Giggling rats help reveal how brain creates joy

Tickle a rat and it will jump for joy, gleefully squeak and beg for more. In addition to describing these delightful reactions to a tickling hand, a new study identifies nerve cells in the brain that help turn rats into squirmy puddles of giggles.

The results, published November 11 in Science, offer insight into how the brain creates glee, an understudied emotion. “People really underrate the positive things — fun, happiness, joy,” says study coauthor Shimpei Ishiyama of Humboldt University of Berlin.
Scientists knew that rats seemed to enjoy a good tickle from a human, but how the brain creates that emotion was a mystery. Although no protocol existed, the tickling part of the experiment turned out to be “surprisingly easy,” Ishiyama says. He simply stuck his hand in the cages and scribbled his fingers in the rats’ fur, to their apparent delight. Tickled rats laughed by emitting an ultrasonic 50-kilohertz giggle that humans can’t hear. They also jumped for joy, an acrobatic feat called “Freudensprünge,” and chased Ishiyama’s hand around the cage. Using laughter as a measurement, Ishiyama and colleagues found that the belly, not back or tail, is a rat’s most ticklish spot.

This joyful response may be created in part by nerve cells in the somatosensory cortex. In people, this brain region responds to tickles and is usually associated with touch perception. In tickled rats, many nerve cells in the part of the somatosensory cortex that corresponds to the rodents’ trunks grew active, electrodes revealed. A light stroke activated some of these nerve cells, but not as many.

Because these nerve cells respond to touch, it’s not surprising that they grew active during a tickle, Ishiyama says. But additional experiments found active nerve cells when the rats were chasing a tickling hand without being touched — suggesting the cells are responding to something specific about a tickle, not just touch in general. What’s more, when the researchers used electrodes to stimulate the somatosensory cortex in untouched rats, the rats giggled.
It turns out that ticklishness is a flighty state, and not just because some rats like to be tickled more than others. Anxious rats on a platform and in bright lights emitted fewer laughlike vocalizations than calm rats, the researchers found. Nerve cells in the somatosensory cortex were less likely to fire off signals, too, results that highlight just how mood-dependent tickling is.

The new study shows for the first time that laughter can result from stimulation of the somatosensory cortex, says neuroscientist Elise Wattendorf of the University of Fribourg in Switzerland. The brain area’s involvement in both the sensory aspects of tickling and its social context is “unexpected, and constitutes an outstanding result,” she wrote in an e-mail. Using brain scans, Wattendorf and colleagues had previously found that the somatosensory cortex was active when people laughed as they were tickled.

Many brain studies focus on troubles such as depression, Ishiyama says. But by taking the opposite approach, he hopes to reveal new insights into how the brain creates and maintains happiness. Besides, he says, “it’s also fun to study fun.”

Chinese patient is first to be treated with CRISPR-edited cells

Chinese scientists have injected a person with CRISPR/Cas9-edited cells, marking the first time cells altered with the technique have been used in humans. Researchers used the powerful gene editor to alter immune cells to fight lung cancer, Nature reports November 15.

Immune cells called CAR-T cells have already been engineered using other gene-editing technologies. A baby’s leukemia was successfully treated in 2015 with CAR-T cells engineered with gene editors known as TALENs.

Chinese researchers led by oncologist Lu You of Sichuan University in Chengdu got approval to conduct the new trial this summer. U.S. researchers have gotten clearance to begin similar clinical trials.

You’s team removed immune cells from a patient with lung cancer. They then used CRISPR/Cas9 as molecular scissors to cut and inactivate the PD-1 gene in T cells. That gene’s protein usually holds immune cells back from attacking tumors. The hope is that the edited cells will now go on the offensive and help the patient fight cancer. Researchers plan to give the patient a second dose of engineered cells, Nature reports.

The researchers’ progress with the technique could spark a space race–style biomedical competition between the United States and China, Carl June, an immunotherapist at University of Pennsylvania in Philadelphia, told Nature. “I think this is going to trigger ‘Sputnik 2.0,’” he said, hopefully improving the end product.

‘The Glass Universe’ celebrates astronomy’s unsung heroines

In the early 1880s, Harvard Observatory director Edward Pickering put out a call for volunteers to help observe flickering stars. He welcomed women, in particular — and not just because he couldn’t afford to pay anything.

