Biology

a-single-peptide-helps-starfish-get-rid-of-a-limb-when-attacked

A single peptide helps starfish get rid of a limb when attacked

You can have it —

A signaling molecule that’s so potent injected animals may drop more than one limb.

A five-armed starfish, with orange and yellow colors, stretched out across a coral.

For many creatures, having a limb caught in a predator’s mouth is usually a death sentence. Not starfish, though—they can detach the limb and leave the predator something to chew on while they crawl away. But how can they pull this off?

Starfish and some other animals (including lizards and salamanders) are capable of autonomy (shedding a limb when attacked). The biology behind this phenomenon in starfish was largely unknown until now. An international team of researchers led by Maurice Elphick, professor of Animal Physiology and Neuroscience at Queen Mary University of London, have found that a neurohormone released by starfish is largely responsible for detaching limbs that end up in a predator’s jaws.

So how does this neurohormone (specifically a neuropeptide) let the starfish get away? When a starfish is under stress from a predatory attack, this hormone is secreted, stimulating a muscle at the base of the animal’s arm that allows the arm to break off.

The researchers confirmed this neuropeptide “acts as an autotomy-promoting factor in starfish and such it is the first neuropeptide to be identified as a regulator of autotomy in animals,” as they said in a study recently published in Current Biology.

Holding on

Elphick’s team studied how the neuropeptide known as ArSK/CCK1 facilitates autonomy in the European Starfish, Asterias rubens. ArSK/CCK1 is already known to inhibit feeding behavior in A. rubens by causing the stomach to contract, and muscle contraction plays a role in limb loss. The researchers found that its ability to trigger contractions goes beyond feeding.

Starfish underwent an experiment that simulated conditions where a predator’s jaw clamped down on one arm. Clamps were placed on one of three sections on a single arm, either on the end, middle, or at the site in the base where autotomy is known to occur, also known as the autotomy plane. The starfish were then suspended by these clamps above a glass bowl of seawater. During the first part of the experiment, the starfish were left to react naturally, but during the second part, they were injected with ArSK/CCK1.

Without the injection, autotomy was seen mostly in animals that had arms that were clamped closest to the autotomy plane. There was not nearly as much of a reaction from starfish when the arms were clamped in the middle or end.

In the second half of the experiment, the clamping used before was combined with an injection of ArSK/CCK1. For comparison, some were injected with the related neuropeptide ArSK/CCK2. A staggering 85 percent of ArSK/CCK1-injected animals that were clamped in the middle of the arm or closer to the autotomy plane exhibited autonomy, and some autotomized additional arms. This only happened in about 27 percent of those injected with ArSK/CCK2.

Letting go

While ArSK/CCK1 proved to be the most effective chemical trigger for autotomy, its activity in the autotomy plane depends on certain aspects of a starfish’s anatomy.

Like all echinoderms, starfish have endoskeletons built of tiny bones, or ossicles, linked by muscles and collagen fibers that allow the animals to change posture and move. Two exclusive features only found in the autotomy plane allow this structure to break. Under the skin of the autotomy plane, there is a region where bundles of collagen fibers are positioned far apart to make breakage easier. The second of these features is a band of muscle close to the region of collagen bundles. Known as the tourniquet muscle, this muscle is responsible for the constriction that allows an arm in danger to fall off.

Analyzing starfish arm tissue while it was undergoing autotomy gave the scientists a new perspective on this process. Right after a starfish has its arm seized by a predator,  ArSK/CCK1 tells nerves in the tourniquet muscle to start constricting in the region right by the autonomy plane. While this is happening, the collagen in the body wall in that region softens and breaks, and so do the muscles and ligaments that hold together ossicles. It is now thought that ArSK/CCK1 is also involved in the softening of this tissue that prepares it for breakage.

After starfish autotomize a limb, that limb eventually regenerates. The same happens in other animals that can use autotomy to their advantage (such as lizards, which also grow their tails back). In the future, finding out why some animals have the ability to regenerate may tell us why we either never evolved it or some of our ancestors lost the ability. Elphick acknowledged that there might still be other unidentified factors working together with ArSK/CCK1, but further insight could someday give us a clearer picture of this process.

“Autotomy is a key adaptation for survival that has evolved in several animal taxa,” the research team said in the same study, “[and] the findings of this study provide a seminal insight into the neural mechanisms that control this remarkable biological process,”

Current Biology, 2024.  DOI: 10.1016/j.cub.2024.08.003

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remembering-where-your-meals-came-from-key-for-a-small-bird’s-survival

Remembering where your meals came from key for a small bird’s survival

Where’d I leave that again? —

For small birds, remembering where the food is beats forgetting when it’s gone.

a small, black and grey bird perched on the branch of a fir tree.

It seems like common sense that being smart should increase the chances of survival in wild animals. Yet for a long time, scientists couldn’t demonstrate that because it was unclear how to tell exactly if a lion or a crocodile or a mountain chickadee was actually smart or not. Our best shots, so far, were looking at indirect metrics like brain size or doing lab tests of various cognitive skills such as reversal learning, an ability that can help an animal adapt to a changing environment.

But a new, large-scale study on wild mountain chickadees, led by Joseph Welklin, an evolutionary biologist at the University of Nevada, showed that neither brain size nor reversal learning skills were correlated with survival. What mattered most for chickadees, small birds that save stashes of food, was simply remembering where they cached all their food. A chickadee didn’t need to be a genius to survive; it just needed to be good at its job.

Testing bird brains

“Chickadees cache one food item in one location, and they do this across a big area. They can have tens of thousands of caches. They do this in the fall and then, in the winter, they use a special kind of spatial memory to find those caches and retrieve the food. They are little birds, weight is like 12 grams, and they need to eat almost all the time. If they don’t eat for a few hours, they die,” explains Vladimir Pravosudov, an ornithologist at the University of Nevada and senior co-author of the study.

