In a white lab coat and blue latex gloves, Neda Vishlaghi peers through a light microscope at six milky-white blobs. Each is about the size of a couscous grain, bathed in the pale orange broth of a petri dish. With tweezers in one hand and surgical scissors in the other, she deftly snips one tiny clump in half.

When growing human brains, sometimes you need to do some pruning.

The blobs are 8-week-old bits of brainlike tissue. While they wouldn’t be mistaken for Lilliputian-sized brains, some of their fine-grained features bear a remarkable resemblance to the human cerebral cortex, home to our memories, decision making and other high-level cognitive powers.

Vishlaghi created these “minibrains” at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, where she’s a research assistant. First she immersed batches of human pluripotent stem cells — which can morph into any cell type in the body — in a special mix of chemicals.
The free-floating cells multiplied and coalesced into itty-bitty balls of neural tissue. Nurtured with meticulously timed doses of growth-supporting ingredients, the cell clumps were eventually transferred to petri dishes of broth laced with Matrigel, a gelatin-like matrix of proteins.

On day 56, the blobs display shadowy clusters of neural “rosettes.” Under a laser scanning microscope, razor-thin slices of those rosettes reveal loose-knit layers of a variety of dividing neural stem cells and the nerve cells, or neurons, they give rise to. The layered structures look similar to the architecture of a human fetal brain at 14 weeks of gestation.
Across the globe, labs such as this one, led by UCLA developmental biologist and neuroscientist Bennett Novitch, are cultivating thousands of these brainy clumps for research. Less than five years ago, a team of biologists in Austria and the United Kingdom and one in Japan wowed the world when they announced they had made rudimentary bits of 3-D human cerebral cortex in a dish. Since then, researchers have been eagerly tinkering with techniques for producing these miniature brain models, like chefs obsessively refining their favorite recipes.

“It’s like making a cake: You have many different ways in which you can do it,” says Novitch, who prefers using the Japanese method with a few tweaks. “There are all sorts of little tricks that people have come up with to overcome some of the common challenges.”

For instance, because the brain blobs lack a built-in blood supply, they must absorb enough oxygen and nutrients from the tissue-culture broth to remain healthy. To help, some labs circulate the broth around the tissue clumps. The UCLA researchers choose instead to grow theirs at higher oxygen levels and chop the blobs at the 35-day mark, when they are as wide as three millimeters, and then about every two weeks after. Sounds radical, but the slicing gives cells on the inside — some of which start dying — exposure to much-needed oxygen and nutrients. Those divided bits then continue growing separately. But cutting can be done only so many times before the expanding rosette structures inside are damaged.

With all the experimenting, researchers have cooked up a lot of innovations, including some nifty progress reported in just the last year. Scientists have concocted tiny versions of several brain regions ranging from the hypothalamus, which regulates body temperature, thirst and hunger, to the movement-controlling basal ganglia. Electrical chatter among neurons, reflecting active brain circuits, has been detected. And research groups have recently begun linking bits of specific regions like Legos. Scientists have even observed some early developmental processes as they happen within the human brain blobs.
Stem cell payoff
The work is part of a broader scientific bonanza that comes from coaxing human stem cells to self-assemble into balls of organlike tissue, known as organoids, that are usually no bigger than a lentil. Although the organoids don’t grow enough to replicate entire human organs, these mini-versions can mimic the 3-D cellular infrastructure of everything from our guts to our lungs. That’s something you can’t get from studies of rodents, which have different biology than humans do.

Mini-organ models promise enormous advantages for understanding basic human biology, teasing apart human disease processes, and offering an accurate testing ground for finding or vetting drug therapies. And by creating personalized organoids from the reprogrammed cells of patients, scientists could study disease in a very individualized way — or maybe even use organoid structures to replace certain damaged tissues, such as in the liver or spinal cord.

“Organoids offer an unprecedented level of access into the inner workings of the human brain,” Novitch says, noting that our brains are largely off-limits to poking and cutting into for research. If scientists can study accurate models of working neural circuits in these brain bits, he and others say, researchers might finally get a handle on uniquely human neurological conditions. Such disorders, which include epilepsy and, experts theorize, schizophrenia and autism (SN Online: 7/17/15), can arise when the brain’s communication networks develop off-kilter.
But the research is still in its early days. Although there’s been exciting headway, studies sometimes overstate the extent to which human brain organoids reproduce features of actual developing brain tissue, says stem cell biologist Arnold Kriegstein of the University of California, San Francisco. The minimodels still lack many basic components, including certain cell types, a blood-vessel network and inputs from other neural regions.

Another stumbling block is that brain organoids can vary a lot from protocol to protocol, or even batch to batch within the same lab. “The major focus now needs to be on reproducibility, and being able to get an approach that you can rely on to give you the same outcome each time,” Kriegstein says.

DIY organs
For decades, biology research has relied on cell lines grown in flat sheets in petri dishes, but those sheets lack the structural complexity of living tissue. Then came pioneering work that unveiled the do-it-yourself magic of stem cells raised free-floating in broth.

