A new study, led by the University of California, Irvine (UCI), reveals how chronic inflammation promotes muscle fibrosis, which could inform the development of new therapies for patients suffering from Duchenne muscular dystrophy (DMD), a fatal muscle disease.
Titled, “A Stromal Progenitor and ILC2 Niche Promotes Muscle Eosinophilia and Fibrosis-Associated Gene Expression,” the study was published today in Cell Reports. Chronic inflammation is a major pathological process contributing to the progression and severity of several degenerative disorders, including Duchenne muscular dystrophy (DMD). Studies directed at establishing a causal link between muscular dystrophy and muscle inflammation have revealed a complex dysregulation of the immune response to muscle damage.
During muscular dystrophy, chronic activation of innate immunity causes scarring of skeletal muscle, or fibrosis, compromising motor function. How immunity is linked to the molecular and cellular regulation of muscle fibrosis was not well defined, until now.
“In our study we found the interaction between two types of cells — a novel stromal progenitor, which is similar to a stem cell, and group 2 innate lymphoid cells (ILC2), which are a type of immune cell that reside in skeletal muscle — promotes the invasion of white blood cells in muscle. This condition is associated with the elevation of genes that promote muscle tissue scarring found in DMD,” said lead author Jenna Kastenschmidt, PhD, an assistant specialist in the UCI School of Medicine Department of Physiology & Biophysics.
The new study not only reveals the interaction of cells contributing to DMD, but it illuminates how muscle eosinophilia is regulated. Eosinophils are white blood cells that infiltrate dystrophic muscle causing fibrosis. In this study, researchers found that eosinophils were elevated in DMD muscle compared to control patients. In addition, researchers found the deletion of ILC2s in dystrophic mice mitigated muscle eosinophilia, reducing the expression of genes associated with muscle fibrosis. These findings contribute to the understanding of the complex regulation of muscle inflammation and fibrosis during muscular dystrophy.
“By further defining the interaction between skeletal muscle-resident immune and stromal cells, we can better understand how chronic inflammation promotes muscle fibrosis and, more importantly, we can facilitate development of novel therapies for DMD,” said senior author Armando Villalta, PhD, assistant professor in UCI’s Department of Physiology & Biophysics.
Ongoing work from Villalta’s lab continues to focus on how distinct facets of the immune system regulate DMD pathogenesis and how these processes influence the efficacy and long-term stability of gene replacement therapy.
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Materials provided by University of California – Irvine. Note: Content may be edited for style and length.

Engineers at the University of California, Berkeley, have created a tiny wireless implant that can provide real-time measurements of tissue oxygen levels deep underneath the skin. The device, which is smaller than the average ladybug and powered by ultrasound waves, could help doctors monitor the health of transplanted organs or tissue and provide an early warning of potential transplant failure.
The technology, created in collaboration with physicians at the University of California, San Francisco, also paves the way for the creation of a variety of miniaturized sensors that could track other key biochemical markers in the body, such as pH or carbon dioxide. These sensors could one day provide doctors with minimally invasive methods for monitoring the biochemistry inside functioning organs and tissues.
“It’s very difficult to measure things deep inside the body,” said Michel Maharbiz, a professor of electrical engineering and computer sciences at UC Berkeley and a Chan Zuckerberg Biohub Investigator. “The device demonstrates how, using ultrasound technology coupled with very clever integrated circuit design, you can create sophisticated implants that go very deep into tissue to take data from organs.”
Maharbiz is the senior author of a new paper describing the device, which appears in the journal Nature Biotechnology.
Oxygen is a key component to cells’ ability to harness energy from the food that we eat, and nearly all tissues in the body require a steady supply in order to survive. Most methods for measuring tissue oxygenation can only provide information about what is happening near the surface of the body. That is because these methods rely on electromagnetic waves, such as infrared light, which can only penetrate a few centimeters into skin or organ tissue. While there are types of magnetic resonance imaging that can provide information about deep tissue oxygenation, they require long scanning times, and so are unable to provide data in real time.
Since 2013, Maharbiz has been designing miniaturized implants that use ultrasonic waves to wirelessly communicate with the outside world. Ultrasonic waves, which are a form of sound too high in frequency to be detected by the human ear, can travel harmlessly through the body at much longer distances than electromagnetic waves and are already the basis of ultrasound imaging technology in medicine. One example of such a device is Stimdust, designed in collaboration with UC Berkeley electrical engineering and computer sciences assistant professor Rikky Muller, which can detect and stimulate electrical nerve firings in the body.

