Newest version of cell-mapping tool can spot boundaries even in cloudy conditions

Picking out individual cells in distorted microscopy images is now as easy as clicking a button.

A new version of Cellpose—the popular tool that maps the boundaries of diverse cells in microscopy images—now works on less-than-perfect pictures that are noisy, blurry, or undersampled.

Many general methods used for segmenting individual cells in microscopy images, including previous versions of Cellpose, have a hard time recognizing cellular boundaries that have been distorted by noise, blurring, or undersampling.

Janelia Group Leaders Carsen Stringer and Marius Pachitariu set out to address this issue with the development of Cellpose3. Unlike previous approaches, which train models to improve the quality of distorted images, Cellpose3 was instead trained to improve the segmentation of distorted images.

The study is published in the journal Nature Methods.

The Cellpose3 restoration algorithm, when applied to distorted images, produces crisp restored images which can then be easily segmented by the original Cellpose segmentation algorithm.

Cellpose3 is also trained on a large, varied collection of images, enabling users to easily use the new method, which is available as a “one-click” button in the Cellpose application, on their own data.

Mighty marine fungi degrade plastic by eating it, and can be conditioned to do it faster

Plastic is the most prevalent marine pollutant, and plastic surfaces are the fastest growing habitat in the ocean. Researchers at the University of Hawai’i (UH) at Mānoa have recently discovered that many species of fungi isolated from Hawai’i’s nearshore environment have the ability to degrade plastic, and some can be conditioned to do it faster.

The work is published in the journal Mycologia.

“Plastic in the environment today is extremely long-lived, and is nearly impossible to degrade using existing technologies,” said Ronja Steinbach, who led this research as a marine biology undergraduate student in the UH Mānoa College of Natural Sciences.

“Our research highlights marine fungi as a promising and largely untapped group to investigate for new ways to recycle and remove plastic from nature. Very few people study fungi in the ocean, and we estimated that fewer than one percent of marine fungi are currently described.”

For consumers, plastics are cheap, strong, and useful, but plastic waste is problematic, because rather than decomposing, it breaks into microplastics when exposed to sunlight, heat, and physical force. Plastics are harmful to marine ecosystems—they can concentrate dangerous chemicals, such as phthalates and bisphenol A; entrap or harm animals; or be ingested and lead to starvation in marine animals due to malnutrition. With the equivalent of about 625,000 garbage trucks of plastic entering the ocean each year, finding ways to degrade these compounds is critical.

Microbes with superpowers

 

Various microbes, including bacteria and terrestrial fungi, have been tested for their ability to degrade plastics, with the hope that biotechnology can one day be deployed at ecologically relevant scales. While many terrestrial fungi have previously been found to degrade various types of plastic, the team of researchers from the UH Mānoa School of Ocean and Earth Science and Technology (SOEST) focused their attention on their large collection of fungi they isolated from sand, seaweed, corals, and sponges in Hawai’i’s nearshore.

“Fungi possess a superpower for eating things that other organisms can’t digest (like wood, or chitin), so we tested the fungi in our collection for their ability to digest plastic,” said Anthony Amend, Pacific Biosciences Research Center professor, who leads the lab where Steinbach and Syrena Whitner, study co-author and marine biology graduate student, conducted the research.

To do this, the team filled small dishes with polyurethane, a common plastic, often used in medical and industrial products such as foams, flexible materials, and adhesives, and measured whether and how fast the fungi consumed plastic. The researchers took the fungi that grew the fastest and experimentally evolved them to see whether—over time, with greater exposure to the polyurethane—these fungi could adapt to eat plastic faster and more efficiently.
“We were shocked to find that more than 60% of the fungi we collected from the ocean had some ability to eat plastic and transform it into fungi,” said Steinbach. “We were also impressed to see how quickly fungi were able to adapt. It was very exciting to see that in just three months, a relatively short amount of time, some of the fungi were able to increase their feeding rates by as much as 15%.”
Because of Hawai’i’s location in the North Pacific Subtropical Gyre, ocean currents deliver to our shores plastic waste from around the world, and nearby is the Great Pacific Garbage Patch.
The UH Mānoa team is now expanding on its research to see if these promising fungi and others can eat different types of plastic, like polyethylene and polyethylene terephthalate—which are even harder to degrade—and even larger sources of marine pollution. The scientists are also trying to understand, at a cell and molecular level, how fungi are able to degrade these compounds.
“We hope to collaborate with engineers, chemists, and oceanographers who can leverage these findings into actual solutions to clean up our beaches and oceans,” shared Steinbach.
Ozempic shown to reduce drinking in first trial in alcohol-use disorder

For years, people taking Ozempic or other drugs in the same class for diabetes and weight loss have noticed the medicines don’t just curb their desire to eat; for some, they also lead them to drink less alcohol.

