Publisher Health

Mayo Clinic researchers mapped how the measles virus mutated and spread in the brain of a person who succumbed to a rare, lethal brain disease. New cases of this disease, which is a complication of the measles virus, may occur as measles reemerges among the unvaccinated, say researchers.
Using the latest tools in genetic sequencing, researchers at Mayo Clinic reconstructed how a collective of viral genomes colonized a human brain. The virus acquired distinct mutations that drove the spread of the virus from the frontal cortex outward.
“Our study provides compelling data that shows how viral RNA mutated and spread throughout a human organ — the brain, in this case,” says Roberto Cattaneo, Ph.D., a Mayo Clinic virologist who is a co-lead author on a new PLOS Pathogens study. “Our discoveries will help studying and understanding how other viruses persist and adapt to the human brain, causing disease. This knowledge may facilitate the generation of effective antiviral drugs.”
What is measles?
Measles is one of the most contagious diseases. The measles virus infects the upper respiratory tract where it uses the trachea, or windpipe, as a trampoline to launch and spread through droplets dispersed when an infected person coughs or sneezes.
Dr. Cattaneo pioneered studies on how the measles virus spreads throughout the body.
He first began to study the measles virus about 40 years ago and was fascinated by the rare, lethal brain disease called subacute sclerosing panencephalitis (SSPE), which occurs in about 1 in every 10,000 measles cases. It can take about five to 10 years after the initial infection for the measles virus to mutate and spread throughout the brain. Symptoms of this progressive neurological disease include memory loss, seizures and immobility. Dr. Cattaneo studied SSPE for several years until the lethal disease nearly disappeared as more people were vaccinated against measles.

However, measles is resurging due to vaccine hesitancy and missed vaccinations. During the COVID-19 pandemic, millions of children missed receiving their measles vaccinations, which has resulted in an estimated 18% increase in measles cases and 43% increase in death from measles in 2021 compared to 2022 worldwide, according to a recent Centers for Disease Control and Prevention (CDC) report.
“We suspect SSPE cases will rise again as well. This is sad because this horrible disease can be prevented by vaccination. But now we are in the position to study SSPE with modern, genetic sequencing technology and learn more about it,” says Iris Yousaf, co-lead author of the study and a fifth-year Ph.D. candidate at Mayo Clinic Graduate School of Biomedical Sciences.
Dr. Cattaneo and Yousaf had a unique research opportunity through a collaboration with the CDC. They studied the brain of a person who had contracted measles as a child and had succumbed to SSPE years later as an adult. They investigated 15 specimens from different regions of the brain and conducted genetic sequencing on each region to piece together the puzzle of how the measles virus mutated and spread.
The researchers discovered that, after the measles virus entered the brain, its genome — the complete set of genetic material for the virus — began to change in harmful ways. The genome replicated, creating other genomes that were slightly different. Then, these genomes replicated again — resulting in more genomes that were each a little different as well. The virus did this multiple times, creating a population of varied genomes.
“In this population, two specific genomes had a combination of characteristics that worked together to promote virus spread from the initial location of the infection — the frontal cortex of the brain — out to colonize the entire organ,” says Dr. Cattaneo.
The next steps in this research are to understand how specific mutations favor virus spread in the brain. These studies will be done in cultivated brain cells and in clusters of cells resembling the brain called organoids. This knowledge may help in creating effective antiviral drugs to combat virus spread in the brain. However, pharmacological intervention in advanced disease stages is challenging. Preventing SSPE through measles vaccination remains the best method.

