A study by Rutgers Health experts of more than 31 million hospital records shows that infertility treatment patients were twice as likely as those who conceived naturally to be hospitalized with heart disease in the year after delivery.
Patients who underwent infertility were particularly likely — 2.16 times as likely as those who conceived naturally — to undergo hospitalization for dangerously high blood pressure or hypertension.
“Postpartum checkups are necessary for all patients, but this study indicates they are particularly important for patients who undergo infertility treatment to achieve a conception,” said Rei Yamada, an obstetrics and gynecology resident at Rutgers Robert Wood Johnson Medical School and lead author of the study.
The study authors say their results support standards of care that now call for an initial postpartum checkup three weeks after delivery, standards that some health systems have yet to adopt. Much of the elevated risk came in the first month after delivery, particularly for patients who developed dangerously high blood pressure.
“And these results aren’t the only ones to indicate that follow-up should occur early,” said Cande Ananth, chief of the Division of Epidemiology and Biostatistics in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Rutgers Robert Wood Johnson Medical School and senior author of the study. “We have been involved in a series of studies over the past few years that have found serious risks of heart disease and stroke to various high-risk patient populations within those initial 30 days after delivery — risks that could be mitigated with earlier follow-up care.”
The study analyzed the Nationwide Readmissions Database, which contains nationally representative data on about 31 million hospital discharges and readmissions per year. The database contains diagnosis codes, which let researchers find specific populations and identify reasons for readmission.
The researchers used data from more than 31 million patients who were discharged following delivery from 2010 to 2018, including 287,813 patients who had undergone any infertility treatment.
Although infertility treatment predicted a sharply elevated risk of heart disease, the study authors said the relative youth of infertility treatment patients kept their overall risk fairly low. Just 550 of every 100,000 women who received infertility treatment and 355 of every 100,000 who conceived naturally were hospitalized with cardiovascular disease in the year after delivery.
The cause of the elevated risk of heart disease associated with infertility treatment remains unclear. The increase in heart disease could stem from the infertility treatments themselves, the underlying medical issues that made patients infertile or some other cause.
“Looking forward, I’d like to see if different types of infertility treatment and, importantly, medications are associated with different risk levels,” said Yamada. “Our data gave no information about which patients had undergone which treatment. More detailed information might also provide insight into how infertility treatment impacts cardiovascular outcomes.”

University of New Mexico researchers have detected significant concentrations of microplastics in the testicular tissue of both humans and dogs, adding to growing concern about their possible effect on human reproductive health.
In a new paper published in the journal Toxicological Sciences, a team led by Xiaozhong “John” Yu, MD, PhD, MPH, a professor in the UNM College of Nursing, reported finding 12 types of microplastics in 47 canine and 23 human testes.
“Our study revealed the presence of microplastics in all human and canine testes,” Yu said. The team was also able to quantify the amount of microplastics in the tissue samples using a novel analytical method that revealed correlations between certain types of plastic and reduced sperm count in the canine samples.
Yu, who studies the impact of various environmental factors on the human reproductive system, said heavy metals, pesticides and endocrine-disrupting chemicals have all been implicated in a global decline in sperm count and quality in recent years. A conversation with his colleague Matthew Campen, PhD, a professor in the UNM College of Pharmacy who has documented the presence of microplastics in human placentas, led him to wonder whether something else might be at work.
“He said, ‘Have you considered why there is this decline (in reproductive potential) more recently? There must be something new,'” Yu said. That led Yu to design a study using the same experimental method Campen’s lab had used in the placenta research.
His team obtained anonymized human tissue from the New Mexico Office of the Medical Investigator, which collects tissue during autopsies and stores it for seven years before disposing of it. The canine tissue came from City of Albuquerque animal shelters and private veterinary clinics that perform spay-neutering operations.
The team chemically treated the samples to dissolve the fat and proteins and spun each sample in an ultracentrifuge, leaving a nugget of plastic at the bottom of a tube. Then, heated the plastic pellet in a metal cup to 600 degrees Celsius. They used a mass spectrometer to analyze gas emissions as different types of plastic burned at specific temperatures.

