Scientists get a glimpse of chemical tagging in live brains

For the first time, scientists can see where molecular tags known as epigenetic marks are altered in the brain.

These chemical tags — which flag DNA or its protein associates, known as histones — don’t change the genes but can change gene activity. Abnormal epigenetic marks have been associated with brain disorders such as Alzheimer’s disease, schizophrenia, depression and addiction.

Researchers at Massachusetts General Hospital in Boston devised a tracer molecule that latches on to a protein that removes one type of epigenetic mark known as histone acetylation.

The scientists then used PET scans to detect where a radioactive version of the tracer appeared in the brains of eight healthy young adult men and women, the researchers report in the Aug. 10 Science Translational Medicine. Further studies could show that the marks change as people grow older or develop a disease. The team studied only healthy young volunteers so can’t yet say whether epigenetic marking changes with age or disease.

Tabby’s star drama continues

A star that made headlines for its bizarre behavior has got one more mystery for astronomers to ponder.

Tabby’s star, also known as KIC 8462852, has been inexplicably flickering and fading. The Kepler Space Telescope caught two dramatic drops in light — by up to 22 percent — spaced nearly two years apart. Photographs from other telescopes dating back to 1890 show that the star also faded by roughly 20 percent over much of the last century. Possible explanations for the behavior range from mundane comet swarms to fantastical alien engineering projects (SN Online: 2/2/16).
A new analysis of data from Kepler, NASA’s premier planet hunter, shows that Tabby’s star steadily darkened throughout the telescope’s primary four-year mission. That’s in addition to the abrupt flickers already seen during the same time period. Over the first 1,100 days, the star dimmed by nearly 1 percent. Then the light dropped another 2.5 percent over the following six months before leveling off during the mission’s final 200 days.

Astronomers Benjamin Montet of Caltech and Josh Simon of the Observatories of the Carnegie Institution of Washington in Pasadena, Calif., report the findings online August 4 at arXiv.org.

The new data support a previous claim that the star faded between 1890 and 1989, a claim that some researchers questioned. “It’s just getting stranger,” says Jason Wright, an astronomer at Penn State University. “This is a third way in which the star is weird. Not only is it getting dimmer, it’s doing so at different rates.”
The slow fading hadn’t been noticed before because data from Kepler are processed to remove long-term trends that might confuse planet-finding algorithms. To find the dimming, Montet and Simon analyzed images from the telescope that are typically used only to calibrate data.
“Their analysis is very thorough,” says Tabetha Boyajian, an astronomer at Yale University who in 2015 reported the two precipitous drops in light (and for whom the star is nicknamed). “I see no flaws in that at all.”

While the analysis is an important clue, it doesn’t yet explain the star’s erratic behavior. “It doesn’t push us in any direction because it’s nothing that we’ve ever encountered before,” says Boyajian. “I’ve said ‘I don’t know’ so many times at this point.”

An object (or objects) moving in front of the star and blocking some of the light is still the favored explanation — though no one has figured out what that object is. The drop in light roughly 1,100 days into Kepler’s mission is reminiscent of a planet crossing in front of a star, Montet says. But given how slowly the light dropped, such a planet (or dim star) would have to live on an orbit more than 60 light-years across. The odds of catching a body on such a wide, slow orbit as it passed in front of the star are so low, says Montet, that you would need 10,000 Kepler missions to see just one. “We figure that’s pretty unlikely.”

An interstellar cloud wandering between Earth and KIC 8462852 is also unlikely, Wright says. “If the interstellar medium had these sorts of clumps and knots, it should be a ubiquitous phenomenon. We would have known about this for decades.” While some quasars and pulsars appear to flicker because of intervening material, the variations are minute and nothing like the 20 percent dips seen in Tabby’s star.

A clump of gas and dust orbiting the star — possibly produced by a collision between comets — is a more likely candidate, although that doesn’t explain the century-long dimming. “Nothing explains all the effects we see,” says Montet.

Given the star’s unpredictable nature, astronomers need constant vigilance to solve this mystery. The American Association of Variable Star Observers is working with amateur astronomers to gather continuous data from backyard telescopes around the globe. Boyajian and colleagues are preparing to monitor KIC 8462852 with the Las Cumbres Observatory Global Telescope Network, a worldwide web of telescopes that can keep an incessant eye on the star. “At this point, that’s the only thing that’s going to help us figure out what it is,” she says.

