Losing one variety of gut bacteria may lead to type 2 diabetes as people age.
Old mice have less Akkermansia muciniphila bacteria than young mice do, researchers report November 14 in Science Translational Medicine. That loss triggers inflammation, which eventually leads cells to ignore signals from the hormone insulin. Such disregard for insulin’s message to take in glucose is known as insulin resistance and is a hallmark of type 2 diabetes.
Researchers have suspected that bacteria and other microbes in the gut are involved in aging, but how the microbes influence the process hasn’t been clear. Monica Bodogai of the U.S. National Institute on Aging in Baltimore and colleagues examined what happens to mice’s gut bacteria as the rodents age. The mice lose A. muciniphila, also called Akk, and other friendly microbes that help break down dietary fiber into short-chain fatty acids, such as butyrate and acetate. Those fatty acids signal bacteria and human cells to perform certain functions. Losing Akk led to less butyrate production, Bodogai’s team found. In turn, loss of butyrate triggered a chain reaction of immune cell dysfunction that ended with mice’s cells ignoring the insulin.
Treating old mice and elderly rhesus macaques with an antibiotic called enrofloxacin increased the abundance of Akk in the animals’ guts and made cells respond to insulin again. Giving old animals butyrate had the same effect, suggesting that there may be multiple ways to head off insulin resistance in older people in the future.
The next NASA Mars rover will hunt for signs of ancient life in what used to be a river delta, the agency announced on November 19.
The rover is expected to launch in July 2020 and to land on Mars around February 18, 2021. It will seek out signs of past life in the sediments and sands of Jezero crater, which was once home to a 250-meter-deep lake and a river delta that flowed into the lake. “This is a major attraction from our point of view for a habitable environment,” said Mars 2020 project scientist Ken Farley of Caltech in a news conference discussing the site. “A delta is extremely good at preserving biosignatures.” Any evidence of life that may once have existed in the lake water, or even evidence that came from the river’s headwaters and flowed downstream, could be preserved in the rocks that are there today.
The 2020 rover’s design is similar to that of the Curiosity rover, which has been exploring a different ancient crater lake, Gale crater, since 2012 (SN: 5/2/15, p. 24). But where Curiosity has an onboard chemistry lab for studying the rocks and minerals in its crater, Mars 2020 will have a specialized backpack for sample storage. A future mission will pick up the cached samples and return them to Earth for more detailed study, possibly sometime in the 2030s.
“The samples will come back to the best labs — not the best labs we have today, but the best labs we will have then,” said science mission directorate administrator Thomas Zurbuchen of NASA headquarters in Washington, D.C.
Mars 2020 will also use a souped-up version of Curiosity’s landing system called Sky Crane, in which a hovering platform lowers the rover onto the ground with a cable. Mars 2020’s version will include a navigation system that will help it avoid hazards on the ground, like cliff faces and boulders. Jezero crater is within striking distance of another site on scientists’ wish list. That region, called Midway, is just 28 kilometers away from Jezero and contains some of the most ancient rocks on Mars. At the final landing site selection workshop in October, scientists floated the idea of visiting both sites in one mission, a feat seen as ambitious but achievable. But a decision on that will have to wait until after the rover is safely on Mars, Farley said.
For the first time, humans have built a set of pushy, destructive genes that infiltrated small populations of mosquitoes and drove them to extinction.
But before dancing sleeveless in the streets, let’s be clear. This extermination occurred in a lab in mosquito populations with less of the crazy genetic diversity that an extinction scheme would face in the wild. The new gene drive, constructed to speed the spread of a damaging genetic tweak to virtually all offspring, is a long way from practical use. Yet this test and other news from 2018 feed one of humankind’s most persistent dreams: wiping mosquitoes off the face of the Earth.
For the lab-based annihilation, medical geneticist Andrea Crisanti and colleagues at Imperial College London focused on one of the main malaria-spreading mosquitoes, Anopheles gambiae. The mosquitoes thrive in much of sub-Saharan Africa, where more than 400,000 people a year die from malaria, about 90 percent of the global total of malaria deaths.
To crash the lab population, the researchers put together genes for a molecular copy-and-paste tool called a CRISPR/Cas9 gene drive. The gene drive, which in this case targeted a mosquito gene called doublesex, is a pushy cheat. It copies itself into any normal doublesex gene it encounters, so that all eggs and sperm will carry the gene drive into the next generations. Female progeny with two altered doublesex genes develop more like males and, to people’s delight, can’t bite or reproduce.
In the test, researchers set up two enclosures, each mixing 150 males carrying the saboteur genes into a group of 450 normal mosquitoes, males and females. Extinction occurred in eight generations in one of the enclosures and in 12 in the other (SN: 10/27/18, p. 6).
This is the first time that a gene drive has forced a mosquito population to breed itself down to zero, says Omar Akbari of the University of California, San Diego, who has worked on other gene drives. However, he warns, “I believe resistance will be an issue in larger, diverse populations.” More variety in mosquito genes means more chances of some genetic quirk arising that counters the attacking gene drive.
But what if a gene drive could monkey-wrench a wild population, or maybe a whole species, all the way to extinction? Should people release such a thing? To make sense of this question, we humans will have to stop talking about “mosquitoes” as if they’re all alike. The more than 3,000 species vary considerably in what they bite and what ecosystem chores they do.
The big, iridescent adults of Toxorhynchites rutilus, for instance, can’t even drink blood. And snowmelt mosquitoes (Ochlerotatus communis) are pollinators of the blunt-leaved orchid (Platanthera obtusata), ecologist Ryo Okubo of the University of Washington in Seattle said at the 2018 meeting of the Society for Integrative and Comparative Biology. Estimating what difference it would make ecologically if a whole mosquito species disappeared has stirred up plenty of speculation but not much data. “I got pretty fed up with the hand-waving,” says insect ecologist Tilly Collins of Imperial College London. So she and colleagues dug through existing literature to see what eats An. gambiae and whether other mosquitoes would flourish should their competitor vanish.