The team chose the chickadees to study the impact cognitive skills had on survival because the failure to find their caches was their most common cause of death. This way, the team hoped, the impact of other factors like predation or disease would be minimized.

First, however, Welklin and his colleagues had to come up with a way to test cognitive skills in a fairly large population of chickadees. They did it by placing a metal square with two smart feeders attached to each side among the trees where the chickadees lived. “The feeders were equipped with RFID receivers that recognized the signal whenever a chickadee, previously marked with a microchip-fitted leg band, landed near them and opened the doors to dispense a single seed,” Welklin says. After a few days spent getting the chickadees familiar with the door-opening mechanism, the team started running tests.

The first task was aimed at testing how good different chickadees were at their most important job: associating a location with food and remembering where it was. To this end, each of the 227 chickadees participating in the study was assigned just one feeder that opened when they landed on it; all the other feeders remained closed. A chickadee’s performance was measured by the number of trials it needed to figure out which feeder would serve it, and how many errors (landings on the wrong feeders) it made over four days. “If you were to find the right feeder at random, it should take you 3.5 trials on average. All the birds learned and performed way better than chance,” Pravosudov says.

The second task was meant to test reversal learning skills, widely considered the best predictor of survival. Once the chickadees learned the location of the reward-dispensing feeders, the locations were changed. The goal was to see how fast the birds would adapt to this change.

Once the results of both tests were in, the team monitored the birds using their microchip bands, catching them and changing the bands every year, for over six years. “Part of the reason that’s never been done in the past is just because it takes so much work,” says Welklin. But the work paid off in the end.

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old-easter-island-genomes-show-no-sign-of-a-population-collapse

Old Easter Island genomes show no sign of a population collapse

A row of grey rock sculptures of human torsos and heads, arranged in a long line.

Rapa Nui, often referred to as Easter Island, is one of the most remote populated islands in the world. It’s so distant that Europeans didn’t stumble onto it until centuries after they had started exploring the Pacific. When they arrived, though, they found that the relatively small island supported a population of thousands, one that had built imposing monumental statues called moai. Arguments over how this population got there and what happened once it did have gone on ever since.

Some of these arguments, such as the idea that the island’s indigenous people had traveled there from South America, have since been put to rest. Genomes from people native to the island show that its original population was part of the Polynesian expansion across the Pacific. But others, such as the role of ecological collapse in limiting the island’s population and altering its culture, continue to be debated.

Researchers have now obtained genome sequence from the remains of 15 Rapa Nui natives who predate European contact. And they indicate that the population of the island appears to have grown slowly and steadily, without any sign of a bottleneck that could be associated with an ecological collapse. And roughly 10 percent of the genomes appear to have a Native American source that likely dates from roughly the same time that the island was settled.

Out of the museum

The remains that provided these genomes weren’t found on Rapa Nui, at least not recently. Instead, they reside at the Muséum National d’Histoire Naturelle in France, having been obtained at some uncertain point in the past. Their presence there is a point of contention for the indigenous people of Rapa Nui, but the researchers behind the new work had the cooperation of the islanders in this project, having worked with them extensively. The researchers’ description of these interactions could be viewed as a model for how this sort of work should be done:

Throughout the course of the study, we met with representatives of the Rapanui community on the island, the Comisión de Desarrollo Rapa Nui and the Comisión Asesora de Monumentos Nacionales, where we presented our research goals and ongoing results. Both commissions voted in favor of us continuing with the research… We presented the research project in public talks, a short video and radio interviews on the island, giving us the opportunity to inquire about the questions that are most relevant to the Rapanui community. These discussions have informed the research topics we investigated in this work.

Given the questionable record-keeping at various points in the past, one of the goals of this work was simply to determine whether these remains truly had originated on Rapa Nui. That was unambiguously true. All comparisons with genomes of modern populations show that all 15 of these genomes have a Polynesian origin and are most closely related to modern residents of Rapa Nui. “The confirmation of the origin of these individuals through genomic analyses will inform repatriation efforts led by the Rapa Nui Repatriation Program (Ka Haka Hoki Mai Te Mana Tupuna),” the authors suggest.

A second question was whether the remains predate European contact. The researchers attempted to perform carbon dating, but it produced dates that made no sense. Some of the remains had dates that were potentially after they had been collected, according to museum records. And all of them were from the 1800s, well after European contact and introduced diseases had shrunk the native population and mixed in DNA from non-Polynesians. Yet none of the genomes showed more than one percent European ancestry, a fraction low enough to be ascribed to a spurious statistical fluke.

So the precise date these individuals lived is uncertain. But the genetic data clearly indicates that they were born prior to the arrival of Europeans. They can therefore tell us about what the population was experiencing in the period between Rapa Nui’s settlement and the arrival of colonial powers.

Back from the Americas

While these genomes showed no sign of European ancestry, they were not fully Polynesian. Instead, roughly 10 percent of the genome appeared to be derived from a Native American population. This is the highest percentage seen in any Polynesian population, including some that show hints of Native American contact that dates to before Europeans arrived on the scene.

Isolating these DNA sequences and comparing them to populations from across the world showed that the group most closely related to the one who contributed to the Rapa Nui population presently resides in the central Andes region of South America. That’s in contrast to the earlier results, which suggested the contact was with populations further north in South America.

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x-ray-footage-shows-how-japanese-eels-escape-from-a-predator’s-stomach

X-ray footage shows how Japanese eels escape from a predator’s stomach

escape artists —

It took escaping eels 56 seconds on average to free themselves from death.

still image of An eel escaping via a fish’s gills

Enlarge / “The only species of fish confirmed to be able to escape from the digestive tract of the predatory fish after being captured.”

Hasegawa et al./Current Biology

Imagine you’re a Japanese eel, swimming around just minding your own business when—bam! A predatory fish swallows you whole and you only have a few minutes to make your escape before certain death. What’s an eel to do? According to a new paper published in the journal Current Biology, Japanese eels opt to back their way out of the digestive tract, tail first, through the esophagus, emerging from the predatory fish’s gills.

