Publisher Health

Nearly 40 percent of people experience syncope, or fainting spells, at least once in their lives. These brief losses of consciousness, whether brought by pain, fear, heat, hyperventilation or other causes, account for a significant portion of hospital emergency room visits. Yet the exact root mechanisms at play when people “pass out” largely have remained a mystery.
Publishing a new report in Nature, University of California San Diego researchers, along with colleagues at The Scripps Research Institute and other institutions, have for the first time identified the genetic pathway between the heart and brain tied to fainting.
One of their unique approaches was to think of the heart as a sensory organ rather than the longstanding viewpoint that the brain sends out signals and the heart simply follows directions. School of Biological Sciences Assistant Professor Vineet Augustine, the paper’s senior author, applies a variety of approaches to better understand these neural connections between the heart and brain.
“What we are finding is that the heart also sends signals back to the brain, which can change brain function,” said Augustine. Information resulting from the study could be relevant to better understanding and treating various psychiatric and neurological disorders linked with brain-heart connections, the researchers note in their paper. “Our study is the first comprehensive demonstration of a genetically defined cardiac reflex, which faithfully recapitulates characteristics of human syncope at physiological, behavioral and neural network levels.”
Augustine, along with Biological Sciences Staff Research Associate Jonathan Lovelace and Graduate Student Jingrui Ma, the first authors of the paper, and their colleagues studied neural mechanisms related to Bezold-Jarisch reflex (BJR), a cardiac reflex first described in 1867. For decades researchers have hypothesized that the BJR, which features reduced heart rate, blood pressure and breathing, may be associated with fainting. But information lacked in proving the idea since the neural pathways involved in the reflex were not well known.
The researchers focused on the genetics behind a sensory cluster known as the nodose ganglia, which are part of the vagus nerves that carry signals between the brain and visceral organs, including the heart. Specifically, vagal sensory neurons, or VSNs, project signals to the brainstem and are thought to be associated with BJR and fainting. In their search for a novel neural pathway they discovered that VSNs expressing the neuropeptide Y receptor Y2 (known as NPY2R) are tightly linked to the well-known BJR responses.
Studying this pathway in mice, the researchers were surprised to find that when they proactively triggered NPY2R VSNs using optogenetics, a method of stimulating and controlling neurons, mice that had been freely moving about immediately fainted. During these episodes they recorded from thousands of neurons in the brains of the mice, as well as heart activity and changes in facial features including pupil diameter and whisking. They also employed machine learning in several ways to analyze the data and pinpoint features of interest. Once NPY2R neurons were activated, they found, mice exhibited rapid pupil dilation and the classic “eye-roll” seen during human fainting, as well as suppressed heart-rate, blood pressure and breathing rate. They also measured reduced blood flow to the brain, an area of collaboration with Professor David Kleinfeld’s laboratory in the UC San Diego Departments of Neurobiology and Physics.

New research from the University of Cincinnati found that daily strawberry consumption could help reduce the risk of dementia for certain middle-aged populations.
The research was recently published in the journal Nutrients.
Research background
In 2022, UC’s Robert Krikorian, PhD, and his team published research that found adding blueberries to the daily diets of certain middle-aged populations may lower the chances of developing late-life dementia. He said the current research into strawberries is an extension to the blueberry research.
“Both strawberries and blueberries contain antioxidants called anthocyanins, which have been implicated in a variety of berry health benefits such as metabolic and cognitive enhancements,” said Krikorian, professor emeritus in the UC College of Medicine’s Department of Psychiatry and Behavioral Neuroscience. “There is epidemiological data suggesting that people who consume strawberries or blueberries regularly have a slower rate of cognitive decline with aging.”
In addition to containing anthocyanins, Krikorian said strawberries contain additional micronutrients called ellagitannins and ellagic acid that have been associated with health benefits.
