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Bird Flu Is Spreading in Alarming New Ways

Bird Flu Is Spreading in Alarming New Ways

As a recent example of what may ensue, Pitesky points to the repeated African swine fever outbreaks across various Asian countries in the past decade, which decimated the pig farming industry to the extent that pork was briefly usurped by poultry as the most widely consumed animal protein on the planet. Pitesky argues, however, that the current model of governments heavily compensating farmers for their livestock losses in the wake of a viral outbreak is financially unsustainable, and more investment needs to be diverted toward AI-driven technologies that can prevent these infections in the first place.

“I work on predictive models, using a combination of weather radar, satellite imagery, and machine learning, to understand how waterfowl behavior around different farms is changing,” says Pitesky. “We can use this information to understand which of the 50,000 to 60,000 commercial poultry facilities in the US are at most risk, and form strategies to protect all the birds in those facilities.”

Technology may ultimately offer a path toward eliminating the virus in commercial poultry. In October, a team of researchers in the UK published a study in the journal Nature Communications demonstrating that it is possible to use the gene-editing tool Crispr to make chickens resistant to avian influenza. This was done through editing genes that make the proteins ANP32A, ANP32B, and ANP32E in chickens, which the virus uses to gain access to chicken cells.

Crispr has been shown to be capable of making livestock resistant to other infections such as the cancer-causing viral disease avian leukosis and porcine reproductive and respiratory syndrome, which is responsible for widespread economic losses in pig farms.

“The currently available methods are the use of strict farm biosecurity, poultry vaccinations in some countries, and massive depopulation of infected or exposed chicken flocks,” says Alewo Idoko-Akoh at the University of Bristol, the lead researcher on the Nature Communications study. “These methods have been partially successful but have so far failed to stop recurrent bird flu outbreaks around the world. Gene editing of chickens to introduce disease resistance should be considered as an additional tool for preventing or limiting the spread of bird flu.”

Pitesky described the paper as “really interesting” but pointed out that it would require widespread public acceptance toward consuming gene-edited chicken for it to become commercially viable. “I think that those technological solutions have a lot of potential, but the issue more than anything, especially in the United States, is sentiment toward chickens that have been genetically modified,” he says.

For now, Iqbal says that the best chance of keeping avian influenza under control is more active surveillance efforts in animal populations around the world, to understand how and where the H5N1 is spreading.

“The surveillance system has been improved, and any infection that appears unusual is thoroughly investigated,” he says of the situation in the US. “This has helped to identify unusual outbreaks, such as infections in goats and cattle.” However, he says, much more work is needed to detect the virus in animals that don’t show signs of disease.

This Is What Your Brain Does When You’re Not Doing Anything

This Is What Your Brain Does When You’re Not Doing Anything

The original version of this story appeared in Quanta Magazine.

Whenever you’re actively performing a task—say, lifting weights at the gym or taking a hard exam—the parts of your brain required to carry it out become “active” when neurons step up their electrical activity. But is your brain active even when you’re zoning out on the couch?

The answer, researchers have found, is yes. Over the past two decades they’ve defined what’s known as the default mode network, a collection of seemingly unrelated areas of the brain that activate when you’re not doing much at all. Its discovery has offered insights into how the brain functions outside of well-defined tasks and has also prompted research into the role of brain networks—not just brain regions—in managing our internal experience.

In the late 20th century, neuroscientists began using new techniques to take images of people’s brains as they performed tasks in scanning machines. As expected, activity in certain brain areas increased during tasks—and to the researchers’ surprise, activity in other brain areas declined simultaneously. The neuroscientists were intrigued that during a wide variety of tasks, the very same brain areas consistently dialed back their activity.

It was as if these areas had been active when the person wasn’t doing anything, and then turned off when the mind had to concentrate on something external.

Researchers called these areas “task negative.” When they were first identified, Marcus Raichle, a neurologist at the Washington University School of Medicine in St. Louis, suspected that these task-negative areas play an important role in the resting mind. “This raised the question of ‘What’s baseline brain activity?’” Raichle recalled. In an experiment, he asked people in scanners to close their eyes and simply let their minds wander while he measured their brain activity.

He found that during rest, when we turn mentally inward, task-negative areas use more energy than the rest of the brain. In a 2001 paper, he dubbed this activity “a default mode of brain function.” Two years later, after generating higher-resolution data, a team from the Stanford University School of Medicine discovered that this task-negative activity defines a coherent network of interacting brain regions, which they called the default mode network.

