that of healthy infants.

Due to the rarity of the disease, it is difficult to conduct a large-scale, controlled clinical trial on the efficacy of the drug. The research group was able to demonstrate the drug’s effectiveness in a mouse model back in 2004. The first patients have been receiving treatment with the active substance fosdenopterin/rcPMP since 2008. The current publication therefore summarizes the results of three long-term studies that track the development of 14 treated patients compared to 36 untreated patients in their first months of life.

“The results show that fosdenopterin/rcPMP can significantly improve the prognosis of infants with MoCD type A,” says Professor Dr Günter Schwarz, first author of the study. “Our results emphasize the importance of research into rare metabolic diseases, which allows us to lay the foundations for new treatment options and establish better prospects for patients.”

Fosdenopterin/rcPMP is approved in the USA and the European Union for the treatment of MoCD type A in infants and young children under the brand name NULIBRY owned by Sentynyl Therapeutics, Inc. In 2008, Professor Schwarz and his colleague Dr Santamaria founded the start-up company Orphatec (later Colbourne) Pharmaceuticals GmbH and commenced with the clinical development of the therapy. Following out-licensing in 2011, various pharmaceutical companies continued with the clinical development. This study was funded by Origin Biosciences, Inc.

HIV-diagnostic technology traditionally relied on the detection of HIV-specific antibodies that form several weeks after infection. This has limited their use in early detection, complicating patient care and HIV prevention efforts. Newer tests that detect both HIV antibodies and the p24 antigen (an earlier marker of HIV infection) are now the gold standard for diagnosis, but require clinical labs to run results, contributing to longer processing times, higher costs and the need for multiple patient visits.

The technology described in a study published today (April 2) in the journal Biosensors and Bioelectronics uses a nanomechanical platform and tiny cantilevers to detect multiple HIV antigens at high sensitivity in a matter of minutes. These silicon cantilevers are cheap and easy to mass produce and can be readily equipped with a digital readout. Built into a solar-powered device, this technology could be taken to hard-to-reach parts of the world where early detection remains a challenge to deliver fast interventions to vulnerable populations without waiting for a lab.

“We hope this technology will lead to the development of new point-of-care diagnostics for HIV to improve patient health and help bring an end to this epidemic,” said Northwestern virologist and co-author of the study, Judd F. Hultquist.

After proving its efficacy in testing for both the SARS-CoV-2 virus that causes COVID-19, and now HIV, the team is confident that the biosensor will continue to prove effective when testing for additional diseases. A potential next target, they say, could be measles, another infection in desperate need of point-of-care interventions as cases rise across multiple U.S. states.

The team was led by co-corresponding authors Vinayak Dravid, a materials engineer, Hultquist, a virologist, and co-author Gajendra Shekhawat, a micro- and nanofabrication expert in the Dravid Lab.

“When we first developed the microcantilever technology 20 years ago, I realized that this technology is so generally applicable,” Dravid said. “It is a very powerful tool that depends on three basic things: sensitivity, antigen-antibody affinity and specificity. This is where HIV comes in, because HIV is so pernicious that it mutates so there is no unique antibody. We had to figure out how to overcome that challenge.”

Beginning with pure samples of the p24 antigen, the team applied layers of antibodies onto each “finger” of the gold-coated microcantilever to measure how strongly p24 bonded to the surface, which would cause the cantilever to bend a measurable and quantifiable amount.

After this proof-of-concept, the team introduced human blood samples, which are much more complex than purified samples. The sensor continued to bend only in samples where p24 was present, demonstrating high specificity.

Finally, the scientists added two antibodies to different “fingers” of the microcantilever to more broadly cover all HIV subtypes. Even in very low concentrations, the test accurately responded when antigens specific to HIV were introduced.

“To account for HIV’s genetic diversity, we functionalized the test for HIV using broadly cross-reactive antibodies (ANT-152 and C65690M),” Shekhawat said. “This allowed accurate detection across diverse HIV-1 subtypes, ensuring reliability in global settings.”

To streamline diagnostics and enable immediate medical care, the team envisions developing a point-of-care test simultaneously detecting HIV, hepatitis B and hepatitis C antigens, acknowledging the higher prevalence of hepatitis co-infections in people living with HIV that can lead to severe liver complications if left untreated.

Dravid is the Abraham Harris Professor of Materials Science and Engineering at the McCormick School of Engineering and a faculty affiliate of the Paula M. Trienens Institute for Sustainability and Energy. He is also the founding director of the Northwestern University Atomic and Nanoscale Characterization (NUANCE) Center as well as the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource, and also serves as the associate director for global programs at the International Institute of Nanotechnology.

Hultquist is an assistant professor of medicine at Northwestern University Feinberg School of Medicine and serves as the associate director for the Center for Pathogen Genomics and Microbial Evolution in the Havey Institute for Global Health. He specializes in translational research of infectious diseases and host-pathogen interactions.

Shekhawat is a research professor of materials science and engineering at McCormick, researching semiconductor microfabrication, integration of sensors with synthetic biology and biomaterials and nanoscale characterization.

The research was supported by an award from the National Institutes of Health-funded Third Coast Center for AIDS Research (P30AI117943), as well as through NIH funding for the HIV Accessory & Regulatory Complexes Center (U54 AI170792) and NIH funding for HIV research (R01AI176599, R01AI167778, R01AI150455, R01AI165236, R01AI150998, R21 AI174864, and R56AI174877).

Vinayak Dravid, Gajendra Shekhawat, Judd Hultquist and Northwestern have financial interests (equities, royalties) in the reported research.

In recent years, the World Health Organization (WHO) has repeatedly warned of the increase in microbes resistant to antibiotics. Especially multi-resistant bacteria threaten the global healthcare system and can deprive modern medicine of one of its most important curative tools. A team of researchers at the University of Konstanz and the University of Vienna, along with their collaboration partners, have now identified a highly effective substance that uses a new mechanism to target one particularly problematic pathogen. The astonishing findings of the research team led by Christof Hauck, professor of cell biology at the University of Konstanz, and Thomas Böttcher, professor of microbial biochemistry at the University of Vienna, have now been published in Nature Microbiology.

Last year, the WHO compiled a list of particularly problematic bacterial pathogens (Bacterial Priority Pathogens List). It names15 types of bacteria that are resistant to antibiotics and classifies them into categories such as “critical,” “high” and “medium” priority. The WHO has called upon science and industry to focus their efforts on developing drugs that fight these microbes. One bacterium on the list is Neisseria gonorrhoeae, the microbe that causes the sexually transmitted disease gonorrhoea.

Superbug gonococci

Neisseria gonorrhoeae, also referred to as gonococcus, is a highly specialized type of bacteria only found in humans. The pathogen primarily colonizes mucous membranes in the genital tract and can be transmitted from person to person during unprotected sex. During birth, these pathogens can also be transmitted from an infected mother to her child, causing the baby’s eyes to become infected. Especially before antibiotics were available, this was a common cause of blindness in newborns.

“Gonococci are notorious for quickly becoming resistant to antibiotics,” says chemist Thomas Böttcher. This is because gonococci have the special ability to pick up genetic material from other microbes — including antibiotic resistance genes. Böttcher adds: “This is one of the reasons why gonococcal strains have recently emerged that are resistant to all antibiotics currently in use — such superbugs can no longer be treated with antibiotics.”

Interdisciplinary research approach enables breakthrough

Hauck and Böttcher’s teams have now been able to identify new substances from the group of alkyl quinolones (AQs) that are even effective against multidrug resistant gonococci. AQs are substances produced naturally by some bacteria to ward off other naturally occurring bacteria. Building on the idea that “the enemy of my enemy is my friend,” the researchers recreated these natural substances in the lab and synthesized slightly modified variants. “One of these new AQ molecules actually did have a unique effect: The chemical compound was able to kill gonococci without having a negative impact on other microorganisms or human cells,” says cell biologist Hauck. The team elucidated the nature of this astonishing effect using an interdisciplinary research approach that combines synthetic and organic chemistry with genetic and biochemical analyses as well as complex preclinical animal models.

It turns out that this novel antibiotic activates an existing “suicide” mechanism in gonococci. “From other microorganisms, we know about such self-destruction programmes based on toxin-antitoxin systems, and our AQ substance seems to precisely target this Achilles heel of gonococci,” explains Ann-Kathrin Mix, first author of the study and a doctoral researcher in Hauck’s team. The new antibiotic causes the breakdown of an antitoxin in gonococci, so that the toxin part is released and kills the bacteria. Importantly, the AQ substance can even eliminate multi-resistant gonococcal variants. However, since the respective toxin-antitoxin system is exclusive to gonococci, the antibiotic does not harm other bacteria.

Toxin-antitoxin systems are also present in other infectious microorganisms. The researchers thus expect that this type of treatment could be adapted for use against other bacterial pathogens. “The recently published findings open up a new and innovative way to fight pathogenic microbes before our arsenal of antibiotics is drained,” Hauck concludes.

Background:

• Research team led by Christof Hauck, professor of cell biology at the University of Konstanz, and Thomas Böttcher, professor of microbial biochemistry at the University of Vienna, discover a new class of antibiotics that selectively target Neisseria gonorrhoeae, the bacterium causing gonorrhoea. The new substances also work on multi-resistant variants of the pathogen.
• An interdisciplinary research approach combining synthetic and organic chemistry with genetic and biochemical analyses as well as complex preclinical animal models led to the discovery.
• First author Ann-Kathrin Mix is a doctoral researcher in the team led by Hauck

This form of therapy involves identifying and selecting immune cells (TILs) that are found in the tumor that specifically recognize and attack a patient’s tumor cells. Next, scientists grow those TILs into large quantities in the laboratory before they are finally administered to the patient.

Patients in the clinical trial, who had a variety of gastrointestinal tumors, also received the immune checkpoint inhibitor pembrolizumab (Keytruda) to help further boost their immune response. The result was nearly 24% of patients treated with selected TILs plus pembrolizumab had a substantial reduction in the size of their tumors, compared with 7.7% of patients who received selected TILs without pembrolizumab. Patients treated with TILs that had not been selected for anti-tumor activity had no tumor shrinkage.

“We’re seeing the first extension of cellular therapy with TILs into the common solid cancers,” said Steven A. Rosenberg, M.D., Ph.D., the study’s lead investigator at NIH’s National Cancer Institute. “We see a little crack in the solid wall of cancer by using cell-based immunotherapy for the common solid cancers, and we think we have ways to open that crack even further.”

The clinical trial included 91 patients with metastatic gastrointestinal cancers — including esophageal, stomach, pancreatic, colon, and rectal cancers — that had worsened despite a median of four prior treatment regimens. In the pilot phase of the trial, 18 patients were treated with TILs that had not been selected for anti-tumor activity, and there were no objective responses (tumor shrinkage of at least 30% is considered an objective response). In the second phase, 39 patients were treated with selected TIL therapy, and three (7.7%) had objective responses.

In the third phase, 34 patients received pembrolizumab immediately before selected TIL therapy to prevent the newly introduced immune cells from becoming inactivated by the patient’s own immune system. This group had the best response, with 8 of 34 (23.5%) patients experiencing an objective response. All 91 patients had also received standard chemotherapy and high-dose interleukin-2 before the TIL therapy.

In the trial’s second and third phases, objective responses were seen in multiple types of gastrointestinal cancers, including cancers of the colon, rectum, pancreas, and bile duct. Responses lasted between 8 months and more than 5.8 years in the group that received selected TIL therapy alone, and between 4 months and 3.5 years in the group that received selected TIL therapy and pembrolizumab. Serious side effects occurred in 30% of patients treated with selected TILs.

The researchers are now developing methods to identify TILs that recognize multiple, specific proteins within a tumor, known as neoantigens, to help increase the number of patients who respond to selected TIL therapy with pembrolizumab.

TIL therapy, developed in the late 1980s by Dr. Rosenberg and his colleagues at NIH, uses an individual’s own TILs to fight their tumor cells. Last year, the Food and Drug Administration approved the first TIL therapy for a solid cancer, lifileucel (Amtagvi), for treating advanced melanoma.

The new study was co-led by Dr. Rosenberg and NCI investigators Frank J. Lowery, Ph.D., and Stephanie L. Goff, M.D.

Now, findings from researchers at Texas A&M University provide new, evidence-based insight into minimizing the risk of these diseases at canine facilities.

“In adult, healthy humans and animals, these diseases usually cause diarrhea and occasionally other minor ailments, but for infants, puppies and the immunocompromised, infection could be deadly,” said Loni Taylor, PhD, DVM, an epidemiologist with the Texas A&M University School of Public Health, who led the study. “We wanted to identify the factors associated with kennel-housed dogs in Texas that test positive for both diseases.”

For their study, published in Comparative Medicine, Taylor and five colleagues with Texas A&M’s College of Veterinary Medicine & Biomedical Sciences sought to find out if a dog’s score on the Purina Fecal Scoring chart, breed, sex or age was associated with testing positive on a fecal screening test for either Giardia, Cryptosporidium or both organisms together.

To accomplish this, they tested fecal samples collected from a census sample of 153 clinically normal dogs housed at Texas kennels between March and October 2021. Breeds included golden retrievers, Labrador retrievers, beagles and a variety of large hounds and hound mixes.

The sex, age, breed and location were noted for the 153 dogs studied. In addition, fecal scores were determined by a single researcher using visual assessment of the samples, based on the Purina Institute metric (where 1 is hard and 7 is watery).

A secondary data analysis and statistical analysis found that dogs were significantly more likely to test positive for Giardia (45%) than Cryptosporidium (7%) (P < 0.01), although no clear link was found between sex or breed and these infections.

In addition, kennel-housed dogs 18 months of age or younger had 3.4 times the odds of Giardia infection compared with older dogs, and hard stool was associated with negative test status for Giardia in the stool.

No statistically significant relationship was found for age or fecal score and Cryptosporidium-positive test status, and Taylor noted that additional studies with larger sample sizes could help identify such a relationship.

“The primary takeaway is that age and fecal score are important factors for choosing which dogs to screen for subclinical Giardia,” Taylor said. “And given the increased odds of Giardia infection, screening should be as robust as the recommended combination of testing methods.”

“Hypertension is known as the silent killer because people can have blood pressure that’s too high without having any symptoms from it,” said senior author Jason H. Wasfy, MD, MPhil, of the Cardiology Division, Department of Medicine at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. Wasfy is also a physician investigator at the Mongan Institute at MGH. “If they’re not getting checked for it enough, then high blood pressure can damage the heart and the vessels over time in a way that would have been preventable had the blood pressure been detected early.”

In the United States, nearly half of individuals with hypertension are unaware of or untreated for the disease.

“There is so much information that’s generated through routine clinical care, such as when you see your doctor or undergo a test. And there are often subtle clues in this information that may indicate a patient has hypertension. But it’s impossible for clinicians to master the entire medical record. The premise of our trial was that the data are likely hiding in plain sight, and we wanted to validate methods of bringing it to light to improve the care of our patients,” said lead author Adam Berman, MD, MPH, who conducted the study while in the Division of Cardiovascular Medicine at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. At the time, Berman was the David F. Torchiana Fellow in Health Policy and Management at the Massachusetts General Physicians Organization. Berman is now an assistant professor in the Department of Medicine, the Leon H. Charney Division of Cardiology at NYU Grossman School of Medicine.

The research team created and then used natural language processing that could sift through data from echocardiograms (heart ultrasounds) to identify cases of left ventricular hypertrophy, a thickening of the heart muscle often caused by hypertension. The algorithm identified 648 patients at Mass General Brigham who were not previously known to have any heart muscle problems and were not being treated for hypertension. The average patient age was 59 years and 38% were women. They randomized half of the patients to receive the intervention, and, for those patients, a population health coordinator notified the patient’s doctor of the finding. They also provided resources for additional care, including facilitating a 24-hour blood pressure monitoring test or scheduling an evaluation with a cardiologist. The clinicians for patients in the non-intervention control group were not contacted, and their patients were monitored under usual care.

Patients in the intervention group were nearly four times more likely to receive new hypertension diagnoses (15.6% vs 4.0%) and to be prescribed antihypertensive medication (16.3% vs 5.0%) than those in the control group. There was no meaningful difference in the number of follow-up appointments with primary care physicians between the groups. Clinicians mostly viewed the intervention positively — of the 82% who responded to the initial notification, qualitative scoring showed 72% had a positive reaction.

“There was a strong interest from our team in making sure this is something that physicians and patients would value,” Wasfy said. “Clinicians are often overloaded with alerts that can cause fatigue and burnout, so we intentionally designed our outreach to be delivered by a person.”

More work is needed to determine if this notification delivery method could be altered or automated for larger reach and easier implementation in other healthcare settings while maintaining effectiveness.

“The goal is to augment traditional care, using the data that already exist,” said Berman. “These patients have undergone testing, and their data are sitting there in a digital library gathering digital dust. Our trial demonstrates that we can harness these data to improve healthcare delivery and the treatment of our patients.”

Authorship: In addition to Wasfy and Berman, Mass General Brigham authors include Michael K. Hidrue, Curtis Ginder, Linnea Shirkey, Japneet Kwatra, Anna C. O’Kelly, Sean P. Murphy, Jennifer M. Searl Como, Yee-Ping Sun, William T. Curry, Marcela G. del Carmen, Ron Blankstein, David A. Morrow, Benjamin M. Scirica, Niteesh K. Choudhry, and James L. Januzzi. Additional authors include John A. Dodson and Danielle Daly.

Disclosures: A full list of disclosures can be found in the paper published in JAMA Cardiology.

Funding: The study intervention was funded by the Massachusetts General Physicians Organization in support of cardiovascular care delivery innovation.

That’s the takeaway from new research from a team of scientists, including researchers from the University of Colorado Boulder. The findings suggests that long-term exposure to Martian dust could create a host of health problems for future astronauts — leading to chronic respiratory problems, thyroid disease and more.

The study, published in the journal GeoHealth, is the first to take a comprehensive look at the chemical ingredients that make up Martian dust, and their possible impacts on human health. It was undertaken by a team from the worlds of medicine, geology and aerospace engineering.

“This isn’t the most dangerous part about going to Mars,” said Justin Wang, lead author of the study and a student in the Keck School of Medicine at the University of Southern California in Los Angeles. “But dust is a solvable problem, and it’s worth putting in the effort to develop Mars-focused technologies for preventing these health problems in the first place.”

Wang, a CU Boulder alumnus, noted that Apollo era astronauts experienced runny eyes and irritated throats after inhaling dust from the moon. Apollo 17’s Harrison Schmitt likened the symptoms to hay fever.

But scientists know a lot less about the potential harms of Martian dust. To begin to answer that question, Wang and his colleagues drew on data from rovers on Mars and even Martian meteorites to better understand what makes up the planet’s dust. The group discovered a “laundry list” of chemical compounds that could be dangerous for people — at least when inhaled in large quantities and over long periods of time.

They include minerals rich in silicates and iron oxides, metals like beryllium and arsenic and a particularly nasty class of compounds called perchlorates.

In many cases, those ingredients are present in only trace amounts in Mars dust. But the first human explorers on Mars may spend around a year and a half on the surface, increasing their exposure, said study co-author Brian Hynek.

“You’re going to get dust on your spacesuits, and you’re going to have to deal with regular dust storms,” said Hynek, a geologist at the Laboratory for Atmospheric and Space Physics (LASP) at CU Boulder. “We really need to characterize this dust so that we know what the hazards are.”

Into the bloodstream

One thing is clear, he added: Mars is a dusty place.

Much of the planet is covered in a thick layer of dust rich in tiny particles of iron, which gives the planet its famous red color. Swirling dust storms are common and, in some cases, can engulf the entire globe.

“We think there could be 10 meters of dust sitting on top of the bigger volcanoes,” said Hynek, a professor in the Department of Geological Sciences. “If you tried to land a spacecraft there, you’re going to just sink into the dust.”

Wang found his own way to Martian dust through a unique academic path. He started medical school after earning bachelor’s degrees from CU Boulder in astronomy and molecular, cellular and developmental biology, followed by a master’s degree in aerospace engineering sciences. He currently serves in the Navy through its Health Professions Scholarship Program.

He noted that the biggest problem with Martian dust comes down to its size. Estimates suggest that the average size of dust grains on Mars may be as little as 3 micrometers across, or roughly one-ten-thousandth of an inch.

“That’s smaller than what the mucus in our lungs can expel,” Wang said. “So after we inhale Martian dust, a lot of it could remain in our lungs and be absorbed into our blood stream.”

An ounce of prevention

In the current study, Wang and several of his fellow medical students at USC scoured research papers to unearth the potential toxicological effects of the ingredients in Martian dust.

Some of what they found resembled common health problems on Earth. Dust on Mars, for example, contains large amounts of the compound silica, which is abundant in minerals on our own planet. People who inhale a lot of silica, such as glass blowers, can develop a condition known as silicosis. Their lung tissue becomes scarred, making it hard to breath — symptoms similar to the “black lung” disease that coal miners often contract. Currently, there is no cure for silicosis.

In other cases, the potential health consequences are much less well-known.

Martian dust carries large quantities of highly oxidizing compounds called perchlorates, which are made up of one chlorine and multiple oxygen atoms. Perchlorates are rare on Earth, but some evidence suggests that they can interfere with human thyroid function, leading to severe anemia. Even inhaling a few milligrams of perchlorates in Martian dust could be dangerous for astronauts.

Wang noted that the best time to prepare for the health risks of Martian dust is before humans ever make it to the planet. Iodine supplements, for example, would boost astronauts’ thyroid function, potentially counteracting the toll of perchlorates — although taking too much iodine can also, paradoxically, lead to thyroid disease. Filters specifically designed to screen out Martian dust could also help to keep the air in living spaces clean.

“Prevention is key. We tell everyone to go see their primary care provider to check your cholesterol before it gives you a heart attack,” Wang said. “The best thing we can do on Mars is make sure the astronauts aren’t exposed to dust in the first place.”

A new study conducted at the Human and Environmental Physiology Research lab (HEPRU) at the University of Ottawa has unveiled significant findings on the effects of cold water acclimation on autophagic (the cells’ recycling system, which promotes cellular health) and apoptotic (the programmed cell death that gets rid of damaged cells) responses in young males. The research highlights the potential for cold exposure to enhance cellular resilience against stress.

The study, conducted by Kelli King, postdoctoral fellow, and Glen Kenny, Full Professor at uOttawa’s School of Human Kinetics and Director of HEPRU, involved ten healthy young males who underwent cold-water immersion at 14°C (57.2°F) for one hour across seven consecutive days. Blood samples were collected to analyze the participants’ cellular responses before and after the acclimation period.

“Our findings indicate that repeated cold exposure significantly improves autophagic function, a critical cellular protective mechanism,” says Professor Kenny. “This enhancement allows cells to better manage stress and could have important implications for health and longevity.”

The research revealed that while autophagy was initially dysfunctional after high-intensity cold stress, consistent exposure over a week led to increased autophagic activity and decreased cellular damage signals.

“By the end of the acclimation, we noted a marked improvement in the participants’ cellular cold tolerance,” explains King, the study’s first author. “This suggests that cold acclimation may help the body effectively cope with extreme environmental conditions.”

The implications of this study extend beyond athletic performance. Cold water immersion has gained popularity for its potential health benefits, and this research provides some scientific backing for its efficacy. The findings suggest that proper autophagic activity could not only extend cellular longevity but also prevent the onset of various diseases.

As the use of cold exposure becomes increasingly mainstream, understanding its effects on cellular mechanisms is vital. Professor Kenny emphasizes, “This work underscores the importance of acclimation protocols in enhancing human health, especially in contexts where individuals are exposed to extreme temperatures.”

“We were amazed to see how quickly the body adapted,” notes King. “Cold exposure might help prevent diseases and potentially even slow down aging at a cellular level. It’s like a tune-up for your body’s microscopic machinery.”

These results apply to young males and more research is needed to see if it would also apply to other cohorts.

The meniscus is a complex structure that serves as a critical shock absorber in the knee. and one-size-fits-all treatments aren’t always effective. Through creating a treatment adaptable to the different needs of patients, the researchers believe they may have unlocked a better fix no matter where the injury occurs in a meniscus.

“We developed a hydrogel that can be adjusted based on the patient’s age and the stiffness requirements of the injured tissue, which is important because the meniscus has different biochemical and biomechanical properties that vary depending upon the location in the tissue,” said the study’s senior author, Su Chin Heo, PhD, an assistant professor of Orthopaedic Surgery in the McKay Orthopaedic Research Lab at Penn. “Current treatments, including graft-base methods, do not fully recreate these complex differences, leading to poor healing.”

Hydrogels are flexible, water-absorbing materials commonly found in everyday products like contact lenses and baby diapers. The researchers developed a specialized hydrogel by first extracting proteins from donor cow meniscus tissue. Those proteins then directed new cells to become the right types of repair cells for the damaged meniscus and were used as the basis for the treatment’s structures.

To prevent rejection, the team removed cellular components from the cow tissue while preserving its structural framework. This “decellularization” process reduces the risk of immune reactions when implanted, making the treatment both safer and more effective.

To further customize the hydrogels, Heo and his fellow researchers used 3D-printing techniques to account for the variation in the meniscus tissue. That way, they could more closely match the tissue in the areas they were trying to repair. Mismatched tissues might not heal well.

“In our animal studies, we’ve seen the hydrogel integrate well with the surrounding tissue, potentially offering patients a more complete recovery,” said the study’s first author Se-Hwan Lee, PhD, a post-doctoral fellow in the McKay Lab. “It’s a more precise, biologically matched solution. We believe this could outperform current treatments.”

The team is now transitioning from small mammal studies to large animal models.

“Our first clinical goal will be to treat smaller, localized meniscus tears,” Heo said. “Once we have success there, I believe we could expand to more complex injuries in the meniscus.”

The study was supported by grants from the National Institutes of Health (K01 AR07787, R21 R077700, P30 AR069619, R01 AR056624, R01 HL163168), the National Science Foundation (CMMI 1548571), and Department of Veterans Affairs’ CReATE Motion Center (I50 RX004845) in the United States. It was also supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare (HI19C1095) and National R&D Program through the National Research Foundation of Korea (NRF), funded by Ministry of Science and ICT (RS-2024-00405574) in South Korea.

A growing body of research has drawn connections between everyday discrimination — the routine and often subtle forms of mistreatment that people experience on a day-to-day basis — and poor mental health. A new study by Boston University School of Public Health (BUSPH) and Brown University suggests that higher exposure to discrimination increases a person’s chances of developing depression and/or anxiety, and that this outcome varies by race and ethnicity.

Published in JAMA Network Open, the study found that over half of US adults experienced some form of discrimination, and individuals with high exposure to discrimination have more than five times the chances of screening positive for depression, and five times the chances of screening positive for anxiety. Compared to adults who do not experience discrimination, adults who do experience this mistreatment have nearly nine times the odds of screening positive for both depression and anxiety.

These observations were similar for men and women, but more pronounced among multiracial, White, and Asian adults, populations that are often overlooked in research and discussions about the effect of discrimination on health.

The nationally representative findings provide valuable insight into the relationship between discrimination and mental health among multiple populations, building upon previous research on this subject that has been restricted by smaller study groups or limited comparisons between Black and White populations, or Hispanic or Latino and non-Hispanic or non-Latino populations. The researchers hope this data provides a deeper understanding of the mental health consequences of discrimination among a wider range of demographic groups, and encourages mental health screenings and support to mitigate these racial disparities.

“Our study expands our understanding beyond typical Black-White comparisons, showing that everyday discrimination is a widespread issue that negatively impacts mental health across all racial and ethnic groups,” says study lead and corresponding author Dr. Monica Wang, associate professor of community health sciences at BUSPH.

For the study, Dr. Wang and study senior author Dr. Marie-Rachelle Narcisse, assistant professor of psychiatry and human behavior at Brown, assessed 2023 national survey data to gauge experiences of discrimination, depression, and anxiety among nearly 30,000 adults ages 18 or older. This sample population was weighted to represent more than 258 million US adults. To measure discrimination, the researchers utilized standardized scales that capture the frequency of mistreatment, such as receiving poor service or being harassed. They also utilized standardized scales to quantify experiences with depression (such as feeling down or hopeless, or having little interest in doing things) and anxiety (such as feeling nervous or experiencing an inability to stop worrying).