At the time, women’s colleges were producing graduates with “abundant training to make excellent observers,” Pickering wrote. His belief in women’s abilities carried over when he hired staff, even though critics of women’s higher education argued that women “originate almost nothing, so that human knowledge is not advanced by their work.”
Pickering and his “harem” sure proved the critics wrong.

In The Glass Universe, science writer Dava Sobel shines a light on the often-unheralded scientific contributions of the observatory’s beskirted “computers” who helped chart the heavens. By 1893, women made up nearly half of the observatory’s assistants, and dozens followed in their footsteps.

These women toiled tirelessly, marking times, coordinates and other notations for photographic images of the sky taken nightly and preserved on glass plates — the glass universe. These women’s routine mapping of the stars gave birth to novel ideas that advanced astronomy in ways still instrumental today — from how stars are classified to how galactic distances are measured.

Using diaries, letters, memoirs and scientific papers, Sobel recounts the accomplishments of these extraordinary women, going into enough scientific detail (glossary included) to satisfy curious readers and enough personal detail to bring these women’s stories to life.

Sobel traces the origin of the glass universe back to heiress Anna Palmer Draper. The book opens in 1882 with her exulting in hosting a party for the scientific glitterati under the glowing and novel Edison incandescent lights. Her husband, Henry Draper, a doctor and amateur astronomer, had pioneered a way to “fix” the stars on glass photographic plates. The resulting durable black-and-white images revealed spectral lines that could provide hints to a star’s elements — and eventually so much more. Henry’s premature death five days after the party launched Anna’s philanthropic support of the Harvard Observatory and the creation of the glass universe.
Other women featured in the book had a more hands-on impact on astronomy. For instance, Williamina Fleming came to the United States as a maid. But Pickering soon recognized her knack for mathematics. At the observatory, she read “the rune-like lines of the spectra,” Sobel writes, noticing patterns that led to the first iteration in 1890 of the Draper stellar classification system. That system, still used today, was later refined by the observations of other women.

Henrietta Leavitt, a promising Radcliffe College astronomy student slowly going deaf, joined the staff in 1895. While meticulously tracking the changing brightness of variable stars, she noticed a pattern: The brighter a star’s magnitude, the longer it took to cycle through all its variations. This period-luminosity law, published in 1912, became crucial in measuring the distance to stars. It underpinned Edwin Hubble’s law on cosmic expansion and led to discoveries about the shape of the Milky Way, our solar system’s place far from the galactic center and the existence of other galaxies.

The story belongs, too, to Pickering and his successor, Harlow Shapley. Perhaps partly motivated by economics at a time of shoestring budgets — in 1888, women computers earned just 25cents per hour — these men not only recognized, but also encouraged and heralded the women’s talent.

Sobel takes readers through World War II and a myriad of other moments starring women: first woman observatory head; first woman professor at Harvard (of astronomy, of course); discoveries of binary stars, the prevalence of hydrogen and helium in stars, and the existence of interstellar dust. In some cases, it took male astronomers to make those findings stick — the glass universe had a glass ceiling.

After World War II, radio astronomy emerged, and “the days of the human computer were numbered — by zeros and ones,” Sobel writes. Using film to photograph the stars ended in the 1970s. But the glass universe is far from obsolete. The roughly half-million plates hold the ghosts of pulsars, quasars and other stellar phenomena not even imagined when the plates were made. They also offer the promise of more discoveries to come, perhaps by the next generation of women astronomers.

Why a mountain goat is a better climber than you

The mountain goat (Oreamnos americanus) might be the world’s best climber, able to scale near-vertical cliffs with an ease rivaled only by the world’s best human rock climbers — who have the advantage of safety equipment and opposable thumbs. Just how the goats manage such climbs has been somewhat of a mystery. Researchers suspected that the big muscles in the animals’ neck and shoulders and their low center of mass play a role, but no one had studied this, in part because of the difficulty of doing research in the goats’ home territory — remote mountainous regions of the United States and Canada.

Enter YouTube.