About 50% of individuals in the U.S. develop insulin resistance, commonly referred to as prediabetes, around middle age, which has been shown to be a factor in chronic diseases. Krikorian said the metabolic and cardiovascular benefits of strawberry consumption have been studied previously, but there were relatively few studies on its cognitive effects.

As people age, the DNA in their cells begins to accumulate genetic mutations. Mosaic chromosomal alterations (mCAs), a category of mutations acquired in blood cells, are linked with a 10-fold increased risk of developing blood cancer.
mCAs hold promise as a tool to identify people at high risk of developing certain cancers and diseases, but they have not yet been studied among a large, diverse cohort of people — a critical step required before such testing can be developed.
University of Kentucky Markey Cancer Center researcher Yasminka A. Jakubek, Ph.D., has led the first large-scale effort to understand the co-occurrence of mCAs among individuals of diverse ancestries. The study was published in Nature Genetics Oct. 30.
The research team — consisting of more than 50 scientists representing institutions across the U.S. — detected mCAs using existing DNA sequencing data from the National Heart, Lung and Blood Institute’s Trans Omics for Precision Medicine Program. The diverse cohort of more than 67,000 included individuals in the U.S. with African, East Asian, European and Hispanic ancestries. Prior studies have mainly focused on individuals with European and Japanese ancestries.
“mCAs are promising biomarkers for cancer risk assessment and early detection,” said Jakubek, an assistant professor in the UK College of Medicine’s Department of Internal Medicine. “Studies that are inclusive are important to ensure that mosaic mutation-based disease risk models and clinical biomarker studies perform equally well regardless of a person’s genetic ancestry.”
While mCAs can arise through unrelated molecular mechanisms, a person’s genetic ancestry can contribute to the risk of developing certain mCAs. Humans have 22 pairs of autosomal chromosomes and one pair of sex chromosomes (XX or XY). The study found that mCAs affecting autosomal chromosomes are more common in people with European ancestry.
The research team also looked at mosaic alterations on specific chromosomes and found differences in the rate of mutations across individuals of different ancestries. The most notable finding was an increased rate of mCAs on chromosome X among people with African and Hispanic ancestries who were born with XX sex chromosomes.
The team also identified new inherited genetic variants that are associated with an increased risk for mCAs and loss of X.
In addition to paving the way for a blood test that could identify people at risk of developing certain cancers, the research gives scientists valuable insights into drivers of genomic instability, a key characteristic of cancer cells.
“The long-term goal of our study is to lay a foundation for advances in precision medicine by studying the mutations that we accumulate as we age,” Jakubek said. “It’s critical that people of diverse background are included and participate in studies such as this one to avoid inequity in future medical advances.”

A new Duke University-led study finds that Gulf War Illness (GWI), which affects approximately 250,000 U.S. veterans, significantly reduces their white blood cells’ ability to make energy and creates a measurable biochemical difference in veterans who have the disease.
“Historically, GWI has been diagnosed based on a veteran’s self-reported symptoms, such as exercise-induced fatigue, indigestion, dizziness, insomnia, or memory problems. There’s been no objective biochemical or molecular measurements doctors could use to diagnose it,” said Joel Meyer, professor of environmental genomics at Duke’s Nicholas School of the Environment, who led the new study.
The new study provides measurements accessible in blood samples, which, though not sufficient to serve as a stand-alone diagnostic test, could be useful to help improve treatment for veterans suffering from Gulf War Illness by giving doctors a new way to assess whether a prescribed treatment is helping, Meyer said.
“Knowing this is an energetic deficiency can help us zero in on more effective ways to relieve the symptoms,” Meyer said. “Blood tests, repeated over the course of the treatment, would show if a veteran’s white blood cells are responding to a treatment and producing more energy.”
He and his coauthors from Duke, the U.S. Department of Veteran Affairs’ War-Related Illness and Injury Study Center, and the New Jersey Medical School published the new peer-reviewed paper Nov. 1 in the open-access journal PLOS ONE.