So far, extermination of this particular mosquito doesn’t look like an ecological catastrophe, Collins says. Prey information is far from perfect, but diets suggest that other kinds of mosquitoes could compensate for the loss. The species doesn’t seem to be any great prize anyway. “As adults, they are small, not juicy, and hard to catch,” she says. The little larvae, built like aquatic caterpillars with bulging “shoulders” just behind their heads, live mostly in small, temporary spots of water. The closest the researchers came to finding a predator that might depend heavily on this particular mosquito was the little East African jumping spider Evarcha culicivora. It catches An. gambiae for about a third of its diet and likes the females fattened with a human blood meal. Yet even this connoisseur “will readily consume” an alternative mosquito species, the researchers noted in July in Medical and Veterinary Entomology.
Collins also thinks about the alternatives to using genetically engineered pests as pest controls. Her personal hunch is that saddling mosquitoes with gene drives to take down their own species is “likely to have fewer ecological risks than broad-spectrum use of pesticides that also kill other species and the beneficial insects.”
Gene drives aren’t the only choice for weaponizing live mosquitoes against their own kind. To pick just one example, a test this year using drones to spread radiation-sterilized male mosquitoes in Brazil improved the chances that the old radiation approach will be turned against an Aedes mosquito that can spread Zika, yellow fever and chikungunya.
Old ideas, oddly enough, may turn out to be an advantage for antimosquito technologies in this era of white-hot genetic innovation. Coaxing the various kinds of gene drives to work is hard enough, but getting citizens to sign off on their use may be even harder.
Mysterious particles called neutrinos constantly barrel down on Earth from space. No one has known where, exactly, the highest-energy neutrinos come from. This year, scientists finally put a finger on one likely source: a brilliant cosmic beacon called a blazar. The discovery could kick-start a new field of astronomy that combines information gleaned from neutrinos and light.
It began with one high-energy neutrino spotted on September 22, 2017, by the IceCube observatory, a giant particle detector with thousands of sensors buried deep in the ice at the South Pole. Alerted by IceCube, astronomers soon spotted a flare from a blazar about 4 billion light-years away. The neutrino had come from the same area of the sky. With that matchup in time and space between the neutrino and the blazar’s light, scientists in 2018 pegged the blazar as the particle’s probable source (SN: 8/4/18, p. 6).
“People have been hoping for this kind of discovery for decades,” says astrophysicist Meg Urry of Yale University. Blazars are active regions at the centers of galaxies that spew jets of high-energy matter and light toward Earth. Both the Earth-orbiting Fermi Gamma-ray Space Telescope and the Major Atmospheric Gamma Imaging Cherenkov, or MAGIC, telescopes in the Canary Islands reported that the blazar was violently flaring up in gamma rays, a type of high-energy light, at about the same time the neutrino was detected.
After combing through old data, IceCube researchers found evidence of even more neutrinos from near the blazar’s location in the sky. With those extra neutrinos, the researchers were finally convinced that the blazar birthed neutrinos. Not only did the detection hint at the source of at least some high-energy spacefaring particles, it also taught physicists a few things about blazars. Scientists weren’t sure what kinds of particles blazars emit, but the detection reveals that the jets contain protons. That’s because scientists know that any neutrino from a blazar would have to be produced in combination with protons.
The discovery, scientists say, could invigorate a nascent field, dubbed multimessenger neutrino astronomy, to reveal secrets of the cosmos, whether from blazars or other sources. Now, says astrophysicist Kohta Murase of Penn State, “we can use neutrinos as very important probes” to learn more about the objects that spit them out. For example, researchers might spot neutrinos from a collision of two neutron stars, like the one detected by the Advanced Laser Interferometer Gravitational-Wave Observatory, LIGO, in 2017 (SN: 11/11/17, p. 6). IceCube didn’t see any neutrinos from that event, but astrophysicists are hopeful that future neutron star smashups will produce a neutrino bounty.
Before scientists are fully confident that blazars can blast out high-energy neutrinos, researchers need to spot more of the wily particles, Murase says. To improve detection, an upgrade to IceCube will make the detector 10 times bigger in volume and should be ready by the mid-2020s, says Francis Halzen, leader of IceCube and an astrophysicist at the University of Wisconsin–Madison. If all goes well, the tiny particles may soon be revealing secrets from new corners of the cosmos.
Cleaning up ocean pollution is no simple task, as an effort to fish plastic out of the Pacific Ocean is revealing.
In September, scientists launched a 600-meter-long boom meant to herd plastic debris from the great Pacific garbage patch into a net (SN Online: 9/7/18). The trash accumulation, which is twice the size of Texas, swirls in waters between California and Hawaii.
But some scientists worry the system, designed by a Dutch organization called Ocean Cleanup, could harm marine wildlife. Others aren’t convinced it will even work. Four months in, some of those concerns appear to be founded: Wind and currents have pushed trash into the rig, but the setup hasn’t kept the trash corralled as planned. Now part of the rig has broken off, and the device is being towed back to shore for repairs and design tweaks. Whether the system will eventually help remove garbage from the Pacific remains to be seen. But it’s not the only option for reducing how much plastic is dumped in the oceans — now at some 5 trillion pieces, per some estimates. Here are a few other approaches seeing success.
Meet Mr. Trash Wheel and friends It’s easier to collect trash from rivers and streams than from the open ocean. Baltimore has deployed three giant waterwheels that trap river plastic before it flows into the harbor. The first installation, adorned with googly eyes and dubbed Mr. Trash Wheel, debuted in 2014, followed by Professor Trash Wheel in 2016 and Captain Trash Wheel in 2018. Collectively, the wheels so far have removed more than 680,000 kilograms of trash.
