Interstellar: Starting over on a new 'Earth'

The movie Interstellar opens in theaters at a time when Earth is facing major losses of biodiversity and ecosystems, says David Lynn, an Emory professor of biomolecular chemistry.

While humanity is challenged to find out what’s happening to Earth and how to make adjustments, we have also begun to realize that billions of Earth-like planets likely exist in habitable zones around the stars of our galaxy.

“In as little as 10 years, we could know whether we’re alone in the universe, whether there are other living systems,” Lynn says. “That’s an exciting prospect. It’s not clear necessarily that we’ll find out that there is intelligent life or not. That may be a lower probability, but that’s also possible.”

Much of the science in Interstellar is not accurate, and its vision of the future may not come true. And yet, it is still an important film, Lynn says, since its themes resonate today, during a critical time in our history.

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Having a Y chromosome doesn't affect women's response to sexual images, brain study shows

The study provides "further evidence that we need to revamp our thinking about what we mean by 'man' and 'woman,'" says psychologist Kim Wallen.

By Carol Clark

Women born with a rare condition that gives them a Y chromosome don’t only look like women physically, they also have the same brain responses to visual sexual stimuli, a new study shows.

The journal Hormones and Behavior published the results of the first brain imaging study of women with complete androgen insensitivity, or CAIS, led by psychologists at Emory.

“Our findings clearly rule out a direct effect of the Y chromosome in producing masculine patterns of response,” says Kim Wallen, an Emory professor of psychology and behavioral neuroendocrinology. “It’s further evidence that we need to revamp our thinking about what we mean by ‘man’ and ‘woman.’”

Wallen conducted the research with Stephan Hamann, Emory professor of psychology, and graduate students in their labs. Researchers from Pennsylvania State University and Indiana University also contributed to the study.

The Y chromosome was identified as the sex-determining chromosome in 1905. Females normally have an XX chromosome pair and males have an XY chromosome pair.

By the 1920s, biochemists also began intensively studying androgens and estrogens, chemical substances commonly referred to as “sex hormones.” During pregnancy, the presence of a Y chromosome leads the fetus to produce testes. The testes then secrete androgens that stimulate the formation of a penis, scrotum and other male characteristics.

Women with CAIS are born with an XY chromosome pair. Because of the Y chromosome, the women have testes that remain hidden within their groins but they lack neural receptors for androgens so they cannot respond to the androgens that their testes produce. They can, however, respond to the estrogens that their testes produce so they develop physically as women and undergo a feminizing puberty. Since they do not have ovaries or a uterus and do not menstruate they cannot have children.

“Women with CAIS have androgen floating around in their brains but no receptors for it to connect to,” Wallen says. “Essentially, they have this default female pattern and it’s as though they were never exposed to androgen at all.”

Wallen and Hamann are focused on teasing out neural differences between men and women. In a 2004 study, they used functional magnetic resonance imaging (fMRI) to study the neural activity of typical men and typical women while they were viewing photos of people engaged in sexual activity.

The patterns were distinctively clear, Hamann says. “Men showed a lot more activity than women in two areas of the brain – the amygdala, which is involved in emotion and motivation, and the hypothalamus which is involved in regulations of hormones and possibly sexual behavior.”

For the most recent study, the researchers repeated the experiment while also including 13 women with CAIS in addition to women without CAIS and men.

“We didn’t find any difference between the neural responses of women with CAIS and typical women, although they were both very different from those of the men in the study,” Hamann says. “This result supports the theory that androgen is the key to a masculine response. And it further confirms that women with CAIS are typical women psychologically, as well as their physical phenotype, despite having a Y chromosome.”

A limitation of the study is that it did not measure environmental effects on women with CAIS. “These women look the same as other women,” Wallen explains. “They’re reared as girls and they’re treated as girls, so their whole developmental experience is feminized. We can’t rule out that experience as a factor in their brain responses.”

The findings may have broader applications in cognition and health. “Anything that we can learn about sex differences in the brain,” Wallen says, “may help answer important questions such as why autism is more common in males and depression more common in females.”

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Images: Thinkstock

Creepy crawlies and the science of fear

 
Tarantulas don't eat people and even try to avoid them. So chill out.

Why are we afraid of spiders, snakes and roaches? WXIA reporter Julie Wolfe explores that question through a new exhibit at the Fernbank Museum of Natural History called "Goose Bumps! The Science of Fear." Below is an excerpt from a report by Wolfe:

"It was my nightmare inside a glass box: A dozen cockroaches hissing and wiggling and waiting to crawl up my nose. Okay, maybe not that last part.

"When Emory Assistant Psychology Professor Seth Norrholm suggested I slip my hand into a box that may lead to that creepy, crawly nightmare, I hesitated. It's a response that was programmed into me stretching back to my caveman ancestors.