The internet is peppered with videos of these animals’ amazing feats, and biomechanics researchers Ryan Lewinson and Darren Stefanyshyn of the University of Calgary saw an opportunity: There was no need to go to the mountain goats when they could simply go to YouTube.

The researchers found a video (below) that they thought would work for analysis. In it, a young male mountain goat climbs a hill in the Canadian Rockies. They focused on a section in which the animal makes a series of galloping leaps, picking out nine frames to analyze. In the first six frames, the mountain goat pushes off the rock face, with its hindlimbs in contact with the hill surface. In the last three frames, the animal pulls itself up the hill with its forelimbs.
During the push-off phase, the researchers found, the front legs stay close to the animal’s body while the back legs extend, creating a strong propulsive force upward. Then, the mountain goat uses those strong muscles in its neck and shoulders to propel its torso up the hill while keeping its elbows tucked in to keep the motion going straight up, the team reports in the December Zoology.

Now the question is, do all mountain goats climb this way? The researchers note that this was a study of just one animal, and a young one at that. Perhaps other mountain goats, either younger or older, climb in a different way. Plus, this was an opportunistic study, in which the researchers had no control over the setting.
“As a result,” they write, “it is not known if all mountain goats show the same movement pattern, or how this movement pattern changes in regards to the mountain slope the animal is climbing.”

In other words, they’ll need more than your YouTube videos to figure it out.

Readers contemplate corals and more

Corals in crisis
Algae that provide nutrients to corals turn toxic and lead the corals to “bleach” and sometimes die when ocean temperatures spike. Researchers are seeding damaged reefs with baby corals and breeding heat-tolerant corals to help these imperiled marine animals, Amy McDermott reported in “Rebuilding reefs” (SN: 10/29/16, p. 18).

Ronald Swager wondered if researchers could use genetic engineering to make heat-stressed algae nontoxic.

Gene-editing tools may help corals survive, but the research is still quite preliminary, says Janelle Thompson, an environmental microbiologist at MIT. Among the difficulties: Scientists do not know how exactly the algae become toxic on a molecular level and they can only guess at the role of most algal genes. “One of the main challenges is the size of the [algae] genome, which … is on par with human genomes,” Thompson says. And there are many genetic variations of algae, some of which are only compatible with specific corals. Researchers would have to engineer more than one type of algae.
Heat-tolerant algae exist, but so far they don’t seem to perform well at normal temperatures, says Peter Harrison of Southern Cross University in Lismore, Australia. Assuming biologists work through the technical hurdles of genetic engineering, many people will be concerned about releasing genetically modified algae into the oceans, Harrison says.

Codex contention
Once regarded as fake by some scientists, a 10-page, bark-paper book called the Grolier Codex is authentic, according to a recent study by Yale archaeologist Michael Coe and colleagues. It may be the oldest known manuscript of ancient America, Bruce Bower wrote in “Maya codex real, analysis claims” (SN: 10/29/16, p. 16).
Physicist and astronomer John Carlson of the University of Maryland in College Park took issue with the study and Science News’ reporting. Carlson’s letter has been edited for brevity.

“I was dismayed to see my own published work establishing the authenticity of the Maya ‘Grolier Codex’ as likely the ‘oldest surviving book on paper from the ancient Americas,’ presented as ‘new analysis’ by Michael Coe and collaborators.

“There was no mention of the source of the most crucial evidence — the only radiocarbon dating of the codex’s bark paper — nor was I contacted for comments. My work, beginning in the late 1970s (and first published in 1983), determined that what had been known as ‘page 11’ was actually the lower portion of ‘page 10.’ That finding, with other primary sources, established a sequence of skeletal Evening Star manifestations of the planet Venus, something that could not have been known to any alleged faker in the mid-1960s when the codex was discovered. This work helped convince the majority of Mesoamericanist experts in Maya epigraphy and codex studies that the codex was genuine.

“I was able to study the codex itself carefully on three occasions and obtained the first carbon-14 dates from the actual codex, placing it in the 13th century. All of this was published in my article ‘The Twenty Masks of Venus’ in Archaeoastronomy in 2014 and presented at the Pre-Columbian Society of Washington, D.C., in November 2014. The scholarly details are available along with many other primary sources on my website: umd.academia.edu/JohnBCarlson.”