Mr. Trash Wheel wasn’t immediately successful, though, says Adam Lindquist, director of Baltimore’s Healthy Harbor Initiative. A waterwheel installed in 2008 didn’t work well. He suggests that the Ocean Cleanup group, in tweaking its device, could also see improvements — though clearing plastic from the ocean is certainly a bigger job than cleaning a river, he says.
Snag it on land Collecting debris as it’s washed onto beaches is another way to tackle the plastic problem. “Lots of published papers show the ocean spits out trash really quickly,” says Marcus Eriksen, an environmental scientist and cofounder of the 5 Gyres Institute based in Los Angeles.
The U.S. National Oceanic and Atmospheric Administration’s Marine Debris Program, for example, has collected more than 450 tons of garbage from the Alaska shoreline since 2006.
Rise of the bans Using less plastic in the first place is the most straightforward way to cut down on ocean pollution. Many cities and 127 countries have imposed regulations on single-use plastic, such as grocery bags or plastic straws, according to a December report from the U.N. Environment Program.
These restrictions can make a difference. In 2010, thousands of volunteers collecting and tallying garbage along the California coast found that 7 percent of the trash consisted of plastic bags. In 2017, after multiple California cities imposed plastic bag bans or restrictions, the bags made up less than 2 percent of trash gathered.
Bans can also fight debris that the Ocean Cleanup’s system won’t snag — microplastics, tiny fragments that can harm the health of people and other animals. The United States banned microbeads in personal care products starting in 2017; the European Union has voted to enact a similar ban by 2020.
Rethink the cycle Plastic can take decades or even centuries to break down, so some scientists are working on alternatives that are easier to recycle. For example, a type of recyclable plastic described in Science in 2018 can be broken down into component pieces and rebuilt again and again (SN: 5/26/18, p. 12). But if recyclable plastic ends up in a landfill or in the ocean, those special properties won’t matter.
“There’s a really big gap between what can be recycled in a perfect world, and what actually gets recycled,” says Miriam Goldstein, the director of ocean policy at the Center for American Progress, a research and lobbying organization in Washington, D.C. Bridging that gap isn’t as simple as telling people to use less plastic, she says. “You cannot opt out of single-use plastics in most of the country,” and lots of products are designed in ways that make them challenging to properly recycle.
That’s one reason why an approach called extended producer responsibility is gaining popularity — essentially, holding companies that make plastic products responsible for the cost of proper disposal. “If you’re going to make anything, you need to think of the recovery,” Eriksen says. Putting a financial burden on the producer provides an incentive for designing products that are easier to recycle or reuse. One example: using just one type of plastic instead of combining plastics that would then need to be separated for proper recycling.
The fishing industry also needs incentives to join in the cleanup, Eriksen says. Surveys of detritus that washes ashore suggest that a substantial portion is left by fishers. Giving them a financial reason to retrieve old nets and buoys could help keep our oceans clean.
The monarch butterfly isn’t the only insect flying up and down North America in a mind-boggling annual migration. Tests show a big, shimmering dragonfly takes at least three generations to make one year’s migratory loop.
Ecologist Michael Hallworth and his colleagues pieced together the migration of the common green darner, described December 19 in Biology Letters, using data on forms of hydrogen in the insects’ wings, plus records of first arrivals spotted by citizen scientists. The study reveals that a first generation of insects emerges in the southern United States, Mexico and the Caribbean from about February to May and migrates north. Some of those Anax junius reach New England and the upper Midwest as early as March, says Hallworth, of the Smithsonian Migratory Bird Center headquartered in Washington, D.C.
Those spring migrant darners lay eggs in ponds and other quiet waters in the north and eventually die in the region. This new generation migrates south from about July until late October, though they have never seen where they’re heading. Some of these darners fly south in the same year their parents arrived and some the next year, after overwintering as nymphs.
A third generation emerges around November and lives entirely in the south during winter. It’s their offspring that start the cycle again by swarming northward as temperatures warm in the spring. With a wingspan as wide as a hand, they devote their whole lives to flying hundreds of kilometers to repeat a journey their great-grandparents made. Scientists knew that these dragonflies migrated. Dragonfly enthusiasts have spotted swarms of the green darners in spring and in fall. But which generations were doing what has been tricky to demonstrate. “Going in, we didn’t know what to expect,” Hallworth says. Tracking devices that let researchers record animals’ movements for more than a week or two haven’t been miniaturized enough to help. The smallest still weigh about 0.3 grams, which would just about double a darner’s weight, Hallworth says. So researchers turned to chemical clues in darner tissues. Conservation biologist and study coauthor Kent McFarland succeeded at the delicate diplomacy of persuading museums to break off a pinhead-sized wing tip fragment from specimens spanning 140 years.
Researchers checked 800 museum and live-caught specimens for the proportion of a rare heavy form of hydrogen that occurs naturally. Dragonfly wings pick up their particular mix of hydrogen forms from the water where the aquatic youngsters grow up. Scientists have noticed that a form called hydrogen-2 grows rarer along a gradient from south to north in North America. Looking at a particular wing in the analysis, “I can’t give you a zip code” for a darner, Hallworth says. But he can tell the native southerners from Yankees.
An adult darner, regardless of where it was born, is “a green piece of lightning,” says McFarland, of the Vermont Center for Ecostudies in White River Junction. Darners maneuver fast enough to snap insect prey out of the air around ponds across North America. The front of an adult’s large head is “all eye,” he says, and trying to catch samples for the study was “like hitting a knuckleball.”
Although the darners’ north-south migration story is similar to that of monarchs (Danaus plexippus), there are differences, says evolutionary biologist Hugh Dingle of the University of California, Davis, who has long studied these butterflies. Monarchs move northward in the spring in stepwise generations, instead of one generation sweeping all the way to the top of its range.
