September 8, 2013
For decades scientists have known that sudden cardiac death–a failure in the heart’s electrical system that leads people to, well, suddenly drop dead–occurs more often in the morning hours. Analysis of data from the ambitious Framingham Heart Study led to the scientific documentation of the curious link as early as 1987. But for just as long, scientists haven’t been able to do much with that knowledge. A flurry of papers in the late 1980s pointed to possible explanations: the assumption of an upright posture, for example, or problems with the process that typically prevents blood clots. Still, scientists have been unable to pin down a basic mechanism to explain the connection between the body’s circadian clock and the electrical mishap that causes sudden death.
Now an international team of researchers has stumbled upon a lead. Mukesh Jain of Case Western Reserve University in Cleveland and his colleagues recently identified a protein whose levels oscillate with the circadian clock and, in mice, cause the ion channels governing the heart’s electrical system to oscillate with the clock too. On September 8 in Indianapolis at a meeting of the American Chemical Society (ACS), Jain reported that these oscillations also occur in human heart cells. The results point to an era when doctors may be capable of preventing sudden cardiac death, which is the leading cause of natural death in the United States, killing more than 300,000 people each year.
the ins and outs of Jain’s finding, one first needs to understand how the heart works. Think: car engine, says James Fang, the chief of cardiovascular medicine at the University of Utah School of Medicine in Salt Lake City. There’s the circulating blood, which is the fuel. There are the muscles, which pump that fuel. And there is an electrical system, with charge separation created not by a battery but by ion pumps and ion channels. Without a working electrical system, the muscles won’t expand and contract and the blood won’t flow. In a heart attack, the flow of fuel to the heart is blocked. But in sudden cardiac death, there is an electrical malfunction that prevents the heart from properly pumping blood to the body and brain. The heart’s beating becomes erratic, often displaying a type of arrhythmia called ventricular fibrillation. Heart attacks can lead to the kind of arrhythmia that can lead to sudden cardiac death, but in other cases there is no obvious trigger. No matter how the heart’s plug is pulled, death typically occurs within minutes.
Though drugs for the heart do exist–think beta blockers, ACE inhibitors–there is no drug that acts specifically to prevent the onset of arrhythmia. The most common medical response is just that: a response. Doctors treat the electrical malfunction after it has happened with a defibrillator, a technology with a history stretching back to the end of the 19th century. In 1899, two physiologists found that electrical shocks could not only create but also stop rhythmic disturbances in the heart of a dog. By the end of the 1960s, cardiac defibrillation was being reliably used on people. And in 1985, a Johns Hopkins University doctor got FDA approval for an implantable defibrillator.
Defibrillation has been the primary solution for life-threatening arrhythmias since. These devices have shrunk from “the size of luggage to the size of a cigarette box,” says Fang, and automated external versions have become popular so bystanders can help a victim without the delay of an ambulance ride. But, “it’s a bit of a crude approach,” Fang says. “Defibrillators have really formed the cornerstone for the past two or three decades, but it is not really much of a management solution,” he adds. “It is not preventing the problem. It is letting it happen and then shocking you out of it.” It’s the equivalent of jump-starting a car after the battery has died.
What’s more, Fang says, because scientists don’t know what triggers the arrhythmia to begin with, it’s tough to predict who needs a defibrillator. Take, say, 100 patients who all have weak hearts. “Probably only 10 are going to die suddenly. We don’t know who those 10 are, so we give defibrillators to all 100 people,” Fang says. “It is overkill because 90 don’t even need it. But I can’t tell which 10 are going to die.”
Here’s where Jain’s work comes in. His team, which has long studied a protein known as KLF15, serendipitously discovered that the amount of the protein in a mouse’s heart tissue cycles–going from low to high and back again over a 24-hour period. Though Jain doesn’t study electrophysiology specifically, he was aware of the link between the clock and sudden cardiac death, and he wondered whether his protein (which had been previously connected to some heart diseases) might play a role. Jain’s team found that levels of KLF15 should be high during transitions from night to day, but instead are low in mice that experience sudden cardiac death–suggesting their hearts don’t have enough of the protein during a crucial window. KLF15 controls the levels of another protein that affects how ions flow into and out of the mouse’s heart, meaning the ion channels also follow a circadian rhythm. When the researchers eliminated the presence of KLF15, “the ion channel expression went down and didn’t oscillate,” Jain says. “And these animals had increased susceptibility to ventricular arrhythmias and sudden death.” The study was published last year in Nature.
