Publisher Health

Scar-like cells that make up a sizable portion of malignant pancreatic tumors and shield these cancers from immune attack are derived from mesothelial cells that line tissues and organs, a new study led by UT Southwestern researchers suggests. The findings, published in Cancer Cell, could offer a new strategy to fight pancreatic cancer, a deadly disease for which no truly effective treatments exist.
“By targeting antigen-presenting cancer-associated fibroblasts, we might someday be able significantly to enhance the activity of immune therapy in pancreatic cancer patients,” said Huocong Huang, M.D., Ph.D., Instructor of Surgery at UTSW. Dr. Huang co-led the study with Rolf A. Brekken, Ph.D., Professor of Surgery, Pharmacology, and in UTSW’s Hamon Center for Therapeutic Oncology Research, and a member of the Harold C. Simmons Comprehensive Cancer Center.
According to the American Cancer Society, about 56,000 people in the U.S. are diagnosed each year with pancreatic ductal adenocarcinoma (PDA), the most common form of pancreatic cancer. Currently the fourth-leading cause of cancer-related deaths in this country, it’s projected to become the second-leading cause by 2030. Despite decades of research, the prognosis for PDA remains dismal, with only 10% of patients surviving five years past diagnosis.
Researchers have long known that cells called cancer-associated fibroblasts (CAFs) make up a significant portion of pancreatic tumors. Much like the fibroblasts that compose scar tissue, CAFs make pancreatic tumors dense and tough, preventing chemotherapies and other treatments from readily reaching cancer cells. Although scientists had considered these pancreatic CAFs to be a uniform population, Dr. Huang explained, he and his colleagues in the Brekken lab showed in an earlier study in 2019 that these cells fall into three categories. One of these is a subtype known as antigen-presenting CAFs (apCAFs), which interact with immune cells by displaying proteins called antigens on their surface.
To determine how apCAFs contribute to PDA progression, Dr. Huang, Dr. Brekken, and their colleagues used a technique known as lineage tracing to learn how these cells arise as a normal pancreas develops cancer. Their findings showed that apCAFs originate from mesothelial cells, which form a protective membrane that lines organs, body cavities, and tissues.
Further experiments showed that the antigens on the surface of apCAFs could convert immune cells called T-cells into a subset known as regulatory T-cells (Tregs), which shield tumors from immune attack. When the researchers dosed mice carrying pancreatic tumors with antibodies against mesothelin, a protein unique to mesothelial cells, the conversion to Tregs was blocked, leaving tumors more vulnerable to an anti-tumor immune response.
Although more research is necessary in animal models, Dr. Huang noted that it may eventually be possible to employ a similar strategy to treat PDA in humans by administering anti-mesothelin antibodies in combination with immunotherapies that stimulate the immune system to fight cancers.
Dr. Brekken, an Effie Marie Cain Research Scholar, noted that the study clarifies the origin and function of apCAFs in PDA but has implications beyond pancreatic cancer, an area that Dr. Huang will continue to investigate.
Other UTSW researchers who contributed to this study include Yuqing Zhang, Debolina Ganguly, Raghav Chandra, Gilbert Murimwa, Steven Wright, Xiaowu Gu, and Ravikanth Maddipati.
This study was funded by the National Institutes of Health (K99 CA252009, R01 CA243577 and U54 CA210181 Project 2), the Effie Marie Cain Fellowship, and the Jean Shelby Fund for Cancer Research at the Communities Foundation of Texas.

Researchers at the University of Missouri are applying a form of artificial intelligence (AI) — previously used to analyze how National Basketball Association (NBA) players move their bodies — to now help scientists develop new drug therapies for medical treatments targeting cancers and other diseases.
The type of AI, called a graph neural network, can help scientists with speeding up the time it takes to sift through large amounts of data generated by studying protein dynamics. This approach can provide new ways to identify target sites on proteins for drugs to work effectively, said Dong Xu, a Curators’ Distinguished Professor in the Department of Electrical Engineering and Computer Science at the MU College of Engineering and one of the study’s authors.