Per the authors, this is the first such study to observe the behavioral patterns and escape processes of prey within the digestive tract of predators. “At this point, the Japanese eel is the only species of fish confirmed to be able to escape from the digestive tract of the predatory fish after being captured,” co-author Yuha Hasegawa at Nagasaki University in Japan told New Scientist.

There are various strategies in nature for escaping predators after being swallowed. For instance, a parasitic worm called Paragordius tricuspidatus can force its way out of a predator’s system when its host organism is eaten. There was also a fascinating study in 2020 by Japanese scientists on the unusual survival strategy of the aquatic beetle Regimbartia attenuata. They fed a bunch of the beetles to a pond frog (Pelophylax nigromaculatus) under laboratory conditions, expecting the frog to spit the beetle out. That’s what happened with prior experiments on bombardier beetles (Pheropsophus jessoensis), which spray toxic chemicals (described as an audible “chemical explosion”) when they find themselves inside a toad’s gut, inducing the toad to invert its own stomach and vomit them back out.

But R. attenuata basically walks through the digestive tract and escapes out of the frog’s anus after being swallowed alive. It proved to be a successful escape route. In the case of the bombardier beetles, between 35 and 57 percent of the toads threw up within 50 minutes on average, ensuring the survival of the regurgitated beetles. R. attenuata‘s survival rate was a whopping 93 percent. In fact, 19 out of 20 walked out of the frog, unharmed, within an hour, although one industrious beetle bolted out in just five minutes. Granted, the beetles often emerged covered in fecal pellets, which can’t have been pleasant. But that didn’t stop them from resuming their little beetle lives; all survived at least two weeks after being swallowed.

Hasegawa co-authored an earlier study in which they observed Japanese eels emerging from a predator’s gills after being swallowed, so they knew this unique strategy was possible. They just didn’t know the details of what was going on inside the digestive tract that enabled the eels to pull off this feat. So the team decided to use X-ray videography to peer inside predatory fish (Odontobutis obscura) after eels had been eaten. They injected barium sulfate into the abdominal cavity and tail of the Japanese eels as a contrast agent, then introduced each eel to a tank containing one O. obscura. The X-ray video system captured the interactions after an eel had been swallowed.

Out through the gills

The escaping behavior of a Japanese eel. Credit: Hasegawa et al./Current Biology

O. obscura swallow their prey whole along with surrounding water, and a swallowed eel quickly ends up in the digestive tract, a highly acidic and oxygen-deprived environment that kills the eels within 211.9 seconds (a little over three minutes). Thirty-two of the eels were eaten, and of those, 13 (or 40.6 percent) managed to poke at least their tails through the gills of their predator. Of those 13, nine (69.2 percent) escaped completely within 56 seconds on average, suggesting “that the period until the tails emerge from the predator’s gill is particularly crucial for successful escape,” the authors wrote. The final push for freedom involved coiling their bodies to extract their head from the gill.

It helps to be swallowed head-first. The researchers discovered that most captured eels tried to escape by swimming back up the digestive tract toward the esophagus and gills, tail-first in the cases where escape was successful. However, eleven eels ended up completely inside the stomach and resorted to swimming around in circles—most likely looking for a possible escape route. Five of those managed to insert their tails correctly toward the esophagus, while two perished because they oriented their tails in the wrong direction.

“The most surprising moment in this study was when we observed the first footage of eels escaping by going back up the digestive tract toward the gill of the predatory fish,” said co-author Yuuki Kawabata, also of Nagasaki University. “At the beginning of the experiment, we speculated that eels would escape directly from the predator’s mouth to the gill. However, contrary to our expectations, witnessing the eels’ desperate escape from the predator’s stomach to the gills was truly astonishing for us.”

Current Biology, 2024. DOI: 10.1016/j.cub.2024.07.023  (About DOIs).

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the-fish-with-the-genome-30-times-larger-than-ours-gets-sequenced

The fish with the genome 30 times larger than ours gets sequenced

Image of the front half of a fish, with a brown and cream pattern and long fins.

Enlarge / The African Lungfish, showing it’s thin, wispy fins.

When it was first discovered, the coelacanth caused a lot of excitement. It was a living example of a group of fish that was thought to only exist as fossils. And not just any group of fish. With their long, stalk-like fins, coelacanths and their kin are thought to include the ancestors of all vertebrates that aren’t fish—the tetrapods, or vertebrates with four limbs. Meaning, among a lot of other things, us.

Since then, however, evidence has piled up that we’re more closely related to lungfish, which live in freshwater and are found in Africa, Australia, and South America. But lungfish are a bit weird. The African and South American species have seen the limb-like fins of their ancestors reduced to thin, floppy strands. And getting some perspective on their evolutionary history has proven difficult because they have the largest genomes known in animals, with the South American lungfish genome containing over 90 billion base pairs. That’s 30 times the amount of DNA we have.

But new sequencing technology has made tackling that sort of challenge manageable, and an international collaboration has now completed the largest genome ever, one where all but one chromosome carry more DNA than is found in the human genome. The work points to a history where the South American lungfish has been adding 3 billion extra bases of DNA every 10 million years for the last 200 million years, all without adding a significant number of new genes. Instead, it seems to have lost the ability to keep junk DNA in check.

Going long

The work was enabled by a technology generically termed “long-read sequencing.” Most of the genomes that were completed were done using short reads, typically in the area of 100–200 base pairs long. The secret was to do enough sequencing that, on average, every base in the genome should be sequenced multiple times. Given that, a cleverly designed computer program could figure out where two bits of sequence overlapped and register that as a single, longer piece of sequence, repeating the process until the computer spit out long strings of contiguous bases.

The problem is that most non-microbial species have stretches of repeated sequence (think hundreds of copies of the bases G and A in a row) that were longer than a few hundred bases long—and nearly identical sequences that show up in multiple locations of the genome. These would be impossible to match to a unique location, and so the output of the genome assembly software would have lots of gaps of unknown length and sequence.