Follow-up observations, presented at the ACS meeting, confirm that the oscillation of KLF15 and the ion channels occur in human heart cells. Those findings “start to build a case that this is potentially important to human biology and human disease,” Jain says.
Jain believes his molecular work and other similar studies on the horizon could lead to drugs that offer a solution better than defibrillation. “We need a fresh start,” he says. “What we are doing ain’t working.” But there is a long way still to go. Future studies will try to find molecules that could boost KLF15 levels, to look for other clock-related molecules at work in the heart and to seek out genetic variants associated with sudden cardiac death.
August 29, 2013
A rocky, icy body the size of Rhode Island is playing follow the leader with the seventh planet from the Sun, whizzing along Uranus’ orbit one-sixth of a revolution ahead of the planet. The body, temporarily dubbed 2011 QF99, is the first of its type found to circle with Uranus. Researchers reporting in the journal Science document its detection and show that it is probably not alone
, promising a clearer picture of the ongoing celestial pinball game in the solar system’s outer reaches.
Thousands of similarly positioned bodies are known to exist around Jupiter; they are called Trojans because each is named for a mythological character in the Trojan War. But scientists had believed that gravitational tug around Uranus and Saturn, particularly the pull of Jupiter, made similar companions there unlikely.
What exactly are Trojans? Their story dates back to the 18th century, when a famous mathematician named Joseph-Louis Lagrange wrote an essay on the problem of three bodies, identifying five positions where the gravitational effects of a body orbiting another body (think of the Earth-Moon system as a single body circling the Sun) would allow a third smaller body to stay balanced. When located at any of these five Lagrange Points, the third body would appear stationary relative to the other two. Three of these five positions, called L1, L3 and L3, would be unstable–if the third body drifted just a bit off course from any of these positions, it could never recover from the misstep. L1 and L2 are ideal locations for placing artificial satellites that study the Sun and space, although the spacecrafts’ trajectories have to be constantly tweaked so that they stay at these points.
But at two Lagrange Points, dubbed L4 and L5, the body would be pulled right back regardless of which way it drifted, causing it to swing around the point like a gymnast on a high bar. In fact, multiple bodies–many thousands–could dance around each point within an elongated region of stability that contours to the orbital path of the planet. One of these points sits 60 degrees ahead on that orbital path and another 60 degrees behind.
Other three-body systems have these same balance points, and in 1906 astronomers found an asteroid in the
L4 region of Jupiter’s orbit around the Sun, naming the body Achilles. In the following years, more Trojan asteroids were discovered around Jupiter’s L4 and L5 and, more recently, Trojans have been found along other planets’ orbits, including Mars’, Neptune’s and even Earth’s.
But none had turned up for Uranus or Saturn–until now. As part of a Canada-France-Hawaii Telescope survey designed to search for small bodies orbiting beyond the most distant planet, Neptune, a team of astronomers spotted 2011 QF99 in three images taken an hour apart on the same patch of sky. The object’s brightness suggested it was 60 kilometers across and its orbit pinned it as distant as Uranus, but further observations in 2011 and 2012 distinguished it from a Centaur, an unstable icy body that orbits the Sun and occasionally crosses, but doesn’t follow or lead, planetary orbits. The team’s study showed 2011 QF99 running out ahead of Uranus like a dog on a leash: It was an L4 Trojan.
“A Uranian Trojan was not the focus of our survey,” says Mike Alexandersen, an astronomer at the University of British Columbia. “When we realized what it was, we were like ‘Whoa, wow.’”
Unlike most other known Trojans, which adopted their current positions early during the solar system’s formation, 2011 QF99 was probably first a Centaur and was captured at L4 later on, caught as it leaked inward from more distant reaches. Numerical analyses of the details of the orbit of 2011 QF99 suggest it will remain as a Trojan for 70,000 years before, after a million years or so, it moves beyond the L4 region of stability and rejoins the Centaurs.
2011 QF99, then, is a temporary Trojan. And simulations by Alexandersen and his team, reported for the first time in the new paper, find that 2011 QF99 is not alone. About 3 percent of the small bodies in the outer solar system share an orbit with Neptune or Uranus at any given time. “There are a lot of asteroids and comets flying around the solar system, and a lot of them cross the orbits of planets and only a tiny fraction get captured,” he says. Capture is “
a low probability event. Intuitively, we thought it had an even lower probability.”
While the more permanent Trojans have quite a lot to to say about primordial jostling, the temporary Trojans–including others discovered orbiting with Neptune and Earth–could reveal information on the amount of Centaurs populating the nether reaches, how exactly they got there and what paths they follow.
