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.
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.
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.
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.
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.
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.
Accidental chair squeaks in a lab have tipped off researchers to a new world of eavesdroppers.
Spiders don’t have eardrums, though their exquisitely sensitive leg hairs pick up vibrations humming through solids like web silk and leaves. Biologists thought that any airborne sounds more than a few centimeters away would be inaudible. But the first recordings of auditory nerve cells firing inside a spider brain suggest that the tiny Phidippus audax jumping spider can pick up airborne sounds from at least three meters away, says Ronald Hoy of Cornell University. During early sessions of brain recordings, Hoy’s colleagues saw bursts of nerve cell, or neuron, activity when a chair moved. Systematic experiments then showed that from several meters away, spiders were able to detect relatively quiet tones at levels comparable to human conversation. In a hearing test based on behavior, the spiders also clearly noticed when researchers broadcast a low droning like the wing sound of an approaching predatory wasp. In an instant, the spiders hunkered down motionless, the researchers report online October 13 in Current Biology.
Jumping spiders have brains about the size of a poppy seed, and Hoy credits the success of probing even tinier spots inside these (anesthetized) brains to Cornell coauthor Gil Menda and his rock-steady hands. “I close my eyes,” Menda says. He listens his way along, one slight nudge of the probe at a time toward the auditory regions, as the probe monitor’s faint popping sounds grow louder. When Menda first realized the spider brain reacted to a chair squeak, he and Paul Shamble, a study coauthor now at Harvard University, started clapping hands, backing away from the spider and clapping again. The claps didn’t seem earthshaking, but the spider’s brain registered clapping even when they had backed out into the hallway, laughing with surprise. Clapping or other test sounds in theory might confound the experiment by sending vibrations not just through the air but through equipment holding the spider. So the researchers did their Cornell neuron observations on a table protected from vibrations. They even took the setup for the scary wasp trials on a trip to the lab of coauthor Ronald Miles at State University of New York at Binghamton. There, they could conduct vibration testing in a highly controlled, echo-dampened chamber. Soundwise, Hoy says, “it’s really eerie.”
Neuron tests in the hushed chamber and at Cornell revealed a relatively narrow, low-pitched range of sensitivity for these spiders, Hoy says. That lets the spiders pick up rumbly tones pitched around 70 to 200 hertz; in comparison, he says, people hear best between 500 and 1,000 Hz and can detect tones from 50 Hz to 15 kilohertz. Spiders may hear low rumbles much as they do web vibes: with specialized leg hairs, Hoy and his colleagues propose. They found that making a hair twitch could cause a sound-responsive neuron to fire. “There seems to be no physical reason why a hair could not listen,” says Jérôme Casas of the University of Tours in France. When monitoring nerve response from hairs on cricket legs, he’s tracked airplanes flying overhead. Hoy’s team calculates that an 80 Hz tone the spiders responded to would cause air velocities of only 0.13 millimeters a second if broadcast at 65 decibels three meters away. That’s hardly a sigh of a breeze. Yet it’s above the threshold for leg hair response, says Friedrich Barth of the University of Vienna, who studies spider senses.
An evolutionary pressure favoring such sensitivity might have been eons of attacks from wasps, such as those that carry off jumping spiders and immobilize them with venom, Hoy says. A mother wasp then tucks an inert, still-alive spider into each cell of her nest where a wasp egg will eventually hatch to feed on fresh spider flesh. Wasps are major predators of many kinds of spiders, says Ximena Nelson of the University of Canterbury in Christchurch, New Zealand. If detecting their wing drone turns out to have been important in the evolution of hearing, other spiders might do long-distance eavesdropping, too.
Rocky Mountain hikers might need to start packing more bear spray: Climate change may reduce the time that grizzly bears spend in hibernation — leaving them more time to scare the crap out of any humans wandering in their territory.
