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Researchers at Indiana University School of Medicine are looking for ways to heal wounds by using a healing protein that is active in fetuses, but largely inactive in adults and absent in diabetic adults.
“We already know from previous studies at other institutions that if a fetus is wounded, it can regenerate the tissue, or repair it to be like new,” said Chandan K. Sen, PhD, associate vice president of military and applied research, the J. Stanley Battersby chair and distinguished professor of surgery and director of the Indiana Center for Regenerative Medicine and Engineering at Indiana University School of Medicine. “But after birth, such regenerative wound healing ability is lost. Healing in adults is relatively inefficient often associated with undesirable scar formation.”
In the study, published recently in Molecular Therapy, the team focused on a protein called nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase, or NPGPx. NPGPx is active in fetal tissue but becomes mostly inactive in the skin after birth.
“Nature essentially hides this fetal regenerative repair pathway in the adult body,” Sen said. “We spotted its absence, and then activated it to improve healing of diabetic wounds.”
Researchers used tissue nanotransfection technology developed by faculty at the ICRME to deliver the NPGPx gene to the wound site. Diabetic wounds, which are complicated skin injuries in people with diabetes, are particularly difficult to treat and often lead to amputations or other complications because of how easily they can become infected.
“This is an exciting new approach to harness fetal repair mechanisms to close diabetic wounds in adults,” Sen said. “The study results show that while NPGPx has been known to be abundant in the fetal skin, but not after birth, it can be reactivated in the skin after an injury. We look forward to continued study aiming to achieve a more complete regenerative repair by improving our understanding of how NPGPx functions.”
In addition to Sen, study authors from IU include Subhadip Ghatak, PhD, Savita Khanna, PhD, Sashwati Roy, PhD, Mohamed El Masry, MD, PhD, Anu Sharma, PhD, Ravichand Palakurti, PhD, Yi Xuan, PhD, and Mervin Yoder, MD. This study was supported by Lilly Indiana Collaborative Initiative for Talent Enrichment (INCITE) fellowships to C.K.S. as well as S.R. This study was also supported by grants from the National Institutes of Health as well as from the US Department of Defense. Read the full publication in Molecular Therapy.
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Brain changes in autism are comprehensive throughout the cerebral cortex rather than just particular areas thought to affect social behavior and language, according to a new UCLA-led study that significantly refines scientists’ understanding of how autism spectrum disorder (ASD) progresses at the molecular level.
The study, published today in Nature, represents a comprehensive effort to characterize ASD at the molecular level. While neurological disorders like Alzheimer’s disease or Parkinson’s disease have well-defined pathologies, autism and other psychiatric disorders have had a lack of defining pathology, making it difficult to develop more effective treatments.
The new study finds brain-wide changes in virtually all of the 11 cortical regions analyzed, regardless of whether they are higher critical association regions — those involved in functions such as reasoning, language, social cognition and mental flexibility — or primary sensory regions.
“This work represents the culmination of more than a decade of work of many lab members, which was necessary to perform such a comprehensive analysis of the autism brain,” said study author Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics, Neurology and Psychiatry at UCLA. “We now finally are beginning to get a picture of the state of the brain, at the molecular level, of the brain in individuals who had a diagnosis of autism. This provides us with a molecular pathology, which similar to other brain disorders such as Parkinson’s, Alzheimer’s and stroke, provides a key starting point for understanding the disorder’s mechanisms, which will inform and accelerate development of disease-altering therapies.”
Just over a decade ago, Geschwind led the first effort to identify autism’s molecular pathology by focusing on two brain regions, the temporal lobe and the frontal lobe. Those regions were chosen because they are higher order association regions involved in higher cognition — especially social cognition, which is disrupted in ASD.
For the new study, researchers examined gene expression in 11 cortical regions by sequencing RNA from each of the four main cortical lobes. They compared brain tissue samples obtained after death from 112 people with ASD against healthy brain tissue.
