Hair Follicles Track the Body's Clock

Those red-eye flights and all nighters may be leaving their mark in your hair. Researchers have found that hair follicles contain a signature of the 24-hour circadian clock that sets our sleeping habits. The method could one day help track patients with sleep disorders and help evaluate health problems in late-night shift workers.

At one point, researchers thought that the circadian clock was located solely in the brain. But after scientists discovered human circadian clock genes in the late 1990s, they found that the genes were expressed in tissues throughout the body. In experiments with mice, researchers have linked these genes to weight gain and even to the "lost in time" feeling of marijuana use, but they've had a harder time studying them in humans. That's because analyzing these genes relies on invasive methods, such as drawing a person's blood several times a day or excising a small chunk of skin.
Makoto Akashi of Yamaguchi University in Japan and his colleagues sought an easier way to check clock gene activity. They turned to hairs plucked from scalps or beards, which contain cell-rich follicles. When they extracted RNA from these cells, they found that circadian gene activities peaked when volunteers were awake and alert, and it peaked earliest in the volunteer who woke up earliest in the morning.

Next, Akashi and colleagues disrupted the sleep-wake cycle of healthy people: They asked volunteers to sleep in later and later over a 3-week period and to shine a bright light on themselves to mimic sunlight for half an hour after they awoke. At the end of 3 weeks, when the volunteers were waking up about 4 hours later than they used to, the activity of their hair follicle circadian genes had shifted too—but only by about two and a half 2½ hours, the team reports online today in the Proceedings of the National Academy of Sciences.
 
Akashi's group saw a similar lag in shift workers. The team examined the hair follicles of volunteers who worked the 6 a.m. to 3 p.m. shift one week, the 3 p.m. to midnight shift the next week, and back to the morning shift on their third week. Clock gene activity lagged 5 hours behind the workers' lifestyles, the researchers found, which indicates that 3 weeks was not long enough for the body clock to adapt to the new schedules.

Tracking clock genes in hair follicles could help researchers better monitor patients with sleep disorders and other circadian rhythm dysfunction, says molecular biologist Ueli Schibler of the University of Geneva in Switzerland. Because these genes control everything from organ function to eating cycles, he says, the lag the team observed in shift workers could help explain some of the serious health problems they develop.

Unhappiness Is in the Eye of the Beholder

smile and a frown mean the same thing everywhere—or so say many anthropologists and evolutionary psychologists, who for more than a century have argued that all humans express basic emotions the same way. But a new study of people's perceptions of computer-generated faces suggests that facial expressions may not be universal and that our culture strongly shapes the way we read and express emotions.

How do you feel? When presented with computer-generated faces, East Asians and Western Caucasians judged emotions differently, particularly for negative emotions.

Credit: Jack et al./PNAS

The hypothesis that facial expressions convey the same meaning the world over goes all the way back to Charles Darwin. In his 1872 book The Expression of the Emotions in Man and Animals, the famed naturalist identified six basic emotional states: happiness, surprise, fear, disgust, anger, and sadness. If facial expressions are just cultural traits, passed down through the generations by imitation, their meanings would have diverged by now, he argued. A smile would signal happiness for some and disgust for others. But that's not what he found, based on his correspondence with researchers around the world using photos of various facial expressions. So Darwin concluded that the common ancestors of all living humans had the same set of basic emotions, with corresponding facial expressions as part of our genetic inheritance. Smiles and frowns are biological, not cultural.

Or are they? Rachael Jack, a psychologist at the University of Glasgow in the United Kingdom, says that there is a fundamental flaw in the facial expression studies carried out since Darwin's time: Researchers have been using Darwin's six basic expressions as their starting point, and yet they were first identified by Western European scientists studying Western European subjects. The fact that non-Western subjects can recognize the emotions from photographs of those facial expressions has been taken as support for the universality hypothesis. But what if non-Western cultures have different basic emotions that underlie their expressions? Those expressions may be similar to those of Westerners, but with subtle differences that have gone undetected because no one has looked.
To test the true universality of Darwin's six emotional categories, Jack and colleagues used a computer program to create virtual faces with 4800 expressions. The program generated the faces by contracting virtual facial muscles, pulling the corners of the mouth up or down, widening or narrowing the eyes, and so forth. Half of the expressions were shown on a Western Caucasian face and half on an East Asian face.

Then Jack's team asked volunteers to decide which emotions the faces were expressing, if any. The researchers tested 15 recently arrived immigrants from East Asia, using a survey to ensure that they had spent minimal time around Westerners. They also recruited 15 Caucasian Westerners as a control group. For each of 4800 faces, the subjects could choose one of Darwin's six basic emotional categories and rate the intensity of the expression on a five-point scale. If they did not perceive a clear expression on a face, the subjects reported, "Don't know." If Darwin's basic emotions are universal, all the subjects should match the same faces with the same emotions.

That's not what Jack's team found. For Western Caucasians, Darwin's six basic emotional expressions popped right out of the data, in type and intensity. But the East Asian subjects didn't see the faces the same way, the team reports online today in the Proceedings of the National Academies of Science. Smiles meant the same thing to everyone, but the responses from the East Asian subjects did not form clear categories, especially for faces expressing surprise, fear, disgust, and anger.

The researchers conclude that Western Caucasians use a distinct set of facial muscles to express basic emotions. Each culture may have fundamental expressions, but they are not necessarily shared by other cultures. For East Asians, Jack speculates that facial expressions are built from other fundamental emotions, such as "shame, pride, or guilt."

The study is "a strong challenge to the widely held belief that certain emotional expressions are biologically basic," says Lisa Feldman-Barrett, a psychologist at Northeastern University in Boston. If wrong, that belief is doing harm, she says. For one thing, difficulty recognizing facial expressions is used to diagnose mental illness. For another, she says, "in the U.S. alone, millions of dollars each year are spent on law enforcement and security training to 'read' emotion in the face." But if those faces belong to people from different cultures, their emotions and intentions may be illegible.

Alternative Therapies Aren't Used as Substitutes for Asthma Meds: Study

Almost one in five parents has turned to an alternative or complementary medicine or treatment for their child's asthma, but new research has found that parents are not abandoning traditional treatments in the process.

"We found that there were really no differences between the groups that used complementary and alternative medicine and those that didn't [in terms of adherence]. It seems that parents are using these therapies as complementary medicine alongside prescribed asthma treatments," said study author Dr. Julie Philp, a pediatrician and a dermatology resident at the University of California, San Francisco.
Results of the study were released online and published in the May issue of Pediatrics.

Complementary and alternative medicine includes health care practices that aren't usually included in more conventional medicine. Such treatment may include herbal remedies, acupuncture and homeopathy. The use of complementary and alternative medicine is on the rise among children, according to background information in the article. Other research has found that children with respiratory problems may be even more likely to be given an alternative medicine treatment.

Health care providers have been concerned that parents who turn to complementary and alternative medicine therapies might cut back on the use of standard medications (for example, the daily use of controller medications such as inhaled corticosteroids). Daily controller medications typically have low adherence rates, even without the addition of other medications or therapies, according to the study.
To assess whether or not the use of complementary and alternative medicines might further lower adherence rates to those medications, Philp and her colleagues used data from a larger study that was designed to assess the impact of physician education on the management of asthma.
The new study included 187 parents of children on daily controller medication for their asthma. The study population was predominantly white and 61 percent had a college education or higher. Eighteen percent of the parents said they had turned to some form of complementary or alternative medicine for their children.

The researchers specifically asked about the use of herbs, teas, dietary changes, breathing exercises, meditation, prayer, massage, biofeedback or homeopathy.

Each week, the children in the study missed an average of 7.7 percent of their daily controller medication doses. The researchers found that the use of complementary or alternative medications didn't seem to affect that rate.

"The data from this study suggest that complementary and alternative medicine use is not necessarily 'competitive' with conventional asthma therapies; families may incorporate different health belief systems simultaneously in their asthma management," the study authors concluded.
Experts still urge parents to be wary when considering alternative medicines or treatments for their child's asthma.

"I would urge parents to proceed with caution any time they use an alternative treatment. They're not magical, and if something works to improve symptoms, then it has the potential to hurt you, too," said Dr. Raoul Wolfe, medical director of asthma medicine at La Rabida Children's Hospital in Chicago.
He added that people should talk with their child's doctor to make sure whatever alternative therapy they might want to try doesn't have the potential to interact with standard medications.
Philp said that one of the study's aims is to get pediatricians to open up a dialogue with patients and their parents. For parents, she recommends, "Share with your child's health care provider what your beliefs are and work with the doctor to find complementary and alternative therapies that are safe. The doctor, parent and child should be a team working together."

Jonathan Feldman, an assistant clinical professor of epidemiology and population health at Albert Einstein College of Medicine in New York City, agreed that parents and providers need to talk about alternative medicine. "The number-one message is the need for open communication," he said. "What we, and others have found, is that if doctors don't ask, families won't tell. Families don't bring up alternative medicine use with providers. It's sort of taboo. But, parents should be more open about what they're giving the kids."

