Their discovery about brain cells called microglia heralds myriad possibilities for treating and even preventing neurodegenerative disorders. The team’s paper appears in the Journal of Experimental Medicine.

When microglia are healthy, they serve as the central nervous system’s resident front-line disease warriors. “However, there is overwhelming evidence that they can become dysfunctional in many neurological conditions,” said Mathew Blurton-Jones, UCI professor of neurobiology & behavior and study co-lead author. “Until recently, scientists have mainly been looking at the mechanisms that drive microglial dysfunction and trying to find drugs to change their activity. But with this study, we’ve found a way to potentially harness microglia themselves to treat those diseases.”

Frederick “Chris” Bennett, assistant professor of psychiatry at Penn and co-lead author, added: “There is an obstacle because once our own microglia develop in the location where they are supposed to be in our brains, they don’t give up that space. They block the ability to deliver new cells that would take their place. If you want to insert donor microglia, you have to deplete the host microglia to open up room.”

Bennett and his laboratory partnered with Blurton-Jones and his lab on the project.

Microglia depend on signaling by a protein on their surface called CSF1R for their survival. The FDA-approved cancer drug pexidartinib has been found to block that signaling, killing them. This process would seem to offer a way to clear space in the brain to insert healthy donor microglia. However, there is a dilemma — unless the pexidartinib is stopped before the donor microglia are added, it will eliminate them, too. But once the drug is terminated, the host microglia regenerate too fast to effectively put in the donor cells.

This quandary has challenged efforts to treat people with certain rare and severe neurologic conditions. One is Krabbe disease, in which the body’s cells can’t digest certain fats that are highly abundant in the brain. Currently, clinicians use bone marrow transplantation and chemotherapy to try to introduce new immune cells similar to microglia into the brain. But this approach can be toxic and must be carried out before Krabbe symptoms manifest.

“Our team believed that if we could overcome the brain’s resistance to accepting new microglia, we could successfully transplant them into patients using a safer, more effective process in order to target a great number of diseases,” said co-first author Sonia Lombroso, a Penn Ph.D. student and member of the Bennett Lab. “We decided to investigate whether we could make the donor microglia resistant to the drug that eliminates their host counterparts.”

The researchers used CRISPR gene-editing technology to create one amino acid mutation, known as G795A, which they introduced into donor microglia produced from human stem cells or a mouse microglial cell line. Then they injected the donor microglia into humanized rodent models while administering pexidartinib, with exciting results.

“We discovered that this one small mutation caused the donor microglia to resist the drug and thrive, while the host microglia continued to die off,” said co-first author Jean Paul Chadarevian, a UCI Ph.D. student who is a member of the Blurton-Jones Lab. “This finding could lead to many options for developing new microglial-based treatments. Pexidartinib is already approved for clinical use and appears to be relatively well tolerated by patients.”

Approaches could range from fighting disease by replacing dysfunctional microglia with healthy ones to designing microglia that can recognize imminent threats and strike against them with therapeutic proteins before they cause harm.

The UCI-Penn team believes treatments based on this kind of microglial method could be developed within a decade. Their next investigations include studying in rodent models how to use the approach to attack the brain plaques associated with Alzheimer’s and to counter Krabbe and other similar diseases.

Support for the project was provided by the National Institutes of Health, National Science Foundation, The Paul Allen Frontiers Group, Klingenstein-Simons Fellowship Award in Neuroscience and the Susan Scott Foundation.

“This is critical information for health care providers who might not otherwise screen for or recognize disordered eating in this population,” said Megan Mikhail, lead author of the study and Ph.D. candidate in the MSU Clinical Psychology program. “It is also important for the public to recognize that eating disorders can affect everyone, including people who do not fit the historical stereotypes.”

The study, published in the Journal of Psychopathology and Clinical Science, is the first to look at associations between multiple forms of disadvantage and risk for disordered eating in boys, as well as how disadvantage may interact with biological risks to impact disordered eating in boys.

Using a large population-based sample of male twins from the Michigan State University Twin Registry, the researchers found that boys from more disadvantaged backgrounds reported greater disordered eating symptoms and had earlier activation of genetic influences on disordered eating, which could lead to increased long-term risk.

The population-based sample allowed the researchers to avoid overlooking individuals who may not be able to afford access to mental health care. They examined factors such as parental income, education and neighborhood disadvantage to see how those factors related to disordered eating symptoms in the boys. Since all the participants were twins, researchers were also able to study genetic influences on disordered eating.