A group of researchers from Kobe University and Chiba University has successfully developed a flexible and simple method of artificially producing genetic switches for yeast, a model eukaryotic organism. The group consisted of Researcher TOMINAGA Masahiro*1, Associate Professor ISHII Jun*2 and Professor KONDO Akihiko*3 (of Kobe University’s Graduate School of Science, Technology and Innovation/Engineering Biology Research Center), and Professor UMENO Daisuke et al. (of Chiba University’s Graduate School of Engineering).
Genetic switches are gene regulatory networks that control gene expression. The researchers established a platform for creating genetic switches that could be applied to the development of sophisticated, artificially controlled yeast cells to produce large quantities of valuable compounds. These research results were published in ‘Nature Communications’ on March 23, 2021.
*1 Technology Research Association of Highly Efficient Gene Design (TRAHED) researcher.
*2 Ibid. Vice Director of the Kobe Center.
*3 Ibid. Director of the Kobe Center.
Main Points Genetic switches are necessary in order to artificially generate new functions in an organism. These switches control the amount of proteins produced by a gene (i.e. gene expression (*1)) and the timing of this production. There has been a lag in the development of genetic switches for eukaryotic organisms in particular, as well as a significant limitation on the number of genes that can be controlled at the same time. The researchers developed a new selection platform in which the cutoff threshold can be set. This enabled them to succeed in creating highly functional, artificial genetic switches for yeast that can be produced easily and flexibly. The developed platform is expected to have a wide range of applications in situations that require precise control of expression levels and timing for a large number of genes. This includes optimizing the balance of metabolic enzyme expression in the construction of cells for producing useful substances that have complex intracellular metabolisms.Research Background

Most young women already know that tanning is dangerous and sunbathe anyway, so a campaign informing them of the risk should take into account their potential resistance to the message, according to a new study.
Word choice and targeting a specific audience are part of messaging strategy, but there is also psychology at play, researchers say — especially when the message is telling people something they don’t really want to hear.
“A lot of thought goes into the content, but possibly less thought goes into the style,” said Hillary Shulman, senior author of the study and an assistant professor of communication at The Ohio State University.
“That’s the argument we’re trying to put out there for people to consider.”
In the study, participants who read a message that combined the most lay-friendly phrasing with references to the specific audience — young women in college — were the most likely to acknowledge the severity of tanning-related risk for skin cancer and say they would curb their own sunbathing behavior.
And that’s because the researchers considered what the young women already thought about soaking in the sun.

Scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory and the University of Illinois Urbana-Champaign (UIUC) have developed a new mathematical model for predicting how COVID-19 spreads. This model not only accounts for individuals’ varying biological susceptibility to infection but also their levels of social activity, which naturally change over time. Using their model, the team showed that a temporary state of collective immunity — what they coined “transient collective immunity” — emerged during early, fast-paced stages of the epidemic. However, subsequent “waves,” or surges in the number of cases, continued to appear because of changing social behaviors. Their results are published in the Proceedings of the National Academy of Sciences.
The COVID-19 epidemic reached the United States in early 2020, rapidly spreading across several states by March. To mitigate disease spread, states issued stay-at-home orders, closed schools and businesses, and put in place mask mandates. In major cities like New York City (NYC) and Chicago, the first wave ended in June. In the winter, a second wave broke out in both cities. Understanding why initial waves end and subsequent waves begin is key to being able to predict future epidemic dynamics.
Here’s where modeling can help. But classical epidemiological models were developed almost 100 years ago. While these models are mathematically robust, they don’t perfectly capture reality. One of their flaws is failing to account for the structure of person-to-person contact networks, which serve as channels for the spread of infectious diseases.
“Classical epidemiological models tend to ignore the fact that a population is heterogenous, or different, on multiple levels, including physiologically and socially,” said Alexei Tkachenko, a physicist in the Theory and Computation Group at the Center for Functional Nanomaterials (CFN), a DOE Office of Science User Facility at Brookhaven Lab. “We don’t all have the same susceptibility to infection because of factors such as age, preexisting health conditions, and genetics. Similarly, we don’t have the same level of activity in our social lives. We differ in the number of close contacts we have and in how often we interact with them throughout different seasons. Population heterogeneity — these individual differences in biological and social susceptibility — is particularly important because it lowers the herd immunity threshold.”
Herd immunity is the percentage of the population who must achieve immunity in order for an epidemic to end.
“Herd immunity is a controversial topic,” said Sergei Maslov, a CFN user and professor and Bliss Faculty Scholar at UIUC, with faculty appointments in the Departments of Physics and Bioengineering and at the Carl R. Woese Institute for Genomic Biology. “Since early on in the COVID-19 pandemic, there have been suggestions of reaching herd immunity quickly, thereby ending local transmission of the virus. However, our study shows that apparent collective immunity reached in this way would not last.”
“What was missing prior to this work was that people’s social activity waxes and wanes, especially due to lockdowns or other mitigations,” added Nigel Goldenfeld, Swanlund Professor of Physics and director of the NASA Astrobiology Institute for Universal Biology at UIUC. “So, a wave of the epidemic can seem to die away due to mitigation measures when the susceptible or more social groups collectively have been infected — what we call transient collective immunity. But once these measures are relaxed and people’s social networks are renewed, another wave can start, as we’ve seen with states and countries opening up too soon, thinking the worst was behind them.”

The COVID-19 pandemic has cast a harsh light on the urgent need for quick and easy techniques to sanitize and disinfect everyday high-touch objects such as doorknobs, pens, pencils, and personal protective gear worn to keep infections from spreading. Now scientists at the U.S. Department of Energy’s (DOE) Princeton Plasma Physics Laboratory and the New Jersey Institute of Technology (NJIT) have demonstrated the first flexible, hand-held, device based on low-temperature plasma — a gas that consists of atoms, molecules, and free-floating electrons and ions — that consumers can quickly and easily use to disinfect surfaces without special training.
Recent experiments show that the prototype, which operates at room temperature under normal atmospheric pressure, can eliminate 99.99 percent of the bacteria on surfaces, including textiles and metals in just 90 seconds. The device has shown a still-higher 99.9999 percent effectiveness when used with the antiseptic hydrogen peroxide. Scientists think it will be similarly effective against viruses. “We’re testing it right now with human viruses,” said PPPL physicist Sophia Gershman, first author of a paper in Scientific Reports that describes the device and the research behind it.
Positive results welcomed
The positive results were welcome at PPPL, which is widening its fusion research and plasma science portfolios. “We are very excited to see plasmas used for a broader range of applications that could potentially improve human health,” said Jon Menard, deputy director for research at PPPL.
The flexible hand-held device, called a dielectric barrier discharge (DBD), is built like a sandwich, Gershman said. “It’s a high-voltage slice of bread on cheese that is an insulator and a grounded piece of bread with holes in it,” she said.
The high-voltage slice of “bread” is an electrode made of copper tape. The other slice is a grounded electrode patterned with holes to let the plasma flow through. Between these slices lies the “cheese” of insulating tape. “Basically it’s all flexible tape like Scotch tape or duct tape,” Gershman said. “The ground electrode faces the users and makes the device safe to use.”
The room-temperature plasma interacts with air to produce what are called reactive oxygen and nitrogen species — molecules and atoms of the two elements — along with a mixture of electrons, currents, and electrical fields. The electrons and fields team up to enable the reactive species to penetrate and destroy bacteria cell walls and kill the cells.