“Previously, drug designers may have known about a couple places on a protein’s structure to target with their therapies,” said Xu, who is also the Paul K. and Dianne Shumaker Professor in bioinformatics. “A novel outcome of this method is that we identified a pathway between different areas of the protein structure, which could potentially allow scientists who are designing drugs to see additional possible target sites for delivering their targeted therapies. This can increase the chances that the therapy may be successful.”
Xu said they can also simulate how proteins can change in relation to different conditions, such as the development of cancer, and then use that information to infer their relationships with other bodily functions.
“With machine learning we can really study what are the important interactions within different areas of the protein structure,” Xu said. “Our method provides a systematic review of the data involved when studying proteins, as well as a protein’s energy state, which could help when identifying any possible mutation’s effect. This is important because protein mutations can enhance the possibility of cancers and other diseases developing in the body.”
“Neural relational inference to learn long-range allosteric interactions in proteins from molecular dynamics simulations” was published in Nature Communications. Juexin Wang at MU; and Jingxuan Zhu and Weiwei Han at Jilin University in China, also contributed to this study. Funding was provided by the China Scholarship Council and the Overseas Cooperation Project of Jilin Province, which were used to support Jingxuan Zhu to conduct this research at MU, as well as the National Institute of General Medical Sciences of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Story Source:
Materials provided by University of Missouri-Columbia. Note: Content may be edited for style and length.

Polygenic risk scores (PRS) are promising tools for predicting disease risk, but current versions have built-in bias that can affect their accuracy in some populations and result in health disparities. However, a team of researchers from Massachusetts General Hospital (MGH), the Broad Institute of MIT and Harvard, and Shanghai Jiao Tong University in Shanghai, China, have designed a new method for generating PRS that more accurately predict disease risk across populations, which they report in Nature Genetics.
Alterations in a gene’s DNA sequence can produce a genetic variant that increases the risk for disease. Some genetic variants are closely linked to certain diseases, such as the BRCA1 mutation and breast cancer. “However, most common human diseases — such as type 2 diabetes, high blood pressure, and depression, for example — are influenced not by single genes, but by hundreds or thousands of genetic variants across the genome. Each variant contributes a small effect.” says Tian Ge, Ph.D., an applied mathematician and biostatistician in the Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine at MGH, and co-senior author of the paper. PRS aggregate the effects of genetic variants across the genome and have shown promise for one day being used to predict individual patients’ chances of developing diseases. That would allow clinicians to recommend preventive measures and monitor patients closely for early diagnosis and intervention.
However, a PRS must be “trained” to predict disease risk using data from studies in which genomic information is collected from large groups of individuals. While many disease-causing variants are shared, explains Ge, there are important differences in the genetic basis of a disease between individuals of different ancestries. For example, a common genetic variant that is associated with a specific disease in one population may have a lower frequency or even be missing in other populations. When a genetic variant linked to a disease is shared across different populations, its effect size, or how much it increases risk, may also vary from one ancestral group to another, explains Ge. PRS trained using data from one population therefore often have attenuated, or reduced, performance when applied to other populations.
“A major problem with existing methods for PRS calculation is that, to date, most of the genomic studies used data collected from individuals of European ancestry,” says Ge. That creates a Eurocentric bias in existing PRS, he says, producing substantially less-accurate predictions and raising the possibility that they could over- or underestimate disease risk in non-European populations.
Fortunately, investigators have increased efforts to collect genomic data from underrepresented populations. Leveraging these resources, Ge and his colleagues created a new tool called PRS-CSx that can integrate data from multiple populations and account for genetic similarities and differences between them. While there’s still significantly more genomic data on individuals of European ancestry, the investigators used computational methods that allowed them to maximize the value of non-European data and improve prediction accuracy in ancestrally diverse individuals.
In the study, the investigators used genomic data from individuals in several different populations to predict a wide range of physical measures (such as height, body mass index, and blood pressure), blood biomarkers (such as glucose and cholesterol), and the risk for schizophrenia. Then they compared the predicted trait or disease risk with actual measures or reported disease status to measure PRS-CSx’s prediction accuracy. The study’s results demonstrated that PRS-CSx is significantly more accurate than existing PRS tools in non-European populations.