Scientists aren’t really concerned about bear hibernation because of unwary hikers, of course. It’s because hibernation is an important time of year for a grizzly bear. By going into hibernation and suppressing their metabolisms, the bears can reduce the amount of energy they expend by some 85 percent and more easily get through months when food supplies are short and weather is bleak. Plus, this is when pregnant females give birth and start raising their young. Disrupt hibernation time and a bear is set for a bad — and potentially deadly — year.
And then there’s the fact that in some places, grizzly bears aren’t doing so well. That’s true in Alberta, Canada, where the bears, already low in number, have been threatened by habitat loss and human hunters and have low reproductive rates.
Karine Pigeon of Laval University in Quebec City and colleagues wanted to know whether they should add climate change to that list of threats. But first they needed more information about the factors that drive the bears into and out of their dens. The bears don’t go into or leave hibernation on specific dates (apparently they don’t use our calendar system), so how do they know when it’s time to hibernate?
To find out, the team captured 15 male and 58 female grizzly bears from 1999 to 2011 in an area along the Alberta-British Columbia border northwest of Calgary. The bears were weighed and measured and fitted with tracking collars. Because the signals from the collars couldn’t be tracked from inside the bears’ dens, the researchers knew when the animals entered and left hibernation. The scientists also collected information about the local weather and the availability of berries, one of the bears’ preferred foods.
No single factor explained the dates on which the grizzlies entered and left hibernation, but some were more important than others, the team reports in the October Behavioral Ecology and Sociobiology. Pregnant females, for instance, entered their dens on average two weeks earlier than males, and the ones that had given birth and had cubs emerged two weeks later. This matched what scientists know about bear denning habits, which are thought to promote the cubs’ safety and development.
The end of hibernation tended to be linked to weather and elevation. A bear denning at high elevation in a year in which spring arrived late would stay snug and warm in its den for longer than a grizzly lower down and when spring arrived early. The den entry date, though, wasn’t tied to weather. It was partially linked to the availability of food: When there were plenty of tasty berries available, grizzlies tended to stay out and keep eating.
And this is where there’s a problem regarding climate change, the researchers note. Because if longer autumns promote the plentiful production of berries, and earlier springs are bringing milder conditions that prompt bears to leave their dens, then grizzlies may hibernate less. That could have repercussions for females with cubs, the researchers note, because it may lead to smaller, more vulnerable cubs being led out into the open — where humans or other bears could kill them.
Most people do not marvel much at sand. We may enjoy how it feels under our bare feet, or get annoyed when someone tracks it into the house. But few of us see those quartz grains the way geologist Walter Alvarez does — as the product of 4.5 billion years of improbable cosmic and geologic events that defined the course of human history.
Sandy beaches exist because silicon — a relatively rare element in the solar system — happened to become concentrated on Earth during the solar system’s early days, Alvarez, of the University of California, Berkeley, writes in A Most Improbable Journey. While powerful solar particles swept lighter, gaseous elements toward the outer planets, more massive, mineral-forming elements such as silicon, magnesium and iron were left behind for Earth. Later on, in the molten crucibles between Earth’s colliding tectonic plates, these elements formed the raw materials for pivotal human inventions, including stone tools, glass and computer chips. The 4.5 billion years of history that led to a computer chip is just one of many stories of scientific happenstance that Alvarez presents. Best known for proposing that an asteroid impact killed off the dinosaurs, Alvarez argues that rare, unpredictable cosmic, geologic and biological events — what he calls “contingencies” — are key to understanding the human condition.
Fans of Bill Bryson’s A Short History of Nearly Everything will appreciate Alvarez’s enthusiastic, clearly written tour of contingencies that have shaped our world, starting with the origins of life on Earth. No matter how distant the event, Alvarez quickly zeroes in on its eventual impact on people: For instance, the formation of oceanic crust helped expose rich deposits of copper ore on Cyprus, later an epicenter of the Bronze Age. A catastrophic Ice Age flood formed the English Channel in which the Spanish Armada would later sink. And ancient rivers in North America smoothed the terrain of the westward trail for American pioneers in covered wagons.