Their research reveals that Gulf War Illness inhibits white blood cells’ energy production by impairing the workings of the cells’ mitochondria, structures within the cell which extract energy from food and convert it into the chemical power needed to fuel growth, movement and other bodily processes and functions. Mitochondria are often referred to as the ‘power plants’ of the cell.
“The idea to investigate the role mitochondria might be playing in GWI came from Mike Falvo, one of my coauthors from Veteran Affairs and the New Jersey Medical School, who had noticed that a lot of GWI symptoms were similar to those associated with mitochondrial diseases,” said Meyer. “So, we analyzed mitochondrial respiration and extracellular acidification, which are proxies for energy generation, in the white blood cells of 114 Gulf War veterans, 80 of whom had been diagnosed with GWI. We also looked for evidence of mitochondrial DNA damage and nuclear DNA damage.”
The analyses revealed no evidence of DNA damage, but they did show significantly lower levels of extracellular acidification and oxygen consumption in the white blood cells from veterans with GWI — signs that their mitochondria were generating less energy.

For years, if you asked the people working to create new pharmaceutical drugs what they wished for, at the top of their lists would be a way to easily replace a carbon atom with a nitrogen atom in a molecule.
But two studies from chemists at the University of Chicago, published in Science and Nature, offer two new methods to address this wish. The findings could make it easier to develop new drugs.
“This is the grand-challenge problem that I started my lab to try to solve,” said Mark Levin, an associate professor of chemistry and the senior author on both papers. “We haven’t totally solved it, but we’ve taken two really big bites out of the problem, and these findings lay a clear foundation for the future.”
Body swap
In chemistry, a single atom can make a huge difference in a molecule. Swap out one carbon atom for a nitrogen atom, and the way the drug molecule interacts with its target can dramatically change. It might make the drug easier to get to the brain, for example, or less likely to grab onto the wrong proteins on its way. So when scientists are creating new pharmaceutical drugs, they often want to try swapping out one particular atom.
The trouble is, this is much easier said than done. To build a molecule, you have to go step by step. If you get to the end, but then start testing and think the drug might work better if you changed just one atom, you have to go back to the beginning and re-invent the entire process.
“There’s a cost-benefit analysis that comes into play. Is it worth it to start over? Or do you just go with what you have?” explained Tyler Pearson, a postdoctoral researcher who is the first author on one of the studies.

A recent study led by Indiana University School of Medicine in collaboration with the University of Chicago Medicine presents exciting future possibilities for the management of type 1 diabetes and the potential reduction of insulin dependency. The researchers’ findings, published in Cell Reports Medicine, suggest repurposing of the drug α-difluoromethylornithine (DFMO) may open doors to innovative therapies in the future.
Type 1 diabetes is a chronic condition wherein the body’s immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas, leading to high blood sugar levels that currently require lifelong insulin treatment to keep patients alive. Many people living with type 1 diabetes find current treatments, including daily insulin injections and frequent blood sugar monitoring, inconvenient and challenging to manage.
These latest translational results represent more than a decade of research. In 2010, the study’s co-corresponding author, Raghu Mirmira, MD, PhD, was operating a research lab at IU School of Medicine in 2010 when his team initially discovered that inhibiting the metabolic pathway affected by DFMO could safeguard beta cells from environmental factors, suggesting potential preservation in type 1 diabetes. The team subsequently validated these findings in mice.
From 2015 to 2019, Linda DiMeglio, MD, MPH, Edwin Letzter Professor of Pediatrics at IU School of Medicine and a pediatric endocrinologist and division chief at Riley Children’s Health, directed a clinical trial that affirmed DFMO’s safety in people newly diagnosed with type 1 diabetes and suggested that it might also stabilize insulin levels by safeguarding beta cells. The trial was funded by the Juvenile Diabetes Research Foundation (JDRF) with drug provided by Panbela Therapeutics.
