After a year caring for patients at the heart of Brazil’s Zika epidemic, pediatric neurologist Vanessa van der Linden has seen some of the worst cases.

She was one of the first researchers to link Zika virus to microcephaly, a now well-known birth defect marked by a small, misshapen head and, sometimes, a forehead that slopes backward. Babies with the defect can have other symptoms, too: Van der Linden has seen 24-hour crying bouts, spasms, extreme irritability and difficulty swallowing.
But microcephaly is just the tip of the Zika iceberg, she said September 22 at a workshop hosted by the National Institutes of Health in North Bethesda, Md. That’s something public health officials have been warning about for months. Now, scientists have begun to describe a head-to-toe assortment of health problems linked to Zika virus infection in utero; they’re calling it congenital Zika syndrome.

Still, the full scope of the problem, including the threat of more subtle neurologic disorders such as learning disabilities or developmental delays, remains murky, says Peter Hotez, a pediatrician and microbiologist at Baylor College of Medicine in Houston.

“That’s the big unknown: There’s probably a spectrum of illness,” similar to autism, he says. And it could take years for scientists to sort it all out.

It’s a problem that Brazil is facing now, and one that Puerto Rico has just begun grappling with.

As of September 23, the U.S. territory had reported 22,358 confirmed cases of Zika infection. Of these cases, 1,871 are pregnant women. Carmen Zorrilla, an obstetrician-gynecologist at the University of Puerto Rico’s Maternal-Infant Studies Center who has examined some of these women and their babies, emphasizes the importance of following up on all babies exposed to Zika in the womb — even those without apparent birth defects.
“Even if they are born normal,” she said, “it doesn’t mean they’ll be OK.”

Insidious problems
At the workshop, Zorrilla described the case of one of the first Puerto Rican babies born to a mother diagnosed with Zika. The baby didn’t have microcephaly, but she did have another unusual problem: She couldn’t open her eyes. A bad case of conjunctivitis (pinkeye) left her needing help opening her eyelids every morning — even 27 days after birth.
Zorrilla can’t say for sure whether the problem was related to Zika, but “it really concerned me,” she said. “This is the first baby I’ve seen with conjunctivitis that lasted for so long.”

The case may be another clue that Zika’s assaults on the body are widespread. And Zorrilla can expect to see more cases soon. Ultrasound examinations of 228 women in Puerto Rico with confirmed Zika infection have spotted brain abnormalities in 13 fetuses, including one with microcephaly.

Another observation could hint at problems yet to come: Most of the Zika-exposed fetuses tended to have slightly smaller heads than average, although “still within the normal limits,” Zorrilla said. But measurements of leg bones and stomach size indicate that the rest of the body is growing normally. Implications remain unclear, but the findings — preliminary results from Alberto de la Vega, also an obstetrician-gynecologist at the University of Puerto Rico — are the latest in a litany of anomalies linked to Zika.

Long-term problems aren’t unusual in babies infected with a different kind of virus that causes microcephaly. Like Zika, cytomegalovirus can infect babies in the womb. Most CMV-infected babies don’t have any obvious symptoms, but asymptomatic kids may have problems as they grow, including intellectual disabilities, hearing loss or cerebral palsy, researchers suggested in the October Brain and Development.

Beyond microcephaly, scientists have recently described other symptoms linked to Zika infection. In some babies, for example, Zika seems to damage hearing. Of 70 Zika-exposed infants born with microcephaly, 10 percent had some hearing loss, researchers noted in a Sept. 2 report published by the U.S. Centers for Disease Control and Prevention.
Zika can leave a mark on the eyes, too. More than a third of 29 babies with microcephaly had some sort of eye oddity, including mottled pigmenting and withered tissue, researchers reported in May in JAMA Ophthalmology.

Van der Linden has also observed a link between Zika and a deformity called arthrogryposis, where a child’s joints can be stuck in contorted positions — even in babies without microcephaly. The condition might stem from problems with infected babies’ motor neurons, the nerve cells that relay messages from the brain to the muscles, van der Linden and colleagues suggested August 9 in BMJ.