And, Feldman added that providers need to be sure they're familiar with the types of alternative treatments that their patient populations might be using. For example, he said that in his area, which has a large black and Puerto Rican population, one of the most common alternative treatments that people use is a menthol chest rub. But, he said, patients often don't think of this as an alternative treatment; it's just something that their families have always used. So it's important for health care providers to be specific when they ask about alternative treatments, he explained.

SOURCES:
Julie Philp, M.D., pediatrician and dermatology resident, University of California, San Francisco; Raoul Wolf, M.D., medical director, asthma medicine, La Rabida Children's Hospital, Chicago; Jonathan Feldman, Ph.D., assistant clinical professor, epidemiology and population health, Albert Einstein College of Medicine, and associate professor, psychology, Yeshiva University, New York City; May 2012, Pediatrics

Even Young Teens Show Signs of Sun Damage

In a new study that used a special type of photography to unveil hidden signs of sun damage, middle schoolers showed evidence of levels of UV exposure that could raise their risk for melanoma later in life.

Not only can the technology spot who is most vulnerable to the ravages of too much time spent tanning, the researchers noted, but it could also be used as a powerful deterrent to teenagers who think basking in UV rays is a healthy habit.

"There's two issues here," explained study co-author Dr. Robert Dellavalle, from the University of Colorado Cancer Center in Denver. "One is that there's nothing better for keeping teenagers out of the tanning booth than showing these pics. What we didn't know before was if these ugly pics were just ugly pics that scare people, or if they actually correlated with skin cancer. Now we've found that they do. When you have lots of moles, have blue eyes or are a redhead -- all things we know are associated with greater melanoma risk -- you have uglier UV photos," he said.

"And another surprising thing," Dellavalle added, "is that at age 12 and 13 we're already seeing a lot of sun damage. And because seeing this damage in UV photo form is sort of like meeting your inner zombie, this could be a great tool in getting kids to think about sun safety in a more personal way."
Dr. Ryan Gamble, who conducted the study while a postdoctoral researcher in Dellavalle's lab and who is now a dermatology resident at the university, and colleagues released their findings online in advance of publication in an upcoming print issue of the Journal of the American Academy of Dermatology.
Gamble pointed out that one in 50 Americans will face a melanoma diagnosis in their lifetime.
UV photography makes visible so-called "mottled pigmentation," dark spots and freckling that indicate sun damage that is otherwise invisible to the naked eye.

The authors noted that the technology has already been used to focus attention on sun safety and the dangers of overexposure among college students and middle schoolers.

However, only one small study of just eight children has explored how the sun damage revealed in such photos correlates with known risk factors (having fair skin, blue eyes, red hair, and/or visible facial freckling) for melanoma.

In this latest study, the researchers focused on 585 boys and girls who were born in 1998, and were 11 or 12 at the study's start. Almost 80 percent were non-Hispanic white youths.

The faces of all the children were photographed with eyes closed and without sunscreen, make-up or moisturizer in three formats: standard photography; so-called cross-polarized photography (using filters to block unwanted light reflection); and UV photography.

At the same time, full-body skin exams were conducted by a team comprised of a dermatologist, pediatrician, medical student and pediatric nurse. Eye color was noted, alongside indications of freckling, and skin and hair color assessments.

The results: sun damage severity revealed in the UV photographs was found to line up very closely with factors that have long been linked to a higher melanoma risk.
In other words, boys and girls who had light-colored skin, blue eyes, red hair, and/or freckles did indeed show more skin damage on the UV photographs than those who did not.
This, the researchers said, means that UV photography does not lie: the more damage the technology highlights, the greater the cancer risk.

"We hope that our research will help make the use of these photographs more mainstream, whether in a clinic setting or as a public health intervention," said Gamble. "With greater awareness of melanoma and increased use of sun prevention and early detection strategies, much of the occurrence of the disease and its complications can be prevented."

Dr. David Leffell, a professor of dermatology and otolaryngology and plastic surgery at the Yale School of Medicine, said that if it were priced right, the technology could indeed help "lead to a recognition that sun protection is important." Currently, such systems cost about $20,000.
"It is true that the appearance of sun-damaged skin in these images is frightening, and patient response is often shock," Leffell noted. "The pediatric population of course is especially important to communicate this message to, and the photographs -- if the price can be brought down -- is a good idea."

But, for the time being, price remains an issue, said Dr. David Pariser, past president of the American Academy of Dermatology Association and a professor of dermatology at Eastern Virginia Medical School in Norfolk, Va.

"It's not an inexpensive modality. So, I'm not sure about the practicality of rolling this out as a screening tool," Pariser said.

"I've used UV photography myself during clinical research, and it certainly is a very dramatic way to show sun damage," Pariser added. "It's sort of like looking at yourself 15 or 20 years later. In fact, I've never had anyone who's seen a photograph of himself who's not reacted by saying they will stop exposing themselves to the harmful effects of the sun."

SOURCES:
Robert Dellavalle, M.D., Ph.D., M.S.P.H., investigator, University of Colorado Cancer Center, and associate professor, dermatology, University of Colorado School of Medicine, Denver; Ryan G. Gamble, M.D., dermatology resident, University of Colorado, Denver; David Pariser, M.D., F.A.A.D., past president, American Academy of Dermatology Association, and professor, dermatology, Eastern Virginia Medical School, Norfolk, Va.; David J. Leffell, M.D., professor, dermatology, and professor, surgery (otolaryngology and plastic), Yale School of Medicine, New Haven, Conn.; March 12, 2012, Journal of the American Academy of Dermatology, online

CT Scans Deliver More Radiation to Obese People: Study

Obese and overweight patients who undergo CT scans are exposed to much more radiation than people of normal weight, researchers say.

The challenge for heavier people is that more radiation is needed to scan their bodies, a radiation specialist said.

"One has to customize the dose based on patient size, increase the power of the X-rays and the quantity that are going inside," said Dr. Dushyant Sahani, director of CT imaging services at Massachusetts General Hospital and an associate professor of radiology at Harvard Medical School.

Nearly 60 percent of U.S. adults are overweight or obese, according to the study. As obesity-related health challenges surface, so do orders for medical scans, the authors said. Because radiation can cause cancer and other ill effects, researchers have been concerned about the risks of exposure derived from medical imaging.
However, Sahani, who was not involved in the study, said the excess body fat of extra-large patients absorbs much of the radiation, meaning that they may face no extra danger.

"Fat is not as sensitive to undergoing any bad changes as the other tissues," said Sahani.
Even if an obese patient gets twice the radiation as a smaller person of the same age, the risk of radiation damage would be higher for the smaller person, he said.

The study authors, all from the Rensselaer Polytechnic Institute in Troy, N.Y., launched their research to better understand how radiation in CT scans affect the bodies of heavier people. Statistics about their radiation haven't been previously available, the study authors said. "We want to fill this gap," said study lead author Aiping Ding, a research associate at the institute.

CT scans are used to create images that divide the body's organs into sections, or slices. Sahani said, "They produce a detailed anatomic picture, as if someone's body has been actually sliced."
In the new study, the researchers created 10 computerized male and female "phantoms" that represented people of various body types, ranging from normal to morbidly obese. (Previous research using phantoms had mostly looked at average-sized people).

The researchers then calculated how much radiation would enter the bodies during CT scans. In some cases, the dose that reached organs was as much as 57 percent higher in the obese patients.
"We want to tell people that obese patients receive high doses and that we can use our phantom to quantify the specific dose for the patient," Ding said. "Our study can be a good reference for radiologists."

What should patients do with this information? Ding suggests that they ask their radiologist about the risk they face when they undergo a CT scan. Patients are at especially high risk at hospitals that take multiple CT scans of individual patients in a day, Ding said.

The study appeared recently in the journal Physics in Medicine & Biology.

SOURCES:
Dushyant Sahani, M.D., director of CT imaging services, Massachusetts General Hospital, and associate professor of radiology, Harvard Medical School, Boston; Aiping Ding, Ph.D., research associate, Rensselaer Polytechnic Institute, Troy, N.Y.; April 6, 2012, Physics in Medicine & Biology

Study Probes How Sad Movies Make Viewers Happy

Watching sad movies makes people happier because it causes them to think about their loved ones, a new study finds.

"Tragic stories often focus on themes of eternal love, and this leads viewers to think about their loved ones and count their blessings," lead author Silvia Knobloch-Westerwick, an associate professor of communication at Ohio State University in Columbus, said in a university news release.

The study included 361 college students who watched a shortened version of the movie Atonement, in which two lovers are separated and die during World War II. Before and after the movie, the participants were asked questions that measured how happy they were with their life.

The more the movie made participants think about their loved ones, the greater their increase in happiness. Participants who had self-centered thoughts during the movie -- such as, "My life isn't as bad as the characters in the movie" -- did not experience increased happiness.