In dogs, the average concentration of microplastics in testicular tissue was 122.63 micrograms per gram of tissue (a microgram is a millionth of a gram). In human tissue the average concentration was 329.44 micrograms per gram — nearly three times higher than in dogs and significantly higher than the average concentration Campen found in placental tissue.
“At the beginning, I doubted whether microplastics could penetrate the reproductive system,” Yu said. “When I first received the results for dogs I was surprised. I was even more surprised when I received the results for humans.”
The researchers found the most prevalent polymer in both human and canine tissue was polyethylene (PE), which is used to make plastic bags and bottles. In dogs that was followed by PVC, which is used in industrial, municipal and household plumbing and in many other applications.
The team was able to count the sperm in the canine samples (but not in the human ones, which had been chemically preserved) and found that higher levels of PVC in the tissue correlated with a lower sperm count, Yu said. There was no correlation with tissue concentration of PE, however.
“The plastic makes a difference — what type of plastic might be correlated with potential function,” he said. “PVC can release a lot of chemicals that interfere with spermatogenesis and it contains chemicals that cause endocrine disruption.”
The study compared human and canine tissue for a couple of reasons, one being that dogs live alongside people and share their environment. They also share some biological characteristics.

“Compared to rats and other animals, dogs are closer to humans,” he said. “Physically, their spermatogenesis is closer to humans and the concentration has more similarity to humans.” Canine sperm counts also seem to be dropping, he added. “We believe dogs and humans share common environmental factors that contribute to their decline.”
Microplastics result when plastic is exposed to ultraviolet radiation in sunlight and degrades in landfills. It can be blown about by the wind or carried into nearby waterways, and some bits are so small they are measured in nanometers (a billionth of a meter). They’re now ubiquitous in the environment — even as global use of plastics continues to grow. Yu noted that the average age of the men in the OMI autopsy samples was 35, meaning their plastics exposure began decades ago, when there was less plastic in circulation. “The impact on the younger generation might be more concerning,” now that there is more plastic than ever in the environment, he said.
The findings point the way for additional research to understand how microplastics might affect sperm production in the testes, he said. “We have a lot of unknowns. We need to really look at what the potential long-term effect. Are microplastics one of the factors contributing to this decline?”
In disseminating his findings, Yu doesn’t want anyone to panic. “We don’t want to scare people,” he said. “We want to scientifically provide the data and make people aware there are a lot of microplastics. We can make our own choices to better avoid exposures, change our lifestyle and change our behavior.”

Highly pathogenic H5N1 avian influenza was detected in dairy cattle for the first time in the United States in March, with nine states reporting outbreaks by May. While the method of transmission among cattle is currently unknown, new research published today (May 15) in Nature Communications demonstrates that a related strain of H5N1, subtype clade 2.3.4.4b, which caused an outbreak in farmed mink in 2022, transmitted through the air to a limited number of ferrets. This is the first time that a member of the group of H5N1 clade 2.3.4.4b viruses has been shown to exhibit this ability. According to the Penn State researchers who led the study, the findings suggest these viruses are evolving to infect mammals and with potentially increased risk to humans.
“While there is no evidence that the strain of H5N1 that is presently affecting dairy cattle is capable of airborne transmission, our study suggests that another member of this family of viruses has evolved some degree of airborne transmissibility,” said Troy Sutton, associate professor of veterinary and biomedical sciences, Penn State, and corresponding author on the paper. “This finding underscores the importance of continued surveillance to monitor the evolution of these viruses and their spillover into other mammals, including humans.”
According to the researchers, assessing a virus’s potential for airborne transmission in mammals could inform the understanding of its potential risk to humans. Since virus samples could not be readily obtained after the outbreak in mink had been controlled, the team reconstructed the virus using publicly available genetic sequences.
Next, the researchers evaluated the ability of the virus to transmit in ferrets, which have respiratory tracts that are more similar to humans in their susceptibility to viral infection and transmission than other model organisms, such as mice. The team measured both direct transmission of the virus by placing infected ferrets in cages with uninfected ferrets and indirect airborne transmission by placing infected and uninfected ferrets in cages that enabled shared airspace but prevented physical contact. To assess disease severity, the team examined the ferrets’ weight loss and signs of clinical illness.
The researchers found that the virus transmitted by direct contact to 75% of exposed ferrets and by respiratory droplets to 37.5% of exposed ferrets after about nine days of exposure. The team also found that the virus had a low infectious dose, meaning that even small amounts of virus caused an infection.
Sutton noted that the mink strain of the virus contained a mutation, called PB2 T271A. To test the influence of this mutation on viral transmission and disease severity, the team engineered the virus without the mutation and found that mortality and airborne transmission in the ferrets infected with this version of the virus was reduced.
“These findings suggest that the PB2 T271A mutation is enhancing viral replication of the virus, contributing to both virulence and transmission in ferrets,” Sutton said. “Understanding the role that this mutation plays means we can monitor for it or for similar mutations to arise in the currently circulating strains of H5N1.”
Sutton added that the ferrets that the team used in its studies had no preexisting immunity to influenza, whereas the majority of humans have been exposed to H1N1 and H3N2 seasonal influenza viruses.