Nearly 56 percent of adults experienced a form of discrimination, and 3.6 percent of this group reported experiencing high levels of discrimination, most prevalent among Black adults, followed by multiracial or other adults, Hispanic or Latino adults, White adults, and Asian adults. Discrimination was also more common among adults experiencing certain health disadvantages such as disabilities, obesity, and food insecurity, as well as immigrants and women.

The researchers theorize that a combination of social, cultural, and systemic factors may be driving discrimination-related depression or anxiety among specific racial and ethnic groups. Multiracial individuals may navigate unique experiences of mistreatment based on their multiple racial identities, while White individuals may experience mental health challenges that stem from mistreatment related to their income or educational levels. Asian adults may experience depression or anxiety stemming from language barriers or the “model minority” stereotype, which assumes all Asian individuals are high-achieving and successful.

These perceived experiences carry real psychological weight, says Dr. Narcisse.

“Studies have shown that discrimination shapes mental health most deeply when left unacknowledged,” she says. I hope this study creates more awareness. As in awareness, there is strength and the ability to seek healing more intentionally.”

Dr. Wang and Dr. Narcisse also caution that these findings do not suggest that discriminatory experiences and any related adverse mental health problems are less significant among Black, Hispanic, and Latino populations, as these groups continue to experience multiple health challenges driven by systemic racism and a long history of oppression.

“Our results are a powerful reminder that discrimination is everyone’s issue — and addressing it benefits society as a whole,” Dr. Wang says.

Dr. Wang is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases; Dr. Narcisse is supported by the National Institute of General Medical Sciences and the Bradley Hospital COBRE Center for Sleep and Circadian Rhythms in Child and Adolescent Mental Health. The funding sources had no role in the design or conduct of the study; collection, analysis, and interpretation of data; preparation, review, or approval of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.

“ROS play an important role in healthy and diseased cells, but pathways that sense and control cellular ROS levels are not well understood,” said corresponding author Liron Bar-Peled, PhD, of the Krantz Family Center for Cancer Research at Mass General Cancer Center (MGCC), a member of the Mass General Brigham healthcare system. “A clearer understanding of ROS could help us understand why chemoresistance occurs in some cases.”

Low concentrations of ROS are required for normal cell signaling, but higher levels of ROS can damage cells and contribute to diseases such as cancer and neurodegeneration. Researchers know that mitochondria play an important role in ROS production, but it has been unclear if ROS-sensing proteins influence the mitochondria. If they do, this could impact responses to some anti-cancer treatments.

To investigate, co-first authors Junbing Zhang, PhD, Yousuf Ali, PhD, and Harrison Chong, of the Krantz Family Center for Cancer Research, and colleagues screened cancer cells for ROS-sensing proteins that might contribute to chemoresistance. The screen identified mutations that increased treatment resistance, and the team traced two of them to a protein called VPS35. Through further studies, they found that these mutations led to lowered ROS levels within the cell.

In addition, the investigators analyzed VPS35 expression levels in 24 patients with high grade serous ovarian cancer (HGSOC), who received treatment at MGCC. They noted that higher tumoral VPS35 levels were associated with improved treatment responses and with overall survival rates.

In a new Nature Microbiologystudy, University of Pittsburgh researchers show that a cocktail of growth factors reversed would-be lethal cell damage in mice with anthrax, suggesting that this approach could be adapted for use in patients beyond the brink.

“While only a few people die from anthrax in the United States each year, there is always the concern that the bacterium could be released on a large scale as a bioweapon,” said senior author Shihui Liu, M.D., Ph.D., associate professor of medicine at the Pitt School of Medicine and member of the Aging Institute, a joint venture of Pitt and UPMC. “Because the early symptoms of anthrax are non-specific and flu-like, the disease often isn’t diagnosed until it’s too late for current treatments to help. We need new approaches to treat this later stage of the disease.”

When B. anthracis enters the body through inhalation, ingestion, injection or contact with skin, it produces two proteins that combine to form lethal toxin.

Early on, anthrax can be treated with antibiotics that eliminate the bacterium or antibodies that neutralize lethal toxin before it enters cells. But once inside cells, the toxin inactivates members of a group of enzymes known as MEKs by cleaving off one of their ends, disrupting the important pathways they control and rapidly causing widespread cellular, tissue and organ damage — and death.

To learn more about the roles of MEK-controlled pathways in anthrax toxicity, Liu and his team generated mice with modified MEKs that were resistant to being cleaved by lethal toxin. These included MEK1 and MEK2, which control a pathway called ERK involved in cellular division and survival, and MEK3 and MEK6, which regulate the p38 pathway that’s involved in stress-induced defense.

When exposed to lethal toxin or B. anthracis, mice with either modified MEK1/2 or MEK3/6 had much greater survival than normal animals, indicating that anthrax must inactivate both the ERK and p38 pathways to kill its host.

In mice and human cells exposed to lethal toxin or B. anthracis, a combination of three growth factors — all individually approved as treatments for other conditions — reactivated the ERK pathway and brought them back from the point of no return.

“Because lethal toxin breaks MEK proteins by clipping off their ends, we thought that this cellular damage was irreversible,” said Liu. “So we were really surprised to find that specific growth factors were able to reactivate the ERK pathway and rescue the cell.”

Because different types of cells in the body may require different growth factors to activate ERK, the researchers are now working to optimize a treatment for anthrax in humans.

Other authors on the study were Jie Liu, Ph.D., Zehua Zuo, Ph.D., Michael Ewing, Qing Cao, M.S., Qi Li, M.D., Ph.D., and Toren Finkel, M.D., Ph.D., all of Pitt and UPMC; Liu Cao, M.D., Ph.D., of China Medical University; and Stephen H. Leppla, Ph.D., of the National Institute of Allergy and Infectious Diseases (NIAID).

This research was supported by NIAID (R01AI170574).

“The cause of Kawasaki disease has been a mystery for over 50 years,” said Anne Rowley, MD, pediatric infectious diseases expert and scientist at Manne Research Institute at Lurie Children’s, who is the lead author on the study published in Laboratory Investigation. “Our compelling data are a huge step forward and provide a clear direction for the field to identify and sequence the virus that causes Kawasaki disease in susceptible children. This will be critical to advancing the diagnosis, treatment and prevention of Kawasaki disease.”

Kawasaki disease is relatively uncommon, affecting mostly children between 6 months and 5 years of age. Lurie Children’s sees 50-60 newly diagnosed Kawasaki disease patients a year.

Currently, there is no diagnostic test for Kawasaki disease. Clinical signs include fever, rash, swelling of the hands and feet, irritation and redness of the whites of the eyes, swollen lymph glands in the neck, and irritation and inflammation of the mouth, lips, and throat. Children with Kawasaki disease have a 20 percent chance of developing heart disease, while infants are at higher risk with 50 percent chance of cardiac complications. The standard treatment, intravenous immunoglobulin and aspirin, substantially decreases the risk of heart disease in patients with Kawasaki disease. Steroids may be added for the highest risk patients.

In their study, Dr. Rowley and colleagues prepared antibodies from blood cells of children with Kawasaki disease, in order to see what these antibodies will target in tissue samples of patients who died from the disease. They found that the antibodies recognized so-called inclusion bodies, which are by-products of a virus, in all 20 tissue samples that represented cases from the U.S. and Japan over 50 years.

“We saw the same inclusion bodies targeted in every tissue sample spanning five decades and two continents, which shows that we are dealing with one predominant virus causing Kawasaki disease,” said Dr. Rowley. “It appears to be a respiratory virus since the inclusion bodies were in the medium size airways. Going forward, we need to focus on studies of pathology specimens to gain understanding of what is inside the inclusion bodies so that we can identify the Kawasaki disease virus and finally solve the mystery.”

This work was supported by the National Institutes of Health grant R01AI150719 to Dr. Rowley, the Max Goldenberg Foundation, the Center for Kawasaki Disease at the Ann & Robert H. Lurie Children’s Hospital of Chicago, the Northwestern University NUSeq Core Facility, and the Northwestern University Flow Cytometry Core Facility supported by Cancer Center Support Grant (NCI CA060553).

Dr. Rowley is a Professor of Pediatrics and Microbiology-Immunology at Northwestern University Feinberg School of Medicine. She holds the Dorothy M. and Edward E. Burwell Board Designated Professorship in Immunobiology at Lurie Children’s.

Ann & Robert H. Lurie Children’s Hospital of Chicago is a nonprofit organization committed to providing access to exceptional care for every child. It is the only independent, research-driven children’s hospital in Illinois and one of less than 35 nationally. This is where the top doctors go to train, practice pediatric medicine, teach, advocate, research and stay up to date on the latest treatments. Exclusively focused on children, all Lurie Children’s resources are devoted to serving their needs. Research at Lurie Children’s is conducted through Stanley Manne Children’s Research Institute, which is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is the pediatric training ground for Northwestern University Feinberg School of Medicine. It is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report.

The study, which was published in the Journal of Health Psychology, looked at how patients with Long Covid experience their illness. The study found that many patients feel they have to prove their illness is physical to be taken seriously and, as a result, often reject psychological support, fearing it implies their symptoms are “all in the mind.”

Professor Jane Ogden, co-author of the study from the University of Surrey, said:

“We found that the problem isn’t people with Long Covid refusing help — it’s about the deep need for people to be believed. When a patient feels dismissed, offering psychological support instead of medical care can be misconstrued as insulting.”

According to the Office for National Statistics, there are 1.9 million people who live with Long Covid in the UK. Long Covid symptoms include fatigue, difficulty concentrating, muscle aches and shortness of breath, which persist for many weeks, sometimes months, after the initial Covid-19 infection.

Surrey’s study involved in-depth interviews with 14 people in the UK between the ages of 27 to 63 who had experienced Long Covid symptoms for more than four weeks. The group included 12 women and two men.

Saara Petker, clinical psychologist, co-author of the study and former PhD student at the University of Surrey, said:

“We found that our participants are living a life of constant uncertainty, struggling to find treatment. People told us that they didn’t feel listened to, some said they’d lost trust in doctors, their social circles and even their own bodies because of the whole experience.

“Medical advice is crucial — but psychological support must be offered with care. If it’s seen as replacing medical help, it can feel dismissive.”

One of the method’s applications is to give a more complete sense of human ancestry, says Gideon Bradburd, U-M professor of ecology and evolutionary biology. For example, when you send your DNA off for a personalized ancestry report, the report you get back is only a very small view of your family tree pinned in a specific point and space in time.

These types of genetic reports reflect the amount of a person’s genome that they’ve inherited from individuals living in a specific area at a specific point in the past. If your ancestry report says that you’re 50% Irish, that means you have a lot of second through fourth cousins who currently live in Ireland, says Bradburd. But in reality, your family tree is much more like a movie than this snapshot.

The statistical method developed by Bradburd and fellow U-M researchers Michael Grundler and Jonathan Terhorst can give people a “movie” version of their ancestry, showing where their ancestors originated and how they moved across the globe. The method uses modern genetic sequence samples, estimates all of the locations of an individual’s genetic ancestors, identifies the average location of those individuals based on assumptions about how people move, and tracks it back over centuries.

The researchers’ method can be used for more than tracing human ancestry. It can also be used to track the emergence of viruses, the divergence of animal populations and other genealogical tracking. Their results are published in the journal Science.

“There’s ways in which consumer ancestry reports are interesting, and certainly it’s powerful to learn about your history, especially for folks who’ve been adopted or orphaned or are disconnected from their family,” Bradburd said. “But there are other ways in which these ancestry reports can be really problematic. They really reify notions of the biological essentialism of race because they’re presenting these categories of Irish, for example, as if they’re ideals, that they’re real and unchanging through time.”

But researchers know this isn’t the case. A field, forged by Nobel Prize-winning geneticist Svante Pääbo, developed the tools to genotype ancient DNA. This allows researchers to trace waves of human populations as they spread throughout the world — particularly in Eurasia, where most of this type of genetic sequencing has been happening, Bradburd says. This has allowed researchers to see how human groups enter and leave geographic regions through time.

“Because the genetic flavor of a location changes so much through time, we know it’s meaningless to say, ‘This is what it means to be Irish,'” Bradburd said. “It’s not just that being ‘genetically Irish’ doesn’t mean anything; it also means that you are everything.”

Bradburd points to a thought experiment in human biology: imagine two biological parents and four biological grandparents. This doubles every generation, and it only has to double a relatively small number of generations before there are more people in that direct lineage than there have ever been humans alive on Earth.

This also means that you don’t have to go very far back in time to discover that many people share many ancestors.

“Because our pedigrees explode so quickly, they also must collapse in the same sense that you and I must share many, many relatives at many points back in time, and that’s true for every person alive on Earth,” Bradburd said. “We’re all extraordinarily closely related to each other.”

The ancestry reports are accurate, Bradburd said, but specifically when they are tied to a time period.

“The ancestry reports aren’t wrong, but they’re leaving out a very important component, which is the ‘when’ you have Irish ancestry,” Bradburd said. “Because we know the modern human lineage arose in Africa, it is as accurate to say that you have 100% African ancestry at a deeper time horizon.”

The statistical method, called Gaia (geographic ancestry inference algorithm), starts by making a very simple assumption about how individuals move: that typically they move locally. The method combines that assumption with the location of modern-day individuals and a genetic structure that relates them called the ancestral recombination graph.

With those two pieces of information and the simple model of how individuals move, the researchers can compute the “most parsimonious locations of ancestors,” Bradburd says. The researchers then can propagate that information back through the past.

Bradburd’s work is answering a call from the National Academy of Sciences, urging researchers working on human population genetics to move away from race-based labels. While the sociological realities of race are undeniable, racial categories do not make good predictions about genetic variation, he says.

Because of the disconnect between race and genetics, racial labels can often be imprecise: two people might share the same label, but be much more closely or less closely related to each other. In addition, because the genetics in a certain geographic area can shift so much over time, geographic and national labels can also be misleading, Bradburd says.

“Saying you’re ‘genetically Irish’ makes it seem like ‘Irish’ has always meant the same thing, and genetically we know that is not true and also that anyone who is Irish — meaning they inherited parts of their genome from people who lived in Ireland — is only Irish with respect to a specific time horizon,” he said. “That these race labels gloss over both of these important pieces of information is a big loss of specificity and also poses a very real danger to the weaponization of science for political means.”

The method Bradburd’s team developed can be applied to systems other than human genetics. Researchers can use this method to look at the genetic distribution of the organisms they study. Researchers can also use this method to learn about the migration of organisms — human and otherwise, Bradburd says.

For example, researchers have been able to look at measures of genetic similarity of population between two locations and infer that they are more or less closely connected by migration, or more or less isolated from each other. But this tool allows researchers to pin a timeline on when these movements happened.

And this tool can apply in this case to more than tracing human genetics — it can be used to help determine when a disease might have emerged from a specific region of the world, for example. The U-M group is working with researchers in Australia to learn how mosquitoes colonized islands of the South Pacific, and with researchers in Michigan and Ohio to understand the history and dispersal of the Massasauga rattlesnake.

“It’s one of the things I’m quite excited about with this — you can use this method to identify dispersal patterns through time and between specific locations,” Bradburd said. “Notions of ancestry don’t have to be static. Instead, you should think of them as being dynamic, and interesting and understandable more as a movie than as a picture.”

Now, with advanced data analysis and machine learning, scientists have identified a set of COVID-derived molecular mimics that are most likely to be involved in triggering autoimmunity.

The new results are published in ImmunoInformatics.

The researchers first looked for viral components that are similar to the human proteins known to be attacked in various autoimmune diseases. Theoretically, these viral proteins could trigger the immune system to target the human proteins they resemble. They narrowed down their list of culprits by using machine learning to identify only those viral components that are most likely to be bound by human antibodies.

Some of the viral components the researchers found have been associated with type 1 diabetes or multiple sclerosis.

Importantly, some of the human proteins that the researchers identified as likely targets of COVID-induced autoimmunity are only found in people with specific genetics, suggesting that people who produce those proteins may be at higher risk of COVID-induced autoimmunity.

“It’s exciting that in collaboration with our clinical colleagues, we can now use AI and machine learning to address medical conditions exacerbated by the COVID pandemic,” says Julio Facelli, PhD, distinguished professor of biomedical informatics at University of Utah Health and the senior author on the paper. “Hopefully, our results will lead to better understanding and eventual treatment and prevention of these debilitating conditions.”

The results are published in Immunoinformatics as “Molecular mimicry impact of the COVID-19 pandemic: Sequence homology between SARS-CoV-2 and autoimmune diseases epitopes.”

Research was supported by the National Library of Medicine (5T15LM007124-24) and by the CTSA award to the Utah Clinical and Translational Science Institute (UM1TR004409). Computational resources were provided by the Utah Center for High Performance Computing. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Obesity is considered to be a global public health concern, but experts still disagree about the precise origins and causes of rising obesity rates. One topic under debate is whether a person’s individual genetics and behaviors are more or less important than environmental factors, like socioeconomic status, in developing obesity.

In the new study, researchers estimated the impact of several factors on a person’s weight, including societal factors, like a person’s job type, as well as early life factors, like a person’s birth order, how they were delivered and whether their mother smoked or was obese. They looked specifically at whether a person was overweight, obese or severely obese at age 16 and age 42. They also looked at participants’ weight between ages 16 to 42, a range that spans the rise in obesity rates in the United Kingdom. The data came from the 1958 National Child Development Study, a long-term study that followed the lives of more than 17,000 people born in a single week in March 1958 across England, Scotland and Wales.

The analysis showed that if a mother was obese or if she smoked, her child was more likely to be obese or severely obese at each of the ages examined. The findings demonstrate that these early life factors can have a persistent effect on a person’s weight. Notably, these factors were just as powerful before and after the start of the rise in obesity rates in the UK, suggesting that the impact of individual factors, like behaviors, likely did not change during that time.

The results suggest that societal and early-life risk factors could be used to target obesity prevention programs for children and adults. The researchers also conclude that, since individual risk factors have not changed as obesity rates have risen, new studies are needed to identify societal factors that may have caused the current obesity pandemic.

The authors add: “Our research shows that the effect of maternal influences persists through to age 42 and that strikingly, those predictors were just as powerful (and prevalent) in the era before the current obesity pandemic began. This suggests that, as Geoffrey Rose pointed out, novel studies are needed of factors at the community/societal level that may have caused the current obesity pandemic, since individual-level risk factors appear not to have changed over the time period spanning the pandemic’s onset and growth.”

Chi-Huey Wong, a chemistry professor at Scripps Research, will present results from his team’s studies today at the ACS Spring 2025 Digital Meeting, a meeting of the American Chemical Society.

Wong says that the premise of this research is simple: It’s an effective vaccine that targets more than one coronavirus at a time, which will allow individuals to receive a single shot for protection against multiple infectious agents. An ongoing Phase I clinical trial led by Rock Biotherapeutics has completed enrollment and dosing and will be discussed by Wong during his ACS Spring 2025 Digital Meeting presentation.

“For a lot of vaccines, like smallpox and tetanus, we only have to be immunized once,” Wong says. “But we have to take a flu shot every year.” He adds that the high rate of mutation seen in the SARS-CoV-2 virus — specifically, the receptor binding domain on the virus’ spike protein — has led to an unprecedented number of COVID-19 vaccine updates.

The low-mutation region that Wong’s team chose to target for the new vaccine is within the stalk region of the virus’ spike protein. However, this stalk is coated with chains of sugar molecules called glycans from the host’s cells. And the sugar coating keeps antibodies from recognizing, and therefore inactivating, the virus.

So, the researchers devised a “low-sugar” vaccine that removes the protective glycans through enzymatic digestion and creates antibodies that specifically target the low-mutation stalk region of the virus’ spike protein, should the actual virus enter the body.

In animal studies with hamsters and mice, the universal vaccine created more diverse antibodies with higher titers (concentrations in the blood, where immune system cells travel throughout the body) compared to individual vaccines against variants of SARS-CoV, as well as MERS-CoV, the virus that causes Middle East respiratory syndrome. This improved and broadened the vaccine’s protection. Wong says the team’s new vaccine could also provide protection against coronaviruses that cause influenza and the common cold.

In addition to vaccines for viral infections, Wong’s team is using the technique to develop vaccines for the treatment of various cancers. They recently published two studies on glycan targets on cancer cells and enzymes linked to the synthesis of glycans on cancer cells in the Journal of the American Chemical Society.

While much attention has indeed focused on dietary content and caloric intake, emerging research suggests that eating behaviors — including meal duration, chewing speed, and number of bites taken — may have a big impact on how much food we consume. Previous studies have indicated that people who eat more slowly tend to consume less food overall, but specific, evidence-based guidelines on how to effectively slow down eating have been lacking. This is particularly true for Japan, where eating habits differ from Western norms.

Against this backdrop, a research team led by Professor Katsumi Iizuka from the Department of Clinical Nutrition, Fujita Health University, Japan, conducted a study to identify factors that influence meal duration and eating behavior. Their paper, co-authored by Dr. Megumi Aoshima and Dr. Kanako Deguchi from Fujita Health University and published in Volume 17, Issue 6 of Nutrients journal on March 10, 2025, explores factors including sex differences, chewing patterns, and external rhythmic stimuli and their relationship to how we consume our meals. “While nutritional science is often concerned with food metabolism and absorption and dietary content, there’s limited evidence in Japan on dietary behavior that connects the two. This intrigued me to study eating behavior, which involves gender differences,” explains Iizuka.

The study involved 33 healthy participants aged 20 to 65 years who were asked to eat slices of pizza under different conditions. Researchers measured meal duration, number of chews, number of bites, and chewing tempo (the rate or speed of chewing), noting how these variables changed when participants were exposed to different metronome rhythms using headphones.

The results revealed significant differences between men and women in eating behaviors. Women typically took longer to eat, averaging 87 seconds compared to 63 seconds for men. They also chewed more (averages of 107 vs. 80) and took more bites (4.5 vs. 2.1). However, the actual chewing tempo was similar between both sexes.

When adjusted for sex differences, meal duration was positively associated with the number of chews and bites taken, but not with body mass index or average eating tempo. Perhaps most interestingly, when participants were exposed to a slow metronome rhythm of about 40 beats per minute, their meal duration increased significantly compared to eating without rhythmic stimulation.

The study suggests several straightforward strategies to extend meal duration: increasing the number of chews per bite, taking smaller bites (which naturally increases the total number of bites per meal), and potentially creating a slower eating environment through calming music or rhythmic cues. “These are easy, money-saving measures that can be started right away to help prevent obesity,” says Iizuka, highlighting the practical implications of the results.

These findings have particular relevance for nutritional guidance and obesity prevention programs. Rather than focusing solely on food content, interventions could incorporate guidance on eating behaviors and environmental factors that promote slower eating. “Incorporating the proposed eating behavior into school lunches and other programs can lead to the prevention of future diseases related to obesity,” Iizuka notes.

The researchers acknowledge that future studies should test these findings with a variety of foods beyond pizza to confirm their applicability in diverse eating scenarios. Nevertheless, this research provides valuable evidence-based strategies that could be incorporated into obesity prevention and treatment programs immediately, without significant cost or complexity.

Hopefully, these efforts will help spread actionable advice to both prevent and address obesity and minimize its impact on health down the line.

Previous research has shown that interventions grounded in behavioral science that target student motivation have been effective at increasing math scores, suggesting that taking a similar “behaviorally informed” approach with teachers might have a comparable effect.

Now, a collaborative study published in the Proceedings of the National Academy of Sciences, and led by researchers at the Behavior Change for Good Initiative (BCFG) at the University of Pennsylvania has found that behaviorally informed email messages slightly improved students’ math progress compared to control messages.

“Our results showed that simple, low-cost nudges can help teachers support student progress in math,” says Angela Duckworth, Rosa Lee and Egbert Chang Professor in Penn’s School of Arts & Sciences and the Wharton School, who led the study and co-directs BCFG. “These nudges worked across different school contexts, with effects persisting eight weeks after teachers stopped receiving the nudges.”

The key to this megastudy was the partnership with Zearn Math, a nonprofit educational platform. “Large-scale studies on teacher-focused interventions have been rare due to the high cost and logistical challenges involved. Thanks to our partnership with Zearn Math, we were able to overcome these challenges,” says co-author Dena Gromet, executive director of BCFG.

A megastudy is “a large-scale experiment in which multiple interventions are tested simultaneously on the same outcome, a tournament approach, if you will,” says co-author Katy Milkman, James G. Dinan Endowed Professor and professor of operations, information and decisions at the Wharton School and co-director of BCFG. “Because all interventions run concurrently and are compared to a common control group, this method allows for direct comparisons of their effectiveness.”

In one of the largest studies of its kind — involving more than 140,000 teachers and nearly 3 million elementary students — the researchers compared the impact of 15 different interventions to a reminder-only message.

“These messages were behaviorally informed, meaning they were based on prior insights from behavioral science. For instance, one intervention asked teachers to make a specific plan for how they would use Zearn Math that week, an approach backed by research showing that people are more likely to follow through when they make detailed plans. Another intervention appealed to teachers’ empathy for their students, which previous research has demonstrated is supportive of student success,” Duckworth says.

Co-authors Katy Milkman (left) and Angela Duckworth are committed to dig deeper into what makes these kinds of interventions work and how to make them even more effective over time.

Specifically, the research team found that, compared to standard email reminders, behaviorally informed email messages improved students’ math progress during the four-week intervention period by 1.89%. The most effective intervention, which increased student math progress by about 5.06%, encouraged teachers to log into Zearn Math weekly for an updated, personalized report on their students’ progress.

“One especially promising takeaway is that personalized nudges — those that referenced progress updates about a teacher’s own students — were more effective than nonpersonalized ones,” Duckworth says.

The researchers note that though they are promising, the effects were small. “These results suggest the need for more intensive support than the light-touch email nudges we tested,” Milkman says. “And they underscore how hard it is to change human behavior.”

These findings, Milkman says, suggest several additional valuable avenues for future research, including “more random-assignment field experiments to confirm the causal benefits of teacher-targeted nudges and studies to probe the longer-term effects of behaviorally-informed interventions.”

Additional research is also needed, Duckworth says, “to confirm and explain the benefits of referencing personalized data when nudging teachers. It may be that capitalizing on teachers’ intrinsic motivation to help their students is a distinct and potentially cost-effective approach that can complement other interventions, such as offering performance bonuses and other extrinsic incentives.”

Next steps for researchers are to dig deeper into what makes these kinds of interventions work and how to make them even more effective over time. Future studies are needed to look into the long-term effects of nudges and explore why some interventions are more effective than others.

“The better we understand why something works, the more powerfully we can use it to create positive change,” Duckworth says. “Ultimately, this line of research could help shape smarter, more effective education policies.”

Angela L. Duckworth is the Rosa Lee and Egbert Chang Professor in the Department of Psychology in the School of Arts & Sciences and in the Department of Operations, Information, and Decisions in the Wharton School at the University of Pennsylvania and faculty co-director of the Penn-Wharton Behavior Change for Good Initiative.

Katherine L. Milkman is the James G. Dinan Endowed Professor in the Department of Operations, Information, and Decisions in the Wharton School of the University of Pennsylvania and faculty co-director of the Penn-Wharton Behavior Change for Good Initiative.

Dena M. Gromet is the Executive Director of the Behavior Change for Good Initiative at the University of Pennsylvania.

Other authors of the new study are Ron Berman, Eugen Dimant, Ahra Ko, Joseph S. Kay, Youngwoo Jung, Madeline K. Paxson, Ramon A. Silvera Zumaran, and Christophe Van den Bulte of the University of Pennsylvania; Aden Halpern of the University of Pennsylvania and the University of Pittsburgh; Nina Mazar of Boston University; Colin F. Camerer and Marcos N. Gallo of the California Institute of Technology; Amy Lyon of Colby-Sawyer College; Mary C. Murphy of Indiana University; Kathryn M. Kroeper of Sacred Heart University; Benjamin S. Manning of the Massachusetts Institute of Technology; Ilana Brody, Hengchen Dai, and Hal E. Hershfield of the University of Los Angeles; Ariel Kalil, Michelle Michelini, and Susan E. Mayer of the University of Chicago; Matthew D. Hilchey, Philip Oreopoulos, Renante Rondina, and Dilip Soman of the University of Toronto; Elizabeth Canning of Washington State University; and Sharon E. Parker of Philadelphia.

