Tight spaces cause spreading cancer cells to divide improperly

Scientists have found a new way to study how cancer cells divide and thrive in difficult-to-reach crannies of the body.

Transparent artificial membranes — just nanometers thick — can be rolled into tubes to mimic capillaries that host spreading cancer cells, researchers report in the June ACS Nano. Cells squished inside such tubes didn’t organize their internal components the way they normally do before splitting. As a result, the cells divided unevenly, potentially introducing new mutations.
Inside the body, cancer cells fight for space. Sometimes they’ll spread, or metastasize, to other organs via tight blood vessels. Although cancer cells are more likely to kill once they spread, scientists still don’t understand how the abnormal cells divide inside such tiny tubes. These cells are difficult to study in the body because they’re tucked away in hard-to-reach places. They’re challenging to study in the lab, too, because they behave differently in a petri dish than in their natural environment.

By replicating that environment more closely, this experiment gives “an appreciation for what it’s like to be a cell in a body,” says Buzz Baum, a biologist at University College London who was not involved in the work.

Other researchers have looked at cells constrained in other ways. But the nanotubes are round, just like blood vessels. They’re transparent, making it easier to visualize what’s happening inside. And it’s possible to study many cells at once by growing nearly a thousand tubes, all exactly the same size, on a chip slightly larger than a postage stamp.

When watching single human cancer cells inside the tubes through high-powered microscopes, the team noticed that the squished cells didn’t divide symmetrically. Instead of sending half the chromosomes to each new cell, some of those cells got extra genetic instructions, while others were shortchanged.

The squished cells also took longer to divide. And the protein structures that help guide the chromosomes and organelles into place before division didn’t develop correctly, says study coauthor Wang Xi, a materials scientist who did the work at the Leibniz Institute for Solid State and Materials Research Dresden in Germany.
Cancer cells succeed by mutating enough that they can evade capture, without becoming too mutated to keep replicating.

“A cell that makes too many mistakes will just die,” says Baum.

When cells are trapped inside blood vessels, “they become misshapen but they’re still able to divide,” says Xi, now at the National University of Singapore.

Xi and his colleagues think that a bulging of the cell membrane in response to pressure, called blebbing, might help the trapped cells divide in a slightly less distorted way. When the researchers prevented the cells from blebbing, the division was even more uneven. But because the team can’t yet explain why this would be the case, it’s too soon to say whether blebbing itself is responsible for the improved division.

Baum says he has shown similar deformities in cancer cells dividing under other types of constraints. But, he adds, it’s important to have systems that more closely replicate the body’s internal environment. Otherwise, it can be a big jump between doing tests in a petri dish and in a live animal.

Study coauthor Christine Schmidt, a biochemist at the University of Cambridge, says understanding how cancer cells manage to divide in tight quarters could eventually inspire ways to kill spreading cancer cells without hurting healthy cells.

Scientists throw a curve at knuckleball explanation

Knuckleballs baffle baseball players with their unpredictable swerves. A new study suggests a possible cause of the pitch’s erratic flight — sudden changes in the drag force on a ball, due to a phenomenon called a drag crisis.

The result is at odds with previous research that attributed the zigzags to the effect of airflow over the baseball’s seams. Scientists report the finding July 13 in the New Journal of Physics.

Knuckleballs are well known in baseball, but similar phenomena also confound players in soccer and volleyball. Knuckleballs occur when balls sail through the air with very little spin, producing unstable flight.
In drag crisis, the thin layer of air surrounding the ball flips between turbulent and smooth flow, abruptly changing the drag forces on the ball. If the transition occurs asymmetrically, it can push the ball to one side. “This phenomenon is intermittent” and hard to predict, says study coauthor Caroline Cohen, a physicist at École Polytechnique in Palaiseau, France. “We can’t know in advance [to] which side it will go.” Balls must move at a certain speed to experience a drag crisis, which may be why knuckleballs tend to be thrown slower than other pitches, the researchers suggest. While the fastest pitches can top 100 miles per hour, knuckleballs are usually closer to 60 or 70 miles per hour.