“This exposure would likely offer some degree of cross-protection against H5N1 if humans are exposed to another H5N1 variant,” he said.
Furthermore, he said that the transmission rate the team observed in the mink virus is lower than is typical for pandemic influenza viruses.
“Pandemic influenza viruses typically transmit via the airborne route to 75% to 100% of contacts within three to five days, whereas the mink virus we studied transmitted to fewer than 40% of contacts after nine days,” Sutton said. “The transmission observed in our studies is indicative of increased pandemic potential relative to previously characterized strains of H5N1; however, the mink virus does not exhibit the same attributes as pandemic strains. The H5N1 strain affecting cattle also has not caused severe disease in cattle or humans, but the longer the virus circulates, and the more exposure humans have to it, the greater the chances that it will evolve to infect humans.”
This research was conducted in Penn State’s Eva J. Pell Advanced Biological Laboratory, a high-containment biosafety level 3 enhanced laboratory that is regularly inspected by the Centers for Disease Control and Prevention and the United States Department of Agriculture.
Other Penn State authors of the paper include Katherine Restori, assistant research professor in veterinary and biomedical sciences, as well as Kayla Septer, Cassandra Field and Devanshi Patel, all graduate students in veterinary and biomedical sciences. David VanInsberghe, postdoctoral fellow; Vedhika Raghunathan, graduate student; and Anice Lowen, professor of microbiology and immunology, all at Emory University, also are authors of the paper.
The National Institutes of Health and National Institute of Food and Agriculture supported this research.

Vegetarian and vegan diets are generally associated with better status on various medical factors linked to cardiovascular health and cancer risk, as well as lower risk of cardiovascular diseases, cancer, and death, according to a new review of 49 previously published papers. Angelo Capodici and colleagues present these findings in the open-access journal PLOS ONE on May 15, 2024.
Prior studies have linked certain diets with increased risk of cardiovascular disease and cancer. A diet that is poor in plant products and rich in meat, refined grains, sugar, and salt is associated with higher risk of death. Reducing consumption of animal-based products in favor of plant-based products has been suggested to lower the risk of cardiovascular disease and cancer. However, the overall benefits of such diets remain unclear.
To deepen understanding of the potential benefits of plant-based diets, Capodici and colleagues reviewed 48 papers published between January 2000 and June 2023 that themselves compiled evidence from multiple prior studies. Following an “umbrella” review approach, they extracted and analyzed data from the 48 papers on links between plant-based diets, cardiovascular health, and cancer risk.
Their analysis showed that, overall, vegetarian and vegan diets have a robust statistical association with better health status on a number of risk factors associated with cardiometabolic diseases, cancer, and mortality, such as blood pressure, management of blood sugar, and body mass index. Such diets are associated with reduced risk of ischemic heart disease, gastrointestinal and prostate cancer, and death from cardiovascular disease.
However, among pregnant women specifically, those with vegetarian diets faced no difference in their risk of gestational diabetes and hypertension compared to those on non-plant-based diets.
Overall, these findings suggest that plant-based diets are associated with significant health benefits. However, the researchers note, the statistical strength of this association is significantly limited by the many differences between past studies in terms of the specific diet regimens followed, patient demographics, study duration, and other factors. Moreover, some plant-based diets may introduce vitamin and mineral deficiencies for some people. Thus, the researchers caution against large-scale recommendation of plant-based diets until more research is completed.
The authors add: “Our study evaluates the different impacts of animal-free diets for cardiovascular health and cancer risk showing how a vegetarian diet can be beneficial to human health and be one of the effective preventive strategies for the two most impactful chronic diseases on human health in the 21st century.”