She has even seen babies born with normal head circumferences who later develop microcephaly or other brain defects. One mother, she says, came in five months after giving birth because she thought her baby wasn’t developing normally. Like children with congenital Zika syndrome, the baby’s head scans revealed “the same pattern of brain damage,” van der Linden says. This pattern includes a malformed cerebral cortex, the wrinkled outer layer of the brain, and calcifications, strange lumps of calcium deposited within the tissue.

Infiltrating the brain
Scientists still don’t know exactly how Zika damages the brain, but they have some ideas.

One recent report found that the virus can infiltrate and kill both neuroepithelial stem cells, which give rise to all sorts of brain cells, and radial glial cells, which can generate newborn neurons and help guide them to their proper place in the brain.

Zika also hinders these cells’ ability to split into new cells, Yale University neuroscientist Marco Onorati and colleagues reported September 6 in Cell Reports.
Stem cells at work in the fetal brain eventually give rise to structures responsible for thought and memory and learning, raising concerns of a cascade of problems down the road. “This is a virus that blocks the development of the fetal brain,” Hotez says. “That’s about the worst thing you can possibly imagine.”

And fetuses might not be the only ones at risk, he points out. “Kids in the first years of life also have growing, developing brains,” he says. “What if they get infected with Zika?”

It’s not an easy question to answer. But another disease could offer clues.

Malaria, for example, can cause severe neurological problems. In children, a condition called cerebral malaria may be linked to mental health disorders such as attention-deficit/hyperactivity disorder, antisocial behavior and depression, researchers reported in March in Malaria Journal.

Researchers will also need to watch out for long-term troubles in Zika-exposed babies born with no obvious symptoms, says the CDC’s Sonja Rasmussen. “We don’t want to make families too scared,” she says. “But we do recognize the possibility of later-on seizures or developmental delay.”

Since most people don’t show signs of Zika infection, pinpointing the total number of pregnant women (and babies) exposed to the virus may be impossible.

In the Americas, at least, the number is probably enormous. Tens of thousands of children may eventually suffer some sort of neurologic or psychiatric illness triggered by Zika, Hotez predicted in a paper published in JAMA Pediatrics in August.

Van der Linden can’t say whether the babies she has seen have learning disabilities or psychiatric illnesses, or other more subtle cognitive problems — most of her patients are between 9 months and 1 year old.

But she plans to follow these patients, and the babies who appeared normal at birth, for years. “We need time to better understand the disease,” she says.

Hotez agrees: “It’s going to take a generation of pediatric neurologists and infectious disease experts to figure this out.”

Figuring out the nuts and bolts of the cell’s recycling machinery has earned the 2016 Nobel Prize in physiology or medicine. Cell biologist Yoshinori Ohsumi of the Tokyo Institute of Technology has received the prize for his work on autophagy, a method for breaking down and recycling large pieces of cellular junk, such as clusters of damaged proteins or worn-out organelles.

Keeping this recycling machinery in good working condition is crucial for cells’ health (SN: 3/26/11, p. 18). Not enough recycling can cause cellular trash to build up and lead to neurological diseases such as Alzheimer’s and Parkinson’s. Too much recycling, on the other hand, has been linked to cancer.
“It’s so exciting that Ohsumi has received the Nobel Prize, which he no question deserved,” says biologist Jennifer Lippincott-Schwartz of Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Va. “He set the framework for an entire new field in cell biology.”

Ohsumi‘s discoveries helped reveal the mechanism and significance of a fundamental physiological process, biologist Maria Masucci of the Karolinska Institute in Sweden said in a news briefing October 3. “There is growing hope that this knowledge will lead to the development of new strategies for the treatment of many human diseases.”