“After several years of bench-to-bedside studies, beginning with Drs. Mirmira and [Sarah] Tersey’s mouse models, it’s exciting to finally share the promising results from our pilot trial in humans,” said DiMeglio, senior author of the study. “Now that we’ve established preliminary safety of DFMO for individuals with type 1 diabetes, we’re thrilled about advancing our collaborative research to explore more of its potential benefits in a larger clinical trial.”
Since 1990, DFMO has been FDA-approved as a high-dose injection to treat African Sleeping Sickness, and in 2020 it received a breakthrough therapy designation for neuroblastoma maintenance therapy after remission. This prior regulatory clearance could streamline its adoption as a type 1 diabetes treatment, potentially shortening the approval process from decades to just a few years.
“Using a new formulation of DFMO as a pill allows patients to take it by mouth instead of needing to undergo regular injections, and it has a very favorable side effect profile,” said Mirmira, who is now a professor of medicine and an endocrinologist at UChicago Medicine. “It’s exciting to say we have a drug that works differently from every other treatment we have for this disease.”
The researchers have already initiated their next steps in investigating DFMO’s potential. The study’s first author and co-corresponding author Emily K. Sims, MD, associate professor of pediatrics at IU School of Medicine and a pediatric endocrinologist at Riley Children’s Health, recently launched a larger, six-center clinical study to robustly define the impact of DFMO treatment to preserve beta cell function in type 1 diabetes. The new study is also funded by JDRF and supported by Panbela Therapeutics.

Researchers have genetically engineered the first mice that get a human-like form of COVID-19, according to a study published online November 1in Nature.
Led by researchers from NYU Grossman School of Medicine, the new work created lab mice with human genetic material for ACE2 — a protein snagged by the pandemic virus so it can attach to human cells as part of the infection. The mice with this genetic change developed symptoms similar to young humans infected with the virus causing COVID-19, instead of dying upon infection as had occurred with prior mouse models.
“That these mice survive creates the first animal model that mimics the form of COVID-19 seen in most people — down to the immune system cells activated and comparable symptoms,” said senior study author Jef Boeke, the Sol and Judith Bergstein Director of the Institute for Systems Genetics at NYU Langone Health. “This has been a major missing piece in efforts to develop new drugs against this virus.”
“Given that mice have been the lead genetic model for decades,” added Boeke, “there are thousands of existing mouse lines that can now be crossbred with our humanized ACE2 mice to study how the body reacts differently to the virus in patients with diabetes or obesity, or as people age.”
Problem of Large DNA
The new study revolves around a new method to edit DNA, the 3 billion “letters” of the genetic code that serve as instructions for building our cells and bodies.
While famous techniques like CRISPR enable the editing of DNA editing just one or a few letters at a time, some challenges require changes throughout genes that can be up to 2 million letters long. In such cases, it may be more efficient to build DNA from scratch, with far-flung changes made in large swaths of code pre-assembled and then swapped into a cell in place of its natural counterpart. Because human genes are so complex, Boeke’s lab first developed its “genome writing” approach in yeast, one-celled fungi that share many features with human cells but that are simpler and easier to study.

Neurons talk to each other using chemical signals called neurotransmitters. Scientists at St. Jude Children’s Research Hospital have drawn on structural biology expertise to determine structures of vesicular monoamine transporter 2 (VMAT2), a key component of neuronal communication. By visualizing VMAT2 in different states, scientists now better understand how it functions and how the different shapes the protein takes influence drug binding — critical information for drug development to treat hyperkinetic (excess movement) disorders such as Tourette syndrome. The work was published today in Nature.
How our neurons talk to each other
Chemical compounds called monoamines, which include dopamine, serotonin and adrenaline, play a central role in neuronal communication. These molecules affect how the brain works, controlling our emotions, sleep, movement, breathing, circulation and many other functions. Monoamines are neurotransmitters (signaling molecules) produced and released by neurons, but before they can be released, they must first be packaged into vesicles.