Wearable Bluetooth devices can shed light on the care that residents of care homes are receiving and which residents are most in need of social contact, according to a new study published this week in the open-access journal PLOS ONE by Carl Thompson of University of Leeds, UK.
In the UK alone, nearly half a million people reside in some form of care home, including long-term care facilities, nursing homes and residential homes. There is no single reliable method that works well to evaluate care home quality, in part because care homes are complex social systems with diverse interacting groups.
In the new study, researchers tested the feasibility of collecting social network metrics on people in care homes by using Bluetooth devices worn by both staff and residents. More than 250 people in four UK care homes were involved in the study. Over two months, the researchers collected data on 204,087 interactions between people.
Just 2% of all interactions recorded by the devices lasted longer than 2 minutes, and more than 65% of those longer interactions were between staff members. Moreover, in only one of the four care homes did residents have as many social interactions as staff. Overall, most interactions between people occurred in communal areas such as dining rooms and lounges, with staff and smoking rooms also being focal points for interactions. The data also allowed researchers to identify staff and residents with the strongest and weakest social connections to their communities, based on the frequency and length of their interactions with other people.
The study was limited by the fact that data was collected in only four homes and was not collected with any context or any information about whether a social interaction generated positive or negative feelings. However, the authors conclude that wearable devices worn by care home residents and staff are capable of generating useful data for quality improvement. Data emerging from this study could be utilized to implement initiatives aimed at improving the lives of residents by reducing their isolation and increasing interaction between staff and residents.
The authors add: “Relationships and social contact are what transforms merely safe and adequate long term care into high-quality, outstanding, long term care. This paper shows how wearable contact tracing technology can help ensure social contact and relationships are a part of quality long term care for more people that live and work in care homes.”

Spending time in nature is good for us. Studies have shown that contact with nature can lift our well-being by affecting emotions, influencing thoughts, reducing stress and improving physical health. Even brief exposure to nature can help. One well-known study found that hospital patients recovered faster if their room included a window view of a natural setting.
Knowing more about nature’s effects on our bodies could not only help our well-being, but could also improve how we care for land, preserve ecosystems and design cities, homes and parks. Yet studies on the benefits of contact with nature have typically focused primarily on how seeing nature affects us. There has been less focus on what the nose knows. That is something a group of researchers wants to change.
“We are immersed in a world of odorants, and we have a sophisticated olfactory system that processes them, with resulting impacts on our emotions and behavior,” said Gregory Bratman, a University of Washington assistant professor of environmental and forest sciences. “But compared to research on the benefits of seeing nature, we don’t know nearly as much about how the impacts of nature’s scents and olfactory cues affect us.”
In a paper published May 15 in Science Advances, Bratman and colleagues from around the world outline ways to expand research into how odors and scents from natural settings impact our health and well-being. The interdisciplinary group of experts in olfaction, psychology, ecology, public health, atmospheric science and other fields are based at institutions in the U.S., the U.K., Taiwan, Germany, Poland and Cyprus.
At its core, the human sense of smell, or olfaction, is a complex chemical detection system in constant operation. The nose is packed with hundreds of olfactory receptors, which are sophisticated chemical sensors. Together, they can detect more than one trillion scents, and that information gets delivered directly to the nervous system for our minds to interpret — consciously or otherwise.
The natural world releases a steady stream of chemical compounds to keep our olfactory system busy. Plants in particular exude volatile organic compounds, or VOCs, that can persist in the air for hours or days. VOCs perform many functions for plants, such as repelling herbivores or attracting pollinators. Some researchers have studied the impact of exposures to plant VOCs on people.
“We know bits and pieces of the overall picture,” said Bratman. “But there is so much more to learn. We are proposing a framework, informed by important research from many others, on how to investigate the intimate links between olfaction, nature and human well-being.”
Nature’s smell-mediated impacts likely come through different routes, according to the authors. Some chemical compounds, including a subset of those from the invisible realm of plant VOCs, may be acting on us without our conscious knowledge. In these cases, olfactory receptors in the nose could be initiating a “subthreshold” response to molecules that people are largely unaware of. Bratman and his co-authors are calling for vastly expanded research on when, where and how these undetected biochemical processes related to natural VOCs may affect us.