The discovery of the default mode network ignited curiosity among neuroscientists about what the brain is doing in the absence of an outward-focused task. Although some researchers believed that the network’s main function was to generate our experience of mind wandering or daydreaming, there were plenty of other conjectures. Maybe it controlled streams of consciousness or activated memories of past experiences. And dysfunction in the default mode network was floated as a potential feature of nearly every psychiatric and neurological disorder, including depression, schizophrenia, and Alzheimer’s disease.

Since then, a flurry of research into the default mode has complicated that initial understanding. “It’s been very interesting to see the types of different tasks and paradigms that engage the default mode network in the past 20 years,” said Lucina Uddin, a neuroscientist at the University of California, Los Angeles.

Scabies Is Making a Comeback

Scabies Is Making a Comeback

The high number of cases in the UK also reflects the difficulty of eradicating an outbreak, says Jo Middleton, a research fellow at Brighton and Sussex Medical School, who is involved in scabies research in the UK and around the globe. Bedding and furniture need to be completely decontaminated, while medicines like permethrin are not the easiest to use.

“Permethrin is a good medicine, but it’s very difficult to put on. You have to cover your whole body, leave it on for 12 hours without washing it off, and then you have to do it again seven days later,” he says. “The reality is that we see a lot of failure, where people put on this medication and end up continuing to have scabies and infecting other people, because the application is so difficult.”

In Britain, there’s also another factor at play: a months-long severe shortage of treatments. Paula Geanau of the British Association of Dermatologists told WIRED in an email that this is due to both lingering pandemic-related supply chain issues and import problems relating to Brexit. With the current high demand, any stock that reaches the UK is swiftly used up.

“We’ve seen a shortage of pharmacy supply in some UK regions, particularly in the north,” says Middleton. “It’s unclear what is causing which. Maybe there’s more cases, so therefore there’s a shortage in medicine, or it might be the other way around.”

Researchers argue that given scabies’ relatively high incidence, there needs to be more rigorous surveillance of potential outbreaks, particularly in the wake of research showing that untreated scabies can lead to secondary skin infections from streptococcus and staphylococcal bacteria. Vulnerable patients—in care homes, for example—are especially at risk, and these bacteria can even go on to cause organ damage. “There’s some links to the cardiac and renal systems,” says Head. “Not fully understood, but it does look like they are genuine, occasional secondary consequences of an initial scabies infection.”

Scabies has long been neglected, perhaps due to the unhelpful stigma surrounding it as a “disease of the unwashed.” Rates have sometimes been reported as being higher in overcrowded conditions—in camps for refugees and asylum seekers, for example. This idea may then be used to blame disadvantaged populations, without evidence, for spreading the disease.

“I’ll strongly say there’s no evidence that any rise in scabies, if it is happening in Europe, is connected to refugees,” says Middleton. “There’s been stuff in the media in the past associating refugees with bringing scabies into a country, but scabies is here, and it’s always been here. Where we see outbreaks is predominantly in care homes and among young people in universities. It’s what’s going on in those places that will explain any rise.”

This isn’t the only piece of misinformation to swirl around the disease. In the global south, scabies is managed effectively through an oral medication, a powerful antiparasitic called ivermectin. Studies have shown that two doses of ivermectin are effective at eliminating the disease in 98 percent of patients.

Yet ivermectin is not routinely used to treat scabies in the UK, something that researchers attribute to the repeated false claims regarding its potential uses for treating Covid-19. At one point endorsed by former US president Donald Trump, ivermectin’s supposed usefulness against the SARS-CoV-2 virus was never backed up with reliable evidence, and Middleton believes this is sadly now inhibiting its use in conditions where it is proven to work.

“Some people were claiming that it had efficacy against Covid,” he says. “To try and control that you had other people describing it as horse paste, because it is—like a lot of human medicines—also a veterinary drug. That then gave it a kind of bad reputation. But we are hoping it will be used more against scabies.”

In the meantime, doctors such as Ijaz are hoping that the current outbreak in the UK can be managed through more effective public health campaigns. “People can often be mismanaged,” he says. “For instance, itching post-treatment can last anywhere up to six weeks post eradication, yet people mistake this for a recurrence of scabies. This leads to them sourcing more permethrin, leading to more shortages.”

Unpicking the Mystery of the Body’s ‘Second Brain’

“We think that they do everything,” Gulbransen said. “The more that people find out about them, it’s less surprising that they do these diverse roles.”

