For the first time, scientists observed a primate in the wild treating a wound with a plant that has medicinal properties.Scientists observed a wild male orangutan repeatedly rubbing chewed-up leaves of a medicinal plant on a facial wound in a forest reserve in Indonesia.It was the first known observation of a wild animal using a plant to treat a wound, and adds to evidence that humans are not alone in using plants for medicinal purposes.The male orangutan, Rakus, lives in the Gunung Leuser National Park on the island of Sumatra and is thought to be around 35 years old. For years researchers have followed orangutans like him on his travels through the forest, threading his way through the canopy in search of fruits to eat.Scientists within the Suaq Balimbing research area of the park first noticed a wound on his face on June 25, 2022, when they saw his self-medication behavior begin.“Once I heard about it, I got extremely excited,” said Isabelle Laumer, a primatologist with the Max Planck Institute of Animal Behavior in Germany, in part because records of animals medicating themselves are rare — even more so when it comes to treating injuries. She and colleagues detailed the discovery in a study published Thursday in the journal Scientific Reports.The plant Rakus used, known as akar kuning or yellow root, is also used by people throughout Southeast Asia to treat malaria, diabetes and other conditions. Research shows it has anti-inflammatory and antibacterial properties.Two months after his self-medication, Rakus’s wound was barely visible.SafruddinOrangutans rarely eat the plant. But in this case, Rakus ingested a small amount and also coated the wound several times. Five days after the wound was noticed, it had closed, and less than a month later “healed without any signs of infection,” Dr. Laumer said.Michael Huffman, a visiting professor at the Institute of Tropical Medicine at Nagasaki University in Japan, who wasn’t involved in the study, said, “This is to the best of my knowledge the first published study to demonstrate an animal using a plant with known biomedical properties for the treatment of a wound.”Primates have been observed appearing to treat wounds in the past, but not with plants. A group of more than two dozen chimpanzees in Gabon in Central Africa have been seen chewing up and applying flying insects to their wounds, said Simone Pika, an expert on animal cognition at Osnabrück University in Germany who documented that observation.Orangutans have been spotted using medicinal plants in a different way: In 2017 scientists reported that six orangutans in Borneo rubbed the chewed-up leaves of a shrub with anti-inflammatory and analgesic properties onto their legs and arms, probably to soothe sore muscles.“The general patterns of application are similar, and that is good for our understanding of the species’ propensity for this type of medication behavior,” Dr. Huffman said.Examples of self-medication in primates remain uncommon and the behavior is incompletely understood. Chimpanzees, bonobos, gorillas and white-handed gibbons are all known to occasionally eat rough, whole leaves, presumably to help them expel parasites. Dr. Huffman and others have also seen chimps chewing the bitter pith of a plant called Vernonia amygdalina to treat worm infections.But that behavior is not unique to primates. Indian civets, a catlike mammal, also swallow whole leaves, most likely to be rid of worms. Various birds engage in a strange behavior, called anting, in which they rub themselves in ants, to help them treat feather mites or other parasites. Hundreds of species of bees also harvest flower extracts that prevent fungal and bacterial growth in their colonies, which could be considered a type of preventative self- or group-medication.Dr. Laumer hopes the study of Rakus will help create more appreciation — and desire to protect — the Sumatran orangutan, a critically endangered species. Even after 30 years of study in the park, researchers are learning new things.Just in the past few years, scientists have shown orangutans can solve complex puzzles, engage in planning for the future, playfully tease one another and laugh — like humans.“There are so many things we still don’t know about these apes,” she said.