Organlike tissue bits can be generated from pluripotent stem cells that are either plucked from embryos or created by taking a person’s adult skin or blood cells and chemically inducing them to revert to an embryonic-like state. Starting in the mid-2000s, Yoshiki Sasai’s team at the RIKEN Center for Developmental Biology in Kobe, Japan, demonstrated how to grow brainlike structures using embryonic stem cells, first from mice and then humans.
In their groundbreaking study in 2013 in Proceedings of the National Academy of Sciences, the researchers used chemical cues to direct human embryonic stem cells to form a specific region of the human cortex. (Tragically, Sasai committed suicide the next year, after two stem cell studies that he coauthored were retracted amid scientific misconduct charges against a research colleague [SN: 12/27/14, p. 25]. Before his death, Sasai was cleared of any direct involvement. The discredited studies were not related to the organoid research.)

A few months before the 2013 Sasai team paper, Madeline Lancaster and Juergen Knoblich of the Institute of Molecular Biotechnology in Vienna and U.K. colleagues demonstrated their more freewheeling, landmark approach to growing brain organoids (SN: 9/21/13, p. 5). The recipe, described in Nature, allows human pluripotent stem cells to spontaneously attempt to assemble into a tiny approximation of a whole brain by making whatever brain structures the stem cells choose.

Meanwhile, biologists elsewhere were whipping up other types of organoids, starting instead with adult stem cells. These rare, damage-repairing cells are found in many organs (including the brain), but the cells can transform into only a limited range of cell types. In 2009, Hans Clevers of the Hubrecht Institute in Utrecht, the Netherlands, announced that his lab unexpectedly created a miniature version of a gut while cultivating adult stem cells that the team had discovered in mouse intestinal tissue. Grown in a drop of Matrigel with a trio of growth-inducing factors, these cells coalesced into little spheres containing tiny projections that resembled the fingerlike villi that absorb nutrients in the gut.

Scientists soon were concocting tiny facsimiles of human stomachs, livers, kidneys, lungs and more (SN: 12/28/13, p. 20). “We essentially are discovering the vitality of what the stem cells actually do,” says Clevers, who is president of the International Society for Stem Cell Research. “We give [the cells] a little push, and they do whatever they’re good at.”

The trick is knowing exactly which ingredients to use to make different organs. For pluripotent stem cells, that means exposing them to just the right growth factors or inhibitors at just the right times, over about a month, says James Wells of the Center for Stem Cell and Organoid Medicine at Cincinnati Children’s Hospital Medical Center. Some of those essential instructions are well-known from decades of research on embryo development in fish, chickens and rodents; the same chemical cues generally work for all animals with spinal cords, including people.
However, for many body parts, organoid makers must suss out recipe instructions from scratch. Working with Jorge Múnera and other colleagues, Wells recently produced a minimodel of a human colon using human induced pluripotent stem cells. But first, the team conducted months of experiments on frog and mouse embryos to identify the signals for forming a colon. “It took a while to figure out what the special sauce was,” Wells says.

Some scientists have distant dreams of using organoid methods to grow full-size livers or kidneys in the lab for transplantation. A more attainable goal may be regenerative tissue transplants, for example, replacing dying liver cells in someone with early-stage liver disease with chunks of healthy stem cells from a personalized liver organoid. Or, in patients who’ve had part of the small intestine removed, tiny pieces of gut organoid tissue could be implanted and, after growing larger, connected to the intestine.

Head games
The human brain, meanwhile, is vastly more complicated than any other organ. It’s unlikely that scientists will ever be able to build a full replica. While the initial brain-making recipes were stunning for what they could achieve, they left much room for improvement. In the years since the 2013 debut of human brain organoids, research groups have worked to grow bigger brain tissue clumps and more uniform structures.

The Austrian method for making whole-brain organoids, in particular, produced a random mix of neural regions laid out in a topsy-turvy manner. But bioengineering tricks may help. In a study last year, Lancaster, now at the MRC Laboratory of Molecular Biology in Cambridge, England, and Knoblich got more consistent results by adding polymer filaments as scaffolding to guide the organization of the minibrain models.
Other scientists, following the Japanese approach, which generally gives more predictable results, have concentrated on coaxing out specific cell types or structural features of the real brain. For instance, one constraint is that the organoids form slowly, more or less sticking to the same timeline of development as does a human brain during gestation. But without a blood supply, growth is limited; the brain bits reach only a few millimeters in size. That means organoid models are often short on cell types from later development stages, such as cells called astrocytes. These star-shaped cells are crucial for creating and curating the connections between neurons, and also may help with forming memories (SN Online: 11/15/17).

Astrocytes don’t fully mature in a baby’s brain until after birth. But Stanford University neuroscientist Sergiu Paşca has crafted a method for making and maintaining 4-millimeter-wide balls of human cortex–like tissue (he calls them spheroids) in 3-D culture for an extended time. Last August in Neuron, his team described organoids that survived for more than 20 months — long enough, analyses showed, for astrocytes to mature and function in ways that mimic their real-brain counterparts.

Of great interest, also, are the outer radial glial (oRG) cells, neural stem cells that are pivotal for constructing the unusually big cortex that’s unique to humans; oRG cells are scarce in mouse brains. When Novitch’s lab group at UCLA tried the original Japanese and Austrian organoid-making recipes, the output of oRG cells was underwhelming. So Novitch worked with Vishlaghi and postdoctoral researcher Momoko Watanabe to refine the protocol to pump up the cells’ production and reliably generate better cerebral blobs.