"People seem to use tragedies as a way to reflect on the important relationships in their own life, to count their blessings," Knobloch-Westerwick said. "That can help explain why tragedies are so popular with audiences, despite the sadness they induce."

The study appears online and in an upcoming print issue of the journal Communication Research.

More information
Mental Health America outlines 10 ways to live your life well.  
(SOURCE: Ohio State University, news release, March 26, 2012)

Researchers ID Genes That May Determine Mental Illness

Genes that increase or reduce the risk of certain mental illnesses and Alzheimer's disease have been identified by an international team of scientists.

The researchers said they also pinpointed a number of genes that may explain individual differences in brain size and intelligence.

"We searched for two things in this study," senior author Paul Thompson, a professor of neurology at the University of California, Los Angeles David Geffen School of Medicine and a member of UCLA's Laboratory of Neuro Imaging, said in a university news release.

"We hunted for genes that increase your risk for a single disease that your children can inherit. We also looked for factors that cause tissue atrophy and reduce brain size, which is a biological marker for hereditary disorders like schizophrenia, bipolar disorder, depression, Alzheimer's disease and dementia," he explained.

The researchers said this was the largest-ever brain study to date, according to the release.
The team of more than 200 scientists at 100 institutions worldwide measured the size of the brain and its memory centers in thousands of MRI images from more than 21,100 healthy people and screened the participants' DNA at the same time.

In people with smaller brains, the researchers found a consistent relationship between subtle differences in the genetic code and smaller memory centers. They also found that the same genes affected the brain in the same ways in people in different populations.

The findings may provide new potential targets for drug development.

"Millions of people carry variations in their DNA that help boost or lower their brains' susceptibility to a vast range of diseases," Thompson said. "Once we identify the gene, we can target it with a drug to reduce the risk of disease. People also can take preventive steps through exercise, diet and mental stimulation to erase the effects of a bad gene."

The researchers also found that a variant in a gene called HMGA2 may affect brain size and intelligence.

"We found fairly unequivocal proof supporting a genetic link to brain function and intelligence. For the first time, we have watertight evidence of how these genes affect the brain. This supplies us with new leads on how to mediate their impact," Thompson said.

The study was published online April 15 in the journal Nature Genetics.

Searching for clues to disorders such as autism and schizophrenia, the researchers also plan to look for genes that influence brain wiring. For that task, Thompson said they will use diffusion imaging, a new type of brain scan that tracks communication pathways among brain cells.

More information
The U.S. National Institute of Neurological Disorders and Stroke has more about the brain.
(SOURCE: University of California, Los Angeles, news release, April 15, 2012)

Drugged Honeybees Do the Time Warp

Waking up from surgery can be disorienting. One minute you're in an operating room counting backwards from 10, the next you're in the recovery ward sans appendix, tonsils, or wisdom teeth. And unlike getting up from a good night's sleep, where you know that you've been out for hours, waking from anesthesia feels like hardly any time has passed. Now, thanks to the humble honeybee (Apis mellifera), scientists are starting to understand this sense of time loss. New research shows that general anesthetics disrupt the social insect's circadian rhythm, or internal clock, delaying the onset of timed behaviors such as foraging and mucking up their sense of direction.

Putting insects to sleep is nothing new. Researchers have used the animals for decades to figure out how anesthetics work, because the drugs elicit the same effects, at the same concentrations, in many different organisms. "You can give the anesthetic to a monkey and a snail, and they'll fall over and stop moving," says study co-author Guy Warman, a chronobiologist at the University of Auckland in New Zealand.

The circadian rhythm's daily cycles are also common across organisms. So-called clock genes help regulate the rhythms that make us feel awake during the day and tired at night, while also prompting honeybees to search for nectar at certain times of day. External inputs, such as light, fine-tune those cycles. In our case, they keep us on a roughly 24-hour schedule.

Warman and his colleagues used the honeybee's sense of timing to study the behavioral and genetic effects of isoflurane, a common anesthetic for human surgeries. "[Honeybees] display behaviors in their everyday life that tell you exactly what time of day they think it is, which isn't possible to do [with] mammals," Warman notes.

First, the researchers tested the insects' ability to navigate back to their hive after being dosed with isoflurane for 6 hours. Honeybees use the sun's position, along with their internal clock, to determine the way home. If anesthetics interrupted that clock, the researchers expected to see a shift in the bees' headings. And indeed, when the team released the insects into novel areas in Germany and New Zealand and watched them try to fly home, post-anesthetic bees were nearly 90° off in the Southern Hemisphere and 62° off in the Northern Hemisphere. This deviation indicated a delay in the honeybees' internal clock, the researchers report online today in the Proceedings of the National Academy of Sciences.

When Warman and his colleagues studied isoflurane's effects on when honeybees started searching for nectar, they saw similar delays. Bees carrying radio frequency identification tags and trained to visit a feeder between 9 a.m. and 10 a.m. every day delayed their post-anesthesia searches by about 3 hours.
The researchers then tested the anesthetic's genetic effects. They sampled bees every 3 hours for 36 hours before and after anesthesia, measuring concentrations of mRNA—molecules carrying protein-building instructions—for three clock genes. They found that mRNA cycles from two of the genes were delayed between 4 and 5 hours after anesthesia. Movements of bees in and out of the hives were delayed by about 5 hours. When the team dosed hives at night, the anesthetic did not produce any delays in mRNA cycles.

"I think [it's] a very creative and provocative paper," adds Gene Robinson, an entomologist and neuroscientist at the University of Illinois, Urbana-Champaign. "I think they've made a compelling case that anesthesia is affecting the [circadian] clock," adds neurobiologist Ravi Allada of Northwestern University in Evanston, Illinois, who was not involved in the research. People have considered anesthesia's effects on movement and sensory perception, but no one has focused on its effects on the circadian clock, he notes.

Next up: seeing if this research will translate to humans. Warman says his team is currently looking at whether shining bright light at someone under anesthesia—a well known way to alter the circadian clock—could also reduce the procedure's disorienting effects.

One in 16 youth play the "choking game:" study

The game -- a misnomer because of its risks, researchers say -- involves putting pressure on the neck with a towel or belt to cut off someone's oxygen supply, then releasing the pressure to give a "high" sensation.

The one-in-16 figure is in line with research from elsewhere in the United States and in other countries where youth are known to play the choking game, according to Dr. Thomas Andrew, New Hampshire's chief medical examiner.

"Of more concern in these studies that have been coming out over the last several years is that among that group... there's a smaller subset that seem to like the phenomenon enough to continue doing it on a regular basis," said Andrew, who has studied asphyxia games but wasn't involved in the new research.
Of Oregon kids who said they'd played the choking game, close to two-thirds reported having done so more than once, and more than a quarter had played at least five times.

"Some kids may experience it and say, 'This is the worst thing that's ever happened to me. I'm never going to do it again,'" Andrew told Reuters Health.

"The kids that go on to repeat it, it may not be in groups anymore. It could escalate into doing it by yourself with a ligature, and of course that's the highest risk of all."

Along with the risk of asphyxiation, the choking game comes with a chance of seizures that can cause brain damage, Andrew said. He's also seen cases of kids with fatal head injuries from when they hit the ground after their air supply was cut off.

"The more times you repeat something like this, the better the chance of a bad outcome," said Robert Nystrom, from the Oregon Public Health Division in Portland, who worked on the study.
His team's findings are based on a 2009 survey given to more than 5,000 Oregon eighth graders. The researchers found that kids who were sexually active and those who used drugs or alcohol were more likely to have played the choking game -- also known as Knock Out, Space Monkey or Flatlining -- than abstainers.
Boys and girls were equally likely to have participated.

The U.S. Centers for Disease Control and Prevention found 82 media reports of kids dying from playing the choking game from 1995 through 2007 -- but that the figure is likely an underestimate, Nystrom and his colleagues write in Pediatrics.

If a kid asphyxiates trying to get high alone, the death could look like a suicide, for example.
While groups of youth have been playing asphyxiation games for generations, researchers said they may be more dangerous and contagious now than they used to be.

"The activity itself is not new, but I think the ability to spread the word about it via the internet is adding some fuel to the fire," said W. Hobart Davies, a psychologist from the University of Wisconsin-Milwaukee who has studied the choking game but didn't participate in the new research.
"If you watched the kids doing it on YouTube, you'd think it was the most fun thing people have ever done," he told Reuters Health.

That's why the most important message is for parents and other adults who work with kids not to be afraid to bring up the choking game and its risks, researchers agreed.

"By eighth grade, kids already know. They're talking about this," Nystrom told Reuters Health.
Teaching kids and teens about the dangers of the game should be part of programs that also address drugs, alcohol and risky sexual behavior, Andrew said.

He pointed to one study that showed 40 percent of kids surveyed in Texas and Canada didn't see any danger in playing the choking game, whether or not they had ever participated themselves.
"I hope that it just becomes a part of the conversation," Andrew said.

