Just like your future body will thank you for the apple, your future ears (specifically your cochlear hair cells) will thank you for protecting them. The most common cause of hearing loss is progressive because these hair cells — the primary cells to detect sound waves — cannot regenerate if damaged or lost. People who have repeated exposure to loud noises, like military personnel, construction workers, and musicians, are most at risk for this type of hearing loss. But, it can happen to anyone over time (even concert goers).

On the other hand, birds and fish can regenerate these hair cells, and now researchers at the Del Monte Institute for Neuroscience are getting closer to identifying the mechanisms that may promote this type of regeneration in mammals, as explained in research recently published in Frontiers in Cellular Neuroscience.

“We know from our previous work that expression of an active growth gene, called ERBB2, was able to activate the growth of new hair cells (in mammals), but we didn’t fully understand why,” said Patricia White, PhD, professor of Neuroscience and Otolaryngology at the University of Rochester Medical Center. The 2018 study led by Jingyuan Zhang, PhD, a postdoctoral fellow in the White lab at the time, found that activating the growth gene ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to multiply and activate other neighboring stem cells to become new sensory hair cells.

“This new study tells us how that activation is happening — a significant advance toward the ultimate goal of generating new cochlear hair cells in mammals,” said White.

Using single-cell RNA sequencing in mice, researchers compared cells with an overactive growth gene (ERBB2 signaling) with similar cells that lacked such signaling. They found the growth gene — ERBB2 — promoted stem cell-like development by initiating the expression of multiple proteins — including SPP1, a protein that signals through the CD44 receptor. The CD44 receptor is known to be present in cochlear-supporting cells. This increase in cellular response promoted mitosis in the supporting cells, a key event for regeneration.

“When we checked this process in adult mice, we were able to show that ERBB2 expression drove the protein expression of SPP1 that is necessary to activate CD44 and grow new hair cells,” said Dorota Piekna-Przybylska, PhD, a staff scientist in the White Lab and first author of the study. “This discovery has made it clear that regeneration is not only restricted to the early stages of development. We believe we can use these findings to drive regeneration in adults.”

“We plan to further investigation of this phenomenon from a mechanistic perspective to determine whether it can improve auditory function after damage in mammals. That is the ultimate goal,” said White.

Additional authors include Daxiang Na, Cameron Baker, and John Ashton, PhD, at the University of Rochester and Medical Center. The research was supported by the U.S. Army Medical Research Mechanism, the National Institute on Deafness and Other Communication Disorders, UR Ventures, and the Schmitt Program on Integrative Neuroscience.

Physical activity at different times of the day can affect the body in different ways since the biological processes depend on the circadian rhythms of the cells. To ascertain how the time of day at which exercise is done affects the burning of fat, researchers at Karolinska Institutet and the University of Copenhagen studied the adipose tissue of mice after a session of high-intensity exercise performed at two points of the daily cycle, an early active phase and early rest phase (corresponding to a late morning and late evening session, respectively, in humans). The researchers studied various markers for fat metabolism and analysed which genes were active in adipose tissue after exercise.

Independent of food intake

The researchers found that physical activity at an early active phase increased the expression of genes involved in the breakdown of adipose tissue, thermogenesis (heat production) and mitochondria in the adipose tissue, indicating a higher metabolic rate. These effects were observed only in mice that exercised in the early active phase and were independent of food intake.

“Our results suggest that late morning exercise could be more effective than late evening exercise in terms of boosting the metabolism and the burning of fat, and if this is the case, they could prove of value to people who are overweight,” says Professor Juleen R. Zierath from the Department of Molecular Medicine and Surgery and the Department of Physiology and Pharmacology, Karolinska Institutet.

Improve the health benefits of exercise

Mice and humans share many basic physiological functions, and mice are a well-established model for human physiology and metabolism. However, there are also important differences, such as the fact that mice are nocturnal.

“The right timing seems to be important to the body’s energy balance and to improving the health benefits of exercise, but more studies are needed to draw any reliable conclusions about the relevance of our findings to humans,” says Professor Zierath.

The study was conducted in close collaboration with the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen and was financed by the Novo Nordisk Foundation, Novo Nordisk, the Swedish Diabetes Foundation, the Swedish Research Council and Karolinska Institutet.