While each profiled cortical region showed changes, the largest drop off in gene levels were in the visual cortex and the parietal cortex, which processes information like touch, pain and temperature. The researchers said this may reflect the sensory hypersensitivity that is frequently reported in people with ASD.Researchers found strong evidence that the genetic risk for autism is enriched in a specific neuronal module that has lower expression across the brain, indicating that RNA changes in the brain are likely the cause of ASD rather than a result of the disorder.
One of the next steps is to determine whether researchers can use computational approaches to develop therapies based on reversing gene expression changes the researchers found in ASD, Geschwind said, adding that researchers can use organoids to model the changes in order to better understand their mechanisms.
Other authors include Michael J. Gandal, Jillian R. Haney, Brie Wamsley, Chloe X. Yap, Sepideh Parhami, Prashant S. Emani, Nathan Chang, George T. Chen, Gil D. Hoftman, Diego de Alba, Gokul Ramaswami, Christopher L. Hartl, Arjun Bhattacharya, Chongyuan Luo, Ting Jin, Daifeng Wang, Riki Kawaguchi, Diana Quintero, Jing Ou, Ye Emily Wu, Neelroop N. Parikshak, Vivek Swarup, T. Grant Belgard, Mark Gerstein, and Bogdan Pasaniuc. The authors declared no competing interests.
This work was funded by grants to Geschwind (NIMHR01MH110927, U01MH115746, P50-MH106438 and R01MH109912, R01MH094714), Gandal (SFARI Bridge to Independence Award, NIMH R01-MH121521, NIMH R01-MH123922 and NICHD-P50-HD103557), and Haney (Achievement Rewards for College Scientists Foundation, Los Angeles Founder Chapter, UCLA Neuroscience Interdepartmental Program).

New research findings show how higher viscosity, or resistance to flow, of the extracellular fluid that surrounds cells enables cancer cells to migrate more rapidly from a primary tumor to other sites in the body.
“We deciphered how cells sense and respond to physiologically relevant levels of fluid viscosity that are commonly found in the body of healthy and diseased patients,” says Konstantinos Konstantopoulos, Ph.D., lead investigator of the study, the William H. Schwarz Professor of Chemical and Biomolecular Engineering with appointments in Biomedical Engineering and Oncology, and member of the Johns Hopkins Kimmel Cancer Center Invasion and Metastasis Program. “We also showed that cells have the ability to form memory when preexposed to elevated fluid viscosities. We believe these findings will compel researchers in other fields, beyond cancer mechanobiology, to consider fluid viscosity as a key physical cue that regulates cell responses.”
The findings, which reveal a novel mechanism that promotes cancer cell dissemination, were published Nov. 2 in Natureand provide a framework for ongoing research that may ultimately lead to the identification of potential new targets to combat cancer metastasis.
Although deregulated viscosity of bodily fluids has been correlated with many diseases for almost half a century, studies on cancer cell dissemination to date were primarily performed using fluids of low viscosity, similar to water, explains Kaustav Bera, Ph.D., a recent graduate from the Konstantopoulos lab and first author of the study. “The expectation was that since there is more resistance in more viscous fluids, cancer cells wouldn’t move or metastasize efficiently, but we showed that the opposite is true,” she says.
The researchers revealed how cells sense and respond to the physical cue of elevated viscosity, and how the cytoskeleton, which controls cell shape and intracellular organization and is involved in cell movement, cooperates with ion channels and ion transporters — the proteins that channel the flow of charged molecules across the membrane of cells — to mediate efficient migration at elevated viscosities.
Extracellular viscosity rises with the degradation of large proteins secreted by both normal and cancer cells and with the compromised drainage of lymphatic vessels due to primary tumor growth. The researchers found that a higher resistance environment drives the formation of a denser actin network, which promotes local enrichment of ion transporters that cooperate with water channels to facilitate water uptake, promote cell swelling and increase membrane tension. At the cell’s leading edge, this increased membrane tension activates a signaling pathway, which includes an ion channel called TRPV4 that senses physical cues. Fluid viscosity instructs the cell to open its TRPV4 channels, facilitating the intake of calcium, which enhances the force- generating capacity of cells and ultimately drives faster cell movement.