"It's not perfectly safe, and that's the message that we need to get across."

SOURCE: bit.ly/jsoh2P Pediatrics, online April 16, 2012.

Nicotine patch may help prevent smoking relapses

"The clear implication is that you shouldn't give up, you should stay on the treatment with patch," said Saul Shiffman, one of the study's authors from the University of Pittsburgh.

People who "lapse," or give in to nicotine cravings when trying to quit, are at high risk of giving up and returning to smoking.

But contrary to common perception, they haven't failed at quitting and may get over initial lapses by continuing to use the patch, Shiffman said.

His team's study, published in the journal Addiction, suggests that along with helping people stop smoking in the first place, nicotine patches could also boost their chances of recovering from occasional lapses while trying to quit.

Experts say most people trying to break the habit manage to do so at first, but are unable to sustain their quit attempt over the long run.

"Patch can help overcome these lapses. We're ignoring what could be a very important benefit of treatment," Shiffman told Reuters Health.

According to the American Lung Association, more than 443,000 Americans die from smoking-related diseases each year. Cigarette smoke contains thousands of chemicals, including tar, carbon monoxide, formaldehyde and toxins known to cause cancer.

Nicotine patches, usually applied on the arm, reduce withdrawal symptoms such as headache and nausea in those who give up smoking. They supply lower doses of nicotine than found in most cigarettes -- without all the other extra chemicals.

Other nicotine replacement therapies (NRTs) include over-the-counter gum and lozenges, prescription nasal sprays and inhalers and non-nicotine prescription drugs.

Two past studies suggested that quitters who have a lapse may be better off if they keep using patches . But unlike in those trials, the new study mimicked "current real-world use of patch" by giving participants little instruction on how to use the product, Shiffman said.

In a second look at past research, he and his colleagues examined data from a trial of nicotine patches at eight sites across the country.

More than 500 heavy smokers who wanted to beat the habit participated. After enrollment, they received a supply of either active nicotine patches or drug-free placebo patches. Neither the subjects nor the study staff knew who had which type of patch.

At follow-up visits during weeks six and ten, people in the study answered questions about whether and when they had smoked since their last appointment.

Focusing on those who smoked at least once -- after an initial two-week grace period -- the researchers found that active patch users were better able to rebound from a lapse than those on the placebo. At week six, people treated with nicotine patches were 11 times more likely than those wearing placebo patches to have stopped smoking for at least a week before their visit.

Similarly, in week 10, close to 10 percent of active patch users reported abstaining from cigarettes for at least a week, versus between two and three percent of placebo users.

The research was funded by GlaxoSmithKline, which markets NRT products. The study authors also act as consultants to the company and have a stake in efforts to develop new smoking-cessation drugs.
According to Shiffman, the findings suggest smokers trying to quit should keep using a nicotine patch even after setbacks, rather than stop wearing it because of the mistaken belief that using patches and cigarettes together poses a health danger.

The warnings on NRT packages against simultaneous use merely offer common-sense advice against smoking while using such products to beat the habit, he added.

"There is really no particular risk," he said, adding that people incorrectly interpret the label to mean the combination is dangerous.

Nicotine patches typically run for about $2 per day, and can be bought without a prescription.
Because nicotine affects the nervous system, heart rate and blood pressure, most experts and package labels do discourage using the patch while smoking cigarettes, to avoid nicotine overdose.
Dr. Alvin Strelnick, chief of community health at Albert Einstein College of Medicine in the Bronx, said the new study confirms a position supported by experts in the field -- namely, smokers should not give up on nicotine patches just because they lapse once or twice during their quit attempt.
But he cautioned that, as noted in the study, it can be tricky to re-analyze data from prior research that was designed for another purpose.

For smoking cessation, the optimal treatment combines the longer-acting nicotine patch with shorter-acting products like nicotine gum, nasal spray or lozenges, Strelnick, who wasn't involved in the new study, told Reuters Health.

"That more closely mimics the way in which nicotine is (present) in the body of most smokers," he said.

SOURCE:
bit.ly/AEUXoX Addiction, online March 22, 2012.

Genetically Engineered Stem Cells Seek Out And Kill HIV In Mouse Model

Expanding on previous research providing proof-of-principal that human stem cells can be genetically engineered into HIV-fighting cells, a team of UCLA researchers have now demonstrated that these cells can actually attack HIV-infected cells in a living organism.

The study, published in the journal PLoS Pathogens, demonstrates for the first time that engineering stem cells to form immune cells that target HIV is effective in suppressing the virus in living tissues in an animal model, said lead investigator Scott G. Kitchen, an assistant professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA and a member of the UCLA AIDS Institute.

"We believe that this study lays the groundwork for the potential use of this type of an approach in combating HIV infection in infected individuals, in hopes of eradicating the virus from the body," he said.

In the previous research, the scientists took CD8 cytotoxic T lymphocytes - the "killer" T cells that help fight infection - from an HIV-infected individual and identified the molecule known as the T cell receptor, which guides the T cell in recognizing and killing HIV-infected cells. However, these T cells, while able to destroy HIV-infected cells, do not exist in great enough quantities to clear the virus from the body. So the researchers cloned the receptor and used this to genetically engineer human blood stem cells. They then placed the engineered stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism.

The engineered stem cells developed into a large population of mature, multi-functional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also discovered that HIV-specific T cell receptors have to be matched to an individual in much the same way an organ is matched to a transplant patient.

In this current study, the researchers similarly engineered human blood stem cells and found that they can form mature T cells that can attack HIV in tissues where the virus resides and replicates. They did so by using a surrogate model, the humanized mouse, in which HIV infection closely resembles the disease and its progression in humans.

In a series of tests on the mice's peripheral blood, plasma and organs conducted two weeks and six weeks after introducing the engineered cells, the researchers found that the number of CD4 "helper" T cells - which become depleted as a result of HIV infection - increased, while levels of HIV in the blood decreased. CD4 cells are white blood cells that are an important component of the immune system, helping to fight off infections. These results indicated that the engineered cells were capable of developing and migrating to the organs to fight infection there.

The researchers did note a potential weakness with the study: Human immune cells reconstituted at a lower level in the humanized mice than they would in humans, and as a result, the mice's immune systems were mostly, though not completely, reconstructed. Because of this, HIV may be slower to mutate in the mice than in human hosts. So the use of multiple, engineered T cell receptors may be one way to adjust for the higher potential for HIV mutation in humans.

"We believe that this is the first step in developing a more aggressive approach in correcting the defects in the human T cell responses that allow HIV to persist in infected people," Kitchen said.

The researchers will now begin making T cell receptors that target different parts of HIV and that could be used in more genetically matched individuals, he said.

Other study authors are Bernard R. Levin, Gregory Bristol, Valerie Rezek, Sohn Kim, Christian Aguilera-Sandoval, Arumugam Balamurugan, Otto O. Yang and Jerome A. Zack, all of UCLA.
The National Institutes of Health, the California HIV/AIDS Research Program, the California Institute for Regenerative Medicine, the UC Multicampus Research Program and Initiatives from the California Center for Antiviral Drug Discovery, and the UCLA Center for AIDS Research (CFAR) funded this study.
University of California - Los Angeles Health Sciences

Locust Legs Show Super Strength

Credit: Wikimedia Commons

A cockroach crunched underfoot may not seem like a model of strength, but scientists have discovered that bug skeletons are tougher than we think. Insects and spiders shield themselves in slick external skeletons made of cuticle, one of the most common natural composites on the planet. Composed mostly of a carbohydrate called chitin, insect cuticle differs from keratin-based human cuticle, the tough skin at the base of our fingernails. Researchers knew little about how this ubiquitous material holds up under pressure, so they plucked hind legs from living locusts and bent them until they snapped. They also nicked the tube-like legs to test their resistance to defects. Cuticle's flexibility, combined with its high tolerance for cracks, meant that a remarkable 5.56 kJ m^-2 (kilojoules per square meter) of energy was needed to rip the material apart, the team reports online today in The Journal of Experimental Biology. This is more energy than is needed to tear cast iron, and makes cuticle one of nature's toughest composite materials: it's sturdier than bone, and on par with bone-based antlers and keratin-sheathed horns. Locusts need such strong legs to withstand high-impact jumps and deliver defensive kicks—something else to fear if they take the world by swarm.

Physicists Discover New Type of Particle--Sort Of

In 1937, after the rise of quantum mechanics, Ettore Majorana, an Italian theoretical physicist, realized that the new physics implied the existence of a novel type of particles, now called Majorana fermions. After a 75-year hunt, researchers have now spotted the first solid evidence of their existence. And their discovery could hold the key to finally creating workable quantum computers .