Published40 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy James Melley and Judith BurnsBBC NewsA 15-year-old child was prescribed dangerous levels of hormones by an unregulated online clinic without speaking to a doctor, a court ruling has revealed.Now 16, the teenager, known as J, was born female but identifies as a boy and has an autism diagnosis. J got a prescription for testosterone and puberty blockers from Singapore-registered GenderGP in late 2022.He had previously been unable to get the treatment through the NHS.Judge Sir Andrew McFarlane said: “There must be very significant concern about the prospect of a young person such as J accessing cross-hormone treatment from any off-shore, online, unregulated private clinic.” The judgement highlights the lack of NHS gender services for children and young people in England and Wales, after the closure of the Tavistock Gender Identity and Development Service (Gids) in April. Gids, rated as “inadequate” by inspectors in 2021, was the only specialist gender clinic for children and young people in the two countries. The judgement says that, as a result: “There is no relevant NHS service available for J.”Child gender clinic closure leaves uncertain futureNew youth gender services further delayedThe case illustrates how vulnerable children questioning their gender face huge waiting lists and sometimes resort to ordering medicines from overseas without adequate oversight from medical professionals.J’s father applied to the High Court last year to stop him continuing to get access to puberty blockers and cross-sex hormones, arguing his son was too young to consent.The judgement was largely finalised before last month’s publication of the Cass report, which made numerous recommendations about the treatment of young people who identify as trans. The review, published by paediatrician Dr Hilary Cass, says children have been let down by a lack of research and “remarkably weak” evidence on medical interventions in gender care. It argues that the “toxicity” of the debate on gender means professionals are “afraid” to discuss their views openly. ‘No medical examination’The High Court judgement says J was diagnosed with autism and anorexia in 2020, and was sectioned under the Mental Health Act for treatment in 2021 after incidents of self-harm.J first made contact with GenderGP in October 2022, with the support of his mother.Two months later, after a fee was paid and a questionnaire completed, a prescription was issued for testosterone and puberty blockers, drugs sometimes used by people born female who identify as male to affirm their preferred gender.The judgement says “no medical examination, blood testing or other clinical evaluation was undertaken. J has not had any direct communication with a doctor at any stage during the referral to GenderGP”.The only communication J had with a representative of GenderGP was with a Manchester-based counsellor, who is not registered with the Health and Care Professions Council regulator.GenderGP did not participate in the court hearing.Although the prescription was from a private doctor, J was given injections of testosterone by his local NHS GP every six weeks between January and August 2023.’Dangerously high’An expert witness in the case, Australia-based consultant paediatric endocrinologist Dr Jacqueline Hewitt, was critical of the lack of physical and psychological checks carried out by GenderGP on J.Dr Hewitt also raised concerns about the size of the doses of testosterone given to J, describing the level of the hormone in his blood during his treatment as “dangerously high”. She added: “In Australia, the treatment provided by GenderGP would be unlawful.”In his judgement, Sir Andrew did not make a ruling about whether J was competent to consent to taking the drugs because the teenager is not on the medication at the moment.J is not currently being treated by GenderGP, but is waiting to be seen at a new private London-based clinic.

University of Central Florida College of Medicine researcher Renee Fleeman is on a mission to kill drug-resistant bacteria, and her latest study has identified a therapy that can penetrate the slime that such infections use to protect themselves from antibiotics.
In a study published recently in Cell Reports Physical Science, Fleeman showed that an antimicrobial peptide from cows has potential for treating incurable infections from the bacterium Klebsiella pneumoniae. The bacteria, commonly found in the intestines, is usually harmless. It becomes a health hazard when it enters other parts of the body and can cause pneumonia, urinary tract and wound infections. Those at highest risk include seniors and patients with other health problems such as diabetes, cancer, kidney failure and liver disease. However, younger adults and people without additional health problems can acquire urinary tract and wound infections from the bacteria that cannot be treated by antibiotics available today.
The CDC reports that antibiotic resistant bacteria are a growing global health threat. A 2019 study found that nearly 5 million people died worldwide that year from drug-resistant infections. A large portion of those deaths are attributable to K. pneumoniae because it has a 50% death rate without antibiotic therapy.
These bacteria are more resistant to drugs when they live in a biofilm — microorganisms that stick together and are embedded in a protective slime. Recent studies have shown that 60-80% of infections are associated with bacteria biofilms, which increase their drug resistance.
“It’s Iike a coat that bacteria put around itself,” Fleeman says.
Her research is examining ways to remove the protective coat and expose the bacteria so it can be killed by the body’s immune system or antibiotics that currently cannot pass through the biofilm. Through that research, Fleeman discovered how the peptides made by cows can quickly kill K. pneumoniae.
She determined that the peptides interact with sugar connections that keep the slime intact. She likened the process to cutting into a chain-linked fence. Once multiple chains are cut, the integrity of the slime structure is damaged, and the peptide can enter and destroy the bacteria that are no longer protected.

