New analysis boosts case for smaller proton

Editor’s Note: After this article was published, Horbatsch and colleagues discovered an error in their analysis, which weakened the conclusions. The new calculation of the proton radius falls in between the two previous estimates, and therefore does not add much additional support for the smaller proton.

A spat over the size of the proton just got a bit more complicated.

Measurements of the proton’s radius disagree, with one group of scientists saying it’s smaller than the accepted estimate. Now, a new analysis of old data bolsters the case for a small proton. But the result may dash hopes that the discrepancy could point the way to new physics.
Scientists at York University in Toronto and the Autonomous University of Barcelona reanalyzed data from a 2010 electron scattering experiment at the Mainz Microtron in Germany, in which physicists bombarded protons with electrons and observed how the electrons ricocheted. That scattering, under the influence of the protons’ spheres of positive charge, allows scientists to tease out the size of a proton. The updated estimate came up small, the scientists report November 1 on arXiv.org.

“I think it’s not going to be easy for the proponents of a relatively large proton radius to just discuss this away,” says physicist Randolf Pohl of the Max Planck Institute of Quantum Optics in Garching, Germany. “But I’m not convinced that people will accept it.”

Until several years ago, scientists’ various techniques for sizing up the proton were in agreement. Electron scattering studies like the Mainz experiment implied the same size proton as a second technique, which involves studying the energy levels of hydrogen atoms. These estimates indicated that the proton’s radius was about 0.88 quadrillionths of a meter. But in 2010, a new technique caused a kerfuffle. Measurements of the proton radius using muonic hydrogen — a hydrogen atom with its electron replaced by a heavier relative called a muon — pegged the proton to a size 4 percent smaller than the other estimates (SN: 7/31/10, p. 7).

The flaw among the three techniques might seem likely to lie with the one outlier, the muon experiment. But “there’s actually quite a bit of certainty about those results,” says physicist Marko Horbatsch of York University, a coauthor of the new paper. So Horbatsch and colleagues decided to revisit electron scattering instead, using a subset of the data from the Mainz experiment. Horbatsch’s team focused on glancing collisions where the electron altered its course only slightly. Those collisions are the most essential for determining the proton radius. Then the researchers used theoretical calculations to account for effects that occur in more extreme collisions. Their analysis revealed a slightly scaled-down proton.

If the result is reinforced by future electron scattering measurements, the hydrogen atom data that resulted in the larger-sized proton would still require explanation. But it would also mean that the discrepancy won’t lead to new insights about the universe. Under the standard model of particle physics, muons and electrons should be identical except for mass. Physicists had hoped that the black sheep status of the muonic hydrogen experiment indicated something was different about muons. Agreement of the electron scattering and muonic hydrogen experiments eliminates that possible explanation.
The new analysis is “undoubtedly sensible,” says physicist Judith McGovern of the University of Manchester. “I’m a bit surprised no one has done it before. In fact, I’m a bit surprised I haven’t done it before.”

But that doesn’t mean scientists are fully convinced. MIT physicist Jan Bernauer, one of the authors of the original electron scattering result, says he doesn’t think the puzzle will be solved by reanalysis of existing data. “I’m positive that new data are needed.”

In some ways, hawks hunt like humans

A hunter’s gaze betrays its strategy. And looking at what an animal looks at when it’s hunting for prey has revealed foraging patterns in humans, other primates — and now, birds.

Suzanne Amador Kane of Haverford College in Pennsylvania and her colleagues watched archival footage of three raptor species hunting: northern goshawks (Accipiter gentilis), Cooper’s hawks (A. cooperii) and red-tailed hawks (Buteo jamaicensis). They also mounted a video camera to the head of a goshawk to record the bird’s perspective (a technique that’s proved useful in previous studies of attack behavior). The team noted how long birds spent fixating on specific points before giving up, moving their head and, thus, shifting their gaze.

When searching for prey, raptors don’t turn their heads in a predictable pattern. Instead, they appear to scan and fixate randomly based on what they see in their environment, Kane and her colleagues report November 16 in The Auk. In primates, a buildup of sensory information drives foraging animals to move their eyes in similar patterns.

Though the new study only examines three species and focuses on head tracking rather than eye tracking, Kane and her colleagues suggest that the same basic neural processes may drive search decisions of human and hawk hunters.

Cretaceous bird find holds new color clue

A 130-million-year-old bird holds a clue to ancient color that has never before been shown in a fossil.

Eoconfuciusornis’ feathers contain not only microscopic pigment pods called melanosomes, but also evidence of beta-keratin, a protein in the stringy matrix that surrounds melanosomes, Mary Schweitzer and colleagues report November 21 in the Proceedings of the National Academy of Sciences.

Together, these clues could strengthen the case for inferring color from dinosaur fossils, a subject of debate for years (SN: 11/26/16, p. 24). Schweitzer, a paleontologist at North Carolina State University in Raleigh, has long pointed out that the microscopic orbs that some scientists claim are melanosomes may actually be microbes. The two look similar, but they have some key differences. Microbes aren’t enmeshed in keratin, for one.