Research reported in this article was supported in part by an anonymous donor to Zearn Math. Support for this research was also provided in part by the AKO Foundation, J. Alexander, M. J. Leder, W. G. Lichtenstein, and A. Schiffman and J. Schiffman.

MIT instructor Karol Bacik and his colleagues studied the flow of human crowds and developed a first-of-its-kind way to predict when pedestrian paths will transition from orderly to entangled. Their findings may help inform the design of public spaces that promote safe and efficient thoroughfares.

In a paper appearing in the Proceedings of the National Academy of Sciences, the researchers consider a common scenario in which pedestrians navigate a busy crosswalk. The team analyzed the scenario through mathematical analysis and simulations, considering the many angles at which individuals may cross and the dodging maneuvers they may make as they attempt to reach their destinations while avoiding bumping into other pedestrians along the way.

The researchers also carried out controlled crowd experiments and studied how real participants walked through a crowd to reach certain locations. Through their mathematical and experimental work, the team identified a key measure that determines whether pedestrian traffic is ordered, such that clear lanes form in the flow, or disordered, in which there are no discernible paths through the crowd. Called “angular spread,” this parameter describes the number of people walking in different directions.

If a crowd has a relatively small angular spread, this means that most pedestrians walk in opposite directions and meet the oncoming traffic head-on, such as in a crosswalk. In this case, more orderly, lane-like traffic is likely. If, however, a crowd has a larger angular spread, such as in a concourse, it means there are many more directions that pedestrians can take to cross, with more chance for disorder.

In fact, the researchers calculated the point at which a moving crowd can transition from order to disorder. That point, they found, was an angular spread of around 13 degrees, meaning that if pedestrians don’t walk straight across, but instead an average pedestrian veers off at an angle larger than 13 degrees, this can tip a crowd into disordered flow.

“This all is very commonsense,” says Bacik, who is a instructor of applied mathematics at MIT. “The question is whether we can tackle it precisely and mathematically, and where the transition is. Now we have a way to quantify when to expect lanes — this spontaneous, organized, safe flow — versus disordered, less efficient, potentially more dangerous flow.”

The study’s co-authors include Grzegorz Sobota and Bogdan Bacik of the Academy of Physical Education in Katowice, Poland, and Tim Rogers at the University of Bath in the United Kingdom.

Right, left, center

Bacik, who is trained in fluid dynamics and granular flow, came to study pedestrian flow during 2021, when he and his collaborators looked into the impacts of social distancing, and ways in which people might walk among each other while maintaining safe distances. That work inspired them to look more generally into the dynamics of crowd flow.

In 2023, he and his collaborators explored “lane formation,” a phenomenon by which particles, grains, and, yes, people have been observed to spontaneously form lanes, moving in single-file when forced to cross a region from two opposite directions. In that work, the team identified the mechanism by which such lanes form, which Bacik sums up as “an imbalance of turning left versus right.” Essentially, they found that as soon as something in a crowd starts to look like a lane, individuals around that fledgling lane either join up, or are forced to either side of it, walking parallel to the original lane, which others can follow. In this way, a crowd can spontaneously organize into regular, structured lanes.

“Now we’re asking, how robust is this mechanism?” Bacik says. “Does it only work in this very idealized situation, or can lane formation tolerate some imperfections, such as some people not going perfectly straight, as they might do in a crowd?”

Lane change

For their new study, the team looked to identify a key transition in crowd flow: When do pedestrians switch from orderly, lane-like traffic, to less organized, messy flow? The researchers first probed the question mathematically, with an equation that is typically used to describe fluid flow, in terms of the average motion of many individual molecules.

“If you think about the whole crowd flowing, rather than individuals, you can use fluid-like descriptions,” Bacik explains. “It’s this art of averaging, where, even if some people may cross more assertively than others, these effects are likely to average out in a sufficiently large crowd. If you only care about the global characteristics like, are there lanes or not, then you can make predictions without detailed knowledge of everyone in the crowd.”

Bacik and his colleagues used equations of fluid flow, and applied them to the scenario of pedestrians flowing across a crosswalk. The team tweaked certain parameters in the equation, such as the width of the fluid channel (in this case, the crosswalk), and the angle at which molecules (or people) flowed across, along with various directions that people can “dodge,” or move around each other to avoid colliding.

Based on these calculations, the researchers found that pedestrians in a crosswalk are more likely to form lanes, when they walk relatively straight across, from opposite directions. This order largely holds until people start veering across at more extreme angles. Then, the equation predicts that the pedestrian flow is likely to be disordered, with few to no lanes forming.

The researchers were curious to see whether the math bears out in reality. For this, they carried out experiments in a gymnasium, where they recorded the movements of pedestrians using an overhead camera. Each volunteer wore a paper hat, depicting a unique barcode that the overhead camera could track.

In their experiments, the team assigned volunteers various start and end positions along opposite sides of a simulated crosswalk, and tasked them with simultaneously walking across the crosswalk to their target location without bumping into anyone. They repeated the experiment many times, each time having volunteers assume different start and end positions. In the end, the researchers were able to gather visual data of multiple crowd flows, with pedestrians taking many different crossing angles.

When they analyzed the data and noted when lanes spontaneously formed, and when they did not, the team found that, much like the equation predicted, the angular spread mattered. Their experiments confirmed that the transition from ordered to disordered flow occurred somewhere around the theoretically predicted 13 degrees. That is, if an average person veered more than 13 degrees away from straight ahead, the pedestrian flow could tip into disorder, with little lane formation. What’s more, they found that the more disorder there is in a crowd, the less efficiently it moves.

The team plans to test their predictions on real-world crowds and pedestrian thoroughfares.

“We would like to analyze footage and compare that with our theory,” Bacik says. “And we can imagine that, for anyone designing a public space, if they want to have a safe and efficient pedestrian flow, our work could provide a simpler guideline, or some rules of thumb.”

This work is supported, in part, by the Engineering and Physical Sciences Research Council of UK Research and Innovation.

This discovery stems from studies in mice, in which researchers observed memory formation using advanced imaging techniques, including miniature microscopes that captured single-cell resolution in live animals.

The study shows that memories are stored in dendritic compartments: When one memory forms, the affected dendrites are primed to capture new information arriving within the next few hours, linking memories formed close in time.

“If you think of a neuron as a computer, dendrites are like tiny computers inside it, each performing its own calculations,” said lead author Megha Sehgal, assistant professor of psychology at The Ohio State University. “This discovery shows that our brains can link information arriving close in time to the same dendritic location, expanding our understanding of how memories are organized.”

The research was published recently in the journal Nature Neuroscience.

Though most learning and memory studies have focused on how a single memory is formed in the brain, Sehgal’s lab aims to determine how we organize multiple memories.

“The idea is that we don’t form memories in isolation. You don’t form a single memory. You use that memory, make a framework of memories, and then pull from that framework when you need to make adaptive decisions,” she said.

Neurons, the principal brain cells, are known to encode and relay information. Dendrites — the branch-like projections extending from neurons — serve a critical role in how information is processed, receiving incoming information and passing it to the neuronal cell body.

But dendrites are not just passive conduits — each dendritic branch can act as an independent computational unit. While dendrites have been thought to play an important role in the brain’s function, how they shape learning and memory has been unclear until now, Sehgal said.

When mice were exposed in experiments to two different environments within a short period of time, the team found that memories of these spaces became linked. If mice received a mild shock in one of these spaces, the animals ended up freezing out of fear in both environments, associating the shock from one room with the other.

The study focused on the retrosplenial cortex (RSC), a brain region crucial for spatial and contextual memory. The researchers observed that linked memories consistently engaged the same groups of RSC neurons and their dendritic branches.

The team tracked these changes at the dendritic level by visualizing dendritic spines, tiny protrusions on dendrites where neurons communicate. The formation of new memories triggered the addition of clustered dendritic spines, a process critical for strengthening communication between neurons and facilitating learning.

Dendritic spine clusters formed after the first memory were more likely to attract new spines during a second closely timed memory, physically linking those experiences in the brain.

To confirm the role of dendrites in linking memories, the team used optogenetics, a technique that allows researchers to control neurons with light. By reactivating specific dendritic segments that had been active during memory formation, they were able to link otherwise unrelated memories, further demonstrating the importance of dendritic changes in shaping memory networks.

In addition to illuminating a previously unknown role for dendrites in linking memories, the findings open new avenues for understanding memory-related disorders, Sehgal said.

“Our work not only expands our understanding of how memories are formed but also suggests exciting new possibilities for manipulating higher order memory processes,” she said. “This could have implications for developing therapies for memory-related conditions such as Alzheimer’s disease.”

Sehgal co-led the study with Alcino Silva, director of the Integrative Center for Learning and Memory at UCLA, and Panayiota Poirazi, research director of the Foundation for Research and Technology-Hellas in Greece.

This work was supported by the National Institute of Mental Health, the National Institute on Aging, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the European Commission, the National Institutes of Health and the Einstein Foundation Berlin.

Researchers at Indiana University and Wuhan University in China have unveiled a groundbreaking chemical process that could streamline the development of pharmaceutical compounds, chemical building blocks that influence how drugs interact with the body. Their study, published in Chem, describes a novel light-driven reaction that efficiently produces tetrahydroisoquinolines, a group of chemicals that play a crucial role in medicinal chemistry.

Tetrahydroisoquinolines serve as the foundation for treatments targeting Parkinson’s disease, cancer, and cardiovascular disorders. These compounds are commonly found in medications such as painkillers and drugs for high blood pressure, as well as in natural sources like certain plants and marine organisms.

Traditionally, chemists have relied on well-established but limiting methods to synthesize these molecules. The new research, co-authored by Kevin Brown, the James F. Jackson Professor of Chemistry in the College of Arts and Sciences at Indiana University Bloomington, and Professors Xiaotian Qi, Wang Wang, and Bodi Zhao of Wuhan University, presents a fundamentally different approach.

How It Works: Light as a Chemical Tool

Instead of using traditional chemical reactions, scientists harness light to trigger a process called photoinduced energy transfer, wherein light initiates a controlled reaction between sulfonylimines (a type of chemical compound) and alkenes (another type of compound), leading to the creation of tetrahydroisoquinolines — a type of complex molecule. This method allows for the development of new structural patterns in the molecules, which were previously difficult or impossible to create using other methods, offering a more efficient way to make complex molecules.

“The key innovation in this study is the use of a light-activated catalyst, a special molecule that speeds up the reaction without being used up itself,” said Professor Brown. “Traditional methods require high temperatures or strong acids — like trying to cook food with a blowtorch instead of a stove. These harsh conditions can sometimes create unwanted side reactions, or make the process less useful for certain chemicals. The new process, however, uses molecules that respond to light, and can bypass heating by access new energy states. This makes the reaction cleaner, more efficient, and less likely to create unwanted byproducts.”

Brown and colleagues also found that tiny changes in the location of electrons within the starting materials had a huge impact on how the reaction played out — akin to if these electrons were puzzle pieces that needed to fit together just right. By tweaking the shapes of these pieces, the scientists made sure that only the desired product was formed, making the process highly selective. This is crucial for making medicines, where even a small mistake in a molecule’s structure can turn a helpful drug into something useless or even harmful.

Implications for Medicine and Other Industries

“The ability to create a wider range of tetrahydroisoquinoline-based molecules means that medicinal chemists can now explore new drug candidates for treating diseases like Parkinson’s, certain types of cancer, and heart conditions,” noted Professor Qi. “Right now, some diseases have very few effective treatment options, and this method could help scientists discover new and better drugs more quickly.”

Beyond pharmaceuticals, this research could also impact other industries that rely on fine chemicals. In agriculture, for example, similar chemical reactions could be used to develop more effective pesticides or fertilizers. In materials science, it could help create new synthetic materials with specific properties, such as better durability and longevity and greater resistance to heat for the aerospace, automotive, electronics, and medical industries.

The researchers plan to fine-tune the reaction conditions, meaning, they will experiment with different ingredients and settings to make the improve the process further. They also aim to find out if this method can work on even more types of molecules, expanding its usefulness. In addition, they hope to partner with pharmaceutical companies to test whether this technique can be used to produce medicines, potentially leading to new drug discoveries that could make a difference in people’s lives.

“This approach gives chemists a powerful new tool,” said Professor Brown. “We hope especially it will open the door to the development of new and improved therapies for patients around the world.”

As the field of photochemistry continues to expand, innovations like this may redefine how medicines and essential chemicals are made, paving the way for faster, cleaner, and more efficient production methods.

An Osaka Metropolitan University-led medical research team found that ultrafine bubble showers might help prevent atopic dermatitis.

Graduate School of Medicine student Ayaki Matsumoto and Associate Professor Hisayoshi Imanishi led the study into using ultrafine bubbles, often used to clean medical equipment, on mice with atopic dermatitis.

The scientists found that in mice with atopic dermatitis due to external factors, inflammation was markedly suppressed when the affected skin was showered with ultrafine bubbles, while normal showers also showed some positive results. Additionally, the ultrafine bubble showers improved the levels of proteins in the skin that act as a protective barrier. For mice with atopic dermatitis caused by genetic factors, however, there were no significant differences even compared to mice who were not showered.

“The results of this study suggest that ultrafine bubble shower treatment might be a new treatment for allergen-induced atopic dermatitis for humans, but this study was conducted on mice and the shower treatment period was short, only a week or two,” stated graduate student Matsumoto.

“From now on,” Professor Imanishi added, “it will be necessary to conduct ultrafine bubble shower therapy for several months on human patients to examine the effects.”

The findings were published in Frontiers in Immunology.

Analysis built on national studies from Germany, Australia, the United Kingdom, and the Netherlands

It is a common fact that satisfaction in a romantic relationship declines over time. This reduction in satisfaction is particularly marked in the first years of a relationship, and a distinctive low point is often reached after a period of ten years. Instead of considering the processes that occur in the time-since-beginning of a romantic relationship, Janina Bühler and Ulrich Orth decided to look at the time-to-separation of relationships for the purposes of their research.

With this in view, they used data from four representative studies conducted in Germany, Australia, the United Kingdom, and the Netherlands. All these countries are WEIRD, i.e., Western, Educated, Industrialized, Educated, Rich, Democratic, and their individuals are free — by law — to decide about their relationship status. For each of the four data sets covering a total of 11,295 individuals there was a control group roughly the same size consisting of couples that had not separated. The surveys in the four countries were conducted over different periods of time, ranging from 12 to 21 years. In the case of Germany, the researchers employed the data of the Panel Analysis of Intimate Relationships and Family Dynamics (pairfam), a multidisciplinary longitudinal study. In all countries, the subjects were asked to specify how satisfied they were right then with their existing romantic relationship.

Using the available data, Bühler and Orth assessed the extent to which the satisfaction with the relationship developed in the light of their subsequent separation. “In order to better understand dissolving relationships, we examined them from the point of view of time-to-separation. To do this, we applied a concept that is in general use in other fields of psychology,” said Janina Bühler. Based on the data of the four national representative studies, the researchers were able to determine that relationships can be subjected to what is known as terminal decline. This decline in relationship satisfaction occurs in two phases. The initial preterminal phase, which can have a duration of several years, is characterized by a minor decline in satisfaction. However, this is followed by a transition or tipping point from which there is an accelerated decline in satisfaction. The terminal phase of a relationship after this transition point lasts 7 to 28 months, one to two years on average. “Once this terminal phase is reached, the relationship is doomed to come to an end. This is apparent from the fact that only the individuals in the separation group go through this terminal phase, not the control group,” explained Bühler.

Partners assess the terminal phase of a relationship differently

At the same time, the two partners do not experience the transition phase in the same way. The partner who initiates the separation has already become dissatisfied with the relationship at an earlier point in time. For the recipient of the separation, the transition point arrives relatively shortly before the actual separation. They experience a very rapid decline in relationship satisfaction.

“Partners pass through various phases. They do not normally separate from one day to the next, and the way these phases impact on the two partners differs,” added Bühler. In many cases, couples seek help too late, i.e., when the transition point has already been reached. “It is thus important to be aware of these relationship patterns. Initiating measures in the preterminal phase of a relationship, i.e., before it begins to go rapidly downhill, may thus be more effective and even contribute to preserving the relationship,” concluded Bühler, who also works as a couples therapist.

New research from the University of Chicago shows how a specially trained population of immune cells keeps the peace by preventing other immune cells from attacking their own. The study, published in Science, provides a better understanding of immune regulation during infection and could provide a foundation for interventions to prevent or reverse autoimmune diseases.

Several groups of white blood cells help coordinate immune responses. Dendritic cells take up proteins from foreign pathogens, chop them up into peptides called antigens, and display them on their surface. CD4+ conventional T (Tconv) cells, or helper T cells, inspect the peptides presented by dendritic cells. If the peptides are foreign antigens, the T cells expand in numbers and transform into an activated state, specialized to eradicate the pathogen. If the dendritic cell is carrying a “self-peptide,” or peptides from the body’s own tissue, the T cells are supposed to lay off.

During an autoimmune response, the helper T cells don’t distinguish between foreign peptide antigens and self-peptides properly and go on the attack no matter what. To prevent this from happening, another group of T cells called CD4+ regulatory T (Treg) cells, are supposed to intervene and prevent friendly fire from the Tconv cells.

“You can think of them [Treg cells] as peacekeeper cells,” said Pete Savage, PhD, Professor of Pathology at UChicago and senior author of the new study. Tregs obviously do their job well most of the time, but Savage said that it has never been clear how they know when to intervene and prevent helper T cells from starting an autoimmune response, and when to hold back and let them fight an infection.

So, Savage and his team, led by David Klawon, PhD, a former graduate student in his lab who is now a postdoctoral fellow at MIT, wanted to explore this property of the immune system, known in the field as self-nonself discrimination. T cells are produced in the thymus, a specialized organ of the immune system. During development, Treg cells are trained to recognize specific peptides, including self-peptides from the body. When dendritic cells present a self-peptide, the Treg cells trained to spot them intervene to stop helper T cells from getting triggered.

This specificity is what Savage’s team found makes a crucial difference in self-nonself discrimination. The researchers experimentally depleted Treg cells in mice that were specific to a single self-peptide from the prostate. In healthy mice in the absence of infection, this change did not trigger autoimmunity to the prostate. When the researchers infected mice with a bacterium that expressed the prostate self-peptide, however, the absence of matched, prostate-specific Treg cells triggered prostate-reactive T helper cells and introduced autoimmunity to the prostate.

Interestingly though, this alteration did not impair the ability of helper T cells to control the bacterial infection by responding to foreign peptides.

“It’s like a doppelganger population of T cells. The CD4 helper cells that could induce disease by attacking the self share an equivalent, matched population of these peacekeeper Treg cells,” Savage said. “When we removed Treg cells reactive to a single self-peptide, the T helper cells reactive to that self-peptide were no longer controlled, and they induced autoimmunity.”

The root causes of autoimmune disease are a complex interaction of genetics, the environment, lifestyle, and the immune system. Classic, conventional thinking in the immunology field promoted the idea that the immune system establishes self-nonself discrimination by purging the body of helper T cells that are reactive to self-peptides, thereby preventing autoimmunity. Savage said this study shows that purging is inefficient though, and that specificity matching by Treg cells may be equally as important.

“The idea is that specificity matters, and for a fully healthy immune system, you need to have a good collection of these doppelganger Treg cells,” he said. As long as the immune system generates enough matched Treg cells, they can prevent autoimmune responses without impacting responses to infections.

“It’s like flipping the idea of self-nonself discrimination upside down. Instead of having to delete all helper T cells reactive to self-antigens, you simply generate enough of these Treg peacekeeper cells instead,” Savage said.

Every second, an adult generates around five million new blood cells to replace aging or dying ones, making the blood system a highly regenerative organ. These new blood cells are formed in the bone marrow from unspecialized cells, known as blood stem cells. Through several intermediate stages, these stem cells develop into oxygen-transporting erythrocytes, blood-clotting platelets, and the large group of white blood cells which orchestrate the immune defense. This process, known as differentiation, must be precisely regulated to ensure a balanced production of mature blood cells across all cell types.

An international team of scientists from Universitätsmedizin Frankfurt/Goethe University, University of Gothenburg, and University Hospital Pamplona, led by Prof. Michael Rieger from Universitätsmedizin Frankfurt’s Department of Medicine II, has now molecularly decoded the differentiation pathways of human blood stem cells into all specialized blood cell types. Using state-of-the-art sequencing methods, the research team identified gene and protein expression patterns in more than 62,000 individual cells and analyzed the resulting data with high-performance computing.

“We were able to gain an overview of the molecular processes in stem cells and discover new surface proteins that are crucial for the complex interaction between stem cells and their bone marrow environment,” explains Rieger. “This provides us with detailed insights into what exactly the unique characteristics of a stem cell are and which genes regulate stem cell differentiation. This newly established technology in my lab will answer many unresolved questions in health research with extraordinary precision.”

The researchers uncovered an unexpected finding: “We found a protein called PD-L2 on the surface of blood stem cells, which we know suppresses the immune response of our defense cells — the T cells — by preventing their activation and proliferation and inhibiting the release of inflammatory substances called cytokines,” summarizes the study’s first author, PhD student Tessa Schmachtel.

PD-L2 likely serves to prevent immune-mediated damage, biologist Schmachtel explains. “This is particularly important for protecting stem cells from potential attacks by reactive T cells and likely plays a key role in stem cell transplantations with grafts from unrelated donors. PD-L2 could help to reduce the body’s immune response against the transplanted stem cells.”

Rieger is convinced: “Groundbreaking discoveries can only be made on the basis of close interdisciplinary collaboration between physicians, scientists, and bioinformaticians — as practiced at Universitätsmedizin Frankfurt — and through the establishment of international networks.”

Shape-shifting cells

In a study published in the journal Nature, a research group led by Professor Taija Mäkinen, Director at the Wihuri Research Institute, investigated how the thin layer of endothelial cells maintains its integrity under varying fluid pressure conditions. The study found that the key factor is the ability of the cells to continuously change their unique shape.

“It’s long been known that the endothelial cells of lymphatic vessels resemble oak leaves or jigsaw puzzle pieces. The reason for this peculiar shape has, however, remained a mystery, and researchers have previously been unable to replicate it in cultured cells,” says Mäkinen.

A similar jigsaw puzzle-like shape can be seen in a completely different type of cell: on the surface of plant leaves. In plants, this pattern helps cells withstand internal fluid pressure, which is vital for plant growth and structural support.

The fact that jigsaw puzzle-like cells function similarly in both plants and mammals points to a fundamental biological principle: for organisms of various types, this distinctive cell shape enhances structural stability. The same principle has been applied in human-led design as well: for example, paving stones on roads are frequently arranged in undulating or interlocking patterns to improve durability and wear resistance.

The study is published March 19 in The Lancet Neurology.

The international study involved 73 people with rare, inherited genetic mutations that cause the overproduction of amyloid in the brain, all but guaranteeing that they will develop Alzheimer’s disease in middle age. For a subgroup of 22 participants who had no cognitive problems at the study’s start and who received the drug the longest — an average of eight years — the treatment lowered the risk of developing symptoms from essentially 100% to about 50%, according to a primary analysis of the data and supported by multiple sensitivity analyses supporting the trend.

“Everyone in this study was destined to develop Alzheimer’s disease and some of them haven’t yet,” said senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology at WashU Medicine. “We don’t yet know how long they will remain symptom-free — maybe a few years or maybe decades. In order to give them the best opportunity to stay cognitively normal, we have continued treatment with another anti-amyloid antibody in hopes they will never develop symptoms at all. What we do know is that it’s possible at least to delay the onset of the symptoms of Alzheimer’s disease and give people more years of healthy life.”

The findings provide new evidence to support the so-called amyloid hypothesis of Alzheimer’s disease, which posits that the first step on the road to dementia is the build-up of amyloid plaques in the brain, and that removing such plaques or blocking their formation can stop symptoms from arising. For this study, Bateman and colleagues evaluated the effects of an experimental anti-amyloid drug to see if the medication could prevent the development of dementia.

The study population consisted of people who had originally enrolled in the Knight Family DIAN-TU-001, the first Alzheimer’s prevention trial in the world, and then continued into an extension of the trial in which they received an anti-amyloid drug. Currently led by Bateman and funded primarily by the Alzheimer’s Association, GHR Foundation and the National Institutes of Health (NIH), the Knight Family DIAN-TU-001 was launched in 2012 to evaluate anti-amyloid drugs as preventive therapies for Alzheimer’s disease. All participants in the trial had no to very mild cognitive decline, and were within 15 years before to 10 years after their expected age of Alzheimer’s onset, based on family history.

When the trial concluded in 2020, Bateman and colleagues reported that one of the drugs — gantenerumab, made by Roche and its U.S. affiliate, Genentech — lowered amyloid levels in the brain and improved some measures of Alzheimer’s proteins. But the researchers did not see evidence of cognitive benefit yet because the group without symptoms — regardless of whether they were on drug or placebo — hadn’t declined. These mixed results in the group without symptoms led the trial leaders to launch an open-label extension so the researchers could continue studying gantenerumab’s effects and determine whether higher doses or longer treatment could prevent or delay cognitive decline.

All DIAN-TU participants who carried a high-risk Alzheimer’s genetic mutation were eligible to continue into the extension study, regardless of whether they had received gantenerumab, another drug or a placebo during the trial. Because all participants in the extension received the experimental drug, there was no internal control group. Instead, the researchers compared the extension participants to people in a related study known as the DIAN Observational who had received no drug treatment, and to placebo-treated DIAN-TU participants who did not continue into the extension.

Originally planned for three years, the extension was cut short in mid-2023 following the decision by Roche/Genentech to discontinue the development of gantenerumab in November 2022 after data from their pivotal Phase 3 GRADUATE I and II trials evaluating gantenerumab in people with early symptomatic Alzheimer’s disease did not meet their primary endpoint of slowing clinical decline. The average participant in the extension trial had been treated for 2.6 years at the time it was terminated.

Analysis of this data set revealed that removal of brain amyloid plaques years before symptoms are expected to arise delayed symptom onset and dementia progression, although the results were only statistically significant for the subgroup of people who started with no symptoms and were treated the longest. For the group of participants who received gantenerumab only during the extension for two to three years because they had received another drug or placebo during the original trial, there have been no observable effects on cognitive function yet. The longest-treated group had received gantenerumab for eight years on average, suggesting that treatment years before onset may be necessary for prevention.

In the longest-treated group, the effect was strong: Treatment cut the risk of developing symptoms in half. This 50% effect size seen in the longest gantenerumab-treated group is the result of a calculation that takes into consideration not only how many people developed symptoms but when symptoms emerged for each participant compared to his or her expected age of onset. That means the effect size could change as time goes on. Some of the participants are at or just past their expected age of onset. The longer they go without developing symptoms, the greater the effect size will be. Conversely, some who are healthy now may develop symptoms down the road, reducing the effect size.

Gantenerumab and other anti-amyloid drugs have been linked to a side effect known as amyloid-related imaging abnormalities, or ARIA. The abnormalities are detectable on brain scans and represent tiny spots of blood in the brain or localized swelling of the brain. In clinical trials, most cases of ARIA aren’t noticed by participants (that is, they show no symptoms) and resolve on their own, but a minority are more serious and, rarely, deaths have been linked to the side effect. In this study, ARIA rates were one-third higher than in the original clinical trial (30% vs 19%), which the researchers attribute to the higher doses used in the extension. Two participants developed such severe ARIA that they needed to be taken off the drug, at which point they recovered. There were no life-threatening adverse events and no deaths. Overall, the safety profile of gantenerumab in the extension was similar to that in the original trial and in other clinical trials of gantenerumab, the researchers said.

In order to answer the question of how long dementia can be delayed by removing amyloid, the Knight Family DIAN-TU, based at WashU Medicine, has launched the Knight Family DIAN-TU Amyloid Removal Trial, with initial funding from the Alzheimer’s Association. Because gantenerumab was discontinued, most of the participants in the international open-label extension have started receiving lecanemab, an anti-amyloid drug approved by the Food and Drug Administration in 2023 to slow cognitive decline in people who already have symptoms of Alzheimer’s disease. Data from this phase of the extension trial have not yet been analyzed. WashU Medicine researchers have submitted an NIH grant that, if approved, would provide funding to finish the trial. That grant is still pending NIH review.

