Nosing Out a Smell Gene

The daily smells of the world—the freshness of spring flowers, the smokiness of charred morning toast, the invigorating aroma of a cup of coffee—are lost on those with anosmia, a complete inability to detect odors. Now, thanks to a trio of people who feel no pain, a new study has pinpointed the first set of mutations that are to blame for this condition. The finding could help scientists better understand the gradual loss of smell that happens with age.

The discovery was somewhat happenchance. It began when neurobiologist Frank Zufall of Saarland University in Homburg, Germany, was contacted by pain researcher John Wood of University College London and geneticist Geoffrey Woods of the University of Cambridge in the United Kingdom. Wood and Woods had been studying three people with an inability to feel pain. In 2006, they found that all had mutations in a gene that codes for a sodium channel called Nav1.7 that is involved in the firing of neurons. The researchers also noticed that the volunteers reported having no sense of smell. When the duo created mice with similar mutations, the pups were free of pain, but they also had difficulty smelling; they seemed unable to pick up the odor of their mother’s teats to suckle, for example.

To investigate how the lack of these channels causes anosmia, Zufall and his team studied the genetically engineered mice. They discovered that although neurons in the rodents’ noses respond to different odors, they were unable to transmit these signals to the olfactory bulb, the region at the front of the brain that processes smell.

The researchers also confirmed that the mice couldn’t smell. In a series of experiments, the rodents didn’t avoid the smell of predators, nor did they retrieve their pups when they were scattered around their cage, the researchers report online today in Nature. “This behavior supports that fact that the mice aren’t smelling,” says Lisa Stowers, a neurobiologist at The Scripps Research Institute in San Diego, California, who studies olfaction.

Zufall hopes to turn up more genes underlying anosmia by encouraging doctors to carry out a smell test in patients who present with neurological problems. Peter Mombaerts, an olfaction neuroscientist at the Max Planck Institute of Biophysics in Frankfurt, Germany, agrees that this would be a good approach. “It is a very cheap test,” he says, but he cautions that few doctors currently do it, even though smell can be an important indicator of neurological disease. For example, in Alzheimer’s patients, smell is often one of the first things to deteriorate.

The number of people that are anosmic from birth is likely quite small, says Mombaerts, but by better understanding how olfactory signals are disrupted in people born with this condition, researchers hope to gain insight into why many more develop it later in life.

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How Hormone Puts a Kick in the Sperm’s Tail

It’s exhausting being a sperm. Having made the long-distance swim up the fallopian tube, a sperm must then rev up its tail to propel itself through the thick jelly-like coating of the egg. The female hormone progesterone, released by the egg, prompts the tail to switch from a smooth swimming motion to a frantic flicking, but exactly how has been puzzling. Researchers have now shown that the hormone acts directly on a sperm surface protein, a discovery that may suggest new nonhormonal contraceptives.

For 10 years, researchers have suspected that progesterone, which the egg releases in huge quantities, is responsible for the asymmetrical, whiplike tail movements that give sperm enough torque to penetrate the ovum. Because sperm respond to progesterone within seconds, scientists reasoned that the hormone must bind to a surface protein and not one within the cells, which would take longer for the progesterone to reach.

In 2001, researchers hoped they had found the progesterone receptor when they discovered that infertile men and mice sometimes had mutations that disrupted a protein, called CatSper, which ferries calcium ions in and out of sperm. This so-called calcium channel is found exclusively within sperms’ tails, but working out whether it responds to progesterone proved a thornier exercise than expected. Sperm are not easy cells to work with—for one thing, they don’t stay still.

Now, two research teams have finally connected progesterone to CatSper by inserting a tiny electrode into individual sperm, a technique usually reserved for measuring the electrical signals in neurons. In independent studies appearing online in Nature today, the groups have documented the change in current inside a sperm as progesterone causes positively charged calcium ions to pass into the cell. And because a working ion channel produces a characteristic electrical fingerprint, the researchers were able to use their electrodes to demonstrate that CatSper was responsible for letting in the calcium.

Such work could ultimately explain why some men whose sperm don’t respond to progesterone have low fertility, says Steve Publicover, a physiologist at the University of Birmingham in the United Kingdom who was not involved in the two studies. Publicover notes that this breakthrough was possible because the teams perfected the electrical monitoring of sperm. Only two or three labs in the world can do this, he confirms.