“It is like the cells under high viscosity have gone to the gym to do hard training and develop muscle (actin and myosin), which improves their performance to reach their final destination faster,” says Selma Serra, Ph.D., study co-author and researcher at Pompeu Fabra University in Barcelona, Spain.
It was previously thought that the mechanosensing cascades begin with ion channels like TRPV4, says Alex Kiepas, Ph.D., a postdoctoral fellow and the second author of the study. “We found that viscosity sensing starts with the formation ofmore dense and highly branched actin, and TRPV4 activation is actually downstream of actin,” he says.
When the researchers knocked down TPRV4, they blocked the faster movement, of cells and their ability to form memory in response to preexposure to elevated viscosities. The researchers used 3-day-old zebrafish embryo models to show that memory of elevated viscosity can enable cells to move faster through blood vessels in vivo. They also used chicken embryo and mouse models to demonstrate that the memory can enhance cancer cell spread out of blood vessels, through a process called extravasation, and lead to a greater number of distant metastatic colonies.
Konstantopoulos says it will be informative to examine, in laboratory animal models, how primary tumors and cancer cells disseminating from primary tumors respond to local changes in extracellular fluid viscosity during disease progression and during invasion into the tissue microenvironment. The development and optimization of biosensors that enable real-time measurement of extracellular fluid viscosity together with imaging cancer cells in living animals will be crucial for addressing this point. They also plan to investigate whether extracellular viscosity affects other physiologically relevant cellular processes.
Other researchers involved in the study were Ines Godet, Pranav Mehta, Brent Ifemembi, Anindya Sen, Se Jong Lee, Yuqi Zhang, Gabriel Shatkin, Adrianna Boen, Daniele M. Gilkes, Andrew P. Feinberg and Sean X. Sun from The Johns Hopkins University. Collaborators from other centers included Yizeng Li, Colin D. Paul, Konstantin Stoletov, Jiaxiang Tao, Panagiotis Mistriotis, John D. Lewis, Chen-Ming Fan, and Miguel A. Valverde.
This work was supported by R01 CA 257647, R01 GM134542, NSF 2045715, R01 AR071976 and R01 AR072644, the Spanish Ministry of Science, Education and Universities through grants RTI2018 099718-B-100, an institutional “Maria de Maeztu” Programme for Units of Excellence in R&D and FEDER funds, and postdoctoral fellowships from the Fonds de recherche du Québec — Nature et technologies and the Natural Sciences and Engineering Research Council of Canada.

Especially for Black patients, inaccurate readings have imperiled care and may have contributed to deaths during the pandemic, experts told an advisory panel.Researchers warned an expert panel of the Food and Drug Administration on Tuesday that flawed readings on devices measuring oxygen levels in the blood — especially among Black and dark-skinned patients — might have contributed to deaths during the coronavirus pandemic. Panelists, in turn, urged the federal agency to raise accuracy standards and to alert doctors and consumers of the potential risks.The devices that measure blood oxygen typically on the fingertip, known as pulse oximeters, can be cheap, small products sold over the counter or medical devices used in hospitals and clinics.Decades before the pandemic, studies showed that they were less accurate on darker skin, often giving a healthy reading when blood tests showed more concerning levels.But in recent years, experts said the flawed readings might have driven some of the racial and ethnic disparities exposed in studies reviewing access to Covid treatments. Authors of the studies emphasized that blood-oxygen levels were often a key factor in deciding who would receive certain medicines, oxygen therapies and even hospital beds at times when all were in short supply.Dr. Amal Jubran, a pulmonary critical care doctor at Loyola Medicine in Chicago, one of the first physicians to identify the problem in 1990, testified on Tuesday that flawed readings were “hazardous” during the height of the pandemic.They “most likely contributed to the several-fold greater number of deaths in Covid-19 in ethnic minority patients than in white patients,” Dr. Jubran told the panel.The F.D.A. reviews prescription pulse oximeters and those used in hospitals under its so-called 510K program, which clears devices that are similar to existing ones — with some additional scrutiny. The over-the-counter versions are deemed “wellness” devices and are subject to virtually no agency oversight.Read More on the Coronavirus PandemicWarnings of a ‘Tripledemic’: An expected winter rise in Covid cases appears poised to collide with a resurgent flu season and a third pathogen straining pediatric hospitals in some states.Updated Boosters for Kids: The Food and Drug Administration broadened access to updated Covid booster shots to include children as young as 5.A Decline Among Seniors: Americans over 65 remain the demographic most