Vesicles are cellular compartments that store neurotransmitters before they are released at the synapses (the junction through which chemical signals pass from one neuron to another). Think of vesicles as the cargo ships of the neuronal cell — neurochemicals are packed inside them and taken to where they need to go. VMATs are proteins on the membrane of these vesicles that move monoamines into the space within, acting like loading cranes for the cargo ships.
“VMATs are transporters that are required for packing these monoamine neurotransmitters into synaptic vesicles,” explained co-corresponding author Chia-Hsueh Lee, Ph.D., St. Jude Department of Structural Biology.
Once the VMAT has packed the vesicle with monoamines, the “cargo ship” moves towards the synaptic gap (the space between neurons), where it releases the chemical compounds.
The many faces of monoamine transporters
There are two types of VMAT: VMAT1 and VMAT2. VMAT1 is more specialized, found only in neuroendocrine cells, whereas VMAT2 is found throughout the neuronal system and has significant clinical relevance.

In a recent publication in the journal Nature, researchers from the Institute of Basic Science (IBS) in South Korea have made significant strides in biomaterial technology and rehabilitation medicine. They’ve developed a novel approach to healing muscle injury by employing “injectable tissue prosthesis” in the form of conductive hydrogels and combining it with a robot-assisted rehabilitation system.
Let’s imagine you are swimming in the ocean. A giant shark approaches and bites a huge chunk of meat out of your thigh, resulting in a complete loss of motor/sensor function in your leg. If left untreated, such severe muscle damage would result in permanent loss of function and disability. How on Earth will you be able to recover from this kind of injury?
Traditional rehabilitation methods for these kinds of muscle injuries have long sought an efficient closed-loop gait rehabilitation system that merges lightweight exoskeletons and wearable/implantable devices. Such assistive prosthetic system is required to aid the patients through the process of recovering sensory and motor functions linked to nerve and muscle damage.
Unfortunately, the mechanical properties and rigid nature of existing electronic materials render them incompatible with soft tissues. This leads to friction and potential inflammation, stalling patient rehabilitation.
To overcome these limitations, the IBS researchers turned to a material commonly used as a wrinkle-smoothing filler, called hyaluronic acid. Using this substance, an injectable hydrogel was developed for “tissue prostheses,” which can temporarily fill the gap of the missing muscle/nerve tissues while it regenerates. The injectable nature of this material gives it a significant advantage over traditional bioelectronic devices, which are unsuitable for narrow, deep, or small areas, and necessitate invasive surgeries.
Thanks to its highly “tissue-like” properties, this hydrogel seamlessly interfaces with biological tissues and can be easily administered to hard-to-reach body areas without surgery. The reversible and irreversible crosslinks within the hydrogel adapt to high shear stress during injection, ensuring excellent mechanical stability. This hydrogel also incorporates gold nanoparticles, which gives it decent electrical properties. Its conductive nature allows for the effective transmission of electrophysiological signals between the two ends of injured tissues. In addition, the hydrogel is biodegrdable, meaning that the patients do not need to get surgery again.
With mechanical properties akin to natural tissues, exceptional tissue adhesion, and injectable characteristics, researchers believe this material offers a novel approach to rehabilitation.

The human heart, often described as the body’s engine, is a remarkable organ that tirelessly beats to keep us alive. At the core of this vital organ, intricate processes occur when it contracts, where thick and thin protein-filaments interact within the sarcomere, the fundamental building block of both skeletal and heart muscle cells. Any alterations in thick filament proteins can have severe consequences for our health, leading to conditions such as hypertrophic cardiomyopathy and various other heart and muscle diseases.
In a remarkable scientific achievement, an international team, led by Stefan Raunser, Director at the Max Planck Institute of Molecular Physiology in Dortmund, in collaboration with Mathias Gautel at King’s College London, has achieved a groundbreaking milestone. They have successfully obtained the world’s first high-resolution 3D image of the thick filament in its natural cellular environment, utilizing a cutting-edge technique known as electron cryo-tomography. This unprecedented accomplishment offers a glimpse into the molecular organization and arrangement of the components within the thick filament. This newfound insight is nothing short of a crucial framework for comprehending how muscles operate in both health and disease. By understanding the intricate mechanics at play, scientists are now better equipped to develop innovative pharmacological approaches and treatments that can target heart and muscle disorders, potentially revolutionizing medical intervention in these areas.