The scientists built a knuckleball machine, designed to launch a beach ball without any spin, and measured how much the ball veered off course. Then they calculated the ball’s expected motion based on the physics of the drag crisis and found that the predicted trajectories matched the experiments. The scientists’ calculations also correctly predict knuckleball-like phenomena in soccer, volleyball, cricket and baseball — but not in sports like tennis or basketball, where knuckleballs aren’t seen due to the properties of the ball, including texture, typical speed and how far it flies.

“It’s a fine piece of work,” says Alan Nathan of the University of Illinois at Urbana-Champaign, who studies the physics of baseball (SN: 3/23/13, p.32). But he is not entirely convinced by the explanation of knuckleballs. “Wind tunnel experiments seem to strongly suggest that it’s associated with the seams on the ball,” Nathan says, which can create turbulence that causes the ball to swerve.

So knuckleballs may remain as much of a challenge to explain as it is to hit them.

Capybaras may be poised to be Florida’s next invasive rodent

Capybaras, giant rodents native to South America, could become Florida’s next big invasive species, a biologist warned August 3 in Columbia, Mo., at the 53rd Annual Conference of the Animal Behavior Society.

“Capybaras have been introduced to northern Florida,” said Elizabeth Congdon of Bethune-Cookman University in Daytona Beach, Fla. And there are enough similarities to nutria — large invasive rodents that have caused havoc in many states — to warrant a closer look at the South American newcomers.

There are currently about 50 capybara loose in northern Florida. Now, that may not seem like an invasion, and it’s not — yet. But these animals are the world’s largest rodent, growing to 50 kilograms or more. In the wild, the semiaquatic animals live in social groups in forests where they can be near bodies of water, such as rivers, lakes or swamps. They are herbivores that can subsist on a wide variety of vegetation, from grass to tree bark. And they reproduce at a fair pace, producing an average of four, and up to eight, pups per litter.

Most people wouldn’t look at those characteristics and think “I want to own one of those animals,” but some have. Capybaras are one of the many exotic creatures that people have tried to turn into pets. (Owning one is legal in some states.) But the animals can get loose, or people may purposely release them when they no longer want to own a giant rodent.

A capybara (or 50) loose in the countryside or city is not automatically an invasive species. The difference between an invasive and a nonnative exotic is whether an organism is causing environmental or economic harm, or harm to human health.

Congdon and her undergraduate students have been studying the potential for capybaras to make that transition from exotic to invasive, and they have been looking for similarities to nutria. Those large rodents were first imported to the United States in the early 1900s; the animals were farmed for their fur in Louisiana. But they escaped — some were also purposely released as weed mitigators — and quickly established themselves in Louisiana’s many swamps. Efforts to control the animals, such as hunting, have largely failed.

Nutria, which are smaller than capybaras, reproduce at about the same rate as the giant rodents. But one of the things that have made nutria such a menace — their propensity to dig into riverbanks, levees and other places that can cause problems when the ground disintegrates — appears to be a trait they don’t share with capybaras.
While coyotes and dogs are know to hunt nutria, it appears that nothing in the United States, other than a human, is big enough to kill a capybara. No animals here are equivalent to the capybara’s natural South American predators, which include anacondas, puma and jaguar, Congdon noted.

The state of Florida says only that a breeding population of capybaras “may exist,” but Congdon is pretty sure that there is one. In 1995, five animals escaped from a wildlife facility near Gainesville, and they are probably at least part of the source of those 50 capybaras now living in Florida. “Several sightings suggest they have been breeding,” Congdon said, including the finding of a juvenile capybara. Given the similarities to the nutria, and the ability of capybaras to adapt to a variety of habitats, including cities, “they might be able to make a go of it in the United States,” Congdon concluded.

But Congdon isn’t advocating that wildlife managers kill all the capybaras in Florida. The animals represent “an opportunity to study the process of invasion,” she said. Plus, a population in Florida would be a lot easier for her to access than the one she studied in Venezuela as a gradate student. “We want to keep them from spreading,” she said, “but can we please not kill them all so I can study them?”