Prior to Majorana's work, Austrian physicist Erwin Schrödinger came up with an equation that describes how quantum particles behave and interact. Paul Dirac, an English physicist, tweaked that equation to apply it to fermions, such as electrons, moving at near-light speed. That work tied together quantum mechanics and Einstein's special theory of relativity. It also implied the existence of antimatter, where every particle has an antimatter counterpart—such as electrons and positrons—and that the two would annihilate each other if they ever met. Dirac's work suggested that some particles, such as photons, could serve as their own antiparticles. But fermions weren't thought to be among them. It was Majorana's manipulations of Dirac's equations that suggested the possible existence of a new type of fermion that could serve as its own antiparticle.

At the time, Majorana thought a type of neutrino, an electrically neutral particle with a tiny mass, might fit the bill for his proposed particle. And scientists continue to search for evidence that neutrinos are or are not their own antiparticles. But decades after Majorana's proposal, theoretical physicists realized that the coordinated motion of large numbers of electrons in electronic devices might mimic the behavior of Majorana fermions. These collective motions aren't elementary bits of matter the way electrons and neutrinos are. Rather, they are "quasiparticles." But they should behave much as would elementary particles of the same type. It is the signs of these quasiparticles that researchers led by physicist Leo Kouwenhoven and colleagues at Delft University of Technology report online today in Science.

To spot their quarry, Kouwenhoven's group created specially designed transistors. In standard transistors, applying a voltage to a metal electrode called a gate turns on the flow of current through a semiconductor between two other metal electrodes. Previous theoretical predictions suggested that if one of the secondary electrodes was a superconductor, and the current was allowed to flow through a special semiconductor nanowire under a magnetic field, the combination would force electrons in the nanowire to behave collectively as if Majorana fermions were present at opposite ends of the wire. Theory further offered that if researchers tried to send an electric current from the normal electrode to the superconducting electrode without the magnetic field turned on, the electrons trying to make the journey would essentially bounce off the superconductor, so no current would be detected at the superconducting electrode. But if the magnetic field is turned on, this would trigger the presence of Majorana fermions, which would enable electrons to enter the superconductor, and that would produce a jump in the current.

This current spike is what Kouwenhoven's team found. When the researchers then removed any one of the conditions needed to induce Majorana fermions—such as the magnetic field, or replacing the superconducting electrode with another metal electrode—the current spike at the second electrode vanished.

The results don't provide a direct detection of Majorana fermions. But the Dutch team did a "very compelling" job of eliminating all other possible explanations, says Jason Alicea, a theoretical physicist at the University of California, Irvine. However, the study doesn't completely nail the case for the presence of Majorana fermions, he cautions. The current spike is only 5% of what theory predicts. But that may be because the equipment used to chill the experimental setup must be improved to get closer to absolute zero, where the signal for Majoranas should be the strongest.

If Majoranas are confirmed, they are expected to have properties that make them ideal for constructing a quantum computer. When you move two Majorana fermions with respect to one another, they essentially "remember" their former position, a property that could be used to encode data at the quantum level. Kouwenhoven's group hasn't spotted that signature yet, but they're on the hunt now.

Dangers of Chinese Medicine Brought to Light by DNA Studies

Traditional Chinese medicine (TCM) is enjoying increasing popularity all over the world. But two molecular genetics studies published this week show that the trendy treatments can be harmful, as well. The papers focus attention on the fact that not all of their ingredients are listed, or even legal, and that some can cause cancer.

"These two studies show very clearly how dangerous the products of TCM can be," says Fritz Sörgel, the head of the Institute for Biomedical and Pharmaceutical Research in Nuremberg, Germany, who was not involved in the work. "The public needs to be better informed about these dangers."

Hundreds of millions of dollars are spent on TCM products each year—a growing portion of it on the Internet—and some scientists are looking at these preparations hoping to discover new pharmacological substances. Many would like to emulate the success of Tu Youyou, the Chinese scientist who isolated artemisinin, now the world's most important malaria drug, from an ancient Chinese medicine. Tu won a Lasker award last year and is rumored to be a Nobel candidate.

But critics have long warned that some mixtures can also contain naturally occurring toxins, contaminants like heavy metals, added substances such as steroids that make them appear more effective, and traces of animals that are endangered and trade-restricted.

Now, researchers at Murdoch University in Australia have investigated the problem using modern sequencing technology. The team, based at the university's Australian Wildlife Forensic Services and Ancient DNA Laboratory in Perth, analyzed 15 samples of traditional Chinese medicine seized by Australian border officials.

"We took these traditional preparations, smashed them to pieces, and extracted the DNA from the powder," explains molecular geneticist Michael Bunce. The scientists then fished out copies of two specific genes, trnL, a chloroplast gene common to all plants, and 16srRNA, conserved among plants and animals, and multiplied and sequenced them. By comparing the sequences to those in genetic databases, they could pinpoint the animals and plants used to make the medicine. "Sometimes we really struggled to assign a particular DNA to a particular species," Bunce says. But as genetic databases expand, this should become easier.

Some products contained material from animals classified as vulnerable or critically endangered, such as the Asiatic black bear and the Saiga antelope—just as the producers claimed. But often, the medicine also harbored ingredients not mentioned on the packaging, the team reports online today in PLoS Genetics. "For example, a product labeled 100 percent Saiga antelope contained considerable quantities of goat and sheep DNA," Bunce writes.

"Using DNA to identify the animal species and thus prove illegal trading is very elegant," says Dietmar Lieckfeldt, who works in molecular forensics at the Leibniz Institute for Zoo and Wildlife Research in Berlin, Germany. Identifying animals by their DNA has been possible for a while, he says, but the next-generation sequencing technology makes it possible to nail different species in a mixture very quickly.

In the herbal preparations, Bunce and his colleagues found members of 68 different plant families, among them plants of the genera Ephedra and Asarum. Both can contain toxic chemicals such as aristolochic acid, a compound banned in many countries because it causes kidney disease and cancer of the upper urinary tract (UUC). While detecting DNA from a certain species does not mean that a toxin produced by that plant is present, chemical analysis of one of the four samples containing Asarum DNA did turn up aristolochic acid.

The threat posed by aristolochic acid is also highlighted in a paper published in the Proceedings of the National Academy of Sciences on Monday. The researchers, led by pharmacologist Arthur Grollman of Stony Brook University, focused on Taiwan, the country with the highest rate of UUC in the world. A previous analysis had shown that roughly one-third of the Taiwanese population consumed herbs likely to contain aristolochic acid.

The scientists sequenced the tumors of 151 patients with UUC. Among patients with characteristic mutations in the important tumor-suppressor gene TP53—which make people more vulnerable to cancer—84% also showed a known molecular signature of exposure to aristolochic acid, they found. The study provides compelling evidence that aristolochic acid is a primary cause of UUC in Taiwan, the authors argue.
Bunce and his colleagues also found DNA from plant families known to contain medicinally important species that could pose risks when used in combination with other drugs, as well as DNA from soybean and plants of the cashew family, which can contain allergens. "This just shows that the ingredients in these preparations aren't accurately declared," Bunce argues. Indeed, says Sörgel, the studies show that partaking in traditional Chinese herbal medicine is a gamble: "We just don't know enough about it."

Understanding Insulin Sensitivity and Diabetes

A new discovery helps explain how adipose tissue (fat) affects insulin sensitivity and results in type 2 diabetes. The finding may lead to new strategies for treating the disease.

Diabetes is a disorder in the way the body uses glucose, a sugar that serves as fuel for the body. When blood glucose levels rise, the pancreas normally makes the hormone insulin, which signals cells to take sugar from the blood. Fat cells store excess glucose in the form of lipids (fats). In the most common form of diabetes, type 2, cells lose their sensitivity to insulin.

About 80% of people with type 2 diabetes are overweight, but the connection between adipose tissue and insulin sensitivity has been difficult to decipher. A research team led by Drs. Barbara Kahn and Mark Herman of Harvard Medical School and Beth Israel Deaconess Medical Center set out to investigate. Their work was funded primarily by NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). It appeared in the advance online edition of Nature on April 1, 2012.

The team began with 2 types of transgenic mice in which insulin resistance and obesity don't correlate. The mice have alterations in GLUT4, the protein primarily responsible for transporting glucose into muscle and fat cells in response to insulin. AG4OX mice overexpress GLUT4 in adipose tissue. They become obese, yet they're able to control blood glucose levels. AG4KO mice, in contrast, don't produce GLUT4 in adipose tissue. They have a normal body weight but develop insulin resistance and type 2 diabetes.

The researchers compared gene expression in adipose tissue from the 2 types of mice. Genes involved in making lipids were expressed at high levels in AG4OX mice but low levels in AG4KO mice. These genes are known to be controlled by certain master regulator genes, so the team examined expression of these genes. One called ChREBP was found to be 50% higher in AG4OX adipose tissue and 44% lower in AG4KO adipose tissue. This suggests that adipose tissue GLUT4 affects fatty acid synthesis and insulin sensitivity by regulating ChREBP.