likely to have received the original series of Covid vaccinations. But fewer are getting booster shots, surveys indicate.Personality Changes: New research suggests that Covid’s disruption of social rituals and rites of passage have made people less extroverted, creative, agreeable and conscientious.The accuracy concerns, which the agency flagged in 2021, led to a 10-hour meeting Tuesday of an F.D.A. advisory panel involving doctors and advisers. They did not formally vote on specific ways that the agency might address the issue, but several suggested measures like adding warnings to product labels and raising the bar manufacturers need to reach — in terms of correct readings — to get new devices approved. Doctors testifying to the panel also said studies gauging device performance on people with a range of skin tones and chronic medical conditions were needed.Veverly Edwards, a community representative and the only African American on the panel of mainly white male doctors, called for manufacturers to be held accountable. She said Black people should have a sustained voice on the matter that also affects people of many ethnicities with dark skin.“I guess my fear is that historically that the disparity in health care is like it never stops,” said Ms. Edwards, who is an assistant professor at the University of Memphis. “When you lump African Americans in with everyone else, we end up on the short end — because this started 30 years ago and here we are today addressing it.”During the hearing, F.D.A. officials said the pulse oximeters used in hospitals were marketed based on studies of as few as 10 healthy people. And the devices that people buy online or at retail pharmacies are not scrutinized by the F.D.A.Panelists agreed that the current rules were too lax for devices that had become a key driver of patient-care decisions, such as prescribing or ending the use of supplemental oxygen.“That should be held to a very different standard,” said Dr. Hugh Cassiere, an adviser and critical care chief at North Shore University Hospital in New York. “We really need to tighten that up.”Doctors who appeared before the panel cited a series of studies that showed how inaccurate readings from the devices used in hospitals affected people with darker skin during the pandemic and were associated with inadequate medical care.One University of Michigan study found that the devices that squeeze the finger gave elevated readings in Black people when a blood test showed a lower rate, suggesting “hidden” hypoxemia, or significantly low blood oxygen. The discrepancy was found in nearly 12 percent of Black people and in nearly four percent of white people.Dr. Ian Wong, a Duke University researcher, confirmed elevated levels of hidden hypoxemia in Black and Hispanic patients. He also told the panel that he found that all patients who had hidden hypoxemia had a risk of in-hospital death that was 70 percent higher than those with accurate readings.Doctors at the Johns Hopkins University School of Medicine confirmed the disparity again and noted the result: Black and Hispanic patients were 29 and 23 percent less likely to be recognized as candidates for Covid treatments.The studies were largely based on self-identified race, and researchers are still looking into the degree that melanin in the skin — which lends the darker pigmentation — affects pulse oximeter performance.The findings underscore the importance of testing the devices on sick patients and those with a range of skin tones, said Dr. Eric Gartman, a Brown University assistant professor testifying for the American College of Chest Physicians. Currently those devices are tested in healthy people in a lab.“We wouldn’t tolerate that in a medicine,” he said, “so I’m not sure we should tolerate that in a device, either.”Dr. Jesse Ehrenfeld, president-elect of the American Medical Association and an anesthesiologist, testified that he wondered if the pulse oximeter he used on a patient Tuesday morning was going to be accurate.“We need to take appropriate steps to remove the growing uncertainty around these devices and ensure the health and safety of the public,” he said.Dr. Ehrenfeld said the F.D.A. should put specific warnings on devices that produce biased readings, make health providers aware of the limitations and increase testing of devices that were already cleared by the agency.For the oximeters that people buy online or from retail stores, the lack of regulation is troubling, said one agency adviser, Dr. Murad Alam, a medicine professor at Northwestern University. People use them, he noted, to monitor oxygen levels at home and decide if they need urgent medical attention.“This is a misclassification problem,” Dr. Alam said. “I don’t know how it happened, but this is not shampoo. So F.D.A. will need to find a way to regulate these.”Advisers urged the agency to provide prominent warnings that the retail devices are not for medical use and are not approved by the F.D.A. The agency said it was working with researchers from Stanford and the University of California, San Francisco, on real-world studies of device performance.

