Publisher Health

Studying mice has filled encyclopedias with breakthrough medical discoveries. But when it comes to brain cancers, the little rodents have long exhibited fundamental limitations.
Among them: the human cerebellum has 750 times as much surface area as a mouse, all of it laced with more types of progenitor cells that help the fetal brain grow during pregnancy. That means many things can go wrong in human brain development that simply cannot be seen by studying mice.
Now a multinational team of scientists led by experts at Cincinnati Children’s has developed an “atlas” of human fetal brain development so detailed that it details growth steps all the way down to changes occurring at the single-cell level. Details were published Nov. 30 in Nature.
The investigators say this atlas will be a vital resource for brain research for years to come. In fact, it has already opened doors that someday may improve lives.
“This study took the effort of 40 experts for nearly three years to complete. Their work included dozens of experiments using several of the very latest technologies in genomic science to reach this point,” says senior author Qing Richard Lu, PhD, scientific director, Brain Tumor Center, Division of Experimental Hematology and Cancer Biology at Cincinnati Children’s. “It was worth so much effort because this new map guided us to a targetable vulnerability for therapeutic intervention of aggressive medulloblastomas.”
Hunting cell-by-cell to pinpoint the birth of a killer
Medulloblastomas are fast-growing malignant tumors that form in the back of the brain. They often disrupt balance and fine motor skills before going on to cause further damage.

A low-cost, prenatal intervention benefits mothers’ mental health up to eight years later, a new UC San Francisco study finds.
In the study, one of the first to look at outcomes so far into the future, pregnant women who participated in a group wellness class that met weekly for eight weeks were half as likely to be depressed eight years later compared to women who received standard care, according to the study published in the Journal of Consulting and Clinical Psychology.
Previous research on the same group of women found the intervention also cut their short-term risk of depression and diabetes, and supported healthier stress responses in their children.
“Given the economic and social burden of maternal depression and its potential impact on offspring, our findings suggest a meaningful benefit of a modest investment during pregnancy that supports well-being across two generations,” said Danielle Roubinov, PhD, UCSF assistant professor of psychiatry and first author of the study.
The eight-week class intervention, led by Elissa Epel, PhD, UCSF professor of psychiatry and her team, involved groups of eight to 10 pregnant women who met for two hours a week to practice mindfulness-based stress reduction exercises, focusing especially on mindful eating, breathing and movement. They were led through group lessons and activities by a master’s degree-level health professional. The women also received two phone sessions and a postpartum “booster” group session with their infants.
BIPOC Study Participants Were Priority
Historically, most studies on prenatal depression have comprised primarily white women — but not this one, noted Nicki Bush, PhD, professor of pediatrics and psychiatry at the UCSF Weill Institute for Neurosciences and senior author on the study.

Understanding of how neuronal activity modulates brain function is a key first step towards creating more effective drugs to treat a variety of neuropsychiatric illnesses, including depression, anxiety, schizophrenia, substance abuse, epilepsy, and others.
To both manipulate and understand this basic feature of neuronal biology, the lab of Bryan L. Roth, MD, PhD, the Michael Hooker Distinguished Professor of Pharmacology at the UNC School of Medicine, created a chemogenetic technology called DREADD — designer receptors exclusively activated by designer drugs — in the mid-2000s. Even though this technology is used ubiquitously in the neurosciences, why the technology was so efficient was unknown.
Now, as reported in the journal Nature, the Roth lab led by postdoctoral researcher Shicheng Zhang, PhD, used cryogenic electron microscopy to determine the detailed, high resolution structures of four DREADDs bound to three drug-like but inert compounds.
This work, made possible through the UNC CryoEM Core Facility, reveals key details of DREADDs that should accelerate the structure-guided discovery of next-generation chemogenetic tools.
“Although DREADDs are widely used, the precise molecular basis for why they are so useful has been obscure until now,” Zhang said. “We think these structures will help scientists around the world, including here at UNC-Chapel Hill, investigate the development of more effective and safer therapeutics for a host of neuropsychiatric conditions.”