Scientists got their first glimpse of autophagy in the 1960s, not long after the discovery of the lysosome, a pouch within cells that acts as a garbage disposal, grinding fats and proteins and sugars into their basic building blocks. (That discovery won Belgian scientist Christian de Duve a share of the Nobel Prize in 1974.) Researchers had observed lysosomes stuffed with big chunks of cellular material — like the bulk waste of the cellular world — as well as another, mysterious pouch that carried the waste to the lysosome.

Somehow, the cell had devised a way to consume large parts of itself. De Duve dubbed the process autophagy, from the Greek words for “self” and “to eat.” But over the next 30 years, little more became known about the process.
“The machinery was unknown, and how the system was working was unknown, and whether or not it was involved in disease was also unknown,” said physiologist Juleen Zierath, also of the Karolinska Institute, in an interview after the prize’s announcement.

That all changed in the 1990s when Ohsumi decided to study autophagy in a single-celled organism called baker’s yeast, microbes known for making bread rise. The process was tricky to catch in action, partly because it happened so fast. So Ohsumi bred special strains of yeast that couldn’t break down proteins in their cellular garbage disposals (called vacuoles in yeast).

“He reasoned that if he could stop the degradation process, he could see an accumulation of the autophagy machinery in these cells,” Zierath said.

And that’s just what Ohsumi saw. When he starved the yeast cells, the “self-eating” machinery kicked into gear (presumably to scrounge up food for the cells). But because the garbage disposals were defective, the machinery piled up in the vacuoles, which swelled like balloons stuffed with sand. Ohsumi could see the bulging, packed bags clearly under a light microscope. He published the work in a 1992 paper in the Journal of Cell Biology.
Finding the autophagy machinery let Ohsumi study it in detail. A year later, he discovered as many as 15 genes needed for the machinery to work. In the following years, Ohsumi and other scientists examined the proteins encoded by these genes and began to figure out how the components of the “bulk waste” bag, or autophagosome, came together, and then fused with the lysosome.

The work revealed something new about the cell’s garbage centers, Zierath said. “Before Ohsumi came on the scene, people understood that the waste dump was in the cell,” she said. “But what he showed was that it wasn’t a waste dump. It was a recycling plant.”

Later, Ohsumi and his colleagues studied autophagy in mammalian cells and realized that the process played a key maintenance role in all kinds of cells, breaking down materials for reuse. Ohsumi “found a pathway that has its counterparts in all cells that have a nucleus,” says 2013 Nobel laureate Randy Schekman, a cell biologist at the University of California, Berkeley. “Virtually every corner of the cell is touched by the autophagic process.”

Since Ohsumi’s discoveries, research on autophagy has exploded, says Lippincott-Schwartz. “It’s an amazing system that every year becomes more and more fascinating.”

Ohsumi, 71, remains an active researcher today. He received the call from the Nobel committee at his lab in Japan. The prize includes an award of 8 million Swedish kronor (equivalent to about $934,000). About his work, he said: “It was lucky. Yeast was a very good system, and autophagy was a very good topic.”

Still, he added in an interview with a Nobel representative, “we have so many questions. Even now we have more questions than when I started.”

A satellite of Saturn joins the club of moons with possible oceans. A subsurface sea of water might hide beneath the icy crust of Dione, one of Saturn’s moons, researchers report online October 9 in Geophysical Research Letters. That puts Dione in good company alongside Enceladus (another moon of Saturn) and several moons of Jupiter, as well as possibly Pluto (SN Online: 9/23/16).

Dione’s ocean is about 100 kilometers below the surface and roughly 65 kilometers deep, Mikael Beuthe, a planetary scientist at the Royal Observatory of Belgium in Brussels, and colleagues report. They inferred the ocean’s presence from measurements of Dione’s gravity made by the Cassini spacecraft.

When babies are ready for solid foods, the meal usually arrives on a spoon. Parents scoop up pureed carrots, liquefied banana or soupy rice cereal and deliver it straight to their baby’s mouth (or forehead). But a different way of introducing solids is gaining ground. Called baby-led weaning, the approach is based on letting the baby feed herself whole foods such as a soft pear or a spear of cooked broccoli — no spoon required.

