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Hibernating Bears Don’t Get Blood Clots. Now Scientists Know Why

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People stuck sitting in tight airplane seats for an entire long-haul flight are at risk of dangerous blood clots. But somehow immobile, hibernating bears are not. Now scientists know why.

Bears settled in for winterlong slumbers have low levels of a key protein that helps blood clots form, researchers report in the April 14 Science. Platelets lacking this protein don’t easily stick together, protecting the animals from developing potentially dangerous blood clots. And low levels of the protein are not just found in bears, the team writes. Mice, pigs and humans with a largely sedentary lifestyle because of long-term mobility problems have the same protection.

The study is a “huge step forward,” says Tinen Iles, a computational biologist at the University of Minnesota in Minneapolis who was not involved with the research. It brought together researchers from a wide variety of backgrounds — from wildlife biologists to health care experts — to show how animals have adapted to stop immobility-related blood clots. Now, researchers have a roadmap to mimic nature’s solutions with drugs.  

Heat shock protein 47, or HSP47, is normally found in the cells that make up connective tissues like bone and cartilage. It’s also found in platelets, where HSP47 attaches to collagen, a protein that helps platelets stick together. This is helpful when the body responds to a cut or other injury; it’s dangerous when a clump of platelets blocks blood flow to the lungs. Potential drugs based on this study’s finding would aim to stop HSP47 from interacting with proteins or immune cells that spark clots, says Tobias Petzold, a cardiologist at University Hospital at Ludwig-Maximilians-Universität München.

Staying still for long periods of time — like during air travel — can put people at risk of developing deep vein thrombosis, rare but dangerous blood clots that usually take shape in the legs (SN: 6/13/06). During such periods of inactivity, inflammation and slow blood flow can make clots more likely to form.  

Hibernating bears spend months in a dormant state, lowering their heart rate below what’s typical in active months. But studies have suggested that the animals don’t die of conditions linked to blood clots in veins during hibernation (SN: 2/10/12). What’s more, people who experience long-term immobility, such as those with spinal cord injuries, do not develop more clots than people with typical mobility, Petzold says. But it was unclear why immobile bears and some people are protected from potentially deadly clots.

Petzold and colleagues analyzed blood samples from 13 wild brown bears (Ursus arctos) in winter and summer. Platelets from blood samples taken during hibernation were less likely to clump together than summer samples, and ones that did clot did so more slowly. That seasonal difference was pinned to HSP47 in platelets: In hibernating bears, levels of the protein were about one-fiftieth the amount found in active animals.

A close up photo of a brown bear laying down in a green plant while a woman kneels in the background with medical supplies.
Researchers took samples from 13 wild brown bears living in Sweden during the winter and summer to learn why the animals don’t develop blood clots while they lie immobile for months. Here a researcher prepares small volumes of liquid for analysis back in the lab.Ole Frøbert and T. Petzold

To confirm that HSP47 could be behind the bears’ lack of blood clots, the team did lab tests with mice. Mice lacking the protein had fewer clots and lower levels of inflammation than animals that did have HSP47. What’s more, pigs that had recently given birth — rendering them largely immobile for up to 28 days while feeding their piglets — also had lower HSP47 levels compared with active pigs.  

These findings extend to people, too. People with long-term immobility because of spinal cord injury had low levels of HSP47 and no other signs of inflammation-related clotting. The same was also true among 10 otherwise healthy people who spent a month participating in a voluntary bed rest study. After 27 days of immobility, their HSP47 levels went down.

Overall, most animals use similar proteins and cells to make clots and prevent blood loss, says Marjory Brooks, a veterinarian and comparative hematologist at Cornell University who wasn’t involved in the study. But there may be some variation among species in the sequence of events that come before the clot.

Understanding how human bodies specifically regulate HSP47 is important so that potential drugs find the right balance between preventing clots and too much bleeding.

The next big question to address, Petzold says, is how motionlessness prompts the body to make less HSP47.