In Eoconfuciusornis’ feathers, Schweitzer and colleagues found round, 3-D structures visible with the aid of an electron microscope. And a molecular analysis revealed bundles of skinny fibers, like the filaments of beta-keratin in modern feathers. The authors don’t speculate on the bird’s color, but they do offer a new way to support claims for ancient pigments.

“Identifying keratin is key to ruling out a microbial source for microbodies identified in fossils,” they write.

Ice gave Pluto a heavy heart

Pluto’s heart might carry a heavy burden.

Weight from massive deposits of frozen nitrogen, methane and carbon monoxide, built up billions of years ago, could have carved out the left half of the dwarf planet’s heart-shaped landscape, researchers report online November 30 in Nature.

The roughly 1,000-kilometer-wide frozen basin dubbed Sputnik Planitia was on display when the New Horizons spacecraft tore past in July 2015 (SN: 12/26/15, p. 16). Previous studies have proposed that the region could be a scar left by an impact with interplanetary debris (SN: 12/12/15, p. 10).

Sputnik Planitia sits in a cold zone, a prime location for ice to build up, planetary scientist Douglas Hamilton of the University of Maryland in College Park and colleagues calculate. Excess ice deposited early in the planet’s history would have led to a surplus of mass. Gravitational interactions between Pluto and its largest moon, Charon, slowed the planet’s rotation until that mass faced in the opposite direction from Charon. Once Charon became synced to Pluto’s rotation — it’s always over the same spot on Pluto — gravity would have held Sputnik Planitia in Pluto’s cold zone, attracting even more ice. As the ice cap grew, the weight could have depressed Pluto’s surface, creating the basin that exists today.

Gut microbe mix may spark Parkinson’s

For clues to Parkinson’s brain symptoms, a gut check is in order.

Intestinal microbes send signals that set off the disease’s characteristic brain inflammation and motor problems in mice, researchers report December 1 in Cell. Doctors might someday be able to treat Parkinson’s by fixing this bacterial imbalance.

“It’s quite an exciting piece of work,” says John Cryan, a neuroscientist at University College Cork in Ireland who wasn’t involved in the study. “The relationship between the brain and gut for Parkinson’s has been bubbling up for many years.” The new research, he says, “brings the microbiome really into the forefront for the first time.”
Parkinson’s affects more than 10 million people worldwide, and roughly 70 percent of those patients also have gastrointestinal issues like constipation. Sometimes the GI symptoms show up years before the muscle weakness and other neurological problems. Several recent studies in humans have suggested a link between gut microbes and Parkinson’s. But it wasn’t clear whether intestinal microbes were actually causing the disease, says study coauthor Sarkis Mazmanian, a microbiologist at Caltech. “What our study adds is a functional, mechanistic role for the microbiome.”

Mazmanian’s team studied mice that produced too much alpha-synuclein, the protein that’s believed to cause Parkinson’s when it clumps in the brain. Mice with extra alpha-synuclein acted like they had Parkinson’s: They traversed a narrow beam more slowly, they couldn’t grip as well to a pole and they struggled to pull stickers off their noses. Their brains showed signs of inflammation, too. But when the researchers raised the same type of mice to be germ-free —that is, to not have any gut microbes — the animals acted less sick.

Those mice were still producing boatloads of alpha-synuclein, but the protein wasn’t clumping in their brains. And without the clumps, the mice didn’t have the unsteady gait and muscle weakness typical of Parkinson’s.

In another experiment, the researchers transferred gut microbes from Parkinson’s patients into germ-free mice making too much alpha-synuclein. Those mice developed motor problems when tested 6 or 7 weeks after the transfer, but mice who got microbes from healthy humans were fine.

“Even though the mice that received the healthy microbiota received hundreds of bacteria, they didn’t get the disease,” says Mazmanian. That suggests it’s not the presence or absence of bacteria that triggers Parkinson’s, but the specific composition of the microbial cocktail.
Alpha-synuclein clumps can move from the gut to the brain, a recent study showed. Now, it seems that gut bacteria themselves are also sending important signals.

Researchers are now trying to figure out which signals — and which microbes —are throwing off the balance.

Fecal samples from the mice implanted with bacteria from Parkinson’s patients had higher than normal levels of certain intestinal bacteria. That could be sparking symptoms, says Caltech microbiologist Tim Sampson, who also worked on the study. “I’m interested in trying to understand if there are potential pathogenic microbes that might be individually driving the disease,” he says. “Once we’ve figured that out we’ll be able to understand whether we can remove that group of organisms or block them.”

Abnormally low levels of other bacteria could also factor in. The analyses aren’t large enough to firmly conclude which microbes are particularly important players. But if scientists can figure out what those missing beneficial bacteria are, Mazmanian says, targeted probiotic therapy might be a treatment option in the future.