But analysis of ChREBP expression in numerous mouse strains and people showed a more complicated releationship. While ChREBP expression usually correlates with GLUT4 levels, it doesn't always. A closer look revealed a new form of the ChREBP gene, ChREBP-β, that begins from a different DNA start site than the previously known one, ChREBP-α, and makes a more active form of the protein.
The researchers found that expression of ChREBP-β isn't induced directly by GLUT4 but by ChREBP-α. This means that increased glucose transport into fat cells activates ChREBP and leads it to produce another, more potent version of itself.

Mice fed a high-fat diet showed reduced adipose ChREBP-β expression, while ChREBP- αlevels remained unchanged. This suggests that ChREBP-β may play a role in insulin resistance. When the researchers examined obese people, they found that expression of ChREBP-β, but not ChREBP-α, in adipose tissue predicts insulin sensitivity.
 
"Two things were surprising—first, that a lone gene could shift the metabolism of the fat cell so dramatically and then, that turning on this master switch selectively in adipose tissue is beneficial to the whole body," says Kahn.

This research revealed a new molecular player in fat cell insulin sensitivity. ChREBP-β might one day prove to be a good drug target to help treat or prevent type 2 diabetes.

Huntington's Disease Linked to Reduced Cancer Risk in Study

People who have Huntington's disease are much less likely to develop cancer than people without the inherited disorder, according to a new study that suggests the diseases share a common genetic mechanism.
The Swedish researchers found that those with Huntington's had a 53 percent lower risk of being diagnosed with cancer compared to the general population.

Besides Huntington's disease, the lower cancer risk applies to the other eight rare neurodegenerative disorders known as polyglutamine (polyQ) diseases. Those diseases, which result in the progressive degeneration of neurons involved in motor control, include spinobulbar muscular atrophy (also known as Kennedy's disease); dentatorubral-pallidoluysian atrophy; and six types of spinocerebellar ataxia.

From 1969 through 2008, the researchers identified 1,510 patients with Huntington's disease; 471 people with spinobulbar muscular atrophy; and 3,425 with hereditary ataxia, a substitute for spinocerebellar ataxia.
Cancer was diagnosed in 6 percent of the Huntington's patients, 7 percent of the spinobulbar muscular atrophy patients and 12 percent with hereditary ataxia.

The study, published online April 11 in The Lancet Oncology, determined those with spinobulbar muscular atrophy had a 35 percent lower risk of cancer, and patients with hereditary ataxia had a 23 percent lower risk. Before being diagnosed with a polyQ disease, the patient's risk of cancer was even lower, the researchers said.
"Our findings suggest a common mechanism in patients with polyQ diseases that protects against the development of cancer," Dr. Jianguang Ji and colleagues from Lund University and Skane University Hospital, in Sweden, wrote in a journal news release. "Future studies should investigate the specific biological mechanisms underlying the reduced cancer risk in patients with polyQ diseases," they concluded.

SOURCE:  
The Lancet Oncology, news release, April 11, 2012

Anti-science in Tennessee Classrooms

Public school educators in Tennessee can now teach their students the tenets of creationism, intelligent design, and global warming skepticism with impunity, according to opponents of a new law in the state. Tennessee Governor Bill Haslam declined to either sign or veto the state’s so-called “monkey bill,” which prohibits public school officials from stopping a teacher who aims to teach alternatives to well-established scientific theories such as evolution and global climate change. As a result, HB 368 became law on Tuesday (April 10).
Proponents of science education had been urging Haslam to veto the bill after Tennessee’s state Senate and House of Representatives passed it by a 3-to-1 margin last month.
The new law—which makes Tennessee the second state to open public school doors to the teaching of creationism, intelligent design, and climate change skepticism after Louisiana enacted a similar law 3 years ago—states that educators “shall be permitted to help students understand, analyze, critique, and review in an objective manner the scientific strengths and scientific weaknesses of existing scientific theories covered in the course being taught.” It highlights specific topics that can stir the pot, “including, but not limited to, biological evolution, the chemical origins of life, global warming, and human cloning, can cause controversy.”
Opponents of the legislation see red flags in the topics the law singles out. “HB 368 and other bills like it are a permission slip for teachers to bring creationism, climate-change denial, and other non-science into science classrooms,” Eugenie Scott, director of the National Center for Science Education (NCSE) in Oakland, California, told Nature.

The World in a Cabinet, 1600s

Europeans extended their power and reach across the globe in the 16th century, collections of all sorts of curiosities and artifacts from around the world became the rage throughout Europe. Inside these sundry collections, called Wunderkammern or Kunstkammern (German for “wonder-rooms” or “art-rooms”), geological curiosities, such as geodes, nestled against South American feathered cloaks, medical rarities, or a painting of Vlad the Impaler. One of the most famous collections, that of the 17th-century Danish doctor Ole Worm, contained hundreds of natural history items carefully arranged in a room in his own home. Upon Worm’s death in 1654, the Danish Royal Kunstkammer, created by King Frederick III of Denmark, subsumed Worm’s collection. Luckily, a detailed catalog of his cabinet, written by Worm himself, was published posthumously in 1655 as Museum Wormianum. This book lists, classifies, and ponders Worm’s vast collection, offering insight into Renaissance beliefs about the world as well as the era’s emerging empiricism.


Worm trained in medicine at the University of Basel and practiced “demonstrative teaching,” using objects from his collection, as a professor of physics at the University of Copenhagen. Aiming for rarity over comprehensiveness, Worm looked for objects that tested accepted knowledge rather than confirmed it, explains Jole Shackelford, a historian of medicine at the University of Minnesota. An illustration of a bird of paradise, drawn from a specimen sent to Worm by a friend, served as proof that the birds did indeed have feet, contrary to what was popularly believed. As he explained in a letter, Worm aimed to give his students firsthand knowledge of the world, to “present my audience with the things themselves to touch with their own hands and to see with their own eyes…”
Worm’s goal of illumination is reflected in the organization of Museum Wormi­anum, which he separated into minerals, plants, animals, and man-made artifacts. A horse’s jawbone embedded in an oak root—one of around 40 original items from Worm’s cabinet that are still on display at the Natural History Museum of Denmark—represented the convergence of two dissimilar categories: plant and animal. Worm’s categorization may surprise modern readers: he placed man in the animal category, but listed mummies under minerals.
Worm suspected a hoax when he realized that he only encountered unicorn horns, considered a potent treatment for poison, and never other parts of the unicorn skeleton. When Worm’s friend and Denmark’s chancellor, Christian Fries, offered what he believed was an intact unicorn skull for examination, Worm determined that it belonged to a whale-like creature, most likely a narwhal. But Worm would also “pass along hearsay if the source was credible,” says Shackelford. Worm included in his collection an egg accompanied by sworn witness testimonials, including a parish priest’s, claiming it had been laid by a Norwegian woman named Anna Omundsdatter. When The Royal Kunstkammer was divided among specialty museums in 1824, the egg was boxed, sold, and lost to history.

Live and In Color

Even with the amazing array of tools available to biologists studying cellular functions, watching these processes unfold inside a living cell remains a challenge. Green fluorescent protein (GFP) revolutionized imaging and the spatial understanding of how proteins interact within living cells, but a lot of information is also embedded within the production, processing, and manifold interactions of RNA.
Researchers are using RNA tracking systems to follow the paths of noncoding RNAs, the transcription of mRNA, splicing patterns, and the trafficking of RNA in development and in RNA-based disease processes. But as with all imaging techniques, you have to consider whether the labeling method will interfere with the process that you’d like to study, says Bruce Armitage, a chemist at Carnegie Mellon University in Pittsburgh, Pennsylvania. “While GFP is extremely useful, there is always a concern when you put a large tag onto your protein that maybe it behaves differently than it does when that tag is not there. Since you can’t see it if the tag’s not there, you don’t always know if the tag is misinforming you,” he says. “The same is true with almost any RNA technology.”
Many RNA tracking techniques are still in development. To find what works best for your experimental system, “you have to go into this expecting to try a few different technologies,” Armitage says. That will require a bit of detective work. Some reagents are available for order from companies, but you may also need to contact principal investigators on the methods papers, either to get reagents or to learn more about how to carry out the experiment.
“Maybe five to ten years from now we’ll have a robust enough technology and enough experimental testing that there will be a nice clearinghouse for information and [researchers will] get their ideal probe,” Armitage says. Until then, to get you started, here’s a guide to the main techniques for tracking RNA within living cells.