One of the major limitations for real-world applications of this technology is that the materials that make superconducting possible typically need to be at extremely cold temperatures to reach that level of electrical efficiency. To get around this limit, researchers need to build a clear picture of what different superconducting materials look like at the atomic scale as they transition through different states of matter to become superconductors.

Scholars in a Brown University lab, working with an international team of scientists, have moved a small step closer to cracking this mystery for a recently discovered family of superconducting Kagome metals. In a new study, they used an innovative new strategy combining nuclear magnetic resonance imaging and a quantum modeling theory to describe the microscopic structure of this superconductor at 103 degrees Kelvin, which is equivalent to about 275 degrees below 0 degrees Fahrenheit.

The researchers described the properties of this bizarre state of matter for what’s believed to be the first time in Physical Review Research. Ultimately, the findings represent a new achievement in a steady march toward superconductors that operate at higher temperatures. Superconductors that can operate at room temperature (or close to it) are considered the holy grail of condensed-matter physics because of the tremendous technological opportunities they would open in power efficiency, including in electricity transmission, transportation and quantum computing.

“If you are ever going to engineer something and make it commercial, you need to know how to control it,” said Brown physics professor Vesna Mitrovi?, who leads a condensed matter NMR group at the University and is a co-author on the new study. “How do we describe it? How do we tweak it so that we get what we want? Well, the first step in that is you need to know what the states are microscopically. You need to start to build a complete picture of it.”

The new study focuses on superconductor RbV3Sb5, which is made of the metals rubidium vanadium and antimony. The material earns its namesake because of its peculiar atomic structure, which resembles a basketweave pattern that features interconnected star-shaped triangles. Kagome materials fascinate researchers because of the insight they provide into quantum phenomena, bridging two of the most fundamental fields of physics — topological quantum physics and condensed matter physics.

Previous work from different groups established that this material goes through a cascade of different phase transitions when the temperature is lowered, forming different states of matter with different exotic properties. When this material is brought to 103 degrees Kelvin, the structure of lattice changes and the material exhibits what’s known as a charge-density wave, where the electrical charge density jumps up and down. Understanding these jumps is important for the development of theories that describe the behavior of electrons in quantum materials like superconductors.

What hadn’t been seen before in this type of Kagome metal was what the physical structure of this lattice and charge order looked like at the temperature the researchers were looking at, which is highest temperature state where the metal starts transitioning between different states of matter.

Using a new strategy combining NMR measurements and a modeling theory known as density functional theory that’s used to simulate the electrical structure and position of atoms, the team was able to describe the new structure the lattice changes into and its charge-density wave.

They showed that the structure moves from a 2x2x1 pattern with a signature Star of David pattern to a 2x2x2 pattern. This happens because the Kagome lattice inverts in on itself when the temperature gets extremely frigid. The new lattice it transitions into is made up largely of separate hexagons and triangles, the researchers showed. They also showed how this pattern connects when they take one plane of the RbV3Sb5 structure and rotate it, “gazing ” into it from a different angle.

“It’s as if this one Kagome now becomes these complicated things that split in two,” Mitrovi? said. “It stretches the lattice so that the Kagome becomes this combination of hexagons and triangles in one plane and then in the next plane over, after you rotate it half a circle, it repeats itself.”

Probing this atomic structure is a necessary step to providing a complete portrait of the exotic states of matter this superconducting material transitions into, the researchers said. They believe the findings will lead to further prodding on whether this formation and its properties can help superconductivity or if it’s something that should be suppressed to make better superconductors. The new unique technique they used will also allow the researchers to answer a whole new set of questions.

“We know what this is now and our next job is to figure out what is the relationship to other bizarre phases at low temperature — does it help, does it compete, can we control it, can we make it happen at higher temperatures, if it’s useful?” Mitrovi? said. “Next, we keep lowering the temperature and learning more.”

The experimental research was led by Jonathan Frassineti, a joint graduate student between Brown and the University of Bologna, Pietro Bonfà from the University of Parma, and two Brown students: Erick Garcia and Rong Cong. Theoretical work was led by Bonfà while all the materials were synthesized at the University of California Santa Barbara. This research included funding from the National Science Foundation.