“The goal of our work was to narrow the gap between the prediction accuracy in underrepresented populations relative to European individuals, and narrow the gap in health disparities when implementing PRS in clinical settings,” says Ge, who notes that the new tool will continue to be refined with the hope that clinicians may one day use it to inform treatment choices and make recommendations about patient care.
PRS-CSx could also have a role in basic research, says the study’s lead author, Yunfeng Ruan, Ph.D., a postdoctoral research fellow at the Broad Institute of MIT and Harvard. It could be used, for example, to explore gene-environment interactions, such as how the effect of genetic risk would depend on the level of environmental risk factors in global populations.
Even with PRS-CSx, the gap in prediction accuracy between European and non-European populations remains considerable. Broadening the sample diversity across global populations is crucial to further improve the prediction accuracy of PRS in diverse populations. “The expansion of non-European genomic resources, coupled with advanced analytic methods like PRS-CSx, will accelerate the equitable deployment of PRS in clinical settings,” says Hailiang Huang, Ph.D., a statistical geneticist in the Analytic and Translational Genetics Unit at MGH and the Stanley Center for Psychiatric Research at the Broad Institute, and co-senior author of the paper.
Ge is also an assistant professor of Psychiatry at Harvard Medical School (HMS). Huang is an assistant professor of Medicine at HMS.
This work was supported by the National Institute on Aging, National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Mental Health, the Brain & Behavior Research Foundation, the Zhengxu and Ying He Foundation, and the Stanley Center for Psychiatric Research.

Screening for colorectal cancer (CRC) in women before the age of 50 can significantly reduce the risk of CRC compared to those who have no endoscopic screening or decide to initiate testing at age 50, according to a new study from Massachusetts General Hospital (MGH). These findings, published in JAMA Oncology, support recommendations from the American Cancer Society and the US Preventive Services Task Force over the past four years to commence screening at age 45 to address the steady increase in cases of younger-onset CRC.
“While there’s been an alarming increase in the incidence of colorectal cancer in recent decades in younger individuals, screening has largely been focused on people over 50,” says Andrew Chan, MD, MPH, a gastroenterologist and epidemiologist at MGH, and senior author of the study. “Our work provides first-of-its-kind data to show that initiating screening at a younger age can reduce an individual’s risk of colorectal cancer and the population’s overall incidence of cancer, thus demonstrating the substantial impact of earlier screening on both individual and population-wide scales.”
Among all cancers, colorectal has the third highest incidence of death in both men and women in the U.S. Even as the overall number of CRC cases has declined, the incidence among people younger than 50 — a group for whom routine screening was not recommended until only recently — increased by 51 percent from 1974 to 2013, according to epidemiological data. To evaluate the association between CRC risk and endoscopies initiated at different ages, MGH conducted a comprehensive study that included 111,801 women from the Nurses’ Health Study II, a large cohort of registered nurses residing in 14 states.
Researchers found a 50 to 60 percent lower risk of CRC among women who started endoscopy screening at age 45 compared to those who had not undergone screening at all. In addition, they learned that starting screening at ages 45 to 49 resulted in a significant reduction in the population’s actual cases of CRC diagnosed through age 60, compared to a strategy in which women began screening at ages 50 to 54. While the study was focused on women, Chan suggests the same benefits likely accrue to men, though he adds further studies are needed.
The traditional CRC screening tool is the colonoscopy, where a physician uses a flexible tube with a camera to examine the colon and rectum. This invasive technique allows for removal of polyps that could over time become malignant, and for detection of early-stage cancers that can be treated more effectively. Options for screening have expanded more recently through stool-based tests that are non-invasive and may be more convenient for individuals.