Aging-associated diseases like Parkinson’s are tricky to study in mice, cautions Stanford University microbiologist Justin Sonnenburg. “They’re typically the result of decades of accumulations of problems,” whereas the mice in the current study were just a couple months old. So the findings will need to be validated in human studies before influencing treatments. Still, he says, “it’s a really important contribution to the growing list of ways that gut microbes can alter our health.”

Year in review: Zika virus devastates Brazil and spreads fear across Americas

A Brazilian mother cradles her baby girl under a bruised purple sky. The baby’s face is scrunched up, mouth open wide — like any other crying child. But her head is smaller than normal, as if her skull has collapsed above her eyebrows.

A week earlier, not far away, a doctor wrapped a measuring tape around the forehead of a 1-month-old boy, held in the arms of his grandmother. This baby too has a shrunken head, a birth defect whose name — microcephaly — has now become seared into the public consciousness.
These images and many more told a harrowing story that case reports alone couldn’t convey: A little-known mosquito-borne virus called Zika appeared to be taking a terrible toll on women and babies, and their families. The world got a gut-wrenching view of microcephaly in 2016, along with a mountain of evidence convincing scientists that Zika bears much of the blame for the dramatic increase in cases.

“Once you’ve seen those pictures from Brazil, you realize what a huge impact this kind of outbreak can have,” says Sonja Rasmussen, a pediatrician at the U.S. Centers for Disease Control and Prevention in Atlanta. Brazil logged its first cases of Zika in 2015, but infections there peaked this spring with perhaps up to 8,000 new infections per week. The virus crept northward and infiltrated many more countries including Panama, Haiti and Mexico. Now, the threat has come to the United States: Cases have been reported in every state except Alaska. They stem mostly from travelers infected abroad, but the virus has staked out new territory in Puerto Rico, the U.S. Virgin Islands, American Samoa and Florida.

As of December 1, Puerto Rico had reported more than 34,000 people with Zika infections. More than 2,700 are pregnant women. And elsewhere in the United States, the CDC has reported well over 4,000 laboratory-confirmed cases of Zika. In these places and others, the images from Brazil have filled expectant mothers (and anyone considering having kids) with uncertainty and fear. “It’s really scary to be pregnant right now,” Rasmussen says. “We don’t know what to tell women.”
The threat to unborn babies wasn’t clear when Zika first hit Brazil, or in earlier, smaller outbreaks on Yap Island in the western Pacific and in French Polynesia. In fact, before 2016, not much was known about the virus at all. The majority of people infected don’t show any symptoms. But in the last year, scientists have thrown themselves at Zika, publishing more than 1,500 papers on different facets of the virus, from what species of mosquito it hides in to what cells it invades.

“We’re learning something new every day,” says obstetrician/gynecologist Catherine Spong, deputy director of the National Institute of Child Health and Human Development in Bethesda, Md.

The studies have scrubbed away some of Zika’s mystery — in particular, what the virus does in the womb. Scientists have found traces of Zika in the brains of human fetuses and confirmed that the virus can infect and kill brain cells in the lab. “This is the year that people became convinced that this mosquito-borne virus could cause birth defects,” Rasmussen says.

Though there was no smoking gun — no single piece of evidence that clinched Zika as the culprit — little clues began adding up, beginning with the conspicuous timing of Brazil’s microcephaly upsurge (SN: 4/2/16, p. 26). In January the CDC first issued a warning to pregnant women to postpone travel to Zika-affected regions. On April 13, a day that may be forever etched into Rasmussen’s memory, she and colleagues reported “a causal relationship” between Zika and microcephaly, along with other birth defects, in a study published online in the New England Journal of Medicine. Since then, Rasmussen says, “The data have become absolutely overwhelming.”
In May, a mouse study offered the first direct proof in animals that in utero Zika infection can lead to microcephaly (SN Online: 5/11/16). In September, researchers reported that a pregnant pigtailed macaque infected with Zika in the third trimester then gave birth to a baby whose brain had stopped growing. In human babies, the range of disorders linked to Zika has ballooned to include problems with the eyes, ears and joints, as well as seizures and extreme irritability (SN: 10/29/16, p. 14). At a workshop in North Bethesda, Md., this fall, a room crowded with doctors and scientists watched videos of inconsolable infants jerking erratically, arms and legs unnaturally stiff. “Heartbreaking,” Rasmussen says.

In December, researchers reported a surge in babies with microcephaly in Colombia (SN Online: 12/9/16), further evidence for Zika’s role in birth defects.

Zika isn’t the first virus to harm babies in the womb. Cytomegalovirus can also cause microcephaly, for example, and rubella, known as “German measles,” can leave babies with hearing, vision and heart problems. Even among these viruses, though, Zika stands out. “It’s such a precedent-setting thing,” Rasmussen says. “Never before has there been a mosquito-borne virus known to cause birth defects.”

Despite what scientists have learned in 2016, there’s little consolation for families already affected by microcephaly. And huge questions remain for expectant mothers. In particular, says Spong, it’s not clear just how risky Zika infection during pregnancy really is. One study published in the New England Journal of Medicine in July estimated that the risk of bearing a child with microcephaly increases to somewhere between 1 and 13 percent for women infected in their first trimester.