Researchers from the Epigenetics and Immune Disease Lab at the Josep Carreras Leukaemia Research Institute have recently shown that vitamin C improves the immunogenic properties of dendritic cells, in vitro. Results recently made public show that treating the cells with vitamin C leads to a more consistent activation of genes involved in the immune response, mainly through DNA demethylation, a kind of epigenetic reprogramming. This discovery may be useful to generate more potent dendritic cell-based therapies in the future.
Since the onset of anticancer cell therapies, those that use living cells to find and eliminate tumors, many types of immune cells have been used. The best-known cell therapies use lymphocytes, as in the highly successful CAR-T therapies. Recently, dendritic cells have attracted the scientists’ attention thanks to its ability to uptake and present antigens (small parts of a pathogen or a cancer cell) to the T-lymphocytes and induce an antigen-specific potent immune activation. On this regard, loading dendritic cells with specific antigens to create immune memory constitute the so-called DC-vaccines.
To study dendritic cells in the lab, researchers differentiate them from monocytes (also an immune cell) using a particular set of molecular signaling. This differentiation is accomplished through a complex set of gene activation processes in the nucleus, mostly thanks to the activity of the chromatin remodeling machinery spearheaded by the TET family of demethylases, proteins that act upon the DNA epigenetic marks.
Vitamin C was known to interact with several TET proteins to enhance its activity, but the specific mechanism was still poorly understood in human cells. In a recent publication in the journal Nucleic Acids Research, a team lead by Dr. Esteban Ballestar hypothesized that treating monocytes in vitro while differentiating into dendritic cells, would help the resulting cells be more mature and active.
The results obtained by Octavio Morante-Palacios, first author of the publication, José Luis Sardina (also from the Josep Carreras Leukaemia Research Institute) and Eva Martínez-Cáceres, Head of Immunology of the Germans Trias i Pujol Research Institute, show that vitamin C treatment triggers an extensive demethylation at NF- kB/p65 binding sites compared with non-treated cells, promoting the activity of genes involved in antigen presentation and immune response activation. Also, vitamin C increases the communication of the resulting dendritic cells with other components of the immune system and stimulates the proliferation of antigen-specific T cells.
Actually, the researchers proved that vitamin C-stimulated dendritic cells loaded with antigens specific for the SARS-CoV-2 virus were able to activate T cells in vitro more efficiently than non-treated cells, showing the superiority of DC-vaccines treated with vitamin C.
Overall, these new findings support the hypothesis that treating monocyte-derived dendritic cells with vitamin C may help generate DC-vaccines with higher performance. After consolidating these results in preclinical models and, hopefully, in clinical trials, a new generation of cell therapies based on dendritic cells may be used in the clinic to fight cancer more efficiently.
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In the 20 years since Barbara Corkey, PhD, was named Editor in Chief of the journal Obesity, obesity among adults has risen significantly. Data from the National Center for Health Statistics show that one third of U.S. adults 20 years of age and older have obesity. Obesity continues to be a common, serious and costly disease.
In an editorial in Obesity, Corkey discusses the many different theories explaining why obesity continues to increase despite best efforts at controlling weight gain in this environment, including increased availability and marketing of high-calorie and high-glycemic-index foods and drinks, larger food portions, leisure time physical activities being replaced with sedentary activities such as watching television and use of electronic devices, inadequate sleep, and the use of medications that increase weight.
According to Corkey, all of these purported explanations assume an environmental cause that is detrimental to the organism involved, (humans). “However, if we use the principle of symbiosis and Darwin’s theory of evolution, perhaps we can understand obesity prevalence as an interim stage in the evolution of man reacting to his environment in order to gain long-term survival and ultimate longevity,” says corresponding author Corkey, professor emeritus of medicine and biochemistry at Boston University Chobanian & Avedisian School of Medicine.