Chan points to the substantial public health implications of his team’s research. “Any trepidation that clinicians might have had about the effectiveness of CRC screening at a younger age will hopefully be allayed by these results,” he says. “Our data show that we have an effective tool to address the epidemic of colorectal cancer among younger adults, and hopefully this will encourage physicians to have a conversation about screening with their younger patients which, in turn, will motivate them to follow through and get screened.”
Chan is chief of the Clinical and Translational Epidemiological Unit at MGH, and director of Epidemiology, Mass General Cancer Center, and the Daniel K. Podolsky Professor of Medicine. Lead author Wenjie Ma, ScD is an instructor in Medicine, and co-senior author Mingyang Song, MD, is assistant professor of Medicine, both in the Clinical and Translational Epidemiology Unit at MGH.
The study was funded by the National Cancer Institute and National Institutes of Health.
Story Source:
Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

One recipe for longevity is simple, if not easy to follow: eat less. Studies in a variety of animals have shown that restricting calories can lead to a longer, healthier life.
Now, new research suggests that the body’s daily rhythms play a big part in this longevity effect. Eating only during their most active time of day substantially extended the lifespan of mice on a reduced-calorie diet, Howard Hughes Medical Institute Investigator Joseph Takahashi and colleagues report May 5, 2022, in the journal Science.
In his team’s study of hundreds of mice over four years, a reduced-calorie diet alone extended the animals’ lives by 10 percent. But feeding mice the diet only at nighttime, when mice are most active, extended life by 35 percent. That combo — a reduced-calorie diet plus a nighttime eating schedule — tacked on an extra nine months to the animals’ typical two-year median lifespan. For people, an analogous plan would restrict eating to daytime hours.
The research helps disentangle the controversy around diet plans that emphasize eating only at certain times of day, says Takahashi, a molecular biologist at the University of Texas Southwestern Medical Center. Such plans may not speed weight loss in humans, as a recent study in the New England Journal of Medicine reported, but they could prompt health benefits that add up to a longer lifespan.
Takahashi’s team’s findings highlight the crucial role of metabolism in aging, says Sai Krupa Das, a nutrition scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging who was not involved with the work. “This is a very promising and landmark study,” she says.
Fountain of youth
Decades of research has found that calorie restriction extends the lifespan of animals ranging from worms and flies to mice, rats, and primates. Those experiments report weight loss, improved glucose regulation, lower blood pressure, and reduced inflammation.

Whether it’s making rash decisions or feeling grumpy, hunger can make us think and act differently — “hangry,” even. But little is known about how hunger signals in the gut communicate with the brain to change behavior. Now, Salk scientists are using worms as a model to examine the molecular underpinnings and help explain how hunger makes an organism sacrifice comfort and make risky decisions to get a meal.
Their latest findings, published in PLOS Genetics on May 5, 2022, reveal that proteins in intestinal cells move dynamically to transmit signals about hunger, ultimately driving worms to cross toxic barriers to reach food. Similar mechanisms may also occur in humans.
“Animals, whether it’s a humble worm or a complex human, all make choices to feed themselves to survive. The sub-cellular movement of molecules could be driving these decisions and is maybe fundamental to all animal species,” says senior author Sreekanth Chalasani, associate professor in Salk’s Molecular Neurobiology Laboratory.
Chalasani and team used a tiny worm called Caenorhabditis elegans as a model to determine how hunger leads to behavioral changes. The researchers created a barrier of copper sulfate, which is a known worm repellant, between the hungry wormsand a food source. They observed that if the worms were deprived of food for two-to-three hours, then they were more willing to traverse the toxic barrier compared to well-fed worms.
Using genetic tools and imaging techniques, the researchers then investigated the gut molecules that might be sending signals to the brain. They found that specific transcription factors, proteins that turn genes “on” and “off,” shifted locations in hungry animals. Normally, transcription factors hang out in the cell’s cytoplasm and move into the nucleus only when activated — similar to the way we live at home but go into the office to get work done.
The team was surprised to discover that these transcription factors, called MML-1 and HLH-30, move back to the cytoplasm when the worm is hungry. When the scientists deleted these transcription factors, hungry worms stopped trying to cross the toxic barrier. This indicates a central role for MML-1 and HLH-30 in controlling how hunger changes animal behavior.