“Those unstable objects, the Centaurs, often go on to become Jupiter-family comets, many of which approach the Earth and could, eventually, pose an impact threat,” says Jonti Horner, an astronomer at the University of New South Wales who wasn’t involved in the study. “Being able to study those objects when they’re far from the Sun, and therefore not hidden by a cometary coma, can tell us a lot about comets and other objects that can threaten Earth.”
“It’s a really exciting discovery for me, and for other people who look at the solar system’s small bodies,” he added.
Alexandersen, who notes that the risk of impact is extremely low, says the results speak to how much is still left to know about our solar system. He predicts that more will be revealed as astronomers continue to detect smaller and smaller objects. “If there is one 60-kilometer Trojan, then there are probably dozens of one-kilometer Trojans,” he says. “We just can’t see them yet.”
August 6, 2013
Media reports have called them the “tigers of the sea” and “white death,” striking potential prey with the “power of a horse
.” Such descriptions are fearsome enough, but it’s the great white shark’s purported appetite for human flesh that sends chills skittering up spines. A 1916 article in the Richmond Times-Dispatch, printed just after the still-famous string of shark-related deaths that year, came to a truly creepy conclusion: Those who believe that the great white’s propensity to dine on humans is real and steadily increasing “have the weight of evidence on their side.”
Thanks to the movie Jaws, the great white’s reputation as a ruthless man-eater pervades to this day. So you can’t be blamed for being slightly concerned if you took
a quiz claiming to match your personality with a shark’s, put together by the Discovery Channel, and found out that you are a great white. Sure, you may indeed be “curious yet cautious” and “aggressive but also recessive;” people may be “dangerously intrigued” by you. But does your personality really match that of such a loathed creature? Can an entire species of sharks be generalized in that way?
Jean Sebastien Finger, a biologist at the Bimini Biological Field Station in the Bahamas may have answers. For a little over a year, Finger has been trying to find out whether sharks have personalit
ies. Personality, by its very name, seems to apply only to a person, e.g., a human. But can a shark actually be shy? Social? A risk-taker? Fierce or mellow?
Though Finger is the first, to his knowledge, to study sharks in this way, he is not alone among animal behaviorists. His work fits with a growing field of research investigating what scientists call “behavioral syndromes,” or ways of acting that differ from one individual to another but are consistent across time and situation. It turns out scientists are finding personality in a whole range of species, sharks now included.
The basic idea that nonhuman animals have personality isn’t all that new. In the 1920s in Conditioned Reflexes, Ivan Pavlov describes his observations of different behavioral responses in dogs “depending on the type of nervous system of the animal.” And in 1938, an American psychologist named Meredith P. Crawford developed a behavior rating scale for young chimpanzees, publishing the work in the Journal of Comparative Psychology. Jane Goodall was a bit more personal, noting in the memoir Through a Window, that the personality of one chimp named Passion was as different from another chimp’s “as chalk from cheese.”
Yet only recently has scientific opinion shifted beyond viewing this variation as meaningless noise. Researchers now want to quantify individual variation and figure out why it exists. For example, scientific observers are increasingly coming to the realization that animals don’t always behave in the best way in a given situation, says Alexander Weiss, a psychologist at the University of Edinburgh who studies evolution of personality. An animal may not go off on its own to look for food, even though that seems like the best choice. “They are behaving suboptimally,” Weiss says, “what is underlying that?”
Imagining primates and even pets with their own personalities isn’t so hard. But some of the most fascinating work stars less predictable animals–birds, fish, hermit crabs and spiders, among others. Unlike the shark quiz offered by the Discovery Channel, the studies distinguish not one species from the next, but individuals within a species.
Finger’s species of choice is the lemon shark, and with good reason. These sharks are the lab mice of the sea. Scientists know a ton about the biology of lemon sharks–they are easy to capture and handle, and they are amenable to captivity. What’s more, Finger works with juveniles, which measure a meter or less in length.
After catching and tagging these sharks in the shallow waters of Bimini, about 60 miles east of Miami, Finger and his colleagues run a battery of tests in experimental pools. In a test looking for sociability, they allow the sharks to swim around together for about 20 minutes, documenting every 30 seconds whether a shark is interacting with its peers. “If you see two sharks following each other, that is typical social behavior,” says Finger. “It’s very similar to humans in the sense that some people will be in groups more often than other people.” In another test looking for an interest in novelty, Finger and his team put sharks, one at a time, in a 40-by-20 foot pen that the sharks have never experienced. The team documented how much each shark explored the pen.