In an e-mail response to Science News, Michael Coe emphasizes that his team’s paper credits Carlson for his work on the Grolier Codex. Coe says that even by 1973, well before Carlson’s publications appeared, specialists in Maya writing were convinced that the codex was genuine. The new paper for the first time examines the full range of drawings and writings in the codex, Coe asserts, fitting them in with what’s now known about ancient Maya religion and gods.

‘Waterworld’ Earth preceded late rise of continents, scientist proposes

SAN FRANCISCO — Earth may have been a water world for much of its history, a new proposal contends. Just like in the Kevin Costner movie, the continents would have been mostly submerged below sea level. Previous proposals have suggested that Earth’s land area has remained comparatively unchanged throughout much of geologic time.

But geoscientist Cin-Ty Lee of Rice University in Houston proposes that Earth’s continents didn’t rise above the waves until around 700 million years ago, when the underlying mantle sufficiently cooled. Though many scientists are unconvinced, that continental rise may have contributed to the rapid diversification of life known as the Cambrian explosion. “The Earth is cooling and that actually has manifestations that dictate how life goes,” Lee said December 15 at the American Geophysical Union’s fall meeting.
Earth’s first continental crust formed billions of years ago. Slabs of this crust “float” above the underlying mantle like icebergs, with relatively cold roots than can extend tens of kilometers into the mantle. A continent’s elevation depends, in part, on the size of its root and the density of the mantle.

Earlier in Earth’s history when the mantle was hotter and less dense, the continents sat largely below sea level with only mountains peeking above the water’s surface, Lee proposed. The cooling of the mantle over time increased the relative buoyancy of the continents and lifted the landmasses above sea level. Considering mantle cooling rates and Earth’s topography, Lee proposes that this expansion of Earth’s dry land took place around 1 billion to 500 million years ago and lasted about 100 million years.

The new land would have altered carbon and nutrient cycles, Lee suggested. These effects could help explain large shifts in Earth’s climate around this time and might have nourished the Cambrian explosion. During that time, around 540 million to 500 million years ago, forerunners of the major groups of animals — from insects to mammals — first emerged.

This tale of rising continents may be overly simplistic, said Laurent Montési, a geodynamicist at the University of Maryland in College Park. Other factors such as the mass of the continents, the amount of water in the oceans and the rate of new crust formation on the seafloor could affect sea levels relative to the continents. The idea is worth considering, he said, “but the evidence is not completely there yet.”

‘Furry Logic’ showcases how animals exploit physics

Warning: Furry Logic is not, as the title might suggest, a detailed exploration of mammals’ reasoning skills. Instead, it’s a fun, informative chronicle of how myriad animals take advantage of the laws of physics.

Science writers Matin Durrani and Liz Kalaugher cite a trove of recent (and often surprising) research findings. They draw on their backgrounds — Durrani is a physicist, Kalaugher a materials scientist — to explain how animals exploit sound, light, electricity and magnetism, among other things, in pursuit of food, sex and survival. These creatures don’t consciously use physics the way that humans design and use tools, of course, but they are evolutionary marvels nonetheless.
Peacocks, for example, produce low-frequency sounds while shimmying their tail feathers (SN Online: 04/27/16). The birds use these sounds — and not just the sight of those colorful plumes — to impress females and fend off competing males. At the other end of the sonic spectrum, some bats use stealth echolocation to track down their preferred prey. Moths targeted by these bats have sensors that can pick up these ultrasonic calls, but the bats squeak so softly that a moth can’t hear its stalker until it is less than a half-second’s flight away.

Durrani and Kalaugher let readers know when the science isn’t settled. Researchers aren’t quite sure how peahens pick up males’ infrasonic signals, for example. Scientists also haven’t figured out how the archerfish spits so precisely (SN: 10/4/14, p. 8), knocking prey off low-hanging branches above the water as often as 94 percent of the time. The submerged fish must somehow gauge the angle at which light bends as it enters the water and then accurately compensate for refraction while spewing a stream of water. Amazingly, this feat may be innate rather than learned via trial and error.