Also, Dingle says, pockets of monarchs can buck the overall scheme. Research suggests that some of the monarchs in the upper Midwest do a whole round trip migration in a single generation. As researchers discover more details about green darners, he predicts, the current basic migration scheme will turn out to have its quirky exceptions, too.
The adolescent saber-toothed cat on a summertime hunt realized too late that she had made a terrible miscalculation.
Already the size of a modern-day tiger, with huge canine teeth, she had crept across grassy terrain to ambush a giant ground sloth bellowing in distress. Ready to pounce, the cat’s front paw sank into sticky ground. Pressing down with her other three paws to free herself, then struggling in what has been called “tar pit aerobics,” she became irrevocably mired alongside her prey.
Scenarios much like this played out repeatedly over at least the last 35,000 years at California’s Rancho La Brea tar pits. Entrapped herbivores, such as the sloth, attracted scavengers and predators — including dire wolves, vultures and saber-toothed Smilodon cats — to what looked like an easy meal. Eventually the animals would disappear into the muck, until paleontologists plucked their fossils from the ground in huge numbers over the last century.
Five million or so fossils have been found at the site. But “it’s not like there was this orgy of death going on,” says Christopher Shaw, a paleontologist and former collections manager at the La Brea Tar Pits and Museum in Los Angeles. He calculates that such an entrapment scenario, dooming 10 or so large mammals and birds, would have needed to occur only once per decade over 35,000 years to account for that bounty of fossils.
At La Brea, the collection of Smilodon fatalis fossils alone includes more than 166,000 bones, from an estimated 3,000 of the ill-fated prehistoric cats. Famed for their fearsome canines, which grew up to 18 centimeters long, S. fatalis weighed as much as 280 kilograms, bigger than most of today’s largest lions and tigers. Fossils of S. fatalis, the second largest of three Smilodon species that roamed the Americas during the Pleistocene Epoch, have been found across the United States and in South America, west of the Andes as far south as Chile. And a recent study put S. fatalis in Alberta, Canada, about 1,000 kilometers north of its previously known range.
But the La Brea fossil site, unique in offering up so many specimens, is the source of the vast majority of knowledge about the species. There, fossils of dire wolves and saber-toothed cats together outnumber herbivores about 9-to-1, leading scientists to speculate that both predators may have formed prides or packs, similar to modern lions and wolves. Yet a small number of experts argue against cooperative behavior for Smilodon, reasoning that pack-living animals would have been too intelligent to get mired en masse. New studies may help settle the debate about Smilodon’s sociality, and answer questions about how the cat lived and why it died out 10,000 to 12,000 years ago.
“We have an innate curiosity to understand what it was doing and why it went extinct,” says Larisa DeSantis, a vertebrate paleontologist at Vanderbilt University in Nashville. Now, she says, “we can answer these questions.”
DeSantis is studying microscopic wear on fossil teeth and chemical signatures in the enamel to reveal Smilodon’s diet. Other scientists are doing biomechanical studies of the skull, fangs and limbs to understand how the powerful cat captured and killed its prey. Some researchers are extracting DNA from fossils, while others are gathering data on the paleoclimate to try to piece together why Smilodon died out.
“It’s the T. rex of mammals … a big, scary predator,” says Ashley Reynolds, a paleontology Ph.D. student and fossil cat researcher at the University of Toronto. She presented the Alberta fossil find in October in Albuquerque at the Society of Vertebrate Paleontology conference. Explaining why Smilodon cats continue to excite researchers, she says, “They’re probably the baddest of all the cats that have ever existed.” Safety in numbers Whether Smilodon was a pack hunter has long been debated (SN: 10/28/17, p. 5) because living in groups is rare among large cats today. But an unusual number of healed injuries in the Smilodon bones at La Brea makes it unlikely that these cats were solitary, DeSantis and Shaw reported in November in Indianapolis at a meeting of the Geological Society of America.
More than 5,000 of the Smilodon bones at La Brea have marks of injury or illness: tooth decay, heavily worn arthritic joints, broken legs and dislocated elbows that would have occurred before the animals’ tar burial. Dramatic examples include crushed chests and spinal injuries, which the cats somehow survived. “You would actually wince to see these horribly, traumatically injured specimens,” says Shaw, who is also coeditor of the 2018 book Smilodon: The Iconic Sabertooth.
One particularly debilitating injury was a crippled pelvis, but evidence of new bone growth shows that the animal lived long enough for healing to occur. “There was a lot of infection, pain and smelly stuff, and just a really awful situation for this animal, but it survived well over a year,” Shaw says. “To me that indicates [the injured cat] was part of a group that helped it survive by letting it feed at kills and protecting it.”
Shaw and DeSantis looked at a series of specimens with what were probably agonizing maladies in the teeth and jaws, including fractured canines and massive infections that left animals with misshapen skulls.
“These animals probably couldn’t have gone out … to kill anything,” Shaw says. “You know how it is when you have a toothache. This is like that times 100.” DeSantis compared microscopic pits and scratches on the surface of the teeth of injured animals with microwear on the teeth of seemingly healthy Smilodon cats. The injured cats’ dental surfaces indicated that the animals were eating softer foods, which would have been less painful to chew, “likely a higher proportion of flesh, fat and organs, as opposed to bone,” she says.
The findings are consistent with the interpretation that Smilodon was a group-living animal, she says, and that the cats “allowed each other access to food when [injured pack members] couldn’t necessarily take down their own prey.”
Reynolds agrees that the healed injuries are persuasive evidence that Smilodon lived in groups. “When you see an animal with really nasty injuries that healed somehow, it does make you wonder if they were cared for.”