To study how brain cells function, scientists need to target specific neural circuits — a network of interconnected cells that constantly send and receive electrical and chemical signals through receptors, such as G protein-coupled receptors, which are the intended targets of many therapeutics. This, though, is no easy task, which is the main reason why many drugs strike several kinds of receptors or activate specific receptors in unintended ways. The result might be a beneficial therapeutic effect, but also side effects.

Researchers at the University of California, Irvine have discovered that removal of cilia from the brain’s striatum region impaired time perception and judgment, revealing possible new therapeutic targets for mental and neurological conditions including schizophrenia, Parkinson’s and Huntington’s diseases, autism spectrum disorder, and Tourette syndrome.
The striatum processes and integrates new environmental sensory information and coordinates the time sequence of motor responses. A common feature across specific mental and neurological disorders is a profound decline in patients’ ability to adjust to variations in their surroundings and accurately estimate the timing and termination of voluntary actions.
The study, recently published online in the journal Molecular Neurobiology, uncovered the first evidence of the important role cilia play in timing-dependent dysfunction.
“Our findings may revolutionize our understanding of brain functions and mental disorders in the context of the critical task performed by these previously unappreciated organelles in the brain’s ‘central clock’ function,” said Amal Alachkar, Ph.D., corresponding author and professor of teaching in UCI’s Department of Pharmaceutical Sciences. “Our results may open new avenues for effective intervention through cilia-targeted therapies for treatment.”
The striatum is part of the brain’s circuitry that performs central clock processes, essential in controlling executive functions such as motor coordination, learning, planning and decision-making, as well as working memory and attention. Cilia protrude from the brain cell surfaces like antennae, working as a signaling hub that senses and transmits signals to generate appropriate reactions.
To examine their physiological role, the researchers removed cilia from the striatum in mice using conditional gene manipulation technology. These rodents were not able to learn new motor tasks, showed repetitive motor behavior and exhibited delays in decision-making. They were also deficient in rapidly recalling information about their location and orientation in space and in their ability to filter irrelevant environmental sensory information. However, the mice maintained habitual or already learned motor skills and long-term memories.
“Successful performance of working memory, attention, decision-making and executive function requires accurate and precise timing judgment, usually within a millisecond to a minute,” Alachkar said. “When that capacity is impaired, it means losing the ability to quickly adjust behavior in response to changes in external stimuli and failing to sustain appropriate, goal-oriented motor responses. Our ongoing work is aimed at understanding the mechanisms by which cilia regulate time perception and developing targeted therapies to improve behavioral deficits.”
Team members also included pharmaceutical sciences graduate students Wedad Alhassen, Sammy Alhassen, Kiki Jiaqi Chen and Roudabeh Vakil Monfared.
This work was funded, in part, by the National Institutes of Health under award numbers R01-HL1473-02S1 and 1F31MH126565-01A1.
Story Source:
Materials provided by University of California – Irvine. Note: Content may be edited for style and length.

The COVID-19 pandemic changed the social and school world for teens as virtual learning or hybrid learning became the norm in 2020-21. The unprecedented shutdown of classroom learning caused undue stress, low levels of social inclusion and low satisfaction with school for many — and mental health issues for some, according to a new study led by researchers at the University of California, Davis.
Problems were especially pronounced for those youth identifying as transgender and gender nonconforming, or TGNC, and youth who attended school online during the pandemic, the researchers found.
“It is clear from this study that certain individuals ended the 2020-21 school year facing more adversity than others,” said Drew Cingel, lead author and associate professor of communication at UC Davis. The study was published last month in the journal PLOS ONE.
The study found that teens who were able to attend school in-person reported more sense of inclusion in their social group than those learning online. And despite the traditionally high use in this age group, social media failed to compensate for real, in-person social connections derived from school, researchers suggest.