Atrial fibrillation, heart failure and stroke — hypertrophic cardiomyopathy can lead to many serious health conditions and is a major cause of sudden cardiac death in people younger than 35. “The heart muscle is a central engine of the human body. Of course, it is easier to fix a broken engine, if you know how it is built and how it functions,” says Stefan Raunser. “At the beginning of our muscle research we have successfully visualized the structure of the essential muscle building blocks and how they interact using electron cryo-microscopy. However, these were static images of proteins taken out of the living cell. They only tell us little about how the highly variable, dynamic interplay of muscle components moves the muscle in its native environment,” says Raunser.
Through thick and thin
Skeletal and heart muscles contract upon the interaction of two types of parallel protein filaments in the sarcomere: thin and thick. The sarcomere is subdivided in several regions, called zones and bands, in which these filaments are arranged in different ways. The thin filament consists of F-actin, troponin, tropomyosin, and nebulin. The thick filament is formed of myosin, titin and myosin binding protein C (MyBP-C). The latter can form links between the filaments, whereas myosin, the so-called motor protein interacts with the thin filament to generate force and muscle contraction. Alterations in the thick filament proteins are associated with muscle diseases. A detailed picture of the thick filament would be of immense importance for developing therapeutical strategies to cure these diseases, but has been missing so far.
Milestones in muscle research
“If you want to fully understand how the muscle works on the molecular level, you need to picture its components in their natural environment — one of the biggest challenges in biological research nowadays that cannot be tackled by traditional experimental approaches,” says Raunser. To overcome this obstacle his team developed an electron cryo-tomography workflow specifically tailored to the investigation of muscle samples: The scientists flash-freeze mammalian heart muscle samples, produced by the Gautel group in London, at a very low temperature (- 175 °C). This preserves their hydration and fine structure and thus their native state. A focused ion beam (FIB milling) is then applied to thin out the samples to an ideal thickness of around 100 nanometers for the transmission electron microscope, which acquires multiple images as the sample is tilted along an axis. Finally, computational methods reconstruct a three-dimensional picture at high resolution. In recent years, Raunser’s group successfully applied the customized workflow, resulting in two recent groundbreaking publications: They produced the first high-resolution images of the sarcomere and of a so far nebulous muscle protein called nebulin. Both studies provide unprecedented insights into the 3D organization of muscle proteins in the sarcomere, e. g. how myosin binds to actin to control muscle contraction and how nebulin binds to actin to stabilize it and to determine its length.
Completing the painting
In their current study the scientists produced the first high-resolution image of the cardiac thick filament spanning across several regions in the sarcomere. “With 500 nm length this makes for the longest and biggest structure ever resolved by cryo-ET,” says Davide Tamborrini from the MPI Dortmund, first-author of the study. Even more impressive are the newly gained insights into the thick filament’s molecular organization and thus into its function. The arrangement of the myosin molecules depends on their position in the filament. The scientists suspect, that this allows the thick filament to sense and process numerous muscle-regulating signals and thus to regulate the strength of muscle contraction depending on the sarcomere region. They also revealed how titin chains run along the filament. Titin chains intertwine with myosin, acting as a scaffold for its assembly and probably orchestrating a length-depending activation of the sarcomere.
“Our aim is to paint a complete picture of the sarcomere one day. The image of the thick filament in this study is ‘only’ a snapshot in the relaxed state of the muscle. To fully understand how the sarcomere functions and how it is regulated, we want to analyze it in different states e. g. during contraction,” says Raunser. Comparison with samples from patients with muscle disease will ultimately contribute to a better understanding of diseases like hypertrophic cardiomyopathy and to the development of innovative therapies.