Advocates say that by having control over what goes in their mouths, babies learn to regulate their food intake, refine motor skills and perhaps even become more adventurous eaters. But critics fret that inexperienced eaters may be more likely to choke on solid foods that they feed themselves. A new study of about 200 Australian babies has some reassuring news: Provided that certain risky foods were avoided, babies who fed themselves solid foods were no more likely to choke than spoon-fed babies.

Half of the babies started solid food the traditional way, with parents spoon-feeding them purees and other mushy foods. The other half were given solid foods on their trays and encouraged to feed themselves. Parents were told that babies ought to be sitting up and in the presence of a caregiver while eating. And parents also received a list of risky foods to avoid: hard crackers, diced or hard meat, raw vegetables and popcorn made the list. (A general rule of thumb for checking whether the food is safe: If you can squish the food against the roof of your mouth, then it’s probably OK for your baby to try.)

Spoon-fed babies choked just as much as babies who fed themselves, the researchers report in the September Pediatrics. At 6 months of age, about 22 percent of spoon-fed babies had choked at least once. In the baby-led weaning group, about 18 percent of babies had choked at least once. Choking rates between the two groups were on par as the babies grew older.

There’s an important distinction here between gagging and true choking. Gagging is common among babies as their mouths learn to handle new textures and flavors. The throat slams shut and the mouth tries to get the offending food out. A gagging baby may have watery eyes, push his tongue out of his mouth and make retching movements. He may even puke. This can be hard for parents to watch, but gagging isn’t dangerous.

True choking is. This is when the airway becomes partially or fully blocked. The baby may cough or sputter in an attempt to dislodge the food. He may make a raspy, squeaky whisper as he tries to communicate distress. Or he may go silent. It’s always good to be up on infant CPR, particularly if you’ve got a new eater.

The babies who fed themselves seemed to quickly hone their skills. Initially, self-feeding babies gagged more often than spoon-fed babies at 6 months of age. But by 8 months old, self-feeders had become experts, gagging less than spoon-fed babies.
Although the news seems good for parents who want to try baby-led weaning, the research also turned up something concerning: Lots of babies were given risky foods, regardless of feeding style. At seven months of age, just over half of babies were given something from the no-feed list. By 12 months, almost all the babies had been given riskier foods that can lead to choking. Hard crackers, meat and whole grapes topped the list.

The results suggest that whether you feed your baby or you let your baby feed herself, it’s still important to pay attention to the type of food that’s going into her cute little mouth.

PASADENA, Calif. — NASA’s Juno spacecraft, in orbit around Jupiter since July 4, is lying low after entering an unexpected “safe mode” early on October 19. A misbehaving valve in the fuel system, not necessarily related to the safe mode, has also led to a delay in a planned engine burn that would have shortened the probe’s orbit.

Juno turned off its science instruments and some other nonessential components this morning at 1:47 a.m. EDT after computers detected some unexpected situation, mission head Scott Bolton reported at an October 19 news conference. The spacecraft was hurtling toward its second close approach to the planet, soaring about 5,000 kilometers from the cloud tops. It has now passed that point and is moving back away from the planet with all science instruments switched off.

The rocket firing was intended to take Juno from a 53.5-day orbit to a 14-day orbit. Juno can stay in its current orbit indefinitely without any impact on the science goals, Bolton said. The goal of the mission — to peer deep beneath Jupiter’s clouds — depends on the close approaches that it makes with every orbit, not how quickly it loops around. “We changed to a 14-day orbit primarily because we wanted the science faster,” he said. “But there’s no requirement to do that.”

For now, mission scientists are trying to figure what happened with the fuel valve and what triggered the safe mode before proceeding with further instructions to the probe.

Scientists have lost their latest round of hide-and-seek with dark matter, but they’re not out of the game.

Despite overwhelming evidence that an exotic form of matter lurks unseen in the cosmos, decades of searches have failed to definitively detect a single particle of dark matter. While some scientists continue down the road of increasingly larger detectors designed to catch the particles, others are beginning to consider a broader landscape of possibilities for what dark matter might be.