Fentanyl’s death toll is rising

For some people, fentanyl can be a life-saver, easing profound pain. But outside of a doctor’s office, the powerful opioid drug is also a covert killer.

In the last several years, clandestine drugmakers have begun experimenting with this ingredient, baking it into drugs sold on the streets, most notably heroin. Fentanyl and closely related compounds have “literally invaded the entire heroin supply,” says medical toxicologist Lewis Nelson of New York University Langone Medical Center.

Fentanyl is showing up in other drugs, too. In San Francisco’s Bay Area in March, high doses of fentanyl were laced into counterfeit versions of the pain pill Norco. In January, fentanyl was found in illegal pills sold as oxycodone in New Jersey. And in late 2015, fentanyl turned up in fake Xanax pills in California.
This ubiquitous recipe-tinkering makes it impossible for users to know whether they’re about to take drugs mixed with fentanyl. And that uncertainty has proved deadly. Fentanyl-related deaths are rising sharply in multiple areas. National numbers are hard to come by, but in many regions around the United States, fentanyl-related fatalities have soared in recent years.

Maryland is one of the hardest-hit states. From 2007 to 2012, the number of fentanyl-related deaths hovered around 30 per year. By 2015, that number had grown to 340. A similar rise is obvious in Connecticut, where in 2012, there were 14 fentanyl-related deaths. In 2015, that number was 188.
In Massachusetts, two-thirds of people who died from opioid overdoses in the first half of 2016 showed signs of fentanyl. This wave of fentanyl-related overdoses is “horrendous,” says Daniel Ciccarone of the University of California, San Francisco. What’s worse, he says, “I think it’s here to stay.”
Fentanyl is not a new drug. Available in the 1960s, it is still used in hospitals as an anesthetic and is available by prescription to fight powerful pain. What’s new, Ciccarone says, is that clandestine drug manufacturers have discovered that the euphoria-producing opioid can be made cheaply and easily — no poppy fields necessary.

Fentanyl is about 30 to 40 times stronger than heroin and up to 100 times more powerful than morphine, which means that a given effect on the body can be achieved with a much smaller amount of fentanyl. Inadvertently taking a bit of fentanyl can cause big trouble. “It’s a dosing problem,” Nelson says. “Because the drug is so potent, little changes in measurements can have very big implications for toxicity. That’s really the problem.”

That problem is made worse by the variability of illegal drugs — users often don’t know what they’re buying. Illegal labs aren’t pumping out products with carefully calibrated doses or uniform chemical makeup. The drugs change from day to day, making it nearly impossible for a user to know what he or she is about to take, Ciccarone says.

He has seen this struggle up close. Drug users have told him that the products they buy are unpredictable. Another thing people are telling him: “That they and their friends and compatriots are dropping like flies.” Tellingly, some of the most experienced drug users have recently begun doing “tester shots,” small doses to get a sense of the type and dose of drug they’re about to use, Ciccarone says.

Users are right to be wary. Typically, opioids can kill by gradually depressing a person’s ability to breathe. Illicit fentanyl, a recent study suggests, can kill within minutes by paralyzing muscles. Doctors have known that when injected quickly, fentanyl can paralyze chest wall muscles, prevent breathing and kill a person rapidly. That effect, called “wooden chest,” might help explain the rise in fentanyl-related deaths, scientists report in the June Clinical Toxicology.

A quick injection of fentanyl “literally freezes the muscles and you can’t move the chest,” says toxicologist Henry Spiller of the Central Ohio Poison Center in Columbus. That’s why doctors who dispense fentanyl in the hospital intentionally proceed very slowly and keep the opioid-counteracting drug naloxone (Narcan) on hand. “If you give it too fast, we know this occurs,” Spiller says. But it wasn’t known whether this same phenomenon might help explain the death rate of people using the drug illegally.

Spiller and colleagues tested post-mortem concentrations of fentanyl and its breakdown product norfentanyl in 48 fentanyl-related deaths. The body usually begins breaking down fentanyl into norfentanyl within two minutes, an earlier study found. Yet in 20 of the cases, the researchers found no signs of norfentanyl, indicating death came almost immediately after first receiving fentanyl.