“This research is particularly relevant following the COVID-19 pandemic when many families experienced financial hardship,” said Kelly Klump, MSU Foundation Professor of Psychology and co-author of the study. “Those financial stressors are putting many young people at risk for an eating disorder, so it’s vital that there be increased screening and access to care for these young people.”

The new research, published in Pacific Conservation Biology, examined the environmental toll of firework displays by reviewing the ecological effects of Diwali festivities in India, Fourth of July celebrations across the United States of America, and other events in New Zealand and parts of Europe.

Examples included fireworks in Spanish festivals impacting the breeding success of House Sparrows, July firework displays being implicated in the decline of Brandt’s Cormorant colonies in California, and South American sea lions changing their behaviour during breeding season as a result of New Year’s fireworks in Chile.

Lead author Associate Professor Bill Bateman, from Curtin’s School of Molecular and Life Sciences, said fireworks remained globally popular despite the overwhelming evidence that they negatively impacted wildlife, domestic animals and the environment.

“Fireworks create short-term noise and light disturbances that cause distress in domestic animals that may be managed before or after a firework event, but the impacts to wildlife can be on a much larger scale,” Associate Professor Bateman said.

“The annual timing of some large-scale firework events coincides with the migratory or reproductive movements of wildlife, and may therefore have adverse long-term population effects on them. Fireworks also produce significant pulses of highly pollutant materials that also contribute significantly to the chemical pollution of soil, water, and air, which has implications for human as well as animal health.”

Associate Professor Bateman said firework bans at sensitive periods for wildlife migration or mating periods could limit the impact, as well as drone or other light-based shows.

“Other than horses, for which there is some evidence that they can be gradually familiarised with flashes of light, there is very little that can be done to address the disturbing impact of noise from fireworks on animals and wildlife,” Associate Professor Bateman said.

“The future of firework displays may be in the use of safer and greener alternatives such as drones, eco-friendly fireworks or visible-wavelength lasers for light shows.

“There is growing evidence that these community events can be managed in a sustainable way and it’s clear that out-dated firework displays need to be replaced by cleaner options that are not harmful to wildlife and the environment.”

Dimethyl sulfide (C₂H₆S) is a small molecule released by phytoplankton in the ocean, which can play a big role in regulating the Earth’s climate. It encourages cloud formation above the sea, and is often called an ‘anti-greenhouse gas’, since clouds block radiation from the sun and lower sea surface temperatures. At least some blocked heat will be retained in the atmosphere, however, so the effects can be complex. Researchers at Hokkaido University have charted evidence for increasing dimethyl sulfide emissions linked to the retreat of sea ice from Greenland as the planet warms. They report their findings in the journal Communications Earth & Environment.

Modelling studies have long suggested that the decline in Arctic sea ice could lead to increased dimethyl sulfide emission, but direct evidence for this has been lacking. Assistant Professor Sumito Matoba and colleagues have inferred dimethyl sulfide levels over 55 years by quantifying the related compound, methane sulfonic acid (MSA), in ice core samples from the south-east Greenland ice sheet. MSA is directly produced from dimethyl sulfide, serving as a stable record of dimethyl sulfide levels. This process is part of a variety of chemical interactions among aerosols in the atmosphere.

The team, including researchers from Nagoya University and Japan’s Aerospace Exploration Agency, reconstructed the annual and seasonal MSA flux from 1960 to 2014, at a monthly resolution. The annual MSA levels decreased from 1960 to 2001, but then markedly increased after 2002.

“We found that July to September MSA fluxes were three to six times higher between 2002 and 2014 than between 1972 and 2001,” says Matoba. “We attribute this to the earlier retreat of sea ice in recent years.”

Supporting evidence comes from satellite data that has monitored the levels of the crucial sunlight-absorbing green pigment chlorophyll-a in the surrounding seas. The chlorophyll-a serves as an indicator of phytoplankton abundance, which in turn should correlate well with the amount of dimethyl sulfide released by the phytoplankton.

Arctic temperatures are rising twice as fast as the global average, and the summer seasonal sea ice extent has declined sharply in recent decades. This increases the amount of light striking the ocean and promotes the growth of phytoplankton.

While the latest results from the Hokkaido team add important confirmation of the changing dimethyl sulfide levels, Matoba emphasises that long-term and continuous monitoring of aerosols is needed. “This will be essential to follow the current impact, and predict future impacts, of dimethyl sulfide emissions on the global climate,” he says.