“We’ve been looking where our best guess told us to look for all these years, and we’re starting to wonder if we maybe guessed wrong,” says theoretical astrophysicist Dan Hooper of Fermilab in Batavia, Ill. “People are just opening their minds to a wider range of options.”

Dark matter permeates the cosmos: The material keeps galaxies from flying apart and has left its imprints in the oldest light in the universe, the cosmic microwave background, which dates back to just 380,000 years after the Big Bang. Indirect evidence from dark matter’s gravitational influences shows that it makes up the bulk of the mass in the universe. But scientists can’t pin down what dark matter is without detecting it directly.
In new results published in August and September, three teams of scientists have come up empty-handed, finding no hints of dark matter. The trio of experiments searched for one particular variety of dark matter — hypothetical particles known as WIMPs, or weakly interacting massive particles, with a range of possible masses that starts at several times that of a proton. WIMPs, despite their name, are dark matter bigwigs — they have long been the favorite explanation for the universe’s missing mass. WIMPs are thought to interact with normal matter only via the weak nuclear force and gravity.

Part of WIMPs’ appeal comes from a prominent but unverified theory, supersymmetry, which independently predicts such particles. Supersymmetry posits that each known elementary particle has a heavier partner; the lightest partner particle could be a dark matter WIMP. But evidence for supersymmetry hasn’t materialized in particle collisions at the Large Hadron Collider in Geneva, so supersymmetry’s favored status is eroding (SN: 10/1/16, p. 12). Supersymmetry arguments for WIMPs are thus becoming shakier — especially since WIMPs aren’t showing up in detectors.

Scientists typically search for WIMPs by looking for interactions with normal matter inside a detector. Several current experiments use tanks of liquefied xenon, an element found in trace amounts in Earth’s atmosphere, in hopes of detecting the tiny amounts of light and electric charge that would be released when a WIMP strikes a xenon nucleus and causes it to recoil.

The three xenon experiments are the Large Underground Xenon, or LUX, experiment, located in the Sanford Underground Research Facility in Lead, S.D.; the PandaX-II experiment, located in China’s JinPing underground laboratory in Sichuan; and the XENON100 experiment, located in the Gran Sasso National Laboratory in Italy. Teams of scientists at the three locations each reported no signs of dark matter particles. The experiments are most sensitive to particles with masses around 40 or 50 times that of a proton. Scientists can’t completely rule out WIMPs of these masses, but the interactions would have to be exceedingly rare.
In initial searches, proponents of WIMPs expected that the particles would be easy to find. “It was thought to be like, ‘OK, we’ll run the detector for five minutes, discover dark matter, and we’re all done,’” says physicist Matthew Szydagis of the University at Albany in New York, a member of LUX. That has turned into decades of hard work. As WIMPs keep failing to turn up, some scientists are beginning to become less enamored with the particles and are considering other possibilities more closely.

One alternative dark matter contender now attracting more attention is the axion. This particle was originally proposed decades ago as part of the solution to a particle physics quandary known as the strong CP problem — the question of why the strong nuclear force, which holds particles together inside the nucleus, treats matter and antimatter equally. If dark matter consists of axions, the particle could therefore solve two problems at once.