Other olfactory cues are picked up consciously, but scientists still don’t fully understand all their impacts on our health and well-being. Some scents, for example, may have “universal” interpretations to humans — something that nearly always smells pleasant, like a sweet-smelling flower. Other scents are closely tied to specific memories, or have associations and interpretations that vary by culture and personal experience, as research by co-author Asifa Majid of the University of Oxford has shown.
“Understanding how olfaction mediates our relationships with the natural world and the benefits we receive from it are multi-disciplinary undertakings,” said Bratman. “It involves insights from olfactory function research, Indigenous knowledge, Western psychology, anthropology, atmospheric chemistry, forest ecology, Shinrin-yoku — or ‘forest bathing’ — neuroscience, and more.”
Investigation into the potential links between our sense of smell and positive experiences with nature includes research by co-author Cecilia Bembibre at University College London, which shows that the cultural significance of smells, including those from nature, can be passed down in communities to each new generation. Co-author Jieling Xiao at Birmingham City University has delved into the associations people have with scents in built environments and urban gardens.
Other co-authors have shown that nature leaves its signature in the very air we breathe. Forests, for example, release a complex chemical milieux into the air. Research by co-author Jonathan Williams at the Max Planck Institute for Chemistry and the Cyprus Institute shows how natural VOCs can react and mix in the atmosphere, with repercussions for olfactory environments.
The authors are also calling for more studies to investigate how human activity alters nature’s olfactory footprint — both by pollution, which can modify or destroy odorants in the air, and by reducing habitats that release beneficial scents.
“Human activity is modifying the environment so quickly in some cases that we’re learning about these benefits while we’re simultaneously making them more difficult for people to access,” said Bratman. “As research illuminates more of these links, our hope is that we can make more informed decisions about our impacts on the natural world and the volatile organic compounds that come from it. As we say in the paper, we live within the chemical contexts that nature creates. Understanding this more can contribute to human well-being and advance efforts to protect the natural world.”

Results from a new Dartmouth-led study, involving collaborators at the University of Pittsburgh and Yale University and published in the journal PLOS Biology, are providing new insights into the therapeutic potential of bacteriophage (phage) therapy for treating diseases like cystic fibrosis (CF).
A major challenge of treating people with CF — an inherited disease that causes sticky, thick mucus to build up in the lungs — are the persistent infections the disease causes which can lead to respiratory failure and death.
“Opportunistic pathogens such as Pseudomonas aeruginosa, one of the pathogens associated with the most lung function decline in CF, have become increasingly resistant to antibiotics, so we have to be creative with new ways to think about treating these infections,” explains Jennifer Bomberger, PhD, a professor of microbiology and immunology at Dartmouth’s Geisel School of Medicine, who served as senior author on the study.
“Developed many decades ago, phage therapy has seen success in Eastern Europe as an antimicrobial for difficult-to-treat infections and is increasingly being used in clinical trials and compassionate use cases through Emergency Use Authorizations in the U.S.,” says Paula Zamora, PhD, a postdoctoral associate at Geisel and first author on the study.
One of the advantages of phage therapy, which uses viruses to kill bacteria, “is that unlike antibiotics which need to be given repeatedly, it has this mechanism of self-amplification,” Zamora continues. “Phages are able to replicate by binding to bacteria and injecting their genetic material — as phages make more phages, they kill more bacteria.”
While phage therapy is thought to be relatively safe with few side effects, key gaps in knowledge related to the interactions between phages and the epithelial cells of the human respiratory tract remain.
“Since very high doses of phages are often needed to elicit a therapeutic effect, we wondered, ‘Do the host cells detect these phages, and do they create an inflammatory response that we should be concerned about?'” says Bomberger.

To find out, the investigators teamed up with researchers at Pitt and Yale,
examining interactions between a panel of Pseudomonas aeruginosa phages with therapeutic potential and human airway epithelial cells derived from a person with CF and grown in cell lines in the lab.
They determined that respiratory epithelial cells do sense and respond to therapeutic phages, and that interactions between phages and epithelial cells are heterogenous in nature — in that they are dependent on specific phage properties, as well as physiochemical features of the airway microenvironment.
“Our research also indicates that immune responses to phages could be harnessed to improve the effectiveness of phage therapy on an individual basis,” Zamora says. “We hope that our findings will lead to more studies that examine the effects that phages have on the human host.”
Considering that the effects of phages on human cells are not currently required to be evaluated as part of phage therapy design, Bomberger adds, “Our suggestion is, as people are screening phages for killing bacteria, they might also want to know what types of immune responses those phages could elicit in the host and let that play into their calculus when picking which phage to treat a patient with.”