The findings may prove important for explaining the 40% of male infertility cases for which no underlying cause is known, explains Benjamin Kaupp, a biophysicist at the Center of Advanced European Studies and Research in Bonn, Germany, who led one of the teams. “If we can identify the molecules involved, we can look to see if the cause of a man’s infertility is because one or more of these molecules is not working properly,” he says. Based on this work, for example, clinicians could investigate whether a man’s sperm is insensitive to progesterone due to problems with CatSper.

Polina Lishko, a physiologist at the University of California, San Francisco, who is a member of the other team that made the progesterone-CatSper connection, suggests a different outcome from the research. Current female contraceptives are hormonal, depending on progesterone or estrogen, and cause side effects such as weight gain. Lishko argues that CatSper “offers a great opportunity to develop a nonhormone contraceptive.” Once researchers have located where progesterone binds to the CatSper channel, they can look for molecules that would block this interaction, rendering sperm sterile, she explains. “CatSper channels only occur in the tails of the sperm; [such a] contraceptive would have no effect on females and only disrupt male sperm,” Lishko says.

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Organ Development in 3D

organdev3dIf you ever wanted to know how the inner organs of a mouse embryo form, this is the movie for you. The animation was created by imaging thin sections of an embryo and then stacking these images to make a 3D movie. “If you look closely, you can see the developing lungs, gut, kidney, and bladder,” says the movie’s creator, Ian Smyth, a developmental biologist at Monash University in Australia. His video was selected from among several for being the most “striking and technically excellent” of the animations submitted to this year’s Wellcome Image Awards in London. Smyth uses these animations to compare normal tissues in embryos with those whose development is disrupted because of disease or exposure to a toxin. The animation was selected because of its ability to illustrate how effective this imaging technique can be for looking at the internal structure of the organs in a noninvasive way, explains Catherine Draycott, one of this year’s judges. “You can almost travel through [the mouse] as it develops.”

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Does Bird Flu + Swine Flu = Superflu?

What do you get if you cross bird flu with the 2009 pandemic human virus, widely known as swine flu? Unfortunately, the answer isn’t funny. A new study predicts that swapping genes between the avian and human influenza viruses may result in an even more dangerous flu.

The human influenza virus H1N1 that caused the 2009 flu pandemic, and H9N2, an avian influenza virus that is endemic in bird populations in Asia, are close cousins—close enough that they can swap genes if they find themselves in the same cell, resulting in new viruses that are a patchwork of the parent strains. Scientists suspect that some gene combinations may result in a particularly potent form of flu and ignite a pandemic in humans. But because these viruses are more likely to meet in the lungs of an Asian chicken farmer than under the nose of a virologist, researchers find it difficult to predict which gene combinations might be the most virulent and contagious.

So instead of waiting and seeing, researchers have played matchmaker and thrust the two viruses together in a test tube. A team in China generated 127 hybrid viruses and injected each one into lab mice. More than half of the hybrids were as good as their parent strains at infecting the mice, and eight of them proved to be more pathogenic, the team led by Jinhua Liu of the China Agricultural University in Beijing reports online today in the Proceedings of the National Academy of Sciences.

“These are important experiments”, says virologist Peter Palese of Mount Sinai Medical Center in New York City, who was not involved in the work. The viral hybrids that the Chinese team has identified are the ones that scientists might want to watch out for worldwide, he says. If these strains were recognized early, governments could launch a speedier response.

Creating highly virulent viruses in the lab is controversial, says virologist Ab Osterhaus of the Erasmus University Medical Center in Rotterdam, the Netherlands. “[But] I don’t think we should shy away from these experiments. … The more information we have, the better,” he says.

He explains, however, that the hybrids that are the most virulent in mice will not necessarily be the most dangerous in humans, nor the most contagious. “Mice mirror, to a certain extent, what happens in humans,” he says, but they are not perfect model animals. Liu agrees. He plans to investigate how contagious his new viral blends are in guinea pigs and ferrets—animals whose respiratory system better reflects our own feverish battle with flu.

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A Woman’s Tears: The Anti-Viagra?

For many a man, few things deflate his passion faster than the sight of a woman crying. But tears may do more than visually tell a man it’s not time for romance. A woman’s tears contain substances that reduce men’s sexual arousal, a new study indicates. It’s the first evidence that human tears contain chemical signals.