Axions are small fry as dark matter goes — they can be as tiny as a millionth of a billionth the mass of a WIMP. The particles interact so feebly that they are extremely difficult to detect. If axions are dark matter, “you’re sitting in an enormous, dense sea of axions and you don’t even notice them,” says physicist Leslie Rosenberg of the University of Washington in Seattle, the leader of the Axion Dark Matter eXperiment. After a recent upgrade to the experiment, ADMX scientists are searching for dark matter axions using a magnetic field and special equipment to coax the particles to convert into photons, which can then be detected.
Although WIMPs and axions remain the front-runners, scientists are beginning to move beyond these two possibilities. In between the featherweight axions and hulking WIMPs lies a broad range of masses that hasn’t been well explored. Scientists’ favorite theories don’t predict dark matter particles with such intermediate masses, says theoretical physicist Kathryn Zurek of Lawrence Berkeley National Laboratory in California, but that doesn’t mean that dark matter couldn’t be found there. Zurek advocates a diverse search over a broad range of masses, instead of focusing on one particular theory. “Dark matter direct detection is not one-size-fits-all,” she says.
In two papers published in Physical Review Letters on January 7 and September 14, Zurek and colleagues proposed using superconductors — materials that allow electricity to flow without resistance — and superfluids, which allow fluids to flow without friction, to detect light dark matter particles. “We are trying to broaden as much as possible the tools to search for dark matter,” says Zurek. Likewise, scientists with the upcoming Super Cryogenic Dark Matter Search SNOLAB experiment, to be located in an underground lab in Sudbury, Canada, will use detectors made of germanium and silicon to search for dark matter with smaller masses than the xenon experiments can.

Scientists have not given up on xenon WIMP experiments. Soon some of those experiments will be scaling up — going from hundreds of kilograms of liquid xenon to tons — to improve their chances of catching a dark matter particle on the fly. The next version of XENON100, the XENON1T experiment (pronounced “XENON one ton”) is nearly ready to begin taking data. LUX’s next generation experiment, known as LUX-ZEPLIN or LZ, is scheduled to begin in 2020. PandaX-II scientists are also planning a sequel. Physicists are still optimistic that these detectors will finally find the elusive particles. “Maybe we will have some opportunity to see something nobody has seen,” says Xiangdong Ji of Shanghai Jiao Tong University, the leader of PandaX-II. “That’s what’s so exciting.”

In the sea of nondetections of dark matter, there is one glaring exception. For years, scientists with the DAMA/LIBRA experiment at Gran Sasso have claimed to see signs of dark matter, using crystals of sodium iodide. But other experiments have found no signs of DAMA’s dark matter. Many scientists believe that DAMA has been debunked. “I don’t know what generates the weird signal that DAMA sees,” says Hooper. “That being said, I don’t think it’s likely that it’s dark matter.”

But other experiments have not used the same technology as DAMA, says theoretical astrophysicist Katherine Freese of the University of Michigan in Ann Arbor. “There is no alternative explanation that anybody can think of, so that is why it is actually still very interesting.” Three upcoming experiments should soon close the door on the mystery, by searching for dark matter using sodium iodide, as DAMA does: the ANAIS experiment in the Canfranc Underground Laboratory in Spain, the COSINE-100 experiment at YangYang Underground Laboratory in South Korea, and the SABRE experiment, planned for the Stawell Underground Physics Laboratory in Australia.

Scientists’ efforts could still end up being for naught; dark matter may not be directly detectable at all. “It’s possible that gravity is the only lens with which we can view dark matter,” says Szydagis. Dark matter could interact only via gravity, not via the weak force or any other force. Or it could live in its own “hidden sector” of particles that interact among themselves, but mostly shun normal matter.

Even if no particles are detected anytime soon, most scientists remain convinced that an unseen form of matter exists. No alternative theory can explain all of scientists’ cosmological observations. “The human being is not going to give up for a long, long time to try to search for dark matter, because it’s such a big problem for us,” says Ji.

SALT LAKE CITY — Flying dinosaurs took off from the ground — no leap from the trees required.

Ancient birds and some nonavian dinosaurs used their wings and powerful legs to launch themselves into the air, a new analysis of 51 winged dinos suggests. Paleontologist Michael Habib of the University of Southern California in Los Angeles reported the findings October 26 at the annual meeting of the Society of Vertebrate Paleontology.

“That’s a big deal, because the classic idea was that early birds started out gliding between trees,” says Yale ornithologist Michael Hanson.
The origin of flight in birds is a sticky subject, says paleontologist Corwin Sullivan of the Chinese Academy of Sciences in Beijing. “There’s been a long-standing controversy over whether flight evolved from the ground up or the trees down.”