Readers need not understand the intricacies of polarized light, Earth’s magnetic field or surface tension to enjoy Furry Logic. Nor is this book an exhaustive account of the characteristics and behavior of every animal that uses such phenomena in interesting ways. There should be plenty of material for a sequel to this fascinating book.

Cancer studies get mixed grades on redo tests

An effort to reproduce findings of five prominent cancer studies has produced a mixed bag of results.

In a series of papers published January 19 in eLife, researchers from the Reproducibility Project: Cancer Biology report that none of five prominent cancer studies they sought to duplicate were completely reproducible. Replicators could not confirm any of the findings of one study. In other cases, replicators saw results similar to the original study’s, but statistical analyses could not rule out that the findings were a fluke. Problems with mice or cells used in two experiments prevented the replicators from confirming the findings.
“Reproducibility is hard,” says Brian Nosek, executive director of the Center for Open Science in Charlottesville, Va., an organization that aims to increase the reliability of science. It’s too early to draw any conclusions about the overall dependability of cancer studies, Nosek says, but he hopes redo experiments will be “a process of uncertainty reduction” that may ultimately help researchers increase confidence in their results.

The cancer reproducibility project is a collaboration between Nosek’s center and Science Exchange, a network of labs that conduct replication experiments for a fee. Replicators working on the project selected 50 highly cited and downloaded papers in cancer biology published from 2010 to 2012. Teams then attempted to copy each study’s methods, often consulting with the original researchers for tips and materials. The five published in eLife are just the first batch. Eventually, all of the studies will be evaluated as a group to determine the factors that lead to failed replications.
Critics charge that the first batch of replication studies did not accurately copy the originals, producing skewed results. “They didn’t do any troubleshooting. That’s my main complaint,” says cancer biologist Erkki Ruoslahti of Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Calif.

Ruoslahti and colleagues reported in 2010 in Science that a peptide called iRGD helps chemotherapy drugs penetrate tumors and increases the drugs’ efficacy. In the replication study, the researchers could not confirm those findings. “I felt that their experimental design was set up to make us look maximally bad,” Ruoslahti says.

Replicators aren’t out to make anyone look bad, says cancer biologist Tim Errington of the Center for Open Science. The teams published the experimental designs before they began the work and reported all of their findings. What Ruoslahti calls troubleshooting, Errington calls fishing for a particular result. Errington acknowledges that technical problems may have hampered replication efforts, but that’s valuable data to determine why independent researchers often can’t reproduce published results. Identifying weaknesses will enable scientists to design better experiments and conduct research more efficiently, he argues.

Other researchers took issue with the replicators’ statistical analyses. One study sought to reproduce results from a 2011 Science Translational Medicine report. In the original study, Atul Butte, a computational biologist at the University of California, San Francisco, and colleagues developed a computer program for predicting how existing drugs might be repurposed to treat other diseases. The program predicted that an ulcer-fighting drug called cimetidine could treat a type of lung cancer. Butte and colleagues tested the drug in mice and found that it reduced the size of lung tumors. The replication attempt got very similar results with the drug test. But after adjusting the statistical analysis to account for multiple variables, the replication study could no longer rule out a fluke result. “If they want a headline that says ‘It didn’t replicate,’ they just created one,” Butte says. Errington says the corrections were necessary and not designed to purposely invalidate the original result. And when replication researchers analyzed both the original and replication study together, the results once again appeared to be statistically sound.

A failure to replicate should not be viewed as an indication that the original finding wasn’t correct, says Oswald Steward, a neuroscientist at the University of California, Irvine, who has conducted replication studies of prominent neuroscience papers but was not involved in the cancer replication studies. “A failure to replicate is simply a call to attention,” Steward says. Especially when scientists are building a research program or trying to create new therapies, it is necessary to make sure that the original findings are rock solid, he says. “We scientists have to really own this problem.”

Editor’s note: This story was updated January 26, 2017, to correct the starting point of the x-axis in the first graph.

Climate change may boost toxic mercury levels in sea life

The muddying of coastal waters by climate change could drastically increase levels of neurotoxic mercury in sea life, contaminating food supplies.

