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Discoveries about the molecular ups and downs of fruit flies’ daily lives have won Jeffrey C. Hall, Michael Rosbash and Michael W. Young the Nobel Prize in physiology or medicine.

These three Americans were honored October 2 by the Nobel Assembly at the Karolinska Institute in Stockholm for their work in discovering important gears in the circadian clocks of animals. The trio will equally split the 9 million Swedish kronor prize — each taking home the equivalent of $367,000.
The researchers did their work in fruit flies. But “an awful lot of what was subsequently found out in the fruit flies turns out also to be true and of huge relevance to humans,” says John O’Neill, a circadian cell biologist at the MRC Laboratory of Molecular Biology in Cambridge, England. Mammals, humans included, have circadian clocks that work with the same logic and many of the same gears found in fruit flies, say Jennifer Loros and Jay Dunlap, geneticists at the Geisel School of Medicine at Dartmouth College.
Circadian clocks are networks of genes and proteins that govern daily rhythms and cycles such as sleep, the release of hormones, the rise and fall of body temperature and blood pressure, as well as other body processes. Circadian rhythms help organisms, including humans, anticipate and adapt to cyclic changes of light, dark and temperature caused by Earth’s rotation. When circadian rhythms are thrown out of whack, jet lag results. Shift workers and people with chronic sleep deprivation experience long-term jet lag that has been linked to serious health consequences including cancer, diabetes, heart disease, obesity and depression.
Before the laureates did their work, other scientists had established that plants and animals have circadian rhythms. In 1971, Seymour Benzer and Ronald Konopka (both now deceased and ineligible for the Nobel Prize) found that fruit flies with mutations in a single gene called period had disrupted circadian rhythms, which caused the flies to move around at different times of day than normal.

“But then people got stuck,” says chronobiologist Erik Herzog of Washington University in St. Louis. “We couldn’t figure out what that gene was or how that gene worked.”
At Brandeis University in Waltham, Mass., Hall, a geneticist, teamed up with molecular biologist Rosbash to identify the period gene at the molecular level in 1984. Young of the Rockefeller University in New York City simultaneously deciphered the gene’s DNA makeup. “In the beginning, we didn’t even know the other group was working on it, until we all showed up at a conference together and discovered we were working on the same thing,” says Young. “We said, ‘Well, let’s forge ahead. Best of luck.’”
It wasn’t immediately apparent how the gene regulated fruit fly activity. In 1990, Hall and Rosbash determined that levels of period’s messenger RNA — an intermediate step between DNA and protein — fell as levels of period’s protein, called PER, rose. That finding indicated that PER protein shuts down its own gene’s activity.

A clock, however, isn’t composed of just one gear, Young says. He discovered in 1994 another gene called timeless. That gene’s protein, called TIM, works with PER to drive the clock. Young also discovered other circadian clockworks, including doubletime and its protein DBT, which set the clock’s pace. Rosbash and Hall discovered yet more gears and the two groups competed and collaborated with each other. “This whole thing would not have turned out nearly as nicely if we’d been the only ones working on it, or they had,” Young says.

Since those discoveries, researchers have found that nearly every cell in the body contains a circadian clock, and almost every gene follows circadian rhythms in at least one type of cell. Some genes may have rhythm in the liver, but not the skin cells, for instance. “It’s normal to oscillate,” Herzog says.
Trouble arises when those clocks get out of sync with each other, says neuroscientist Joseph Takahashi at the University of Texas Southwestern Medical Center in Dallas. For instance, genes such as cMyc and p53 help control cell growth and division. Scientists now know they are governed, in part, by the circadian clock. Disrupting the circadian clock’s smooth running could lead to cancer-promoting mistakes.

But while bad timing might lead to diseases, there’s also a potential upside. Scientists have also realized that giving drugs at the right time might make them more effective, Herzog says.

Rosbash joked during a news conference that his own circadian rhythms had been disrupted by the Nobel committee’s early morning phone call. When he heard the news that he’d won the prize, “I was shocked, breathless really. Literally. My wife said, ‘Start breathing,’” he told an interviewer from the Nobel committee.