Data was collected from 1,256 United States adolescents, ages 14 to 16, to examine how their school context related to feelings of school satisfaction and success, social connection, mental health and media use. The findings suggest that current school interventions may be necessary to help teens recover from the disparities experienced during this unique time, researchers said.
Particularly susceptible to health and academic disparities were TGNC adolescents and adolescents in virtual learning only. Both reported a more significant drop in academic success and less satisfaction with school in 2020-21 compared to the previous school year.
Youth participating in virtual learning also reported feeling less social connection and higher rates of mental health problems, in comparison to their peers who could attend school in-person or in a hybrid model.
Social media
And while the use of social media by teens was reported as more pronounced than before the pandemic, the increased socialization online was perceived both positively and as problematic at the same time.
“Importantly, while adolescent youth are adept and frequent media users, and report using media for social purposes, in this instance in which so much of their in-person social connection was lost, social media and gaming do not appear able to provide a protective mechanism enough to compensate for that loss,” researchers said in the study.
“In fact, problematic media use (both social media and video gaming) was highest by those in virtual learning contexts. It is critical that we recognize that all youth are not returning to school with the same consequences of the pandemic, and that resources need to be in place to specifically support TGNC youth and those who were studying virtually at the end of last year, particularly around social connection and mental health,” Cingel said.
Co-authors included Alexis R. Lauricella, Erickson Institute, Chicago; Sarah M. Coyne, School of Family Life, Brigham Young University, Provo, Utah; Ellen Wartella, Department of Communications Studies, Northwestern University, Evanston, Illinois; and Lauren B. Taylor and Hannah R. Stevens, UC Davis.
Story Source:
Materials provided by University of California – Davis. Original written by Karen Nikos-Rose. Note: Content may be edited for style and length.

Researchers at Children’s Hospital of Philadelphia (CHOP) have discovered a specific genetic variant in SCN1A, the most common genetic epilepsy, that leads to an earlier onset of epilepsy, with clinical features distinct from other epilepsies. The researchers also identified a potentially effective treatment strategy. The findings were recently published in the journal Epilepsia.
Most genetic variants in SCN1A are associated with Dravet syndrome. Dravet syndrome is a form of genetic epilepsy that is characterized by seizures that begin in the first year of life, along with differences in childhood development and features of autism spectrum disorder. In these cases, there is a loss-of-function variant of SCN1A, meaning that the resulting protein is not able to carry out its normal functions. However, this study focused on a gain-of-function variant of SCN1A, which means the resulting protein carries out additional functions in ways that may be harmful.
“This genetic change does exactly the opposite of what it should do, which in turn causes a peculiar clinical presentation,” said senior study author Ingo Helbig, MD, a pediatric neurologist in the Division of Neurology and co-director of the Epilepsy Neurogenetics Initiative (ENGIN) at CHOP. “A better understanding of what this variant does is critical for us to determine which treatments to choose for affected patients.”
In this study, researchers used diagnostic testing to identify four patients with an identical gain-of-function variant in SCN1A. All four patients had an early-onset developmental and epileptic encephalopathy (DEE), which is characterized by a combination of seizures and developmental delays. In these specific cases, patients experienced focal tonic seizures, which are seizures that cause stiffening of the body in one specific area, and additional seizure types starting in the first few weeks of life. The study also found that patients with this recurrent gain-of-function variant in SCN1A-related epilepsies had earlier onset of their disease compared with patients with loss-of-function variants.
Additionally, the study found that oxcarbazepine, a seizure control medication for children and adults, may help patients. One of the patients responded to treatment with the medication, and the variant exhibited sensitivity to the drug.
“Our findings may provide an explanation for why we had previously diagnosed some patients as having atypical Dravet Syndrome, as the earlier onset of symptoms associated with this gain-of-function variant allow us to properly distinguish these cases,” said the study’s first author Jérôme Clatot, PhD, director of the ENGIN Ion Channel/Electrophysiology Core at CHOP. “We hope to raise awareness of this and other potential gain-of-function variants, particularly if common anti-seizure medications may be able to help them.”