Spong hopes that a new study will clarify things. It’s called the Zika in Infants and Pregnancy Cohort Study, or ZIP, and the plan is to enroll 10,000 women in their first trimester. They’ll come from Puerto Rico, as well as Brazil and other countries, Spong says, and include both infected and uninfected women.

Tracking these women through pregnancy, birth and their baby’s first year of life could fill in some answers, like whether an infected pregnant woman who doesn’t have symptoms is better off than one who does. It’s also possible that some type of cofactor, like environmental toxins or other infections, is working with Zika to cause birth defects.

“You’re supposed to avoid stress when you’re pregnant,” Rasmussen says. “How do you avoid stress when you’re thinking that your baby could have these problems related to Zika?”

In the best-case scenario, a Zika vaccine could still be a few years away. And though infection rates may be winding down in some places, in areas with seasonally high temperatures and rainfall, such as Puerto Rico, Zika could become a local fixture. Still, any scrap of new information might help. Results from ZIP and other studies won’t erase the damage, but they could offer a pinprick of light following a year darkened by disease.

Dawn spacecraft maps water beneath the surface of Ceres

Water ice lies just beneath the cratered surface of dwarf planet Ceres and in shadowy pockets within those craters, new studies report. Observations from NASA’s Dawn spacecraft add to the growing body of evidence that Ceres, the largest object in the asteroid belt between the orbits of Mars and Jupiter, has held on to a considerable amount of water for billions of years.

“We’ve seen ice in different contexts throughout the solar system,” says Thomas Prettyman, a planetary scientist at the Planetary Science Institute in Tucson and coauthor of one of the studies, published online December 15 in Science. “Now we see the same thing on Ceres.” Ice accumulates in craters on Mercury and the moon, an icy layer sits below the surface of Mars, and water ice slathers the landscape of several moons of the outer planets. Each new sighting of H2O contributes to the story of how the solar system formed and how water was delivered to a young Earth.
A layer of ice mixed with rock sits within about one meter of the surface concentrated near the poles, Prettyman and colleagues report. And images of inside some craters around the polar regions, from spots that never see sunlight, show bright patches, at least one of which is made of water ice, a separate team reports online December 15 in Nature Astronomy.

“Ceres was always believed to contain lots of water ice,” says Michael Küppers, a planetary scientist at the European Space Astronomy Center in Madrid, who was not involved with either study. Its overall density is lower than pure rock, implying that some low-density material such as ice is mixed in. The Herschel Space Observatory has seen water vapor escaping from the dwarf planet (SN Online: 1/22/14), and the Dawn probe, in orbit around Ceres since 2015, spied a patch of water ice in Oxo crater, though the amount of direct sunlight there implies the ice has survived for only dozens of years (SN Online: 9/1/16). The spacecraft has also found minerals on the surface that formed in the presence of water.

But researchers would like to know where Ceres’ water is. Knowing whether it is blended throughout the interior or segregated from the rock could help piece together the story of where Ceres formed and how the tiny world was put together. That, in turn, could provide insight into how diverse the worlds around other stars might be.

To map the subsurface ice, Prettyman and colleagues used a neutron and gamma-ray detector onboard Dawn. As Ceres is bombarded with cosmic rays — highly energetic particles that originate outside the solar system — atoms in the dwarf planet spray out neutrons. The amount and energy of the neutrons can provide a clue to the abundance of hydrogen, presumably locked up in water molecules and hydrated minerals.

Finding patches of ice was a bit more straightforward. Planetary scientist Thomas Platz and colleagues pinpointed permanently shadowed spots on Ceres, typically in crater floors near the north and south poles. The team then scoured images of those locations for bright patches. Out of the more than 600 darkened craters they identified, the researchers found 10 with bright deposits that could be surface ice. One had a chunk sticking out into just enough sunlight for Dawn to measure the spectrum of the reflected light and detect signs of water.
Water vapor escaping from inside the dwarf planet likely falls back to Ceres, where some of it gets trapped in these cold spots, says Platz, of the Max Planck Institute for Solar System Research in Göttingen, Germany.

Just because there is water doesn’t mean Ceres is a good place for life to take hold. Temperatures in the shadows don’t get above –216° Celsius. “It’s pretty cold, there’s no sunlight. We don’t think that’s a habitable environment,” Platz says. Although, he adds, “one could mine for future missions to get fuel.”

Ceres is now the third major heavily cratered body, along with Mercury and the moon, with permanently shadowed regions where ice builds up. “All the ones we’ve got info on to test this show you’ve accumulated something,” says Peter Thomas, a planetary scientist at Cornell University, who is not a part of either research team. Those details improve researchers’ understanding of how water interacts with a variety of planetary environments.

How scientists are hunting for a safer opioid painkiller

An opioid epidemic is upon us. Prescription painkillers such as fentanyl and morphine can ease terrible pain, but they can also cause addiction and death. The Centers for Disease Control and Prevention estimates that nearly 2 million Americans are abusing or addicted to prescription opiates. Politicians are attempting to stem the tide at state and national levels, with bills to change and monitor how physicians prescribe painkillers and to increase access to addiction treatment programs.