Young’s sleep was untroubled by the call from Sweden. His home phone is the kitchen, and he didn’t hear it ring, so the committee was unable to reach him before making the announcement. “The rest of the world knew, but I didn’t,” he says. Rockefeller University president Richard Lifton called him on his cell phone and shared the news, throwing Young’s timing off, too. “This really did take me surprise,” Young said during a news conference. “I had trouble even putting my shoes on this morning. I’d go pick up the shoes and realize I needed the socks. And then ‘I should put my pants on first.’”

A new insect-inspired tiny robot that can move between air and water is a lightweight.

Weighing the same as about six grains of rice, it is the lightest robot that can fly, swim and launch itself from water, an international team of researchers reports October 25 in Science Robotics. The bot is about 1,000 times lighter than other previously developed aerial-aquatic robots. In the future, this kind of aquatic flier could be used to perform search-and-rescue operations, sample water quality or simply explore by air or sea.
To hover, the bot flaps its translucent wings 220 to 300 times per second, somewhat faster than a housefly. Once submerged, the tiny robot surfaces by slowly flapping its wings at about nine beats per second to maintain stability underwater.

For the tricky water-to-air transition, the bot does some chemistry. After water has collected inside the machine’s central container, the bot uses a device to split water into hydrogen and oxygen gas. As the chamber fills with gas, the buoyancy lifts the vehicle high enough to hoist the wings out of the water. An onboard “sparker” then creates a miniature explosion that sends the bot rocketing about 37 centimeters — roughly the average length of a men’s shoe box — into the air. Microscopic holes at the top of the chamber release excess pressure, preventing a loss of robot limbs.
Still, the design needs work: The machine doesn’t land well, and it can only pierce the water’s surface with the help of soap, which lowers the surface tension. More importantly, the experiment points to the possibilities of incorporating different forms of locomotion into a single robot, says study coauthor Robert Wood, a bioengineer at Harvard University.

Emma Watson, Jake Gyllenhaal, journalist Fiona Bruce and Barack Obama all walk into a sheep pen. No, this isn’t the beginning of a baaa-d joke.

By training sheep using pictures of these celebrities, researchers from the University of Cambridge discovered that the animals are able to recognize familiar faces from 2-D images. Given a choice, the sheep picked the familiar celebrity’s face over an unfamiliar face the majority of the time, the researchers report November 8 in Royal Society Open Science.
Even when a celeb’s face was slightly tilted rather than face-on, the sheep still picked the image more often than not. That means the sheep were not just memorizing images, demonstrating for the first time that sheep have advanced face-recognition capabilities similar to those of humans and other primates, say neurobiologist Jennifer Morton and her colleagues.

Sheep have been known to pick out pictures of individuals in their flock, and even familiar handlers (SN: 10/6/12, p. 20). But it’s been unclear whether the skill was real recognition or simple memorization. Sheep now join other animals, including horses, dogs, rhesus macaques and mockingbirds, that are able to distinguish between individuals of other species.
Morton and her colleagues released eight sheep one-by-one into a pen outfitted with two computer screens. A celebrity’s face would appear on one screen, while a different image appeared on the other. First, the team familiarized the sheep with the celebrities’ faces by showing the faces opposite a black screen or random objects. Picking the celebrity earned a sheep a food-pellet reward.
Next, researchers paired a celebrity mug, like Gyllenhaal’s now-familiar face, with an unfamiliar person. By the end of this experiment, the sheep chose a familiar celebrity’s face over a stranger’s face about 79 percent of the time on average.

To see if the sheep were just memorizing shapes, researchers did the same test, but with pictures in which the celebs’ heads were tilted right or left. The sheep didn’t do as well but still passed, recognizing the celebrities about 67 percent of the time on average — a drop in performance comparable to that seen in humans performing the same task.

In a final test, the sheep had to choose between a picture of one of their handlers’ faces and an unfamiliar face. On her first try, one sheep appeared taken aback by the new face in the mix. She did a double take of both faces before ultimately choosing her handler. Since the handler cares for the sheep daily, the animals were familiar with her — although they had never seen a 2-D photo of her face. Recognizing a person that is familiar from 3-D life requires “complex image processing,” the authors say, because the sheep must translate their memory of the person to a 2-D picture.