This creates extreme difficulty for genomes like that of the lungfish, which is filled with non-functional “junk” DNA, all of which is typically repetitive. The software tends to produce a genome that’s more gap than sequence.

Long-read technology gets around that by doing exactly what its name implies. Rather than being able to sequence fragments of 200 bases or so, it can generate sequences that are thousands of base pairs long, easily covering the entire repeat that would have otherwise created a gap. One early version of long-read technology involved stuffing long DNA molecules through pores and watching for different voltage changes across the pore as different bases passed through it. Another had a DNA copying enzyme make a duplicate of a long strand and watch for fluorescence changes as different bases were added. These early versions tended to be a bit error-prone but have since been improved, and several newer competing technologies are now on the market.

Back in 2021, researchers used this technology to complete the genome of the Australian lungfish—the one that maintains the limb-like fins of the ancestors that gave rise to tetrapods. Now they’re back with the genomes from African and South American species. These species seem to have gone their separate ways during the breakup of the supercontinent Gondwana, a process that started nearly 200 million years ago. And having the genomes of all three should give us some perspective on the features that are common to all lungfish species, and thus are more likely to have been shared with the distant ancestors that gave rise to tetrapods.

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520-million-year-old-larva-fossil-reveals-the-origins-of-arthropods

520-million-year-old larva fossil reveals the origins of arthropods

Loads of lobopods —

Early arthropod development illuminated by a microscopic fossil.

Image of a small grey object, curved around its abdomen, with a series of small appendages on the bottom.

Enlarge / The fossil in question, oriented with its head to the left.

Yang Jie / Zhang Xiguang

Around half a billion years ago, in what is now the Yunnan Province of China, a tiny larva was trapped in mud. Hundreds of millions of years later, after the mud had long since become the black shales of the Yuan’shan formation, the larva surfaced again, a meticulously preserved time capsule that would unearth more about the evolution of arthropods.

Youti yuanshi is barely visible to the naked eye. Roughly the size of a poppy seed, it is preserved so well that its exoskeleton is almost completely intact, and even the outlines of what were once its internal organs can be seen through the lens of a microscope. Durham University researchers who examined it were able to see features of both ancient and modern arthropods. Some of these features told them how the simpler, more wormlike ancestors of living arthropods evolved into more complex organisms.

The research team also found that Y. yuanshi, which existed during the Cambrian Explosion (when most of the main animal groups started to appear on the fossil record), has certain features in common with extant arthropods, such as crabs, velvet worms, and tardigrades. “The deep evolutionary position of Youti yuanshi… illuminat[es] the internal anatomical changes that propelled the rise and diversification of [arthropods],” they said in a study recently published in Nature.

Inside out and outside in

While many fossils preserved in muddy environments like the Yuan’shan formation are flattened by compression, Y. yuanshi remained three-dimensional, making it easier to examine. So what exactly did this larva look like on the outside and inside?

The research team could immediately tell that Y. yuanshi was a lobopodian. Lobopodians are a group of extinct arthropods with long bodies and stubby legs, or lobopods. There is a pair of lobopods in the middle of each of its twenty segments, and these segments also get progressively shorter from the front to back of the body. Though soft tissue was not preserved, spherical outlines suggest an eye on each side of the head, though whether these were compound eyes is unknown. This creature had a stomodeum—the precursor to a mouth—but no anus. It would have had to both take in food and dispose of waste through its mouth.

Youti yuanshi has a cavity, known as the perivisceral cavity, that surrounds the outline of a tube that is thought to have once been the gut. The creature’s gut ends without an opening, which explains its lack of an anus. Inside each segment, there is a pair of voids toward the middle. The researchers think these are evidence of digestive glands, especially after comparing them to digestive glands in the fossils of other arthropods from the same era.

A ring around the mouth of the larva was once a circumoral nerve ring, which connected with nerves that extend to eyes and appendages in the first segment. Inside its head is a void that contained the brain. The shape of this empty chamber gives some insight into how the brain was structured. From what the researchers could see, the brain of Y. yuanshi had wedge-shaped frontal portion, and the rest of the brain was divided into two sections, as evidenced by the outline of a membrane in between them.

Way, way, way back then and now

Given its physical characteristics, the researchers think that Y. yuanshi displays features of both extinct and extant arthropods. Some are ancestral characteristics present in all arthropods, living and extinct. Others are ancestral characteristics that may have been present in extinct arthropods but are only present in some living arthropods.

Among the features present in all arthropods today is the protocerebrum; its evolutionary precursor was the circumoral nerve ring present in Y. yuanshi. The protocerebrum is the first segment of the arthropod brain, which controls the eyes and appendages, such as antennae in velvet worms and the mouthparts in tardigrades. Another feature of Y. yuanshi present in extant and extinct arthropods is its circulatory system, which is similar to that of modern arthropods, especially crustaceans.

Lobopods are a morphological feature of Y. yuanshi that are now found only in some arthropods—tardigrades and velvet worms. Many more species of lobopodians existed during the Cambrian. The lobopodians also had a distinctively structured circulatory system in their legs and other appendages, which is closest to that of velvet worms.

“The architecture of the nervous system informs the early configuration of the [arthropod] brain and its associated appendages and sensory organs, clarifying homologies across [arthropods],” the researchers said in the same study.

Yuti yuanshi is still holding on to some mysteries. They mostly have to do with the fact that it is a larva—what it looked like as an adult can only be guessed at, and it’s possible that this species developed compound eyes or flaps for swimming by the time it reached adulthood. Whether it is the larva of an already-known species of extinct lobopod is an open question. Maybe the answers are buried somewhere in the Yuan’shan shale.

Nature, 2024. DOI: 10.1038/s41586-024-07756-8

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human-muscle-cells-come-back-from-space,-look-aged

Human muscle cells come back from space, look aged

Putting some muscle into it —

Astronauts’ muscles atrophy in space, but we can identify the genes involved.