Not all of Alvarez’s arguments are convincing — his claim in the final chapter that every individual is a “contingency” in his or her own right, given how many other people could have been born instead, feels more flattering than important. Still, it’s hard to argue with his observation that impulsive human actions can transform the planet just as much as earthquakes, asteroids and other difficult-to-predict, occasionally world-changing phenomena.
Critics of this macro view, described in academia as “Big History,” say that the approach sacrifices important nuance and detail. At roughly 200 pages of text, however, A Most Improbable Journey does not claim to be a comprehensive account of history or a replacement for more detailed, focused examinations of the past. Instead, it makes a compelling case for Big History as a fun, perspective-stretching exercise — a way to dust off familiar topics and make them sparkle.
Editor’s Note: After this article was published, Horbatsch and colleagues discovered an error in their analysis, which weakened the conclusions. The new calculation of the proton radius falls in between the two previous estimates, and therefore does not add much additional support for the smaller proton.
A spat over the size of the proton just got a bit more complicated.
Measurements of the proton’s radius disagree, with one group of scientists saying it’s smaller than the accepted estimate. Now, a new analysis of old data bolsters the case for a small proton. But the result may dash hopes that the discrepancy could point the way to new physics. Scientists at York University in Toronto and the Autonomous University of Barcelona reanalyzed data from a 2010 electron scattering experiment at the Mainz Microtron in Germany, in which physicists bombarded protons with electrons and observed how the electrons ricocheted. That scattering, under the influence of the protons’ spheres of positive charge, allows scientists to tease out the size of a proton. The updated estimate came up small, the scientists report November 1 on arXiv.org.
“I think it’s not going to be easy for the proponents of a relatively large proton radius to just discuss this away,” says physicist Randolf Pohl of the Max Planck Institute of Quantum Optics in Garching, Germany. “But I’m not convinced that people will accept it.”
Until several years ago, scientists’ various techniques for sizing up the proton were in agreement. Electron scattering studies like the Mainz experiment implied the same size proton as a second technique, which involves studying the energy levels of hydrogen atoms. These estimates indicated that the proton’s radius was about 0.88 quadrillionths of a meter. But in 2010, a new technique caused a kerfuffle. Measurements of the proton radius using muonic hydrogen — a hydrogen atom with its electron replaced by a heavier relative called a muon — pegged the proton to a size 4 percent smaller than the other estimates (SN: 7/31/10, p. 7).
The flaw among the three techniques might seem likely to lie with the one outlier, the muon experiment. But “there’s actually quite a bit of certainty about those results,” says physicist Marko Horbatsch of York University, a coauthor of the new paper. So Horbatsch and colleagues decided to revisit electron scattering instead, using a subset of the data from the Mainz experiment. Horbatsch’s team focused on glancing collisions where the electron altered its course only slightly. Those collisions are the most essential for determining the proton radius. Then the researchers used theoretical calculations to account for effects that occur in more extreme collisions. Their analysis revealed a slightly scaled-down proton.
If the result is reinforced by future electron scattering measurements, the hydrogen atom data that resulted in the larger-sized proton would still require explanation. But it would also mean that the discrepancy won’t lead to new insights about the universe. Under the standard model of particle physics, muons and electrons should be identical except for mass. Physicists had hoped that the black sheep status of the muonic hydrogen experiment indicated something was different about muons. Agreement of the electron scattering and muonic hydrogen experiments eliminates that possible explanation. The new analysis is “undoubtedly sensible,” says physicist Judith McGovern of the University of Manchester. “I’m a bit surprised no one has done it before. In fact, I’m a bit surprised I haven’t done it before.”
But that doesn’t mean scientists are fully convinced. MIT physicist Jan Bernauer, one of the authors of the original electron scattering result, says he doesn’t think the puzzle will be solved by reanalysis of existing data. “I’m positive that new data are needed.”