This study was supported by The Hartwell Foundation Individual Biomedical Research Award and the National Institues of Health National Institute of Neurological Disorders and Stroke grants K02 NS112600, U54 NS108874 and R01 NS110869 and the Burroughs Wellcome Fund Career Award for Medical Scientists.
Story Source:
Materials provided by Children’s Hospital of Philadelphia. Note: Content may be edited for style and length.

Researchers from Children’s Hospital of Philadelphia (CHOP) have identified several genetic variants associated with increased risk of cancer in children with non-chromosomal birth defects, such as congenital heart disease and defects of the central nervous system. While the risk of developing cancer is not as high as children with chromosomal birth defects, it is significantly higher than children with no birth defects at all, and the findings may provide a basis for early detection in these understudied patients.
The findings were recently published in the journal Biomarker Research.
Children with birth defects are more likely to develop cancer, and that increased risk of cancer persists into adulthood. Prior studies have demonstrated that children with chromosomal birth defects, such as Down syndrome and Klinefelter syndrome, are more than 11 times more likely to be diagnosed with cancer than children without any birth defects. However, children with non-chromosomal birth defects are up to 2.5 times more likely to be diagnosed with cancer than those without birth defects. With birth defects of any kind occurring in 1 in every 33 births in the United States each year, that increased risk implicates a significant number of children.
The underlying genetics of non-chromosomal birth defects have not been studied in great detail. Researchers at the Center for Applied Genomics (CAG) at CHOP wanted to determine what molecular mechanisms were at play and potentially identify genetic clues that could lead to early identification of cancer in these patients.
“We assembled one of the largest pediatric oncology and birth defects projects in children as part of the Gabriella Miller Kids First program project, which helps to uncover new insights into childhood cancer and structural birth defects,” said Hakon Hakonarson, MD, PhD, director of the CAG at CHOP and senior author of the study. “With this partnership, we sought to identify functional molecular pathways based on mutations we identified as part of this study.”
In this study, researchers used data obtained from whole genome sequencing of blood samples from 1,653 individuals without chromosomal abnormalities that were acquired from the Kids First Data Resource Center. These samples included 541 birth defect probands — the first person in a family to receive genetic counseling or testing for hereditary risk of a disease — with at least one type of malignant tumor, 767 birth defect probands without malignant tumors, and 345 healthy family members who are parents or siblings of the aforementioned probands. Additionally, once variants were identified, whole genome sequencing data from 40 birth defect probands from outside the data resource center, including 25 patients with at least one type of cancer, were used to further validate the study.
The study identified thousands of variants of interest, including 119 genes with at least two variants in coding regions — regions of the gene that will eventually be transcribed and translated into proteins to carry out essential functions — and 478 genes with at least 20 variants in their non-coding regions. Five genes in particular — AXIN2, BMP1, CR1, ERBB2, and RYR1 – are associated with birth defects and increased risk of cancer. Additionally, the researchers built a deep learning model to assess the variants of interest identified in the Kids First cohort when compared with the 40 validation samples and found that they had achieved approximately 75% accuracy, with even greater accuracy for variants that were associated with non-coding regions.
Further detailed analysis of this data could identify genes and noncoding mutations that not only result in specific birth defects but also identify which types of cancer they are more prone to and whether the risk is more pronounced in childhood or adulthood.
“While more research is needed to delve into the variants of interest we identified, this study represents a critical step toward the earlier detection of cancer children with non-chromosomal birth defects,” Hakonarson said.
The sequencing data was provided through the Gabriella Miller Kids First Pediatric Research Program consortium (Kids First), supported by the Common Fund of the Office of the Director of the National Institutes of Health. The study was supported by Institutional Development Funds from CHOP to the CAG.