Not everyone is convinced, however. Ecologist Christian Kiffner of the Center for Wildlife Management Studies in Karatu, Tanzania, has studied modern carnivores such as African lions and spotted hyenas. “Relatively long survival of Smilodon fatalis individuals after dental injuries had occurred does not necessarily provide airtight evidence for a specific social system in this species,” he says. “It is very, very difficult to use patterns in Pleistocene carnivore [fossil] assemblages to make inferences about behavior of an extinct species.”
Even if the saber-toothed cats did live in groups, the animals’ exact social structure remains an open question, Reynolds says. Modern lion prides have numerous females and several younger males led by an alpha male, with intense competition between male lions. As a result, males are much bigger than females, as the males must work hard to defend their positions.
Despite searching, scientists have not found obvious evidence of a size difference between the sexes in Smilodon; researchers can’t even tell which La Brea fossils are male or female. Size differences between the sexes, if they existed, may have been small.
“That lack of sexual dimorphism is odd,” says Blaire Van Valkenburgh, a UCLA paleontologist who studies fossil carnivores. Sex-related size differences are seen in many big cats today, most particularly lions. She thinks the lack of sexual dimorphism in Smilodon might hint at a different social structure. Perhaps males weren’t competing quite so intensely for access to females. Maybe there was no single alpha male preventing the majority of males from making a move.
Family affair Perhaps Smilodon groups had an alpha female rather than an alpha male, or an alpha pair. Such is the case in modern wolves and coyotes, which have less pronounced size differences between sexes than lions do. The prehistoric cats “could have had extended family structures [similar to wolves] where uncles and aunts hung around, because it probably took a while to raise the young saber-toothed cats,” Van Valkenburgh suspects.
Kittens may have taken a long time, as long as 22 months, to get most of their adult teeth, she says. The upper canines took even longer, as much as three years or more, to reach their massive size, researchers reported in PLOS ONE in 2015. Modern lions, in contrast, typically have all of their adult teeth by 17 months, Van Valkenburgh says.
Smilodon kittens also probably went through a substantial learning curve before attempting to take down large prey. “It took longer for them to learn how to safely kill something without breaking their teeth or biting in the wrong place and hurting themselves,” Van Valkenburgh speculates.
Pack living would enable this slower development: “If you’re a social species, you can afford to grow at a slower rate than a nonsocial species because you have a family safety net,” Reynolds says. She is studying Smilodon fossils from Peru’s Talara tar pits for evidence of slow bone development using bone histology, examining thin cross sections under a microscope to determine such things as age and growth rate. To understand how saber-toothed cats eventually took down prey, Van Valkenburgh joined paleobiologist Borja Figueirido of the University of Málaga in Spain and others. The group studied the biomechanics of Smilodon’s killing bite and how the animal used its sabers. That work, published in the October 22, 2018 Current Biology, adds to a consensus that the cat used its powerful forelimbs, which existed even in the youngsters (SN Online: 9/27/17), to pin prey before applying a lethal bite to the neck.
“The specialization of being a saber-toothed appears to have been partly to effectively take prey larger than yourself and to do that very quickly,” Van Valkenburgh says. With the prey tightly gripped, a Smilodon cat would position itself so that one or two really strong canine bites would rip open the pinned animal’s throat.
In contrast, lions suffocate prey — one lion may clamp its jaws around the neck, crushing the windpipe, while another uses its mouth to cover the victim’s nose and mouth. Using this slower method would have increased Smilodon’s chances of injuring or damaging those precious canine teeth.
Diverging senses Smilodon and its extinct saber-toothed relatives are on a branch of the cat family tree that is far from today’s cats. Scientists think Smilodon’s branch diverged from the ancestors of all living cats about 20 million years ago. Given the evolutionary distance, researchers are still trying to determine how similar — or different — Smilodon was from its living feline cousins. A recent focus has been the cat’s sounds and senses.
At the October vertebrate paleontology conference, Shaw presented evidence that Smilodon may have roared, as do lions, tigers, leopards and their close relatives. The clues come from 150 La Brea fossils that were once part of the hyoid arch, or larynx, in the Smilodon throat. (Tar pits stand out for preserving tiny bones rarely found elsewhere.) The small fossils are very similar in shape and style to those of roaring cats. House cats and others that purr have a different arrangement of bones. Smilodon may have “used this type of communication as an integral part of social behavior,” Shaw says. Roaring, however, is not a sure sign of pack living, Reynolds notes; most roaring cats today do not live in large groups.
How Smilodon’s sense of smell compared with living cats’ is something else researchers wonder about. To probe this part of the extinct animal’s biology, a team lead by Van Valkenburgh looked at Smilodon’s cribriform plate — a small, perforated bone inside the skull. Smell-sensing nerve cells pass through holes in the plate from the olfactory receptors in the nose to the brain. The size and number of holes are thought to correlate with the number of receptors and, therefore, the extent of an animal’s sense of smell.
To confirm this link, Van Valkenburgh’s team combined CT scans and 3-D images of skulls from 27 species of living mammals with information on the number of olfactory receptor genes. A CT scan of a skull revealed that Smilodon may have had slightly fewer olfactory receptor nerve cells than a domestic cat, the researchers reported at the paleontology conference. Smilodon’s sense of smell was perhaps 10 to 20 percent less keen than a modern lion’s, says Van Valkenburgh, whose team reported the findings in the March 14, 2018 Proceedings of the Royal Society B.
Smilodon “might have relied more heavily on their eyes and their ears,” she says. Perhaps, in an ancient evolutionary divergence, Smilodon’s level of reliance on smell went in a slightly different direction than in modern big cats.