Animals

The Sonoran Desert Toad Can Alter Your Mind — It’s Not The Only Animal

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The adage “all attention is good attention” may be true for marketers — not so for the Sonoran Desert toad. Last fall, the U.S. National Park Service sent out a message on Facebook asking visitors to “refrain from licking” the toad (technically Incilius alvarius but commonly called Bufo alvarius). That message came months after a New York Times article covered the booming interest in the psychedelic compound that the toad excretes from its skin — along with the “poaching, over-harvesting and illegal trafficking” that have accompanied that interest.

People don’t typically lick the toads to get high, says Robert Villa, a community outreach specialist at the University of Arizona’s Desert Laboratory on Tumamoc Hill. The secretions the toads produce are toxic when ingested. They “work orally, through the mucous membranes, and cause really dangerous side effects, like cardiac arrest,” Villa says.

Instead, for decades, people have been collecting the secretions, then drying and smoking them. When inhaled, a compound within, 5-MeO-DMT, can cause auditory and visual hallucinations. “It’s a very powerful psychedelic sometimes called the ‘God molecule,’ ” says pharmacologist and chemist David Nichols of Purdue University in West Lafayette, Ind.

The drug’s growing popularity could be bad news for toad populations. “If you relocate it outside of its home territory,” Villa says, which often happens when people collect a toad for its secretions, “it gets lost and its chances for survival go way down.” What’s more, collecting large numbers of toads increases the risk of disease transmission, like chytrid fungus, between toads.

We at Science News heard the PSA loud and clear: Just leave this toad alone. But we couldn’t help but wonder: What other amazing animals may have psychedelic potential? Join us on a tour, by land and sea, of some of the world’s mind-altering fauna.

Sonoran Desert toad (Incilius alvarius)

Habitat: The Sonoran Desert, in the southwestern United States and northern Mexico

A photo of a Sonoran Desert toad siting on small rocks.
The Sonoran Desert toad secretes an enzyme that converts bufotenine, a compound also made by other toads, into 5-MeO-DMT, a powerful hallucinogen related to the psychedelic drug DMT.HOLGER KRISP/WIKIMEDIA COMMONS (CC BY 3.0)

All toads secrete toxins from their skin. These secretions, whose specific compounds vary from species to species, probably evolved as a way to keep a toad’s body moist. Over time, the compounds, which can also act on the brain and affect heart muscle when ingested, came to aid in self-defense.

But the Sonoran Desert toad, also known as the Colorado River toad, appears to have taken evolution one step further.

The toad, one of the largest in North America, secretes an enzyme that converts bufotenine, a compound also made by other toads, into 5-MeO-DMT, a powerful hallucinogen related to the psychedelic drug DMT.

A frightened Sonoran Desert toad gushes its toxic mix, which includes 5-MeO-DMT, from its parotoid glands — located behind each eye — and from glands on its legs. It’s a way to say, “Please don’t eat me! I don’t taste good!” When swallowed in large quantities by a potential predator, the toxins can cause coma, cardiac arrest and even death.

Scientists aren’t yet sure why the Sonoran Desert toad produces 5-MeO-DMT, and why it is the only toad known to make it. “There’s a lot of mystery,” Villa says.

Giant monkey frog (Phyllomedusa bicolor)

Habitat: The Amazon Basin in South America

A photo of a giant monkey frog resting on the fingers of a person.
Some people who use kambô, the toxic secretion produced by the giant monkey frog, report having spiritual experiences.© BEASTMASTER/INATURALIST (CC BY-NC 4.0)

There’s no scientific consensus on whether kambô, the name for the toxic secretion produced by the giant monkey frog, should be considered a psychedelic. The term psychedelic comes from Greek meaning “mind manifesting,” Nichols says. “You can imagine, it’s enhancing the properties of your mind, rather than just intoxicating you.” Other compounds such as stimulants and depressants modify the activity of the brain, but they don’t leave users with the kind of new insights and memorable experiences that come with psychedelics.