Brad Duchaine, a brain scientist at Dartmouth College, doesn’t find the sheep’s ability surprising. “My guess is that the ability of sheep to recognize human faces is a by-product of selection to discriminate between different sheep faces,” he says. “Either the human face is similar enough to the sheep face that [it] activates the sheep face-processing system, or human-face recognition relies on more general-purpose recognition systems.”

Et tu, antibody? In humans, dengue can be more severe the second time around. Now, a study implicates an immune system treachery as the culprit.

The study suggests that the amount of anti-dengue antibodies a person has matters. In a 12-year study of Nicaraguan children, low levels of dengue antibodies left over in the blood from a prior infection increased the risk of getting a life-threatening form of the disease the next time around, researchers report online November 2 in Science.

Four related viruses cause dengue. The theory that antibodies protective against one type of dengue can collude with a different type of the virus to make a second infection worse was proposed in the 1960s. Such antibody-dependent enhancement has been shown in cells and lab animals. But “there’s been this controversy for five decades about, does this antibody-dependent enhancement really happen in dengue” in humans, says coauthor Eva Harris, a viral immunologist at the University of California, Berkeley’s School of Public Health. “And this says, yes, it does.”

About 2.5 billion people live where there is a risk of dengue infection. The virus infects 50 million to 100 million people every year, the World Health Organization estimates, but many cases go unreported. Infection with the mosquito-transmitted virus often leads to no symptoms, but can cause fever, joint and muscle pain and other flulike symptoms. The most severe form, which affects about half a million people annually, can include internal bleeding, respiratory distress or organ failure, and may be fatal.
Getting sick with one of the four virus types can protect against a future infection of the same type. But in some cases, the theory goes, leftover antibodies from the first illness can actually help the second infection invade cells, increasing the risk of severe dengue disease.

“This study provides support for this idea that antibodies under certain conditions can be bad and actually cause severe disease when people are infected with dengue,” says viral immunologist Sujan Shresta of the La Jolla Institute for Allergy and Immunology in California. The next step, she says, is to learn more about the antibodies involved and see whether the findings hold up in other populations.

From 2004 to 2016, Harris and her colleagues studied more than 6,500 children aged 2 to 14 in Managua, Nicaragua. The researchers took blood samples each year, at a time when the kids were healthy, and assessed their antibody levels. The scientists also monitored which kids developed dengue and how severe the disease was.

An analysis showed that kids with a specific low range of anti-dengue antibodies had around a 7½ times higher risk of developing the most severe form of the disease than those who had either no antibodies or a high amount. The team’s test couldn’t tell what kind of dengue antibodies each child had. Harris and colleagues are now working on characterizing the antibodies measured in their test, to learn what makes them protective or harmful.

The new study supports the theory of antibody-dependent enhancement in humans, says Anna Durbin, an infectious diseases physician at Johns Hopkins Bloomberg School of Public Health. But she also argues that the risk of developing severe disease depends on the quality of the antibody — that is, how potent it is — as much as, or more than, the quantity. “A number in and of itself doesn’t tell you a whole lot.”

In the scientific version of her obituary, Dolly the Sheep was reported to have suffered from severe arthritis in her knees. The finding and Dolly’s early death from an infection led many researchers to think that cloning might cause animals to age prematurely.