Saber-toothed swan song As the pieces of the Smilodon puzzle fall into place, perhaps the biggest remaining mystery is why the animal disappeared 10,000 to 12,000 years ago. Debate about the extinction of some of North America’s large mammal species swings between blaming humans and climate change (SN: 11/10/18, p. 28). While humans, who probably arrived on the continent more than 15,000 years ago, and Smilodon certainly knew one another in the Americas, they may not have overlapped at La Brea, Shaw says. The earliest evidence of people in the Los Angeles Basin is about 11,000 years ago, by which time Smilodon may or may not already have gone. Nevertheless, human hunting of large prey elsewhere in the Americas could have led to a scarcity of food for the big cats, he says.
One theory holds that Smilodon went through tough times at La Brea when lack of prey forced the saber-toothed cats to consume entire carcasses including bones. This has been posited as the reason for all those broken teeth among the La Brea fossils. But DeSantis isn’t convinced; she thinks breakages happened during scuffles with prey. She says dental microwear suggests that Smilodon was not eating great quantities of bone. Some opportunistic carnivores, such as cougars, did eat bone and managed to survive to the modern day. Perhaps Smilodon couldn’t adapt to hunting smaller prey when larger herbivores disappeared, also around 10,000 to 12,000 years ago (SN: 11/24/18, p. 22).
“A lot of the large prey on the landscape go extinct,” DeSantis says. “You lose out on the horses, camels, giant ground sloths, mammoths and mastodon. That’s got to have had an impact.”
The challenge of dating fossils from the tar pits has been one hurdle to understanding exactly what was going on with Smilodon over time. Bones deposited over many thousands of years get jumbled by movement in the tar, for reasons experts don’t fully understand. Plus, the tar itself becomes embedded in each specimen, complicating carbon dating.
However, new methods of chemically pretreating fossils to remove the tar have made carbon dating much easier and cheaper — and a multi-institutional project is now dating hundreds of Smilodon and other bones. Researchers will soon be able to track changes in Smilodon over the 35,000 years of prehistory recorded at La Brea and correlate fossil changes to known changes in climate over that time.
“We’re going to have a much better handle,” Van Valkenburgh says, “on what was going on towards the end of their existence.”
This article appears in the March 30, 2019 issue of Science News with the headline, “The Baddest Cat of All: Fresh details say saber-toothed Smilodon helped injured pack members.”
A tweaked laboratory protocol has revealed signs of thousands of newborn nerve cells in the brains of adults, including an octogenarian.
These immature neurons, described online March 25 in Nature Medicine, mark the latest data points in the decades-old debate over whether people’s brains churn out new nerve cells into adulthood. The process, called neurogenesis, happens in the brains of some animals, but scientists have been divided over whether adult human brains are capable of such renewal (SN Online: 12/20/18). Researchers viewed slices of postmortem brains of 13 formerly healthy people aged 43 to 87 under a microscope, and saw thousands of what appeared to be newborn nerve cells. These cells were in a part of the hippocampus called the dentate gyrus, a suspected hot spot for new neurons. Brain samples from 45 people with Alzheimer’s disease, however, had fewer of these cells — a finding that suggests that neurogenesis might also be related to the neurodegenerative disease.
Most of the brain samples used in the study were processed within 10 hours of a donor’s death, and spent no more than 24 hours soaking in a chemical that preserves the tissue. Those factors may help explain why the new neurons were spotted, the researchers write. Some earlier experiments that didn’t find evidence of neurogenesis used samples that were processed later after a donor’s death, and that had sat for longer in the fixing chemical.
An ancient four-legged whale walked across land on hooved toes and swam in the sea like an otter.
The newly discovered species turned up in 2011 in a cache of fossilized bones in Playa Media Luna, a dry coastal area of Peru. Jawbones and teeth pegged it as an ancient cetacean, a member of the whale family. And more bones followed.
“We were definitely surprised to find this type of whale in these layers, but the best surprise was its degree of completeness,” says Olivier Lambert, a paleontologist at the Royal Belgian Institute of Natural Sciences in Brussels. Jaw, tooth and spine features, described April 4 in Current Biology, don’t quite match anything else in the fossil record, setting the skeleton apart as a new species, dubbed Peregocetus pacificus (meaning “the traveling whale that reached the Pacific Ocean”). At 42.6 million years old, it’s the oldest whale skeleton found in the New World, though some fossilized whale teeth from North America may be even older.
Big, possibly webbed feet and long toes would have allowed P. pacificus to dog-paddle or swim freestyle. And like modern otters and beavers, this whale’s vertebrae suggest that its tail also functioned as a paddle. With tiny hooves and strong legs and hips, the animal could walk on land. But “it was definitely a better swimmer than walker,” Lambert says.
Whales got their start on land and gradually adapted to a water-dwelling lifestyle. The first amphibious whales emerged more than 50 million years ago near what’s now India and Pakistan. The new species shares some similar features with Maiacetus and Rodhocetus, two early whales from that area. P. pacificus’ age supports the idea that whales migrated across the South Atlantic and around South America to the Pacific Ocean in their first 10 million years of existence.
DNA is the glamour molecule of the genetics world. Its instructions are credited with defining appearance, personality and health. And the proteins that result from DNA’s directives get credit for doing most of the work in our cells. RNA, if mentioned at all, is considered a mere messenger, a go-between — easy to ignore. Until now.
RNAs, composed of strings of genetic letters called nucleotides, are best known for ferrying instructions from the genes in our DNA to ribosomes, the machines in cells that build proteins. But in the last decade or so, researchers have realized just how much more RNAs can do — how much they control, even. In particular, scientists are finding RNAs that influence health and disease yet have nothing to do with being messengers.
The sheer number and variety of noncoding RNAs, those that don’t ferry protein-building instructions, give some clues to their importance. So far, researchers have cataloged more than 25,000 genes with instructions for noncoding RNAs in the human genome, or genetic instruction book (SN: 10/13/18, p. 5). That’s more than the estimated 21,000 or so genes that code for proteins.