Among other tweaks, Novitch’s team added a dash of a molecule dubbed LIF, which recent studies by others had suggested can spur the oRGs to multiply. It worked, leading to a threefold increase in the oRG populations and enhanced growth of upper neuron layers. The researchers shared their revised protocol last October in Cell Reports.
On a different front, labs have begun assembling more complex minibrain models, like playing with self-directed Legos. For two months, Paşca’s team at Stanford grew spheroids in separate sets of dishes that mimicked either cortex tissue or an adjacent underlying region known as the subpallium. Then the researchers put the different bits side-by-side and left them overnight in a culture tube. Similar to how the two regions normally connect in the developing brain, the little pieces knew what to do. “By the next day they are essentially fused to each other,” says Paşca, who announced the results in May in Nature.

During the fusion process, the researchers took time-lapse videos of long, spaghetti-like cells called interneurons migrating from a spheroid of the subpallium into a cortexlike spheroid.

“They don’t crawl, they actually jump,” Paşca says. The images capture aspects of a hallmark phenomenon that normally unfolds during the second and third trimester of fetal gestation.

Testing ground
Once on the other side, interneurons form a circuit with — and quell the activity of — excitatory neurons in the cortexlike tissue, electrophysiological tests suggest. If not quieted, excitatory neurons will trigger neighboring cells to fire. In the real brain, maintaining a proper balance in neural network activity is important; disruptions in it appear to foster disorders such as epilepsy, and perhaps schizophrenia and autism.

Indeed, in the same paper, the Stanford team reported new discoveries using personalized brain spheroids derived from induced pluripotent stem cells of patients with Timothy syndrome — a rare condition caused by an overactive calcium channel found mainly in the brain and heart. Patients with the disorder have epilepsy, autism and heart problems. In the patients’ spheroids, interneurons migrated inefficiently but, by adding drugs that blocked the dysfunctional calcium channel, the researchers could reverse the problem. The brain organoids made these intriguing observations possible, Paşca says. “We couldn’t have done this in any other way.”
Organoid experiments by others have, meanwhile, helped confirm that the Zika virus targets and kills oRG cells and other neural precursor cells, contributing to small brain size in infected infants.

In a 2016 study, Johns Hopkins University neuroscientists Guo-li Ming and Hongjun Song reported on their own techniques for creating brain bits that have a well-defined zone of oRG cells. After infecting these organoids with the Zika virus, the researchers observed a collapse of cortexlike tissue that may partly explain the stunted brain growth (SN: 4/2/16, p. 26). 2-D cell-culture and mouse experiments also provided key evidence of the virus’s modus operandi; although the rodent brain doesn’t harbor the full contingent of human neural stem cells, it has blood vessels and immune-system components that organoids lack.

In search of Zika-fighting treatments, Ming and Song, both now at University of Pennsylvania, and their colleagues have been screening thousands of compounds in 2-D cell cultures, and then validating the most promising candidates with tests in 3-D brain organoids. The team has found several potential antiviral and neuron-protecting agents to pursue. Novitch’s UCLA lab group has likewise used its brain organoids to pinpoint additional receptors by which the virus may gain entry into neural stem cells, and identified a few other drug leads for blocking infection.

Organoids may also prove valuable for tailoring treatments for patients, says David Panchision, chief of the developmental neurobiology program at the National Institute of Mental Health in Bethesda, Md. Researchers might generate personalized brain organoids from the reprogrammed skin cells of individuals with, say, schizophrenia and test which medications work best for patients with particular genetic profiles of the illness.

In the Netherlands, based on research reported in 2016 in Science Translational Medicine, Clevers and colleagues are already using personalized gut organoids, derived from rectal biopsies, to test whether cystic fibrosis patients will benefit from available drugs. Tailored regenerative therapies with 3-D substructures of neural tissue may also be possible, Panchision adds, for conditions like Parkinson’s disease or spinal cord injury.
Growing pains
For now, though, scientists have hefty challenges to overcome. Much work remains in optimizing how faithfully the bits of tissue reproduce normal brain function and architecture, Panchision says. For one thing, the organoids are developmentally young and don’t reflect a mature brain. And researchers must figure out how to build in some core features: the necessary blood vessels, immune-system cells called microglia and connections from other brain regions, such as the thalamus and cerebellum. Not to mention steroid and thyroid hormones, which also shape brain growth.

However, scientists don’t necessarily need or want to create a comprehensive replica of the human brain in a dish, Panchision and others point out. Rather, the goal is to build robust and reliable models for studying specific aspects of brain function.

Thus the pressing need for standardized, reproducible organoid-making recipes. Novitch’s group and many other labs are still trying to figure out why the brain bits can vary so much in size, composition and structure. Part of the trouble is the ingredients: Subtle variations in tissue-culture chemicals and Matrigel, or in different stem cell lines and how they are grown first in 2-D culture, can have a big impact on how the organoids turn out, Novitch says.

At the same time, researchers need to do a more thorough job of analyzing brain organoids to know what’s actually in them at different developmental time points, compared with actual human fetal brain tissue, says UCSF’s Kriegstein. It’s otherwise hard to say whether a brain blob truly recapitulates the neural tissue that scientists claim it does. Labs have started tackling the problem with a tool called single-cell transcriptome analysis, which gives readouts of all the genes that are active in individual cells.

“Greater rigor is needed,” Kriegstein says. “And I am sure we will eventually get there.”

“Pop” goes the knuckle — but why?

Scientists disagree over why cracking your knuckles makes noise. Now, a new mathematical explanation suggests the sound results from the partial collapse of tiny gas bubbles in the joints’ fluid.