In a follow-up experiment, the researchers also discovered that a protein called insulin-like peptide INS-31 is secreted from the gut when MML-1 and HLH-30 are on the move. Neurons in the brain, in turn, make a receptor that might detect the INS-31secretions.
To sum it up: A lack of food leads to movement of MML-1 and HLH-30, which could promote the secretion of INS-31. INS-31 peptides then bind receptors on neurons to relay hunger information and drive risky food-seeking behavior.
“C. elegans are more sophisticated than we give them credit for,” says co-first author Molly Matty, a postdoctoral fellow in Chalasani’s lab. “Their intestines sense a lack of food and report this to the brain. We believe these transcription factor movements are what guide the animal into making a risk-reward decision, like traversing an unpleasant barrier to get to food.”
Next, the scientists will further investigate the dynamic nature of these transcription factors and underlying mechanisms. With further work, these findings could provide insight into how other animals, such as humans, prioritize basic needs over comfort.
This work was supported by the Rita Allen Foundation, W.M. Keck Foundation, National Institutes of Health (grant R01MH096881), National Science Foundation (postdoctoral research fellowship 2011023 and two graduate research fellowships), Glenn Foundation and Socrates Program (grant NSF-742551).
Story Source:
Materials provided by Salk Institute. Note: Content may be edited for style and length.

Two-thirds of working parents surveyed met the criteria for parental burnout. Here’s how to spot the signs — and get help.For two years, working parents in America have been running on fumes, hammered by the stress of remote schooling, day care closures, economic instability and social isolation.Now, a new report says that 66 percent of working parents meet the criteria for parental burnout — a nonclinical term that means they are so exhausted by the pressure of caring for their children, they feel they have nothing left to give.The report, published Thursday by researchers with Ohio State University, is based on an online survey of 1,285 working parents that was conducted between January 2021 and April 2021. It gives a snapshot of a different time, when America was deep in pandemic lockdownsBut its authors believe parental burnout is here to stay, because working parents don’t have enough practical, structural supports to overcome the relentless stress, which isn’t abating. Any parent can experience burnout, but the new report focuses on working parents, who, the researchers believe, are at particular risk for exhaustion.“Parental burnout isn’t just going to end magically when the pandemic finally ends,” said Bernadette Melnyk, dean of the College of Nursing at Ohio State and an author of the report. “The chronicity of the pandemic has taken a toll and depleted many parents’ coping reserves that will take time and patience to build up again.”What are the signs of parental burnout?Parental burnout isn’t a clinical diagnosis that would end up in anyone’s medical chart, but many psychologists recognize it as a subtype of burnout — a work-related phenomenon now recognized as a syndrome by the World Health Organization. (It is not included in the DSM-5, often called the “bible” of psychiatry in the United States.)“As with burnout, parental burnout is defined as physical, emotional and mental exhaustion due to the ongoing demands of caring for one’s children,” said Dr. Jennifer Yen, a psychiatrist at UTHealth Houston.Of course, raising children is demanding in all those ways, which makes it difficult to draw a clear line between normal periods of stress and burnout. Dr. Yen said parents should be on the lookout for signs like fatigue, irritability, changes in sleep, appetite and mood, or aches and pains. What sets parental burnout apart is how severe those symptoms are, as well as how much they affect daily functioning.“It’s a state where you have been giving, and giving, and giving and giving — until you’re totally empty,” said Kate Kripke, a clinical social worker and the founder of the Postpartum Wellness Center in Boulder, Colo.Dr. Yen also noted other red flags that are specific to parental burnout, like feeling angry or resentful about having to care for your children, and starting to isolate from them physically or emotionally. Parents with burnout may also feel trapped or fantasize about leaving, she added.Though the new report may be useful to clinicians, the researchers wrote it directly for working parents. It includes a new burnout scale they hope parents will use to gauge how they are doing, which includes 10 statements such as: “I wake up exhausted at the thought of another day with my children” or “I feel like I am in survival mode as a parent.” Parents can