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.