Those efforts may make access to painkillers more difficult for some. But pain comes to everyone eventually, and opioids are one of the best ways to make it go away.

Morphine is the king of pain treatment. “For hundreds of years people have used morphine,” says Lakshmi Devi, a pharmacologist at the Ichan School of Medicine Mount Sinai in New York City. “It works, it’s a good drug, that’s why we want it. The problem is the bad stuff.”

The “bad stuff” includes tolerance — patients have to take higher and higher doses to relieve their pain. Drugs such as morphine depress breathing, an effect that can prove deadly. They also cause constipation, drowsiness and vomiting. But “for certain types of pain, there are no medications that are as effective,” says Bryan Roth, a pharmacologist and physician at the University of North Carolina at Chapel Hill. The trick is constructing a drug with all the benefits of an opioid painkiller, and few to none of the side effects. Here are three ways that scientists are searching for the next big pain buster, and three of the chemicals they’ve turned up.

Raid the chemical library
To find new options for promising drugs, scientists often look to chemical libraries of known molecules. “A pharmaceutical company will have libraries of a few million compounds,” Roth explains. Researchers comb through these libraries trying to find those compounds that connect to specific molecules in the body and brain.

When drugs such as morphine enter the brain, they bind to receptors on the outside of cells and cause cascades of chemical activity inside. Opiate drugs bind to three types of opiate receptors: mu, kappa and delta. The mu receptor type is the one associated with the pain-killing — and pleasure-causing — activities of opiates. Activation of this receptor type spawns two cascades of chemical activity. One, the Gi pathway, is associated with pain relief. The other — known as the beta-arrestin pathway — is associated with slowed breathing rate and constipation. So a winning candidate molecule would be one that triggered only the Gi pathway, without triggering beta-arrestin.
Roth and colleagues set out to find a molecule that fit those specifications. But instead of the intense, months-long process of experimentally screening molecules in a chemical library, Roth’s group chose a computational approach, screening more than 3 million compounds in a matter of days. The screen narrowed the candidates down to 23 molecules to test the old fashioned way — both chemically and in mice. Each of these potential painkillers went through even more tests to find those with the strongest bond to the receptor and the highest potency.

In the end, the team focused on a chemical called PMZ21. It activates only the pathway associated with pain relief, and is an effective painkiller in mice. It does not depress breathing rate, and it might even avoid some of the addictive potential of other opiates, though Roth notes that further studies need to be done. He and his colleagues published their findings September 8 in Nature.

Letting the computer handle the initial screen is “a smart way of going about it,” notes Nathanial Jeske, a neuropharmacologist at the University of Texas Health Science Center in San Antonio. But mice are only the first step. “I’m interested to see if the efficacy applies to different animals.”

Making an opiate 2.0
Screening millions of compounds is one way to find a new drug. But why buy new when you can give a chemical makeover to something you already have? This is a “standard medicinal chemistry approach,” Roth says: “Pick a known drug and make analogs [slightly tweaked structures], and that can work.”

That was the approach that Mei-Chuan Ko and his group at Wake Forest University School of Medicine in Winston-Salem, N.C., decided to take with the common opioid painkiller buprenorphine. “Compared to morphine or fentanyl, buprenorphine is safer,” Ko explains, “but it has abuse liability. Physicians still have concerns about the abuse and won’t prescribe it.” Buprenorphine is what’s called a partial agonist at the mu receptor — it can’t fully activate the receptor, even at the highest doses. So it’s an effective painkiller that is harder to overdose on — so much so that it’s used to treat addiction to other opiates. But it can still cause a high, so doctors still worry about people abusing the drug.

So to make a version of buprenorphine with lower addictive potential, Ko and his colleagues focused on a chemical known as BU08028. It’s structurally similar to buprenorphine, but it also hits another type of opioid receptor called the nociceptin-orphanin FQ peptide (or NOP) receptor.

The NOP receptor is not a traditional target. This is partially because its effect in rodents — usually the first recipients of a new drug — is “complicated,” says Ko. “It does kill pain at high doses but not at low doses.” In primates, however, it’s another matter. In tests in four monkeys, BU08028 killed pain effectively at low doses and didn’t suppress breathing. The monkeys also showed little interest in taking the drug voluntarily, which suggests it might not be as addictive as classic opioid drugs. Ko and his colleagues published their results in the Sept. 13 Proceedings of the National Academy of Sciences.*

Off the beaten path
Combing through chemical libraries or tweaking drugs that are already on the market takes advantage of systems that are already well-established. But sometimes, a tough question requires an entirely new approach. “You can either target the receptors you know and love … or you can do the complete opposite and see if there’s a new receptor system,” Devi says.

Jeske and his group chose the latter option. Of the three opiate receptor types — mu, kappa and delta — most drugs (and drug studies) focus on the mu receptor. Jeske’s group chose to investigate delta instead. They were especially interested in targeting delta receptors in the body — far away from the brain and its side effects.