Image of two astronauts in an equipment filled chamber, standing near the suits they wear for extravehicular activities.

Enlarge / Muscle atrophy is a known hazard of spending time on the International Space Station.

Muscle-on-chip systems are three-dimensional human muscle cell bundles cultured on collagen scaffolds. A Stanford University research team sent some of these systems to the International Space Station to study the muscle atrophy commonly observed in astronauts.

It turns out that space triggers processes in human muscles that eerily resemble something we know very well: getting old. “We learned that microgravity mimics some of the qualities of accelerated aging,” said Ngan F. Huang, an associate professor at Stanford who led the study.

Space-borne bioconstructs

“This work originates from our lab’s expertise in regenerative medicine and tissue engineering. We received funding to do a tissue engineering experiment on the ISS, which really helped us embark on this journey, and became curious how microgravity affects human health,” said Huang. So her team got busy designing the research equipment needed to work onboard the space station. The first step was building the muscle-on-chip systems.

“A lot of what was known about how space affects muscles was gathered through studying the astronauts or studying animals like mice put in microgravity for research purposes,” Huang said. “In some cases, there were also in vitro cultured cells on a Petri dish—something very basic. We wanted to have something more structurally complex.” Her team developed a muscle-on-chip platform in which human myotubes, cells that organize into long parallel bundles that eventually become muscle fibers in a living organism, were grown on collagen scaffolds. The goal was to make the samples emulate real muscles better. But that came with a challenge: keeping them alive on the ISS.

“When we grow cells on Earth, we pour the medium—basically a liquid with nutrients that allow the cells to grow—over the cells, and everything is fine,” Huang said. “But in space, in the absence of gravity, we needed a closed, leak-proof, tightly sealed chamber. The medium was sloshed around in there.”

Oxygen and carbon dioxide levels were maintained with permeable membranes. Changing the medium was a complicated procedure involving syringes and small custom-designed ports. But getting all this gadgetry up and running was worth it in the end.

Genes of atrophy

Huang’s team had two sets of muscle-on-chip systems: one on the ground and one on the ISS. The idea of the study was to compare the genes that were upregulated or downregulated in each sample set. It turned out that many genes associated with aging saw their activity increase in microgravity conditions.

This result was confirmed when the team analyzed the medium that was taken off after the cells had grown in it. “The goal was to identify proteins released by the cells that were associated with microgravity. Among those, the most notable was the GDF15, which is relevant to different diseases, particularly mitochondrial dysfunction or senescence,” said Huang.

Overall, the condition of cells on the ISS was somewhat similar to sarcopenia, an age-related muscle loss disease. “There were some similarities, but also a lot of differences. The reason we didn’t make sarcopenia the main focus of this study is that we know our muscle-on-chip system is a model. It’s mostly muscle cells on a scaffold. It doesn’t have blood vessels or nerves. Comparing that to clinical, real muscle samples is a bit tricky, as it is not comparing apples to apples,” said Huang.

Nevertheless, her team went on to use their ISS muscle-on-chip samples to conduct proof-of-concept drug screening tests. Drugs they tested included those used to treat sarcopenia, among other conditions.

Space drugs

“One of the drugs we tested was the [protein] IGF 1, which is a growth factor naturally found in the body in different tissues, especially in muscles. When there is an injury, IGF 1 activates within a body to initiate muscle regeneration. Also, IGF 1 tend to be declined in aging muscles,” said Huang. The second drug tested was 15-PGDH-i, a relatively new inhibitor of enzymes that hinder the process of muscle regeneration. Used on the muscles-on-chip on the ISS, the drugs partially reduced some of the microgravity-related effects.

“One of the limitations of this work was that on the ISS, the microgravity is also accompanied by other factors, such as ionizing radiation, and it is hard to dissociate one from the other,” said Huang. It’s still unclear if the effects observed in the ISS samples were there due to radiation, the lack of gravity, both, or some additional factor. Huang’s team plans to do similar experiments on Earth in simulated microgravity conditions. “With some of the specialized equipment we recently acquired, it is possible to look at just the effects of microgravity,” Huang said. Those experiments are aimed at testing a wider range of drugs.

“The reason we do this drug screening is to develop drugs that could either be taken preemptively or during the flight to counteract muscle atrophy. It would probably be more feasible, lighter, and cheaper than doing artificial gravity concepts,” Huang said. The most promising candidate drugs selected in these ground experiments will be tested on Huang’s muscle-on-chip systems onboard the ISS in 2025.

Stem Cell Reports, 2024. DOI: 10.1016/j.stemcr.2024.06.010

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karaoke-reveals-why-we-blush

Karaoke reveals why we blush

Singing for science —

Volunteers watched their own performances as an MRI tracked brain activity.

A hand holding a microphone against a blurry backdrop, taken from an angle that implies the microphone is directly in front of your face.

Singing off-key in front of others is one way to get embarrassed. Regardless of how you get there, why does embarrassment almost inevitably come with burning cheeks that turn an obvious shade of red (which is possibly even more embarrassing)?

Blushing starts not in the face but in the brain, though exactly where has been debated. Previous thinking often reasoned that the blush reaction was associated with higher socio-cognitive processes, such as thinking of how one is perceived by others.

After studying subjects who watched videos of themselves singing karaoke, however, researchers led by Milica Nicolic of the University of Amsterdam have found that blushing is really the result of specific emotions being aroused.

Nicolic’s findings suggest that blushing “is a consequence of a high level of ambivalent emotional arousal that occurs when a person feels threatened and wants to flee but, at the same time, feels the urge not to give up,” as she and her colleagues put it in a study recently published in Proceedings of the Royal Society B.

Taking the stage

The researchers sought out test subjects who were most likely to blush when watching themselves sing bad karaoke: adolescent girls. Adolescents tend to be much more self-aware and more sensitive to being judged by others than adults are.