But new X-rays of Dolly’s skeleton and those of other cloned sheep and Dolly’s naturally conceived daughter Bonnie indicate that the world’s first cloned mammal had the joints of normal sheep of her age. Just like other sheep, Dolly had a little bit of arthritis in her hips, knees and elbows, developmental biologist Kevin Sinclair of the University of Nottingham in England and colleagues report November 23 in Scientific Reports.
The researchers decided to reexamine Dolly’s remains after finding that her cloned “sisters” have aged normally and didn’t have massive arthritis (SN: 8/20/16, p. 6). No formal records of Dolly’s original arthritis exams were kept, so Sinclair and colleagues got Dolly’s and Bonnie’s skeletons and those of two other cloned sheep, Megan and Morag, from the National Museums Scotland in Edinburgh. Megan and Bonnie were both older than Dolly at the time of their deaths and had more bone damage than Dolly did. Morag died younger and had less damage.
Dolly’s arthritis levels were similar to those of naturally conceived sheep her age, indicating that cloning wasn’t to blame. “If there were a direct link with cloning and osteoarthritis, we would have expected to find a lot worse, and it would be more extensive and have a different distribution than what we’re finding in ordinary sheep,” says study coauthor Sandra Corr, a veterinary orthopedic specialist at the University of Glasgow in Scotland.
Dolly’s slightly creaky joints may have stemmed from giving birth to six lambs, including Bonnie. Pregnancy is a risk factor for arthritis in sheep.

For decades, the name “virus” meant small and simple. Not anymore. Meet the giants.

Today, scientists are finding ever bigger viruses that pack impressive amounts of genetic material. The era of the giant virus began in 2003 with the discovery of the first Mimivirus (SN: 5/23/09, p. 9). The viral titan is about 750 nanometers across with a genetic pantry boasting around 1.2 million base pairs of DNA, the information-toting bits often represented with A, T, C and G. Influenza A, for example, is roughly 100 nanometers across with only about 13,500 base pairs of genetic material.

In 2009, another giant virus called Marseillevirus was identified. It is different enough from mimiviruses to earn its own family. Since 2013, mega-sized viruses falling into another eight potential virus families have been found, showcasing a long-unexplored viral diversity, researchers reported last year in Annual Review of Virology and in January in Frontiers in Microbiology.

Giant viruses mostly come in two shapes: polyhedral capsules and egglike ovals. But one, Mollivirus, skews more spherical. Pacmanvirus was named for the broken appearance of its outer shell. Both represent potential families. Two newly discovered members of the mimivirus family, both called tupanviruses and both with tails, have the most complete set of genes related to assembling proteins yet seen in viruses (SN Online: 2/27/18). Once unheard of, giant viruses may be common in water and soils worldwide. Only time — and more discoveries — will tell.
Virus length and genome size for a representative from each of two recognized giant virus families (mimivirus and marseillevirus families) and eight potential families are shown. Circles are scaled to genome size and shaded by size range, with influenza A and E. coli bacterium included for comparison. Years indicate when the first viruses were described.

Graphic: C. Chang; Sources: P. Colson, B. La Scola and D. Raoult/Annual Review of Virology 2017; J. Andreani et al/Frontiers in Microbiology 2018

THE WOODLANDS, Texas — Mars’ missing magnetic field may have drowned in the planet’s core.

An excess of hydrogen, split off from water molecules and stored in the Martian mantle, could have shut down convection, switching the magnetic field off forever, planetary scientist Joseph O’Rourke proposed March 21 at the Lunar and Planetary Science Conference.

Planetary scientists think magnetic fields are produced by the churning of a planet’s molten iron core. Convection relies on denser materials sinking into the core, and lighter stuff rising to the surface. The movement of iron, which can carry a charge, generates a strong magnetic field that can protect a planet’s atmosphere from being ravaged by solar wind (SN Online: 8/18/17).
But if lighter material, like hydrogen, settles close to the iron core, it could block dense material from sinking deep enough to keep convection going, said O’Rourke, of Arizona State University in Tempe.

“Too much hydrogen and you can shut down convection entirely,” he said. “Hydrogen is a heartless killer.”

O’Rourke and his ASU colleague S.-H. Dan Shim suggested the hydrogen could come from water locked up in Martian minerals. Near the hot core, water would split into hydrogen and oxygen. The oxygen would form compounds with other elements and stay high in the mantle, but the hydrogen could sit atop the core and effectively suffocate the dynamo.
The question is whether Mars’ minerals would have had what it took to deliver the hydrogen at the right time. Mars’ crust is rich in the mineral olivine, which does not bond well with water and so is relatively dry.