The delta receptor has an unfortunate quirk. When activated by a drug, it can help kill pain. But most of the time, it can’t be activated at all. The receptor is protected — bound up tight by another molecule — and only released when an area is injured. So Jeske’s goal was to find out what was binding up the delta receptor, and figure out how to get rid of it.

Working in rat neurons, Jeske and his group found that when a molecule called GRK2 was around, the delta receptor was inactive. “Knock down GRK2 and the receptor works just fine,” Jeske says. By genetically knocking out GRK2 in rats, Jeske and his group left the delta receptor free to respond to a drug — and to prevent pain. The group published their results September 6 in Cell Reports.

It’s “a completely new target and that’s great,” says Devi. “But that new target with a drug is a tall order.” A single drug is unlikely to be able to both push away GRK2 and then activate the delta receptor to stop pain.

Jeske agrees that a single molecule probably couldn’t take on both roles. Instead, one drug to get rid of GRK2 would be given first, followed by another to activate the delta receptors.

Each drug development method has unearthed drug candidates with early promise. “We’ve solved these problems in mice and rats many times,” Devi notes. But whether sifting through libraries, tweaking older drugs or coming up with entirely new ones, the journey to the clinic has only just begun.

*Paul Czoty and Michael Nader, two authors on the PNAS paper, were on my Ph.D. dissertation committee. I have had neither direct nor indirect involvement with this research.

These acorn worms have a head for swimming

Certain marine worms spend their larval phase as little more than a tiny, transparent “swimming head.” A new study explores the genes involved in that headfirst approach to life.

A mud flat in Morro Bay, Calif., is the only known place where this one species of acorn worm, Schizocardium californicum, is found. After digging up the creatures, Paul Gonzalez, an evolutionary developmental biologist at Stanford University, raised hordes of the larvae at Stanford’s Hopkins Marine Station in Pacific Grove, Calif.
Because a larva and an adult worm look so different, scientists wondered if the same genes and molecular machinery were involved in both phases of development. To find out, Gonzalez and colleagues analyzed the worm’s genetic blueprint during each phase, they report online December 8 in Current Biology.

Genes linked to trunk development were switched off during the larval phase until just before metamorphosis. Instead, most of the genes switched on were associated with head development, Gonzalez says.

The larvae hatch from eggs laid on the mud. When tides flood the area, the squishy, gel-filled animals use hairlike cilia to swim upwards to devour bits of algae. “They’re feeding machines,” Gonzalez says. He speculates that being balloon-shaped noggins, rather than wriggling noodles, may help the organisms float and feed more efficiently.

After about two months of gorging at the algae buffet, the larvae, which grow to roughly 2 millimeters across, transform and sink back into the muck. There, they eventually grow a body that can stretch up to about 40 centimeters.

Evidence falls into place for once and future supercontinents

Look at any map of the Atlantic Ocean, and you might feel the urge to slide South America and Africa together. The two continents just beg to nestle next to each other, with Brazil’s bulge locking into West Africa’s dimple. That visible clue, along with several others, prompted Alfred Wegener to propose over a century ago that the continents had once been joined in a single enormous landmass. He called it Pangaea, or “all lands.”

Today, geologists know that Pangaea was just the most recent in a series of mighty super-continents. Over hundreds of millions of years, enormous plates of Earth’s crust have drifted together and then apart. Pangaea ruled from roughly 400 million to about 200 million years ago. But wind the clock further back, and other supercontinents emerge. Between 1.3 billion and 750 million years ago, all the continents amassed in a great land known as Rodinia. Go back even further, about 1.4 billion years or more, and the crustal shards had arranged themselves into a supercontinent called Nuna.

Using powerful computer programs and geologic clues from rocks around the world, researchers are painting a picture of these long-lost worlds. New studies of magnetic minerals in rock from Brazil, for instance, are helping pin the ancient Amazon to a spot it once occupied in Nuna. Other recent research reveals the geologic stresses that finally pulled Rodinia apart, some 750 million years ago. Scientists have even predicted the formation of the next supercontinent — an amalgam of North America and Asia, evocatively named Amasia — some 250 million years from now.
Reconstructing supercontinents is like trying to assemble a 1,000-piece jigsaw puzzle after you’ve lost a bunch of the pieces and your dog has chewed up others. Still, by figuring out which puzzle pieces went where, geologists have been able to illuminate some of earth science’s most fundamental questions.
For one thing, continental drift, that gradual movement of landmasses across Earth’s surface, profoundly affected life by allowing species to move into different parts of the world depending on what particular landmasses happened to be joined. (The global distribution of dinosaur fossils is dictated by how continents were assembled when those great animals roamed.)

Supercontinents can also help geologists hunting for mineral deposits — imagine discovering gold ore of a certain age in the Amazon and using it to find another gold deposit in a distant landmass that was once joined to the Amazon. More broadly, shifting landmasses have reshaped the face of the planet — as they form, supercontinents push up mountains like the Appalachians, and as they break apart, they create oceans like the Atlantic.