Through an international collaboration, scientists at St. Jude Children’s Research Hospital leveraged data science, pharmacology and structural information to conduct an atomic-level investigation into how each amino acid in the receptor that binds adrenaline contributes to receptor activity in the presence of this natural ligand. They discovered precisely which amino acids control the key pharmacological properties of the ligand. The adrenaline receptor studied is a member of the G protein-coupled receptor (GPCR) family, and this family is the target of one-third of all Food and Drug Administration (FDA)-approved drugs. Thus, understanding how GPCRs respond to natural or therapeutic ligands is critical for developing new therapies with precise effects on receptor activity. The work was published today in Science.
To understand how a watch works, one might take it apart, piece by piece, and study the role played by each component in its timekeeping function. Similarly, in a protein such as a GPCR, each amino acid might play a different role in how the protein responds to an external signal. Researchers at St. Jude, in collaboration with scientists from Stanford University, the University of Montreal, the MRC Laboratory of Molecular Biology and Cambridge University, investigated the β2-adrenergic receptor (β2AR) by substituting one amino acid at a time to understand the contribution of each amino acid in this receptor to mediate a signaling response.
“Scientists learn how genes contribute to cell function by disrupting them one at a time. We asked, ‘Why don’t we take this one level deeper? Let’s understand how every amino acid contributes to the functioning of a receptor by mutating them, one amino acid at a time,'” said co-corresponding author M. Madan Babu, PhD, from St. Jude’s Department of Structural Biology, Center of Excellence for Data-Driven Discovery director and the George J. Pedersen Endowed Chair in Biological Data Science. “Through evolution, every amino acid in the receptor has been sculpted in some way or another to ensure that it binds the natural ligand, in this case adrenaline, and elicits the appropriate physiological response.”
Finding function in the form
GPCRs are proteins that span the cell’s membrane and connect the outside of the cell to its internal environment by transmitting external signals to the inside of the cell. In the case of the β2AR, adrenaline binds to the GPCR on the part outside of the cell, inducing a response inside the cell.
When a ligand binds, it causes changes in the shape of the receptor, especially in the intracellular region of the receptor where a G protein binds. The binding sites for the ligand and the G protein are on opposite sides of the protein but connect through a complex network of amino acid contacts that span the entire protein. Conformational (shape) changes within the GPCR activate the G protein to trigger a downstream signaling response within the cell. Through effects on multiple tissues and GPCRs, including the β2AR, adrenaline can trigger the fight-or-flight response, such as during an adrenaline surge.
To understand the role of each amino acid in a GPCR, Franziska Heydenreich, PhD, now of the Philipps University of Marburg, the lead and co-corresponding author of this project, mutated each of the 412 amino acids in the β2AR. She then evaluated each mutant’s response to the ligand adrenaline and determined the classical pharmacological properties of efficacy and potency. Efficacy measures the maximum response a ligand can elicit, and potency measures the amount of ligand required to elicit half of the maximum response. The aim was to reveal, on an atomic scale, how each amino acid contributes to these pharmacological properties.

“Surprisingly, only about 80 of the more than 400 amino acids contributed to these pharmacological properties. Of these pharmacologically relevant amino acids, only one-third were located within regions where the ligand or G protein bound to the receptor,” Heydenreich said.
“It was fascinating to observe that there are some amino acids that control efficacy, some that control potency and then there are others that affect both,” Babu said. “It means if you want to make a more potent or efficacious drug, you now know there are specific residues that the new ligand needs to influence.” The researchers also noted that the individual contribution of each residue to efficacy and potency was not equal, implying even more opportunities for fine-tuning drug responses while designing new therapeutic ligands.
“Efficacy and potency have been measured for numerous ligand-receptor signaling systems for several decades. Now we can understand how specific amino acids in a protein’s sequence can influence these pharmacological properties,” Babu explained.
“A fascinating aspect of the results is that potency and efficacy can be regulated independently of each other through distinct mechanisms. This provides a basis for understanding how genetic variation influences drug responses among individuals,” Michel Bouvier, PhD, co-corresponding author from the Department of Biochemistry and Molecular Medicine and General Director of the Institute for Research in Immunology and Cancer of the University of Montreal added.
A beautiful network
Prior research illustrated the structure of both the active and inactive states of the β2AR. Building on this knowledge, the researchers embarked on a new investigation. They explored whether the two-thirds of pharmacologically relevant amino acids previously demonstrated to be not involved in ligand or G-protein binding might play a role in the transition between the active and inactive states of the receptor.

“We systematically started looking at every residue contact unique to the active state,” Heydenreich said, “to understand whether all the amino acids that make an active-state contact are important.”
The researchers developed a data science framework to integrate pharmacological and structural data systematically and revealed the first comprehensive picture of GPCR signaling. “When we mapped the pharmacological data onto the structure, they formed a beautiful network,” said Babu.
“It provided new insights into the allosteric network linking the ligand binding pocket to the G protein binding site that governs efficacy and potency.” Added Brian Kobilka, co-corresponding author and the 2012 Nobel Prize winner in Chemistry from Stanford University School of Medicine.
By understanding GPCR signaling at the atomic level, the researchers are optimistic that they can begin probing even deeper — to see the transient sub-states between the active and inactive conformations and to explore the conformational landscape of proteins.
“We now know which mutants to go after, those that only affect efficacy, potency or both,” Heydenreich said.
“Now, we can perform molecular dynamics calculations and single-molecule experiments on those mutants to reveal the exact mechanisms by which the allosteric network influences efficacy and potency to mediate a signaling response. This is a direction we are pursuing through a St. Jude Research Collaborative on GPCRs that includes PIs from several institutions.” Babu explained.
Apart from these “driver” residues that are involved in mediating active state-specific contacts and affect pharmacology when mutated, Babu and his colleagues intend to probe other key findings revealed by this work. They aim to study “passenger” amino acids that, despite making contacts in the active state, do not affect efficacy or potency when mutated. They are also interested in “modulator” residues that don’t mediate active state-specific contacts but alter pharmacology when mutated. Their data science approach, integrating structural information and pharmacological measurements, isn’t limited to the β2AR. It can be extended to any GPCR to enhance our understanding of the mechanics governing this crucial class of drug targets.