agree or disagree with each on a scale from “not at all” to “very much so.” They are then given a final score that can help indicate whether they have what the researchers would consider to be mild, moderate or severe burnout.What to do about parental burnoutNo matter where working parents fall on that spectrum, it may be helpful for them to first acknowledge that many of the challenges they’re facing are beyond their control. It is impossible to be a dedicated employee and a dedicated caregiver simultaneously without adequate support. Self-compassion is important, Dr. Melnyk said.But parents facing mild burnout may be able to make immediate changes that will prevent more severe exhaustion. Find small ways to ask for help, the researchers say. If you are able, ask a family member or neighbor to pitch in with child care, even if it’s just to give you a short break. If you’re responsible for getting your children to and from school, activities and play dates, find others to car pool with so you aren’t running yourself ragged.The report found that 68 percent of working moms say they’re burned out compared with 42 percent of working dads, so it may be especially important for women to take breaks and ask for help — though that may not be simple or easy.Stressed-out parents may also find it helpful to tap into a sense of quiet and calm by practicing mindfulness. Research shows that mindfulness can help reduce parental stress, which may in turn help improve children’s psychological outcomes. It can be as simple as intentionally feeling the bottom of your foot on the floor and taking a deep breath, Ms. Kripke said.But breathing alone won’t solve this. Parents with more serious burnout should reach out to a primary care practitioner or mental health provider immediately. They can screen for issues like anxiety and depression. (If you are unsure how to find a mental health provider, it may be helpful to start by searching free online directories, like Alma, ZocDoc, Monarch or Headway.)Keep in mind that some mental health providers feel conflicted about the notion of parental burnout.“This is the first I’m hearing of the term,” said Dr. Catherine Birndorf, the C.E.O. and medical director of the Motherhood Center in New York City. She said she likes the concept, and the idea of a parental burnout scale, if they help parents who wouldn’t otherwise recognize they are struggling. But she worries that some parents may write off what they’re experiencing as burnout, instead of getting treated for an underlying condition like anxiety or depression.Dr. Birndorf also emphasized that the onus should not be solely on parents to recognize — and manage — their own burnout. They have been stuck in a situation she called “untenable,” caused not just by the pandemic, but also by a longstanding gap in policies that would offer working parents the day-to-day support they need.“The issues are systemic,” Dr. Birndorf said. “Burnout is happening in the context of a national crisis, which is about paid parental leave and universal child care. Without those things, what are we supposed to do?”

SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesThe US is approaching one million Covid deaths – the highest total officially recorded anywhere in the world.But a new report from the World Health Organization (WHO) shows several other countries recorded more deaths above their normal levels than the US over the last two years.So does the US really have the highest Covid death toll, and by what measure? US deaths above global averageThere’s no international standard for measuring deaths or their causes, and countries record deaths in different ways, which makes comparison difficult.But experts say one of the most accurate measures is how many extra deaths are recorded in a country above the number that would have been expected to die in an average year.Many countries publish excess death data, but some poorer nations don’t or do it far less frequently.The WHO has published a report calculating every country’s excess death count for 2020 and 2021.This measure takes into account deaths not directly due to Covid, but as a consequence of the pandemic, such as people being unable to access hospitals for the care they needed.It also accounts for poor record-keeping in some regions.The report concludes that, although the US was not the worst hit country in the world by this measure, it remained in the top five in terms of overall numbers of deaths.According to the WHO, in 2020 and 2021 the US recorded more than 930,000 excess deaths, behind India (4.7m), Russia (1.1m) and Indonesia (1m).The WHO’s numbers are largely consistent with statistics from the Economist which run into 2022, as well as other excess death studies.When adjusted for population size, the US slips down the rankings with 140 excess