Now, the first clinical trial – although relatively small and limited in duration – has confirmed it.

A study of 48 people with signs of moderate alcohol-use disorder found that those taking low doses of semaglutide – the generic name of Ozempic – for nine weeks saw significantly greater reductions in how much alcohol they drank, as well as cravings for alcohol, compared with people on a placebo. The results were published Wednesday in the journal JAMA Psychiatry.

The findings underscore what multiple analyses of real-world use of the so-called GLP-1 medicines, as well as studies in animals, had already hinted at: Ozempic and similar drugs, already incredibly popular, could help reduce risks of overconsuming alcohol, if the results bear out in larger and longer trials.

“We hoped to see a reduction in drinking and craving,” said Dr. Christian Hendershot, director of clinical research at the USC Institute for Addiction Science and the lead author of the study. “What I didn’t expect was the magnitude of the effects looks fairly good … compared to other alcohol-use disorder medications.”

Alcohol-use disorder, or AUD, affects almost 30 million people in the United States, according to the 2023 National Survey on Drug Use and Health, and it’s characterized by having trouble stopping or controlling alcohol use despite negative consequences from it.

And increasingly, health guidance points to consuming less alcohol or abstaining to improve health; last month, former US Surgeon General Dr. Vivek Murthy issued an advisory warning that alcohol raises the risk of at least seven types of cancer, and called for updated health warning labels on alcoholic beverages.

Whether Ozempic and other similar drugs present a new way of treating AUD will depend on larger trials in patients more heavily afflicted by the disorder, experts said, and potentially whether research can yield a better understanding of how the medicines work to reduce drinking.

There are three medicines approved by the US Food and Drug Administration for AUD, but fewer than 2% of people with the disorder receive treatment with them, Hendershot and his co-authors wrote in their paper, noting few people may know about them and that stigma may pose a barrier to treatment.

One of the medicines, naltrexone, has shown a small effect size on alcohol-use disorder, Hendershot told CNN. The semaglutide trial showed effect sizes “in the medium to large range,” he said, although he urged caution about the results since the trial “was the first to look at this question in a controlled way.”

Semaglutide, sold by Novo Nordisk as Ozempic for type 2 diabetes and Wegovy for obesity, is part of a class of drugs known as GLP-1 receptor agonists, mimicking the hormone GLP-1 to reduce appetite, slow stomach emptying and regulate insulin. Eli Lilly sells the other major drugs in the class, Mounjaro for diabetes and Zepbound for obesity, based on the active ingredient tirzepatide. In addition to GLP-1, they also mimic another hormone called GIP.

The drugs work in both the gut and the brain – which may be the way they could help with AUD, said Dr. Lorenzo Leggio, a physician-scientist at the National Institutes of Health who wasn’t involved in this study.

“More research is needed to understand the mechanism(s) of action of these medications in AUD,” Leggio, who’s published research on semaglutide’s ability to reduce alcohol drinking in animals, wrote in an email to CNN. “Nonetheless, the work done now suggests that mechanisms may include their effect in reducing alcohol craving and in reducing the rewarding effects of alcohol.”

A bar in a lab

The study, funded by the National Institute on Alcohol Abuse and Alcoholism and conducted at the University of North Carolina-Chapel Hill School of Medicine, enrolled people with alcohol-use disorder who weren’t seeking treatment. They reported drinking more than seven drinks in a week, if they were women, or 14 if they were men, within the last month, with two or more heavy drinking episodes, defined as at least four drinks at a time for women or five for men.

Half received low-dose injections of semaglutide each week and half received a placebo shot. They came in weekly for visits.

Their first was a bit unusual for a clinical trial, although not for one studying alcohol: participants spent two hours in a lab made to feel like a living room, complete with National Geographic episodes playing on TV – and a bar stocked with their favorite alcoholic drink.

“They were free to drink as much as they wanted to, up to a limit we set” for safety, Hendershot said. Someone from the study would come in every half an hour to take breath alcohol measurements and administer some questionnaires.

They did it again at the end of the nine weeks of treatment. Then the researchers compared the results.

When participants returned to the living room lab at the end of the study, those taking semaglutide drank about 40% less alcohol than those on placebo, the study found. In additional measures in the study, participants on the medicine also drank fewer drinks per day overall and had fewer heavy drinking days, as well as reduced cravings for alcohol.

“It’s one of the first trials that’s a randomized, controlled trial that have said, ‘You know what, there is evidence that people will drink less if they’re taking this medicine,’” Dr. Daniel Drucker, a professor of medicine at the University of Toronto who pioneered research on GLP-1, told CNN.

Drucker noted, though, he’d like to see more detailed information about the side effects individual participants experienced, and whether they had any correlation with how much alcohol they drank.