“The assembly and breakup of these continents have profoundly influenced the evolution of the whole Earth,” says Johanna Salminen, a geophysicist at the University of Helsinki in Finland.
Push or pull
For centuries, geologists, biogeographers and explorers have tried to explain various features of the natural world by invoking lost continents. Some of the wilder concepts included Lemuria, a sunken realm between Madagascar and India that offered an out-there rationale for the presence of lemurs and lemurlike fossils in both places, and Mu, an underwater land supposedly described in ancient Mayan manuscripts. While those fantastic notions have fallen out of favor, scientists are exploring the equally mind-bending story of the supercontinents that actually existed.
Earth’s constantly shifting jigsaw puzzle of continents and oceans traces back to the fundamental forces of plate tectonics. The story begins in the centers of oceans, where hot molten rock wells up from deep inside the Earth along underwater mountain chains. The lava cools and solidifies into newborn ocean crust, which moves continually away from either side of the mountain ridge as if carried outward on a conveyor belt. Eventually, the moving ocean crust bumps into a continent, where it either stalls or begins diving beneath that continental crust in a process called subduction.

Those competing forces — pushing newborn crust away from the mid-ocean mountains and pulling older crust down through subduction — are constantly rearranging Earth’s crustal plates. That’s why North America and Europe are getting farther away from each other by a few centimeters each year as the Atlantic widens, and why the Pacific Ocean is shrinking, its seafloor sucked down by subduction along the Ring of Fire — looping from New Zealand to Japan, Alaska and Chile.

By running the process backward in time, geologists can begin to see how oceans and continents have jockeyed for position over millions of years. Computers calculate how plate positions shifted over time, based on the movements of today’s plates as well as geologic data that hint at their past locations.

Those geologic clues — such as magnetic minerals in ancient rocks — are few and far between. But enough remain for researchers to start to cobble together the story of which crustal piece went where.

“To solve a jigsaw puzzle, you don’t necessarily need 100 percent of the pieces before you can look at it and say it’s the Mona Lisa,” says Brendan Murphy, a geophysicist at St. Francis Xavier University in Antigonish, Nova Scotia. “But you need some key pieces.” He adds: “With the eyes and nose, you have a chance.”

No place like Nuna
For ancient Nuna, scientists are starting to find the first of those key pieces. They may not reveal the Mona Lisa’s enigmatic smile, but they are at least starting to fill in a portrait of a long-vanished supercontinent.

Nuna came together starting around 2 billion years ago, with its heart a mash-up of Baltica (the landmass that today contains Scandinavia), Laurentia (which is now much of North America) and Siberia. Geologists argue over many things involving this first supercontinent, starting with its name. “Nuna” is from the Inuktitut language of the Arctic. It means lands bordering the northern oceans, so dubbed for the supercontinent’s Arctic-fringing components. But some researchers prefer to call it Columbia after the Columbia region of North America’s Pacific Northwest.

Whatever its moniker, Nuna/Columbia is an exercise in trying to get all the puzzle pieces to fit. Because Nuna existed so long ago, subduction has recycled many rocks of that age back into the deep Earth, erasing any record of what they were doing at the time. Geologists travel to rocks that remain in places like India, South America and North China, analyzing them for clues to where they were at the time of Nuna.

One of the most promising techniques targets magnetic minerals. Paleomagnetic studies use the minerals as tiny time capsule compasses, which recorded the direction of the magnetic field at the time the rocks formed. The minerals can reveal information about where those rocks used to be, including their latitude relative to where the Earth’s north magnetic pole was at the time.

Salminen has been gathering paleomagnetic data from Nuna-age rocks in Brazil and western Africa. Not surprisingly, given their current lock-and-key configuration, these two chunks were once united as a single ancient continental block, known as the Congo/São Francisco craton. For millions of years, it shuffled around as a single geologic unit, occasionally merging with other blocks and then later splitting away.

Salminen has now figured out where the Congo/São Francisco puzzle piece fit in the jigsaw that made up Nuna. In 1.5-billion-year-old rocks in Brazil, she unearthed magnetic clues that placed the Congo/São Francisco craton at the southeastern tip of Baltica all those years ago. She and her colleagues reported the findings in November in Precambrian Research.

It is the first time scientists have gotten paleomagnetic information about where the craton may have been as far back as Nuna. “This is quite remarkable — it was really needed,” she says. “Now we can say Congo could have been there.” Like building out a jigsaw puzzle from its center, the work essentially expands Nuna’s core.

Rodinia’s radioactive decay
By around 1.3 billion years ago, Nuna was breaking apart, the pieces of the Mona Lisa face shattering and drifting away from each other. It took another 200 million years before they rejoined in the configuration known as Rodinia.

Recent research suggests that Rodinia may not have looked much different than Nuna, though. The Mona Lisa in its second incarnation may still have looked like the portrait of a woman — just maybe with a set of earrings dangling from her lobes.
of Carleton University in Ottawa, Canada, recently explored the relative positions of Laurentia and Siberia between 1.9 billion and 720 million years ago, a period that spans both Nuna and Rodinia. Ernst’s group specializes in studying “large igneous provinces” — the huge outpourings of lava that build up over millions of years. Often the molten rock flows along sheetlike structures known as dikes, which funnel magma from deep in the Earth upward.