Naloxone can counteract the effects of opioids if someone nearby can administer the antidote. But for people whose chests quickly freeze from fentanyl, resuscitation becomes more unlikely. Fentanyl “is just a bad drug,” Spiller says.
Fentanyl’s danger is magnified for people not accustomed to taking opioids, such as those addicted to cocaine, a situation illustrated by a recent tragedy in New Haven, Conn.

New Haven authorities noticed a string of suspicious overdoses in late June, leaving three people dead. Drug users thought they were buying cocaine, but the drugs contained fentanyl, says analytical toxicologist Kara Lynch of the University of California, San Francisco. As one of the handful of labs capable of testing blood and urine for fentanyl, hers was called on to identify the culprit. Her lab spotted fentanyl in Norco tablets back in March.

Lynch’s group uses high-resolution mass spectrometry to detect many drugs’ chemical signatures. But this method reveals only the drugs scientists suspect. “We can look for what we know to look for,” she says. And success depends on getting the samples in the first place.

The logistical hurdles of figuring out exactly what a person took, and how much, and when, are large. Ciccarone contrasts the situation with cases of food poisoning. When people start getting sick, public health officials can figure out what lettuce people ate and test it for pathogens. The same kind of tracking system doesn’t exist for drugs. His efforts to develop a system for testing illegal drugs in Baltimore broke down in part because no one had time to do the work. “The coroner is so busy right now with dead bodies,” he says. “They don’t have the time to test the ‘lettuce.’ ”

In the quest to curb fentanyl-related deaths, scientists and public health officials are searching for new strategies. Spiller advocates a more targeted public health message to users, one that emphasizes that fentanyl is simply a deadly drug, not just a more potent high. Ciccarone says that facilities where drug users can take illegal drugs under the care of medical personnel might reduce the number of fatalities.

For now, the scope of the problem continues to grow, Nelson says. The situation is made worse by the ingenuity of illicit drugmakers, who readily experiment with new compounds. Fentanyl itself can be tweaked to create at least 16 related forms, one of which, acetyl fentanyl, has been linked to overdose deaths. New drugs and new tweaks to old drugs rapidly evolve (SN: 5/16/15, p. 22), Nelson says, creating a game of whack-a-mole in which designer drugs confound public health officials and law enforcement.

“There is no single easy solution to this problem,” he says.

Water plays big role in shaping dwarf planet Ceres

Ice volcanoes, patches of water ice and a slew of hydrated minerals paint a picture of dwarf planet Ceres as a geologically active world — one where water has played a starring role. That’s the theme of six papers in the Sept. 2 Science that describe data collected by the Dawn spacecraft.

A 4-kilometer-high mountain dubbed Ahuna Mons, with its bowl-shaped summit and ridged flanks, has the appearance of a cryovolcano — one that erupts water instead of magma. The relatively young Oxo crater also appears to be home to splotches of frozen water. Given that ice should last only tens to hundreds of years on Ceres’ surface, the patches must be recent additions, possibly exposed by a landslide or impact with a meteorite. The surface is also slathered with a class of minerals known as phyllosilicates — silicon-bearing substances that form in the presence of water — which further support the idea that water has been present throughout Ceres’ history.

Ceres is the largest body between Mars and Jupiter. Dawn has been orbiting Ceres since March 6, 2015 (SN: 4/4/15, p. 9), studying its geology and composition to better understand the formation of rocky worlds.

Preteen tetrapods identified by bone scans

Better bone scanning of fossils offers a glimpse of preteen life some 360 million years ago.

Improved radiation scanning techniques reveal accumulating growth zones in chunks of four fossil upper forelimb bones from salamander-shaped beasts called Acanthostega, scientists report online September 7 in Nature. Vertebrate bones typically show annual growth zones diminishing in size around the time of sexual maturity. But there’s no sign of that slowdown in these four individuals from East Greenland’s mass burial of Acanthostega, says study coauthor Sophie Sanchez of Uppsala University in Sweden. They were still juveniles.
The bones came from tropical Greenland of the Devonian Period. Aquatic vertebrates were developing four limbs, which would serve tetrapods well when vertebrates eventually conquered land. This mass die-off doomed at least 20 individuals, presumably when a dry spell after a flood trapped them all in a big, vanishing puddle.
This find makes the strongest case yet for identifying genuine youngsters among ancient tetrapods, Sanchez says. She suspects other individuals trapped could have been juveniles too.