The subjects couldn’t pick just any song. Nicolic and her team had made sure to give them a choice of four songs that music experts had deemed difficult, which is why they selected “Hello” by Adele, “Let it Go” from Frozen, “All I Want For Christmas is You” by Mariah Carey, and “All the Things You Said” by tATu. Videos of the subjects were recorded as they sang.

On their second visit to the lab, subjects were put in an MRI scanner and were shown videos of themselves and others singing karaoke. They watched 15 video clips of themselves singing and, as a control, 15 segments of someone who was thought to have similar singing ability, so secondhand embarrassment could be ruled out.

The other control factor was videos of professional singers disguised as participants. Because the professionals sang better overall, it was unlikely they would trigger secondhand embarrassment.

Enough to make you blush

The researchers checked for an increase in cheek temperature, as blood flow measurements had been used in past studies but are more prone to error. This was measured with a fast-response temperature transducer as the subjects watched karaoke videos.

It was only when the subjects watched themselves sing that cheek temperature went up. There was virtually no increase or decrease when watching others—meaning no secondhand embarrassment—and a slight decrease when watching a professional singer.

The MRI scans revealed which regions of the brain were activated as subjects watched videos of themselves. These include the anterior insular cortex, or anterior insula, which responds to a range of emotions, including fear, anxiety, and, of course, embarrassment. There was also the mid-cingulate cortex, which emotionally and cognitively manages pain—including embarrassment—by trying to anticipate that pain and reacting with aversion and avoidance. The dorsolateral prefrontal cortex, which helps process fear and anxiety, also lit up.

There was also more activity detected in the cerebellum, which is responsible for much of the emotional processing in the brain, when subjects watched themselves sing. Those who blushed more while watching their own video clips showed the most cerebellum activity. This could mean they were feeling stronger emotions.

What surprised the researchers was that there was no additional activation in areas known for being involved in the process of understanding one’s mental state, meaning someone’s opinion of what others might think of them may not be necessary for blushing to happen.

So blushing is really more about the surge of emotions someone feels when being faced with things that pertain to the self and not so much about worrying what other people think. That can definitely happen if you’re watching a video of your own voice cracking at the high notes in an Adele song.

Proceedings of the Royal Society B, 2024.  DOI: 10.1098/rspb.2024.0958

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researchers-track-individual-neurons-as-they-respond-to-words

Researchers track individual neurons as they respond to words

Pondering phrasing —

When processing language, individual neurons respond to words with similar meanings.

Human Neuron, Digital Light Microscope. (Photo By BSIP/Universal Images Group via Getty Images)

Enlarge / Human Neuron, Digital Light Microscope. (Photo By BSIP/Universal Images Group via Getty Images)

BSIP/Universal Images Group via Getty Images

“Language is a huge field, and we are novices in this. We know a lot about how different areas of the brain are involved in linguistic tasks, but the details are not very clear,” says Mohsen Jamali, a computational neuroscience researcher at Harvard Medical School who led a recent study into the mechanism of human language comprehension.

“What was unique in our work was that we were looking at single neurons. There is a lot of studies like that on animals—studies in electrophysiology, but they are very limited in humans. We had a unique opportunity to access neurons in humans,” Jamali adds.

Probing the brain

Jamali’s experiment involved playing recorded sets of words to patients who, for clinical reasons, had implants that monitored the activity of neurons located in their left prefrontal cortex—the area that’s largely responsible for processing language. “We had data from two types of electrodes: the old-fashioned tungsten microarrays that can pick the activity of a few neurons; and the Neuropixel probes which are the latest development in electrophysiology,” Jamali says. The Neuropixels were first inserted in human patients in 2022 and could record the activity of over a hundred neurons.

“So we were in the operation room and asked the patient to participate. We had a mixture of sentences and words, including gibberish sounds that weren’t actual words but sounded like words. We also had a short story about Elvis,” Jamali explains. He said the goal was to figure out if there was some structure to the neuronal response to language. Gibberish words were used as a control to see if the neurons responded to them in a different way.

“The electrodes we used in the study registered voltage—it was a continuous signal at 30 kHz sampling rate—and the critical part was to dissociate how many neurons we had in each recording channel. We used statistical analysis to separate individual neurons in the signal,” Jamali says. Then, his team synchronized the neuronal activity signals with the recordings played to the patients down to a millisecond and started analyzing the data they gathered.

Putting words in drawers

“First, we translated words in our sets to vectors,” Jamali says. Specifically, his team used the Word2Vec, a technique used in computer science to find relationships between words contained in a large corpus of text. What Word2Vec can do is tell if certain words have something in common—if they are synonyms, for example. “Each word was represented by a vector in a 300-dimensional space. Then we just looked at the distance between those vectors and if the distance was close, we concluded the words belonged in the same category,” Jamali explains.

Then the team used these vectors to identify words that clustered together, which suggested they had something in common (something they later confirmed by examining which words were in a cluster together). They then determined whether specific neurons responded differently to different clusters of words. It turned out they did.

“We ended up with nine clusters. We looked at which words were in those clusters and labeled them,” Jamali says. It turned out that each cluster corresponded to a neat semantic domain. Specialized neurons responded to words referring to animals, while other groups responded to words referring to feelings, activities, names, weather, and so on. “Most of the neurons we registered had one preferred domain. Some had more, like two or three,” Jamali explained.

The mechanics of comprehension

The team also tested if the neurons were triggered by the mere sound of a word or by its meaning. “Apart from the gibberish words, another control we used in the study was homophones,” Jamali says. The idea was to test if the neurons responded differently to the word “sun” and the word “son,” for example.

It turned out that the response changed based on context. When the sentence made it clear the word referred to a star, the sound triggered neurons triggered by weather phenomena. When it was clear that the same sound referred to a person, it triggered neurons responsible for relatives. “We also presented the same words at random without any context and found that it didn’t elicit as strong a response as when the context was available,” Jamali claims.