In the planet’s interior, pressure forces olivine to transform into the minerals wadsleyite and ringwoodite, which hold more water. Deeper still, the mineral turns into bridgmanite and becomes dry again. For a time, that bridgmanite layer could act as a buffer against water, allowing the core to keep convecting. But as the mantle cooled, the bridgmanite layer would shrink and eventually disappear, O’Rourke’s study suggests.

Whether Mars’ interior ever had that saving layer of bridgmanite depends on how big its core is — a property that may be tested by NASA’s InSight Mars lander, launching on May 5, O’Rourke said. Mars did have a magnetic field more than 4 billion years ago. Scientists have struggled to explain how it vanished, leaving the planet vulnerable to solar winds, which probably stripped away its atmosphere and surface water (SN: 12/12/15, p. 31).

If hydrogen shut down the planet’s generator, it would have had to act fast. Previous observations suggest the magnetic field disappeared relatively rapidly, over 100 million years.

Another theory by James Roberts of the Johns Hopkins Applied Physics Lab in Laurel, Md., suggests a large impact could have shut down the dynamo by heating the outermost core, which would have kept it from sinking.

“It’s actually a similar idea to O’Rourke’s,” Roberts says. It may take many more sophisticated Mars missions to figure out what really happened.

Honeybee royal jelly is food meant to be eaten on the ceiling. And it might also be glue that keeps a royal baby in an upside-down cradle.

These bees raise their queens in cells that can stay open at the bottom for days. A big blob of royal jelly, abundantly resupplied by worker bees, surrounds the larva at the ceiling. Before the food is deposited in the cell, it receives a last-minute jolt of acidity that triggers its proteins to thicken into goo, says Anja Buttstedt, a protein biochemist at Technische Universität Dresden in Germany. Basic larva-gripping tests suggest the jelly’s protein chemistry helps keep future queens from dropping out of their cells, Buttstedt and colleagues propose March 15 in Current Biology.
Suspecting the stickiness of royal jelly might serve some function, researchers tweaked its acidity. They then filled small cups with royal jelly with different pH levels and gently turned the cups upside down. At a natural royal jelly acidity of about pH 4.0, all 10 larvae dangled from their gooey blobs upside down overnight. But in jelly boosted to pH 4.8 (and thinned in the process), four of the 10 larvae dropped from the cups. At pH 5.9, all of them dropped.

Honeybees build several forms of royally oversized cells for raising a queen. Those for queens who will swarm with their workers to a new home hang from the rim of an array of regular cells. A hole stays open at the bottom of the cell until the larva nears pupation from her fat grub shape into a queen with wings. That hole at the bottom is big enough for a royal larva to fall through, confirms insect physiologist Steven Cook at the honeybee research lab in Beltsville, Md., run by the U.S. Department of Agriculture’s Agricultural Research Service.

Buttstedt and colleagues propose that the stickiness of royal jelly may be what keeps the larva in place. The team worked out how the jelly’s proteins change as it is made, and how those changes affect its consistency.

Royal jelly is secreted as a brew of proteins from the glands above a worker bee’s brain. At that point, it has a neutral pH, around 7, like water’s. The worker bee then adds fatty acids from glands in her mouthparts, which take the pH to around 4.
“It has a quite sour smell,” Buttstedt says. As for taste? “Really weird.” A steady diet of this jelly is what turns a larvae into a queen instead of a worker.

At pH 4, the jelly’s most common protein, MRJP1, goes complicated. When the protein leaves the glands above the brain, it’s clustered in groups of four along with smaller proteins called apisimins, the team found. When the acidity shifts, the MRJP1 foursomes and the apisimins hook together in slender fibers and get gluey.

“The most puzzling question,” Buttstedt says, is “why build upside-down queen cells in the first place?”

Delusional infestation
de-LU-zhen-al in-fes-TAY-shun n.
A deep conviction that one’s skin is contaminated with insects or other objects despite a lack of medical evidence.

She was certain her skin was infested: Insects were jumping off; fibers were poking out. Fearful her condition could spread to others, the 50-year-old patient told doctors at the Mayo Clinic in Rochester, Minn., that she was avoiding contact with her children and friends.