Most explanations of knuckle noise involve bubbles, which form under the low pressures induced by finger manipulations that separate the joint. While some studies pinpoint a bubble’s implosion as the sound’s source, a paper in 2015 showed that the bubbles don’t fully implode. Instead, they persist in the joints up to 20 minutes after cracking, suggesting it’s not the bubble’s collapse that creates noise, but its formation (SN: 5/16/15, p. 16).
But it wasn’t clear how a bubble’s debut could make sounds that are audible across a room. So two engineers from Stanford University and École Polytechnique in Palaiseau, France, took another crack at solving the mystery.

The sound may come from bubbles that collapse only partway, the two researchers report March 29 in Scientific Reports. A mathematical simulation of a partial bubble collapse explained both the dominant frequency of the sound and its volume. That finding would also explain why bubbles have been observed sticking around in the fluid.

Shimmering, gelatinous comb jellies wouldn’t appear to have much to hide. But their mostly see-through bodies cloak a nervous system unlike that of any other known animal, researchers report in the April 21 Science.

In the nervous systems of everything from anemones to aardvarks, electrical impulses pass between nerve cells, allowing for signals to move from one cell to the next. But the ctenophores’ cobweb of neurons, called a nerve net, is missing these distinct connection spots, or synapses. Instead, the nerve net is fused together, with long, stringy neurons sharing a cell membrane, a new 3-D map of its structure shows.
While the nerve net has been described before, no one had generated a high-resolution, detailed picture of it.

It’s possible the bizarre tissue represents a second, independent evolutionary origin of a nervous system, say Pawel Burkhardt, a comparative neurobiologist at the University of Bergen in Norway, and colleagues.

Superficially similar to jellyfish, ctenophores are often called comb jellies because they swim using rows of beating, hairlike combs. The enigmatic phylum is considered one of the earliest to branch off the animal tree of life. So ctenophores’ possession of a simple nervous system has been of particular interest to scientists interested in how such systems evolved.

Previous genetics research had hinted at the strangeness of the ctenophore nervous system. For instance, a 2018 study couldn’t find a cell type in ctenophores with a genetic signature that corresponded to recognizable neurons, Burkhardt says.

Burkhardt, along with neurobiologist Maike Kittelmann of Oxford Brookes University in England and colleagues, examined young sea walnuts (Mnemiopsis leidyi) using electron microscopes, compiling many images to reconstruct the entire net structure. Their 3-D map of a 1-day-old sea walnut revealed the funky synapse-free fusion between the five sprawling neurons that made up the tiny ctenophore’s net.
The conventional view is that neurons and the rest of the nervous system evolved once in animal evolutionary history. But given this “unique architecture” and ctenophores’ ancient position in the animal kingdom, it raises the possibility that nerve cells actually evolved twice, Burkhardt says. “I think that’s exciting.”

But he adds that further work — especially on the development of these neurons — is needed to help verify their evolutionary origin.

The origins of the animal nervous system is a murky area of research. Sponges — the traditional competitors for the title of most ancient animal — don’t have a nervous system, or muscles or fundamental vision proteins called opsins, for that matter. But there’s been mounting evidence to suggest that ctenophores are actually the most ancient animal group, older even than sponges (SN: 12/12/13).

If ctenophores arose first, it “implies that either sponges have lost a massive number of features, or that the ctenophores effectively evolved them all independently,” says Graham Budd, a paleobiologist at Uppsala University in Sweden who was not involved in the research.

If sponges emerged first, it’s still possible that ctenophores evolved their nerve net independently rather than inheriting it from a neuron-bearing ancestor, Burkhardt says. Ctenophores have other neurons outside the nerve net, such as mesogleal neurons embedded in a ctenophore’s gelatinous body layer and sensory cells, the latter of which may communicate with the nerve net to adjust the beating of the combs. So, it’s possible they’re a mosaic of two nervous systems of differing evolutionary origins.

But Joseph Ryan, a bioinformatician at the University of Florida in Gainesville, doesn’t think the results necessarily point to the parallel evolution of a nervous system. Given how long ctenophores have been around — especially if they are older than sponges — the ancestral nervous system may have had plenty of time to evolve into something weird and highly-specialized, says Ryan, who was not part of the study. “We’re dealing with close to a billion years of evolution. We’re going to expect strange things to happen.”

The findings are “one more bit of the jigsaw puzzle,” Budd says. “There’s a whole bunch we don’t know about these rather common and rather well-known animals.”

For instance, it’s unclear how the nerve net works. Our neurons use rapid changes in voltage across their cell membranes to send signals, but the nerve net might work quite differently, Burkhardt says.

There are reports of potentially similar systems in other animals, such as by-the-wind-sailor jellies (Velella velella). Studying them in detail, along with nerve nets in other ctenophore species, could determine just how unusual this synapse-less nervous system is.

Northern elephant seals are the true masters of the power nap.

On long trips out to sea, the seals snooze less than 20 minutes at a time, researchers report in the April 21 Science. The animals average just two hours of shut-eye per day while swimming offshore for months — rivaling African elephants for the least sleep measured among mammals (SN: 3/1/17).

“It’s important to map these extremes of [sleep behavior] across the animal kingdom to get a better sense of the evolution and the function of sleep for all mammals, including humans,” says Jessica Kendall-Bar, an ecophysiologist at the University of California, San Diego. Knowing how seals catch their z’s could also guide conservation efforts to protect places where they sleep.
Northern elephant seals (Mirounga angustirostris) spend most of the year out in the Pacific Ocean. On these odysseys, the animals forage around the clock for fish, squid and other food to sustain their enormous bodies, which can be as hefty as a car (SN: 2/4/22). Because northern elephant seals are most vulnerable to sharks and killer whales at the surface, they come up for air only a couple minutes at a time between 10- to 30-minute deep dives (SN: 9/28/02).