Those protein-coding genes make up less than 2 percent of the DNA in the human genome. Most of the rest of the genome is copied into noncoding RNAs, and the vast majority of those haven’t been characterized yet, says Pier Paolo Pandolfi of Boston’s Beth Israel Deaconess Medical Center. “We can’t keep studying just two volumes of the book of life. We really need to study them all.” Scientists no longer see the RNAs that aren’t envoys between DNA and ribosomes as worthless junk. “I believe there are hundreds, if not thousands, of noncoding RNAs that have a function,” says Harvard University molecular biologist Jeannie Lee. She and other scientists are beginning to learn what these formerly ignored molecules do. It turns out that they are involved in every step of gene activity, from turning genes on and off to tweaking final protein products. Those revelations were unthinkable 20 years ago.
Back in the 1990s, Lee says, scientists thought only proteins could turn genes on and off. Finding that RNAs were in charge “was a very odd concept.”
Here are five examples among the many noncoding RNAs that are now recognized as movers and shakers in the human body, for good and ill. Sometimes anticancer drugs stop working for reasons researchers don’t entirely understand. Take the chemotherapy drug cytarabine. It’s often the first drug doctors prescribe to patients with a blood cancer called acute myeloid leukemia. But cytarabine eventually stops working for about 30 to 50 percent of AML patients, and their cancer comes back.
Researchers have looked for defects in proteins that may be the reason cytarabine and other drugs fail, but there still isn’t a complete understanding of the problem, Pandolfi says. He and colleagues now have evidence that drug resistance may stem from problems in some of the largest and most bountiful of the newly discovered classes of RNAs, known as long noncoding RNAs. Researchers have already cataloged more than 18,000 of these “lncRNAs” (pronounced “link RNAs”). Pandolfi and colleagues investigated how some lncRNAs may work against cancer patients who are counting on chemotherapy to fight their disease. “We found hundreds of new players that can regulate response to therapy,” he says.
When the researchers boosted production of several lncRNAs in leukemia cells, the cells became resistant to cytarabine, Pandolfi and colleagues reported in April 2018 in Cell. They also found that patients with AML who had higher than normal levels of two lncRNAs experienced a cancer recurrence sooner than people who had lower levels of those lncRNAs.
Researchers are just beginning to understand how these lncRNAs influence cancer and other diseases, but Pandolfi is hopeful that someday he and other researchers will devise ways to control the bad actors and boost the helpful ones.
MicroRNAs Sparking a tumor’s spread
MicroRNAs are barely more than 20 RNA units, or bases, long, but they play an outsized role in heart disease, arthritis and many other ailments. These pipsqueaks can also lead to nerve pain and itchiness, researchers reported last year in Science Translational Medicine and in Neuron (SN Online: 8/13/18).
Hundreds of clinical studies are testing people’s blood and tissues to determine if microRNAs can be used to help doctors better diagnose or understand conditions ranging from asthma and Alzheimer’s disease to schizophrenia and traumatic brain injury. Some researchers are beginning to develop microRNAs as drugs and seeking ways to inhibit rogue microRNAs.
So far, the little molecules’ most firmly established roles are as promoters of and protectors against cancer (SN: 8/28/10, p. 18). Pancreatic cancer, for example, is a deadly foe. Only 8.5 percent of people are still alive five years after being diagnosed with this disease, according to U.S. National Cancer Institute statistics.
Cancer biologist Brian Lewis of the University of Massachusetts Medical School in Worcester and colleagues have learned that some microRNAs spur this lethal cancer’s initial attack and help the tumor spread from the pancreas to other organs.
MicroRNAs are mirror images of portions of the messenger RNAs that shuttle protein-making instructions from DNA to the ribosomes, where proteins are built. The microRNAs pair up with their larger messenger RNA mates and slate the bigger molecules for destruction, or at least prevent their instructions from being translated into proteins. One microRNA might have hundreds of mates, or targets, through which it influences many different body functions.
Lewis studies one gang of six microRNAs, known as the miR-17~92 cluster, the first group of microRNAs found to play a role in cancer. The six normally help strike a balance between cell growth and death, but an imbalance of these little molecules can push cells toward cancer.
Tumors in pancreatic cancer patients tend to have elevated levels of the cluster. To learn what the microRNAs were doing to goad cancer into taking hold, Lewis and colleagues used a genetic trick to remove the microRNAs from the pancreas in mice that were genetically engineered to develop pancreatic tumors. Early in their lives, mice with and without the microRNA cluster had about the same number of precancerous cells. But by the time the animals were 9 months old, a clear difference emerged. In mice with the miR-17~92 microRNAs, nearly 60 percent of the pancreas was tending toward cancer, compared with less than 20 percent in mice lacking the cluster. The finding, reported in 2017 in Oncotarget, suggests that the microRNAs aid the cancer’s start.
The researchers developed bits of RNA that block some of the cluster members from spurring on the tumor. Using human pancreatic cancer cells grown in lab dishes, Lewis and colleagues found that taking out two of the six cluster members, miR-19a and miR-19b, stopped cancer cells from forming structures called invadopodia. As their name suggests, invadopodia allow tumors to break through blood vessel walls and other barriers to spread through the body.
Transfer RNA fragments The virus helpers
For some young children and older adults, an infection with respiratory syncytial virus, or RSV, feels like a simple cold. But each year in the United States, more than 57,000 children younger than age 5 and about 177,000 people older than 65 are hospitalized because of the virus, the U.S. Centers for Disease Control and Prevention estimates. The infection kills hundreds of babies and about 14,000 adults over 65 annually.
Slightly higher than normal levels of some microRNAs had been linked to severe RSV infections. But molecular virologist Xiaoyong Bao of the University of Texas Medical Branch in Galveston wasn’t convinced that modestly increasing amounts of a few microRNAs could really mean the difference between a child getting a slight cold and dying from the respiratory virus.