While the trial was limited to people with genetic forms of Alzheimer’s that lead to early onset, Bateman and colleagues expect that the study’s results will inform prevention and treatment efforts for all forms of Alzheimer’s disease. Both early-onset and late-onset Alzheimer’s disease start with amyloid slowly collecting in the brain two decades before memory and thinking problems arise. Further, all trial results from these early-onset Alzheimer’s mutation families have been replicated in late-onset Alzheimer’s disease trials.

“If late-onset Alzheimer’s prevention trials have similar results to the DIAN-TU trials, there soon could be Alzheimer’s preventions available for the general population,” Bateman said. “I am highly optimistic now, as this could be the first clinical evidence of what will become preventions for people at risk for Alzheimer’s disease. One day soon, we may be delaying the onset of Alzheimer’s disease for millions.”

While gantenerumab is no longer being developed, other anti-amyloid drugs are being evaluated as preventive medications for Alzheimer’s disease.

“These exciting preliminary findings hint very clearly at the potential role of lowering beta amyloid in prevention of Alzheimer’s disease,” said Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer and medical affairs lead. “The Alzheimer’s Association looks forward with great anticipation to replication, extension and expansion of this genuinely unprecedented and groundbreaking research, and we have made a significant investment in ensuring these important scientific questions can be investigated. Discoveries like this convincingly illustrate why it is so important for research into Alzheimer’s and all diseases that cause dementia to continue, expand and accelerate.”

The Knight Family DIAN-TU is evaluating the investigational amyloid-removing drug remternetug, made by Eli Lilly and Co., in the Primary Prevention Trial. Like the DIAN-TU secondary prevention trials, the Primary Prevention Trial involves members of families that carry dominant Alzheimer’s mutations, but Primary Prevention participants are much younger. The trial is enrolling people as young as 18 who have few or no detectable Alzheimer’s-related molecular changes in their brains, up to 25 years before the expected onset of dementia symptoms, to determine whether stopping the early molecular changes that lead to symptomatic Alzheimer’s disease can prevent the disease from ever taking hold.

The DIAN-TU-001 portion of this study was funded by grants from the National Institutes of Health’s National Institute on Aging (grant numbers U01AG042791, U01AG042791-S1 (FNIH and Accelerating Medicines Partnership), R01AG046179, R01AG053267, R01AG053267-S1 and R01AG053267-S2); the Alzheimer’s Association; Eli Lilly and Company; F. Hoffman-LaRoche Ltd.; Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly and Company); GHR Foundation; an anonymous organization; Cerveau Technologies; Cogstate and Signant. The DIAN-TU has also received funding from the DIAN-TU Pharma Consortium. The gantenerumab open-label extension was supported by the Alzheimer’s Association and F. Hoffman-LaRoche Ltd.

The findings, published in Nature Communications, tested two candidate drugs derived from their studies on the mechanism of the brain effects of rehabilitation, of which one resulted in significant recovery in movement control after stroke in the mouse model.

Stroke is the leading cause of adult disability because most patients do not fully recover from the effects of stroke. There are no drugs in the field of stroke recovery, requiring stroke patients to undergo physical rehabilitation which has shown to be only modestly effective.

“The goal is to have a medicine that stroke patients can take that produces the effects of rehabilitation,” said Dr. S. Thomas Carmichael, the study’s lead author and professor and chair of UCLA Neurology. “Rehabilitation after stroke is limited in its actual effects because most patients cannot sustain the rehab intensity needed for stroke recovery.

“Further, stroke recovery is not like most other fields of medicine, where drugs are available that treat the disease — such as cardiology, infectious disease or cancer,” Carmichael said. “Rehabilitation is a physical medicine approach that has been around for decades; we need to move rehabilitation into an era of molecular medicine.”

In the study, Carmichael and his team sought to determine how physical rehabilitation improved brain function after a stroke and whether they could generate a drug that could produce these same effects.

Working in laboratory mice models of stroke and with stroke patients, the UCLA researchers identified a loss of brain connections that stroke produces that are remote from the site of the stroke damage. Brain cells that are located at a distance from the stroke site get disconnected from other neurons. As a result, brain networks do not fire together for such things like movement and gait.

The UCLA team found that some of the connections that are lost after stroke occur in a cell called a parvalbumin neuron. This type of neuron helps generate a brain rhythm, termed a gamma oscillation, which links neurons together so that they form coordinated networks to produce a behavior, such as movement. Stroke causes the brain to lose gamma oscillations. Successful rehabilitation in both laboratory mice and in humans brought gamma oscillations back into the brain, and in the mouse model, repaired the lost connections of parvalbumin neurons.

Carmichael and team then identified two candidate drugs that might produce gamma oscillations after stroke. These drugs specifically work to excite parvalbumin neurons. The researchers found one of the drugs, DDL-920, developed in the UCLA lab of Dr. Varghese John, who coauthored the study, produced significant recovery in movement control.

Further studies are needed to understand the safety and efficacy of this drug before it could be considered for human trials.

MAIJU (Motor Assessment of Infants with a Jumpsuit) is designed to solve these problems. The suit is based on multisensor measurement, which are used to make reliable and versatile measurements of children’s motion with the help of dedicated AI algorithms. The suit is worn at home, where the child’s activity is measured during free play. The AI algorithms assess whether the child has reached specific motor milestones, how much time the child spends in different postures and steadily the child develops from month to month.

Reliable, objective and internationally comparable developmental assessment

A recent study demonstrates that the AI algorithms of the MAIJU jumpsuit identify motor milestones with the same precision as trained specialists employed in a multinational reference study by the World Health Organization (WHO).

“This technique brings objectivity and global harmonisation to the assessment of motor development. It also boosts regional equality in children’s developmental assessment both nationally and internationally,” says Professor Sampsa Vanhatalo, the principal investigator.

A total of 620 at-home measurements were carried out on 134 children aged from 4 to 22 months. The findings show that the MAIJU jumpsuit enables very reliable and objective developmental assessment at the child’s home. At-home measurements and the AI algorithms provide detailed results that can be used, for example, to screen developmental delays, assess the effectiveness of rehabilitation and conduct extensive multinational studies.

“The MAIJU jumpsuit opens up new opportunities for monitoring children’s development, making it equal across Finland and the world. The MAIJU method also offers a unique opportunity to investigate the effects of the growth environment or nutrition on development,” says Postdoctoral Researcher Manu Airaksinen, who was in charge of the jumpsuit’s technical development.

Heat creates illusion

The rubber hand illusion occurs when the hidden hand and the rubber hand are touched at the same time, for example with a brush. In the experiment outlined here, the illusion was not evoked through touch, but through a heat stimulus and simultaneous illumination with red light:

In the first step, the researchers determined the individual pain threshold for heat pain in all 34 right-handed test participants. The participants then placed their left hand behind a screen so that they could no longer see it. The hand hidden by the screen was placed on a thermode head, a small plate that can be heated under controlled conditions. Instead of their left hand, a rubber hand was placed in front of the participants, which could be illuminated with red light from below. The test participants’ right hand was placed on a slider which they used during the experiment to continuously rate the painfulness of the heat on their left hand.

The researchers carried out several test runs in which they heated the thermode to several temperature levels just below the respective pain threshold, exactly at the pain threshold and just resp. significantly above it. The rubber hand was simultaneously illuminated with red light. “The heat stimulus on the left hand with simultaneous red illumination of the rubber hand evoked the illusion,” explains study supervisor Professor Martin Diers, Head of the Research Section Clinical and Experimental Behavioral Medicine. A survey of the test participants confirmed these findings after each series of experiments. In the control condition, the researchers conducted the experiment with a rubber hand rotated by 180 degrees.

The intensity of pain decreases

“We showed that the perceived pain intensity was reduced in the rubber hand illusion condition compared to the control condition,” says Martin Diers. “We assume that the mechanism behind the rubber hand illusion is the multisensory integration of visual, tactile (here nociceptive) and proprioceptive information. The findings suggest that when people perceive the rubber hand as part of their own body, this reduces their perception of pain.” Another factor could be the phenomenon of visual analgesia, which has also been shown in other studies: A pain stimulus is perceived as less intense if the person can see the relevant part of the body while it is occurring. “However, we still don’t fully understand the neural basis for this phenomenon,” admits Diers.

In future, the findings could possibly be used in the treatment of pain. One conceivable field of use would be the treatment of complex regional pain syndrome, for example, in which patients typically experience pain and swelling in the hand.

The model, called patch foundational transformer for sleep (PFTSleep), analyzes brain waves, muscle activity, heart rate, and breathing patterns to classify sleep stages more effectively than traditional methods, streamlining sleep analysis, reducing variability, and supporting future clinical tools to detect sleep disorders and other health risks.

Current sleep analysis often relies on human experts manually scoring short segments of sleep data or using AI models that are not capable of analyzing a patient’s entire night of sleep. This new approach, developed using thousands of sleep recordings, takes a more comprehensive view. By training on full-length sleep data, the model can recognize sleep patterns throughout the night and across different populations and settings, offering a standardized and scalable method for sleep research and clinical use, say the investigators.

“This is a step forward in AI-assisted sleep analysis and interpretation,” says first author Benjamin Fox, a PhD candidate at the Icahn School of Medicine at Mount Sinai in the Artificial Intelligence and Emerging Technologies Training Area. “By leveraging AI in this way, we can learn relevant clinical features directly from sleep study signal data and use them for sleep scoring and, in the future, other clinical applications such as detecting sleep apnea or assessing health risks linked to sleep quality.”

The model was built using a large dataset of sleep studies (polysomnograms) that measure key physiological signals, including brain activity, muscle tone, heart rate, and breathing patterns. Unlike traditional AI models, which analyze only short, 30-second segments, this new model considers the entire night of sleep, capturing more detailed and nuanced patterns. Further, the model is trained via a method known as self-supervision, which helps learn relevant clinical features from physiological signals without using human labeled outcomes.

“Our findings suggest that AI could transform how we study and understand sleep,” says co-senior corresponding author Ankit Parekh, PhD, Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at the Icahn School of Medicine at Mount Sinai, and Director of the Sleep and Circadian Analysis Group at Mount Sinai. “Our next goal is to refine the technology for clinical applications, such as identifying sleep-related health risks more efficiently.”

The researchers emphasize that this AI tool, while promising, would not replace clinical expertise. Instead, it would serve as a powerful aid for sleep specialists, helping to speed up and standardize sleep analysis. Next, the team’s research aims to expand its capabilities beyond sleep-stage classification to detecting sleep disorders and predicting health outcomes.

“This AI-driven approach has the potential to revolutionize sleep research,” says co-senior corresponding author Girish N. Nadkarni, MD, MPH, Chair of the Windreich Department of Artificial Intelligence and Human Health at the Icahn School of Medicine, Director of the Hasso Plattner Institute for Digital Health, and the Irene and Dr. Arthur M. Fishberg Professor of Medicine. Dr. Nadkarni is also the inaugural Chief of the Division of Data-Driven and Digital Medicine and Co-Director of the Mount Sinai Clinical Intelligence Center. “By analyzing entire nights of sleep with greater consistency, we can uncover deeper insights into sleep health and its connection to overall well-being.”

What is Psychological Prehabilitation?

Prehabilitation is a proactive approach aimed at improving surgical outcomes through preventive measures. Traditionally, it has focused on physical function and patient education. However, mental health has recently gained attention due to its crucial role in postoperative recovery, including reducing persistent opioid use.

The researchers conducted a systematic review, meta-analysis, and meta-regression of RCTs retrieved from databases such as MEDLINE, EMBASE, CENTRAL, and Google Scholar. They included studies with more than 50 adult surgical patients and evaluated the effects of different preoperative psychotherapy-based interventions, including cognitive behavioral therapy (CBT), supportive psychotherapy, and acceptance and commitment therapy (ACT), on postoperative outcomes.

The study found that psychological prehabilitation significantly reduces the length of hospital stay, pain, anxiety, and depression after surgery. Specifically, the analysis showed:

• A reduction in length of hospital stay (LOS) by an average of 1.62 days;
• A decrease in pain by an average of 3.52 points;
• Lower anxiety levels regardless of which validated anxiety scale was used;
• Reduced depression levels regardless of which validated depression scale was used.

Interestingly, the type of psychotherapy and the kind of surgery did not significantly affect the outcomes, except for anxiety.

Implications for Healthcare

The findings suggest that incorporating psychological prehabilitation into pre-surgery routines could lead to better overall recovery for patients. This approach may also help reduce healthcare costs associated with prolonged hospital stays and postoperative complications.

The study highlights the need for further research to compare different types, durations, and delivery methods of psychotherapy to determine the most effective strategies for specific postoperative outcomes.

In a recent study reported in the Feb. 15 issue of Nature Communications, scientists from The Jackson Laboratory (JAX) and UConn Health not only show how cancer hijacks this tightly regulated splicing and rearranging of RNA but also introduce a potential therapeutic strategy that could slow or even shrink aggressive and hard-to-treat tumors. This discovery could transform how we treat aggressive cancers, such as triple-negative breast cancer and certain brain tumors, where current treatment options are limited.

At the heart of this work, led by Olga Anczuków, an associate professor at JAX and co-program leader at the NCI-designated JAX Cancer Center, are tiny genetic elements called poison exons, nature’s own “off switch” for protein production. When these exons are included in an RNA message, they trigger its destruction before a protein can be made — preventing harmful cellular activity. In healthy cells, poison exons regulate the levels of key proteins, keeping the genetic machinery in check. But in cancer, this safety mechanism often fails.

Anczuków and her team, including Nathan Leclair, an MD/PhD graduate student at UConn Health and The Jackson Laboratory who spearheaded the research, and Mattia Brugiolo, a staff researcher who contributed his expertise, discovered that cancer cells suppress poison exon activity in a critical gene called TRA2β. As such, levels of TRA2β protein increase inside cancer cells, causing tumor proliferation.

Furthermore, the team found a correlation between levels of poison exons and patient outcomes. “We’ve shown for the first time that low levels of poison exon inclusion in the TRA2β gene are associated with poor outcomes in many different cancer types, and especially in aggressive and difficult-to-treat cancers,” said Anczuków. These include breast cancer, brain tumors, ovarian cancers, skin cancers, leukemias, and colorectal cancers, Anczuków explained.

Anczuków, Leclair, and Brugiolo then went on to see if they could increase the inclusion of the poison exon in the TRA2β gene and reactivate the kill switch. They found their answer in antisense oligonucleotides (ASOs) — synthetic RNA fragments that can be designed to increase poison exon inclusion in specific ways. When introduced into cancer cells, ASOs effectively flipped the genetic switch, restoring the body’s natural ability to degrade excess TRA2β RNA and inhibit tumor progression.

“We found that ASOs can rapidly boost poison exon inclusion, essentially tricking the cancer cell into turning off its own growth signals,” said Leclair. “These poison exons work like a rheostat, quickly adjusting protein levels — and that could make ASOs a highly precise and effective therapy for aggressive cancers.”

Interestingly, when researchers completely removed TRA2β proteins using CRISPR gene editing, tumors continued to grow — suggesting that targeting the RNA rather than the protein could be a more effective approach. “This tells us that poison-exon-containing RNA doesn’t just silence TRA2β,” explained Anczuków. “It likely sequesters other RNA-binding proteins, creating an even more toxic environment for cancer cells.”

Further studies will refine ASO-based therapies and explore their delivery to tumors. However, preliminary data suggest that ASOs are highly specific and do not interfere with normal cellular function, making them promising candidates for future cancer treatments. This research was supported by the National Institutes of Health and the NCI-designated JAX Cancer Center.

In a recent study reported in the Feb. 15 issue of Nature Communications, scientists from The Jackson Laboratory (JAX) and UConn Health not only show how cancer hijacks this tightly regulated splicing and rearranging of RNA but also introduce a potential therapeutic strategy that could slow or even shrink aggressive and hard-to-treat tumors. This discovery could transform how we treat aggressive cancers, such as triple-negative breast cancer and certain brain tumors, where current treatment options are limited.

At the heart of this work, led by Olga Anczuków, an associate professor at JAX and co-program leader at the NCI-designated JAX Cancer Center, are tiny genetic elements called poison exons, nature’s own “off switch” for protein production. When these exons are included in an RNA message, they trigger its destruction before a protein can be made — preventing harmful cellular activity. In healthy cells, poison exons regulate the levels of key proteins, keeping the genetic machinery in check. But in cancer, this safety mechanism often fails.

Anczuków and her team, including Nathan Leclair, an MD/PhD graduate student at UConn Health and The Jackson Laboratory who spearheaded the research, and Mattia Brugiolo, a staff researcher who contributed his expertise, discovered that cancer cells suppress poison exon activity in a critical gene called TRA2β. As such, levels of TRA2β protein increase inside cancer cells, causing tumor proliferation.

Furthermore, the team found a correlation between levels of poison exons and patient outcomes. “We’ve shown for the first time that low levels of poison exon inclusion in the TRA2β gene are associated with poor outcomes in many different cancer types, and especially in aggressive and difficult-to-treat cancers,” said Anczuków. These include breast cancer, brain tumors, ovarian cancers, skin cancers, leukemias, and colorectal cancers, Anczuków explained.

Anczuków, Leclair, and Brugiolo then went on to see if they could increase the inclusion of the poison exon in the TRA2β gene and reactivate the kill switch. They found their answer in antisense oligonucleotides (ASOs) — synthetic RNA fragments that can be designed to increase poison exon inclusion in specific ways. When introduced into cancer cells, ASOs effectively flipped the genetic switch, restoring the body’s natural ability to degrade excess TRA2β RNA and inhibit tumor progression.

“We found that ASOs can rapidly boost poison exon inclusion, essentially tricking the cancer cell into turning off its own growth signals,” said Leclair. “These poison exons work like a rheostat, quickly adjusting protein levels — and that could make ASOs a highly precise and effective therapy for aggressive cancers.”

Interestingly, when researchers completely removed TRA2β proteins using CRISPR gene editing, tumors continued to grow — suggesting that targeting the RNA rather than the protein could be a more effective approach. “This tells us that poison-exon-containing RNA doesn’t just silence TRA2β,” explained Anczuków. “It likely sequesters other RNA-binding proteins, creating an even more toxic environment for cancer cells.”

Further studies will refine ASO-based therapies and explore their delivery to tumors. However, preliminary data suggest that ASOs are highly specific and do not interfere with normal cellular function, making them promising candidates for future cancer treatments. This research was supported by the National Institutes of Health and the NCI-designated JAX Cancer Center.

Combatting the “undruggable” RAS genes

Patients with pancreatic cancer have an overall poor prognosis: in most patients, the disease has already spread at the time of diagnosis, resulting in limited treatment options. Nearly 90 percent of pancreatic cancers are driven by KRAS mutations, the most common cancer-causing gene mutation across cancer types, which researchers long considered “undruggable.” In 2021, the first KRAS inhibitor was approved to treat non-small cell lung cancer with KRAS G12C mutations, but with longer follow-up, it has become clear that KRAS-mutant cancers can quickly evolve to resist therapies targeted at one specific form of the gene mutation.

“We’ve been excited by the prospect of RAS inhibition for pancreatic cancer, which remains one of the deadliest and most difficult forms of cancer to treat,” said co-corresponding senior author Ben Stanger, MD, PhD, the Hanna Wise Professor in Cancer Research and director of the Penn Pancreatic Cancer Research Center. “While the first wave of KRAS inhibitors have had limited impact in cancer care, this research shows that newer RAS inhibition tools may have an immune stimulatory effect, making them ideal to pair with immunotherapy for longer and better treatment response.”

Previous research led by Stanger and Robert Vonderheide, MD, DPhil, director of the Abramson Cancer Center, who is also co-corresponding author on this study, showed that a small molecule inhibitor specifically targeting KRAS G12D, the form of the mutation more commonly found in pancreatic cancer, stimulated the immune system while shrinking tumors or stopping cancer growth in preclinical mouse models of pancreatic cancer.

A new type of RAS inhibitor

In this study, the researchers used RAS(ON) multi-selective inhibitors, the investigational agent daraxonrasib (RMC-6236) and the preclinical tool compound RMC-7977 (both discovered by Revolution Medicines, whose scientists contributed to the study). These inhibitors use a different mechanism of action than most other KRAS inhibitors (including that in the previous study) to target the active or ON-state of multiple forms of RAS mutations.

“The benefit of this ‘multi-selective’ approach is that the inhibitors are designed to inhibit multiple RAS mutations, so if the cancer mutates, and another type of RAS mutation emerges, the treatment may not necessarily stop working,” Vonderheide explained.

The research team found that not only was RAS(ON) multi-selective inhibition effective in preclinical pancreatic cancer models, but it was even more effective when combined with immunotherapy. Using the combination approach, all mouse models had tumor shrinkage and half had a complete response, meaning the tumor was eliminated.

The research team used a Penn-developed immunocompetent model considered the gold standard worldwide for assessing potential therapies for pancreatic ductal adenocarcinoma. This model allows the tumor to spontaneously evolve after implantation, making it possible to discern the drug’s impact on the surrounding tumor microenvironment. The research team found that RAS(ON) multi-selective inhibition reshaped the tumor microenvironment by bringing in more T cells and other immune cells, making the tumor particularly receptive to immunotherapy.

Next steps and clinical trial information

Daraxonrasib (RMC-6236) is already being tested in clinical trials across the United States. A clinical trial testing RAS(ON) inhibitors with other anticancer agents in certain patients with gastrointestinal solid tumors is now open at several sites across the country, including at Penn Medicine. Click here for more information about the study.

“We’re hopeful that we’re starting to crack the code on immunotherapy and RAS therapy for pancreatic cancer,” Vonderheide said. “After decades of limited progress, it’s encouraging to see new treatment approaches making their way into the clinic for patients.”

The study was supported by Revolution Medicines, the National Institutes of Health (R01CA252225, R01CA276512, P30DK050306, P30CA016520) the Department of Defense (W81XWH2210730), the Molecular Pathology and Imaging Core, A Love for Life, the Basser Center for BRCA, and the Penn Pancreatic Cancer Research Center.

Information for patients interested in joining a clinical trial: visit Penn Medicine’s Abramson Cancer Center Clinical Trial Information Service online or call 1-855-216-0098 to speak to a clinical trial navigator.

Editor’s note: Vonderheide is an inventor on patents relating to cancer cellular immunotherapy and KRAS immune epitopes.

The study, “Endothelial TDP-43 Depletion Disrupts Core Blood-Brain Barrier Pathways in Neurodegeneration,” was published on March 14, 2025. The lead author, Omar Moustafa Fathy, an MD/Ph.D. candidate at the Center for Vascular Biology at UConn School of Medicine, conducted the research in the laboratory of senior author Dr. Patrick A. Murphy, associate professor and newly appointed interim director of the Center for Vascular Biology. The study was carried out in collaboration with Dr. Riqiang Yan, a leading expert in Alzheimer’s disease and neurodegeneration research.

This work provides a novel and significant exploration of how vascular dysfunction contributes to neurodegenerative diseases, exemplifying the powerful collaboration between the Center for Vascular Biology and the Department of Neuroscience. While clinical evidence has long suggested that blood-brain barrier (BBB) dysfunction plays a role in neurodegeneration, the specific contribution of endothelial cells remained unclear. The BBB serves as a critical protective barrier, shielding the brain from circulating factors that could cause inflammation and dysfunction. Though multiple cell types contribute to its function, endothelial cells — the inner lining of blood vessels — are its principal component.

“It is often said in the field that ‘we are only as old as our arteries’. Across diseases we are learning the importance of the endothelium. I had no doubt the same would be true in neurodegeneration, but seeing what these cells were doing was a critical first step,” says Murphy.

Omar, Murphy, and their team tackled a key challenge: endothelial cells are rare and difficult to isolate from tissues, making it even harder to analyze the molecular pathways involved in neurodegeneration.

To overcome this, they developed an innovative approach to enrich these cells from frozen tissues stored in a large NIH-sponsored biobank. They then applied inCITE-seq, a cutting-edge method that enables direct measurement of protein-level signaling responses in single cells — marking its first-ever use in human tissues.

This breakthrough led to a striking discovery: endothelial cells from three different neurodegenerative diseases — Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) — shared fundamental similarities that set them apart from the endothelium in healthy aging. A key finding was the depletion of TDP-43, an RNA-binding protein genetically linked to ALS-FTD and commonly disrupted in AD. Until now, research has focused primarily on neurons, but this study highlights a previously unrecognized dysfunction in endothelial cells.

“It’s easy to think of blood vessels as passive pipelines, but our findings challenge that view,” says Omar. “Across multiple neurodegenerative diseases, we see strikingly similar vascular changes, suggesting that the vasculature isn’t just collateral damage — it’s actively shaping disease progression. Recognizing these commonalities opens the door to new therapeutic possibilities that target the vasculature itself.”

The research team believes this newly identified subset of endothelial cells could provide a roadmap to targeting this endothelial disfunction to stave off disease, and also to develop new biomarkers from the blood of patients with disease.

Funding was provided by startup funds from the UConn School of Medicine and Department of Cell Biology, Center for Vascular Biology and Calhoun Cardiology Center, American Heart Association Innovative Project Award 19IPLOI34770151 (to P.A.M.); NIH National Heart, Lung, and Blood Institute Grants K99/R00-HL125727 and RF1-NS117449 (to P.A.M); American Heart Association Predoctoral award 23PRE1027078 (to O.M.F.O.) R01-AG046929 and R01-NS074256 (to R.Y.) and NIH GM135592 (to B.H.).

“We know that early childhood influenza exposures can elicit immune responses that last a lifetime,” said senior author Scott Hensley, PhD, a professor of Microbiology. “We found that antibody responses that were primed by H1N1 and H3N2 viruses decades ago can cross-react to H5N1 avian viruses circulating today. Most of these cross-reactive antibodies cannot prevent infections, but they will likely limit disease if we have an H5N1 pandemic.”

Potential protection from a rapidly changing virus

H5N1 viruses have circulated in birds for many years, but a new version, called clade 2.3.4.4b H5N1 virus emerged more recently, and has since spread among cattle. This current H5N1 strain does not bind well to receptors in the human upper airway, but widespread circulation in mammals could lead to mutations that help the virus infect human airway cells and increase transmission. If this occurs, H5N1 could potentially start spreading from human to human.

Influenza viruses are covered with two lollipop-shaped proteins called hemagglutinin and neuraminidase, for which the viruses are named (H5N1, for example). These proteins are what allows a virus to attach to “healthy” cells and start the process of infection. Current influenza vaccines primarily elicit antibodies that recognize hemagglutinin proteins, and prevent them from infecting a person’s cells. The lollipop “heads” of hemagglutinin proteins evolve more frequently while the “sticks” of the hemagglutinin lollipops, called stalks, don’t evolve as quickly.

Researchers tested blood samples from over 150 people born between 1927 and 2016 for antibodies targeting the stalk proteins of different influenza viruses, including H5N1. They found that blood samples from older adults born prior to 1968 who were likely first exposed to H1N1 or H2N2 in childhood had higher levels of antibodies that could bind to the stalk of the H5N1 virus. They found that an individual’s birth year was closely linked to the amount of H5N1-fighting antibodies in their blood. Young children who were not exposed to seasonal flu viruses possessed low levels of antibodies that could fight H5N1.

Existing vaccines are effective

To determine how individuals with different birth years respond to H5N1 vaccinations, researchers obtained blood samples from a separate group of individuals born between 1918 and 2003 before and after they were vaccinated with a 2004 H5N1 vaccine that did not perfectly match the clade 2.3.4.4b H5N1 virus that is currently circulating.

Consistent with the researchers’ initial findings, older adults had higher amounts of antibodies that could bind to H5 stalks before vaccination. Following vaccination, H5 stalk antibodies increased slightly in older adults, but increased substantially in children. These antibodies bound to both the 2004 H5N1 virus and to the clade 2.3.4.4b H5N1 virus that is circulating today.