“Our research has shown polyproline peptide can penetrate and begin to break the slime barrier down in as little as an hour after treatment,” says Fleeman.
The peptide has another advantage — once it breaks through the protective slime barrier, tests showed it killed the bacteria better than antibiotics used as a last resort to treat incurable infections. Peptides kill the bacteria by punching holes in their cell membrane, causing death quickly compared to other antibiotics that inhibit growth from inside the cell.
The peptide could also be used as a topical treatment for a wide range of uses, especially for the military, to treat open wounds in the field. “Bacteria divide every 30 minutes, so you have to act fast,” Fleeman says.
The next phase of her research will seek to understand the biology behind the peptide’s efficacy and if combinations of other drugs would aid in its application.
Her research is funded through a three-year National Institutes of Health funding Pathway to Independence R00 grant and is in its second year. Her study initially started as a K99 award at University of Texas at Austin, where she worked before joining UCF in September of 2022.
Fleeman says research into resistant infections must continue because they pose such a threat to health.
“It is estimated that by 2050, antibiotic resistant bacterial infections will be the number one cause of human deaths,” she says. “Our work is focused on preparing for this post-antibiotic era battle, where common antibiotics that we take for granted will no longer be effective, jeopardizing cancer therapy, organ transplants, and any modern medical advancement that relies on effective antibiotic therapies.”

Nonsense-mediated RNA decay, or NMD, is an evolutionarily conserved molecular mechanism in which potentially defective messenger RNAs, or mRNAs (genetic material that instructs the body on how to make proteins), are degraded. Disruption of the NMD pathway can lead to neurological disorders, immune diseases, cancers, and other pathologies. Mutations in human NMD regulators are seen in neurodevelopmental disorders, including autism and intellectual disability.
Why NMD mutations are enriched in neurodevelopmental disorders remains a mystery. Sika Zheng, a professor of biomedical sciences in the School of Medicine and the founding director of the Center for RNA Biology and Medicine at the University of California, Riverside, has now led a study, published in the journal Neuron, that reveals the molecular cellular mechanism underlying NMD regulation of brain size and its dysregulation in causing microcephaly — a condition in which a baby’s head is much smaller than expected.
The team’s finding suggests that maintaining the neuronal NMD function is essential for early brain development to prevent microcephaly. According to Zheng, modulating NMD targets can be a potential treatment for microcephaly and other related neurodevelopmental diseases.
The study explains the functional roles of NMD in brain development and the underlying mechanistic action. It also demonstrates for the first time the link between mRNA decay regulation and brain size control. Additionally, it reveals the intricate connection between NMD and the most famous tumor suppressor gene, p53, suggesting possible new connections between NMD and cancer.
The research was supported by grants from the National Institutes of Health and the California Institute of Regenerative Medicine. The title of the research paper is “Epistatic Interactions between NMD and TRP53 Control Progenitor Cell Maintenance and Brain Size.” Zheng was joined in the study by Liang Chen of the University of Southern California, Chun-Wei Chen of the City of Hope, Gene Yeo of UC San Diego, and members of their labs.