How to get Ötzi’s look

Ötzi had Copper Age style.

The 5,300-year-old Tyrolean Iceman, whose body was found poking out of a glacier in the Italian Alps in 1991, incorporated hides from at least five domesticated and wild animal species into his apparel, a new genetic study finds. Comparing mitochondrial DNA extracted from nine ancient leather fragments with DNA of living animals revealed the makeup of Ötzi’s clothes and a key accessory, says a team led by paleogeneticist Niall O’Sullivan. Mitochondrial DNA typically gets passed from mothers to their offspring.
Little is known about what people wore during Ötzi’s time. The findings provide a glimpse into how ancient European populations exploited domesticated animals to make clothes and other items.

Ötzi’s coat consisted of hides from at least three goats and one sheep, the scientists report August 18 in Scientific Reports. This garment may have been periodically patched with leather from whatever animals were available, the team suggests.

Goats also provided skin for the Iceman’s leggings, the new analysis indicates.

A sheepskin loincloth and a shoelace derived from European cattle round out Ötzi’s attire made from domesticated animals.

As for wild animals, Ötzi wore a brown-bear cap and toted a quiver made from roe deer. It’s impossible to know if the ancient man attached any special meaning to brown bears, “but he may have been an opportunistic hunter or a scavenger,” says O’Sullivan, of University College Dublin and EURAC Research in Bolzano, Italy.
A 2012 analysis of proteins from fur samples taken from Ötzi’s clothing identified sheep and a goatlike animal called a chamois as sources for the Iceman’s coat. A team led by biochemist Klaus Hollemeyer of Saarland University in Saarbrücken, Germany, also pegged goats and dogs or wolves as sources of skin for Ötzi’s leggings.

Disparities between Hollemeyer’s and O’Sullivan’s studies may stem from the two groups having sampled different parts of patchwork garments. In addition, the new report used advanced techniques for extracting and analyzing ancient DNA. That enabled O’Sullivan’s team to retrieve six complete mitochondrial genomes from Ötzi’s leather belongings.

O’Sullivan’s investigation “opens a new field of potential identification procedures for mammalian species in ancient leathers and furs,” Hollemeyer says.

A roughly 4,200-year-old legging found in the Swiss Alps in 2004 also features goat hide. Mitochondrial DNA extracted from that garment came from an ancient line of European goats that has largely been replaced by a genetically distinct goat population, a team led by archaeologist Angela Schlumbaum of the University of Basel in Switzerland reported in 2010.

The Swiss legging was found with pieces of bows and arrows, woolen clothes and many other artifacts where an ice patch in a mountain pass had partly melted. No human bodies have been found there.

“Possibly, goat leather was most comfortable” as legging material, says University of Bern archaeologist Albert Hafner, a coauthor of the Swiss legging study. “Modern leather trousers often use goat as well.”

For snowy owls, wintering on the prairie might be normal

White, fierce and fluffy, snowy owls are icons of Arctic life. But some of these owls are not cool with polar winters.

Every year, part of the population flies south to North American prairies. Ornithologists thought those birds fled the Arctic in desperation, haggard and hungry. But the prairie owls are doing just fine, researchers report August 31 in The Auk: Ornithological Advances.

Over 18 winters, wild snowy owls caught and banded in Saskatchewan, Canada — one of the species’ southerly destinations­­ — were 73 percent heavier than emaciated owls in rescue shelters. Females were heavier and had more fat than males, and adults were in better condition than youngsters. But regardless of age or sex, most snowy owls that made the journey south were in relatively good health.

That means southern winters may not be such a desperate move after all. Prairies are probably just a normal wintering ground for some of the Arctic snowy owl population, the researchers say. Snowbirds, indeed.

Philae lander spotted on comet 67P

Philae has been found, nestled in a shadowy crevice on comet 67P/Churyumov-Gerasimenko. The comet lander, lost since its tumultuous touchdown on the comet on November 12, 2014, turned up in images taken by the Rosetta orbiter on September 2.