Immunotherapy has revolutionized the way we treat cancer in recent years. Instead of targeting the tumor itself, immunotherapies work by directing patients’ immune systems to attack their tumors more effectively. This has been especially impactful in improving outcomes for certain difficult-to-treat cancers. Still, fewer than half of all cancer patients respond to current immunotherapies, creating an urgent need to identify biomarkers that can predict which patients are most likely to benefit.
Recently, scientists have noticed that patients whose tumors have a mutation in a gene called ARID1A are more likely to respond positively to immune checkpoint blockade, a type of immunotherapy that works by keeping cancer-fighting immune cells called T cells turned “on” when they’d otherwise be turned “off.” Since this ARID1A gene mutation is present in many cancers — including endometrial, ovarian, colon, gastric, liver, and pancreatic cancers — researchers at the Salk Institute wondered how it contributes to treatment sensitivity, and how clinicians can use this information to customize cancer treatments to each patient.
The new study, published in Cell on May 15, 2024, reveals that ARID1A mutation renders tumors sensitive to immunotherapy by inviting cancer-fighting immune cells into the tumor through an antiviral-like immune response. The researchers suggest this mutation and antiviral immune response could be used as a biomarker to better select patients for specific immunotherapies, like immune checkpoint blockade. The findings also encourage the development of drugs that target ARID1A and related proteins as a way of sensitizing other tumors to immunotherapy.
“This could really make a difference in patient outcomes from cancer treatment,” says Associate Professor Diana Hargreaves, senior author of the study. “These ARID1A mutation cancer patients are already having an immune response, so all we need to do is upregulate that response using immune checkpoint blockade to help them destroy their tumors from the inside.”
While it was reported that people with ARID1A mutations responded well to immune checkpoint blockade, the exact relationship between the two remained unclear. To elucidate the mechanism behind this, Salk scientists turned to mouse models of melanoma and colon cancer with either mutated ARID1A or functional ARID1A.
The team observed a powerful immune response in all animal models with mutated ARID1A tumors but not those with functional ARID1A tumors, supporting the idea that the ARID1A mutation was, indeed, driving the response. But how did this work on a molecular level?
“We found that ARID1A plays an important role in the nucleus of keeping DNA properly arranged,” says Matthew Maxwell, first author of the study and a graduate student in Hargreaves’ lab. “Without functional ARID1A, loose DNA can be excised and escape into the cytosol, which activates a coincidentally desirable antiviral immune response that can be further enhanced by immune checkpoint blockade.”
The ARID1A gene codes for a protein that helps regulate the shape of our DNA and maintain genome stability. When ARID1A is mutated, a microscopic chain of events analogous to a Rube Goldberg machine is set off in the cancer cell. First, the lack of functional ARID1A leads to escape of DNA into the cytosol. Next, the cytosolic DNA activates an antiviral alarm system — the cGAS-STING pathway — since our cells are adapted to flag any DNA in the cytosol as foreign to protect us against viral infections. Finally, the cGAS-STING pathway calls on the immune system to recruit T cells into the tumor and activates them into specialized cancer-killing T cells.