But the scope of the outbreak among cattle remains uncertain, and little human testing has been done.Additional testing of retail dairy products from across the country has turned up no signs of live bird flu virus, strengthening the consensus that pasteurization is protecting consumers from the threat, federal health and agriculture officials said at a news briefing on Wednesday.But the scope of the bird flu outbreak in cattle remains unclear, as dairy herds are not routinely tested for the infection, scientists and other experts have noted.Just one human infection, which was mild, has been reported, in a dairy worker in Texas who had direct contact with sick cows. But scientists fear there may be many more undetected infections, particularly among farm workers.Barely two dozen people have been tested for bird flu, federal officials said at the briefing. There have been no unusual increases in flu cases around the country, even in areas with infected cows, they added.But Dr. Keith Poulsen, director of the Wisconsin Veterinary Diagnostic Laboratory, said that farms are not required to test employees, many of whom are migrant workers who are reluctant to work with state health officials.“How much are we ignoring because of anxiety and fear of what happens if you don’t get an answer that you like?” Dr. Poulsen said.Until last week, potentially tainted dairy products had seemed to be the most immediate threat to the public. Federal regulators last week announced early test results of around 95 retail milk samples: Roughly one in five was found to contain genetic fragments of the virus, a fact that health officials said did not present a threat to consumers.More advanced testing later in the week turned up no live virus in the samples, a relief to federal regulators.On Wednesday, Dr. Donald A. Prater, the acting director of the Center for Food Safety and Applied Nutrition at the Food and Drug Administration, said federal scientists had examined an additional 201 commercial dairy samples, including milk, cottage cheese and sour cream.So far the scientists have not found evidence of potentially infectious virus. “Findings from the U.S. government partners, as well as academic researchers, do not change our assessment of the safety of the milk,” Dr. Prater said.Dr. Prater said that the F.D.A. still strongly advised against consuming raw, unpasteurized dairy products. Federal scientists are still reviewing data on whether the virus in raw milk could be infectious, he added.As of Wednesday, the outbreak had spread to 36 herds in nine states, according to the Department of Agriculture. Scientists have criticized the Biden administration for not conducting more testing of animals in order to determine the scope of the outbreak.Some dairy farms have been difficult to gain access to, and owners are at times reluctant to grant government workers entry to production facilities, federal officials have said.“There’s a lot of farms out there that are not reporting,” Dr. Poulsen, the Wisconsin expert, said. “They’re not reporting because they’re really afraid of what would happen if they’re not negative.”The Department of Agriculture has ruled that lactating cows must test negative for influenza A viruses, a class that includes bird flu, before they are transported across state lines. The rule also requires owners of herds with positive tests to provide data on the whereabouts of cattle to help investigators trace the disease.But further guidance released last week revealed that farmers need to test only 30 cows in a group, potentially allowing infected cows in larger herds to move between states undetected.Dr. Rosemary Sifford, a senior U.S.D.A. official, defended the scope of the order, saying that 30 cows were a “statistically significant number to be able to determine the status of the lot.” The department now requires laboratories and state veterinarians to report any positive tests from cattle to the agency.The U.S.D.A. also has turned its attention to meat. Colombia last week become the first country to ban beef and beef products from certain U.S. states because of the bird flu outbreak.Dr. José Emilio Esteban, a senior food safety official at the U.S.D.A., said at the briefing that beef was safe to eat, but that the agency was conducting three studies to “enhance our scientific knowledge to make sure we have additional data points.”The department is testing ground beef from grocery stores, as well as the remnants of slaughtered animals, in states known to have infected dairy cattle, Dr. Esteban said. The agency is also examining the effectiveness of cooking at killing the virus by heating beef patties to three different temperatures.Officials are also considering possible ways to compensate dairy farmers for “their cooperation and taking up of additional biosecurity practices,” Dr. Sifford said.Underlying much of the concern about the cattle outbreak is a fear among scientists that the bird flu virus is adapting to mammals. Dr. Sifford said at the briefing that federal scientists had not detected any changes in the virus that would allow it to spread more easily between humans.Dr. Demetre Daskalakis, a senior official at the Centers for Disease Control and Prevention, conceded that only around 25 people had been tested for infection, about the same number reported last week.More than 100 people are being monitored for symptoms. Dr. Daskalakis said that the numbers of people who were being tested and monitored were “dynamic,” in part because the monitoring period for people goes away as infected herds recover.Emily Anthes contributed reporting.