While people may expect suicide rates to rise during a worldwide crisis such as the COVID-19 pandemic, a University of Michigan study suggests the onset of the pandemic and state of emergency executive orders likely did not increase suicide-related behavior in the early months of the outbreak.
The report, led by U-M researchers Rachel Bergmans and Peter Larson, found that emergency room visits related to suicide attempt and self-harm decreased by 40% during the first eight months of Michigan’s lockdown. Their results are published in the Journal of Epidemiology and Community Health.
The study compared emergency room reports of suicide attempt and intentional self-harm at a hospital in Michigan’s Washtenaw County during the first 8 months of the COVID-19 pandemic. The researchers used what’s called a time-series analysis to look at what happened to suicide attempt and self-harm trends before and after the COVID-19 pandemic.
They compared the rate of suicide attempt and self-harm from Oct. 1, 2015, to March 9, 2020, to the rates between March 10, 2020, to October 31, 2020, and found that average daily visits to the ER because of suicidal behavior decreased from 8.6 visits per day to 5.5 per day.
Bergmans, a research fellow in the Survey Research Center at the U-M Institute for Social Research, says a strengthened social structure could be the reason for the decline in these visits.
“More research is needed to confirm why there was a decrease, but the earlier phase of the pandemic came with a lot of communitywide and individual changes including changes in unemployment. These types of factors can increase the risk of suicide,” she said. “However, it’s possible that things like financial assistance from stimulus checks, the eviction moratorium and student loan support that people are receiving might have buffered against some of these other effects.”
The specific method Bergmans and Larson used, called an autoregressive integrated moving average modeling approach, also took into account seasonal variations of suicide rates, which are higher in the spring and fall.

Researchers have found a long-sought enzyme that prevents cancer by enabling the breakdown of proteins that drive cell growth, and that causes cancer when disabled.
Publishing online in Nature on April 14, the new study revolves around the ability of each human cell to divide in two, with this process repeating itself until a single cell (the fertilized egg) becomes a body with trillions of cells. For each division, a cell must follow certain steps, most of which are promoted by proteins called cyclins.
Led by researchers at NYU Grossman School of Medicine, the work revealed that an enzyme called AMBRA1 labels a key class of cyclins for destruction by cellular machines that break down proteins. The work finds that the enzyme’s control of cyclins is essential for proper cell growth during embryonic development, and that its malfunction causes lethal cell overgrowth. Moreover, the study further suggests that an existing drug class may be able to reverse such defects in the future.
As in a developing fetus, restraints on cell division are central to the prevention of abnormal, aggressive growth seen in cancers, and the new study finds that cells have evolved to use AMBRA1 to defend against it.
“Our study clarifies basic features of human cells, provides insights into cancer biology, and opens new research avenues into potential treatments,” says corresponding study author Michele Pagano, MD, chair of the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health, and an investigator with the Howard Hughes Medical Institute.
New Tumor Suppressor
The current study addresses the three D-type cyclins, the subset that must link up with enzymes called cyclin-dependent kinases (CDKs), specifically CDK4 and CDK6, if cells are to divide. The authors found that AMBRA1, as a ligase, attaches molecular tags to all three D-type cyclins, labeling them for destruction. Previously proposed mechanisms for how D-type cyclins are eliminated by the cell could not be reproduced by the scientific community. Thus, prior to the new study, a central regulator of D-type cyclins had remained elusive for a quarter of a century, Pagano says.
The new work also revealed the role of AMBRA1 in development. Mice lacking the AMBRA1 gene, which codes for the AMBRA1 enzyme, developed uncontrolled, lethal tissue growth that distorted the developing brain and spinal cord. The researchers also found for the first time that treating with a CDK4/6 inhibitor pregnant mice carrying embryos without the AMBRA1 gene reduced these neuronal abnormalities.
In terms of cancer, the authors analyzed patient databases to conclude that those with lower-than-normal expression of AMBRA1 were less likely to survive diffuse large B-cell lymphoma, the most common form of non-Hodgkin lymphoma in the United States. The causes of lower expression of AMBRA1 may include random changes that delete the gene or make its encoded instructions harder to read.
To confirm the role of AMBRA1 as a tumor suppressor, the researchers monitored cancer cell growth in mouse models of diffuse large B-cell lymphoma, in collaboration with study author Luca Busino, PhD, at the University of Pennsylvania. When human B-cell lymphoma cells were transplanted into mice, for instance, tumors without the AMBRA1 gene grew up to three times faster than those with the gene. While the NYU Langone-led study looked at diffuse large B-cell lymphoma, two other studies led by Stanford University and the Danish Cancer Society Research Center, published in the same issue of Nature, found missing or disabled AMBRA1 to be a key factor in lung cancer.
Further, D-type cyclins are known to assemble with CDK4 and CDK6 into enzymes that encourage both normal and abnormal cell growth. Drugs that inhibit CDK4 and CDK6 have been FDA-approved in recent years as cancer therapies, but some patients have a weaker response to the drugs. Providing insight into this problem, the current team found that lymphomas lacking AMBRA1 are less sensitive to CDK4/6 inhibitors. When the AMBRA1 gene is missing, levels of D-type cyclins become high enough to form complexes with another CDK (CDK2), which, due to its structure, cannot be inactivated by CDK4/6 inhibitors.
“This makes AMBRA1 a potential marker for the selection of patients best suited for CDK4/6 inhibitor therapy,” says first author Daniele Simoneschi, PhD, a senior research coordinator in the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health. As a next step, he says the team plans to study the effect of combining CDK4/6 inhibitors with CDK2 inhibitors in tumors with low AMBRA1, as well as in those with mutations in D-type cyclins that make them insensitive to AMBRA1.