With each step relying on the last, this chain of events — ARID1A mutation, DNA escape, cGAS-STING alarm, T cell recruitment — results in more cancer-fighting T cells in the tumor. Immune checkpoint blockade can then be used to ensure these T cells stay “on,” supercharging them to defeat the cancer.
“Our findings provide a novel molecular mechanism by which ARID1A mutation can promote an anti-tumor immune response,” says Hargreaves. “What’s most exciting about these results is their translational potential. Not only can we use ARID1A mutations to help select patients for immune checkpoint blockade, but we now also see a mechanism by which drugs that inhibit ARID1A or its protein complex could be used to further enhance immunotherapy in other patients.”
By outlining the mechanism by which immune checkpoint blockade is more effective for ARID1A mutant cancers, the researchers have provided cause for clinicians to prioritize the immunotherapy for patients with mutated ARID1A. The findings are a major step in personalizing cancer treatment and inspiring novel therapies that target and inhibit ARID1A and its protein complex.
In the future, the Salk team hopes its findings can improve patient outcomes across the many cancer types associated with ARID1A mutations and is set to explore this clinical translation with collaborators at UC San Diego.
Other authors include Jawoon Yi, Shitian Li, Samuel Rivera, Jingting Yu, Mannix Burns, Helen McRae, Braden Stevenson, Josephine Ho, Kameneff Bojorquez Gastelum, Joshua Bell, Alexander Jones, Gerald Shadel, and Susan Kaech of Salk; Marianne Hom-Tedla and Katherine Coakley of Salk and UC San Diego; Ramez Eskander of UC San Diego; and Emily Dykhuizen of Purdue University.
The work was supported by the National Institutes of Health (NCI CCSG P30 014195, T32DK007541, R01 CA228211, R01 CA285867, R01 CA216101, R01 CA240909, R01 AI066232, R21 MH128678, S10-OD023689), National Science Foundation, Howard Hughes Medical Institute, Cancer Research Institute, Pew-Stewart Scholars for Cancer Research, American Cancer Society, and Padres Pedal the Cause.

Some proteins shift their shape when exposed to different temperatures, revealing previously unknown binding sites for medications.
The findings, published today in Nature, could revolutionize wide swathes of biology by fundamentally changing how protein structure is studied and leveraged for drug design. The study was led by Van Andel Institute’s Juan Du, Ph.D., and Wei Lü, Ph.D.
Proteins generally are investigated at low temperatures to ensure their stability. However, the new study demonstrates that certain proteins are highly sensitive to temperature and change their shape when viewed at body temperature.
“For a long time, the methods we’ve used to study proteins require them to be cold or frozen. But in the real world, human proteins exist and function at body temperature,” Du said. “Our study describes a new way to study proteins at body temperature and reveals that some proteins drastically alter their structures when warm, opening up new opportunities for structure-guided drug development.”
Proteins are the molecular workhorses of the body. Their shape governs how they interact with other molecules to do their jobs. By determining protein structure, scientists can create blueprints that guide development of more effective medications, much like locksmiths designing keys to fit into specific locks.
Although it is well known that temperature affects molecular function in the body, studying proteins at physiological temperature has been technologically challenging. Today’s study by the Du and Lü laboratories details how they overcame these issues and provides scientists a roadmap for doing so in their own experiments.
The study focused on a protein called TRPM4, which supports heart function and metabolism, including the release of insulin. As such, TRPM4 is linked to stroke, heart disease and diabetes, among other health conditions.
To visualize TRPM4 at body temperature, the team leveraged VAI’s powerful suite of cryo-electron microscopes (cryo-EM), which allow scientists to flash freeze proteins and assemble detailed images of their structures. Rather than using a low-temperature sample, Postdoctoral Fellow Jinhong Hu, Ph.D., and colleagues in the Du and Lü laboratories heated the sample to body temperature before flash freezing it. By doing so, they found that ligands — molecules that bind to proteins — interact with totally different sites on TRPM4 at body temperature than at lower temperatures.
The implications of today’s study are far-reaching and reinforce the importance of studying proteins at body temperature to ensure identification of physiologically relevant drug binding sites.

Among public school students in New York City, some of the greatest increases in childhood obesity in recent years were among those socioeconomic and demographic groups already bearing the greatest burden of obesity, including Black and Hispanic students and youth living in poverty. That is the conclusion of a new study published this week in the open-access journal PLOS ONE by Emily D’Agostino of Duke University, US, and colleagues.
Childhood obesity is a major public health concern associated with chronic health conditions and adverse mental health outcomes into adulthood. In the new study, researchers analyzed height, weight and socioeconomic and demographic data on 1.37 million unique students in the New York City public school system aged 5 to 15 from school years 2011-2012 through 2019-2020.
Among a study sample representative of over 600,000 youth in the school year 2019-20, 20.9% had obesity and 6.4% had severe obesity. Overall, rates of obesity and severe obesity decreased slightly between 2011-12 and 2019-20 (2.8% relative decrease in obesity and 0.2% in severe obesity, p