The outbreak linked to shelled organic walnuts distributed by Gibson Farms has sickened 12 people and hospitalized seven in California and Washington State, federal officials said.A California company is recalling organic walnuts that were sold at natural food stores and coop retailers in 19 states because of an E. coli outbreak that has sickened 12 people and hospitalized seven, federal officials said.Gibson Farms, the company based in Hollister, Calif., is voluntarily recalling its shelled walnuts branded as Organic Light Halves and Pieces after discovering that the nuts could carry the E. coli strain 0157: H7 that “causes a diarrheal illness often with bloody stools,” the Food and Drug Administration said in a notice on Tuesday.The recall came after the Centers for Disease Control and Prevention notified the company of 12 recorded illnesses that were linked to the walnuts. They were distributed at more than 300 food retailers, including Whole Foods Market, New Seasons Market and Rosauers Supermarkets, the F.D.A. said.An investigation is underway to determine the potential source of the contamination, the F.D.A. said. The company did not immediately respond to inquiries on Wednesday.E. coli symptoms can vary from person to person and may include cramping, diarrhea or gastrointestinal distress. Other common symptoms include vomiting and fever. People begin to feel symptoms three to four days after ingesting food or drinks containing the E. coli bacteria, according to the C.D.C.A Whole Foods spokesman said the recalled walnuts were shipped to 10 of their Whole Foods Market stores across Arkansas, Louisiana and Texas and used only as an ingredient in a salad offered on salad bars in those stores. The salad item was removed from the salad bars and the recalled walnuts were destroyed immediately, the spokesman said.This particular strain of E. coli is associated with a toxin called Shiga that can cause bloody diarrhea and “for a small number of people, can cause severe disease,” Dr. Richard Ellison, an epidemiologist at UMass Memorial Medical Center in Worcester, Mass., said on Wednesday.Although most healthy adults would fully recover within a week, some people may develop a form of kidney failure called hemolytic uremic syndrome, which is most likely to occur in young children and older adults, the F.D.A. said in its notice.Dr. Ellison said that about 90 percent of people will get better on their own without requiring antibiotics, and about 10 percent will develop the illness that can cause anemia and kidney damage.“Generally, we recommend providing supportive care and keeping people well hydrated,” he added.Consumers who have symptoms should contact their health care providers to receive care, the F.D.A. said.So far, the people who were sickened in the outbreak have been in California and Washington State. No deaths have been reported.The Organic Light Halves and Pieces were sold in bulk bins of 25-pound quantities, according to the F.D.A. The expiration dates for the affected product are between May 21, 2025, and June 7, 2025, the agency said.A list of store locations where the walnuts were sold can be found on the F.D.A.’s website.Consumers who bought the walnuts from bulk containers should check their pantries, refrigerators and freezers, and “not eat or use them,” the F.D.A. said. They should also “clean and sanitize surfaces” touched by the product, the agency said.Retailers that received the recalled products should discard the walnuts and sanitize bins before refilling them, the F.D.A. said.

Madagascar is one of the last places where outbreaks of human bubonic plague still happen regularly.
Fleas carrying the plague bacterium Yersinia pestis can spread the disease through their bites. And while a species commonly known as “the rat flea” has been fingered as the main culprit in plague outbreaks, a species known as “the human flea” may play a secondary role.
As an investigator during plague outbreaks in rural Madagascar, medical entomologist Adelaide Miarinjara knew that many households were teeming with these human fleas. Miarinjara grew up in the island nation off the east coast of Africa and is now a postdoctoral fellow at Emory University, collaborating with the Pasteur Institute in Madagascar.
“We have observed huge variability in the number of fleas in different households in the same village,” she says. “We might collect three or five fleas in one house and hundreds of them in another house.”
Miarinjara led a study to solve the mystery of this variability.
PLoS Neglected Diseases published her team’s findings: The abundance of human fleas is primarily associated with households that have a traditional dirt floor covered by a plant-fiber mat, as opposed to households with cement or board floors. A secondary risk factor was keeping animals in the house at night.
“Flea larvae need humidity, but not too much humidity, to survive,” Miarinjara says, “so the dirt covered by the plant-fiber mat may be holding just the right amount of moisture for them to thrive.”
She hopes that agencies seeking to improve people’s lives in plague-endemic areas of Madagascar focus on upgrading the flooring in homes and constructing sheds separate from the households for animals.

“Flea infestation raises the risk for getting diseases and it has a big impact on the quality of life,” Miarinjara says. “The constant bites are annoying and lead to lack of sleep.”
Household flea infestations also promote the overuse of insecticides. Surveys by the researchers reveal that 80% of the households use insecticide to try to battle the fleas. Many people are buying liquid insecticides that are repackaged in empty plastic or glass containers, without labels or instructions for how to apply them, and sold in small, open-air markets.
Improper use of insecticides is a health risk to people who may be overexposed to the chemicals. “Overuse of these chemicals is also dangerous because some fleas are developing resistance to insecticides — the frontline tools for battling plague outbreaks,” Miarinjara says.
“Poverty related to housing construction is a primary challenge that this research identified,” adds Thomas Gillespie, senior author of the study and professor and chair of Emory’s Department of Environmental Sciences. “Resurfacing dirt floors in homes with concrete could improve a range of health and quality-of-life issues, from reducing flea populations in homes to making the floors easier to clean of contaminants such as fecal matter tracked in from the outside.”
The Gillespie lab is a pioneer in the “one health” approach to epidemics — studying the interactions of people, domestic animals, wildlife and ecosystems to understand how germs jump across species.
The plague has afflicted humans at least as far back as the Bronze Age and has persisted through the centuries. The advent of antibiotics — which can effectively treat plague — turned the disease into a horror story from the past for much of the world.