The human genome contains the instructions to make tens of thousands of proteins. Each protein folds into a precise shape — and biologists are taught that defined shape dictates the protein’s destined function. Tens of thousands of singular shapes drive the tens of thousands of needed functions.
In a new Cell Reports study, researchers at La Jolla Institute for Immunology demonstrate how Ebola virus has found a different way to get things done. The virus encodes only eight proteins but requires dozens of functions in its lifecycle. The new study shows how one of Ebola virus’s key proteins, VP40, uses molecular triggers in the human cell to transform itself into different tools for different jobs.
“We’re all taught that proteins have ‘a’ structure,” says study co-leader Erica Ollmann Saphire, Ph.D., professor at La Jolla Institute for Immunology (LJI) and member of the LJI Center for Infectious Disease and Vaccine Research. “Ebola virus’s VP40 protein, however, changes itself into different structures at different times, depending on the function needed.”
VP40 is the protein that gives Ebola virus its distinctive string-like shape. Saphire’s previous studies showed that VP40 can take on a two-molecule, butterfly-shaped “dimer” or an eight-molecule, wreath-like “octamer” form.
There are dramatic rearrangements of the protein as it transforms from one to the other. The dimer is what physically constructs new viruses that emerge and release from infected cells. The octamer functions only inside the infected cell, in a controlling role, directing other steps of the viral life cycle.
The new study shows exactly what triggers these structural changes. The researchers found that VP40 senses and relies on particular human mRNA to make the transformation from the dimer to octamer.

Food waste and obesity are major problems in developed countries. They are both caused by an overabundance of food, but strategies to reduce one can inadvertently increase the other. A broader perspective can help identify ways to limit food waste while also promoting healthy nutrition, two University of Illinois researchers suggest.
“You can reduce food waste by obtaining less or eating more. Our concern was that if people are reducing waste by eating more, what does that mean for nutrition? And how do we think about these tradeoffs in a way that promotes both good nutrition outcomes and good food waste outcomes? Public policies have generally focused on either obesity or food waste, but rarely considered them together, says Brenna Ellison, associate professor in the Department of Agricultural and Consumer Economics (ACE) at U of I.
Ellison and Melissa Pflugh Prescott, assistant professor in the Department of Food Science and Human Nutrition (FSHN) at U of I, discuss a systems approach to addressing food waste and nutrition in a new paper, published in Journal of Nutrition Education and Behavior.
Food waste refers to the loss of edible food that is not consumed for various reasons. It occurs at all levels of the supply chain, from farm to transportation, processing, retail, food service, and consumer levels.
Food waste is often calculated by weight or by calories, Ellison explains. If you calculate by weight, dairy products, vegetables, grain products, and fruit account for the majority of food loss. But when converted to calories, added fats and oils, grain products, and added sugars and sweeteners are the top categories for food waste. Encouraging increased consumption of those foods could have negative health consequences, she notes.
In their paper, Ellison and Prescott provide strategies for reducing food waste in a variety of settings, including food service, retail, schools, and homes.