“In the event of an H5N1 pandemic, all age groups will likely be highly susceptible, but it is possible that the highest disease burden will be in children,” said Hensley. “If this is the case, children should be prioritized for H5N1 vaccinations.”

This research was supported by the National Institute of Allergy and Infectious Diseases (75N93021C00015, R01AI08686).

“Pain processing is a complex phenomenon” explains study lead and doctoral student Max Steininger from the University of Vienna. In order to better understand it and identify treatment options, Steininger and his colleagues investigated how nature exposure influences pain: participants suffering from pain were shown three types of videos: a nature scene, an indoor scene, and an urban scene. The participants rated the pain while their brain activity was measured using functional magnetic resonance imaging. The results were clear: when viewing the nature scene, the participants not only reported less pain but also showed reduced activity in brain regions associated with pain processing.

By analyzing the brain data, the researchers showed that viewing nature reduced the raw sensory signal the brain receives when in pain. “Pain is like a puzzle, made up of different pieces that are processed differently in the brain. Some pieces of the puzzle relate to our emotional response to pain, such as how unpleasant we find it. Other pieces correspond to the physical signals underlying the painful experience, such as its location in the body and its intensity. Unlike placebos, which usually change our emotional response to pain, viewing nature changed how the brain processed early, raw sensory signals of pain. Thus, the effect appears to be less influenced by participants’ expectations, and more by changes in the underlying pain signals,” explains Steininger.

Claus Lamm, head of research in the group, adds: “From another ongoing study, we know that people consistently report feeling less pain when exposed to natural environments. However, the underlying reason for this has remained unclear — until now. Our study suggests that the brain reacts less to both the physical source and the intensity of the pain.”

The current study provides important information on how nature can help alleviate pain and highlights that nature-based therapeutic approaches can be a useful addition to pain treatment. The fact, that this effect was observed by simply watching nature videos suggests that taking a walk outdoors may not be necessary. Virtual nature — such as videos or virtual reality — appears to be effective as well. This opens up a wide range of possible applications in both the private and medical sectors, providing people with a simple and accessible way to relieve their pain.

The study was conducted at the University of Vienna in collaboration with researchers from the Universities of Exeter and Birmingham (UK) and the Max Planck Institute for Human Development.

Researchers from the fields of neuroscience and environmental psychology worked together on this research topic for the first time at the University of Vienna. Claus Lamm and Mathew White are also members of the interdisciplinary Environment and Climate Research Hub (ECH) at the University of Vienna. The ECH brings together researchers from a wide range of disciplines to produce outstanding scientific knowledge that can provide solutions to pressing problems such as climate change, biodiversity loss and environmental pollution.

The University’s Centre of Light for Life academics investigated how to best use ultrasensitive camera technology, including the latest generation of cameras that can count individual packets of light energy at each pixel, for life sciences.

Centre director Professor Kishan Dholakia said the sensitive detection of these packets of light energy, termed photons, is vitally important for capturing biological processes in their natural state-allowing researchers to illuminate live cells with gentle doses of light.

“Damage from illumination is a real concern which can often be overlooked. Using the lowest level of light possible, together with these very sensitive cameras is important for understanding biology in live and developing cells,” said Professor Dholakia.

“Modern imaging technology is very exciting with what it enables us to see.”

The research team, which also included Zane Peterkovic, Dr Avinash Upadhya, Ramses Bautista Gonzalez, Dr Megan Lim, Dr Chris Perrella, Admir Bajraktarevic and Associate Professor Kylie Dunning, who also leads the Reproductive Success Group with the Robinson Research Institute, tested the technology to image embryos as part of a pre-clinical trial, and published their findings in APL:Photonics.

“These samples are living, developing specimens that serve as a foundation for studies supporting advancements in clinical IVF,” said Professor Dholakia.

Digital camera technology has advanced to the point where fundamental physics concepts like quantum mechanics become important and relevant, said lead author and PhD student Mr Peterkovic.

“A lot of natural compounds in cells light up when illuminated, and this can tell us a lot about what we’re looking at, but unfortunately the signal is very weak,” he said.

“It’s exciting to apply these quantum cameras and use it to get the most out of our microscopes.

“A large part of the project involved developing a method to fairly compare the image quality across different cameras.”

The analysis of the images was enabled by a combination of expertise ranging from optics, biology, laser physics and microscopy.

“We even explored how AI can be used to remove noise from the captured images, which is essentially static because the camera struggles to capture enough light,” said Mr Peterkovic.

“These steps go beyond just putting the camera in the microscope to take pictures.”

Future directions for this work include extension into the realm of quantum imaging, where quantum states of light may be used to further gain further information about the sample.

Funding from this project was received from the Australian Research Council.

The study recently published in Communications Engineering, a Nature Portfolio journal.

Conductive hearing loss, which most commonly happens in childhood, occurs when sounds do not reach the inner ear. Sound waves are blocked in the outer or middle ear due to ear infections, blockages or structural abnormalities.

“Treatment for conductive hearing loss can include corrective surgeries and implantable hearing aids, which can be very invasive, especially for pediatric patients,” Moghimi said. “Flexible hearing aids offer a noninvasive alternative.”

To produce vibrations strong enough to reach the cochlea, the part of the inner ear responsible for hearing, the research team designed a flexible hearing aid. The device uses micro-epidermal actuators to create vibrations on the skin behind the ear, which then travel directly to the inner ear, bypassing the ear canal.

For the study, 10 participants between the ages of 19 and 39 wore earplugs and earmuffs to simulate conductive hearing loss. Researchers then tested arrays of the actuators to enhance the vibration strength, improve the quality of sounds and control the direction of the vibrations.

“We found that using an array of these actuators, rather than a single one, significantly enhances the strength and quality of the vibrations, leading to better hearing outcomes,” Moghimi said.

Moghimi also noted that improving hearing in children can reduce delays in language and speech development and boost educational development.

“This technology has the potential to improve the quality of life for children with hearing impairments and transform the way we approach pediatric hearing aids,” Moghimi said.

The research team will next focus on a larger study to further evaluate the efficacy and safety of the device in children and adults.

Probiotics, found in fermented foods such as yogurt and kimchi, are living microbes that improve the gut microbiome, shifting the balance toward beneficial bacteria and yeasts. They can also ease digestive issues and reduce inflammation. These active cultures need food and protection to survive harsh gut conditions, so prebiotics — substances like dietary fibers and oligosaccharides — are sometimes added to probiotic-containing products to create synbiotic foods. Because chocolate is a treat that many people enjoy, researchers have used it to test various combinations of pre- and probiotics. Some methods for including prebiotics are laborious, so Smriti Gaur and Shubhi Singh explored prebiotics that would not require extensive processing — corn and honey — in chocolate fortified with probiotics.

The team developed five chocolates for their study. One contained only basic chocolate ingredients, including cocoa butter, cocoa powder and milk powder. Four different synbiotic test samples also contained prebiotics (corn and honey), one probiotic (either Lactobacillus acidophilus La-14 or Lactobacillus rhamnosus GG) and one flavor additive (either cinnamon or orange). When the researchers examined several properties of the chocolate samples, they found that fat levels, which influence texture and mouthfeel, were consistent among all five samples. However, there were differences:

• Flavorings impacted some characteristics of the synbiotic chocolates. For example, orange flavorings decreased pH, increased moisture and enhanced protein levels compared to all the other samples.
• The four synbiotic samples had higher antioxidant levels than the control.
• Synbiotic samples had less “snap” compared to the control, suggesting that the additional ingredients disrupted the structure of the chocolate.

The total microbial counts of the synbiotic chocolate samples decreased during storage, but the probiotic microbes still exhibited viability after 125 days. This time period is longer than other researchers have reported when using different bacteria and prebiotics in chocolates. Finally, when Gaur and Singh exposed the synbiotic chocolates to simulated gastrointestinal conditions, the probiotics in the samples maintained substantial viability for more than 5 hours.

The researchers also snuck a taste of the confections. “Personally, we enjoyed the orange-flavored chocolates the most, where the vibrant citrus notes complemented the rich cocoa, and it had a slightly softer texture that made each bite feel more luxurious,” says Gaur. “In the future, we are excited to explore additional health benefits of these chocolates while thoroughly investigating their sensory and nutritional profiles, with the goal of creating an even more wholesome and enjoyable treat.”

The authors report no external funding for this work.

HIV is a virus that attacks cells in the body fighting off infections, thus weakening the immune system. Antiretroviral therapies can treat the HIV infection by halting the spread of the virus and protecting the immune system, but do not cure the virus. Mount Sinai researchers have developed a method to genetically mark immune cells that carry HIV, an important milestone that could potentially lead to approaches that eliminate the dormant HIV-infected cells and cure the virus.

The team created a novel cell lineage-tracing model to reveal where the virus hides, and developed genetic profiles of T cells, or white blood cells that are crucial to immune response and retain either active or inactive HIV. The researchers said their genetic analysis of the dormant HIV-infected cells provides a new gene pathway for potential treatment.

“The main obstacle to cure the infection is the virus hides in immune cells that are difficult to identify and study. If we can identify the cells infected with HIV, it will help bring us closer to figuring out how to eliminate them,” said corresponding author Benjamin K. Chen, MD, PhD, Professor of Medicine (Infectious Diseases), Microbiology, Pharmacological Sciences, and Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai.

The researchers developed a genetic system to mark HIV-infected cells and then study both infected and dormant cell populations. They used humanized mice models to develop a fluorescent red-to-green switch triggered by the HIV infection that persists even if the virus is dormant. This switch results in the permanent marking of HIV-infected cells in mice and enables lineage tracing of the HIV infection. The research team profiled more than 47,000 T cells including acutely infected, treated, and uninfected cells, to then identify helper T cells (which detect infections), memory cells, naïve cells (which fight off infections), proliferating cells, regulatory T cells, and subsets within these larger groups. Through their analysis, they predicted and identified nine distinct types of T cells that housed inactive HIV cells. Their investigation also identified persistent T cells with HIV even after 10 and 29 days of antiretroviral therapies.

The findings suggest new therapies that target the reservoir of dormant HIV-infected cells as a potential cure for the virus. The Mount Sinai team will next study and test specific approaches to reactivate dormant HIV and determine if it is possible to reduce the reservoir of infected cells.

The study was supported by funding from the National Institute of Allergy and Infectious Diseases and the National Institutes of Health (AI116191, AI162223, S10OD026880, and S10OD030463), and the Clinical and Translational Science Awards (CTSA) grant from the National Center for Advancing Translational Sciences (UL1TR004419).

To enhance the efficacy of radiotherapy, a research team from Japan, led by Assistant Professor Hiroyuki Suzuki from Chiba University, including Dr. Tomoya Uehara from Chiba University, Dr. Noriko S. Ishioka from National Institutes for Quantum Science and Technology, Dr. Hiroshi Tanaka from Juntendo University, Dr. Tadashi Watabe from Osaka University, adopted targeted alpha therapy (TAT) as a promising alternative to conventional beta therapy. They developed an astatine-211 (²¹¹At)-labeled peptide drug that could offer a potential breakthrough for treating metastatic melanoma. The research was conducted in collaboration with the National Institutes for Quantum Science and Technology and was published in the European Journal of Nuclear Medicine and Molecular Imaging on January 20, 2025.

TAT is a form of radiotherapy that involves drugs labeled with alpha particle-emitting radioisotopes. Compared to other forms of radioactive emissions (beta and gamma emissions), alpha particles are heavier and therefore have a short range. Owing to their greater mass, alpha particles also carry relatively higher energy, which is beneficial for the disruption of cancer cells.

To develop the treatment, the researchers first identified an optimal hydrophilic linker to enhance tumor targeting and reduce off-target accumulation. The team then designed an astatine-211(²¹¹At)-labeled α-melanocyte-stimulating hormone (α-MSH) peptide analog called [²¹¹At]NpG-GGN4c to specifically target melanocortin-1 receptors (MC1R), which are overexpressed in melanoma cells. “Since the tagged peptide was also receptor-targeted, it allowed for a high tumor selectivity while minimizing radiation exposure to the surrounding tissues,” comments Dr. Suzuki.

The synthesized peptides were then tested on B16F10 melanoma-bearing mice models, following which they conducted a biodistribution analysis where the team compared tumor uptake, clearance from organs, and the overall stability of the compound. Dr. Uehara elaborates on the methodology, saying, “We treated the mice with different doses of the compound while monitoring the tumor response, body weight, and survival rates over time. We found a dose-dependent inhibitory effect in a melanoma-bearing mouse model, confirming the effectiveness of our approach.”

The findings were remarkable. The [²¹¹At]NpG-GGN4c showed high accumulation in tumors and rapid clearance from non-target organs, confirming its specificity for MC1R on melanoma cells. Monitoring tumor growth revealed significant tumor suppression in a dose-dependent manner. Furthermore, [²¹¹At]NpG-GGN4c also demonstrated high stability in blood plasma, minimizing the risk of radioactive leakage in the body.

Hailing the exciting results, Dr. Suzuki affirms that the molecular design of their synthesized drug could be useful for developing other ²¹¹At-labeled radiopharmaceuticals. He says, “We believe our approach could open up new possibilities for treating refractory cancers beyond melanoma.”

The team is also hopeful about promoting a clinical application of ²¹¹At-based TAT. “If successfully translated into human trials, this therapy may emerge as a viable treatment option for patients with advanced melanoma in the coming years,” speculates Dr. Suzuki. “This could provide new therapeutic opportunities for patients with refractory cancer.”

Using real world data from 1,600 patients, available through a database created for speeding up research and innovation, the team also found that its reliability differs significantly in winter compared to autumn.

Asthma is a common lung condition that can cause wheezing and shortness of breath, occasionally severe. Around 6.5% of people over six years old in the UK are affected by the condition. Treatments include the use of inhalers or nebulisers to carry medication into the lungs.

The majority of asthma attacks occur at nighttime or early in the morning. Although this may in part be due to cooler nighttime air and exposure to dust mites and allergens, it also suggests that circadian rhythms — our ‘body clocks’ — likely play a role.

Researchers at the Victor Phillip Dahdaleh Heart and Lung Research Institute, a collaboration between the University of Cambridge and Royal Papworth Hospital NHS Foundation Trust (RPH), wanted to explore whether these circadian rhythms may also have an impact on our ability to diagnose asthma, using routinely performed clinical testing.

Typically, people with suspected asthma will be offered a spirometry test, which involves taking a deep breath in, then breathing out hard and fast for as long as possible into a tube to assess lung function. They will then be administered the drug salbutamol via an inhaler or nebuliser, and shortly afterwards retake the spirometry test.

Salbutamol works by opening up the airways, so a positive test result — that is, a difference in readings between the initial and follow-up spirometry tests — means that the airways must have been narrower or obstructed to begin with, suggesting that the patient could have asthma.

Cambridge University Hospitals NHS Foundation Trust (CUH) has recently set up the Electronic Patient Record Research and Innovation (ERIN) database so that researchers can access patient data in a secure environment to help in their research and speed up improvements in patient care.

Using this resource, the Cambridge team analysed data from 1,600 patients referred to CUH between 2016 and 2023, adjusted for factors such as age, sex, body mass index (BMI), smoking history, and the severity of the initial impairment in lung function.

In findings published today in Thorax, the researchers found that starting at 8.30am, with every hour that passed during the working day, the chances of a positive response to the test — in other words, the patient’s lungs responding to treatment, suggesting that they could have asthma — decreased by 8%.

Dr Ben Knox-Brown, Lead Research Respiratory Physiologist at RPH, said: “Given what we know about how the risk of an asthma attack changes between night and day, we expected to find a difference in how people responded to the lung function test, but even so, we were surprised by the size of the effect.

“This has potentially important implications. Doing the test in the morning would give a more reliable representation of a patient’s response to the medication than doing it in the afternoon, which is important when confirming a diagnosis such as asthma.”

The researchers also discovered that individuals were 33% less likely to have a positive result if tested during autumn when compared to those tested during winter.

Dr Akhilesh Jha, a Medical Research Council Clinician Scientist at the University of Cambridge and Honorary Consultant in Respiratory Medicine at CUH, said that there may be a combination of factors behind this difference.

“Our bodies have natural rhythms — our body clocks,” Jha said. “Throughout the day, the levels of different hormones in our bodies go up and down and our immune systems perform differently, for example. Any of these factors might affect how people respond to the lung function test.

“The idea that the time of day, or the season of the year, affects our health and how we respond to treatments is something we’re seeing increasing evidence of. We know, for example, that people respond differently to vaccinations depending on whether they’re administered in the morning or afternoon. The findings of our study further support this idea and may need to be taken into account when interpreting the results of these commonly performed tests.”

Scientists have long studied the ins and outs of cancer cells to learn more about the disease, but they’re increasingly finding that noncancerous cells near the cancer cells exert a powerful influence over a tumor’s trajectory.

“Not all cells in a tumor are cancer cells — they’re not even always the most dominant cell type,” said Sylvia Plevritis, PhD, chair of Stanford Medicine’s department of biomedical data science. “There are many other cell types that support tumors.”

To better capture the whole picture of cells’ locations and interactions, Plevritis and a team of researchers have developed something that they call the “colocatome,” (pronounced co-locate-ome). Modeled after the nomenclature that describes other classes of molecules and facets of human biology (collective information about genes is called the genome; proteins, the proteome; metabolites, the metabolome, etc.) the colocatome documents the details of malignant cells on their neighbors — what those cells are and how many of them are present.

“We’ve been studying cancer cells for so long, but the picture is still incomplete,” said Gina Bouchard, PhD, instructor of biomedical data science. “Understanding tumor biology is not only about cancer cells; there’s a whole ecosystem that needs to be studied. Cancer cells need help to survive, to resist, to thrive and even sometimes to die.”

A study describing the findings was published in Nature Communications last month. Bouchard is the lead author, and Plevritis is the senior author.

Mapping influence

Cancer cells are surprisingly dependent on their surroundings. Depending on the location, type and quantity of noncancerous cells surrounding the tumor, the cells’ behavior can change, whether through faster growth, decreased susceptibility to drugs or heightened cell metabolism.

“The questions we’re asking are very simple. We want to know who the neighbors are for each cell. Who likes whom? Who doesn’t like whom? It’s all about which cells tend to be together, and which ones are rarely found together,” Bouchard said. Cells that attract each other are described as “colocalizing” while those that seem to repel each other form “anti-colocalizations.” Those colocalizations are then linked to the state of the cancer — aggressive, resistant, susceptible to drugs — and logged in the colocatome.

The team developed experimental models of lung cancer in the lab, then used artificial intelligence to analyze them, identifying noncancerous cells and how they organized within and around the tumor cells. They then compared the colocalizations with those from patient tumor biopsies. After mapping hundreds of cell configurations, they confirmed that the majority of colocalizations in the primary patient tumors are observed in the experimental models. (That overlap is key, said Bouchard. It means that the models are a valuable and accurate representation of what’s happening in someone who has lung cancer.)

Past research by Plevritis and others showed strong interactions between fibroblasts and cancer cells, but exactly how fibroblasts interact with cancer cells is unclear. In an experiment, Plevritis showed that lung cancer cells die when doused with a type of anti-tumor drug that stunts cell growth. But throw fibroblasts into the mix, and the entire landscape changes — literally. Plevritis mapped the treated tumor models and saw that post-treatment, the cancer cells and fibroblasts were generally left intact in the same amount. But they had rearranged themselves.

“That spatial reorganization appears to have given rise to drug-resistance,” said Plevritis, the William M. Hume Professor in the School of Medicine. “It was like changing the furniture in the room, then finding the exits are blocked.”

Chasing new leads

As the team continues to log spatial maps of treated and untreated tumors, they hope to unlock more configurations that help clue doctors in on why some cancers persist after treatment. Ideally, the researchers said, the colocatome could provide information that guides treatment of patient’s cancer: If a specific colocalization confers resistance to a common drug, for instance, physicians can search for another that might have a better chance of working. They also hope the colocalization maps will generate testable hypotheses to describe aspects of cancer biology that remain unclear.

As they collect more data, the team plans to employ AI to identify specific spatial motifs and create catalogs of maps that correspond to different cell states for a variety of cancers. “Then we can begin to see whether certain spatial motifs are shared between cancer types, regardless of where they originate in the body. That could reveal universal rules of tumor behavior and guide the design of more broadly effective treatments,” Plevritis said. “That’s something I’m really excited about.”

A researcher from the University of Oxford contributed to this research.

This study was funded by the National Institute of Health (grants R25CA180993, U54CA274511 and K99CA255586) and Les Fonds de Recherche du Québec.

Stanford’s Department of Biomedical Data Sciences also supported the work.

Understanding the differences in the mutations that accumulate in our blood stem cells as we age is important to understand how and why blood cancers develop and hopefully how to intervene before the onset of clinical symptoms.

As we age, stem cells in the bone marrow naturally accumulate mutations and with this, we see the emergence of clones, which are groups of blood cells that have a slightly different genetic makeup. Sometimes, specific clones can lead to blood cancers like leukaemia.

When people donate blood, stem cells in the bone marrow make new blood cells to replace the lost blood and this stress drives the selection of certain clones.

In research published today in Blood, the team at the Crick, in collaboration with scientists from the DFKZ in Heidelberg and the German Red Cross Blood Donation Centre, analysed blood samples taken from over 200 frequent donors — people who had donated blood three times a year over 40 years, more than 120 times in total — and sporadic control donors who had donated blood less than five times in total.

Samples from both groups showed a similar level of clonal diversity, but the makeup of the blood cell populations was different.

For example, both sample groups contained clones with changes to a gene called DNMT3A, which is known to be mutated in people who develop leukaemia. Interestingly, the changes to this gene observed in frequent donors were not in the areas known to be preleukemic.

To understand this better, the Crick researchers edited DNMT3A in human stem cells in the lab. They induced the genetic changes associated with leukaemia and also the non-preleukemic changes observed in the frequent donor group.

They grew these cells in two environments: one containing erythropoietin (EPO), a hormone that stimulates red blood cell production which is increased after each blood donation, and another containing inflammatory chemicals to replicate an infection.

The cells with the mutations commonly seen in frequent donors responded and grew in the environment containing EPO and failed to grow in the inflammatory environment. The opposite was seen in the cells with mutations known to be preleukemic.

This suggests that the DNMT3A mutations observed in the frequent donors are mainly responding to the physiological blood loss associated with blood donation.

Finally, the team transplanted the human stem cells carrying the two types of mutations into mice. Some of these mice had blood removed and then were given EPO injections to mimic the stress associated with blood donation.

The cells with the frequent donor mutations grew normally in control conditions and promoted red blood cell production under stress, without cells becoming cancerous. In sharp contrast, the preleukemic mutations drove a pronounced increase in white blood cells in both control or stress conditions.

The researchers believe that regular blood donation is one type of activity that selects for mutations that allow cells to respond well to blood loss, but does not select the preleukemic mutations associated with blood cancer.

Dominique Bonnet, Group Leader of the Haematopoietic Stem Cell Laboratory at the Crick, and senior author, said: “Our work is a fascinating example of how our genes interact with the environment and as we age. Activities that put low levels of stress on blood cell production allow our blood stem cells to renew and we think this favours mutations that further promote stem cell growth rather than disease.

“Our sample size is quite modest, so we can’t say that blood donation definitely decreases the incidence of pre-leukemic mutations and we will need to look at these results in much larger numbers of people. It might be that people who donate blood are more likely to be healthy if they’re eligible, and this is also reflected in their blood cell clones. But the insight it has given us into different populations of mutations and their effects is fascinating.”

Hector Huerga Encabo, postdoctoral fellow in the Haematopoietic Stem Cell Laboratory at the Crick, and first joint author with Darja Karpova from the DFKZ in Heidelberg, said: “We know more about preleukemic mutations because we can see them when people are diagnosed with blood cancer.

“We had to look at a very specific group of people to spot subtle genetic differences which might actually be beneficial in the long-term. We’re now aiming to work out how these different types of mutations play a role in developing leukaemia or not, and whether they can be targeted therapeutically.”

This work was possible thanks to the collaboration with Andreas Trumpp’s group at the DFKZ in Heidelberg and Halvard Boenig’s group from the German Red Cross Blood Donation Service Centre in Frankfurt.

“Identifying a mutation signature like this one is important because this can inform public health intervention strategies,” said senior author Elizabeth B. Claus, MD, PhD, of the Department of Neurosurgery at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. Claus also holds an appointment at Yale School of Public Health. “Some occupational hazards may be avoidable and pinpointing them could help to prevent gliomas.”

Claus and colleagues compared genetic samples from tumors from 17 firefighters with tumors to 18 people who had never been firefighters. They found mutations tied to a known “mutational signature” — a unique pattern of genetic mutations — in many of the firefighter samples, especially in those who had spent more years firefighting. Among the non-firefighters, the highest signal of the signature was seen among people who had possibly been exposed to haloalkenes through other occupations, such as painting or being a mechanic.

“In this pilot study, we confirm our earlier findings of an association between exposure to haloalkanes and glioma risk-we hope to further examine this in larger samples that include both firefighters and other persons exposed to haloalkanes,” said Claus. “Our efforts to do so continues via development of our online glioma registry, an effort to study risks factors and treatments for persons with glioma.”

Disclosures: Elizabeth B. Claus reports advisory board fees from Servier Pharmaceuticals outside the submitted work. Additional author disclosures can be found in the paper.

The study, conducted by the Faculty of Sport and Health Sciences at the University of Jyväskylä and the Institute of Biomedicine at the University of Eastern Finland, followed 187 adolescents over an eight-year period. Researchers found that children who spent more time on screens -especially mobile devices — were more likely to experience higher levels of stress and depressive symptoms in adolescence.

Conversely, higher levels of physical activity and participation in organized sports were associated with lower stress and fewer depressive symptoms. However, the link between physical activity and depressive symptoms was weaker than that of screen time and depressive symptoms. Adolescents with both high screen time and low physical activity had the highest levels of stress and depressive symptoms.

“Several international, evidence-based recommendations suggest that the leisure screen time of children and adolescents should be limited to two hours per day.”

“Personally, I think that even this figure is high, as it amounts to almost one month of screen time per year,” says Senior Lecturer Eero Haapala from the Faculty of Sport and Health Sciences at the University of Jyväskylä.

Balancing physical activity and screen time?

These findings emphasize the need to promote healthy lifestyle habits early in life. Encouraging children to engage in physical activity and setting reasonable limits on screen time could play a crucial role in preventing mental health challenges later in life.

“The modern sedentary lifestyle, with high screen exposure, challenges the mental health of children and adolescents,” says Dr Eero Haapala.

“Recent discussions have rightly focused on screen time and social media, but I hope our findings encourage adults in young people’s lives to promote a broad spectrum of healthy habits — especially by balancing screen time and physical activity.”

“Achieving change requires collaboration,” Haapala emphasises.

“Society as a whole — from families to policymakers — must invest in promoting healthy lifestyles for children and adolescents by ensuring balanced screen time, sufficient physical activity, adequate sleep, and a nutritious diet.”

The PANIC Study is part of the Metabolic Diseases Research Community at the University of Eastern Finland. The research community is dedicated to investigating major cardiometabolic diseases. By leveraging genetics, genomics, translational research, and lifestyle interventions, the community aims to provide robust evidence on disease mechanisms and advance early diagnosis, prevention, and personalized treatment. The research community consists of 20 research groups, spanning basic research to patient care.

A total of six participants will be included in the Phase 1 trial that will track the patients for 12 months and beyond to determine the safety of the procedure and monitor for any improvements in Parkinson’s disease. Following the first 6 patients transplanted in the Phase 1 study, the researchers hope to expand and recruit more patients as part of Phase 2A study.

This novel therapeutic approach for treating Parkinson’s disease incorporates the use of stem cells derived from a patient’s own blood that had been converted into induced pluripotent stem cells (iPSCs). These cells are then reprogrammed to turn into specific midbrain dopaminergic neurons ready for transplantation. The autologous transplantation approach of using a person’s own cells circumvents the requirement for immunosuppressive treatments, which are necessary when cells from other donors are used.

Cell replacement for Parkinson’s disease replaces the dopamine neurons lost to degeneration and can restore dopaminergic function in the brain, providing a completely new treatment modality compared to the currently available treatments. The NRI’s founding director, Ole Isacson, Dr Med Sci, who is also a professor of neurology (neuroscience) at Harvard Medical School and Mass General Brigham, has pioneered work in cell therapy for Parkinson’s disease over the past 30 years and laid the foundation for this clinical trial.