“If you have persistent low-grade nausea and you’re not feeling well, well of course you wouldn’t drink as much,” Drucker said – although he noted this is not the main reason people lose weight on the medicines, as the side effects usually are worst when people begin treatment and when they increase their doses.

The most common side effects of GLP-1 medicines are nausea, constipation and other gastrointestinal issues, and participants on semaglutide in the trial experienced generally mild effects of that nature as well, the researchers said.

Hendershot said the size of the study meant they didn’t feel they had enough data to measure the correlation of side effects with drinking, but said that since side effects are generally a bigger issue at the beginning of treatment and during dosage increases, “we don’t think that GI side effects can fully account for the findings.” In the study, the effects on drinking were generally largest at the end. Hendershot said it’s something to study more definitively in the future.

Where Ozempic didn’t work

The trial found that semaglutide didn’t appear to affect how many days out of the week people chose to drink alcohol – just that when they drank, they drank less. And that may be a helpful goal for people seeking treatment for AUD, said Dr. Raymond Anton, an addiction psychiatrist and emeritus professor at the Medical University of South Carolina.

“The field in general has been pushing for a reduction goal in clinical trials and the FDA is moving in that direction,” Anton told CNN by email. “Most people seeking treatment do not want a goal of abstinence for the rest of their lives.”

Anton also said he’d like to see data on whether side effects like nausea and fatigue had an effect on alcohol drinking, and also whether there was a correlation between weight loss and drinking reduction. In the study, participants on semaglutide lost about 5% of their body weight over nine weeks.

He also noted the people in the study were different from those who typically seek treatment for AUD; it had a lot more women than men – atypical of most AUD trials, he said – and they were of higher than normal weight, which he said also isn’t typical of the average person seeking treatment for AUD. And, Anton said, those seeking treatment generally drink more than people in this trial reported – seven to eight drinks per day, and often much more, on the majority of days.

There are already more trials underway to better understand the promise of GLP-1 drugs in AUD, including one at the NIH. But to obtain FDA approval for the disorder, pharmaceutical companies likely need to get involved.

Novo Nordisk and Eli Lilly have been slower to pursue addiction indications for the medicines, while running trials proving their cardiovascular benefits, effects on kidney disease, heart failure and sleep apnea. Novo Nordisk is even evaluating semaglutide for Alzheimer’s disease, with results expected late this year.

But last year, the Danish drug giant said it would look at semaglutide’s effects on alcohol consumption as part of a trial in alcohol-related liver disease. And Lilly’s CEO told an audience at an event in December that the company planned to start large studies in alcohol abuse, nicotine use and drug abuse this year.

Key questions remain, including how the drugs should be used in people who don’t have excess weight. In Hendershot’s study, anyone with a body mass index, or BMI, of at least 23 could enroll, which would include people considered to have a healthy body weight; the medicines are approved by the FDA for people with a BMI of 30, indicating obesity, or of at least 27 – overweight – and a weight-related health condition. Only one person in the trial started with a BMI of less than 24.9, the researchers said.

And there’s still more data to come. Hendershot and his team also assessed cigarette use among a subsection of participants who smoked. Though the sample size was small – just 13 of the 48 participants reported smoking cigarettes – the study found those on semaglutide tended to smoke fewer cigarettes per day, mirroring anecdotes from patients prescribed the drugs for weight loss.

“Should GLP-1 receptor agonists prove efficacious for both alcohol reduction and smoking cessation,” the researchers concluded, “potential health implications could be substantial.”

FDA approves new genetic disorder drug

The Food and Drug Administration (FDA) approved a new drug to treat a disorder causing the growth of noncancerous tumors on nerves throughout the body.

The federal agency said on Tuesday it greenlighted SpringWorks Therapeutics’s drug Gomekli for patients dealing with neurofibromatosis type 1 (NF1) “who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.”

The drug was approved after a multicenter, single-arm trial of 114 patients — 58 adults — with “symptomatic, inoperable NF1-associated PN causing significant morbidity,” according to the FDA.

Gomekli showcased at least a 20 percent reduction in the volume of the tumor in more than 50 percent of pediatric patients and 41 percent of adult patients, Reuters noted.

“The NF1-PN patient community has a great need for more treatment options. With today’s approval, we are honored to serve both adults and children with NF1-PN and provide them with a therapy that has the potential to shrink their tumors and offer meaningful symptomatic relief,” SpringWorks CEO Saqib Islam said in a statement on Tuesday.

“We are grateful to each clinical trial participant, their families, the investigators, and the patient advocacy groups involved in the journey towards making GOMEKLI available in the U.S.,” Islam added. “I am proud that we are delivering on our commitment to patients with devastating diseases with our company’s second FDA approval in less than 18 months.”

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