In both cases, sharks are tested again after a week and after six months (returning to their natural habitat during the longer interim, only to be caught once again). The repetition allows the researchers to test for consistency. Preliminary results presented in July in Albuquerque, New Mexico, at the Joint Meeting of Ichthyologists and Herpetologists show that individual lemon sharks do have different degrees of sociability and novelty-seeking. “They are not machines, they have personality,” Finger says.
What’s more, initial data hint at a trade-off: Sharks more interested in novelty tend to be less social, and vice versa. Finger suspects that animals that have the safety of a group take fewer risks. Novelty-seekers venture off on their own and, though more prone to danger, they also don’t have to share the food they find with others. It’s sort of how the risk-takers and game-changers in human societies aren’t always so good at playing well with others.
In time, scientists hope to compare personality data from a range of species to try to understand why animals, including people, have personality and how it evolved. Personality, and even a mix of personalities within a group, may turn out to have huge consequences for survival. “We find in the human literature that personality is massively important for things like work satisfaction, marital stability, how long we live, whether we get heart attacks,” Weiss says.
Until then, Finger’s big message is that “you can’t generalize behavior of one individual to a species.” Even if a species as a whole tends to be more aggressive than another, some individuals within that species could still be pretty mellow.
So although your concept of self isn’t likely to be wrapped up in an online quiz, you may find comfort in Finger’s words. Maybe
you are a great white, but not every great white is the same.
July 12, 2013
A glass of merlot may make the world look rosy, but it can also be a source of frustration for a physicist. The wine pours, splashes and swirls, yet the glass remains stiff as a solid vessel.
Zoom in on the merlot and you’ll see molecules held close together but moving about with no fixed position. Zoom in on the wine glass and you’ll also see this disordered arrangement, but no movement.
On an atomic level, the two forms of matter look the same. Even though a glass is frozen solid, it lacks the rigid crystalline structure found in, say, ice cubes.
Though artisans have been making glass for millennia and scientists have been studying its structure for decades, until now there has been no clear experimental evidence to confirm what prevents liquids that form glasses from crystallizing. In a new paper published online in Science, a team of Japanese researchers used a high-powered electron diffraction microscope to view glass at the tiniest scales yet. At such high resolution they saw what looks to be a basic unit of some glasses–atoms packed in a distorted version of an icosahedron, a three dimensional shape with 20 faces.
With sophisticated geometric tools, the team characterized those distortions, reporting in the paper that they allow the system to “retain dense atomic packing and a low energy state.” Certain arrangements of atoms, the researchers conclude, are the very essence of glassiness because they interfere with the development of a well-organized crystal.
Though the researchers were studying a glass made of zirconium and platinum, not your average windowpane, the results may hold for glasses more broadly. By understanding the ways atoms organize, material scientists can find ways to make new glasses and manipulate the ones they’ve got.
But glass is far from figured out. While the study explains why some liquids form glasses instead of crystallizing, it doesn’t explain why these liquids can become sluggish enough to be solid, says Duke University chemist Patrick Charbonneau.
A large community of scientists have been attempting to resolve the sluggishness since the 1980s, but they can’t agree on the solution and they even argue about the best approach.
One popular strategy takes a step back to try to understand how atoms fill a given space. It treats the atoms in glass as hard spheres packed together. Simple, right? “There is no quantum mechanics, there is no string theory, you don’t have to invoke outer space,” Charbonneau says. And yet even studying glass in this way has proven incredibly difficult because of the complications that come with figuring out what positions so many particles could occupy. On top of the inherent challenge of describing the arrangement of the spheres, the approach is a simplification and it is not clear how relevant it would be for real-world glasses.
Still, Charbonneau appears energized when he talks about such research problems. His glass of merlot is half full, because he believes the last few years have brought immense progress. Scientists, he says, have become more creative in asking questions about glass. Charbonneau’s own research simulates glass in higher dimensions, findings that could have important implications for the degree of disorder in three-dimensional glass. Other researchers are considering what would happen if you immobilized some particles in a supercooled liquid, hoping to illuminate how such liquids achieve a glassy state. Still more are considering atoms in glass as entities that can move on their own, sort of like biological cells. All of these efforts are trying to determine the types of interactions that contribute to the formation of glass, so that scientists will recognize a really good sluggishness theory when they see it.
Despite all this talk about movement, don’t expect your wine glass to flow in any visible way anytime soon. This glass “will last longer than the timescale of the universe,” Charbonneau says. Claims that the stained glass in medieval cathedrals is thicker at the bottom because glass flows are bunk. But exactly why it doesn’t flow still remains a mystery.