“People had known that these seals dive almost all the time when they’re out in the ocean, but it wasn’t known if and how they sleep,” says Niels Rattenborg, a neurobiologist at the Max Planck Institute for Biological Intelligence in Seewiesen, Germany, who was not involved in the study.

To find out if the seals sleep while diving, Kendall-Bar and her colleagues developed a watertight EEG cap for the animals. Using the cap and other sensors, the team tracked the brain waves, heart rates and 3-D motion of 13 young female seals, including five at a lab and six hanging out at coastal Año Nuevo State Park north of Santa Cruz, Calif. EEG data recorded while seals were slumbering revealed what the animals’ naptime brain waves looked like.

Kendall-Bar’s team also took two sensor-strapped seals from Año Nuevo and released them at another beach about 60 kilometers south. To swim home, the seals had to cross the deep Monterey Canyon — a locale similar to the deep, predator-fraught waters frequented by seals on months-long foraging trips. Matching the seals’ EEG readings to their diving motions on this journey showed how northern elephant seals sleep on long voyages.

The animals first swim 60 to 100 meters below the surface, then relax into a glide, Kendall-Bar says. As they nod off into slow-wave sleep, the animals keep holding themselves upright for several minutes. But as REM sleep sets in, so does sleep paralysis. The animals flip upside-down and drift in gentle spirals toward the seafloor. Seals can descend hundreds of meters deep during these naps — far below where their predators normally prowl. When the seals wake after five to 10 minutes of sleep, they swim up to the surface. The whole routine takes about 20 minutes.

Looking for that distinct sleep dive motion, the researchers could pick out naps in the dive records of 334 adult seals that had been outfitted with tracking tags from 2004 to 2019. Those sleep patterns revealed that northern elephant seals conk out, on average, around two hours per day while on months-long foraging missions. But the seals sleep nearly 11 hours per day while on land to mate and molt, where they can indulge in long, beachside siestas without worrying about predators.
“What the seals are doing might be something like what we do when we sleep in on the weekend, but it’s on a much longer timescale,” Rattenborg says. He and his colleagues have found a similar feast-and-famine style of sleep in great frigate birds, which fly over the ocean (SN: 6/30/16). “Although they can sleep while they’re flying,” he says, “they sleep less than an hour a day for up to a week at a time, and once back on land, they sleep over 12 hours a day.”

Curiously, northern elephant seals’ sleep habits are quite different from how other marine mammals have been seen sleeping in labs. “Many of them … sleep in just half of their brain at a time,” Kendall-Bar says. That half-awake state allows dolphins, fur seals and sea lions to practice constant vigilance, literally sleeping with one eye open.

“I think it’s pretty cool that elephant seals are doing this without [one-sided] sleep,” Kendall-Bar says. “They’re shutting off both halves of their brain completely and leaving themselves vulnerable.” It seems the key to enjoying such deep sleep is sleeping deep in the sea.

MINNEAPOLIS — Bubbles of radiation billowing from the galactic center may have started as a stream of electrons and their antimatter counterparts, positrons, new observations suggest. An excess of positrons zipping past Earth suggests that the bubbles are the result of a burp from our galaxy’s supermassive black hole after a meal millions of years ago.

For over a decade, scientists have known about bubbles of gas, or Fermi bubbles, extending above and below the Milky Way’s center (SN: 11/9/10). Other observations have since spotted the bubbles in microwave radiation and X-rays (SN: 12/9/20). But astronomers still aren’t quite sure how they formed.
A jet of high-energy electrons and positrons, emitted by the supermassive black hole in one big burst, could explain the bubbles’ multi-wavelength light, physicist Ilias Cholis reported April 18 at the American Physical Society meeting.

In the initial burst, most of the particles would have been launched along jets aimed perpendicular to the galaxy’s disk. As the particles interacted with other galactic matter, they would lose energy and cause the emission of different wavelengths of light.

Those jets would have been aimed away from Earth, so those particles can never be detected. But some of the particles could have escaped along the galactic disk, perpendicular to the bubbles, and end up passing Earth. “It could be that just now, some of those positrons are hitting us,” says Cholis, of Oakland University in Rochester, Mich.

So Cholis and Iason Krommydas of Rice University in Houston analyzed positrons detected by the Alpha Magnetic Spectrometer on the International Space Station. The pair found an excess of positrons whose present-day energies could correspond to a burst of activity from the galactic center between 3 million and 10 million years ago, right around when the Fermi bubbles are thought to have formed, Cholis said at the meeting.

The result, Cholis said, supports the idea that the Fermi bubbles came from a time when the galaxy’s central black hole was busier than it is today.

Since early 2022, sea urchins have been mysteriously dying off across the Caribbean. Now scientists say they have identified the main culprit: a type of relatively large, single-celled marine microorganism called a scuticociliate.

The discovery is a little surprising given that “ciliates are not normally seen as agents of mass mortality,” says Ian Hewson, a marine microbial ecologist at Cornell University. But the evidence, described April 19 in Science Advances, all points to the organism, Philaster apodigitiformis, infecting the urchins, he says. “In all of my years of investigating marine diseases, this is the one which we are 100 percent confident about.”
Scuticociliates are found across the world’s oceans. Given their ubiquity, it’s unknown what conditions may have allowed P. apodigitiformis to become so detrimental to the urchins. It’s also unclear how it causes infection.