Insights into how uterine tumors grow could give hope to millions of women who deal with painful fibroids.
Nearly 8 in 10 women develop fibroids, noncancerous tumors that develop in the uterus during child-bearing years. They can be extremely painful, cause extensive bleeding and lead to infertility.
Researchers at the University of Cincinnati found different signaling pathways being used by the fibroid cells compared to the uterine cells.
“That’s important for identifying therapeutic targets because we want to target the tumor without affecting the surrounding tissue,” said Stacey Schutte, an assistant professor of biomedical engineering in UC’s College of Engineering and Applied Science.
The study was published in the journal F&S Science.
Treating fibroids is often invasive and expensive, costing patients and their insurers billions of dollars each year, according to the National Institutes of Health. Treatments can often lead to infertility as well, Schutte said.
“One in nine women will have a hysterectomy in their lifetime. And one-third to one-half of those are [because of] uterine fibroids,” Schutte said.

Schutte has experience in this research field. She was a postdoctoral fellow at the Emory University School of Medicine’s Department of Gynecology and Obstetrics.
“It usually isn’t life-threatening, but the pain can be immense,” she said. “Contractions push the tumors into the muscle tissue.”
During each menstrual cycle, the body releases estrogen and progesterone, which causes the tissue lining inside the uterus to thicken in anticipation of possible pregnancy. These hormones also help fibroids grow.
But Schutte said cells likewise can react to physical strain — like a defense mechanism to protect the cells.
UC researchers grew fibroid cells and uterine cells on plates with an elastic bottom. Then they used a device to expose the cells to mechanical strain to mimic the environment that fibroids encounter in the uterus.
“We have a flexible tension device. We grew cells on plates with an elastic bottom. Then we used a vacuum to pull and stretch it,” Schutte said. “It stretches cells in a single direction.”
“We found that fibroid cells were more sensitive to strain,” said study lead author Rachel Warwar, MD, in UC’s College of Medicine.

Warwar said they identified differences in the ways the cells held their shape.
Warwar works in UC’s Department of Obstetrics and Gynecology. She said the findings highlight the importance of incorporating not just hormones but mechanical strain into the study of fibroid cells.
“The more we are able to mimic the environment of these cells in the uterus, the more we will understand the pathology of these cells and can then work to target anomalous pathways in fibroid cells,” she said.
Nearly 4 in 5 women have fibroids during their lifetimes. Because they are so common, they represent a major health care cost — as much as $9 billion per year in the United States.
Common noninvasive treatments target hormones responsible for fibroid growth.
“We are looking for nonhormonal treatments for fibroids,” said study coauthor Andreja Moset Zupan, a research associate in Schutte’s biomedical engineering lab.
“It’s another option we could use to preserve the fertility of women who still want to get pregnant,” she said.
Once researchers understand the cell pathology, Warwar said, they can study fibroids using 3D simulations and modeling, which could help them further understand how fibroids develop and the best ways to treat them.
Schutte said the next step is to create more complex tissue models to mimic tumor growth to learn ways to inhibit it.
“It makes me really happy to think we can find a target.”