Story Source:
Materials provided by Children’s Hospital of Philadelphia. Note: Content may be edited for style and length.

Cartilage degeneration and injuries affect 350 million people worldwide. Patients with these conditions experience increased pain and discomfort over time. However, an exciting breakthrough in tissue regeneration research offers the promise of meaningful relief. The study, led by faculty at The Forsyth Institute, suggests a new approach for making cartilage cells with huge implications in regenerative medicine for future cartilage injuries and degeneration treatments.
As any weekend warrior understands, cartilage injuries to joints such as knees, shoulders, and hips can prove extremely painful and debilitating. In addition, conditions that cause cartilage degeneration, like arthritis and temporomandibular joint disorder (TMJ), affect 350 million people in the world and cost the US public health system more than $303 billion every year. Patients suffering from these conditions experience increased pain and discomfort over time.
However, an exciting study led by faculty at The Forsyth Institute suggests new strategies for making cartilage cells with huge implications in regenerative medicine for future cartilage injuries and degeneration treatments. In a paper, entitled “GATA3 mediates nonclassical β-catenin signaling in skeletal cell fate determination and ectopic chondrogenesis,” co-first authors Takamitsu Maruyama and Daigaku Hasegawa, and senior author Wei Hsu, describe two breakthrough discoveries, including a new understanding of a multifaced protein called β-catenin.
Dr. Hsu is a senior scientist at the Forsyth Insitute and a Professor of Developmental Biology at Harvard University. He is also an affiliate faculty member of the Harvard Stem Cell Institute. Other members conducting the study included Swiss scientists Tomas Valenta and Konrad Basler, and Canadian scientists Jody Haigh and Maxime Bouchard. The study appears in the most recent issue of Science Advances.
“The goal of this study,” said Dr. Maruyama of Forsyth, “was to figure out how to regenerate cartilage. We wanted to determine how to control cell fate, to cause the somatic cell to become cartilage instead of bone.”
Previously, it was thought that the Wnt signal transduction pathway was the determinant of whether a cell became bone or cartilage. The master factor transducing the Wnt signals is β-catenin. The basis for this belief was the result that when β-catenin was disrupted, the bone became cartilage.
However, β-catenin also acts as a cell adhesion molecule to facilitate cell-cell interaction — the original function identified prior to the discovery of its role in Wnt signaling. “We know that this molecule is important for cell fate determination, but the mechanism remained open to study,” said Dr. Hsu.
The team tested what would happen when β-catenin was only partially impaired for signaling, finding that, in that case, the cells were unable to form bone or cartilage. After these tests, the scientists concluded that Wnt signaling is a determinant for bone formation, but that it isn’t sufficient for cartilage generation.
“We wanted to know what the factor was for cell fate determination,” said Dr. Maruyama. “What reprograms a cell to become cartilage if it isn’t Wnt signaling?”
This question led to a second major discovery: GATA 3, an alternative action of β-catenin responsible for skeletal cell fate switching. GATA3 is a single gene regulator, which turns on cartilage-specific gene expression in cells. “Basically,” said Dr. Wei Hsu, “GATA3 binds to the genome sequences required for the reprogramming. GATA3 is a game changer because we can use it to potentially change any somatic cell to become a cartilage-forming cell, similar to using four stem cell factors to generate embryonic stem cell-like cells called induced pluripotent stem cells (iPSC).”
Being able to control the cell fate in this way makes it possible to direct a cell to become bone, cartilage, or fat, which has tremendous implications for creating new treatments for the 1 in 4 people living with cartilage injuries and cartilage degeneration. There is currently no treatment that can regenerate cartilage, and current treatments are unable to improve joint function.
This research opens new avenues for scientists to explore and is an exciting breakthrough in tissue regeneration research with the promise of meaningful relief for thousands of patients. This work is supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award numbers R01DE015654 and R01DE026936 to Dr. Wei Hsu.
Story Source:
Materials provided by Forsyth Institute. Note: Content may be edited for style and length.