deaths per 100,000 people. But it remains a long way above the global average of 96 per 100,000 – and it’s also one of the worst performing among the most developed nations. Prabhat Jha, an epidemiologist who worked on the WHO report, says: “The US has about a 15% undercount using excess deaths compared to official Covid deaths – that’s mostly a result of some of the early problems that occurred with nursing home deaths being missed.””On the whole the US isn’t missing many deaths compared with, say, India,” he adds.WHO: India’s Covid-19 toll highest in the worldWhat about the official Covid death numbers?The US has recorded the most deaths from coronavirus in the world – over 300,000 more than the next closest country, Brazil.But the US has a larger population than many other countries.When you look at the same top 10 countries in per capita terms, the US is below both Brazil and Peru for recorded Covid deaths.Overall the US ranks 18th in the world in recorded Covid deaths per capita, according to Johns Hopkins University data.”Short term I think the per capita confirmed death rate is a pretty good indicator” says Justin Lessler, professor of epidemiology at the University of North Carolina.”The US is not the highest, but it’s certainly on the higher end.”Experts say it’s also important to take the average age of a country’s population into account.”We should compare with countries which have similar age structures as we know Covid has a higher fatality rate in the elderly – so we should compare apples to apples,” says Bhramar Mukherjee, professor of epidemiology at the University of Michigan.When comparing with Spain, UK, and France, as well as neighbouring Canada – developed countries with similarly aged populations to the US – the US has performed worse.”A lot of the European countries – like the UK, France and Spain – are reasonable to compare, and they’ve had lower per capita death rates. It’s not night and day, but the US is on the upper end of that spectrum,” says Professor Lessler.Read more from Reality CheckSend us your questions

In a prospective study of young, lean adults, PET/CT imaging revealed that higher levels of active brown adipose tissue (also known as “brown fat”) are more prevalent in individuals who exhibit very early indications of metabolic disorders. Published ahead of print in The Journal of Nuclear Medicine, the study suggests that active brown fat is recruited to counteract “pre-prediabetic” states, potentially serving as a first-line protective mechanism against very early metabolic or hormonal abnormalities.
Brown fat is a type of fat that is activated when a person gets cold, producing heat to warm the body. The presence of brown fat was initially recognized on oncologic FDG PET/CT scans, which are now the most commonly used technique for the in vivo detection of brown fat. Studies using PET with FDG and/or other fatty-acid tracers have demonstrated that brown fat consumes glucose and fatty acids, making it a potential target for the treatment of obesity and other metabolic disorders.
“The primary aim of this study was to assess if there are differences in baseline glucose, insulin, lipid, and other metabolite levels between subjects with varying amounts of brown fat. We also examined patient blood samples and lifestyles to assess their association with brown fat levels,” noted John P. Crandall, BS, clinical research coordinator at the Mallinckrodt Institute of Radiology at Washington University School of Medicine in St. Louis, Missouri.
Thirty-four healthy adult volunteers between the ages of 18 and 35 and with a body mass index (BMI) between 18 and 25 were enrolled in the study. Blood samples were taken, and lifestyle interviews were performed. To activate the brown fat, participants wore cooling suits to bring their body’s temperature to just above the shivering point. After two hours, subjects removed the cooling suits and were imaging with FDG PET/CT. Post-cooling blood samples were also taken after removal of the cooling suits.
Activated brown fat was analyzed for each subject, and glucose, insulin, lipid and other metabolite levels were correlated with volume and intensity of the active brown fat. Using a median cut-off, participants were classified as having high brown fat levels or low brown fat levels.
A higher level of activated brown fat was associated with early metabolic dysfunction. Pre-cooling glucose, insulin, thyroid stimulating hormone and triglyceride levels were significantly higher in the high brown fat group than the low brown fat group. In addition, a significant difference in BMI was found, with subjects with high brown fat levels having a higher BMI than subjects with low levels of brown fat. Those with low brown fat levels were more likely to report observing a controlled diet and exercising regularly.