A new methodology that allows for the categorisation and organisation of single-cell data has been launched. It can be used to create a harmonised dataset for the study of human health and disease.
Researchers at the Wellcome Sanger Institute, the University of Cambridge, EMBL’s European Bioinformatics Institute (EMBL-EBI), and collaborators developed the tool, known as CellHint. CellHint uses machine learning to unify data produced across the world, allowing it to be accessed by the wider research community, potentially driving new discoveries.
In a new study, published today (21 December) in Cell, researchers applied CellHint to reveal underexplored connections between healthy and diseased lung cell states. They looked at eight diseases, such as interstitial lung disease and chronic obstructive pulmonary lung disease, and showed the possible benefits of this tool. They also applied CellHint to 12 tissues from 38 datasets, providing a deeply curated cross-tissue database with around 3.7 million cells.
Cellhint is freely available worldwide and was created as part of the Human Cell Atlas initiative1 which aims to map every cell type in the human body to transform understanding of health and disease.
Single-cell genomics enables the understanding of every cell in the context of the human body at high resolution. Currently, a challenge in assembling the diverse datasets produced by single-cell research is that there is no unified system for naming and organising data.
To address this, researchers from the Wellcome Sanger Institute, and collaborators developed CellHint, which can unify cell types produced by independent laboratories. CellHint then places the data into a defined graph that shows the relationships between cell subtypes, giving a full picture of all the cells identified across different datasets.
The team applied CellHint to current data and revealed underexplored relationships between healthy and diseased lung cell states in eight diseases. It also identified cell types in adult human hippocampus that could be of potential interest for future research.
The researchers also applied CellHint to 12 tissues from 38 datasets, providing a deeply curated cross-tissue database with around 3.7 million cells. Each cell was annotated, which is the process of labelling cells with particular information. They also showed how it can create various models for automatic cell annotation across human tissues.
Dr Chuan Xu, first author from the Wellcome Sanger Institute, said: “CellHint stands out from other tools because it makes full use of the often inconsistent but valuable cell annotation information from individual studies, to achieve biologically-driven data integration. We are excited that with CellHint, cells from independent laboratories can be re-annotated and researchers can utilise the resulting information to put each cell into different contexts beyond the original study. We hope that this tool will greatly facilitate the reuse of molecular and cellular data and information across laboratories, potentially driving new discoveries in biology.”
Dr Sarah Teichmann, senior author from the Wellcome Sanger Institute and co-founder of the Human Cell Atlas, said: “The Human Cell Atlas is creating detailed reference maps of all cells in the human body to transform our understanding of biology, health and disease, and single-cell technologies underpin this hugely ambitious project. Global collaboration and open data sharing are vital to achieve the aim of a representative Human Cell Atlas that will benefit humanity worldwide. CellHint enables the unification and sharing of single-cell data, which allows the global research community to contribute to and benefit from the ongoing research that is happening around the world, and help drive advances in health and healthcare.”

Back in 2018, the lab of Christine Mayr, MD, PhD, at Memorial Sloan Kettering Cancer Center (MSK) introduced the world to a key cellular component that had been hiding in plain sight.
Now the lab is back with important results that build on that discovery. New findings published in Molecular Cell provide details about the hidden organization of the cytoplasm — the soup of liquid, organelles, proteins, and other molecules inside a cell. The research shows it makes a big difference where in that cellular broth that messenger RNA (mRNA) get translated into proteins.
“You know the old real estate saying, ‘location, location, location.’ It turns out it applies to how proteins get made inside of cells, too,” says Dr. Mayr, a molecular and cell biologist at the Sloan Kettering Institute, a hub for basic and translational research within MSK. “If it’s translated over here, you get twice as much protein as if it’s translated over there.”
This first-of-its-kind study highlights the degree to which the cytoplasm is “beautifully organized,” rather than being just a big jumble of stuff, she says.
Not only do the findings shed new light on fundamental cellular biology, but the knowledge also holds promise for increasing or altering the production of proteins in mRNA vaccines and therapies, the researchers note.
The study was led by former lab member Ellen Horste, PhD, whom Mayr tapped for the daunting but exciting project when she joined the lab several years ago. Dr. Horste received her doctorate from the Gerstner Sloan Kettering Graduate School in June and now works for a gene therapy company.
“When we started, we had a hard time getting funding for this project,” Dr. Mayr says. “Everyone thought isolating the individual components would be totally impossible. This was really Ellen’s project from her first day in the lab to her last day. It was quite challenging, and I couldn’t be more proud of her.”
Adapting an approach commonly used by immunologists, the team was able to color-code individual particles within cells using antibodies and then sort them by color. They used RNA sequencing to identify which RNAs were associated with which particles.