In Madagascar, however, plague returns regularly to claim new victims. Cases typically originate in the rural rice-growing region of the central Highlands during the rainy season. Outbreaks there are associated with agriculture, deforestation, the black rat — and fleas.
Different flea species have evolved to prefer the blood of one animal over another, although they may feed on a variety of organisms if they are hungry enough.
Most plague research is centered on the rat flea, or Xenopsylla cheopis. Just one of its bites can transmit enough bacteria to infect someone with plague. In contrast, several bites from the human flea, Pulex irritans, are required to transmit the bacteria, making it a less potent spreader of plague but still a threat.
For the current paper, the researchers collected fleas from 126 households in four different villages. Rural Madagascar homes typically consist of more than one level. The bottom level is often used to keep livestock overnight and the second and third floors are where members of the family sleep, cook and eat.
The fleas were collected overnight on the second floor of the homes using simple traps — a lit candle set in a dish of soapy water. The fleas are attracted to the flickering light and drown when they hop into the dish.
The researchers painstakingly removed each drowned flea using tweezers, set them to dry on absorbent paper, and then transferred them to test tubes for laboratory identification and analyses.
The results showed that around 95% of the species collected in households were human fleas, mixed at times with a few rat fleas and a few from a third species that prefers to feed on cats and dogs. Collections were conducted in both the dry and rainy seasons with similar results.
“We’re now looking deeper into what’s going on with insecticide use in households,” Miarinjara says. “We want to both sort out what is driving insecticide resistance among fleas and find ways to help people use insecticides safely and more effectively.”
Co-authors of the current study include: Annick Reveloson, a PhD student at the University of Antananarivo in Madagascar; Stephen Mugel, an Emory PhD student set to graduate this May; Nick An, who graduated last year from Emory’s BS/MPH program; Andry Andriamiadanarivo, a technician at Centre ValBio in Madagascar; and Minoarisoa Rajerison, Rindra Randremanana and Romain Girod, research scientists at the Pasteur Institute in Madagascar.
The research was funded by the Branco Weiss Society in Science Fellowship and the American Society of Tropical Medicine and Hygiene.

St. Jude Children’s Research Hospital scientists have identified specific DNA variants in the non-coding regions of the genome contributing to chemotherapy resistance in acute lymphoblastic leukemia (ALL). The results guided the team to unravel the mechanism behind a previously unknown contributor to therapeutic resistance. The discovery was enabled by combining new technologies to overcome previous limitations in understanding the non-coding genome, which could be adapted to other types of cancer and diseases. The findings were published today in Nature Communications.
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Survival rates are over 94% due to modern therapy. However, those with relapsed or recurrent disease, often due to chemotherapy resistance, have a much poorer 30-40% survival rate.
The researchers studied resistance variants found in the non-coding genome, which makes up 98% of DNA and does not contain genes. Previous attempts to identify resistance mechanisms to chemotherapy focused on DNA that encoded genes. Looking directly at genes is simpler because non-coding DNA can have complex relationships with gene function, but the St. Jude group showed it is possible.
“We demonstrated that we now have the tools to find relevant non-coding genetic factors that contribute to chemotherapy resistance,” said corresponding author Daniel Savic, PhD, St. Jude Department of Pharmacy and Pharmaceutical Sciences. “The end goal is to understand the mechanisms of drug resistance so we can develop novel therapeutics and optimize existing chemotherapies based on the individual’s unique genetic makeup.”
Sorting through non-coding DNA to find the root of chemotherapy resistance
“The non-coding 98% of the genome contains instructions,” said co-first author Jackson Mobley, PhD, St. Jude Department of Pharmacy and Pharmaceutical Sciences. “If we are making a building, genes encode the iron bars, wires and concrete; non-coding DNA are the blueprints. We found the small changes in the blueprints that impact how well you respond to certain therapies.”
The group explored novel non-coding resistance variants by combining state-of-the-art technologies to examine patient samples and clinical data on treatment outcomes. In the past, research focused on a single gene or variant. However, combining high-throughput DNA sequencing methods allowed the St. Jude researchers to perform massively parallel variant screens. Those large screens enabled the testing of over 1,600 variants simultaneously to identify which were functional. That huge increase made the results more comprehensive, leading to the discovery of over 500 functional non-coding DNA variants associated with chemotherapy resistance.