They can also move between roles. They’ve been shown to change their identities, shifting from one glial cell type to another, in lab dishes—a useful ability in the ever-changing gut environment. They’re “so dynamic, endowed with the functional capacity to do so many different things, sitting in this incredibly fluctuating and complex environment,” Scavuzzo said.

Even as excitement builds about glia in the enteric nervous system, scientists like Scavuzzo have fairly basic questions still to work out—such as how many types of enteric glia even exist.

A Force to Reckon With

Scavuzzo became fascinated with digestion in childhood when she witnessed her mother’s medical troubles due to a congenitally shortened esophagus. Watching her mother go through gastrointestinal complications compelled Scavuzzo to study the gut in adulthood to find treatments for patients like her mom. “I grew up knowing and understanding this stuff is important,” she said. “The more we know, we can intervene better.”

In 2019, when Scavuzzo started her postdoctoral research at Case Western under Paul Tesar, a world expert in glial biology, she knew she wanted to unravel the diversity of enteric glia. As the only scientist in Tesar’s lab examining the gut and not the brain, she often joked with her colleagues that she was studying the more complex organ.

The first year, she struggled massively in trying to map out the individual cells in the gut, which proved to be a harsh research environment. The very start of the small intestine, the duodenum, where she focused her studies, was especially tough. The bile and digestive juices of the duodenum degraded RNA, the genetic material that held clues to the cells’ identities, making it nearly impossible to extract. Over the next few years, however, she developed new methods to work on the delicate system.

Those methods allowed her to get the “first glimpse into the diversity of these glial cells” across all tissues of the duodenum, Scavuzzo said. In June, in a paper published on the preprint server that has not yet been peer-reviewed, she reported her team’s discovery of six subtypes of glial cells, including one that they named “hub cells.”

Hub cells express genes for a mechanosensory channel called PIEZO2—a membrane protein that can sense force and is typically found in tissues that respond to physical touch. Other researchers recently found PIEZO2 present in some gut neurons; the channel allows neurons to sense food in the intestines and move it along. Scavuzzo hypothesized that glial hub cells can also sense force and instruct other gut cells to contract. She found evidence that these hub cells existed not only in the duodenum, but also in the ileum and colon, which suggests they’re likely regulating motility throughout the digestive tract.

She deleted PIEZO2 from enteric glia hub cells in mice, which she thought would make the cells lose the ability to sense force. She was right: Gut motility slowed, and food contents built up in the stomach. But the effect was subtle, which reflects the fact that other cells are also playing a role in physically moving partially digested food through the intestine, Scavuzzo said.

Biophysicists Uncover Powerful Symmetries in Living Tissue

Biophysicists Uncover Powerful Symmetries in Living Tissue

“It was pretty amazing how well the experimental data and numerical simulation matched,” Eckert said. In fact, it matched so closely that Carenza’s first response was that it must be wrong. The team jokingly worried that a peer reviewer might think they’d cheated. “It really was that beautiful,” Carenza said.

The observations answer a “long-standing question about the type of order present in tissues,” said Joshua Shaevitz, a physicist at Princeton University who reviewed the paper (and did not think they’d cheated). Science often “gets murky,” he said, when data points to seemingly conflicting truths—in this case, the nested symmetries. “Then someone points out or shows that, well, those things aren’t so distinct. They’re both right.”

Form, Force, and Function

Accurately defining a liquid crystal’s symmetry isn’t just a mathematical exercise. Depending on its symmetry, a crystal’s stress tensor—a matrix that captures how a material deforms under stress—looks different. This tensor is the mathematical link to the fluid dynamics equations Giomi wanted to use to connect physical forces and biological functions.

Bringing the physics of liquid crystals to bear on tissues is a new way to understand the messy, complicated world of biology, Hirst said.

The precise implications of the handoff from hexatic to nematic order aren’t yet clear, but the team suspects that cells may exert a degree of control over that transition. There’s even evidence that the emergence of nematic order has something to do with cell adhesion, they said. Figuring out how and why tissues manifest these two interlaced symmetries is a project for the future—although Giomi is already working on using the results to understand how cancer cells flow through the body when they metastasize. And Shaevitz noted that a tissue’s multiscale liquid crystallinity could be related to embryogenesis—the process by which embryos mold themselves into organisms.

If there’s one central idea in tissue biophysics, Giomi said, it’s that structure gives rise to forces, and forces give rise to functions. In other words, controlling multiscale symmetry could be part of how tissues add up to more than the sum of their cells.

There’s “a triangle of form, force, and function,” Giomi said. “Cells use their shape to regulate forces, and these in turn serve as the running engine of mechanical functionality.”

Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.