A new study suggests that people with high levels of neuroticism and stress may be at greater risk for depressive symptoms, but those links could be buffered for people who observe the five precepts of Buddhism — a fundamental system of ethics for the religion’s followers. Nahathai Wongpakaran of Chiang Mai University, Thailand, and colleagues present these findings in the open-access journal PLOS ONE on November 30, 2022.
The five precepts of Buddhism guide followers not to kill, steal, engage in sexual misconduct, tell ill-intentioned lies, or use intoxicants. Previous research suggests that observing the five precepts can boost wellbeing and quality of life for the general public, including nonserious followers. However, it has been less clear whether the five precepts could ease symptoms of depression for those at higher risk.
To address this question, Wongpakaran and colleagues focused on known links between neuroticism, stress, and depression. Prior research has shown that greater neuroticism is associated with greater risk of depression, both directly as well as indirectly through perceived stress — how people think and feel after stressful life events.
From late 2019 through September 2022, the researchers conducted an online survey of 644 adults in Thailand. The survey included standard questionnaires to measure each participant’s levels of perceived stress, neuroticism, and depressive symptoms, as well as their observance of the five precepts of Buddhism.
Statistical analysis of the survey results showed that observing the five precepts to a high degree appeared to buffer the influence of perceived stress on depression. These results suggests that people with high levels of neuroticism and stress may be less likely to develop depressive symptoms if they follow the five precepts closely.
The researchers note that, while their study suggests potential benefits for the five precepts in the context of depression, it does not confirm a cause-effect relationship. A large proportion of participants were female and people who lived alone, and participants’ religious involvement was unknown, although 93.3% reported that they were Buddhist. More research will be needed to determine whether these findings might extend to the general population of Thailand and beyond, as well as to non-Buddhists.
The authors add: “The five precepts practice makes other people feel safe, as all these behaviors are harmless, and it potentially provides the stressful practitioner with a buffer against depression.”
Story Source:
Materials provided by PLOS. Note: Content may be edited for style and length.

Almost 200 species of bacteria colonize microfibers in the Mediterranean Sea, including one that causes food poisoning in humans, according to a new study led by Maria Luiza Pedrotti of Sorbonne Université, published November 30 in the open-access journal PLOS ONE.
Synthetic and natural microfibers from plastic pollution, the textile industry and fishing activities have increased dramatically in the environment, becoming the most common type of particles in the ocean. These microfibers likely pose a threat to aquatic ecosystems and human health, because once they become colonized by microorganisms, they smell like food and are consumed by marine organisms. Due to their persistence, the microfibers likely build up in marine organisms as they move through the food chain.
To find out what types of bacteria live on floating microfibers, researchers used advanced microscopy techniques and DNA sequencing to identify microorganisms living on microfibers collected from the northwestern Mediterranean Sea. They discovered that more than 2,600 cells on average live on each microfiber. These cells belong to 195 bacterial species, including Vibrio parahaemolyticus, a potentially dangerous bacterium that causes food poisoning from seafood.
This new study is the first to report the presence of pathogenic Vibrio species on microfibers in the Mediterranean Sea. The discovery is important for assessing health risks, because the bacterium’s presence can be a threat to bathing and seafood consumption.
The study also raises the question of the environmental risk of microfibers. The increasing amount of persistent plastic waste in the environment may be transporting dangerous bacteria and other pollutants throughout the ocean, thus increasing the risk of contamination compared to short-lived natural particles, such as wood or sediments.
Maria Luiza Pedrotti adds: “The role of climate change also has an influence on the spread of this potentially pathogenic bacteria. Studies have shown that temperature has a significant correlation with the increase of Vibrio spp and the emergence of infections. At the time we found this vibrio, coastal summer temperatures ranged from 25.2-26.5°C, while this year, at the same location, they reached 29°C.”
Story Source:
Materials provided by PLOS. Note: Content may be edited for style and length.