“Our work represents the largest functional investigation of inherited non-coding variants associated with pharmacological traits, especially in ALL,” said co-first author Kashi Raj Bhattarai, PhD, St. Jude Department of Pharmacy and Pharmaceutical Sciences. “We verified that identified variants also have a similar effect in cell lines and patient samples.”
A novel resistance mechanism
By surveying many non-coding variants at once, the researchers could find the most impactful ones across different subtypes of ALL and connect them to a specific gene using innovative 3D genome mapping technologies. By finding the mechanism behind how variants in the non-coding genome affect target gene activity, they can figure out how it affects cancer’s response to treatment.
For example, the top variant from the screen led to the discovery of a new resistance mechanism. The resistance was to the chemotherapy drug vincristine. The researchers examined how DNA containing the functional variant physically looped to its target gene and which transcription factors, proteins that guide gene expression, were involved. The scientists found the variant bound near the gene for EIF3A,which is known to be involved in cell proliferation and survival. When they deleted the DNA containing the variant or reverted the mutation to the original sequence, they could alter the cells’ sensitivity to the chemotherapeutic agent vincristine.
The study serves as a proof of principle of how to take non-coding DNA variants and mechanistically connect them to a trait, such as chemotherapy resistance. That has been a long-standing issue holding back genomics research on inherited variants, from cancer to neurological issues.
“In any genome-wide association study, nearly all associated variants reside in the non-coding genome,” Savic said. “Therefore, connecting that variation to gene function and then to an actual trait, such as chemotherapy resistance or disease predisposition, is challenging. We showed that we have harnessed tools and technologies to systematically examine the non-coding genome and understand what it’s doing. We hope that our findings can be utilized to improve clinical outcomes in ALL patients.”

Combining time-restricted eating with high-intensity functional training may improve body composition and cardiometabolic parameters more than either alone, according to a study published May 1, 2024 in the open-access journal PLOS ONE by Ranya Ameur and Rami Maaloul from the University of Sfax, Tunisia, and colleagues.
Changes in diet and exercise are well-known ways to lose weight and improve cardiometabolic health. However, finding the right combination of lifestyle changes to produce sustainable results can be challenging. Prior studies indicate that time-restricted eating (which limits when, but not what, individuals eat) and high-intensity functional training (which combines intense aerobic and resistance exercise) may be beneficial and easier for individuals to commit to long term.
In a new study, researchers investigated the impact of time-restricted eating and high-intensity functional training on body composition and markers of cardiometabolic health such as cholesterol, blood glucose, and lipid levels. 64 women with obesity were assigned to one of three groups: time-restricted eating (diet only), high-intensity functional training (exercise only), or time-restricted eating plus high-intensity functional training (diet + exercise). Participants following the time-restricted eating regimen ate only between 8:00 am and 4:00 pm. Those in the functional training groups worked out three days per week with an instructor.
After 12 weeks, all three groups had significant weight loss and decreases in waist and hip circumference. Likewise, all groups showed favorable changes in lipid and glucose levels.
Some differences were seen between groups. For example, fat-free mass (a combination of lean mass and skeletal muscle mass) and blood pressure improved in the diet + exercise and exercise groups but did not change in the diet-only group.
Participants in the diet + exercise group generally experienced more profound changes in body composition and cardiometabolic parameters than either diet or exercise alone.
The researchers noted that this is a relatively small study, and it is difficult to tease out the contributions of specific exercise routines or of time-restricted eating and calorie reduction since both groups reduced their calorie intake. However, they note that combining time-restricted eating with high-intensity functional training might show promise in improving body composition and cardiometabolic health.
The authors add: “Combining time-restricted eating with High Intensity Functional Training is a promising strategy to improve body composition and cardiometabolic health.”