While there are no available treatments for the disease, knowing the pathogen’s identity allows for the development of possible options.
Long-spined sea urchins (Diadema antillarum) play a crucial role in Caribbean coral reefs, grazing algae that would otherwise smother corals (SN: 9/27/22). In the 1980s, the urchins nearly disappeared during a massive die-off, the cause of which remains unknown (SN: 6/16/84).

Decades of restoration efforts had made some progress when an alarmingly similar mortality event began to spread in January 2022, wiping out thousands of urchins. This time, scientists across the United States and the Caribbean sprang into action.

Three teams independently reached the same conclusion about P. apodigitiformis, using different approaches. Hewson’s team compared the entire set of active genes, or the transcriptome, of healthy and sick urchins from 23 sites across the Caribbean. The researchers noticed that some of the active genes in the sick urchins’ transcriptomes weren’t from the urchins but from the microorganism. Meanwhile, teams in Florida and Hawaii observed the scuticociliates in the tissues and fluids of sick urchins, reinforcing the genetic finding.

Upon a closer look, the scuticociliates tended to cluster in the sick urchins’ body walls and at the base of their spines. The microorganisms were absent from healthy urchins.
The next step was to isolate the pathogen and infect healthy urchins. Four days after infection, six of 10 infected urchins lost many spines — a common symptom of sick urchins. None of the uninfected urchins lost spines.

“It was really exciting to see,” says Michael Sweet, a marine disease ecologist at the University of Derby in England, who wasn’t involved in the study. “Scary, but also exciting to see the [ciliate’s] name mentioned in a different context because Philaster has never been related to urchin diseases before.” His research points to the involvement of the genus in several coral diseases.

While the scuticociliate clearly plays a pivotal role, Sweet says, there are almost certainly other factors at play, such as other microorganisms or environmental stressors, that could help explain what triggered the start of the recent die-off.

For now, it’s unknown if the same pathogen was involved in the 1980s die-off. Hewson’s team hopes to answer that question by looking at museum specimens from the period.

The classical view of how the human brain controls voluntary movement might not tell the whole story.

That map of the primary motor cortex — the motor homunculus — shows how this brain region is divided into sections assigned to each body part that can be controlled voluntarily (SN: 6/16/15). It puts your toes next to your ankle, and your neck next to your thumb. The space each part takes up on the cortex is also proportional to how much control one has over that part. Each finger, for example, takes up more space than a whole thigh.
A new map reveals that in addition to having regions devoted to specific body parts, three newfound areas control integrative, whole-body actions. And representations of where specific body parts fall on this map are organized differently than previously thought, researchers report April 19 in Nature.

Research in monkeys had hinted at this. “There is a whole cohort of people who have known for 50 years that the homunculus isn’t quite right,” says Evan Gordon, a neuroscientist at Washington University School of Medicine in St. Louis. But ever since pioneering brain-mapping work by neurosurgeon Wilder Penfield starting in the 1930s, the homunculus has reigned supreme in neuroscience.

Gordon and his colleagues study synchronized activity and communication between different brain regions. They noticed some spots in the primary motor cortex were linked to unexpected areas involved in action control and pain perception. Because that didn’t fit with the homunculus map, they wrote it off as a result of imperfect data. “But we kept seeing it, and it kept bugging us,” Gordon says.

So the team gathered functional MRI data on volunteers as they performed various tasks.

Two participants completed simple movements like moving just their eyebrows or toes, as well as complex tasks like simultaneously rotating their wrist and moving their foot from side to side.

The fMRI data revealed which parts of the brain activated at the same time as each task was done, allowing the researchers to trace which regions were functionally connected to one another. Seven more participants were recorded while not doing any particular task in order to look at how brain areas communicate during rest.

Testing only a few participants, each for many hours, offers unique insights into neural connectivity, Gordon says. “When we collect this much data in individuals, we constantly start seeing things that people have never really noticed before.”
The team discovered that while the brain-body part connections vaguely follow the pattern discovered by Penfield, the primary motor cortex is organized into three distinct sections. Each represents different body regions: lower body, torso and arms, and head.

Within each of these sections, the outermost body part of that region is mapped to the center of that section. For example, the area of the primary motor cortex assigned to the lower body has the toes in the middle with other leg parts radiating out in each direction from it. As a result, the entire section is organized like this: hip, knee, ankle, toes, ankle, knee, hip.
The team also unexpectedly found three mysterious spots not linked to a specific body part. Dubbed intereffector regions, they connect to an external network involved in action control and the sensing of pain. These regions alternate with the sections devoted to specific body parts. The team suspects that intereffector regions may integrate action goals and body movements involving multiple body parts, while the spaces in between are used for precise movements of isolated body parts.

Using previous data from three large fMRI studies, which include data from around 50,000 people, the team verified that this organization was consistent across a wide swath of people. Similar patterns also appeared in existing datasets from macaque monkeys, children and clinical populations.

“I think it was just easy to miss anything that seemed anomalous — must be noise,” says Michael Graziano, a neuroscientist at Princeton University who was not involved in the research. But with access to these huge datasets, “you get these vast numbers of subjects, and the pattern is crystal clear, and you can’t ignore it …. This is really the best example I’ve seen in a long, long time of looking at humans and trying to figure out at a detailed level what is the organization.”