“And it was really striking to see that in each of these intracellular neighborhoods, very different types of mRNAs were being translated,” Dr. Mayr says.
Welcome to the Cellular Neighborhood
Most of the well-known components inside a cell have a defined shape and come wrapped in an exterior membrane: the nucleus, mitochondria, lysosomes, the Golgi apparatus.
Two of the key components at the heart of the Mayr team’s study don’t have membranes — which is what has made them so hard to find in the first place, and a challenge to isolate and study in the lab.
A quick biology review: Cells build proteins using instructions encoded in DNA. Those DNA sequences are transcribed into mRNA inside the cell nucleus. These messenger RNA then move out into the cytoplasm where they are translated into a useful protein.
The new study demonstrated that where in the cytoplasm this translation step happens isn’t random, and that there’s an underlying logic or “code” that directs mRNAs to specific neighborhoods within the cell.

“The whole cytoplasm is nicely compartmentalized,” Dr. Mayr says. “We were able to demonstrate there is a code at work that’s based on the mRNA’s biophysical features — their size and shape — and the particular RNA-binding proteins they partner with. This code directs the mRNAs to different locations for translation.”
Investigating Translation in 3 Locations Inside the Cell
Through a painstaking series of experiments, the research team was able to show that mRNAs of different lengths and shapes tend to gravitate to specific neighborhoods. And that if you intervene to redirect them to a different location, it can have a profound impact on the amount of protein that gets produced and on the protein’s function.
The researchers looked at mRNAs that locate to the surface of the endoplasmic reticulum (an organelle involved in protein synthesis and other cellular functions). It’s well established that proteins associated with cellular membranes and those that get secreted by the cell for use elsewhere are translated there. The research revealed that nearly 15% of mRNAs that encode non-membrane proteins are also translated at the ER — and they encode large and highly expressed proteins.
Meanwhile, the mRNAs that get translated in the cytosol (the liquid part of the cytoplasm) tend to be very small proteins.
And mRNAs that locate to TIS granules tend to be transcription factors (proteins that regulate the transcription of genes). TIS granules are a membrane-less cellular component Mayr’s lab discovered in 2018. They form a network of interconnected proteins and mRNAs, and are closely allied with the endoplasmic reticulum, forming a distinct space where mRNA and proteins can collect and interact.
A fluorescent microscopy image of a cell, with TIS granules shown in red and the endoplasmic reticulum is shown in green. The central black area is the cell’s nucleus.
Cracking the Code
Cracking the code for how mRNA localize to different locations revealed some surprising findings.
After discovering the TIS granule network five years ago, the lab had turned its attention to understanding which of the many thousands of mRNAs in a cell localize there, and whether they have shared characteristics.
The team homed in on one part of the mRNA that doesn’t usually get much attention — the tail. It’s separate from the middle part of the mRNA, which contains the instructions for building the protein. Scientists call the tail the three prime untranslated region (3? UTR), and it turns out to be critical for the localization process.
“The tail usually contains a longer sequence than the part of the RNA that’s actually used to make the protein,” Dr. Mayr says. “But for a long time, people didn’t pay that much attention to the tail regions since you can still make the protein without them.” (They’re also important in other ways, as Dr. Mayr outlined in a 2019 review article.)
It turns out that the tail is essential for partnering with RNA-binding proteins so that, together, the mRNA goes to the correct translation region within the cell. (RNA-binding proteins are a type of protein that attaches to RNA molecules and can modulate various aspects of their activity.)
At first the team thought it was primarily these RNA-binding proteins that directed the action — guiding the mRNAs to neighborhood one, neighborhood two, and so forth, Dr. Mayr says.
“But the really surprising finding was that the RNA-binding proteins actually play a secondary role rather than a primary role in the process,” she says.
The default sorting of mRNA to a location, the researchers found, is based on the overall size and shape of the mRNAs. But being in partnership with a binding protein can override this default and redirect them.
“Our data show that if you translate an mRNA in the TIS granules, the resulting protein will perform one function, and if you translate it outside of the TIS granules, it will perform a different function,” she says. “And this is how, in higher organisms like us, one protein can have more than one function.”
Toward Future Applications
One specific protein the team examined during the study is MYC. The MYC gene is one of the more famous oncogenes, and mutations in MYC underlie the development of many cancers.
“We observed that several MYC protein complexes were only formed when MYC mRNA was translated in the granules and not when it was translated in the cytosol,” Dr. Mayr says. “Our results show there’s an important biological relevance to these neighborhoods, even when only about 20% of mRNAs get translated in the TIS granules.”
Together, these insights suggest that mRNA could be targeted to achieve different functions, as well as to vary the amount of a protein that gets produced, she adds.
“So, we hope that in the future we can make smarter medicines by making more or less of a particular factor, and also by manipulating its function,” Dr. Mayr says. “This probably won’t happen in the next five years, but it’s something we are paving the way to do.”