Humans have developed a method to feed the billions of people on the planet, by developing processed foods with preservatives and other chemicals that can make food last longer and can be made cheaply to increase calorie density in small packages. Corkey points out that those who develop obesity store body fat in response to excess calories. “Therefore the cause of obesity has as much to do as the human reaction to overfeeding as it does the production of foods that are being overfed,” she states.
Corkey notes that key developments in the obesity/diabetes field include bariatric surgery as well as multiple agents (drugs) with different mechanisms of action to treat obesity and prevent weight regain. “Novel drug combinations are beginning to close the gap with bariatric surgery and appear to be very powerful new tools to treat obesity as a disease.”
Corkey believes recognition of obesity as a disease and earlier diagnosis of diabetes and other consequences of obesity will support early and more effective treatment and prevention. “Importantly, disease recognition will help to support insurance coverage of effective obesity treatments,” she adds.
Lastly, Corkey examines culinary medicine as an emerging evidence-based field that brings together nutrition and culinary knowledge and skills to assist patients in maintaining health and preventing and treating food-related disease by choosing high-quality, healthy food in conjunction with appropriate medical care. “Culinary medicine has the advantage of being an intervention that can be implemented at the earliest time point in the development of obesity with no negative side effects,” says Corkey.
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During the growth and development of living organisms, different types of cells must come into contact with each other in order to form tissues and organs together. A small team working with Prof. Dr. Anne Classen of the Excellence Cluster CIBSS — Centre for Integrative Biological Signalling Studies of the University of Freiburg has discovered that complex changes in form, or morphogenesis, during development are driven exclusively via the affinity of cells to each other. The researchers examined the egg chambers of fruit flies (Drosophila melanogaster) and combined genetic methods and mathematical modeling in their work. The study has been published in the scientific journal Nature Communications.
Complex organization processes in egg chamber
The lead author of the study and a member of Classen’s lab, Dr. Vanessa Weichselberger, summarized the team’s work: “We wanted to find out how different types of cells organize their morphogenesis with each other in order to form functional units.” She continues, “The egg chamber is a good example, because within it, different cell populations must self-organize into functional units.” The egg chamber is the structure in which an immature egg cell, or oocyte, matures until it is ready for fertilization. Drosophila’s egg chamber looks like a tiny football. Inside, the growing egg cell is located on one side, and on the other are 15 nurse cells that provide nutrients for the immature egg cell. In order to produce an egg, the egg cell must mature, while the nurse cells are ultimately removed.
Both processes — the maturation of the egg cell and the removal of the nurse cells, are dependent on an external layer of epithelial cells. For this purpose, the epithelial cells are divided into specialized groups, which — based on their function — must either make contact with the nurse cells or the egg cell. This partnering between the inner and outer cells is a complex process which takes place while simultaneously the size relationships within the egg chamber continually change. “Until now, the mechanisms that could robustly control such a dynamic process were unknown,” says Classen.
Eya controls the affinity of cells
The researchers observed that the epithelial cells specialized in removal of the nurse cells spread out and flatten over the nurse cells. This creates a particularly large contact area with the nurse cells underneath. Weichselberger explains, “That could be explained by heightened affinity between the two cell types. So we hypothesized that the matching of inner and outer cells took place through simple mechanical processes of attraction and repulsion.” A heightened affinity of one specialized group of epithelial cells to the nurse cells would lead to the rest of the epithelial cells being displaced from the nurse cells onto the egg cell. The researchers found that a protein, Eya, which can control the activity of genes, influences the contact behavior between epithelial cells and nurse cells. If the researchers increased the concentration of Eya in the epithelial cells, these increased their contact surface area with the nurse cells. If they removed Eya, the contact surface was minimized.
Cell affinity decisive for development
In order to test their hypothesis, the developmental biologists used mathematical models. To do this, they worked with Prof. Dr. Patrick Dondl of the Faculty of Mathematics and Physics of the University of Freiburg. Dondl created mathematical models that could simulate different degrees of mechanical affinity between the cells. “The mathematical models allowed us to show that a change in affinity dependent on Eya levels was sufficient to control the complex process of matching cell types,” explains Weichselberger. “That meant that we could use Eya as a set screw to genetically control partner location,” she says.