Traditionally, scientists have thought that early birds scrambled up trees to get an altitude assist. The birds would then start their flight with a jump, like a hang glider diving off a cliff. Over time, descendants of those gliding birds would have evolved larger wings and, eventually, the ability to flap. Flapping “means you can push yourself forward on your own power,” Habib said. That’s how modern birds fly.

But in recent years, several lines of evidence have begun to dismantle the trees-down approach to flight evolution. Birds descended from terrestrial animals, for one, not tree dwellers. Habib’s team wondered whether early birds needed an elevation boost from trees at all — perhaps they could take off directly from the ground.

He and colleagues examined 51 fossil specimens from 37 different winged dinosaur genera that lived from 150 million to 70 million years ago, from the Late Jurassic to Late Cretaceous epochs. The sample included both avian and nonavian dinosaurs.

The specimens all had stiff, flightlike feathers on their forelimbs. But not all animals with feathered wings can fly, Habib says. To figure out if his specimens once could, he and colleagues analyzed wing length, body mass and hind limb muscle power, among other fossil features. Dinos that could fly (by flapping their wings) had to have enough leg strength to propel them up and enough wing speed to carry them forward.
Just 18 specimens (representing nine of the 37 groups) had the right stuff to get off the ground: every one of the avian specimens in the sample, as well as a few of the nonavian dinos too, including a tiny, four-winged dinosaur called Microraptor.

“Little guys did well,” Habib says. “Anything over four to five kilograms was struggling.”

Whether the early fliers could sustain flight for long distances is a different ball game, Habib says. “But there’s a big difference between flying a little and not flying at all.”

Early flying dinosaurs may have burst off the ground to escape from predators. This bursting behavior could have set the stage for the powered flight systems of modern birds, Habib says. Quick, powerful takeoffs “put a premium on large wings, large flight muscles and really fast wings” — all characteristics of today’s best fliers.

A protein that can switch shapes and accumulate inside brain cells helps fruit flies form and retrieve memories, a new study finds.

Such shape-shifting is the hallmark move of prions — proteins that can alternate between two forms and aggregate under certain conditions. In fruit flies’ brain cells, clumps of the prionlike protein called Orb2 stores long-lasting memories, report scientists from the Stowers Institute for Medical Research in Kansas City, Mo. Figuring out how the brain forms and calls up memories may ultimately help scientists devise ways to restore that process in people with diseases such as Alzheimer’s.
The new finding, described online November 3 in Current Biology, is “absolutely superb,” says neuroscientist Eric Kandel of Columbia University. “It fills in a lot of missing pieces.”

People possess a version of the Orb2 protein called CPEB, a commonality that suggests memory might work in a similar way in people, Kandel says. It’s not yet known whether people rely on the prion to store long-term memories. “We can’t be sure, but it’s very suggestive,” Kandel says.

When neuroscientist Kausik Si and colleagues used a genetic trick to inactivate Orb2 protein, male flies were worse at remembering rejection. These lovesick males continued to woo a nonreceptive female long past when they should have learned that courtship was futile. In different tests, these flies also had trouble remembering that a certain odor was tied to food.
Si and colleagues found a different protein, JJJ2, that helped Orb2 switch shapes, a change that then allows Orb2 to aggregate. When the researchers boosted levels of JJJ2 protein, a situation that led to more Orb2 accumulation, flies had sharper memories. Usually, flies need about six hours of training to learn that an unreceptive female really doesn’t want to mate. But after a boost of JJJ2, flies learned that courtship was futile in only two hours. What’s more, this memory lasted for days, researchers found.
Kandel, whose work has turned up evidence for CPEB holding memories in sea slugs and mice, says that the new study makes the concept that prions can stabilize memories “quite definitive now.”

JJJ2 didn’t lead to supersmart flies that could learn everything quickly, though. The boost only came for memories that would have been formed anyway, Si says. The change “lowered the threshold for memory formation, but it has not created a situation where now all information that comes in is turned into long-term memory,” he says. “It can only [affect] memory when the conditions are right to produce a memory.”