Wuelton Monteiro, a tropical medicine researcher at the Universidade do Estado do Amazonas in Manaus, Brazil, points to a 2020 study in Scientific Reports as an example of why the classification has been unclear. In the small study, nearly half of participants who reported using kambô said they had a spiritual experience, and some experiences came with what resembled the afterglow often associated with hallucinogens. But kambô doesn’t activate the 5-HT2A receptor, a protein that senses the chemical messenger serotonin, while classic psychedelics do.

Among Indigenous populations in the southwestern Amazon, the frog’s skin secretions have been used for centuries as a stimulant in shamanistic rituals. According to Villa, the secretions are usually applied on small, superficial burns on the body to increase the stamina of hunters.

In predators attempting to gobble the frog, kambô might cause regurgitation, seizures and a change in heart function. Researchers are still trying to decipher the specific compounds that explain these effects, but they do know that species of Phyllomedusa collectively produce over 200 short protein fragments that can influence body function. Some might be promising for future medicines.

California harvester ant (Pogonomyrmex californicus)

Habitat: Southwestern United States and northern Mexico

A close up photo of eight California harvester ants standing on sand.
Indigenous peoples of central California once ate California harvester ants during rituals including vision quests.© MATT REALA/INATURALIST (CC BY-NC 4.0)

The venom of the California harvester ant is made up of enzymes that aren’t known to cause hallucinations on their own, but the Indigenous peoples of central California once ate them during rituals including vision quests. Ethnographic reports suggest people would swallow hundreds of live ants in balls of eagle down feathers. No doubt the people were stung, likely on the insides.

Justin Schmidt, an entomologist at the Southwestern Biological Institute and University of Arizona in Tucson who died in February, said the pain of being stung by so many ants, along with extreme cold, fasting and in some cases sleep deprivation, triggered hallucinations that connected the people with spiritual guides.

A harvester ant’s sting is “nothing like a bee sting,” Schmidt wrote in The Sting of the Wild (SN: 8/6/16, p. 26). “The pain is intense, comes in waves, and is deeply visceral.” Lasting from four to eight hours, the pain is accompanied by a numb sensation at the site of the sting. The ants deliver stings to defend their colonies from large predators, including lizards, birds and people. (Smaller enemies such as other insects and spiders are bitten.)

A person who eats 1,000 ants would probably die; according to Schmidt’s book, one ant is enough to kill a mouse. But some predators have defenses: The regal horned lizard (Phrynosoma solare) has a mucus lining its mouth and digestive system that allows it to eat hundreds of ants and a substance in its blood that neutralizes the venom. Some birds somehow avoid getting stung too.

It’s hard to get more information on how the ants were used in rituals and the nature of the experience. Disease and violence that came with Westerners during California’s gold rush destroyed the Indigenous communities in the Central Valley and their way of life.

Salema (Sarpa salpa)

Habitat: Temperate and tropical ocean waters, from the Atlantic coast of Africa to the Mediterranean Sea

A close up photo of a Sarpa Salpa fish on a black background.
Some fish including Sarpa salpa can cause auditory and visual hallucinations when eaten.BRIAN GRATWICKE/FLICKR (CC BY 2.0)

Fishes including this species of sea bream, as well as some sea chubs and clownfish, can cause auditory and visual hallucinations when eaten, though reports are rare. Sarpa salpa was known as the “dream fish” in ancient Rome, according to a 2018 review of psychedelic fauna published in Frontiers in Psychiatry. Two cases of hallucinatory fish poisoning were documented in 2006 in the journal Clinical Toxicology. In one case, a 40-year-old man ate baked S. salpa and later experienced hallucinations of screaming animals and giant arthropods surrounding his car. The symptoms went away, with medical attention, 36 hours after he ate the fish.

Researchers don’t know what compounds cause this ichthyoallyeinotoxism, or fish poisoning, which can include nightmares. Evolutionary biologist Leo Smith of the University of Kansas in Lawrence, who studies fish history and diversification, says he and other scientists suspect that the compounds are a by-product of the fishes’ diets.