Duke researchers have opened a new avenue in the attack against influenza viruses by creating a vaccine that encourages the immune system to target a portion of the virus surface that is less variable.
Their approach worked well in experiments with mice and ferrets and may lead to more broadly-protective influenza vaccines and less reliance on an annual shot tailored to that year’s versions of the virus. Even with vaccines, influenza kills about a half-million people each year around the world.
This new vaccine approach, described May 1 in the journal Science Translational Medicine, is part of a 5-year-old effort to develop a longer-lasting universal flu vaccine that would be able to foil all versions of the virus.
Influenza strains are referred to by a shorthand code, H5N1 for example, that describes which flavors of two particular surface proteins it carries. The H (sometimes HA), is hemagglutinin, a lollipop-shaped protein that binds to a receptor on a human cell, the first step toward getting the virus inside the cell. The N is neuraminidase, a second protein that enables a newly made virus to escape the host cell and go on to infect other cells.
“On the virus particle, there’s five to 10 times more hemagglutinin than neuraminidase,” said Nicholas Heaton, PhD, an associate professor of molecular genetics and microbiology at Duke who led the research. “If we took your blood to see if are you likely to be protected from a strain of flu, we’d be measuring what your antibodies do to hemagglutinin as the best metric of what’s likely to happen to you. The strongest correlates of protection have to do with hemagglutinin-directed immunity.”
Vaccines teach the immune system to react to pieces of the virus that have been specifically tailored to the versions of influenza that are expected to be the most threatening in the coming flu season. The reason we need a new flu shot every fall isn’t because the vaccine wears out; it’s because the influenza virus is constantly changing the surface proteins that vaccines target.
Flu shots — and immune systems — tend to target the bulb-like “head” of hemagglutinin rather than the stalk. But the details of that head region also change constantly, creating an arms race between vaccine design and viruses. The stalk, by comparison, changes much less.

“A number of groups have gone through and experimentally mutagenized the whole hemagglutinin and asked ‘which areas can change and still allow the hemagglutinin to function?'” Heaton explained. “And the answer is, you can’t really change the stalk and expect it to continue to function.”
So the Duke team sought to design proteins that elicit an immune response more focused on the stalk rather than the head. “The virus has evolved to have the immune system recognize these (features on the head region). But these are the shapes the virus can change. That is an insidious strategy,” Heaton said.
Using gene-editing, they created more than 80,000 variations of the hemagglutinin protein with changes in one portion right on the top of the head domain and then tested a vaccine filled with a mixture of these variations on mice and ferrets.
Because of the broad variety of head conformations being presented to the immune system and the relative consistency of the stalks, these vaccines produced more antibodies to the stalk portion of hemagglutinin in response. “The opportunity for the immune system to see that (head portion) over and over and over like it needs to is compromised because there’s diversity there,” Heaton said.
In lab tests and animals, the experimental vaccine caused the immune system to respond more strongly to stalk regions because they stayed consistent. This boosted the immune response to the vaccine overall, and in some cases, even improved antibody responses to the head region of the protein as well.
“Antibodies against the stalk work differently,” Heaton said. “Their mechanism of protection is not necessarily to block the first step of infection. So then our idea was, ‘What if we can come up with a vaccine that gives us both? What if we can get good head antibodies and at the same time also get stalk antibodies in case the vaccine selection was wrong, or if there’s a pandemic?'”
“Essentially, the paper says, Yes, we can accomplish that,” Heaton said.

After a shot of the highly variant vaccine was administered in some experiments, 100 percent of the mice avoided illness or death from what should have been a lethal dose of flu viruses.
The next steps of the research will attempt to understand whether the same level of immunity can be achieved by presenting fewer than 80,000 hemagglutinin variants.
This research was funded in part with a contract from the NIH/National Institute of Allergy and Infectious Diseases (75N93019C00050). It also involved the use of the Duke Regional Biocontainment Laboratory, which received partial support for construction from the NIH/NIAID (UC6 AI058607)
Zhaochen Luo and Nicholas Heaton have a patent on the methods used to create large antigen libraries for this study.