Gordon’s team now plans to see whether these intereffector regions play a role in certain kinds of pain. More broadly, the team hopes their findings will prompt more in-depth research of what specific areas of the brain do. With new techniques and equipment, there is much left to explore, Gordon says. “Brain mapping isn’t dead.”

An animal bone fragment full of human-made pits hints at how prehistoric people in Western Europe may have crafted clothing.

The nearly 40,000-year-old artifact probably served as a punch board for leatherwork, researchers report April 12 in Science Advances. They suggest that the bone fragment rested beneath animal hide while an artisan pricked holes in the material, possibly for seams. If so, it’s the earliest-known tool of its kind and predates eyed needles in the region by about 15,000 years.
Found at an archaeological site south of Barcelona, the roughly 11-centimeter-long bone fragment contains 28 punctures scattered across one flat side, with 10 of them aligned and fairly evenly spaced.

The marks don’t seem to have been a notation system or decoration, given that some holes are hard to see and the bone fragment wasn’t otherwise shaped, says archaeologist Luc Doyon of the University of Bordeaux in France. He thought leatherwork could have made the marks. But it wasn’t until he visited a cobbler shop and saw one of the artisan’s tools that the hypothesis solidified, guiding Doyon’s next steps.

He and colleagues attempted to re-create the artifact’s holes by puncturing cattle rib bones with tools including sharpened flint, horns and antlers. Piercing leather atop bone with a burin — a pointed stone chisel — by tapping it with a hammerlike tool created pits that resemble those on the bone fragment.

Further experiments suggested the artifact’s 10 orderly punctures were made by the same tool and intentionally aligned and regularly spaced. This hints that holes were created in the leather to make a seam sewn with a threading tool.

Scientists knew that humans wore clothing long before the oldest-known eyed needles existed (SN: 4/20/10). “What [the new finding] tells us is that the first modern humans who lived in Europe had the technology in their toolkit for making fitted clothes,” Doyon says.

Methane is a greenhouse gas with dual personalities. It heats Earth’s atmosphere 28 times as potently as carbon dioxide, gram for gram. But its absorption of the sun’s radiation high in the atmosphere also alters cloud patterns — casting a bit of shadow on its warming effect.

So rather than adding even more thermal energy to the atmosphere, as previously thought, methane’s solar absorption sets off a cascade of events that reduces its overall warming effect by about 30 percent, researchers report March 16 in Nature Geoscience.
“These are really interesting and important results,” says Rachael Byrom, a climate scientist at the CICERO Center for International Climate Research in Oslo who wasn’t involved in the new study. Nonetheless, she says, “methane still remains a really key gas that we need to target in emissions reductions.”

Humans are responsible for most of the methane entering the atmosphere, where it worsens global warming. Concentrations of the potent greenhouse gas have risen about 162 percent since preindustrial times, according to the U.S. National Oceanic and Atmospheric Administration.

The largest sources of anthropogenic methane include fossil fuel use, livestock, rice farming, landfills and biomass burning (SN: 9/29/22; SN: 7/14/20). Scientists fear that as warming triggers thaw of permafrost in the Arctic regions, this could also lead to increased methane emissions, as microbes in the soil consume dead plant material and release the gas (SN: 9/25/19).
Greenhouse gases like methane exert their strongest effects by absorbing infrared “longwave” radiation emitted from the planet’s surface. Earth emits this longwave radiation when it is struck by “shortwave” radiation coming directly from the sun. Most studies of greenhouse gases focus on longwave absorption.

But scientists are learning that greenhouse gases, including methane, also absorb some of the sun’s shortwave radiation. Recent estimates suggested that methane might contribute up to 15 percent more thermal energy to the atmosphere than previously thought, due to this additional shortwave absorption.

However, the new study reveals that methane’s shortwave absorption has the opposite effect. This finding is based on a detailed analysis of the gas’s absorption at various wavelengths.

The result is “counterintuitive,” says climate scientist Robert Allen of the University of California, Riverside. It happens because of the way that methane’s shortwave absorbance affects clouds in different layers of the atmosphere, Allen and colleagues’ simulations suggest.

When methane absorbs shortwave radiation in the middle and upper troposphere, above about three kilometers, it further warms the air — leading to fewer clouds in that upper layer. And because methane absorbs shortwave radiation high up, less of that radiation penetrates down to the lower troposphere. This actually cools the lower troposphere, leading to more clouds in that layer.

These thicker low-level clouds reflect more of the sun’s shortwave radiation back out to space — meaning that less of this solar radiation reaches Earth’s surface, to be converted into longwave radiation.

Meanwhile, upper-level clouds, in addition to greenhouse gases, are known to absorb longwave radiation. So fewer of these clouds means that less of the longwave radiation emitted by Earth is captured in the atmosphere — and more of it escapes to space without contributing to climate change.

With methane’s shortwave absorption, “you expect warming of the climate system,” Allen says. “But these cloud adjustments actually overwhelm the heating due to absorption, leading to a cooling effect.”

Allen and his colleagues conducted the study using a computational model of Earth’s climate. When they took the traditional approach — considering only methane’s longwave absorbance — they estimated that the gas has caused 0.2 degrees Celsius of warming since preindustrial times, out of 1.06 degrees C total warming. But when they also included shortwave absorbance, methane’s contribution to warming fell to about 0.16 degrees C.