Philae is on its side with one leg sticking out into sunlight. Its cockeyed posture probably made it difficult for Philae to reliably get in touch with Rosetta, explaining why scientists had trouble reestablishing communication. The discovery came about a month before the end of the Rosetta mission; the orbiter was scheduled to land on the comet on September 30and then shut down.

Philae spent just a few days transmitting data from the comet’s surface (SN: 8/22/15, p. 13). It had a rough landing, bouncing twice before stopping. Sitting in the shadow of a cliff, Philae was unable to use solar power to recharge its battery. Rosetta picked up intermittent communication in June and July 2015. Since January, temperatures on the comet have been too chilly for Philae’s electronics; scientists stopped listening for radio signals in July.

Qian Chen makes matter come alive

Qian Chen, 30
Materials scientist
University of Illinois

The SN 10
In a darkened room, bathed in the glow of green light, materials scientist Qian Chen watches gold nanorods dance. They wiggle across a computer screen displaying real-time video from a gigantic microscope — a tall, beige tube about as wide as a telephone pole.

Chen has observed these and other minuscule specks of matter swimming, bumping into one another and sometimes organizing into orderly structures, just like molecules in cells do. By pioneering the design of new biologically inspired materials, she’s exploring what it means to be “alive.” Next, Chen wants to get an up-close and personal view of cellular molecules themselves: the nimble, multitasking proteins that work day and night to keep living organisms running.

At age 30, Chen is already racking up high-profile publications and turning some far-out ideas into reality. Her ultimate goal: To mimic the machinery that living cells have already perfected. To create life, or something like it, out of nonliving materials.

“If you can see it, you can start to understand it,” Chen said when I visited her lab at the University of Illinois at Urbana-Champaign earlier this year. “And if you understand it, you can start to control it.”

Chen didn’t always want to be a scientist. Growing up in China, she imagined one day becoming a writer. In middle school, she wrote an award-winning story about a girl who figures out how to repair the ozone layer. “My idea was to get some material that can be stretched, like the skin of the balloon,” Chen says.
Her interest in inventing new and unusual materials took off years later, in the United States. After graduating from college in China in 2007 — Chen was the first in her family to do so — she headed to Illinois to work with materials scientist Steve Granick.

From the start, Chen stood out. “She made hard things look easy,” says Granick, now at the Ulsan National Institute of Science and Technology in South Korea. He recalls one experiment in particular, when Chen performed a feat some scientists thought impossible: She got thousands of tiny beads to form an open and orderly two-dimensional structure — all by themselves.

Chen had been studying colloidal particles, microscopic specks roughly a micrometer in size. People normally think of these particles as a component of paint, not all that interesting.

But Chen had the idea to cover the particles with a kind of sticky coating that acted something like Velcro. When the particles bumped into one another, they stuck together. At first, “It looked like a mess, like a failed experiment,” says Granick. “Most graduate students would have just chalked it up to a mistake and gone home.”

After a day of knocking around in solution, sticking together and tearing apart, the particles finally settled into something stable. The special coating and the way Chen applied it (capping the top and bottom of each particle) led to a “kagome lattice,” something sort of like a honeycomb. Never before had scientists coaxed colloidal particles into such an open, porous framework. Usually, the particles pack together more tightly, like apples stacked on the shelf at a grocery store, Chen says.
That work led in 2011 to a publication in Nature: “Directed self-assembly of a colloidal kagome lattice.” A week earlier, Chen and Granick had published a different paper in Science, “Supracolloidal reaction kinetics of Janus spheres,” about particles that self-assemble into a twisting chain, or helix. At the time, Chen was 24.

“Her work is at the leading edge,” says Penn State chemist Christine Keating. “She’s so full of enthusiasm for science, and energy and creative ideas.”

Exactly how such particles might one day be used is still anybody’s guess. Some researchers envision self-assembling materials building smart water filters or adaptable solar panels that change shape in response to the sun. But the full range of possibilities is hard to fathom. Chen is “trying to invent the rules of the game,” Granick says. “She’s laying the groundwork for future technologies.”