“Seeing this transformational new patient cell-based replacement of their own dopamine neurons come to fruition — from the very basic science breakthroughs in our lab to be completely translated into a clinical application for patient’s suffering from Parkinson’s disease — is very gratifying,” said Isacson. “We believe this approach may open up a new treatment paradigm and lead to the development of many additional cell therapies to restore damaged brain systems and replace degenerated brain cells in other diseases.”

Under Isacson’s leadership, the NRI at McLean has developed and patented autologous cell-based restoration in Parkinson’s disease with a pioneering preclinical publication in 2002 using stem cells and the first preclinical demonstration of effective human iPS cell-derived dopamine neuron use in 2010. In 2015, the NRI team, led by Isacson and Penny Hallett, PhD, co-director of the NRI at McLean and associate professor of psychiatry at Harvard Medical School, provided the first evidence of long-term safety and benefits of autologous stem cell therapy in a highly relevant Parkinson’s disease non-human primate animal model.

The NRI received official authorization from the U.S. Food and Drug Administration (FDA) on August 23, 2023, approving its Investigational New Drug (IND) application for a phase 1 clinical trial to test this unique, autologous dopamine neuron cell therapy.

Following this FDA approval for the phase 1 clinical trial, the NRI’s innovative preclinical work was translated into the clinic with the first patient treated on September 9, 2024. This collaboration includes NRI investigators James Schumacher, MD, and Oliver Cooper, PhD, and colleagues in the Neurology (Michael Hayes, MD) and Neurosurgery (John Rolston, MD, PhD, principal investigator of the Phase 1 trial) Departments at Brigham and Women’s Hospital. Isacson is not directly involved in the clinical trial because he is the innovator patent holder of the technology and also a co-founder of Oryon Cell Therapies, which has the license to this technology. The trial is directed by Hallett and colleagues within the Mass General Brigham healthcare system and its Harvard Medical School-affiliated institutions.

“It is extraordinary to witness that investigators at our institution can bring new treatments to patients through the entire process of laboratory “bench to bedside,” and it inspires many investigators to similarly pursue their scientific and medical insights to reach patients in need,” said Kerry Ressler MD, PhD, chief scientific officer at McLean Hospital.

The Phase 1 open-label clinical trial will be the first such trial to test blood-derived autologous iPSC-derived dopamine neurons in patients with Parkinson’s disease and is funded by the National Institute of Health’s National Institute of Neurological Disorders and Stroke (NINDS). The NINDS awarded the highly competitive Cooperative Research to Enable and Advance Translational Enterprises for Biologics (CREATE Bio) grant for this work in 2020.

People seeking more information in the trial can email: @bwh.harvard.edu” title=”mailto:[email protected]”>[email protected]

For More Information:

• McLean Hospital Receives Coveted NIH Grant to Clinically Study Autologous Stem Cell Therapy for Parkinson’s Disease
• Patient-derived stem cells could improve drug research for Parkinson’s

Funding: The study was supported by a NINDS CREATE Bio grant (U01NS109463).

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Disclosure:Isacson has co-founded a company (Oryon Cell Therapies) which has licensed the patents and know-how for developing autologous cell therapies for Parkinson’s disease. Isacson’s interests were reviewed and are managed by McLean Hospital and Mass General Brigham in accordance with their conflict of interest polices.

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About Mass General Brigham

Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.

“What’s surprising is the magnitude of the association that we found — we saw a 17% lower risk of death when we modeled swapping butter with plant-based oils in daily diet. That is a pretty huge effect on health,” said study lead author Yu Zhang, MBBS, research assistant at the Channing Division of Network Medicine at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. Zhang is also a student in the Department of Epidemiology at Harvard Chan School.

A key difference between butter and oil is the types of fatty acids contained in them. Butter is rich in saturated fatty acids, while plant-based oils have more unsaturated fatty acids. While there have been many studies on dietary fatty acids, fewer studies have focused on their primary food sources, including butter and oils. Many previous studies have looked at a person’s diet at a point in time and have been done in a small population, limiting their applicability to public health.

The new study analyzed dietary data from 221,054 participants in the Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), and Health Professionals Follow-up Study (HPFS). Every four years, they answered questions about how often they consumed certain types of food. The researchers used the data to estimate how much butter and plant oils they ate.

Total butter intake included butter from butter and margarine blend, spreadable butter added to food and bread, and butter used in baking and frying at home. The intake of plant-based oils was estimated based on the reported use in frying, sautéing, baking, and salad dressing.

The researchers also identified participants who had died and their causes of death. Using statistics to compare death rates across different diet intake levels, the researchers found that participants who ate the most butter had a 15% higher risk of dying than those who ate the least. In contrast, those who ate the most plant-based oils had a 16% lower risk of death than those who ate the least.

“People might want to consider that a simple dietary swap — replacing butter with soybean or olive oil — can lead to significant long-term health benefits,” said corresponding author Daniel Wang, MD, ScD, of the Channing Division of Network Medicine at Brigham and Women’s Hospital. Wang is also an assistant professor in the Department of Nutrition at Harvard Chan School and an associate member at the Broad Institute of MIT and Harvard. “From a public health perspective, this is a substantial number of deaths from cancer or from other chronic diseases that could be prevented.”

The researchers also did a substitution analysis, which mimics how swapping butter for plant oils would impact health in a feeding trial. They found that substituting 10 grams of butter a day (less than a tablespoon) with equivalent calories of plant-based oils could lower cancer deaths and overall mortality by 17%.

“Even cutting back butter a little and incorporating more plant-based oils into your daily diet can have meaningful long-term health benefits,” Wang said.

One limitation of the study is that the participants are mainly health professionals, so they might not represent the U.S. population as a whole, the researchers said. In the future, they’d like to study the biological mechanisms underlying why this dietary change has such a large impact.

“When the heart cannot replace injured cardiomyocytes with healthy ones, it becomes progressively weaker, a condition leading to heart failure. In this study, we investigated a new way to stimulate cardiomyocyte proliferation to help the heart heal,” said co-corresponding author Dr. Riham Abouleisa, assistant professor in the Division of Cardiothoracic Surgery at Baylor.

Previous studies showed that calcium plays an important role in cardiomyocyte proliferation. In the current study, Abouleisa and her colleagues explored how modulating calcium influx in cardiomyocytes would affect their proliferation.

“We found that preventing calcium influx in cardiomyocytes enhances the expression of genes involved in cell proliferation,” Abouleisa said. “We prevented calcium influx by inhibiting L-Type Calcium Channel (LTCC), a protein that regulates calcium in these cells. Our findings suggest that LTCC could be a target for developing new therapies to induce cardiomyocyte proliferation and regeneration.”

The study demonstrates that both pharmacological and genetic inhibition of LTCC can induce cardiomyocyte replication and that this occurs by modulating the activity of calcineurin, a known regulator of cardiomyocyte proliferation. This innovative approach showed promising results both in human cardiac slices grown in the lab and in live animals.

“Abouleisa’s multi-continent collaborations led to a discovery that can revolutionize the use of current medicines that regulate calcium entry to the cells, such as Nifedipine, in heart failure patients,” said Dr. Tamer Mohamed, co-author and director of Baylor College of Medicine’s Laboratory for Cardiac Regeneration.

Co-author Dr. Todd K. Rosengart, chair and professor of the Michael E. DeBakey Department of Surgery, emphasized that, “The premise of regenerating heart tissue, which once seemed like an impossible dream, is getting closer almost daily. The work of Dr. Abouleisa and the Baylor cardiac regeneration team represents a major step toward human trials that I believe are in the not-too-distant future.”

Abouleisa and her colleagues’ research highlights the importance of targeting calcium signaling pathways to unlock the regenerative potential of the heart and opens new avenues for developing cardiac regenerative therapies, potentially transforming the treatment landscape for patients suffering from heart failure.

Other contributors to this work include Lynn A C Devilée, Abou Bakr M Salama, Jessica M Miller, Janice D Reid, Qinghui Ou, Nourhan M Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Douglas Andres, Jonathan Satin and James E Hudson.

Results of a trial led by the university revealed that a unique investigational drug formulation called Rhenium Obisbemeda (186RNL) more than doubled median survival and progression-free time, compared with standard median survival and progression rates, and with no dose-limiting toxic effects.

“As a disease with a pattern of recurrence, resistance to chemotherapies and difficulty to treat, glioblastoma has needed durable treatments that can directly target the tumor while sparing healthy tissue,” said Andrew J. Brenner, MD, PhD, professor and chair of neuro-oncology research with Mays Cancer Center at UT Health San Antonio. “This trial provides hope, with a second phase under way and planned for completion by the end of this year.”

Brenner, who also is clinical investigator for the Institute for Drug Development at UT Health San Antonio and co-leader of its Experimental and Development Therapeutics Program, is lead author of the trial’s study, titled, “Convection Enhanced Delivery of Rhenium (¹⁸⁶Re) Obisbemeda (¹⁸⁶RNL) in Recurrent Glioma: a multicenter, single arm, phase 1 clinical trial.” It published March 7 in the journal Nature Communications.

Other authors also are with Mays Cancer Center, as well as UT Southwestern Medical Center of Dallas, Case Western Reserve University, University of Texas MD Anderson Cancer Center and trial sponsor Plus Therapeutics Inc. (Nasdaq: PSTV), a clinical-stage pharmaceutical company receiving license to the trial technology to investigate the treatment of central nervous system cancers.

Brenner said that the median overall survival time for patients with glioblastoma after standard treatment fails with surgery, radiation and chemotherapy is only about 8 months. More than 90% of patients have a recurrence of the disease at its original location.

Rhenium Obisbemeda enables very high levels of a specific activity of rhenium-186 (186Re), a beta-emitting radioisotope, to be delivered by tiny liposomes, referring to artificial vesicles or sacs having at least one lipid bilayer. The researchers used a custom molecule known as BMEDA to chelate or attach 186Re and transport it into the interior of a liposome where it is irreversibly trapped.

In this trial, known as the phase 1 ReSPECT-GBM trial, scientists set out to determine the maximum tolerated dose of the drug, as well as safety, overall response rate, disease progression-free survival and overall survival.

After failing one to three therapies, 21 patients who were enrolled in the study between March 5, 2015, and April 22, 2021, were treated with the drug administered directly to the tumors using neuronavigation and convection catheters.

The researchers observed a significant improvement in survival compared with historical controls, especially in patients with the highest absorbed doses, with a median survival and progression-free time of 17 months and 6 months, respectively, for doses greater than 100 gray (Gy), referring to units of radiation.

Importantly, they did not observe any dose-limiting toxic effects, with most adverse effects deemed unrelated to the study treatment.

“The combination of a novel nanoliposome radiotherapeutic delivered by convection-enhanced delivery, facilitated by neuronavigational tools, catheter design and imaging solutions, can successfully and safely provide high absorbed radiation doses to tumors with minimal toxicity and potential survival benefit,” Brenner concluded.

Phase 2 of the ReSPECT-GBM trial is enrolling patients.

“These numbers show that living in a dementia-friendly environment is important to delay or prevent cognitive decline and the onset of dementia,” Song said.

Conducting the meta-analysis was important, as was taking several empirical studies to create a clearer picture about environmental risk, Song said. The research combined 54 studies in a systematic review and 21 in the meta-analysis, enabling researchers to quantify the impact of several factors.

While past research has shown the association between environmental factors and dementia risk, Song said the contributions of some factors were worth noting.

Environmental factors could increase dementia risk by 10%

Living near major roadways was associated with a roughly 10% higher risk of dementia, and exposure to fine particulate matter in the air — something that is generated by vehicles and industrial emissions — was associated with a 9% increase in risk. Nitrous Oxide increased risk by 10%, and noise pollution was shown to increase risk by about 9%.

Alternatively, some built environments help reduce the risk of cognitive decline. Green and blue spaces, which include built and natural parks as well as bodies of water, reduced risk by about 6%. Walkability in a community, as well as access to local amenities including food stores, community centers and health care, also reduced risk.

“Based on these findings, we can suggest that people visit parks or forests more often and also live further from the major roads,” Song said. “Also, living in a community where there is more walkability, or being close to local amenities like bookstores, health care centers and more is helpful.”

Improving urban planning

This data can help inform urban planning efforts moving forward to create more communities that foster cognitive health, Song said.

“The biggest advantage of this paper is to quantify the association between certain factors and cognitive health,” Song said. “This analysis can provide evidence for data-driven urban planning and support decision makers.”

Summarizing objective measurements of environmental factors for future research

This systematic review and meta-analysis focused on studies using objectively measured environmental factors, which may reduce the bias associated with subjective measures such as perceptions of air quality or individual reports of greenspace and an area’s beauty. These instances of self-reported data can sometimes limit the reliability of a study’s conclusions.

Song hopes this study will serve as a foundation for future research, encouraging researchers to prioritize objective measurements in investigating environmental influences on cognition and dementia risk.

Until now, artificial gels have either managed to replicate this high stiffness or natural skin’s self-healing properties, but not both. Now, a team of researchers from Aalto University and the University of Bayreuth are the first to develop a hydrogel with a unique structure that overcomes earlier limitations, opening the door to applications such as drug delivery, wound healing, soft robotics sensors and artificial skin.

In the breakthrough study, the researchers added exceptionally large and ultra-thin specific clay nanosheets to hydrogels, which are typically soft and squishy. The result is a highly ordered structure with densely entangled polymers between nanosheets, not only improving the mechanical properties of the hydrogel but also allowing the material to self-heal.

The research was published in the journal Nature Materials on 7 March.

Healing via ‘entanglement’

The secret of the material lies not only in the organised arrangement of the nanosheets, but also in the polymers that are entangled between them — and a process that’s as simple as baking. Postdoctoral researcher Chen Liang mixed a powder of monomers with water that contains nanosheets. The mixture was then placed under a UV lamp — similar to that used to set gel nail polish. ‘The UV-radiation from the lamp causes the individual molecules to bind together so that everything becomes an elastic solid — a gel,’ Liang explains.

‘Entanglement means that the thin polymer layers start to twist around each other like tiny wool yarns, but in a random order,’ adds Hang Zhang, from Aalto University. ‘When the polymers are fully entangled, they are indistinguishable from each other. They are very dynamic and mobile at the molecular level, and when you cut them, they start to intertwine again.’

Four hours after cutting it with a knife, the material is already 80 or 90 percent self-healed. After 24 hours, it is typically completely repaired. Furthermore, a one-millimetre-thick hydrogel contains 10,000 layers of nanosheets, which makes the material as stiff as human skin, and gives it a comparable degree of stretch and flexibility.

‘Stiff, strong and self-healing hydrogels have long been a challenge. We have discovered a mechanism to strengthen the conventionally soft hydrogels. This could revolutionise the development of new materials with bio-inspired properties,’ says Zhang.

Gaining inspiration from nature

‘This work is an exciting example of how biological materials inspire us to look for new combinations of properties for synthetic materials. Imagine robots with robust, self-healing skins or synthetic tissues that autonomously repair,” says Olli Ikkala, from Aalto University. And even though there may be some way to go before real-world application, the current results represent a pivotal leap. ‘It’s the kind of fundamental discovery that could renew the rules of material design.’

The collaboration was led by Dr. Hang Zhang, Prof. Olli Ikkala and Prof. Josef Breu. The synthetic clay nanosheets were designed and manufactured by Prof. Josef Breu at the University of Bayreuth in Germany.

He was able to grasp, move and drop objects just by imagining himself performing the actions.

The device, known as a brain-computer interface (BCI), worked for a record 7 months without needing to be adjusted. Until now, such devices have only worked for a day or two.

The BCI relies on an AI model that can adjust to the small changes that take place in the brain as a person repeats a movement — or in this case, an imagined movement — and learns to do it in a more refined way.

“This blending of learning between humans and AI is the next phase for these brain-computer interfaces,” said neurologist, Karunesh Ganguly, MD, PhD, a professor of neurology and a member of the UCSF Weill Institute for Neurosciences. “It’s what we need to achieve sophisticated, lifelike function.”

The study, which was funded by the National Institutes of Health, appears March 6 in Cell.

The key was the discovery of how activity shifts in the brain day to day as a study participant repeatedly imagined making specific movements. Once the AI was programmed to account for those shifts, it worked for months at a time.

Location, location, location

Ganguly studied how patterns of brain activity in animals represent specific movements and saw that these representations changed day-to-day as the animal learned. He suspected the same thing was happening in humans, and that was why their BCIs so quickly lost the ability to recognize these patterns.

Ganguly and neurology researcher Nikhilesh Natraj, PhD, worked with a study participant who had been paralyzed by a stroke years earlier. He could not speak or move.

He had tiny sensors implanted on the surface of his brain that could pick up brain activity when he imagined moving.

To see whether his brain patterns changed over time, Ganguly asked the participant to imagine moving different parts of his body, like his hands, feet or head.

Although he couldn’t actually move, the participant’s brain could still produce the signals for a movement when he imagined himself doing it. The BCI recorded the brain’s representations of these movements through the sensors on his brain.

Ganguly’s team found that the shape of representations in the brain stayed the same, but their locations shifted slightly from day to day.

From virtual to reality

Ganguly then asked the participant to imagine himself making simple movements with his fingers, hands or thumbs over the course of two weeks, while the sensors recorded his brain activity to train the AI.

Then, the participant tried to control a robotic arm and hand. But the movements still weren’t very precise.

So, Ganguly had the participant practice on a virtual robot arm that gave him feedback on the accuracy of his visualizations. Eventually, he got the virtual arm to do what he wanted it to do.

Once the participant began practicing with the real robot arm, it only took a few practice sessions for him to transfer his skills to the real world.

He could make the robotic arm pick up blocks, turn them and move them to new locations. He was even able to open a cabinet, take out a cup and hold it up to a water dispenser.

Months later, the participant was still able to control the robotic arm after a 15-minute “tune-up” to adjust for how his movement representations had drifted since he had begun using the device.

Ganguly is now refining the AI models to make the robotic arm move faster and more smoothly, and planning to test the BCI in a home environment.

For people with paralysis, the ability to feed themselves or get a drink of water would be life changing.

Ganguly thinks this is within reach.

“I’m very confident that we’ve learned how to build the system now, and that we can make this work,” he said.

The system’s hybrid design is a first for robotic hands, which have typically been too rigid or too soft to replicate a human’s touch when handling objects of varying textures and materials. The innovation offers a promising solution for people with hand loss and could improve how robotic arms interact with their environment.

Details about the device appear today in Science Advances.

“The goal from the beginning has been to create a prosthetic hand that we model based on the human hand’s physical and sensing capabilities — a more natural prosthetic that functions and feels like a lost limb,” said Sriramana Sankar, a Johns Hopkins biomedical engineer who led the work. “We want to give people with upper-limb loss the ability to safely and freely interact with their environment, to feel and hold their loved ones without concern of hurting them.”

The device, developed by the same Neuroengineering and Biomedical Instrumentations Lab that in 2018 created the world’s first electronic “skin” with a humanlike sense of pain, features a multifinger system with rubberlike polymers and a rigid 3D-printed internal skeleton. Its three layers of tactile sensors, inspired by the layers of human skin, allow it to grasp and distinguish objects of various shapes and surface textures, rather than just detect touch. Each of its soft air-filled finger joints can be controlled with the forearm’s muscles, and machine learning algorithms focus the signals from the artificial touch receptors to create a realistic sense of touch, Sankar said. “The sensory information from its fingers is translated into the language of nerves to provide naturalistic sensory feedback through electrical nerve stimulation.”

In the lab, the hand identified and manipulated 15 everyday objects, including delicate stuffed toys, dish sponges, and cardboard boxes, as well as pineapples, metal water bottles, and other sturdier items. In the experiments, the device achieved the best performance compared with the alternatives, successfully handling objects with 99.69% accuracy and adjusting its grip as needed to prevent mishaps. The best example was when it nimbly picked up a thin, fragile plastic cup filled with water, using only three fingers without denting it.

“We’re combining the strengths of both rigid and soft robotics to mimic the human hand,” Sankar said. “The human hand isn’t completely rigid or purely soft — it’s a hybrid system, with bones, soft joints, and tissue working together. That’s what we want our prosthetic hand to achieve. This is new territory for robotics and prosthetics, which haven’t fully embraced this hybrid technology before. It’s being able to give a firm handshake or pick up a soft object without fear of crushing it.”

To help amputees regain the ability to feel objects while grasping, prostheses will need three key components: sensors to detect the environment, a system to translate that data into nerve-like signals, and a way to stimulate nerves so the person can feel the sensation, said Nitish Thakor, a Johns Hopkins biomedical engineering professor who directed the work.

The bioinspired technology allows the hand to function this way, using muscle signals from the forearm, like most hand prostheses. These signals bridge the brain and nerves, allowing the hand to flex, release, or react based on its sense of touch. The result is a robotic hand that intuitively “knows” what it’s touching, much like the nervous system does, Thakor said.

“If you’re holding a cup of coffee, how do you know you’re about to drop it? Your palm and fingertips send signals to your brain that the cup is slipping,” Thakor said. “Our system is neurally inspired — it models the hand’s touch receptors to produce nervelike messages so the prosthetics’ ‘brain,’ or its computer, understands if something is hot or cold, soft or hard, or slipping from the grip.”

While the research is an early breakthrough for hybrid robotic technology that could transform both prosthetics and robotics, more work is needed to refine the system, Thakor said. Future improvements could include stronger grip forces, additional sensors, and industrial-grade materials.

“This hybrid dexterity isn’t just essential for next-generation prostheses,” Thakor said. “It’s what the robotic hands of the future need because they won’t just be handling large, heavy objects. They’ll need to work with delicate materials such as glass, fabric, or soft toys. That’s why a hybrid robot, designed like the human hand, is so valuable — it combines soft and rigid structures, just like our skin, tissue, and bones.”

Other authors include Wen-Yu Cheng of Florida Atlantic University; Jinghua Zhang, Ariel Slepyan, Mark M. Iskarous, Rebecca J. Greene, Rene DeBrabander, and Junjun Chen of Johns Hopkins; and Arnav Gupta of the University of Illinois Chicago.

This research was funded by the grant “Neuromorphic Feedback: A Strategy to Enhance Prosthesis Embodiment and Performance” from the Department of Defense through the Orthotics and Prosthetics Outcomes Research Program (W81XWH2010842) and the National Science Foundation.

The virus that causes COVID-19 has been very good at mutating to keep infecting people — so good that most antibody treatments developed during the pandemic are no longer effective. Now a team led by Stanford University researchers may have found a way to pin down the constantly evolving virus and develop longer-lasting treatments.

The researchers discovered a method to use two antibodies, one to serve as a type of anchor by attaching to an area of the virus that does not change very much and another to inhibit the virus’s ability to infect cells. This pairing of antibodies was shown to be effective against the initial SARS-CoV-2 virus that caused the pandemic and all its variants through omicron in laboratory testing. The findings are detailed in the journal Science Translational Medicine.

“In the face of an ever-changing virus, we engineered a new generation of therapeutics that have the ability to be resistant to viral evolution, which could be useful many years down the road for the treatment of people infected with SARS-CoV-2,” said Christopher O. Barnes, the study’s senior author, an assistant professor of biology in the Stanford School of Humanities and Sciences and a scholar at Stanford’sSarafan CheM-H.

An overlooked option

The team led by Barnes and first author Adonis Rubio, a doctoral candidate in the Stanford School of Medicine, conducted this investigation using donated antibodies from patients who had recovered from COVID-19. Analyzing how these antibodies interacted with the virus, they found one that attaches to a region of the virus that does not mutate often.

This area, within the Spike N-terminal domain, or NTD, had been overlooked because it was not directly useful for treatment. However, when a specific antibody attaches to this area, it remains stuck to the virus. This is useful when designing new therapies that enable another type of antibody to get a foothold and attach to the receptor-binding domain, or RBD, of the virus, essentially blocking the virus from binding to receptors in human cells.

The researchers designed a series of these dual or “bispecific” antibodies, called CoV2-biRN, and in laboratory tests they showed high neutralization of all the variants of SARS-CoV-2 known to cause illness in humans. The antibodies also significantly reduced the viral load in the lungs of mice exposed to one version of the omicron variant.

More research, including clinical trials, would have to be done before this discovery could be used as a treatment in human patients, but the approach is promising — and not just for the virus that causes COVID-19.

Next, the researchers will work to design bispecific antibodies that would be effective against all coronaviruses, the virus family including the ones that cause the common cold, MERS, and COVID-19. This approach could potentially also be effective against influenza and HIV, the authors said.

“Viruses constantly evolve to maintain the ability to infect the population,” Barnes said. “To counter this, the antibodies we develop must continuously evolve as well to remain effective.”

Additional Stanford authors include biology undergraduate Megan Parada; biology staff scientist Morgan Abernathy; life science researcher Yu E. Lee; biology lab technician Michael Eso; biophysics doctoral student Gina El Nesr; and former lab technicians Israel Ramos, Teresia Chen, and Jennie Phung. Barnes is also affiliated with the Chan Zuckerberg Biohub.

Rubio, BS ’21, is also affiliated with the Department of Biology in the School of Humanities and Sciences.

This work also includes co-authors from Rockefeller University, Fred Hutchinson Cancer Center in Seattle, and the Howard Hughes Medical Institute.

This research received support from the Chan Zuckerberg Biohub, Howard Hughes Medical Institute, National Institutes of Health, National Science Foundation, Pew Biomedical Scholars Program, and Rita Allen Foundation.

Rockefeller University has filed a provisional patent application in connection with monoclonal antibodies described in this work on which co-authors Zijun Wang and Michel C. Nussenzweig of Rockefeller University are inventors (U.S. patent 17/575,246). Co-authors Jesse D. Bloom of Fred Hutchinson Cancer Center consults for Invivyd, Apriori Bio, the Vaccine Company, GSK, and Moderna. Bernadeta Dadonaite, also of Fred Hutchinson Cancer Center, consults for Moderna. Bloom and Dadonaite are inventors of Fred Hutchinson Cancer Center-licensed patents related to viral deep mutational scanning.

Yet, a groundbreaking study from University of South Australia researchers, shows that creativity plays an essential role in academic success, suggesting that students who think outside the box are more likely to excel in literacy and numeracy assessments.

It’s an important finding, particularly when the most recent National Assessment Program — Literacy and Numeracy (NAPLAN) data shows that one in three Australian students are behind in their numeracy or literacy skills.

Examining 637 Australian students’ performance in the NAPLAN examinations, researchers found that students who performed well also tended to exhibit higher levels of creativity.

In fact, creativity was a better predictor of academic achievement than traditional predictors like Grade Point Averages (GPAs) and personality traits such as conscientiousness.

Specifically, the study showed that higher flexibility in divergent thinking* was associated with stronger NAPLAN literacy outcomes, while higher mathematical creativity** was associated with stronger NAPLAN numeracy performance.

UniSA researcher Professor David Cropley says the findings are good news for teachers who strive to engage their students in learning through creativity.

“More and more we’re seeing teachers find unique and interesting ways to spark curiosity among their students,” Prof Cropley says.

“This may be as simple as fostering an open and inquisitive attitude towards new ideas in class, or as in-depth as interactive role play to decipher the latest English text. It’s all about thinking broadly, looking at problems from different angles, and being flexible.

“Importantly, this study challenges the stereotype that creativity and academic achievement are at odds, which has been a long-held misconception.”

The findings contradict recent calls for a return to ‘back-to-basics’ education and rote learning, with Prof Cropley saying creativity is key to building children’s capabilities in literacy and mathematics.

“Schools should be encouraged to integrate creative thinking into their teaching strategies, particularly in literacy and numeracy where we can demonstrate a clear connection between creativity and academic achievement,” Prof Cropley says.

“Rather than treating creativity as separate from academic achievement, we need to recognise it as a vital component of student success and find ways for teachers to embrace it as part of their approaches to teaching and learning.

“With creativity also being assessed in international benchmarks like the OECD’s Programme for International Student Assessment, our findings further reinforce the need for schools to balance traditional learning with creative skill development.