But ichthyoallyeinotoxism is distinct from two other forms of fish poisoning. Symbiotic bacteria within puffer fish produce a neurotoxin called tetrodotoxin, or TTX, that can cause paralysis and death. And ciguatera fish poisoning comes from eating fish contaminated with a neurotoxin produced by some dinoflagellates. It can cause diarrhea, vomiting and weakness, as well as a reverse sensory disruption, where hot things seem cold and vice versa. But it does not cause hallucinations, says Sandric Leong, a biological oceanographer at the National University of Singapore.

How and why many of these neurotoxins are produced is still being worked out. “There are so many relationships with the marine environment which we are not very sure of,” Leong says.

Pitted sponge (Verongula rigida)

Habitat: The Caribbean

An underwater photo of pitted sponge.
The pitted sponge and some other sponges contain 5-bromo-DMT and 5,6-dibromo-DMT, compounds related to the psychedelic drug DMT.SMITHSONIAN TROPICAL RESEARCH INSTITUTE

The pitted sponge and some other sponges including Smenospongia aura and S. echina contain 5-bromo-DMT and 5,6-dibromo-DMT. Because of their relationship with the psychedelic drug DMT, these compounds are plausible psychedelics. American chemist Alexander Shulgin, famous for his research into psychedelic compounds and for introducing the world to the synthetic hallucinogen MDMA, or ecstasy, and his wife Ann Shulgin wrote in TIHKAL: The Continuation that they don’t know whether the sponge compounds are activated by smoking or not. They are, however, “quantitatively reduced to DMT by stirring under hydrogen in methanol, in the presence of palladium on charcoal.”

The pitted sponge is known to concentrate in its tissue chemicals called monoamines that can modify the behavior of nerve cells. Not only can these compounds make the sponge taste bitter, but they can also alter the behavior of predatory fish that dine on the sponge.

“They wouldn’t prevent the fish from ever trying to take a bite, but it would prevent it from persisting or consuming the sponge any beyond an initial several bites,” says Mark Hamann, a pharmacologist from the Medical University of South Carolina in Charleston.

V. rigida’s ability to alter animal behavior intrigued Hamann, who reported in a 2008 study in the Journal of Natural Products that 5,6-dibromo-DMT acted like an antidepressant in rats, while 5-bromo-DMT acted like a sedative. Hamann says that related compounds may one day be isolated and might make for promising antidepressants, anxiety-reducing drugs or pain relievers in people.

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Why Some Hammerhead Sharks Seem To

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Even fish sometimes hold their breath in cold, dark, deep water.

Scalloped hammerhead sharks living near Hawaii spend their days basking in warm surface waters. But at night, these fish hunt for squid and other prey in the cold ocean depths hundreds of meters below the surface. The sharks may hold on to body heat in the frigid waters by suppressing the use of their gills while diving, essentially “holding their breath” for around an hour at a time, researchers report in the May 12 Science.

Whales and other deep-diving mammals are known to hold their breath (SN: 9/23/20). But this is the first time the behavior has been spotted in diving fish, says Mark Royer, a shark physiology and behavior researcher at the University of Hawaii at Manoa in Honolulu.

Sharks and other fish are ectotherms, meaning that their body temperature is largely controlled by the warmth of the water around them. Fish lose and gain a lot of body heat while breathing through their gills, which snag oxygen from water passing through the organ.

“Gills are like giant radiators strapped to your head,” Royer says, explaining that they leak heat. Because of this, a lot of shark species in the tropics tend to stick to roughly the first 100 meters of sun-heated water near the ocean surface, where temperatures hover around 26° Celsius. But tags attached to scalloped hammerhead sharks (Sphyrna lewini) — a species found in coastal waters all over the tropics — revealed that these sharks take nightly, hour-long dives up to 1,000 meters below the surface.