Researchers have identified a previously unrecognized class of antibodies — immune system proteins that protect against disease — that appear capable of neutralizing multiple forms of flu virus. These findings, which could contribute to development of more broadly protective flu vaccines, will publish December 21 by Holly Simmons of the University of Pittsburgh School of Medicine, US, and colleagues in the open access journal PLOS Biology.
A flu vaccine prompts the immune system to make antibodies that can bind to a viral protein called hemagglutinin on the outside of an invading flu virus, blocking it from entering a person’s cells. Different antibodies bind to different parts of hemagglutinin in different ways, and hemagglutinin itself evolves over time, resulting in the emergence of new flu strains that can evade old antibodies. New flu vaccines are offered each year based on predictions of whatever the most dominant strains will be.
Extensive research efforts are paving the way to development of flu vaccines that are better at protecting against multiple strains at once. Many scientists are focused on antibodies that can simultaneously protect against flu subtypes known as H1 and H3, which come in multiple strains and are responsible for widespread infection.
Simmons and colleagues homed in on a particular challenge in this endeavor — a small change found in some H1 strains in the sequence of building blocks that makes up hemagglutinin. Certain antibodies capable of neutralizing H3 can also neutralize H1, but not if its hemagglutinin has this change, known as the 133a insertion.
Now, in a series of experiments conducted with blood samples from patients, the researchers have identified a novel class of antibodies capable of neutralizing both certain H3 strains and certain H1 strains with or without the 133a insertion. Distinct molecular characteristics set these antibodies apart from other antibodies capable of cross-neutralizing H1 and H3 strains via other means.
This research expands the list of antibodies that could potentially contribute to development of a flu virus that achieves broader protection through an assortment of molecular mechanisms. It also adds to growing evidence supporting a move away from flu vaccines grown in chicken eggs — currently the most common manufacturing approach.
The authors add, “We need annual influenza virus vaccines to keep pace with continuing viral evolution. Our work suggests that the barriers to eliciting more broadly protective immunity may be surprisingly low. Given the right series of influenza virus exposures/vaccinations, it is possible to for humans to mount robust antibody responses that neutralize divergent H1N1 and H3N2 viruses, opening new avenues to design improved vaccines.”

Dog owners may need to learn to appreciate their best friend’s urine. Scientists at Osaka Metropolitan University have devised an efficient, non-invasive, and pain-free method to reprogram canine stem cells from urine samples, bringing furry companions one step closer to veterinary regenerative treatment.
Induced pluripotent stem cells (iPSCs) have been widely employed in studies on human generative medicine. With the growing importance of advanced medical care for dogs and cats, there is an expectation that new therapies utilizing iPSCs will be developed for these companion animals, just as they have been for humans. Unfortunately, canine somatic cells exhibit lower reprogramming efficiency compared to those of humans, limiting the types of canine cells available for generating iPSCs. IPSC induction often involves using feeder cells from a different species. However, considering the associated risks, minimizing xenogeneic components is often advisable, signifying the need to improve the efficiency of reprogramming various types of canine cells in dogs without using feeder cells.
A research team led by Professor Shingo Hatoya and Dr. Masaya Tsukamoto from the Graduate School of Veterinary Science at Osaka Metropolitan University has identified six reprogramming genes that can boost canine iPSC generation by about 120 times compared to conventional methods using fibroblasts. The iPSCs were created from urine-derived cells using a non-invasive, straightforward, and painless method. Additionally, the researchers succeeded in generating canine iPSCs without feeder cells, a feat that had been impossible until now. The team aims to disseminate their findings in the global research community, contributing to advances in regenerative medicine and genetic disease research in veterinary medicine.
“As a veterinarian, I have examined and treated many animals,” explained Professor Hatoya. “However, there are still many diseases that either cannot be cured or have not been fully understood. In the future, I am committed to continue my research on differentiating canine iPSCs into various types of cells and applying them to treat sick dogs, hopefully bringing joy to many animals and their owners.”
Their findings are set for publication in Stem Cell Reports on December 21, 2023.