But the language processing in our brains will need to involve more than just different semantic categories being processed by different groups of neurons.

“There are many unanswered questions in linguistic processing. One of them is how much a structure matters, the syntax. Is it represented by a distributed network, or can we find a subset of neurons that encode structure rather than meaning?” Jamali asked. Another thing his team wants to study is what the neural processing looks like during speech production, in addition to comprehension. “How are those two processes related in terms of brain areas and the way the information is processed,” Jamali adds.

The last thing—and according to Jamali the most challenging thing—is using the Neuropixel probes to see how information is processed across different layers of the brain. “The Neuropixel probe travels through the depths of the cortex, and we can look at the neurons along the electrode and say like, ‘OK, the information from this layer, which is responsible for semantics, goes to this layer, which is responsible for something else.’ We want to learn how much information is processed by each layer. This should be challenging, but it would be interesting to see how different areas of the brain are involved at the same time when presented with linguistic stimuli,” Jamali concludes.

Nature, 2024.  DOI: 10.1038/s41586-024-07643-2

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500-million-year-old-fossil-is-the-earliest-branch-of-the-spider’s-lineage

500 million-year-old fossil is the earliest branch of the spider’s lineage

Creepy, but no longer crawly —

A local fossil collector in Morocco found the specimen decades ago.

Image of a brown fossil with a large head and many body segments, embedded in a grey-green rock.

In the early 2000s, local fossil collector Mohamed ‘Ou Said’ Ben Moula discovered numerous fossils at Fezouata Shale, a site in Morocco known for its well-preserved fossils from the Early Ordovician period, roughly 480 million years ago. Recently, a team of researchers at the University of Lausanne (UNIL) studied 100 of these fossils and identified one of them as the earliest ancestor of modern-day chelicerates, a group that includes spiders, scorpions, and horseshoe crabs.

The fossil preserves the species Setapedites abundantis, a tiny animal that crawled and swam near the bottom of a 100–200-meter-deep ocean near the South Pole 478 million years ago. It was 5 to 10 millimeters long and fed on organic matter in the seafloor sediments. “Fossils of what is now known as S. abundantis have been found early on—one specimen mentioned in the 2010 paper that recognized the importance of this biota. However, this creature wasn’t studied in detail before simply because scientists focused on other taxa first,” Pierre Gueriau, one of the researchers and a junior lecturer at UNIL, told Ars Technica.

The study from Gueriau and his team is the first to describe S. abundantis and its connection to modern-day chelicerates (also called euchelicerates). It holds great significance, because “the origin of chelicerates has been one of the most tangled knots in the arthropod tree of life, as there has been a lack of fossils between 503 to 430 million years ago,” Gueriau added.

An ancestor of spiders

The study authors used X-ray scanners to reconstruct the anatomy of 100 fossils from the Fezouata Shale in 3D. When they compared the anatomical features of these ancient animals with those of chelicerates, they noticed several similarities between S. abundantis and various ancient and modern-day arthropods, including horseshoe crabs, scorpions, and spiders.

For instance, the nature and arrangement of the head appendages or ‘legs’ in S. abundantis were homologous with those of present-day horseshoe crabs and Cambrian arthropods that existed between 540 to 480 million years ago. Moreover, like spiders and scorpions, the organism exhibited body tagmosis, where the body is organized into different functional sections.

Setapedites abundantis contributes to our understandings of the origin and early evolution of two key euchelicerate characters: the transition from biramous to uniramous prosomal appendages, and body tagmosis,” the study authors note.

Currently, two Cambrian-era arthropods, Mollisonia plenovenatrix and Habelia optata are generally considered the earliest ancestors of chelicerates (not all scientists accept this idea). Both lived around 500 million years ago. When we asked how these two differ from S. abundantis, Gueriau replied, “Habelia and Mollisonia represent at best early-branching lineages in the phylogenetic tree. While S. abundantis is found to represent, together with a couple of other fossils, the earliest branching lineage within chelicerates.”

This means Habelia and Mollisonia are relatives of the ancestors of modern-day chelicerates. On the other side, S. abundantis represents the first group that split after the chelicerate clade was established, making it the earliest member of the lineage. “These findings bring us closer to untangling the origin story of arthropods, as they allow us to fill the anatomical gap between Cambrian arthropods and early-branching chelicerates,” Gueriau told Ars Technica.

S. abundantis connects other fossils

The researchers faced many challenges during their study. For instance, the small size of the fossils made observations and interpretation complicated. They overcame this limitation by examining a large number of specimens—fortunately, S. abundantis fossils were abundant in the samples they studied. However, these fossils have yet to reveal all their secrets.

“Some of S. abundantis’ anatomical features allow for a deeper understanding of the early evolution of the chelicerate group and may even link other fossil forms, whose relationships are still highly debated, to this group,” Gueriau said. For instance, the study authors noticed a ventral protrusion at the rear of the organism. Such a feature is observed for the first time in chelicerates but is known in other primitive arthropods.

“This trait could thus bring together many other fossils with chelicerates and further resolve the early branches of the arthropod tree. So the next step for this research is to investigate deeper this feature on a wide range of fossils and its phylogenetic implications,” Gueriau added.

Nature Communications, 2023. DOI: 10.1038/s41467-024-48013-w  (About DOIs)

Rupendra Brahambhatt is an experienced journalist and filmmaker. He covers science and culture news, and for the last five years, he has been actively working with some of the most innovative news agencies, magazines, and media brands operating in different parts of the globe.

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much-of-neanderthal-genetic-diversity-came-from-modern-humans

Much of Neanderthal genetic diversity came from modern humans

A large, brown-colored skull seen in profile against a black background.

The basic outline of the interactions between modern humans and Neanderthals is now well established. The two came in contact as modern humans began their major expansion out of Africa, which occurred roughly 60,000 years ago. Humans picked up some Neanderthal DNA through interbreeding, while the Neanderthal population, always fairly small, was swept away by the waves of new arrivals.