TAGGING RNA WITH GFP

LIGHTING UP RNA: Bacteriophage MS2 coat protein fused with GFP binds to mRNAs containing copies of the MS2’s RNA-binding sequence in the nucleus of cultured cells.Robert Singer, Albert Einstein College of Medicine

The back-story
The original technique for tracking RNA inside living cells, developed about 15 years ago, uses GFP as the fluorescent reporter molecule. Previously, researchers had used the coat protein from the MS2 bacteriophage, which binds to a defined 19-nucleotide sequence of RNA, as a way to capture RNA and RNA-binding proteins. By fusing GFP to this MS2 protein, Robert Singer and his colleagues at Albert Einstein College of Medicine in Bronx, New York, first demonstrated that they could follow RNA as it migrated within cells (Molecular Cell, 2:437-45, 1998).
The Method
The first step is adding copies of MS2’s RNA-binding sequence, which forms a characteristic stem loop structure, to the noncoding region of the gene of interest. In addition, the cells need to be transfected with a plasmid so that they can express the MS2-GFP fusion protein. There’s also an inherent problem to surmount—the background fluorescence of the fusion protein before it binds to the target RNA. Singer and his colleagues realized that they’d need to insert many copies—24, and sometimes even 48—of the MS2 stem loop within the RNA of interest to overcome this “haze of GFP” and get sufficient signal to track a single molecule moving within the cell in real time.
Researchers have used the technique in many different cell types, including yeast, Drosophila, and various mammalian cells. Singer and his colleagues have even developed MS2-GFP transgenic mice that track mRNA generated by the β-actin gene (Nat Methods, 8:165-70, 2011). They are currently developing a second transgenic mouse, and others could use the technique to develop their own mouse models.
Pros & Cons
On the plus side, because the probes are expressed within the cell, you don’t have to worry about delivering large, highly charged reagents across the cell membrane. One potential problem, however, is that the MS2 protein includes a nuclear trafficking signal, prompting questions about whether that signal could modify the localization behavior of the RNA-protein complex. Right now, because there is only one targeting sequence, you can only track one RNA sequence at a time. The Singer lab is working on a two-color system.
Equipment and cost
Singer has contributed the plasmids encoding the MS2-GFP fusion protein and 24 copies of the MS2 stem loops to the nonprofit repository Addgene, which sells them for $65 each. Addgene receives nearly 300 requests per month for these reagents, Singer says.

PLAYING TAG

TRACKING mRNA: The green lines show individual mRNA molecules labeled with molecular beacons moving around the chromatin (blue) within a mammalian cell nucleus. Red dots show dense locations where mRNA cannot move freely; yellow dots show more open spaces within the chromatin.Sanjay Tyagi, University of Medicine and Dentistry of New Jersey

When MS-2 GFP fusion isn’t enough
Let’s say you want to track multiple RNAs at the same time, or you’re concerned about the effects of a bulky MS2-GFP fusion protein on the mobility of your RNA. A newer approach addresses these needs by employing smaller probes that recognize their RNA targets through complementary Watson-Crick base pairing.
The Method
Sanjay Tyagi and his colleagues at the University of Medicine and Dentistry of New Jersey in Newark developed molecular beacons designed to recognize specific sequences engineered into the noncoding region of a gene of interest. The molecular beacons are hairpin sequences of RNA with a fluorescent dye at one end and a quencher molecule at the other. When these free structures move around a cell in a closed conformation, the quencher blocks fluorescence. As the hairpin binds to the complementary RNA target, it opens and the dye lights up.
Pros & Cons
Because some RNAs are relatively rare within a cell, with an expression rate of just 20 to 50 copies, getting a reliable signal for a single molecule of RNA can still require some tweaking, says Tyagi. You’ll need multiple probes, typically 32, or multiple copies of the same probe. On the plus side, molecular beacons can be designed to recognize different sequences and glow with different colors, so you can monitor more than one RNA molecule at the same time. Tyagi and his team recently used molecular beacons labeled with two different dyes to follow splicing patterns of genes (Cell, 147:1054-65, 2011). To deliver these synthetic probes across the cell membrane, Tyagi’s team microinjects the probes directly into the cells they are studying.
Cost
Tyagi’s technology is licensed to several companies. For example, BioSearch Technologies sells molecular beacons starting at $95 for 10 nanomoles of a short oligonucleotide hairpin sequence labeled at both ends.

TRACKING AU NATUREL

Hands off that RNA
Both of the previous techniques require modifying the noncoding region of the RNA you’d like to track. If you’d like to understand the behavior of completely natural, unmodified RNA molecules, you need a different system.
The method
Philip Santangelo and his team at Georgia Institute of Technology solved this problem using multiply labeled tetravalent RNA imaging probes (MTRIPs). These probes use oligonucleotides that are each labeled with two or three fluorophores of a single color and then covalently attached to biotin, which binds strongly to streptavidin, clumping the oligonucleotides together to produce clusters of about 10 fluorophores. Two or three MTRIPs targeted to different sequences on the native RNA can achieve sufficient signal for single molecules to stand out from background with up to three different dye colors (Meth Enzymol, 505:383-99, 2012).
Pros & Cons
You’ll have to find a way to deliver the MTRIPs into cells, Santangelo says. His group typically uses streptolysin O, a bacterial toxin that reversibly opens pores in the cell membrane, though it’s also possible to microinject them as Tyagi does with his probes.
Availability and cost
Although these probes are not commercially available, the components are easy to obtain and are not difficult to assemble, Santangelo says. His group estimates that it costs $0.15 per well to make a 30 nM concentration of MTRIPs using a 24-well plate (Nat Meth, 6:347-49, 2009).

STRIPPING DOWN GFP

Tracking hope
A new technique on the block may circumvent some of the limitations of other RNA tracking approaches.
The method
Samie Jaffrey and his colleagues at Weill Cornell Medical College in New York stripped GFP’s fluorescence down to its essence—the fluorophore that glows as the protein folds around it in a rigid structure.  But instead of stabilizing the fluorophore with a protein scaffold, he prepared an RNA library and did selection experiments to pull out RNA sequences that stabilized a small synthetic version of the GFP fluorophore and allowed it to fluoresce (Science, 333:642-46, 2011).
The minimum sequence required to induce fluorescence with the small molecule is 80 nucleotides long, and Jaffrey has christened it “Spinach.” The vegetable nomenclature riffs on widely used fluorescent proteins—such as mCherry, developed by Roger Tsien’s lab at the University of California, San Diego—that are named for fruit. Jaffrey is also working on orange and red versions of Spinach he’s calling Carrot and Radish. (See “It’s Easy Being Green,” The Scientist, January 2012.)
Pros & Cons
The method removes a step from the design process, says Tyagi, who is testing the technique in his own lab. “Now we don’t have to engineer the GFP, all we have to do is engineer the RNA.” It also avoids the delivery problems in some of the hybridization methods: the RNA sequences that bind the fluorophore are incorporated into the noncoding regions of the gene of interest, while the small-molecule fluorophore is added to the cell medium and easily crosses the cell membrane. Another perk is that unlike GFP, which can take up to 20 minutes to fold and fluoresce, Spinach becomes maximally fluorescent almost immediately, which could be useful for monitoring short-lived processes within cells, Jaffrey says. Initially, Jaffrey tested Spinach with a high-abundance, noncoding RNA in the cell. As with the other techniques, imaging low-abundance RNAs such as mRNAs may require tweaking the system, either by using concatenated sequences of Spinach, employing other colors such as red (which have less natural background fluorescence in the cell), or both.
Availability and cost
According to Jaffrey, Cornell has already licensed the technology, which could soon lead to commercially available plasmids that are specialized for particular applications. “I give [the plasmid] away to anyone who asks,” Jaffrey says, adding that chemists could synthesize the fluorophore relatively easily. The fluorophore is also commercially available: Lucerna Technologies sells 5 mg for $299.99.

What Is Obesity Hypoventilation Syndrome?

Obesity hypoventilation (HI-po-ven-tih-LA-shun) syndrome (OHS) is a breathing disorder that affects some obese people. In OHS, poor breathing results in too much carbon dioxide (hypoventilation) and too little oxygen in the blood (hypoxemia).
OHS sometimes is called Pickwickian syndrome.

Overview

To understand OHS, it helps to understand how the lungs work. When you breathe, air passes through your nose and mouth into your windpipe. The air then travels to your lungs' air sacs. These sacs are called alveoli (al-VEE-uhl-eye).
Small blood vessels called capillaries (KAP-ih-lare-ees) run through the walls of the air sacs. When air reaches the air sacs, oxygen passes through the air sac walls into the blood in the capillaries. At the same time, carbon dioxide moves from the capillaries into the air sacs. This process is called gas exchange.
In people who have OHS, poor breathing prevents proper gas exchange. As a result, the level of carbon dioxide in the blood rises. Also, the level of oxygen in the blood drops.
These changes can lead to serious health problems, such as leg edema (e-DE-mah), pulmonary hypertension (PULL-mun-ary HI-per-TEN-shun), cor pulmonale (pul-meh-NAL-e), and secondary erythrocytosis (eh-RITH-ro-si-TOE-sis). If left untreated, OHS can even be fatal.
The cause of OHS isn't fully known. Researchers think that several factors may work together to cause the disorder.
Many people who have OHS also have obstructive sleep apnea. Obstructive sleep apnea is a common disorder in which the airway collapses or is blocked during sleep. This causes pauses in breathing or shallow breaths while you sleep.
Obstructive sleep apnea disrupts your sleep and causes you to feel very tired during the day. (For more information, go to the Health Topics Sleep Apnea article.)