“Extremely flexible and robust”
By genetically changing the Eya concentrations in the epithelial cells and simulating these experiments on the computer, the researchers were able to test if the Eya-regulated affinity between the epithelial cells and nurse cells is responsible for self-organization. They observed that solely by manipulating Eya, they could deliberately control which epithelial cells spread out on the nurse cells and which epithelial cells came into contact with the egg cell. This showed that Eya — via affinity regulation — is the main regulator of self-organization between the epithelial cells and the inner cells — the nurse cells and the egg cell. The results surprised Classen, who led the study. She explains, “Specific affinity is actually sufficient as a mechanism for controlling such complex development processes. And in a way that is extremely flexible, robust, and independent from the volume of the egg chamber.”
Similar process in males
This mechanism is not limited solely to the egg chamber. The development of sperm cells in Drosophila males is also dependent on Eya. Here, too, the protein Eya controls the affinity between the developing, interior sperm cells and the exterior epithelial cells. It is unclear if these results can also be applied to other animals or humans. But comparable structures and developmental processes during oogenesis in other species make this seem possible.
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As our brains develop, cells within it ‘eat’ neuronal elements to clear out debris, pathogens and help improve efficiency. A recent study showed that motor learning in mice helped enhance the engulfing of synapses by Bergmann glial cells.
Tohoku University researchers have shown that Bergmann glial cells, astrocyte-like cells in the cerebellum, ‘eat’ their neighboring neuronal elements within healthy living brain tissue.
Synapses — structures that allow neurons to pass signals to one another — are regularly pruned throughout a brain’s development to improve its efficiency. Disruption of this is thought to lead to various brain disorders.
The researchers’ findings, which were detailed in the journal Nature Neuroscience, discovered that Bergmann glial engulfing of synapses was enhanced during motor learning in mice’s cerebellum, an important brain region for learning.
Moreover, pharmacological blocking this engulfment inhibited synaptic structural changes, resulting in part of the learning and memory process being lost.
Glial cells, non-neuronal cells occupying about half of the brain, were previously believed to be like glue — merely filling the gap between neurons. However, recent findings show that glia encode information in their own unique way.

Researchers have developed a three-dimensional model that shows how exposure to cadmium might lead to congenital heart disease. Affecting nearly 40,000 newborns a year, congenital heart disease is the most common type of birth defect in the United States. The model was created by scientists at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.
Cadmium is a metal that can be released into the environment through mining and various industrial processes, and it has been found in air, soil, water, and tobacco. The metal can enter the food chain when plants absorb it from soil. Previous studies suggested that maternal exposure to cadmium might be a significant risk factor for congenital heart disease.
Using models derived from human cells and tissues, called in vitro models, researchers designed a 3D organoid model that mimics how the human heart develops. The researchers saw how exposure to low levels of cadmium can block usual formation of cardiomyocytes, which are the major type of cells that form the heart. In doing so, they revealed the biological mechanisms that might explain how cadmium could induce heart abnormalities.
“The models we created are useful for not only studying cadmium, but for studying other chemicals and substances as well,” said study lead Erik Tokar, Ph.D., from the Mechanistic Toxicology Branch of the NIEHS Division of Translational Toxicology (DTT).
For the study, the researchers developed three different models to evaluate the effects of cadmium on different stages of heart development.
First, they used human pluripotent stem cells to develop 3D embryoid bodies to mimic early steps in tissue and organ formation in humans. They then used a 2D in vitro model that included a fluorescent regulatory protein system (NKX2-5) known to be involved in heart development, which allowed them to look at cadmium toxicity after exposure.
The 3D cardiac organoid model, which can simulate the beating heart, confirmed what was seen in the other two models, showing how low doses of cadmium can inhibit the cardiomyocytes from functioning properly.
The study, published in the journal Environmental Health Perspectives, builds on decades of work by toxicology researchers to advance knowledge about how environmental exposures may contribute to human diseases including cancer, cardiovascular disease, autism, and other conditions.