But there are some aspects of this big-picture view that don’t entirely line up with the data. While it nicely explains the fact that Neanderthal sequences are far more common in non-African populations, it doesn’t account for the fact that every African population we’ve looked at has some DNA that matches up with Neanderthal DNA.

A study published on Thursday argues that much of this match came about because an early modern human population also left Africa and interbred with Neanderthals. But in this case, the result was to introduce modern human DNA to the Neanderthal population. The study shows that this DNA accounts for a lot of Neanderthals’ genetic diversity, suggesting that their population was even smaller than earlier estimates had suggested.

Out of Africa early

This study isn’t the first to suggest that modern humans and their genes met Neanderthals well in advance of our major out-of-Africa expansion. The key to understanding this is the genome of a Neanderthal from the Altai region of Siberia, which dates from roughly 120,000 years ago. That’s well before modern humans expanded out of Africa, yet its genome has some regions that have excellent matches to the human genome but are absent from the Denisovan lineage.

One explanation for this is that these are segments of Neanderthal DNA that were later picked up by the population that expanded out of Africa. The problem with that view is that most of these sequences also show up in African populations. So, researchers advanced the idea that an ancestral population of modern humans left Africa about 200,000 years ago, and some of its DNA was retained by Siberian Neanderthals. That’s consistent with some fossil finds that place anatomically modern humans in the Mideast at roughly the same time.

There is, however, an alternative explanation: Some of the population that expanded out of Africa 60,000 years ago and picked up Neanderthal DNA migrated back to Africa, taking the Neanderthal DNA with them. That has led to a small bit of the Neanderthal DNA persisting within African populations.

To sort this all out, a research team based at Princeton University focused on the Neanderthal DNA found in Africans, taking advantage of the fact that we now have a much larger array of completed human genomes (approximately 2,000 of them).

The work was based on a simple hypothesis. All of our work on Neanderthal DNA indicates that their population was relatively small, and thus had less genetic diversity than modern humans did. If that’s the case, then the addition of modern human DNA to the Neanderthal population should have boosted its genetic diversity. If so, then the stretches of “Neanderthal” DNA found in African populations should include some of the more diverse regions of the Neanderthal genome.

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giant-salamander-species-found-in-what-was-thought-to-be-an-icy-ecosystem

Giant salamander species found in what was thought to be an icy ecosystem

Feeding time —

Found after its kind were thought extinct, and where it was thought to be too cold.

A black background with a brown fossil at the center, consisting of the head and a portion of the vertebral column.

C. Marsicano

Gaiasia jennyae, a newly discovered freshwater apex predator with a body length reaching 4.5 meters, lurked in the swamps and lakes around 280 million years ago. Its wide, flattened head had powerful jaws full of huge fangs, ready to capture any prey unlucky enough to swim past.

The problem is, to the best of our knowledge, it shouldn’t have been that large, should have been extinct tens of millions of years before the time it apparently lived, and shouldn’t have been found in northern Namibia. “Gaiasia is the first really good look we have at an entirely different ecosystem we didn’t expect to find,” says Jason Pardo, a postdoctoral fellow at Field Museum of Natural History in Chicago. Pardo is co-author of a study on the Gaiasia jennyae discovery recently published in Nature.

Common ancestry

“Tetrapods were the animals that crawled out of the water around 380 million years ago, maybe a little earlier,” Pardo explains. These ancient creatures, also known as stem tetrapods, were the common ancestors of modern reptiles, amphibians, mammals, and birds. “Those animals lived up to what we call the end of Carboniferous, about 370–300 million years ago. Few made it through, and they lasted longer, but they mostly went extinct around 370 million ago,” he adds.

This is why the discovery of Gaiasia jennyae in the 280 million-year-old rocks of Namibia was so surprising. Not only wasn’t it extinct when the rocks it was found in were laid down, but it was dominating its ecosystem as an apex predator. By today’s standards, it was like stumbling upon a secluded island hosting animals that should have been dead for 70 million years, like a living, breathing T-rex.

“The skull of gaiasia we have found is about 67 centimeters long. We also have a front end of her upper body. We know she was at minimum 2.5 meters long, probably 3.5, 4.5 meters—big head and a long, salamander-like body,” says Pardo. He told Ars that gaiasia was a suction feeder: she opened her jaws under water, which created a vacuum that sucked her prey right in. But the large, interlocked fangs reveal that a powerful bite was also one of her weapons, probably used to hunt bigger animals. “We suspect gaiasia fed on bony fish, freshwater sharks, and maybe even other, smaller gaiasia,” says Pardo, suggesting it was a rather slow, ambush-based predator.

But considering where it was found, the fact that it had enough prey to ambush is perhaps even more of a shocker than the animal itself.

Location, location, location

“Continents were organized differently 270–280 million years ago,” says Pardo. Back then, one megacontinent called Pangea had already broken into two supercontinents. The northern supercontinent called Laurasia included parts of modern North America, Russia, and China. The southern supercontinent, the home of gaiasia, was called Gondwana, which consisted of today’s India, Africa, South America, Australia, and Antarctica. And Gondwana back then was pretty cold.

“Some researchers hypothesize that the entire continent was covered in glacial ice, much like we saw in North America and Europe during the ice ages 10,000 years ago,” says Pardo. “Others claim that it was more patchy—there were those patches where ice was not present,” he adds. Still, 280 million years ago, northern Namibia was around 60 degrees southern latitude—roughly where the northernmost reaches of Antarctica are today.

“Historically, we thought tetrapods [of that time] were living much like modern crocodiles. They were cold-blooded, and if you are cold-blooded the only way to get large and maintain activity would be to be in a very hot environment. We believed such animals couldn’t live in colder environments. Gaiasia shows that it is absolutely not the case,” Pardo claims. And this turned upside-down lots of what we knew about life on Earth back in gaiasia’s time.

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