Not many other species were found in the mass burial. So young tetrapods may have stuck together much as today’s young fish school, Sanchez speculates. The limb shape clearly indicates that the youngsters took a long time to start adding hard bone to the initial soft cartilage, she says. So these early tetrapods were at least 6-year-olds and probably 10 years old or more.
For identifying stages of life, the improved technique “allows greater resolution and rigor, so in that regard it is a plus,” says Neil Shubin of the University of Chicago, who studies a fossil fish with some tetrapod-like features called Tiktaalik. There are Tiktaalik preteens, too, he notes.

What interests Nadia Fröbisch of Museum für Naturkunde in Berlin is that some of Acanthostega individuals were different sizes but had reached the same stage of bone development. She muses that they might even have been developing along different trajectories of growth, a flexibility that would be useful in a changeable environment.

Primordial continental crust re‑created in lab

New experiments have re-created the genesis of Earth’s first continents.

By putting the squeeze on water and oceanic rocks under intense heat, researchers produced material that closely resembles the first continental crust, created around 4 billion years ago. The work suggests that thick slabs of oceanic crust helped build the first continents: After plate tectonics pushed the thick slabs underground, the rocks melted, transformed and then erupted to the surface to make continents, the researchers report online August 31 in Geology.
This continental origin story relies on two characteristics that make Earth unlike other rocky planets in the solar system, says study coauthor Alan Hastie, a geologist at the University of Birmingham in England. Earth has both oceans and a network of shifting tectonic plates that can force sections of the planet’s exterior underground, a process known as subduction. “Without liquid oceans and without subduction from plate tectonics, you don’t get continents,” Hastie says. “The only reason I’m sitting here on land today is because of this process.”

The scenario proposed by Hastie and colleagues doesn’t necessarily require active plate tectonics to work, says geochemist Kent Condie of the New Mexico Institute of Mining and Technology in Socorro. Plate tectonics may have started hundreds of millions of years after the first continental crust formed. If thick enough, oceanic crust could have sunk deep enough on its own to create continental crust without the need for subduction, Condie says. “We shouldn’t make the assumption that we need subduction.”

Initially after Earth formed, only oceanic crust and stacks of volcanic rock coated the planet’s surface. Continental crust — which is made of less dense rock than oceanic crust and therefore rises to higher elevations — came perhaps hundreds of millions of years later. The oldest continental crust still around today, found in Greenland, dates back to about 4 billion years ago.
Re-creating the formation of the earliest continental crust involves a lot of trial and error. Scientists compress bits of various rocks at high temperatures that mimic the sinking of various types of rock into the planet’s depths. The rocks transform into different minerals under the intense heat and pressure. The goal is to create rock that looks like ancient continental crust. Using this “cook and look” method, scientists have gotten a few decent matches, but never anything that perfectly replicated the first continents.
Last year, Hastie and colleagues reported finding Jamaican rocks that closely resembled early continental crust, only much younger. The researchers wondered whether the nearby Caribbean Ocean Plateau was partially to blame for the odd rocks. Ocean plateaus are slabs of oceanic crust thickened by hot plumes of material that rise from Earth’s depths. This thick crust, while somewhat rare today, was probably more common billions of years ago when Earth’s interior was much hotter, Hastie says.

Using a special press, the researchers squeezed and melted small samples of water and ocean plateau rock at pressures of up to 2.2 gigapascals — equivalent to three adult African elephants stacked on a postage stamp — and at temperatures up to 1,000° Celsius. These extreme conditions imitate the fate of a chunk of ocean plateau around 30 to 45 kilometers thick forced deep underground.

The experiment transformed the water and rock into a dead ringer for the oldest known continental crust. Once created underground, the new crust would have erupted to the surface via volcanism and formed the forerunners of the modern continents, Hastie says.

Old-school contraptions still work for weighing astronauts

New method to measure mass in space devised — A scale for measuring weight in space that does not depend upon the attraction of gravity has been devised…. In [William Thornton’s] method, the weight of the mass is determined [by] mechanically oscillating a weight in a tray. The heavier the mass, the slower the oscillation rate. The scale is tied to an electronic unit measuring the time required for five cycles of oscillation. A reference to a chart gives the mass’s weight. — Science News, October 1, 1966

UPDATE
Not much has changed. The International Space Station has two spring-based contraptions for weighing in astronauts. An individual rides the Body Mass Measurement Device like a pogo stick — in four or five bounces, it calculates weight. The Space Linear Acceleration Mass Measurement Device uses springs to pull an astronaut; the acceleration reveals weight. In 2012, researchers in Europe experimented with compact computer imaging technology — developed for video games — using photos to estimate mass based on a person’s shape and size.