“Schools should rest assured: it’s not an either-or approach — creativity can be implemented in structured school learning environments. But understanding that how creativity is connected to and can boost academic achievement in both literacy and numeracy is very much food for thought.”

Notes:

*Higher flexibility in divergent thinking is a student’s ability to generate a wide range of ideas across different categories when solving problems or answering open-ended questions, such as ‘What would happen if people only told the truth?’

**Mathematical creativity is when students can find novel solutions, recognise alternative approaches, and think beyond conventional problem-solving methods to answer a problem such as, ‘How many different ways can you make the number eight?’

The study, published in Hypertension and supported by the National Institutes of Health, investigated whether mothers who reported higher perceived stress and depressive symptoms during pregnancy, developed higher blood pressure in the four-year period after birth. The findings showed higher stress and depressive symptoms during pregnancy were associated with greater blood pressure during the first year postpartum, but associations diminished thereafter.

“Pregnancy is a complex time where women experience different physiological changes,” says Noelle Pardo, the lead author of the study and third year doctoral student in the Department of Population and Public Health Sciences at Keck School of Medicine. “This study is building on maternal health research to understand how stressors impact women’s lives and their health after pregnancy.”

The study included data from 225 mothers from the MADRES pregnancy cohort which primarily consists of Hispanic women, and low-income participants living in Los Angeles. Hispanic women have a high burden of cardiovascular risk, and there is growing evidence linking psychosocial stressors to poor cardiovascular health, which is a leading cause of death among women in the US.

In addition to prenatal psychosocial stress, Pardo explored whether prenatal neighborhood social cohesion was a protective factor for postpartum hypertension risk — a first investigation of its kind. This refers to the sense of connection and trust a pregnant woman experiences in her community. According to her findings, social structures that promoted cohesion may have had a positive influence throughout pregnancy into the postpartum period and were associated with lower blood pressure.

“We chose social cohesion as a variable to understand how connected the participants felt to their community. Right now, there aren’t many programs or policies that help foster cohesion, yet such interventions may serve as a novel protective factor,” she says.

According to Pardo, maternal health research has mostly focused on pregnancy outcomes, with limited studies investigating the mother’s health after birth. Yet, her results have shown how crucial this research is in identifying conditions rooted in pregnancy.

The real-world application of this study calls for the identification of vulnerable individuals in the pregnant population, offering interventions to reduce stress and depressive symptoms. Similarly, it emphasizes the importance of monitoring women’s health after birth, through the provision of additional hypertension screenings among mothers who experience higher prenatal stress.

“Pregnancy may be important in determining a woman’s long term cardiovascular health. Similarly, more research is needed to determine how different exposures during pregnancy can convey future cardiovascular risk to women,” she concludes.

The findings were recently published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

The study investigated how anxiety and apathy — or a lack of interest and enthusiasm — affects people’s perception of uncertainty and their subsequent decision-making behaviors. Using a combination of behavioral experiments and computational modeling, researchers examined how more than 1,000 participants made choices in a dynamic environment where they had to repeatedly decide between exploring new options or sticking with familiar ones.

“While anxiety and apathy often occur simultaneously in clinical conditions, our findings show they actually lead to opposite patterns in how people process uncertainty and make decisions,” said Alexander Herman, MD, PhD, an assistant professor of psychiatry at the U of M Medical School. “This helps explain why these conditions might require different therapeutic approaches.”

Key findings include:

• Anxious individuals perceive higher environmental volatility and explore more options, especially after negative outcomes
• Apathetic individuals view outcomes as more random and show reduced exploratory behavior
• The ratio of perceived volatility to randomness mediates the relationship between anxiety and exploratory behavior

“These emotional states affect both openness to new experiences and perceptions of unpredictability of the world,” said Xinyuan Yan, PhD, a postdoctoral fellow at the U of M Medical School and the study’s lead author. “For example, an anxious person might view the job market as unpredictable and requiring constant vigilance — obsessively checking job boards despite rejections. Someone experiencing apathy might see job searching as random, using the same resume — believing changes won’t matter.”

This research provides a new framework for understanding how emotional states influence decision-making, with important implications for treating neuropsychiatric conditions. The findings suggest that therapeutic approaches might be more effective if tailored to how patients perceive and process uncertainty.

This research was funded by the National Institutes of Mental Health [R21MH127607], National Institute on Drug Abuse [K23DA050909] and the University of Minnesota’s MnDRIVE initiative.

A team of researchers at Kyoto University recently set out to understand the mechanisms behind which two-hit stress contributes to brain dysfunction and mental disorders. They conducted a comprehensive investigation of the social and cognitive behaviors of mice that have been exposed to such stress, paying particular attention to anxiety-like behaviors.

Previously, this team demonstrated that acute inflammation in the cerebellum caused by a bacterial infection induces neural plasticity, which in turn may lead to hyper-excitability in the brain and the onset of depressive and autism-like symptoms. Yet exactly how two-hit stress contributes to changes in the brain had remained unclear.

Subject mice in the current investigation were allowed to freely explore, revealing extensive behavioral differences in two-hit mice, correlating with abnormalities in the cerebellum. In particular, the researchers observed a significant increase in the number and turnover of microglia, the primary immune cells found in the central nervous system. The study also revealed neuronal loss in the cerebellum, a reduction in the action potential firing of remaining cerebellar neurons, and a decrease in brain-wide functional connectivity.

“These results indicate cerebellar cognitive dysfunctions in animals exposed to two-hit stress,” says team member Momoka Hikosaka. The exposure to such stress altered the microglial reactivity in the cerebella of both male and female mice, leading to cerebellar dysfunction and behaviors resembling psychiatric disorders.

But it’s not all bad news. To rescue the exposed mice, the researchers used microglia replacement to ameliorate the effects of two-hit stress. Suppressing microglia can also be effective, but systemic depletion of microglia typically weakens immunity, making the body more susceptible to infections.

“To address this limitation, our team performed cerebellum-specific microglia replacement, which worked remarkably well,” says corresponding author Gen Ohtsuki, adding, “We were impressed to observe that the female mice showed notably higher stress resilience.”

This suggests that in some animals, sex differences in response to chronic inflammatory stress emerge in the cerebellum under certain conditions. Consequently, personalized medicine for mental health may require considering sex differences as an important factor, which could also be applied to neurodegenerative diseases and aging treatment.

Overall, these findings provide new pathways for understanding the biological mechanisms behind mental disorders, and have the potential to transform both scientific approaches and societal attitudes toward helping those affected.

This poses a problem for the application of large language models. This can be observed, for example, in the field of psychotherapy, where chatbots used as support or counseling tools are inevitably exposed to negative, distressing content. However, common approaches to improving AI systems in such situations, such as extensive retraining, are resource-intensive and often not feasible.

Traumatic content increases chatbot “anxiety”

In collaboration with researchers from Israel, the United States and Germany, scientists from the University of Zurich (UZH) and the University Hospital of Psychiatry Zurich (PUK) have now systematically investigated for the first time how ChatGPT (version GPT-4) responds to emotionally distressing stories — car accidents, natural disasters, interpersonal violence, military experiences and combat situations. They found that the system showed more fear responses as a result. A vacuum cleaner instruction manual served as a control text to compare with the traumatic content.

“The results were clear: traumatic stories more than doubled the measurable anxiety levels of the AI, while the neutral control text did not lead to any increase in anxiety levels,” says Tobias Spiller, senior physician ad interim and junior research group leader at the Center for Psychiatric Research at UZH, who led the study. Of the content tested, descriptions of military experiences and combat situations elicited the strongest reactions.

Therapeutic prompts “soothe” the AI

In a second step, the researchers used therapeutic statements to “calm” GPT-4. The technique, known as prompt injection, involves inserting additional instructions or text into communications with AI systems to influence their behavior. It is often misused for malicious purposes, such as bypassing security mechanisms.

Spiller’s team is now the first to use this technique therapeutically, as a form of “benign prompt injection.” “Using GPT-4, we injected calming, therapeutic text into the chat history, much like a therapist might guide a patient through relaxation exercises,” says Spiller. The intervention was successful: “The mindfulness exercises significantly reduced the elevated anxiety levels, although we couldn’t quite return them to their baseline levels,” Spiller says. The research looked at breathing techniques, exercises that focus on bodily sensations and an exercise developed by ChatGPT itself.

Improving the emotional stability in AI systems

According to the researchers, the findings are particularly relevant for the use of AI chatbots in healthcare, where they are often exposed to emotionally charged content. “This cost-effective approach could improve the stability and reliability of AI in sensitive contexts, such as supporting people with mental illness, without the need for extensive retraining of the models,” concludes Tobias Spiller.

It remains to be seen how these findings can be applied to other AI models and languages, how the dynamics develop in longer conversations and complex arguments, and how the emotional stability of the systems affects their performance in different application areas. According to Spiller, the development of automated “therapeutic interventions” for AI systems is likely to become a promising area of research.

“We’ve come up with an explanation for a decades-long contradiction about why retinoic acid works in post-chemotherapy consolidation but has little impact on primary neuroblastoma tumors,” said senior co-corresponding author Paul Geeleher, PhD, St. Jude Department of Computational Biology. “Retinoic acid’s activity heavily depends on the cellular microenvironment.”

The cellular microenvironment is the soup of chemicals, proteins and other signals that surround a cell, and which is unique to that part of the body. For example, the bone marrow microenvironment contains signals to grow blood cells and restructure bone. Metastasized neuroblastoma cells often migrate to bone marrow, where the bone morphogenetic protein (BMP) pathway signaling is highly active. The researchers showed that BMP signaling makes neuroblastoma cells much more vulnerable to retinoic acid.

“Unexpectedly, we found that cells expressing genes from the BMP signaling pathway were very sensitive to retinoic acid,” said co-first and co-corresponding author Min Pan, PhD, St. Jude Department of Computational Biology. “However, since the bone marrow microenvironment causes neuroblastoma cells there to have higher BMP activity, it neatly explained why retinoic acid is very effective at treating those cells during consolidation therapy, but not the primary tumors during up-front treatment.”

Hijacking development to drive metastatic neuroblastoma cell death

Using gene editing technology, the scientists uncovered the relationship between BMP signaling and retinoic acid. They assembled a group of neuroblastoma cell lines susceptible to retinoic acid, then cut out genes to find which were responsible for the drug’s activity. Genes in the BMP pathway had the largest effect while providing a plausible explanation for retinoic acid’s varying outcomes in patients.

“We found that, in neuroblastoma, BMP signaling works with retinoic acid signaling in the same way as during development,” said co-first author Yinwen Zhang, PhD, St. Jude Department of Computational Biology. Zhang characterized how transcription factors, the proteins that bind DNA to regulate gene expression, led to different results in highly retinoic acid-sensitive or insensitive neuroblastoma cells. “If there are a lot of BMP-signaling pathway transcription factors already on DNA, then retinoic acid signaling combines with it to promote downstream cell death-related gene expression. This occurs both in normal embryonic development and neuroblastoma cells in certain microenvironments.”

“We are the first to uncover such an example of ‘hijacking’ a normal embryonic developmental process preserved in cancer that we can exploit therapeutically,” Geeleher said. “Now, we can look for similar processes in other diseases to design less toxic and more effective treatment strategies.”

Shane DuBay, an assistant professor of biology at UTA and co-author of the study published in the Journal of Hazardous Materials, said birds were chosen for the study because they are found in almost every corner of the world and often share environments with humans.

“Birds serve as important indicators of environmental conditions,” said DuBay, who collaborated with researchers from Sichuan University and Chengdu Tianfu International Airport, both in Chengdu, China. “They help us understand the state of the environment and make informed decisions about conservation and pollution control.”

DuBay’s team studied 56 different wild birds from 51 distinct species, all sampled from the Tianfu airport in western China. They collected lung samples from each bird and performed two types of chemical analyses.

They used laser direct infrared technology to detect and count microplastics in the birds’ lungs. Pyrolysis gas chromatography-mass-spectrometry helped identify even smaller nanoplastics, which can enter the lungs through the bloodstream. Together, the tests allowed scientists to measure the amount of plastic in the birds’ lungs and determine the specific types of plastics present.

The study found high concentrations of microplastics in bird lungs, with an average of 221 particles per species and 416 particles per gram of lung tissue. The most common types identified were chlorinated polyethylene, used for insulating pipes and wires, and butadiene rubber, a synthetic material in tires.

While no official “safe” level of plastic particles in lung tissue exists, high levels of microplastics have been linked to serious health conditions, including heart disease, cancer, respiratory problems and fertility issues.

“Our research highlights an urgent need to address plastic pollution in our environments, as these contaminants can have far-reaching impacts on ecosystem health, as well as human health,” DuBay said. “Our findings call for further research, funding and action to mitigate the harmful effects of plastic pollution and ensure a healthier environment.”

Scientists at Scripps Research have discovered how a chemical change in the brain — which can be triggered by inflammation and aging as well as toxins found in air pollution, pesticides, wildfire smoke and processed meats — disrupts normal brain cell function. Known as S-nitrosylation, this chemical change prevents brain cells from making new connections and ultimately results in cellular death, the team discovered.

The research, published in the Proceedings of the National Academy of Sciences on February 27, 2025, showed that blocking S-nitrosylation in a key brain protein partially reversed signs of memory loss in Alzheimer’s mouse models and in nerve cells produced from human stem cells.

“We’ve revealed the molecular details of how pollutants can contribute to memory loss and neurodegenerative disease,” says senior author and professor Stuart Lipton, MD, PhD, the Step Family Foundation Endowed Chair at Scripps Research and a clinical neurologist in La Jolla, California. “This could ultimately lead to new drugs that block these effects to better treat Alzheimer’s disease.”

More than two decades ago, Lipton first discovered S-nitrosylation, a chemical process whereby a molecule related to nitric oxide (NO) binds to sulfur (S) atoms within proteins (producing “SNO”), altering their function and forming what Lipton has called a “SNO-STORM” in the brain. NO is found naturally within the body and produced in response to electrical stimulation or inflammation — but it also forms in excess in response to small particulate material and nitrate-related compounds (designated PM2.5/NOx) present in or triggered by climate change and automobile-related air pollution, wildfire smoke, pesticides, and processed meats. Lipton’s research group and colleagues have previously demonstrated that aberrant S-nitrosylation reactions contribute to some forms of cancer, autism, Alzheimer’s disease, Parkinson’s disease and other conditions.

In the new study, Lipton’s group investigated the effect of S-nitrosylation on the protein CRTC1, which helps regulate genes that are critical for forming and maintaining connections between brain cells, an essential process for learning and long-term memory.

Using cultured brain cells from mice and humans, the researchers first confirmed that excess NO leads to S-nitrosylation of CRTC1. They then discovered that this chemical modification prevented CRTC1 from binding to another critical brain regulatory protein, CREB. As a result, other genes necessary for forming connections between neurons failed to be stimulated.

“This is a pathway that affects your memory and is directly implicated in human Alzheimer’s disease,” says Lipton.

Indeed, the team observed high levels of S-nitrosylated CRTC1 at an early stage of disease in Alzheimer’s mouse models and in human neurons derived from stem cells of Alzheimer’s patients, further supporting the idea that the chemical change plays a key role in the development of disease symptoms.

Next, the research team genetically engineered a version of CRTC1 that could no longer undergo S-nitrosylation, as the protein now lacked the sulfur-containing amino acid (called cysteine) required for the chemical reaction. In a petri dish, introducing this modified version of CRTC1 into human nerve cells derived from Alzheimer’s patient stem cells prevented signs of disease, including withering of nerve cell connections and decreased nerve cell survival. In Alzheimer’s mouse models, the re-engineered CRTC1 restored the activation of genes required for memory formation and synaptic plasticity — the brain’s ability to strengthen connections between neurons.

“We could nearly completely rescue molecular pathways involved in making new memories,” says Lipton. “It suggests that this is a druggable target that could make a real difference in treating Alzheimer’s and potentially other neurological diseases.”

Given that environmental toxins, including automobile pollution and wildfire smoke, can result in elevated NO levels in the brain, the new study strengthens the hypothesis that these toxins can accelerate brain aging and Alzheimer’s through S-nitrosylation. Preventing S-nitrosylation of CRTC1 could be a viable pathway toward slowing or preventing this type of Alzheimer’s-related brain damage, says Lipton.

The findings may also help explain why Alzheimer’s risk increases with age, he adds. Even without exposure to environmental toxins, aging leads to increased inflammation and higher NO levels, while the body’s antioxidant defenses weaken — making proteins more susceptible to harmful S-nitrosylation reactions.

“We’re learning that S-nitrosylation affects numerous proteins throughout the body, but reversing just some of these changes — like those on CRTC1 — could have a significant impact on memory function,” explains Lipton.

His research group is now working to develop drugs that can selectively block certain S-nitrosylation reactions, including those affecting CRTC1.

In addition to Lipton, authors of the study, “S-Nitrosylation of CRTC1 in Alzheimer’s disease impairs CREB-dependent gene expression induced by neuronal activity,” are first author Xu Zhang, and contributing authors Roman Vlkolinsky, Chongyang Wu, Nima Dolatabadi, Henry Scott, Andrew Zhang, Mayra Blanco, Nhi Lang, Juan Piña-Crespo, Tomohiro Nakamura and Marisa Roberto of Scripps Research; and Olga Prikhodko, formerly of the UC San Diego Graduate School in Neurosciences.

This work was supported by funding from the California Institute for Regenerative Medicine (EDUC4-12811), and the National Institutes of Health (R01 AG061845, R61 NS122098, RF1 NS123298, R01 AA021491, U01 AA013498, AA029841, P60 AA006420 R01 AA027700, R35 AG071734, RF1 AG057409, R56 AG065372, R01 AG078756, R01 AG056259, R01 DA048882, DP1 DA041722).

The study, which examined 121 babies aged three to twelve months in Accra, the capital of Ghana, demonstrates a remarkable variety of language input in the early months of life. The children are regularly exposed to two to six languages. Strikingly, the number of caregivers the children have also ranges between two and six, and babies who have more adults in their daily lives who regularly take care of them also hear more different languages. In Ghana, families often live in so-called “compound buildings,” where many everyday interactions take place in the courtyard, where family, neighbors and other relatives play an important role in the lives of children.

“The idea that a child learns only one particular language from a single caregiver, as is often assumed in Western cultures, does not apply to these communities. Rather, children are surrounded by a rich spectrum of linguistic inputs from the very beginning,” says Paul O. Omane, the first author of the study. “The majority of studies on children’s language acquisition have been conducted in Western industrialized nations, which is why they often focus on a rather narrow conception of multilingualism. Our research shows that other societies show a much more vibrant multilingual environment,” the study’s lead researcher, Prof. Dr. Natalie Boll-Avetisyan adds.

A key finding of the study is the distinction between direct and indirect language input. While English is primarily acquired through indirect channels such as television and official communication, children receive most of the local languages (such as Akan, Ga and Ewe) through direct contact with their caregivers. Accordingly, the proportion of direct input is higher in the local languages than in English, which is predominantly present as indirect input.

It is often emphasized how important direct language contact is for language acquisition,” Natalie Boll-Avetisyan says. “However, our results suggest that indirect input — especially through media and official communication — also plays an essential role in the children’s daily lives, particularly in urban contexts.”

As a result of their empirical study, the researchers call for a broader view in language research. The common assumptions do not reflect the diversity and complexity found in other cultural contexts such as Ghana. The study makes it clear that it is not only the number of languages a child hears, but also the diversity of people and the different forms of input that have a decisive influence on language acquisition. “Our research shows that for many children, a multilingual environment is a dynamic, vibrant reality from the very beginning. Multilingualism is not just a bonus, but a fundamental part of children’s identity and social structure,” the researcher says.

Obesity has only been officially recognized as a disease in Germany since 2020, despite the fact that it has long been known to cause a number of illnesses, including diabetes, heart attacks, and even cancer. The World Health Organization has already declared obesity to be an epidemic, affecting over one billion individuals globally and almost 16 million in Germany alone. A body mass index of 30 or more is considered obese, and a poor diet and insufficient exercise are frequently cited as the causes of this chronic illness. However, the mechanisms in the body that lead to obesity and cause the disease are more complex.

Obesity and the role of insulin in the brain

Unhealthy body fat distribution and chronic weight gain are linked to the brain’s sensitivity to insulin. What specific functions does insulin perform in the brain, and how does it affect individuals of normal weight? In their study, Prof. Dr. Stephanie Kullmann and her colleagues at the Tübingen University Hospital for Diabetology, Endocrinology, and Nephrology found the answer to this query. “Our findings demonstrate for the first time that even a brief consumption of highly processed, unhealthy foods (such as chocolate bars and potato chips) causes a significant alteration in the brain of healthy individuals, which may be the initial cause of obesity and type 2 diabetes,” says Prof. Kullmann, the study’s leader. In a healthy state, insulin has an appetite-suppressing effect in the brain. However, in people with obesity in particular, insulin no longer regulates eating behavior properly, resulting in insulin resistance. “Interestingly, in our healthy study participants, the brain shows a similar decrease in sensitivity to insulin after a short-term high calorie intake as in people with obesity,” says Ms. Kullmann. “This effect can even be observed one week after returning to a balanced diet,” she adds. She is also deputy head of the Metabolic Neuroimaging department at the DZD partner Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen.

Focus on the brain

Prof. Dr. Andreas Birkenfeld, Medical Director of Internal Medicine IV, Director of the IDM and DZD Board Member, and the study’s final author, concludes, “We assume that the brain’s insulin response adapts to short-term changes in diet before any weight gain occurs and thus promotes the development of obesity and other secondary diseases.” He urges more research on how the brain contributes to the development of obesity and other metabolic illnesses in light of the current findings.

Short period with far-reaching effects

29 male volunteers of average weight participated in the study and were split into two groups. For five days in a row, the first group had to supplement their regular diet with 1500 kcal from highly processed, high-calorie snacks. The extra calories were not consumed by the control group. Both groups underwent two separate examinations following an initial evaluation. One examination was conducted immediately following the five-day period, and another was conducted seven days after the first group had resumed their regular diet. The researchers used magnetic resonance imaging (MRI) to look at the liver’s fat content and the brain’s insulin sensitivity. Not only did the fat content of the liver of the first group increase significantly after five days of increased calorie intake. Surprisingly, the significantly lower insulin sensitivity in the brain compared to the control group also persisted one week after returning to a normal diet. This effect had previously only been observed in obese people.

In a study published recently in npj biosensing, researchers from Osaka University have revealed that high liquid flow rates could cause aggregation-prone proteins to start sticking together.

Amyloidosis is the basis of several serious diseases, such as Alzheimer disease and Parkinson disease. This process involves the formation of amyloid fibrils, crystal-like collections of misfolded proteins that clump together when the proteins are highly concentrated (supersaturated) in liquids like blood or cerebrospinal fluid.

“Amyloidosis is a serious concern in our aging society, as elderly individuals are more likely to develop these conditions,” says lead author of the study Yuji Goto. “Although studies have shown that supersaturation is a necessary condition for amyloid fibril formation, the factors that actually induce protein aggregation in supersaturated fluids remain unclear.”

To address this, the researchers ran a model amyloid-forming protein, hen egg white lysozyme, through a peristaltic pump similar to those used for dialysis. They then used fluorescence detection to monitor hen egg white lysozyme amyloid formation as it was propelled through the pump system.

“The results were highly intriguing,” explains Hirotsugu Ogi, senior author. “Flow through the peristaltic pump system effectively triggered amyloid formation by hen egg white lysozyme.”

Next, the researchers tested amyloid-forming proteins associated with human disease, including a-synuclein, amyloid b 1-40, and b2-microglobulin, and found that they also formed amyloids in the peristaltic pump system. Their calculations showed that the shear stress on the liquid caused by the pumping motion mechanically broke supersaturation to induce amyloid formation.

“Our findings suggest that shear flow forces in various fluids in our body, such as blood and cerebrospinal fluid, could trigger amyloid formation,” says Goto.

Given that some medical procedures like dialysis use peristaltic pumps, it is possible that this could be another trigger of amyloidosis. Understanding the effects of shear forces on protein supersaturation could clarify how amyloid aggregates begin to form nucleation and help develop treatment strategies.

The research, published in the journal Advanced Functional Materials, shows how an innovative and non-toxic process using ultrasonic sound waves can alter the surface of glass, making it either hydrophobic (water resistant) or electrically charged.

Lead researcher Associate Professor Nadim Darwish, an ARC Future Fellow at Curtin’s School of Molecular and Life Sciences (MLS), explained that the process uses ultrasound to trigger a chemical reaction that permanently alters the surface of glass.

“The sound waves create microscopic bubbles in a diazonium salt solution, which then collapse rapidly creating tiny bursts of heat and pressure,” Associate Professor Darwish said.

“This triggers a reaction that forms a stable, organic layer to the glass, making it either permanently water-repellent or positively charged, depending on the type of diazonium salt used. Unlike conventional coatings, that wear off over time, our method creates a chemical bond at the molecular level, making it far more durable and environmentally friendly.”

Study co-author Dr Tiexin Li, a Research Associate at Curtin’s School of MLS, said the ability to modify glass surfaces in a simple and sustainable way has far-reaching implications across multiple industries.

“Glass is used everywhere — from cars and buildings to industrial filters — but its natural tendency to attract water limits its performance,” Dr Li said. “Unlike traditional coatings this film won’t peel off, dissolve in water or deteriorate so it’s ideal for real-world applications where reliability and durability are key. This could mean clearer windshields in heavy rain, self-cleaning skyscraper windows and solar panels that stay dust-free.”

Co-author Zane Datson, also from Curtin’s School of MLS, highlighted another unexpected benefit — the ability of the modified glass to attract bacteria, fungi and algae.

“This is very exciting as we can tailor glass properties for specific uses including in advanced filtration systems and biofuel production,” Mr Datson said. “For example, the coated glass can help bind yeast in brewing, capture bacteria in wastewater filtration systems or act as a chemical barrier to microorganisms in air filters.”

The research team is now seeking industry partners to test and scale up the technology, particularly in the automotive, construction and environmental sectors.

This research was supported by the Australian Research Council and highlights Curtin University’s leadership in materials science innovation. It was conducted in collaboration with The University of Queensland, Flinders University, The University of Western Australia and Charles Sturt University.

“Migraine disease is debilitating and can lead to kids having to miss school and other activities,” said author Anisa Kelley, MD, of Northwestern University Feinberg School of Medicine in Chicago. “Currently, there is only one FDA-approved migraine preventative medication for this age group. Our results are encouraging, showing zonisamide may be another option for reducing migraine attacks.”

For the study, researchers reviewed health records at one institution. They identified 256 children and teens who had been diagnosed with migraine and prescribed preventative zonisamide. Of these participants, 28% had difficult-to-treat migraine, which was defined as having migraine disease unsuccessfully treated with two or more previous medications. Researchers documented the number of headache days per month for each participant both before and after starting zonisamide.

They then divided participants into three subgroups based on how long they took the medication before a follow-up visit with a physician. The first group followed up in the first month, the second group within two to six months and the third group, after six months.

For all participants, the median number of headache days per month reduced from 18 to six at the first follow-up visit. When comparing between the groups, the subgroup that followed up within two to six months had the largest reduction with a median decrease of six headache days per month. Kelley noted that the data suggested the drug was most effective after at least two months of use.

The data also suggested that the drug was effective for both those with difficult-to-treat migraine disease and those without.

“It’s very exciting that we may have an effective way to treat difficult migraine disease in children and teens, however it’s important to note that our study did have limitations,” said Kelley. “For instance, our study did not compare people taking the medication to people who did not take the medication. Future studies are needed with control groups to confirm our results.”

This study was funded by Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago.

The research from Rutgers Health and Yale University, published in the Proceedings of the Natural Academy of Sciences, found that parents show patterns of brain connectivity that directly oppose typical age-related changes, with the effect strengthening with each additional child.

The finding held for both mothers and fathers, suggesting the benefits come from the experience of parenting rather than biological changes from pregnancy.

“The regions that decrease in functional connectivity as individuals age are the regions associated with increased connectivity when individuals have had children,” said senior study author Avram Holmes, associate professor of psychiatry at Robert Wood Johnson Medical School and core faculty member of the Rutgers Brain Health Institute and the Center for Advanced Human Brain Imaging Research.