By using the radioactive decay of elements in the dike rock, such as uranium decaying to lead, scientists can precisely date when a dike formed. With enough dates on a particular dike, researchers can produce a sort of bar code that is unique to each dike. Later, when the dikes are broken apart and shifted over time, geologists can pinpoint the bar codes that match and thus line up parts of the crust that used to be together.

Ernst’s team found that dikes from Laurentia and Siberia matched during four periods between 1.87 billion and 720 million years ago — suggesting they were connected for that entire span, the team reported in June in Nature Geoscience. Such a long-term relationship suggests that Siberia and Laurentia may have stuck together through the Nuna-Rodinia transition, Ernst says.

Other parts of the puzzle tend to end up in the same relative locations as well, says Joseph Meert, a paleomagnetist at the University of Florida in Gainesville. In each supercontinent, Laurentia, Siberia and Baltica knit themselves together in roughly the same arrangement: Siberia and Baltica nestle like two opposing knobs on one end of Laurentia’s elongated blob. Meert calls these three continental fragments “strange attractors,” since they appear conjoined time after time.

It’s the outer edges of the jigsaw puzzle that change. Fragments like north China and southern Africa end up in different locations around the supercontinent core. “I call those bits the lonely wanderers,” Meert says.

Getting to know Pangaea
While some puzzle-makers try to sort out the reconstructions of past supercontinents, other geologists are exploring deeper questions about why big landmasses come together in the first place. And one place to look is Pangaea.

“Most people would accept what Pangaea looks like,” Murphy says. “But as soon as you start asking why it formed, how it formed and what processes are involved — then all of a sudden you run into problems.”
Around 550 million years ago, subduction zones around the edges of an ancient ocean began dragging that oceanic crust under continental crust. But around 400 million years ago, that subduction suddenly stopped. In a major shift, a different, much younger seafloor began to subduct instead beneath the continents. That young ocean crust kept getting sucked up until it all disappeared, and the continents were left merged in the giant mass of Pangaea.

Imagine in today’s world, if the Pacific stopped shrinking and all of a sudden the Atlantic started shrinking instead. “That’s quite a significant problem,” Murphy says. In unpublished work, he has been exploring the physics of how plates of oceanic and continental crust — which have different densities, buoyancies and other physical characteristics — could have interacted with one another in the run-up to Pangaea.

Supercontinent breakups are similarly complicated. Once all the land amasses in a single big chunk, it cannot stay together forever. In one scenario, its sheer bulk acts as an electric blanket, allowing heat from the deep Earth to pond up beneath it until things get too hot and the supercontinent splinters (SN: 1/21/17, p. 14). In another, physical stressors pull the supercontinent apart.

Peter Cawood, a geologist at the University of St. Andrews in Fife, Scotland, likes the second option. He has been studying mountain ranges that arose when the crustal plates that made up Rodinia collided, pushing up soaring peaks where they met. These include the Grenville mountain-building event of about 1 billion years ago, traces of which linger today in the eroded peaks of the Appalachians. Cawood and his colleagues analyzed the times at which such mountains appeared and put together a detailed timeline of what happened as Rodinia began to break apart.

They note that crustal plates began subducting around the edges of Rodinia right around the time of its breakup. That sucking down of crust caused the supercontinent to be pulled from all directions and eventually break apart, Cawood and his colleagues wrote in Earth and Planetary Science Letters in September. “The timing of major breakup corresponds with this timing of opposing subduction zones,” he says.
The future is Amasia
That stressful situation is similar to what the Pacific Ocean finds itself in today. Because it is flanked by subduction zones around the Ring of Fire, the Pacific Plate is shrinking over time. Some geologists predict that it will vanish entirely in the future, leaving North America and Asia to merge into the next supercontinent, Amasia. Others have devised different possible paths to Amasia, such as closing the Arctic Ocean rather than the Pacific.

“Speculation about the future supercontinent Amasia is exactly that, speculation,” says geologist Ross Mitchell of Curtin University in Perth, Australia, who in 2012 helped describe the mechanics of how Amasia might arise. “But there’s hard science behind the conjecture.”

For instance, Masaki Yoshida of the Japan Agency for Marine-Earth Science and Technology in Yokosuka recently used sophisticated computer models to analyze how today’s continents would continue to move atop the flowing heat of the deep Earth. He combined modern-day plate motions with information on how that internal planetary heat churns in three dimensions, then ran the whole scenario into the future. In a paper in the September Geology, Yoshida describes how North America, Eurasia, Australia and Africa will end up merged in the Northern Hemisphere.

No matter where the continents are headed, they are destined to reassemble. Plate tectonics says it will happen — and a new supercontinent will shape the face of the Earth. It might not look like the Mona Lisa, but it might just be another masterpiece.