Gene linked to autism in people may influence dog sociability

Dogs may look to humans for help in solving impossible tasks thanks to some genes previously linked to social disorders in people.

Beagles with particular variants in a gene associated with autism were more likely to sidle up to and make physical contact with a human stranger, researchers report September 29 in Scientific Reports.

That gene, SEZ6L, is one of five genes in a particular stretch of beagle DNA associated with sociability in the dogs, animal behaviorist Per Jensen and colleagues at Linköping University in Sweden say. Versions of four of those five genes have been linked to human social disorders such as autism, schizophrenia and aggression.
“What we figure has been going on here is that there are genetic variants that tend to make dogs more sociable and these variants have been selected during domestication,” Jensen says.

But other researchers say the results are preliminary and need to be confirmed by looking at other dog breeds. Previous genetic studies of dog domestication have not implicated these genes. But, says evolutionary geneticist Bridgett vonHoldt of Princeton University, genes that influence sociability are “not an unlikely target for domestication — as humans, we would be most interested in a protodog that was interested in spending time with humans.”

Most dog studies take DNA samples from pets or village dogs and wild wolves. Jensen’s team instead studied beagles that had been raised in a lab. None of the dogs had been trained. To test sociability, the researchers gave the dogs an unsolvable problem in a room with a female human observer whom the beagles had never seen before. The puzzle was a device with three treats that the dogs could see and smell under sliding lids. One lid was sealed shut and could not be opened.

After opening two lids, the dogs “get very confident that this is not a difficult task, but then they encounter the third lid and that’s where the problem gets impossible,” Jensen says. Wolves would have kept trying to solve the problem on their own (SN: 10/17/15, p. 10). But after some futile attempts, many of the beagles looked to the human observer for help. Some dogs tried to catch her eye, glancing back and forth between the woman and the stuck lid. Other dogs made physical contact with or just tried to stay to close to the woman.

The researchers then looked for places in the dogs’ DNA where the most and least human-friendly dogs differed. A region on chromosome 26 kept popping up, indicating that genes in that region could be involved in social interactions with people.
The finding is a statistical signal, but doesn’t establish what the genes might be doing to influence the dogs’ behavior, says Adam Freedman, an evolutionary geneticist at Harvard University. And since the researchers only examined the beagles, it’s not clear that the same genes would affect behavior in other dogs, he says.

Trio wins physics Nobel for math underlying exotic states of matter

The 2016 Nobel Prize in physics is awarded for discoveries of exotic states of matter known as topological phases that can help explain phenomena such as superconductivity.

The prize is shared among three researchers: David J. Thouless, of the University of Washington in Seattle, F. Duncan M. Haldane of Princeton University and J. Michael Kosterlitz of Brown University. The Royal Swedish Academy of Sciences announced the prize October 4.

At the heart of their work is topology, a branch of mathematics that describes steplike changes in a property. An object can have zero, one or two holes, for example, but not half a hole. This year’s Nobel laureates found that topological effects could explain behaviors seen in superconductors and superfluids. “Like most discoveries, you stumble onto them and you just come to realize there is something really interesting there,” Haldane said in a phone call during the announcement.

African elephants walk on their tippy-toes

Elephants don’t wear high heels, but they certainly walk like they do.

Foot problems plague pachyderms in captivity. But it hasn’t been clear what about captivity drives these problems.

Olga Panagiotopoulou of the University of Queensland in Australia and colleagues tested walking in nearly wild elephants. The team trained five free-ranging elephants at a park in South Africa to walk over pressure-sensing platforms to map the distribution of weight on their feet. The team compared the data with similar tests of Asian elephants in a zoo in England.

Regardless of species or setting, a trend emerged: Elephants put the most pressure on the outside toes of their front feet and the least pressure on their heels, the team reports October 5 in Royal Society Open Science. Thus, elephants naturally walk on their tiptoes. The harder surfaces of captive environments must cramp a natural walking style, the researchers conclude.