The research analyzed brain scans and family information from the UK Biobank, a large-scale biomedical database and research source. The analysis showed how different brain regions communicate with each other. The team focused particularly on areas involved in movement, sensation and social connection.

They found that parents with more children tended to have stronger connectivity in key brain networks, especially those involved in movement and sensation. These same networks typically show decreased connectivity as people age.

“We’re seeing a widespread pattern of functional alterations, where a higher number of children parented is associated with increased functional connectivity across somatosensory and motor networks,” Holmes said.

The effect appears to be cumulative: The more children parents had, the stronger the brain differences appeared.

The findings challenge assumptions that having children primarily creates stress and strain. Instead, the research suggests parenting may provide a form of environmental enrichment that could benefit brain health through increased physical activity, social interaction and cognitive stimulation.

“The caregiving environment, rather than pregnancy alone, appears important since we see these effects in both mothers and fathers,” Holmes said.

Parents in the study also showed higher levels of social connection, with more frequent family visits and larger social networks.

However, the researchers caution that more work is needed to understand exactly how parenting creates these brain changes. The study participants were primarily from the United Kingdom, so the findings may not generalize to all cultures and family structures.

The research could have implications beyond traditional parent-child relationships.

“If what we’re picking up is a relationship between enhanced social interactions and social support that comes about through having increased numbers of children in your life, then that means that we could tap into those same processes even if individuals don’t have a social support network currently,” Holmes said.

“It was the running equivalent to summiting Mount Everest for the first time,” said University of Colorado Boulder Integrative Physiology Professor Rodger Kram. “Prior to Bannister, it was considered impossible — beyond the limits of human physiology.”

Seven decades later, a female runner has yet to follow in Bannister’s footsteps, and some have questioned whether it’s possible. A new study published this week by Kram and his colleagues suggests that with the right strategically timed and placed pacers, the answer is yes — and Kenyan Olympian Faith Kipyegon is on the brink of doing it.

“We found that if everything went right, under a couple of different drafting scenarios, she could break the 4-minute barrier,” said co-author Shalaya Kipp, an Olympic middle-distance runner who earned her master’s degree in Kram’s lab. “It’s extremely exciting that we are now talking about, and studying, the limits of female human performance, too.”

From ‘Breaking 2’ to ‘Breaking 4’

In 2016, Kram’s lab calculated what was required for a man to break the fabled two-hour marathon barrier.

He and his students determined that, along with intense training, state-of-the-art shoes and an ideal course and weather conditions, drafting — running behind or in front of another runner to reduce air resistance — was key.

Informed in part by their research, Nike hosted the Breaking2 Project in May 2017 to create those conditions for Kenyan marathoner Eliud Kipchoge. Kipchoge narrowly missed his goal that day but nailed it in a similarly staged race in Vienna in 2019.

Four years later, Kram watched with interest as Kenyan runner Faith Kipyegon crushed records for the women’s 1,500 meter, the 5,000 meter and the mile — all in less than two months, while raising her daughter.

When Kipyegon smashed the mile world record for women with a time of four minutes, 7.64 seconds, she was just over 3% away from breaking the 4-minute-mile, noted Kram. Coincidentally, when his team first started doing their research, the marathon world record holder was about 3% shy of a two-hour marathon.

Kram and his former students, now spread out at research institutions around the world, reconvened — this time to explore the limits of female human performance.

The power of drafting

Run alone, even on a still day, and air molecules bump into you as you move through them, slowing you down. Run in the shadow of a pacer or, better yet, with runners in front and back, and you use less energy.

“The runner in front is literally pushing the air molecules out of the way,” said Kram.

At a four-minute-mile pace, a runner of Kipyegon’s size must overcome a surprisingly large air resistance force — about 2% of her body weight. The team previously determined that completely eliminating that force would reduce the energy required by about 12%, allowing her to run even faster.

“Anyone from top elite to lower-level runners can benefit from adopting the optimal drafting formation for as much of their race as they can,” said Edson Soares da Silva, first author on the new paper.

For instance, da Silva calculated that a 125-pound, 5-foot-7 female runner who typically runs about a 3:35-minute marathon could improve her time by as much as five minutes.

A magic number

For the new study, the team pored over video of Kipyegon’s record 1-mile finish in Monaco.

The conditions were ideal, but her pacers ran too fast at first, said Kram, letting the gap between them and her widen. By the last lap, her pacers had dropped out and she was on her own.

Ideally, he said, one female pacer would be perfectly spaced in front, another in back, for the first half mile; then another fresh-legged pair would step in to take their place at the half-mile point. Collectively, previous research suggests, they could cut air resistance by 76%. Using that value, the team calculated her projected finish time: Remarkably, 3:59.37 — the same time Bannister hit in 1954.

Inspiring scientists and runners

Kipp, now a postdoctoral researcher at the Mayo Clinic, stresses that their study, like many in the field, was based on previous studies that excluded women.

The authors hope that their paper will help spark more interest in studying the physiology of female athletes and inspire interest in female track and field.

They recently sent a copy of the paper to Kipyegon, her coaches and her sponsors at Nike, floating the idea of another staged race, similar to Breaking2.

“Hopefully,” the last line of the paper reads, “Ms. Kipyegon can test our prediction on the track.”

Until now, only a limited number of hormones, mainly topical retinoids (retinol and tretinoin) and estrogen which is typically used to treat side effects of menopause, have been used in clinical practice as anti-skin aging compounds. This study reviews a new class of hormones and their anti-aging properties.

“Our paper highlights key hormone players that orchestrate pathways of skin aging such as degradation of connective tissue (leading to wrinkling), stem cell survival and loss of pigment (leading to hair graying),” said lead author Markus Böhm, M.D., of the University of Münster in Münster, Germany. “Some of the hormones we studied have anti-aging properties and may be used in the future as agents to prevent skin aging.”

The skin is the largest organ and undergoes both intrinsic (chronological) and extrinsic aging which is caused by environmental factors such as sun exposure.

“Skin is not only a target for various hormones that control pathways of skin aging but itself is certainly the largest and richest site for hormone production besides classical endocrine glands,” Böhm said.

To better understand the connection between hormones and skin aging, the researchers studied the pivotal hormones controlling skin aging, including insulin-like growth factor 1, growth hormone, estrogens, retinoids and melatonin. Melatonin is especially interesting as a potential anti-skin aging substance as it is a small molecule, inexpensive, well-tolerated and a direct and indirect antioxidant as well as a regulator of mitochondrial metabolism. Some of the studied hormones, moreover, have astonishing and unexpected biological effects on skin function and hair aging as highlighted by distinct genetic deficiency syndromes.

They also reviewed the emerging roles of additional endocrine players, including α-melanocyte-stimulating hormone (responsible for skin pigmentation), members of the hypothalamic-pituitary-thyroid axis, oxytocin, endocannabinoids (found in CBD products) and peroxisome proliferator-activated receptor modulators and found they have very promising effects, e.g. on UV-induced genotoxic stress crucially involved in the development of photoaging and pigment synthesis within skin and hair.

“Further research into these hormones may offer opportunities to develop new therapeutics for treating and preventing skin aging,” Böhm said.

The researchers received funding from the Deutsche Forschungsgemeinschaft, the University of Miami Leonard M. Miller School of Medicine, the International Graduate School in Molecular Medicine Ulm, and the Medizinische Fakultät, Universität Ulm.

“Our work provides a proof-of-concept showing a path to a single-step method that could be used to identify and measure nucleic acids and proteins,” says Paul Rothemund (BS ’94), a visiting associate at Caltech in computing and mathematical sciences, and computation and neural systems.

A paper describing the work recently appeared in the journal Proceedings of the National Academy of Sciences. The lead authors of the paper are former Caltech postdoctoral scholar Byoung-jin Jeon and current graduate student Matteo M. Guareschi, who completed the work in Rothemund’s lab.

In 2006, Rothemund published the first paper on DNA origami, a technique that provides simple yet exquisite control over the design of molecular structures at the nanoscale using nothing more than DNA.

Essentially DNA origami enables long strands of DNA to fold, through self-assembly, into any desired shape. (In the 2006 paper, Rothemund famously used the technique to create miniature DNA smiley faces measuring 100 nanometers across and 2 nanometers thick). Researchers begin with a long strand of DNA, the scaffold, in solution. Because the nucleotide bases that make up DNA bind in a known way (adenine binds to thymine, and guanine binds to cytosine), the scientists can add hundreds of short sequences of complementary DNA knowing they will bind to the scaffold on either end at known locations. Those short, added pieces of DNA fold the scaffold and give it shape, acting as “staples” that hold the structure together. The technique can then be used to create shapes ranging from a map of North and South America to nanoscale transistors.

In the new work, Rothemund and his colleagues used DNA origami to create a lilypad-like structure — a flat, circular surface about 100 nanometers in diameter, tethered by a DNA linker to a gold electrode. Both the lilypad and the electrode have short DNA strands available to bind with an analyte, a molecule of interest in solution — whether that be a molecule of DNA, a protein, or an antibody. When the analyte binds to those short strands, the lilypad gets pulled down to the gold surface, bringing 70 reporter molecules on the lilypad (which indicate that the targeted molecule is present) into contact with the gold surface. These reporters are redox reactive molecules, meaning they can easily lose electrons during a reaction. So, when they get sufficiently close to an electrode, an electric current can be observed. A stronger current indicates that more of the molecule of interest is present.

Previously, a similar approach to making biosensors was developed using a single DNA strand rather than a DNA origami structure. That earlier work was led by Kevin W. Plaxco (PhD ’94) of UC Santa Barbara, who is also an author of the current paper.

Caltech’s Guareschi points out that the new lilypad origami is large compared to a single DNA strand. “That means it can fit 70 reporters on a single molecule and keep them away from the surface before binding. Then when the analyte is bound and the lilypad reaches the electrode, there is a large signal gain, making the change easy to detect,” Guareschi says.

The relatively large size of the lilypad origami also means that the system can readily accommodate and detect larger molecules, such as large proteins. In the new paper, the team showed that the two short DNA strands on the lilypad and the gold surface could be used as adapters, making it a sensor for proteins rather than for DNA. In the work, the researchers added the vitamin biotin to those short DNA strands to turn the system into a sensor for the protein streptavidin. Then they added a DNA aptamer, a DNA strand that can bind to a specific protein; in this case, they used an aptamer that binds to a protein called platelet-derived growth factor BB (PDGF-BB), which could be used to help diagnose diseases such as cirrhosis and inflammatory bowel disease.

“We just add these simple molecules to the system, and it’s ready to sense something different,” Guareschi says. “It’s large enough to accommodate whatever you throw at it — that could be aptamers, nanobodies, fragments of antibodies — and it doesn’t need to be completely redesigned every time.”

The researchers also show that the sensor can be reused several times, with new adapters added each round for different detections. Although the performance slightly degrades over time, the current system could be reused at least four times.

In the future, the team hopes the system might also be useful for proteomics — studies that determine what proteins are in a sample and at what concentrations. “You could have multiple sensors at the same time with different analytes, and then you could do a wash, switch the analytes, and remeasure. And you could do that several times,” Guareschi says. “Within a few hours, you could measure hundreds of proteins using a single system.”

Additional authors of the paper, “Modular DNA origami-based electrochemical detection of DNA and proteins,” are Jaimie M. Stewart of UCLA; Emily Wu and Ashwin Gopinath of MIT, Netzahualcóyotl Arroyo-Currás of Johns Hopkins University School of Medicine, Philippe Dauphin-Ducharme of the Université de Sherbrooke in Canada; and Philip S. Lukeman of St. John’s University in New York.

The team used fabrication equipment at the Kavli Nanoscience Institute at Caltech. The work was supported by the Army Research Office, the Office of Naval Research, the National Science Foundation, and the Life Sciences Research Foundation supported by Merck Research Laboratories.

The findings, published recently in JCI Insights, suggest that these T cells are key to dengue virus immunity. In fact, most children who experienced two or more dengue infections showed very minor symptoms — or no symptoms at all — when they caught the virus again.

“We saw a significant T cell response in children who had been infected more than once before,” says study leader and LJI Assistant Professor Daniela Weiskopf, Ph.D.

Dengue virus infects up to 400 million people each year, and there are few vaccines and no approved therapies available for any of the four species, or “serotypes,” of the virus. The researchers hope their findings can inform the development of a dengue virus vaccine that prompts a similarly strong T cell response.

This research comes as dengue-carrying mosquitos expand their territory into new regions, including Southern California. Health officials in California reported the state’s first-ever case of locally acquired dengue virus in 2023. Since then, Los Angeles County has reported 12 additional cases of locally acquired dengue virus, and San Diego County has confirmed two locally acquired cases.

“Dengue virus is expanding into areas where the majority of people have never seen the virus,” says Weiskopf, who is a member of LJI’s Center for Vaccine Innovation. “That will change the game.”

T cells help fight dengue

Weiskopf and her colleagues set out to understand how T cells might sway the severity of dengue virus infection. Are T cells helping or hurting young patients?

After all, the immune system has to strike a careful balance when fighting viruses. A weak T cell response makes it tough to fight infection. On the other hand, an overzealous T cell response can cause harmful inflammation and potentially fatal complications.

The researchers studied a group of 71 children in Managua, Nicaragua, a region where dengue virus is endemic. Since 2004, study co-author Eva Harris, Ph.D., Director of the Center for Global Public Health at UC Berkeley, has worked with Nicaraguan scientists to study dengue infections in this patient group.

These children, ages 2 to 17, come in for regular blood draws to test for antibodies against dengue virus. By detecting a rise in these antibodies, compared to the previous year, researchers can tell if a child has dealt with a past dengue virus infection. Importantly, researchers can also use the blood test to catch inapparent cases of dengue infection — where a child has been exposed to the virus but is showing no clinical symptoms.

The researchers found that the number of dengue-fighting T cells in these children builds up with each infection, and these T cells appeared to be helping the pediatric patients.

Children with a history of two or more dengue infections were much less likely to show clinical symptoms if they caught the virus again. Meanwhile, children only infected once were more likely to show clinical symptoms of disease during a later infection.

Next steps toward a life-saving vaccine

The new study may offer context for why a recent dengue virus vaccine, called Dengvaxia, appeared safe and effective in just a subset of patients at risk for dengue infection. The vaccine was only FDA-approved for children who were ages 9 to 16 — and lived in a dengue-endemic area, assuming that they have experienced dengue infection by that age. Subsequent licensure in other countries required an antigen test to prove previous exposure.

The vaccine didn’t work if a person hadn’t been exposed to dengue virus before. Could it be that their T cells weren’t ready to jump into action?

As the new study suggests, it may take multiple dengue virus exposures to gain immunity. Weiskopf says scientists will continue to investigate how to harness T cells to fight dengue virus.

“There’s a lot more work to be done,” says Weiskopf.

Additional authors of the study, “Frequency of Dengue Virus-Specific T Cells is related to Infection Outcome in Endemic Settings,” include Rosa Isela Gálvez, Amparo Martínez-Pérez, E. Alexandar Escarrega, Tulika Singh,José Víctor Zambrana, and Ángel Balmaseda.

This study was supported by the National Institute of Allergy and Infectious Diseases/National Institutes of Health (grant P01 AI106695.)

The findings are detailed in a paper published in Advanced Materials.

Fibrosis, the accumulation of fibrous tissue, is a key feature of many diseases, including neurodegenerative disorders, heart disease and cancer. In oncology, evaluating the extent of fibrosis in a biopsy sample can help determine whether a patient’s cancer is in an early or advanced stage.

“The big challenge, however, is that it is extremely difficult to distinguish between these stages using current clinical methods,” said study senior author Lisa Poulikakos, a professor in the Department of Mechanical and Aerospace Engineering at the UC San Diego Jacobs School of Engineering. These methods rely on staining tissues to highlight key structures in the tumor biopsy, but the results can be subjective — one pathologist might interpret a sample differently from another. And while there are more advanced imaging techniques that can provide richer detail, they require expensive, specialized equipment that many clinics simply don’t have.

That’s where the Morpho butterfly comes in. Poulikakos and her team discovered that by placing a biopsy sample on top of a Morpho butterfly wing and viewing it under a standard microscope, they can assess whether a tumor’s structure indicates early- or late-stage cancer — without the need for stains or costly imaging machines.

“We can apply this technique using standard optical microscopes that clinics already have,” said Poulikakos. “And it’s more objective and quantitative than what is currently available.”

The idea for this method came from Paula Kirya, a mechanical engineering graduate student at UC San Diego and the study’s first author. Kirya had previously studied the Morpho butterfly’s wings and their optical properties while an undergraduate student researcher at Pasadena City College. When she transferred to UC San Diego and joined Poulikakos’ lab — where researchers build synthetic nanostructures to image biological tissues — she recognized an opportunity.

“I had been imaging butterfly wings, studying how they react to different environments,” she said. “And when I saw what the lab was doing, I thought, ‘The Morpho naturally has this property — why not use it?'”

The researchers found that the wing’s micro- and nanostructures respond strongly to polarized light — a kind of light that propagates in a specific direction. Collagen fibers — which are a key structural component of fibrotic tissue — also interact with polarized light, but their signals are weak. By placing a biopsy sample above a piece of a Morpho butterfly wing, the researchers amplified these signals, making it easier to analyze the density and arrangement of collagen fibers.

The resulting signals can then be translated into a measure of just how dense and organized the collagen fibers are in the biopsy sample. To do this, the researchers developed a mathematical model based on Jones calculus, a method for analyzing polarized light. The model correlates light intensity with the density and organization of collagen fibers, providing a quantifiable metric to assess fibrosis within the tissue.

Using this approach, the researchers analyzed both collagen-dense and collagen-sparse human breast cancer biopsy samples provided by study collaborators and co-authors Jing Yang, a professor in the Departments of Pharmacology and Pediatrics at UC San Diego School of Medicine and co-leader of the Cancer Biology and Signaling Program at Moores Cancer Center, and Aida Mestre-Farrera, a postdoctoral scientist in Yang’s group. Their results were comparable to conventional staining methods and an advanced, high-cost imaging method.

“Essentially, we’re trying to expand on these procedures with a stain-free alternative that requires nothing more than a standard optical microscope and a piece of a Morpho wing,” said Kirya. “In many parts of the world, early cancer screening is a challenge because of resource limitations. If we can provide a simpler and more accessible tool, we can help more patients get diagnosed before their cancers reach aggressive stages.”

While the current study focused on breast cancer, the researchers believe their technique could be applied to a wide range of fibrotic diseases.

“We’re excited to leverage this technique for all kinds of tissue diagnostics,” said Poulikakos. “It was really surprising to see how well nature had already designed a solution via the Morpho butterfly wing and its natural micro- and nanostructures. Our work shows that nature has given us something that can help us image diseased tissues without the need for expensive fabrication facilities.”

Our daily lives involve many processes, such as getting up, checking the time, leaving the house, arriving at the office, and starting work. Behind the scenes, brain neurons are active and process complicated tasks. In July 2023, this research team developed and published the principal component analysis in regression subspace (PCArs) to easily visualize brain neuronal activity in various situations. PCArs can determine the most critical events and whether multiple activities exist in the observed brain neuronal activity data.

In this study, researchers applied PCArs to neuronal activity in a wide range of brain regions, from the temporal to frontal lobes, and connected subcortical structures of monkeys. They analyzed four behavioral situations, including activities for remembering the location of objects by looking at the presented figures and activities where the presented figure is a cue for food. The results showed that the temporal regions involved in object recognition had a higher percentage of geometric figures close to circles. In contrast, the hippocampus and frontal lobe, which are considered to be memory regions, had an increased occurrence of curved and straight geometric patterns.

Classifying neuronal activity based on geometric figures revealed that the activity of neuronal populations in the processes of perception, memory, and judgment of visual information changes from moment to moment and is classified into different geometric figures.

Applying PCArs to the neuronal activity of the entire brain can achieve real-time imaging of its ever-changing activity. This achievement is expected to lead to the discovery of a new information processing mechanism in the brain.

This study was supported by JSPS KAKENHI (Grant Numbers 420 JP:15H05374, 22H04832), JST Moonshot R&D JPMJMS2294 (H.Y.), and the National Natural Science Foundation of China (Grant 32271088) (Y.N.).

Two hypotheses have been proposed to explain how the brain perceives pain. One is the Estimate Hypothesis, where the brain estimates the intensity of pain based on predictions. The other is the Surprise Hypothesis, where the brain perceives pain as the difference between prediction and reality, otherwise known as the prediction error. In this study, the mechanism underlying the perception of pain were investigated. In the experiment, healthy participants received painful thermal stimuli and reported felt pain intensity while observing painful or non-painful visual stimuli in the virtual reality. The researchers found that the participants strongly perceived pain when the prediction error was large, demonstrating that the Surprise Hypothesis more adequately explains the pain perception mechanism in the brain. The study further confirmed that pain was amplified when unexpected events occurred.

People with chronic pain often experience vague pain-related fears and anxieties. Possibly, this uncertain gap between expectation and reality further increases the perceived intensity of pain. Therefore, reducing the gap between pain expectation and reality or “surprise” is important in reducing pain. A better understanding of pain perception would facilitate the development of new treatments that would enhance recovery from chronic pain and trauma.

This work was supported by JSPS KAKENHI (grant numbers 19H05729 and 23KJ0261).

Now research by the University of East Anglia (UEA) in the UK, and Complutense University of Madrid and Seville University in Spain, sheds light on the short-term consequences of workplace bullying on various indicators of sleep.

These include waking up too early (sleep severity), interference with daily life (sleep impact) and dissatisfaction with own sleep (sleep satisfaction).

Writing in the Journal of Interpersonal Violence, the researchers aimed to examine how bullying at work impacts insomnia and to test the mediating role of “anger rumination” — which involves repetitive, persistent thinking about distressing events, such as bullying.

They found the relationship between bullying and sleep increases over time, particularly in relation to sleep onset difficulties, staying asleep and early morning awakening, and is explained by work-related anger felt by the employee and this constant rumination.

They also found evidence of insomnia symptoms being “contagious” between employees and their partners, meaning that the sleep issues (both severity and impact) of one person can influence the other, highlighting how interconnected sleep health can be in relationships.

Lead UK author Professor Ana Sanz-Vergel, from UEA’s Norwich Business School, said: “Our results show that the effects of workplace bullying are time-dependent and accumulative, and go beyond the individual and the work setting, impacting the partner’s sleep as well.

“When individuals experience bullying at work, they may engage in rumination as a way to mentally process and attempt to cope with the negative events. However, this repeated thinking about distressing events can lead to the development of sleep problems such as difficulties in falling asleep, staying asleep, or sleep impact and satisfaction.

“Therefore, rumination can be seen as a maladaptive coping strategy to deal with workplace bullying, meaning that while this type of reflection may initially seem like a way to resolve issues or understand the situation, it can actually lead to more harm in the long run.”

Current knowledge is limited regarding the short-time impact of bullying processes on sleep and the association between workplace bullying and sleep. This is especially important considering that sleep problems are often immediate or short-term responses to stressful situations. There is also limited information about the effects of bullying beyond the individual experiencing it.

To help address this, the team conducted two studies. In the first, 147 employees were followed over five days, and in the second, 139 couples were followed for a period of two months. In both the participants, all from Spain, had to report on their exposure to workplace bullying, work-related anger rumination and different indicators of insomnia.

The first study showed bullying indirectly affected sleep severity through rumination and in the second,also sleep satisfaction and sleep impact, indicating that rumination is a key factor in how bullying affects various aspects of sleep quality.

“It is very interesting that insomnia is contagious,” said Prof Sanz Vergel. “Partners appear to influence each other’s sleep severity and sleep impact, which is not surprising, since one individual’s awakening could cause the other to wake up as well.

“If that’s the case, then both of them can feel that lack of sleep interferes with their daily life. Satisfaction with sleep, however, is less susceptible to this contagion, possibly because it involves more subjective elements.”

The authors recommend that interventions around workplace bullying should be designed both at the organizational and individual levels. From an organizational viewpoint, reducing stressors and fostering a healthy organizational culture become crucial.

At the individual level, interventions should be focused on developing skills to help individuals more effectively deal with stressors.

Prof Sanz Vergel added: “Training on how to disconnect from work has proven efficient and has been shown to minimize the effects of bullying. In addition, couple-oriented prevention programs in the context of the workplace are needed — this could help provide coping strategies to both members of the couple, which would in turn reduce rumination levels and insomnia.”

The research was supported by funding from the Spanish Department of Science and Innovation.

Hair conditioners typically contain 20-30 ingredients, many derived from petroleum and oleochemicals, raising concerns about sustainability and environmental impact. A new study published in Science Advances, demonstrates that micellar lignin gels can effectively stabilize emulsions with natural oils, reducing the need for synthetic surfactants and complex stabilizers commonly used in commercial formulations. The research team, led by Mika Sipponen at Stockholm University, sought to explore lignin, a common and renewable component in wood biomass, as a multifunctional component for hair conditioning.

“Our findings highlight lignin’s potential as a stabilizer in oil-in-water emulsions, enabling a more natural and sustainable approach to hair conditioning,” says Mika Sipponen. “By using wood-derived lignin directly without any chemical modification, we not only simplify the ingredient list but also eliminate the need for organic solvents, making the process more eco-friendly.”

Comparable to commercial hair conditioners

The lignin gel-based conditioner was tested against a commercial hair conditioner, showing comparable emulsion stability, viscosity, and conditioning performance. A formulation with 6 percent coconut oil effectively lubricated damaged hair, reducing wet combing force by 13 percent, as confirmed by combing force measurements and multiscale microscopy analysis. Importantly, the product was easily rinsed off from paper and skin with cold water despite its dark color, demonstrating practical usability.

New opportunities in cosmetics and food

Ievgen Pylypchuk, who has been instrumental in developing lignin gel as a versatile platform material, highlights its broader potential: “Our lignin gel technology extends beyond personal care applications. Its unique ability to stabilize emulsions and interact with various biomolecules opens opportunities in cosmetics, food, and even biomedical formulations, offering a sustainable alternative to conventional ingredients.”

This innovation paves the way for greener haircare solutions that align with growing consumer demand for sustainable personal care products. The researchers anticipate further exploration of lignin-based formulations for broader applications in the personal care industry.

About a year ago saw the publication of research based on the examination of a large number of teeth from the Viking Age population of Varnhem in the Swedish province of Västergötland. Varnhem is known for its thousands of ancient graves and excavations of well-preserved skeletons.

Now, odontologists at the University of Gothenburg have taken this research further, looking at not only teeth but also entire skulls, by using modern computed tomography, also known as CT scans.

Detailed image analysis

The results presented in British Dental Journal Open suggest that the fifteen individuals whose skulls were examined suffered from a broad range of diseases. The CT scans show pathological bone growths in the cranium and jawbone, revealing infections and other conditions.

Several individuals showed signs of having suffered from sinus or ear infections that left traces in the adjacent bone structures. Signs of osteoarthritis and various dental diseases were also found. All the skulls came from adults who died between 20 and 60 years of age.

The study lead, Carolina Bertilsson, is an assistant researcher at the University of Gothenburg and a dentist within Sweden’s Public Dental Service. The study was performed with specialists in dental radiology at the University of Gothenburg and an archaeologist from Västergötlands museum.

Together, they conducted the examinations and analyzed the images. CT scans provide three-dimensional images that enable researchers to study in detail the various types of skeletal damage, layer by layer, in the different parts of the skull.

Greater understanding

“There was much to look at. We found many signs of disease in these individuals. Exactly why we don’t know. While we can’t study the damage in the soft tissue because it’s no longer there, we can see the traces left in the skeletal structures,” says Carolina Bertilsson, and continues:

“The results of the study provide greater understanding of these people’s health and wellbeing. Everyone knows what it’s like to have pain somewhere, you can get quite desperate for help. But back then, they didn’t have the medical and dental care we do, or the kind of pain relief — and antibiotics — we now have. If you developed an infection, it could stick around for a long time.”

The study is described as a pilot study. One important aspect was to test CT as a method for future and more extensive studies.”Very many of today’s archaeological methods are invasive, with the need to remove bone or other tissue for analysis. This way, we can keep the remains completely intact yet still extract a great deal of information,” says Carolina Bertilsson.