The NewsMore than 15 million people have signed up for health insurance plans offered on the Affordable Care Act’s federal marketplace, a 33 percent increase compared to the same time last year, according to preliminary data released by the Biden administration on Wednesday.Federal health officials project that more than 19 million people will enroll in 2024 coverage by the end of the current enrollment period next month. That total would include those who gain coverage through state marketplaces, continuing the record-setting pace.“It means more Americans have the peace of mind of knowing that going to the doctor won’t empty their bank account,” Xavier Becerra, the health and human services secretary, said in a statement.An Affordable Care Act sign-up kiosk in a mall in Miami this month.Rebecca Blackwell/Associated PressWhy It Matters: The Affordable Care Act is expanding its reach.Despite a recent warning from former President Donald J. Trump, the front-runner in the race for the 2024 Republican presidential nomination, that he was “seriously looking at alternatives” to the Affordable Care Act, the latest surge in marketplace enrollment is a testament to the law’s enduring power.Legislation passed earlier in the Covid-19 pandemic increased federal subsidies for people buying plans, lowering the costs for many Americans. The Biden administration also lengthened the sign-up period and increased advertising for the program and funding for so-called navigators who help people enroll.“More and more people are realizing they can come onto the marketplace,” said Cynthia Cox, the director of the Program on the Affordable Care Act at KFF, a nonprofit health policy research group.She added: “Just because the A.C.A. has been around for a while doesn’t mean people who need to sign up for it know how to do that.”One Eye-Popping Statistic: 750,000 sign-ups in a single day.On Dec. 15 — the deadline to sign up for coverage that begins on Jan. 1 — nearly 750,000 people opted for a marketplace plan on HealthCare.gov. It was the largest single-day total yet.Dr. Benjamin Sommers, a health economist at Harvard who served in the Biden administration, said that improved outreach helped explain the record sign-ups. “I’m pleasantly surprised,” he said.With years of increased subsidies, he added, “it might be this is the natural growth rate over a few years in a new policy environment.”Kody Kinsley, the top health official in North Carolina, said that his state had gotten creative by using its efforts expanding Medicaid to also sign people up for marketplace plans.“We’ve had a very broad educational and outreach campaign — with civic organizations, churches, navigators — built around expansion to educate folks about eligibility,” he said in a text message.He added: “As part of that, we support folks to get coverage on the marketplace, if they’re not eligible” for Medicaid.What’s Next: Sign-ups will continue for almost a month.The open-enrollment period on Healthcare.gov runs through mid-January, ending at 5 a.m. Eastern time on Jan. 17. People who enroll by then will have coverage beginning in February.Biden administration officials said that they were encouraging enrollees who were already covered through HealthCare.gov to continue shopping for plans, in case a new option turns out to be better and more affordable.The Affordable Care Act’s marketplaces have become particularly valuable to the people losing Medicaid coverage this year after a federal policy that guaranteed coverage earlier the pandemic lapsed in April.The millions of people dropping off Medicaid rolls has contributed to the uptick in marketplace enrollment, Ms. Cox said, and to surges during normally sleepier periods outside open enrollment. (Certain life events, such as the sudden loss of other health coverage, allow some Americans to get new plans outside the open enrollment period.)According to federal health officials, from March to September enrollment in marketplace plans increased by 1.6 million people, or 1.5 million more than during the same period last year.

The Health Dept. is looking into the public hospital’s use of unlicensed technicians during some bariatric surgeries.The New York State Department of Health is scrutinizing Bellevue Hospital’s use of unlicensed technicians to assist doctors in weight-loss surgeries.Bellevue, a large public hospital in Manhattan, churns thousands of low-income patients through bariatric surgery every year, The New York Times reported this month. Doctors are paid in part based on the volume of surgeries.In their push for speed, bariatric surgeons have at times asked equipment technicians to scrub in and participate in surgeries because the surgeons were short on assistants, two Bellevue doctors told The Times. Those technicians, who worked for an outside vendor called Surgical Solutions, were not licensed to treat patients.The state health agency has begun an inquiry into the allegations, which could lead to a formal investigation.“The department is looking into the matter,” an agency spokeswoman, Danielle De Souza, said Wednesday.Christopher Miller, a spokesman for Bellevue, said the inquiry was preliminary and might not result in an actual investigation. “We are reviewing your allegations and will pursue action as appropriate if the facts warrant it,” he added.Surgical Solutions did not respond to requests for comment.The use of unlicensed technicians was one of many red flags that Bellevue employees described to The Times about the bariatric program. Two surgeons raced to see how many operations they could perform in a day. And anesthesiologists reduced doses of pain medication so that patients woke up sooner and operating rooms were cleared faster.Bellevue even recruited patients from New York City’s Rikers Island jail complex who had virtually no chance of maintaining the required diets after surgery. Two said they became malnourished as a result.After the Times article was published, executives for Health and Hospitals Corporation, the New York City agency that oversees Bellevue, emailed employees and told them that “the article left out important context.” They praised the bariatric surgery department for offering “comprehensive care and affordable, high quality surgical services” to low-income New Yorkers.