The Orb2 results come from just long-term memory. “There could be other biochemical processes for other types of memory,” such as immune cells’ memories of former threats, Si says. Still, it’s possible that protein accumulation is one of the fundamental ways memory works.

In empty space, quantum particles flit in and out of existence, electromagnetic fields permeate the vacuum, and space itself trembles with gravitational waves. What may seem like nothingness paradoxically teems with activity.

In Void: The Strange Physics of Nothing, physicist and philosopher James Owen Weatherall explores how physicists’ beliefs about nothingness have changed over several revolutionary periods. The void, Weatherall argues, is physics distilled to its bare essence. If physicists can’t agree on the properties of empty space, they won’t be able to explain the physics of planets or particles either.
Scientists have argued over nothingness since the early days of physics. Vacant space was unthinkable to Aristotle, and Descartes so abhorred the idea of a vacuum that he posited that an invisible “plenum” suffused the gaps between objects. But Isaac Newton upended this view, arguing that space was just a barren container into which matter is placed.

Since then, physicists have continued to flip-flop on this issue. The discovery in the mid-1800s that light is an electromagnetic wave led scientists to conclude that a vibrating medium, an “ether,” filled space. Just as sound waves vibrate the air, physicists thought there must be some medium for light waves to ripple. Albert Einstein tore down that idea with his special theory of relativity. Since the speed of light was the same for all observers, no matter their relative speeds, he reasoned, light could not be traveling through some absolute, stationary medium. But he later predicted, as part of his general theory of relativity, that space itself can ripple with gravitational waves (SN: 3/5/16, p. 6) — suggesting that the void is not quite empty.

Under the modern view of quantum physics, various fields pervade all of space, and particles are simply excitations, or waves, in these fields. Even in a vacuum, experiments show, fluctuating fields produce a background of transient particles and antiparticles. Does a space pulsating with gravitational waves and bubbling with particles really qualify as empty? It depends on the scientific definition of “nothing,” Weatherall argues, which may not conform to intuition.

Weatherall serves readers a fairly typical buffet of physics theories, dishing up Newtonian mechanics, relativity, quantum mechanics and a small helping of string theory. But he does this through a lens that highlights connections between those theories in a novel way. Weatherall contends, for instance, that differing notions of nothingness between theories of general relativity and quantum mechanics could help explain why scientists are still struggling to unite the two ideas into one theory of quantum gravity.

Exploring the physics of nothing demands quite a bit of wading through the physics of something, and it’s not always clear how the threads Weatherall is following will lead back to the void. When he finally makes these connections, though, they often reveal insights that are missed in the typical focus on things of substance.

SAN DIEGO — A small number of people maintain razor-sharp memories into their 90s, despite having brains chock-full of the plaques and tangles linked to Alzheimer’s disease. Researchers suspect that these people’s brains are somehow impervious to the usual devastation thought to be caused by those plaques and tangles.

Researchers studied the brains of people 90 years old or older who had excellent memories, performing as well as people in their 50s and 60s on some tests. Postmortem brain tissue from eight such people revealed a range of Alzheimer’s features. Two participants had remarkably clean brains with few signs of amyloid-beta plaques and tangles of tau protein. Four participants had middling levels.
Surprisingly, the other two samples were packed with plaques and tangles, enough to qualify those people for an Alzheimer’s diagnosis based on their brains. “These people, for all practical purposes, should be demented,” study coauthor Changiz Geula of Northwestern University’s medical school said November 15 in a news briefing at the annual meeting of the Society for Neuroscience.

Further tests revealed that even in the midst of these Alzheimer’s hallmarks, nerve cells survived in people with strong memories. Those people had more healthy-looking nerve cells than people with dementia and similar plaque and tangle levels. The researchers don’t know how these mentally sharp people avoid the ravages thought to be caused by plaques and tangles. “What’s surprising is this segment of people does exist,” Geula says. “We have to find out why.”