She consulted her Texas Medical Branch colleague, cancer researcher Yong Sun Lee, for advice on studying microRNAs. Lee said Bao would need to deeply examine, or sequence, RNA in cells infected with the virus. That was an expensive proposition in 2012 when Bao started the project. “But I squeezed from my [lab’s] dry bank account,” she says, to pay for the experiment. The investment paid off. Cells infected with RSV had more of one particular RNA than did uninfected cells. Surprisingly, it was a piece of a transfer RNA. Transfer RNAs, or tRNAs, are the assembly line workers of protein building. tRNAs read instructions in a messenger RNA and deliver the amino acids the ribosome needs to make a protein. Scientists knew that working tRNAs are essential employees. Fragments, when they were found, were considered leftover bits of decommissioned tRNAs. But the fragments that Bao and colleagues discovered aren’t just worn out bits of tRNAs. Each fragment, about 30 bases long, is precisely cut from a tRNA when RSV infects cells. The fragments aid the virus’s infection in more than one way. For instance, two fragments help the virus make copies of itself in cells, Bao and colleagues reported in 2017 in the Journal of General Virology.
tRNA fragments may also boost the body’s susceptibility to a virus. Last year, Bao’s group described in Scientific Reports how exposure to some heavy metals, via air or water pollution, can produce tRNA fragments that trigger inflammation, which may make people more susceptible to respiratory infections such as RSV.
SINE RNAs Sacrificing infected cells
Another type of RNA may help protect against infection by certain viruses, including herpesvirus. Virologist Britt Glaunsinger has long marveled at the way viruses manipulate host cells by controlling RNAs in the cell. She became intrigued by transposons, mobile stretches of DNA that can jump from one location to another in the genome. Transposons make up nearly half of all the DNA in the human genome (SN: 5/27/17, p. 22). “We tend to think of [transposons] as parasites and things our own cells are constantly trying to shut down,” says Glaunsinger, a Howard Hughes Medical Institute investigator at the University of California, Berkeley. That’s because some are relics of ancient viruses. “While they may have initially been bad, some of them may actually be useful to us,” she says.
One class of transposons, called SINEs for short interspersed nuclear elements, are peppered throughout the genome. People have more than a million of one type of SINE known as Alu elements. Mice have similar SINEs, called B2s.
When active, SINE transposons make RNA copies of themselves. These SINE RNAs don’t carry instructions for building proteins and alone don’t enable the transposons to jump around the genome. So researchers puzzled over their role. Glaunsinger and colleagues discovered that some SINE RNAs may protect against viral infections. Normally, cells keep a tight lock on transposons, preventing them from making any RNA. But in Glaunsinger’s experiments, cells infected with herpesvirus “were producing tons of these noncoding RNAs in response to infection,” she says. “That sort of captured our interest.”
Details of the process are still being worked out, but Glaunsinger and others have discovered that SINE RNA production triggers a cascade of events that eventually kills infected human and mouse cells. Once the RNA production gets going, Glaunsinger says, “the cell is destined to die.” Inflammation appears to be an important step in the cell-killing chain reaction. It’s all for the greater good: Killing the infected cell may protect the rest of the organism from the infection’s spread.
But there’s a wrinkle: In mice, at least, one type of herpesvirus benefits from the flood of B2 RNAs in the cells it infects. The virus hijacks part of the inflammation chain reaction to boost its own production, Glaunsinger and colleagues reported in 2015 in PLOS Pathogens. “This is an example of the back-and-forth battle that’s always going on between virus and host,” she says. “Now the ball is back in the host’s court.”
piRNAs Shielding the brain from jumping genes
Autopsies of people who died with Alzheimer’s disease show a buildup of a protein called tau in the brain. That tau accumulation is tied to loss of some guardian RNAs, according to work by Bess Frost, a neurobiologist at UT Health San Antonio.
Frost studies fruit flies genetically engineered to make a disease-causing version of human tau in their nerve cells. Flies with the disorderly tau get a progressive nerve disease that causes movement problems and kills nerves. The insects live shorter lives than normal.
Part of the reason the flies, as well as people with tau tangles, have problems is because some RNAs known to guard the genome fall down on the job, Frost and colleagues discovered. These piwi-interacting RNAs, or piRNAs (pronounced “pie RNAs”), help keep transposons from jumping around. When transposons jump, they may land in or near a gene and mess with its activity. Usually cells prevent jumping by stopping transposons from making messenger RNA, which carries instructions to make proteins that eventually enable the transposon to hop from place to place. If a transposon gets past the cell’s defenses and produces its messenger RNA, piRNAs will step up to pair with the messenger and cause its destruction.
When disease-causing tau builds up in flies (and maybe in people), a class of transposon with a lengthy name — class I long terminal repeat retrotransposons — makes much more RNA than usual. And when flies have the disease-causing version of tau, they also have lower than normal levels of piRNAs, Frost and colleagues reported in August 2018 in Nature Neuroscience. “Both arms of control are messed up,” Frost says. Brains of people who died with Alzheimer’s disease or supranuclear palsy, another tau-related disease, also show signs that transposons were making extra RNA, suggesting that when tau goes bad, it can beat piRNA’s defenses.
In search of a work-around, Frost’s team found that genetically boosting piRNA production in flies or giving a drug that stops transposon hops reduced nerve cell death in the insects. The researchers are preparing to test the drug in mice prone to a rodent version of Alzheimer’s disease. The team is also examining human brain tissue to see if the increase in transposon RNAs actually leads to transposon jumping in Alzheimer’s patients. If transposons don’t hop more than usual, the finding may suggest that transposon RNAs themselves can cause mischief — no jumping necessary.
This story appears in the April 13, 2019 issue of Science News with the headline, “The Secret Powers of RNA: Overlooked molecules play a big role in human health.”