Outlook

Doctors treat OHS in a number of ways. One way is with positive airway pressure (PAP) machines, which are used during sleep.
PAP therapy uses mild air pressure to keep your airways open. Your doctor might recommend CPAP (continuous positive airway pressure) or BiPAP (bilevel positive airway pressure).
If your doctor prescribes PAP therapy, you'll work with someone from a home equipment provider to select a CPAP or BiPAP machine. The home equipment provider will help you select a machine based on your prescription and the features that meet your needs.
Other treatments for OHS include ventilator (VEN-til-a-tor) support and medicines. (A ventilator is a machine that supports breathing.)
OHS occurs with obesity, so your doctor will likely recommend weight loss as part of your treatment plan. Successful weight loss often involves setting goals and making lifestyle changes, such as following a healthy diet and being physically active.
OHS can lead to other serious health problems, so following your treatment plan is important. Your health care team, home equipment provider, and family can help you manage your treatment.
Obesity hypoventilation syndrome (OHS) is a breathing disorder that affects some obese people. Why these people develop OHS isn't fully known. Researchers think that several factors may work together to cause OHS. These factors include:

• A respiratory (RES-pih-rah-tor-e) system that has to work harder than normal and perhaps differently because of excess body weight. (The respiratory system is a group of organs and tissues, including the lungs, that helps you breathe.)
• A slow response by the body to fix the problem of too much carbon dioxide and too little oxygen in the blood.
• The presence of sleep apnea, usually obstructive sleep apnea.

Mobile Stroke Units Might Trim Time to Treatment

Clot-busting drugs can help stave off lasting disability after a stroke, but they must be given within a 4.5-hour window and many people arrive at the hospital too late to use them.

Now, German researchers report that they think they have found a solution to the problem: mobile stroke units. Equipped with what is needed to diagnose and treat a stroke, these ambulances are stocked with clot-busting tissue plasminogen activator (tPA) and the CT scanning technology needed to confirm whether an ischemic stroke has occurred, blood flow is blocked and it is safe to use tPA.

Unfortunately, while the mobile stroke units did speed the time to treatment, this did not lead to improvements in neurological outcomes or increase the number of people who received tPA. The findings are published in the April 11 online edition of The Lancet Neurology.

In the study conducted by Dr. Klaus Fassbender and his colleagues from the University of the Saarland in Homburg, 100 people with suspected stroke were either treated in the mobile stroke units or at the hospital. Use of mobile stroke units roughly halved the time from the initial emergency call to treatment decision, from 76 minutes to 35 minutes.

What's more, treatment in a mobile stroke unit also lowered the time from symptom onset to therapy decision to less than an hour for 57 percent of people. By contrast, just 4 percent who were treated in the hospital were evaluated in under an hour.

The time from calling emergency services to administering treatment was 38 minutes among people treated in the mobile unit versus 73 minutes among those who were treated at the hospital, the investigators found.

Commenting on the study, Dr. Larry Goldstein, director of the Duke Stroke Center in Durham, N.C., said that while an interesting concept, mobile stroke units may not be feasible in the United States due to cost. "There might be some circumstances where such a thing might be considered, but that would really have to be thought through very carefully."

Unless and until that occurs, the best way to make sure that people with suspected stroke get treatment promptly is to have 911 operators trained to recognize that a caller may be having a stroke and dispatch the appropriate unit to take them to the nearest stroke center where they can be evaluated and treated as quickly as possible, Goldstein said.

Dr. Robert Glatter, an emergency medicine physician at Lenox Hill Hospital in New York City, added that "the concept of a mobile stroke unit is a promising approach to more rapidly and effectively assess and treat patients with acute strokes in the field."

Some potential downsides include the cost of the set-up, Glatter pointed out. "We will need an adequately powered, larger multi-center trial to answer the question of whether largely urban-based mobile stroke units ultimately improve outcome of stroke patients in the 'time is brain' paradigm," he noted.

Glatter agreed that knowing the symptoms of a stroke is the most important way to make sure that care is delivered in timely fashion. Stroke symptoms may include facial drooping, difficulty speaking, sudden numbness, dizziness and confusion.

More information
Is it a stroke? Learn the symptoms at the National Stroke Association.

SOURCES: Larry B. Goldstein, M.D., director, Duke Stroke Center, Durham, N.C.; Robert Glatter, M.D., emergency medicine physician, Lenox Hill Hospital, New York City; April 11, 2012, The Lancet Neurology, online.

Physicists Create First Long-Distance Quantum Link

For more than a decade, physicists have been developing quantum mechanical methods to pass secret messages without fear that they could be intercepted. But they still haven't created a true quantum network—the fully quantum-mechanical analog to an ordinary telecommunications network in which an uncrackable connection can be forged between any two stations or "nodes" in a network. Now, a team of researchers in Germany has built the first true quantum link using two widely separate atoms. A complete network could be constructed by combining many such links, the researchers say.
"These results are a remarkable achievement", says Andrew Shields, applied physicist and assistant managing director at Toshiba Research Europe Ltd. in Cambridge, U.K., who was not involved in the work. "In the past we have built networks that can communicate quantum information, but convert it into classical form at the network switching points. [The researchers] report preliminary experiments towards forming a network in which the information remains in quantum form."
Quantum communications schemes generally take advantage of the fact that, according to quantum theory, it's impossible to measure the condition or "state" of a quantum particle without disturbing the particle. For example, suppose Alice wants to send Bob a secret message. She can do the encrypting in a traditional way, by writing out the message in the form of a long binary number and zippering it together in a certain mathematical way with a "key," another long stream of random 0s and 1s. Bob can then use the same key to unscramble the message.
But first, Alice must send Bob the key without letting anybody else see it. She can do that if she encodes the key in single particles of light, or photons. Details vary, but schemes generally exploit the fact that an eavesdropper, Eve, cannot measure the individual photons without altering their state in some way that Alice and Bob can detect by comparing notes before Alice encodes and sends her message. Such "quantum key distribution" has already been demonstrated in networks, such as a large six-node network in Vienna in 2008, and various companies offer quantum key distribution devices.
Such schemes suffer a significant limitation, however. Although the key is passed from node to node in a quantum fashion, it must be read out and regenerated at each node in the network, leaving the nodes vulnerable to hacking. So physicists would like to make the nodes of the network themselves fully quantum mechanical—say, by forming them out of individual atoms.
According to quantum mechanics, an atom can have only certain discrete amounts of energy depending on how its innards are gyrating. Bizarrely, an atom can also be in two different energy states—call them 0 and 1—at once, although that uncertain two-states-at-once condition "collapses" into one state or the other as soon as the atom is measured. "Entanglement" takes weirdness to its absurd extreme. Two atoms can be entangled so that both are in an uncertain two-ways-at-once state, but their states are perfectly correlated. For example, if Alice and Bob share a pair of entangled atoms and she measures hers and finds it in the 1 state, then she'll know that Bob is sure to find his in the 1 state, too, even before he measures it.
Obviously, Alice and Bob can generate a shared random key by simply entangling and measuring their atoms again and again. Crucially, if entanglement can be extended to a third atom held by Charlotte, then Alice and Charlotte can share a key. In that case, if Eve then tries to detect the key by surreptitiously measuring Bob's atom, she'll mess up the correlations between Alice's and Charlotte's atoms in a way that will reveal her presence, making the truly quantum network unhackable, at least in principle.
But first, physicists must entangle widely separated atoms. Now, Stephan Ritter of the Max Planck Institute of Quantum Optics in Garching, Germany, and colleagues have done just that, entangling two atoms in separate labs on opposite sides of the street, as they report online today in Nature.
As simple as this may sound, the researchers still needed a complete lab room full of lasers, optical elements, and other equipment for each node. Each atom sat between two highly reflective mirrors 0.5 mm apart, which form an "optical cavity." By applying an external laser to atom A, Ritter's team caused a photon emitted by that atom to escape from its cavity and travel through a 60-meter-long optical fiber to the cavity across the street. When the photon was absorbed by atom B, the original quantum information from the first atom was transferred to the second. By starting with just the right state of the first atom, the researchers could entangle the two atoms. According to the researchers, the entanglement could in principle be extended to a third atom, which makes the system scalable to more than two nodes.
"Every experimental step had to be just right to make this work," says Ritter, who works in the group of Gerhard Rempe. "Take, for example, the optical cavity. All physicists agree that atoms and photons are great stuff for building a quantum network, but in free space they hardly interact. We needed to develop the cavity for that."
"This is a very important advance," says Toshiba's Shields, because it would enable technologists to share quantum keys on networks where the intermediate nodes can't be trusted and could also lead to more complex multiparty communication protocols based on distributed entanglement. "However," Shields cautions, "there is still a great deal of work to be done before the technology is practical." Miniaturization of the components that constitute one node will no doubt be on the researchers' wish list.