Tears have largely been considered just a visual signal among people: Studies have shown that people looking at a sad face perceive it as sadder when tears are added. In contrast, some animals seem to use their waterworks to communicate chemically. The tears of male mice, for example, contain a protein that makes females more receptive to mating. But given that people, unlike rodents, don’t preen each other, researchers assumed that we rarely come in close enough contact to perceive chemical cues in tears.

Noam Sobel, a neurobiologist at the Weizmann Institute of Science in Rehovot, Israel, wasn’t convinced. Human tears shed under duress differ chemically from those shed to clear the eye of irritants, and he wondered whether human tears might also carry messages for the opposite sex.

To find out, he recruited two women who claimed they could cry on demand. He showed them a sad film—a scene from Franco Zeffirelli’s 1979 film The Champ, in which a son cries over the body of his dying father, a boxer—and collected their tears in vials (see video). Within minutes, the vials were handed to 24 men, aged 23 to 32, who took 10 deep breaths over the open receptacles. Researchers also stuck a tear-soaked cotton square under each man’s nose for the duration of the experiment. As a control, Sobel and his team did the same with saline solution, which they trickled down the women’s cheeks to account for perfumes and face creams they might have been wearing.

The men were then asked to judge the emotion and attractiveness of images of women’s faces that had been made emotionally ambiguous by morphing together happy and sad faces. The men couldn’t smell the difference between tears and saline, and the tears did not influence how sad they thought the faces seemed. Nevertheless, the men found the women less attractive after smelling the tears, the researchers report online today in Science.

The men’s heart and breathing rates, skin temperature, and testosterone levels also sank, indicating a drop in sexual arousal. Peering into the subjects’ brains using functional magnetic resonance imaging, the researchers found that on average the regions of the brain that usually light up when an individual is aroused, the hypothalamus and fusiform gyrus, responded normally to moderately erotic images. However, this neural activity was dampened when the men were exposed to the tears.

Shedding tears is just another way, along with pheromones and body language, that the sexes can communicate, says Sobel. Women shed tears significantly more often during menstruation, when there is a low chance of conceiving, he notes. “This makes perfect sense because it is signaling that sexual activity is inappropriate from an evolutionary point of view,” says Sobel.

The study’s results expose “a hidden, underlying origin” for tears, says Adam Anderson, a neuroscientist at the University of Toronto in Canada. Tears originally functioned to simply shed irritants from the eyes. They were then co-opted to contain chemosignals and then perhaps further co-opted to express sadness, Anderson says.

But many questions remain, says Kazushige Touhara, a molecular biologist at the University of Tokyo who works on biochemical signaling among mice. The substances that dampen male arousal remain unidentified, and it’s not clear whether the men sensed them with their olfactory system or through their skin. Without knowing such details, says Touhara, it is difficult to know how important tears are as a biochemical signaling route in human interactions.

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Do Chimps Play With Dolls?

In the tropical rainforest of Uganda’s Kibale National Park, a young female chimpanzee seems to have adopted a stick. She’s holding it close to her abdomen and carrying it with her everywhere she goes. In a new study, the first to document this behavior in the wild, researchers argue that stick cradling may be akin to human children playing with dolls. And because the team observed it far more frequently in female chimps, the findings suggest that certain gender-specific behaviors are hard-wired.

Making the observations was no easy task. Harvard University primatologist Richard Wrangham and colleagues spent 12 hours a day—much of it crouched behind vegetation—tracking a group of 68 chimps through thick rainforest. During the study period, they observed about 300 instances of chimps picking up sticks. In 40% of cases, the chimps cradled the sticks in the crook of their arm or tucked between their abdomen and thigh (see picture), whereas the rest of the time they used sticks to probe trees and fight each other. More than three-quarters of the stick cradlers were female, the team reports online today in Current Biology. Females were also 10 times more likely to use the sticks as tools than males were—the first time such a large disparity has been reported.

Wrangham says stick cradling reminded him of doll play in girls. And because chimp mothers don’t play with sticks, young female chimps probably aren’t learning the behavior from watching their moms. Instead, it may be hard-wired. Given the close evolutionary relationship between chimps and humans, the implication is that doll playing and other gender-specific behaviors seen in young human children may be hard-wired as well, he says.

Rebecca Jordan-Young isn’t willing to go that far. A sociomedical scientist who studies sex, gender, and sexuality at Barnard College in New York City, Jordan-Young says she doesn’t think anyone should draw sweeping interpretations about innate differences between the sexes from this study. She says that the researchers cannot rule out that females carry sticks because they are mimicking the behavior of other adolescent females. It could also just be a cultural fad.