Her next big focus will take her field from self-assembly 101 to the master class level, by mimicking how biological molecules behave. But first she has to see them in action.

Into the cell
In 2012, Chen traveled west to the University of California, Berkeley to work with National Medal of Science winner Paul Alivisatos on a new microscopy technique.

Scientists today can view the details of proteins and DNA close up under a microscope, but the results are typically still-life images, frozen in time. It’s harder to get action shots of proteins morphing in their natural, fluid world. That view could unveil what roles different protein parts play.

Even a technique that won its developers a Nobel Prize in 2014 (SN: 11/2/14, p. 15) — it relies on fluorescent molecules to illuminate a cell’s moving parts — can’t always reveal the intricacies of proteins, Chen says. They’re just glowing dots under the microscope. Imagine, for example, looking at a dump truck from an airplane window. You can’t see how the truck actually works, how the pistons help lift the bed and the hinges open the tailgate.

“I use this as inspiration,” Chen says, grabbing her laptop and starting up a video that may well be the fantasy of anyone exploring biology’s secret world. The computer animation shows molecules whizzing and whirling deep inside a cell. Gray-green blobs snap together in long chains and proteins haul giant, gelatinous bags along skinny tracks. No one yet has gotten a view as clear as this hypothetical one, but a technique Chen is now helping to develop at Illinois could change that.

It’s called liquid-phase transmission electron microscopy, and it’s a slick twist on an old method. In standard TEM, researchers create subnanometer-scale images by shooting an electron beam through samples placed in a vacuum. But samples have to be solid — still as stone — because liquids would evaporate.

By sandwiching beads of liquid between thin sheets of graphene, though, Chen gets around the problem. It’s like putting droplets of water in a plastic baggie. The liquid doesn’t dry up, so researchers can observe the particles inside jittering around. Chen has used the technique to see gold nanorods assembling tip-to-tip and DNA-linked nanocrystals moving and rotating in 3-D. Now, she may be on the verge of a big advance.

With liquid-phase microscopy, Chen is attempting to see cellular machinery with a clarity no scientist has achieved before. She is cautious about revealing too many details. But if Chen succeeds, she may be on her way to cracking the code that links biological structure to function — figuring out the parts of a protein, the pistons and hinges, that let it do its specific job. Knowing the structural building blocks of life, she says, will help scientists create them — and everything they can do — out of artificial materials.

“We’re not there yet,” Chen says, “but that’s the big dream.”

First ‘three-parent baby’ born from nuclear transfer

A baby boy born on April 6 is the first person to be born from a technique used to cure mitochondrial diseases, New Scientist reports.

The child’s mother carries Leigh syndrome, a fatal disease caused by faulty mitochondria. Mitochondria generate most of a cell’s energy and perform other functions that keep cells healthy. Each mitochondria has a circle of DNA containing 37 genes needed for mitochondrial function. A mutation in one of those genes causes Leigh syndrome. The woman herself is healthy, but previously had two children who both died of Leigh syndrome.

John Zhang, a fertility doctor at New Hope Fertility Center in New York City, and colleagues transferred a structure called the spindle with chromosomes attached to it from one of the woman’s eggs into a healthy, empty donor egg. The resulting egg was then fertilized with sperm from the woman’s husband. The procedure was done in Mexico.

The technique, called spindle nuclear transfer, is one of two ways of creating “three-parent babies” to prevent mitochondrial diseases from being passed on. Such three-parent babies inherit most of their DNA from the mother and father, but a small amount from the donor. Other three-parent children who carried mitochondria from their mothers and from a donor were born in the 1990s, but the baby boy is the first to be born using a nuclear transfer technique. Zhang and colleagues will report the successful birth October 19 in Salt Lake City at the American So

Big Viking families nurtured murder

Murder was a calculated family affair among Iceland’s early Viking settlers. And the bigger the family, the more bloodthirsty.

Data from three family histories spanning six generations support the idea that disparities in family size have long influenced who killed whom in small-scale societies. These epic written stories, or sagas, record everything from births and marriages to deals and feuds.