“These new models are leveraging advances in technology that allow us to model human biology in a way that identifies real human health hazards,” noted Brian Berridge, D.V.M., Ph.D., scientific director, DTT. “They also help reduce our reliance on animal testing.
“We found that early exposure to human-relevant levels of cadmium lead to a dramatic inhibitory effect on cardiomyocyte differentiation, whereas later stage exposures did not have this effect,” said Xian Wu, Ph.D., who conducted these studies. “This cadmium exposure also damaged the cardiac organoid functionality.”

Diabetes, which affects millions of people worldwide, develops when the body either generates insufficient amounts of the hormone insulin- a hormone that maintains healthy blood sugar — or when the body cannot effectively use the insulin it produces. When the number of beta cells is too low or they aren’t functioning properly, there isn’t enough insulin getting released. Beta cells communicate with each other to secrete insulin in a coordinated manner. An international team of scientists from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, the Paul Langerhans Institute Dresden (PLID), and the Universities of Oulu, Finland and Copenhagen, Denmark now shows that the gene Wnt4 in beta cells enables them to sense glucose and release the hormone insulin that enables other cells in the body to store glucose. These insights could help to create replacement beta cells for diabetes therapy in the future.
At birth, a baby starts to eat food and turns it into energy. Many nutrients can be converted to sugar (glucose) and be released into the bloodstream. Higher blood sugar levels signal the beta cells in the pancreas to release insulin, which lets the blood sugar into the cells to use or store it as energy. However, at different stages of life, the food-sensing beta cells need to adapt to different foods and needs. In a recent study in Nature Communications, Anne Grapin-Botton, director at MPI-CBG, and her team in Dresden and at the Novo Nordisk Foundation Center for Stem Cell Biology in Copenhagen, Denmark, together with colleagues from the Faculty of Medicine Carl Gustav Carus of the Technische Universität Dresden found that the gene Wnt4 becomes active in food-sensing beta cells as they mature in early postnatal life.
How it all began
The discovery of the role of Wnt4 in the development of a pancreas started in the 1990s at Harvard University, when Anne Grapin-Botton, a postdoctoral researcher at that time, discussed with Seppo Vainio, now a research unit leader at the University of Oulu. “I remember that when I worked with Wnt4 in kidney development, we speculated that this signal would have a role in the development of the pancreas too,” says Seppo Vainio. But the researchers were lacking the right tools at that time. Over 20 years later, postdoctoral researcher Keiichi Katsumoto in the lab of Anne Grapin-Botton was keen on finding out what function the gene Wnt4 has in pancreas development. In the meantime, the lab of Vainio at Oulu had further developed their mouse models: “With all these tools, we could target Wnt4 function in pancreas development and physiology with Anne Grapin-Botton’s research lab,” says Seppo Vainio.
Exciting communication between beta cells
Keiichi Katsumoto describes what he observed, “We found that the gene Wnt4 is expressed in beta cells during the maturation of the cell. The cells that start expressing Wnt4 stop proliferating and become more functional. We saw that with less Wnt4, the beta cell secretes less insulin.” The team found that even though the beta cells were able to detect sugar in the blood, they secreted less insulin in response to glucose.
“When we saw that mice without the gene Wnt4 were becoming diabetic, we knew we had found something important, but we did not understand how it was acting,” says Anne Grapin-Botton, who supervised this study. “We understood from work in other organs, notably our collaborator Seppo Vainio and his colleagues, that this gene is a signal sent by cells to others. It was exciting to find communication between beta cells in the pancreas, its conservation across several animal species and the mechanisms by which it operates, notably the profound metabolic changes it provokes in beta cells. However, we do not understand yet if beta cells release Wnt4 constantly or under special circumstances. This will be something, we want to explore in the future.”
“The results also suggest that the increase of Wnt4 shortly after birth enables beta cells to mature,” says Katsumoto. Our next step is to understand why Wnt4 becomes expressed as the cells mature.” Those results could support the development replacement beta cells for diabetes therapy with added Wnt4 to promote maturation.