In addition, Jordan-Young questions the emphasis the authors placed on the doll-carrying observations. Just as intriguing, she says, is the fact that female chimps use tools much more often than males do. But those types of findings, she says, don’t grab headlines.

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Poop Scoop

New baby? Feeling like you’re waist deep in dirty diapers? Forget diaper-collection services; just volunteer your infant for a poop study and researchers will take them off your hands for free. Dirty diapers, it seems, hold the key to measuring infant hormone levels.

Sex hormones, such as estrogen, are important for babies’ healthy development. But some endocrinologists worry that children are exposed to too much additional estrogen via soy formula, plant fertilizers, and even plastics, which could cause faster-than normal development and future problems with reproduction. However, few infants tolerate a frequent finger or heel prick, and so “very little is know about hormone levels in infants,” explains Michelle Lampl, an anthropologist at Emory University in Atlanta.

Diapers, however, can be collected frequently and over a long period of time, perfect for a
longitudinal study. Practicing on eight to 10 diapers collected from each of 32 largely breast-fed
infants over 6 months, Lampl’s group perfected a technique for extracting hormone levels from the
poop, they reported online last month in Frontiers in Systems Biology.

They also perfected their diaper-collection technique. “It took years to fi nd the right nappy
and work out how you get the diaper fresh from the home to the lab,” says Lampl. The secret: a
cotton diaper, a Ziploc bag, and an ice pack.

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How to Feed a 180-Ton Whale

feed180tonwhale

For the blue whale, feeding is an Olympic event. The largest animal on Earth dives 500 meters at speeds of up to 3 meters per second, U-turns toward the surface, and then opens its colossal mouth to scoop up clouds of krill and filter them from the water with its brushlike teeth. A new study reveals that this massive energy expenditure is worth it. Although the whales are feasting on some of the smallest creatures on the planet, the dive fills them with enough sustenance to survive.

To understand the energetics of the blue whale’s feeding behavior, Robert Shadwick, a biomechanic at the University of British Columbia in Canada, and colleagues analyzed data collected from digital tags suctioned-cupped to the whales’ back. The tags, which travel with the animal on its descent to the clouds of shrimplike krill, measure the animal’s speed, depth, orientation and the number of times it beats its tail; they then pop off and float to the surface, ready to be retrieved by pursuing biologists. Combining data from these tags with measurements of whale jaws from museum specimens, the team modeled the drag experienced by the whale as it performs its complex underwater acrobatics.

The whales use about 63,000 kilojoules of energy on each dive, the researchers report online today in The Journal of Experimental Biology. But they also eat about 1260 kilograms of krill, as calculated from the average number of krill present in the 80 metric tons of water they gulp. And that provides the whales with about 100 times more energy from the tiny creatures than they spend capturing them.

Blue whales need that extra energy because they devote such a small proportion of their lives to feeding, says Ann Pabst, a functional morphologist at the University of North Carolina, Wilmington, who was not involved with the study. She notes that the animals spend many months either migrating to and from feeding grounds or reproducing, and during these periods they must survive off their fat reserves.

Pabst adds that the new study was possible only because of new tagging technologies, which were developed by the U.S. Navy to measure pressure deep in the ocean. The tags provide so much information that “we can almost visualize what is going on at [these] depths,” she says.

The researchers hope the work aids conservation efforts. Due in part to increased human consumption of krill as fish stocks run low, blue whale numbers are only 3% of what they were in the 1800s. The data could help conservationists make a stronger argument for how much krill the whales need to survive.

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Odor Exposure in the Womb Primes the Palate

Moms, want your children to eat their greens? Then you have to eat them, too, at least while you’re pregnant. Researchers have found that offspring of mouse mothers fed a diet enhanced with cherry and mint flavors during pregnancy continued to prefer these flavors into adulthood, while mice from mothers fed on a bland diet had no food preference. The rodents with a penchant for mint-cherry food developed larger glomeruli, the region of the brain responsible for processing odor—the first evidence that exposure to odors in the womb alters the way the brain develops. From the fetus’ point of view, this is a good evolutionary strategy; eat the foods that your mother ate because they are probably safe. It is likely that all mammals, including humans, develop their sense of taste in this same way, the researchers report online today in the Proceedings of the Royal Society B, so expectant moms, be careful the next time you have a hankering for anchovies with chocolate sauce.

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