Shifting rainfall patterns may send 10 to 40 percent more water filled with dissolved bits of organic debris into many coastal areas by 2100. The material can cloud the water, disrupting marine ecosystems by shifting the balance of microbes at the base of the food web, new laboratory experiments suggest. That disruption can at least double methylmercury concentrations in microscopic grazers called zooplankton, researchers report January 27 in Science Advances.
The extra mercury could reverberate up the food web to fish that humans eat, warns study coauthor Erik Björn, a biogeochemist at Umeå University in Sweden. Even small amounts of methylmercury, a form of the metal easily absorbed by humans and other animals, can cause birth defects and kidney damage, he notes.

Pollution from human activities such as fossil fuel burning has already tripled the amount of mercury that has settled in the surface ocean since the start of the Industrial Revolution (SN: 9/20/14, p. 17). Climate changes spurred by those same activities are washing more dark organic matter into the oceans by, for instance, boosting wintertime rainfall in some regions.

Björn and colleagues replicated this increased runoff using 5-meter-tall vats filled with marine microbes and dashes of methylmercury. Vats darkened by extra organic matter showed an ecosystem shift from light-loving phytoplankton to dark-dwelling bacteria that eat the extra material, the researchers found.

Zooplankton nosh on phytoplankton, but they don’t directly eat the bacteria. Instead the bacteria are consumed by protozoa, which zooplankton then hunt. Methylmercury accumulates with each step up the food web. So the addition of the protozoa middle step, the researchers report, resulted in zooplankton methylmercury levels two to seven times higher than in vats without the extra organic matter. Methylmercury levels will continue to increase up the food web to fish and the humans who eat them, the researchers warn.

The results suggest that curbing mercury contamination is more complicated than simply controlling emissions, says Alexandre Poulain, an environmental microbiologist at the University of Ottawa. “First we need to control emissions, but we also need to account for climate change.”

Faint, distant galaxies may have driven early universe makeover

Two cosmic magnifying glasses are giving astronomers a glimpse of some extremely faint galaxies that existed as far back as 600 million years after the Big Bang (13.8 billion years ago). Such views suggest that tiny galaxies in the early universe played a crucial role in cosmic reionization — when ultraviolet radiation stripped electrons from hydrogen atoms in the cosmos.

“That we detected galaxies as faint as we did supports the idea that a lot of little galaxies reionized the early universe and that these galaxies may have played a bigger role in reionization than we thought,” says Rachael Livermore, an astronomer at the University of Texas at Austin. She and colleagues report the results in the Feb. 1 Astrophysical Journal.
The team identified the dim galaxies in images taken with the Hubble Space Telescope while it was pointed at two closer clusters of galaxies. Those clusters act as a gravitational lens, brightening and magnifying the light of fainter objects much farther away. Subtracting the clusters’ light revealed distant galaxies up to one-tenth as bright as those spotted in previous studies (SN Online: 11/4/15).

Finding such faint galaxies implies that stars can form in much smaller galaxies than models have predicted and that there were enough of these small galaxies to drive reionization almost entirely by themselves. Reionization radically refashioned the universe so that charged atoms instead of neutral ones pervaded space. Understanding that transition may help astronomers explain how stars and galaxies arose in the early universe.

“Such measurements are really challenging to make,” says Brant Robertson, an astronomer at the University of California, Santa Cruz, who was not involved with the study. “They’re really at the forefront of this field, so there are some questions about the techniques the team used to detect these galaxies and determine how bright they actually are.”

A team of astronomers led by Rychard Bouwens of Leiden University in the Netherlands argues in a paper submitted to the Astrophysical Journal and posted October 2 online at arXiv.org that Livermore and colleagues haven’t, in fact, detected galaxies quite as faint as they have claimed. That keeps the door open for other objects, such as black holes accreting matter and spitting out bright light, to have played a part in reionization.

Robertson says the disagreements motivate further work, noting that Livermore and colleagues used a clever approach to spot what appear to be superfaint galaxies in the early universe. Now, the teams will have to see if that technique stands the test of time.

Livermore and colleagues plan to use the technique to search for faint galaxies lensed by other clusters Hubble has observed. Both teams, along with Robertson, are also looking to the October 2018 launch of the James Webb Space Telescope, which should be able to spot even fainter and more distant galaxies, to determine what drove reionization in the early universe.