Iceland’s Viking killers had on average nearly three times as many biological relatives and in-laws as their victims did, says a team led by evolutionary psychologist Robin Dunbar of the University of Oxford. Prolific killers responsible for five or more murders had the greatest advantage in kin numbers, the scientists report online September 20 in Evolution and Human Behavior.
Particularly successful killers chose their victims carefully, knowing that their large families would deter revenge attacks by smaller families of the slain, the researchers contend. Those killings were motivated by land grabs, they suspect. One-time killers tended to have only slightly bigger families than those of their victims; insults or goading possibly prompted those murders.
Strikingly, around 18 percent of all men mentioned in the sagas were murdered. Similarly high homicide rates, mainly due to cycles of revenge killing between feuding families, have been reported for some modern hunter-gatherer and village-based societies ( SN Online: 9/27/12 ). Lethal raids by competing groups may go back 10,000 years or more ( SN: 2/20/16, p. 9
Murder rates rise in the absence of central authorities that enforce social order, Dunbar proposes. “The real issue is not that there were so many murders among Icelandic Vikings, but that murders were carefully calculated based on knowing whether one had a sufficient family advantage to take the risk.”

That idea relates to mathematical formulas of fighting strength developed during World War I by British engineer Frederick Lanchester. One of Lanchester’s laws calculates that the fighting advantage of a larger group over a smaller group grows disproportionately as the disparity in the size of war parties increases. That rule also holds for family-size differences in small-scale societies, such as Icelandic Vikings, Dunbar’s group concludes.

Tests of the possibility that greater kin numbers encourage lethal attacks in preindustrial groups, such as the Vikings, are rare, says Oxford evolutionary biologist and political scientist Dominic Johnson, who did not participate in the new study. Johnson has reviewed evidence suggesting that humans, chimps and social hunters such as wolves have evolved ways to monitor group sizes and launch attacks when they can gang up on a few opponents.

Dunbar and his colleagues studied three Icelandic family sagas covering events from around 900 to 1100. Iceland’s first settlers arrived from Scandinavia and northern Europe in the late 800s (SN: 5/14/16, p. 13).

The sagas contained information about events, including feuds and murders, involving 1,020 individuals. For everyone mentioned, the researchers identified a network of biological and in-law relationships.

Under Norse law, a murder entitled a victim’s relatives to compensation, either via a revenge murder or blood money. Icelandic sagas describe the importance of avenging murdered relatives to save face and prevent further attacks, regardless of family size.

In the three sagas, a total of 66 individuals caused 153 deaths; two or more attackers sometimes participated in the same killing. No killers were biologically related to their victims (such as cousins or closer), but one victim was a sister-in-law of her killer.

About two-thirds or more of killers had more biological kin on both sides of their families, and more in-laws, than their victims did.

Six men accounted for about 45 percent of all murders, each killing between five and 19 people. Another 23 individuals killed two to four people. The rest killed once. Frequent killers had many more social relationships, through biological descent and marriage, than their victims did, suggesting that they targeted members of families in vulnerable situations, the researchers say.

AI system learns like a human, stores info like a computer

A GPS app can plan the best route between two subway stops if it has been specifically programmed for the task. But a new artificial intelligence system can figure out how to do so on the fly by learning general rules from specific examples, researchers report October 12 in Nature.

Artificial neural networks, computer programs that mimic the human brain, are great at learning patterns and sequences, but so far they’ve been limited in their ability to solve complex reasoning problems that require storing and manipulating lots of data. The new hybrid computer links a neural network to an external memory source that works somewhat like RAM in a regular computer.

Scientists trained the computer by giving it solved examples of reasoning problems, like finding the shortest distance between two points on a randomly generated map. Then, the computer could generalize that knowledge to solve new problems, like planning the shortest route between stops on the London Underground. Rather than being programmed, the neural network, like the human brain, responds to training: It can continually integrate new information and change its response accordingly.

The development comes from Google DeepMind, the same team behind the Alpha Go computer program that beat a world champion at the logic-based board game.