The patient had delusional infestation, explains Mayo Clinic dermatologist Mark Davis. Sufferers have an unshaking belief that pathogens or inanimate objects pollute their skin despite no medical evidence. Davis and colleagues report online April 4 in JAMA Dermatology that the disorder is not as rare as previously assumed.
In the first population-based study of the disorder’s prevalence, the researchers identified 35 cases from 1976 to 2010 reported in Minnesota’s Olmsted County. Based on the findings, the authors estimate 27 out of every 100,000 people in the United States have delusional infestation. Due to the county’s lack of diversity — the population of about 150,000 is predominantly white — the researchers used only the nationwide white population to estimate prevalence, so the result may not be representative of other populations.

Delusional infestation has been recognized for decades, albeit under different names. Patients insist they’ve been overtaken with creatures, such as insects, worms or parasites, or inanimate materials like fibers — or both.
“It’s like aliens have infested their skin,” Davis says. Some present bagged samples of the claimed culprits, which turn out to be such debris as sand, dander or, as in the case of the 50-year-old woman, bits of skin and scabs. When lab tests confirm no infestation, patients often seek another opinion rather than accept the findings. Some attempt risky self-treatments, such as bathing in kerosene or bleach, or tweezing or cutting the skin.

Schizophrenia, dementia or other psychiatric illnesses can trigger delusional infestation. So can such drugs as amphetamines or cocaine. But when no other illness is involved, patients often reject the notion that the issue is psychiatric and tend to refuse the antipsychotic medications that can help, Davis says.

As for the 50-year-old patient, upset with the doctors’ diagnosis, she no longer comes to the Mayo Clinic.

Scientists playing peekaboo with dark matter have entered a new stage of the game.

For the first time, physicists are snooping on some of the likeliest hiding places for hypothetical subatomic particles called axions, which could make up dark matter. So far, no traces of the particles have been found, scientists with the Axion Dark Matter Experiment, ADMX, report April 9 in Physical Review Letters. But the researchers have now shown that their equipment is sensitive enough to begin searching in earnest.

An ethereal substance that makes up much of the matter in the universe, dark matter is necessary to explain the motions of stars within galaxies, among other observations. Scientists don’t know what dark matter is, but axions, extremely lightweight particles that may permeate the cosmos, are one of the major contenders.

Most past searches for dark matter particles have focused on a different candidate particle, known as a weakly interacting massive particle, or WIMP. But those efforts have so far come up empty (SN: 11/12/16, p. 14). Now, the spotlight is on the underdog axions.
“We have to make sure we are considering all the possibilities,” says theoretical physicist Matthew Buckley of Rutgers University in Piscataway, N.J., who was not involved with the new result. Axions, he says, are a plausible candidate for dark matter.

Axions would produce incredibly feeble signals, so pinning down evidence for the minuscule particles is no easy undertaking. But ADMX, located at the University of Washington in Seattle, is now up to the task, says ADMX member Aaron Chou, a physicist at Fermilab in Batavia, Ill. Previous experiments have searched for axions, but those efforts weren’t sensitive enough to have a good chance of detecting the particles.

“It’s an experimental tour de force; it’s amazing work,” says theoretical physicist Helen Quinn of SLAC National Accelerator Laboratory in Menlo Park, Calif., who was not involved with the research.

ADMX uses what is essentially a supersensitive radio, isolated from external sources of radio waves and cooled to temperatures near absolute zero (‒273.15° Celsius). Scientists use the apparatus to search for axions converting into radio waves in a strong magnetic field. If axions exist, they are expected to interact with photons, particles of light, from the magnetic field. In the process, they would produce radio waves at a frequency that depends on the axion’s mass, which is unknown. Like scanning the dial for a good oldies station, scientists will gradually change the frequency at which they search, trying to “listen in” on the axion signal.

While the new study came up empty, scientists scanned only a small range of frequencies, ruling out some possible masses for axions, from 2.66 to 2.81 microelectron volts. Those tiny masses are less than a billionth of an electron’s mass. In the future, ADMX will study other possible masses. “There’ll be a lot of excitement in the next few years,” Chou says. “A discovery could come at any time.”