At these depths, water temperatures can get as low as 5° C — far too cold for a tropical shark. To find out how the sharks endured such frigid temperatures, Royer and his colleagues attached specially designed instruments to the backs of sharks that had gathered in a shallow bay off Oahu to mate.

For the next 23 days, these sensors tracked how the sharks moved, how deep they swam, and how their internal temperature changed. “It was kind of like attaching a Fitbit to a shark,” says Royer. “It allowed me to get precise details on what the shark was doing.”

Sharks, the data show, went on V-shaped dives to the depths — plunging hundreds of meters before firing straight back up “like a missile,” says Royer. But strangely, the body temperature of diving sharks barely budged for the bulk of the dive. It was only when the sharks slowed their ascent at a depth of around 290 meters, where the water is a little cooler than at the surface, that their body temperature dropped by an average of 2.8 degrees C.  

The fish had to be shutting off their gills for most of the dive to hold on to their heat, the researchers concluded. It was only when the sharks had returned to a safer depth temperature-wise that they may have reactivated their gills — taking in oxygen for the first time in around an hour and sucking in cold water in the process.

Holding on to their heat while diving could help sharks move quickly in the deep ocean, says Julia Spaet, a shark ecologist at the University of Cambridge. While it is “absolutely possible” that these hammerhead sharks do this by suppressing gill activity, scientists will need to get direct evidence using cameras or other means to prove that it is true, she says.

At least one video from a deep-sea dive hints that this is the case. The gills of a scalloped hammerhead roaming at a depth of 1,000 meters near Tanzania appeared to be closed in footage captured a few years ago, the researchers note in their paper. This, along with the new study’s find that hammerheads hold on to their body heat, makes Royer “very confident” that sharks are in fact holding their breath. “It just goes to highlight how extraordinary this species is,” he says.

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Pregnancy May Hamper Bats

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Pregnancy can do weird things to the body. For some bats, it can hamper their ability to “see” the world around them.

Kuhl’s pipistrelle bats (Pipistrellus kuhlii) echolocate less frequently while pregnant, researchers report March 28 in BMC Biology. The change may make it harder for the tiny bats to detect prey and potential obstacles in the environment.

The study is among the first to show that pregnancy can shape how nonhuman mammals sense their surroundings, says Yossi Yovel, a neuroecologist at Tel Aviv University in Israel.

Nocturnal bats like Kuhl’s pipistrelles famously use sound to navigate and hunt prey in the dark (SN: 9/20/17). Their calls bounce off whatever is nearby and bats use the echoes to reconstruct what’s around them, a process aptly named echolocation. The faster a bat makes calls, the better it can make out its surroundings. But rapid-fire calling requires breathing deeply, which is something that pregnancy can get in the way of.

“Although I’ve never been pregnant, I know that when I eat a lot, it’s more difficult to breathe,” Yovel says. So pregnancy — which can add a full gram to a 7-gram Kuhl’s pipistrelle and may push up on the lungs — might hamper echolocation.

Yovel and colleagues tested their hypothesis by capturing 10 Kuhl’s pipistrelles, five of whom were pregnant, and training the bats to find and land on a platform. Recordings of the animals’ calls revealed that bats that weren’t pregnant made around 130 calls on average while searching for the platform. But bats that were pregnant made only around 110 calls, or 15 percent fewer.   

A decline in calls among pregnant bats could impede hunting, the team says. A computer simulation showed that the study’s expectant moms would catch 15 percent fewer insects than nonpregnant bats. That finding could help explain why some bat species chase after larger and slower prey once they become pregnant, focusing their energy on easier-to-spot food. Figuring out whether diminished echolocating ability is responsible for these diet shifts will require more fieldwork, Yovel says.

However, the idea that carrying a fetus would interfere with echolocation makes a lot of sense, says behavior ecologist Erin Gillam of North Dakota State University in Fargo. “As a mammal who has been pregnant, I don’t think these results are surprising at all.” 

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