Increased sedentary time as a child through adolescence is directly linked to childhood obesity, but new research has found light physical activity may completely reverse the adverse process.
The study — conducted in collaboration with between University of Exeter, University of Eastern Finland, University of Bristol, and University of Colorado and published in Nature Communications — is the largest and longest follow-up to objectively measure physical activity and fat mass, using the University of Bristol’s Children of the 90s data (also known as the Avon Longitudinal Study of Parents and Children). The study included 6,059 children (53 percent female) aged 11 years who were followed up until the age of 24.
Recent reports concluded that more than 80 percent of adolescents across the globe do not meet the World Health Organization’s (WHO) recommended average of 60 minutes a day of moderate-to-vigorous physical activity. It is estimated that physical inactivity will have caused 500 million new cases of heart disease, obesity, diabetes, or other noncommunicable diseases by 2030, costing £21-million annually. This alarming forecast regarding the morbid danger of physical inactivity necessitates urgent research on the most effective preventive approach.
Yet results from this new study shows that moderate-to-vigorous physical activity is up to ten times less effective than light physical activity in decreasing overall gain in fat mass.
Dr Andrew Agbaje of the University of Exeter led the study and said: “These new findings strongly emphasise that light physical activity may be an unsung hero in preventing fat mass obesity from early life. It is about time the world replaced the mantra of ‘an average of 60 minutes a day of moderate-to-vigorous physical activity’ with ‘at least 3 hours a day of light physical activity’. Light physical activity appears to be the antidote to the catastrophic effect of sedentary time in the young population.”
During the study, a waist-worn accelerometer measured sedentary time, light physical activity, and moderate-to-vigorous physical activity among participants at ages 11, 15, and 24 years. Dual-energy X-ray absorptiometry-measured fat mass and skeletal muscle mass were also collected at the same ages and fasting blood samples were repeatedly measured for glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and high-sensitivity C-reactive protein. In addition, blood pressure, heart rate, smoking status, socio-economic status, and family history of cardiovascular disease were measured and controlled for in the analyses.
During the 13-year follow-up, sedentary time increased from approximately six hours a day in childhood to nine hours a day in young adulthood. Light physical activity decreased from six hours a day to three hours a day, while moderate-to-vigorous physical activity was relatively stable at around 50 minutes a day from childhood through young adulthood.

It was observed that each minute spent sedentary was associated with a 1.3-gram increase in total body fat mass. Both male and female children gained an average of 10kg of fat mass during growth from childhood until young adulthood. However, sedentary time potentially contributed 700 grams to 1kg of fat mass (approximately seven to ten percent) of the total fat mass gained during growth from childhood until young adulthood. A 1kg increase in fat has been linked to a 60-percent higher risk of premature death in a person’s early 50s.
Each minute spent in light physical activity during growth from childhood through young adulthood was associated with a 3.6-gram reduction in total body fat mass. This implies that cumulative light physical activity decreased total body fat mass by 950 grams to 1.5kg during growth from childhood to young adulthood, (approximately 9.5 to 15 percent decrease in overall gain in fat mass during the 13-year observation period). Examples of light physical activity are long walks, house chores, slow dancing, slow swimming, and slow bicycling.
In contrast, time spent in moderate-to-vigorous physical activity — including meeting the 60 minutes a day recommended by the WHO — during growth from childhood through young adulthood was associated with 70 to 170 grams (approximately 0.7 to 1.7 percent) reduction in total body fat mass. Prior to this study, it has not been possible to quantify the long-term contribution of sedentary time to fat mass obesity and the magnitude by which physical activity may reduce it. But this study confirmed the report from a recent meta-analysis of 140 school-based randomised controlled trials across the globe that engaging in moderate-to-vigorous physical activity had minimal or no effect in reducing childhood BMI-obesity.
Dr Andrew Agbaje of the University of Exeter said: “Our study provides novel information that would be useful in updating future health guidelines and policy statements. Public health experts, health policymakers, health journalists and bloggers, paediatricians, and parents should encourage continued and sustained participation in light physical activity to prevent childhood obesity.”