In addition to warming the planet, methane is also thought to increase global precipitation, due to greater evaporation of water with higher temperatures. But the researchers found that inclusion of shortwave absorbance also reduced methane’s precipitation effect, from a predicted 0.3 percent increase in precipitation (based on longwave absorbance alone), down to an increase of about 0.18 percent.
It will be important to include methane’s shortwave effects in future climate projections, says Daniel Feldman, an atmospheric scientist at the Lawrence Berkeley National Laboratory in California, who was not involved in the study. But he thinks that more work needs to be done to clarify those effects.

The new study analyzed methane’s shortwave impact using only one comprehensive model that included both the atmosphere and ocean, he says. “I would just like to see that sort of analysis done across multiple models,” increasing confidence in the results.

People have different tastes. It turns out that octopuses, squid and cuttlefish do too.

These soft-bodied cephalopods have proteins on suckers along their tentacles that allow them to “taste” by touching objects. But the species have evolved to detect different compounds, researchers report in two studies published in the April 13 Nature. And the differing tastes may be tied to the species’ hunting styles.

All the species have modified versions of proteins called neurotransmitter receptors, which detect brain chemicals. Evolution morphed the brain proteins to take on new roles as taste-sensing proteins. But octopus evolution led them to develop a taste for greasy things, while squid and cuttlefish evolution tweaked the brain proteins to detect bitter compounds, the researchers discovered.
“This is an entirely new sensory system,” says Maude Baldwin, an evolutionary biologist at the Max Planck Institute for Biological Intelligence in Seewiesen, Germany, who was not involved in the work. “Together these papers offer unprecedented insight into how sensory systems evolve.”

Studying cephalopod receptors might also shed some light on how human taste-sensing proteins evolved. “It greatly enhances our understanding of how proteins evolve in general,” Baldwin says, as well as how proteins and even entire organisms acquire new functions.

Octopuses can taste many “greasy, sticky” molecules
In a previous study, Harvard physiologist Nicholas Bellono and colleagues discovered that barrel-shaped proteins known as chemotactile receptors in the suckers of California two-spot octopuses (Octopus bimaculoides) allow the animals to taste terpenes — “greasy,” insoluble molecules — with their arms (SN: 10/29/20).

To get a detailed look at these proteins, Bellono teamed up with structural biologist Ryan Hibbs of the University of Texas Southwestern Medical Center at Dallas. Hibbs and colleagues used cryoelectron microscopy to examine the three-dimensional structure of the protein.

When looking at the structure of the octopus protein, the researchers found an unexpectedly large molecule stuck in a special pocket used to detect certain chemicals. Finding a molecule stuck in one of these pockets can give clues to the protein’s function.
The mystery molecule turned out to be part of the detergent the researchers used to prepare the protein for the microscope. That’s very different from the types of molecules that bind to the neurotransmitter receptors from which chemotactile receptors evolved, says Hibbs, now at the University of California, San Diego. “Neurotransmitters are small and soluble. This thing is bulky and greasy.”

By testing a variety of molecules collected from neighboring labs, Bellono’s team determined that the octopus receptors can detect a variety of “greasy, sticky molecules” that don’t dissolve in water. Because octopuses feel around for their prey, it makes sense that their taste receptors evolved to detect molecules that remain stuck to underwater surfaces such as crab shells or their own eggs, rather than small chemicals that easily diffuse in water, Hibbs says.
But octopuses don’t seem to find all greasy molecules tasty. In one experiment, the researchers tested the response of a severed tentacle to one such chemical. The arm crawled off the measuring apparatus and right out of the bath.

Squid and cuttlefish can discern bitter compounds
To see if other cephalopods share octopuses’ tastes, the researchers turned to genetic analyses. Octopuses have 26 genes that each encode a slightly different chemotactile receptor protein. Those proteins can come together in combinations of five to detect a wide variety of molecules, the team found.

Examining genes from squid and cuttlefish, the researchers discovered that these cephalopod species also have modified neurotransmitter receptors in their suckers. But some of the squid and cuttlefish receptors detect bitter compounds which can diffuse in water, not the greasy ones octopuses taste. (Squid could also taste some terpenes, but not all of the greasy molecules octopuses detect.)

Bitter taste is often a signal that something is spoiled or poisonous, so animals usually avoid bitter compounds, says Harold Zakon, a neuroscientist and evolutionary biologist at the University of Texas at Austin who was not involved in the work.

Bitter compounds also caused squid to turn up their noses — or in this case, tentacles — at prey. Squid given shrimp soaked in a bitter compound handled the food longer before eating it than they did with undoctored prey. Or the squid rejected the bitter shrimp, something researchers never saw the animals do with regular prey.

The type of receptors the species have reflect their hunting strategies. Octopuses ”explore everything with their arms,” Bellono says, and likely use chemotactile receptors to guide their explorations. While octopuses use sight to catch prey out in the light of day, chemotactile receptors help them hunt in the dark and to find prey hidden in cracks and crevices, Bellono says. Squid and cuttlefish are ambush predators that rely on eyesight alone. The bitter receptors help squid decide whether to eat their prey only after they have it in their grasp.

The octopus and squid receptors evolved about 300 million years ago, early in the species’ histories. But it’s impossible to tell whether hunting style or receptor type came first or if the traits evolved together.

Octopuses also have another type of chemotactile receptor, the researchers found, but they don’t yet know what sorts of molecules those receptors sense.

It will take years to work out the details of what all the cephalopods’ receptors detect and how they influence animals’ behavior, Zakon says. “This is really a first announcement that these receptors have changed in fundamentally important ways.”