“Our study suggests brown adipose tissue may considerably influence (and be influenced by) overall metabolic health. Molecular imaging with FDG remains the most useful non-invasive method for studying brown fat in humans,” said Richard L. Wahl, MD, FACR, director of the Mallinckrodt Institute of Radiology and chair of the Department of Radiology at Washington University School of Medicine. “Our findings show that molecular imaging potentially may be useful for identifying patients who are at risk of developing metabolic disorders and suggests activation of brown fat is a metabolic coping mechanism in ‘pre-pre-diabetes.’ Further studies in larger populations are warranted to confirm and expand upon our findings.”
This study was made available online in April 2022.
Story Source:
Materials provided by Society of Nuclear Medicine and Molecular Imaging. Note: Content may be edited for style and length.

The human body consists of trillions of cells that constantly communicate with each other. A central role in this communication process is played by receptor proteins on the cell surface. Since they often serve as drug targets, they have been the subject of intensive research. Often there are whole families of receptors. The signal messengers as well as the receptors are very similar to each other, so it is not clear how the signals are distinguished from each other at the molecular level. Now, in a joint research project, scientists from Collaborative Research Centre 1423 at Leipzig University, the Hangzhou Institute for Advanced Study and the Chinese Academy of Sciences in Shanghai have succeeded in determining high-resolution structures for three related signalling complexes that occur naturally in the body for the neuropeptide Y (NPY) receptor family, thus shedding light on the “small but essential differences.”
The NPY family consists of a total of three related peptide ligands: NPY, PP and PYY, which have different functions in the body. These act as messengers both locally in the tissues, especially in the brain, and via the bloodstream. They bind to four different receptors (Y1R, Y2R, Y4R and Y5R), with different combinations of peptide ligand and receptor occurring in different situations: while NPY in conjunction with Y1R signals hunger in the brain, PP bound to Y4R conveys a strong satiety signal. NPY receptors are also of interest for modern cancer therapies. A high number of Y1R is characteristic for breast cancer cells, which is why NPY variants that selectively bind only to this receptor could be used to deliver drugs specifically to these cells. Healthy breast tissue, on the other hand, contains mainly the receptor Y2R. It would make sense to ‘bypass’ this in order to spare the healthy tissue.
To be able to develop targeted active substances, it is therefore highly important to know the molecular blueprint of these complexes and the underlying regulatory mechanisms. In addition to the molecular structures visualised by Professor Qiang Zhao from the Hangzhou Institute for Advanced Study and Professor Beili Wu of the Chinese Academy of Sciences using cryogenic electron microscopy, Professor Annette Beck-Sickinger and Dr Anette Kaiser of Leipzig University conducted biochemical studies that shed more light on the complex mechanisms that bind the peptides to their receptors and supported the results of the structural studies. It was possible to find the relevant regions in the peptides and receptors in the complex.
The working groups have been conducting joint research in this field for over ten years, and these new results build on extensive preliminary work. This makes this joint publication — the third by the working groups — all the more valuable. This is because a novel test system showed that the peptides use different ‘docking pathways’ and that this can lead to different signals in the cell. The flexibility and mobility of the complexes in certain areas plays an important role. Professor Annette Beck-Sickinger explains: “Some of the flexibility of the peptide and receptor is thus retained even in the bound state. The causes and consequences of this are now being further investigated in ongoing studies in CRC 1423, as is the question of what other factors influence the recognition between peptides and receptors.”
The investigation of this NPY receptor family with its endogenous ligands as well as other clinically relevant compounds is one focus of Collaborative Research Centre 1423. It is a research project being funded for four years by the German Research Foundation (DFG), in which four institutions are involved: Leipzig University, the Martin Luther University Halle-Wittenberg, Charité — Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine in Berlin. Researchers from these institutions with backgrounds in biochemistry, biomedicine and computational science are collaborating on an interdisciplinary basis to gain a comprehensive understanding of the effects of structural dynamics on the GPCR function. The latest findings and approaches in GPCR research will also be presented at 4GPCRnet ’22, an international conference co-organised by CRC 1423. This high-level meeting will take place on the Leipzig University company at Augustusplatz from 26 to 29 September 2022.
Story Source:
Materials provided by Universität Leipzig. Original written by Susann Huster. Note: Content may be edited for style and length.