"All fears can fit into three categories: Innate fears, learned fears and preparatory fear.

"'An innate fear is something that you're born with, and it's a survival instinct type of fear,' Norrholm explained. Fear of animals and insects fall into that category. Among the most common fears: Spiders, cockroaches and snakes."

Watch a video of her report on the WXIA web site.

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Teeth, sex and testosterone reveal secrets of aging in wild mouse lemurs

A brown mouse lemur in the wild. Mouse lemurs, weighing a mere 30 to 80 grams, are the world's smallest primates. Photos, above and below, by Jukka Jernvall.

By Carol Clark

Mouse lemurs can live at least eight years in the wild – twice as long as some previous estimates, a long-term longitudinal study finds.

PLOS ONE published the research on brown mouse lemurs (Microcebus rufus) led in Madagascar by biologist Sarah Zohdy, a post-doctoral fellow in Emory's Department of Environmental Sciences and the Rollins School of Public Health. Zohdy conducted the research while she was a doctoral student at the University of Helsinki.

“It’s surprising that these tiny, mouse-sized primates, living in a jungle full of predators that probably consider them a bite-sized snack, can live so long,” Zohdy says. “And we found individuals up to eight years of age in the wild with no physical symptoms of senescence like some captive mouse lemurs start getting by the age of four.”

It is likely that starvation, predation, disease and other environmental stressors reduce the observed rate of senescence in the wild, Zohdy notes, but a growing body of evidence also suggests that captive conditions may affect mental and physical function.

“We focused on wild mouse lemurs because we want to know what happens naturally when a primitive primate is exposed to all of the extrinsic and intrinsic mortality factors that shaped them as a species,” Zohdy says. “Comparing longevity data of captive and wild mouse lemurs may help us understand how the physiological and behavioral demands of different environments affect the aging process in other primates, including humans.”

The study determined ages of wild mouse lemurs in Madagascar’s Ranomafana National Park through a dental mold method that had not previously been used with small mammals. In addition to the high-resolution tooth-wear analysis for aging, fecal samples underwent hormone analysis.



The researchers found no difference between the longevity of male and female mouse lemurs, unlike most vertebrates where males tend to die first.

“And even more interestingly, we found no difference in testosterone levels between males and females,” Zohdy says. Mouse lemurs are female dominant, which may explain why their testosterone levels are on a par with males.

“While elevated male testosterone levels have been implicated in shorter lifespans in several species, this is one of the first studies to show equivalent testosterone levels accompanying equivalent lifespans,” Zohdy says.

A co-author of the study is primatologist Patricia Wright of the Centre ValBio Research Station in Madagascar and Stony Brook University. Other institutions involved in the study include Colorado State University, Duke University and the University of Arizona, Tucson.

Mouse lemurs, found only on the island of Madagascar, are the world’s smallest primates. They are among nearly 100 species of lemurs that arrived in Madagascar some 65 million years ago, perhaps floating over from mainland Africa on mats of vegetation.

Mouse lemurs weigh a mere 30 to 80 grams but in captivity they live six times longer than mammals of similar body size, such as mice or shrews. Captive gray mouse lemurs (Microcebus murinus) can live beyond age 12. By age four, however, they can start exhibiting behavioral and neurologic degeneration. In addition to slowing of motor skills and activity levels, reduced memory capacity and sense of smell, the captive four-year-olds can start developing gray hair and cataracts, Zohdy says.


Brown mouse lemurs evolved in isolation, along with nearly 100 other species of lemurs.

The wild brown mouse lemurs in the study were trapped, marked and released during the years 2003 to 2010. A total of 420 dental impressions were taken from the lower-right mandibular tooth rows of 189 unique individuals. Over the course of seven years, 270 age estimates were calculated. For 23 individuals captured three or more times during the duration of the study, the regression slopes of wear rates were calculated and the mean slope was used to calculate ages for all individuals.

“We found that wild brown mouse lemurs can live at least eight years,” Zohdy says. “In the population that we studied, 16 percent lived beyond four years of age. And we found no physical signs of senescence, such as graying hair or cataracts, in any wild individual.”

Limitations of the study include the inability to document gradual physiological symptoms of senescence in the wild. “Our results do not provide information about wild brown mouse lemurs that can be directly compared to senescence in captive gray mouse lemurs,” Zohdy says. “Further research, using identical measures of senescence, will help to reveal whether patterns of physiological senescence occur consistently across the genus and in both captive and wild conditions.”

Another confounding factor Zohdy cites is “the Sleeping Beauty effect,” the fact that wild mouse lemurs hibernate for half the year, possibly boosting their life span.

“We now know that mouse lemurs can live a relatively long time in the wild,” she says, “but we don’t know the exact mechanisms behind why they live so long.”

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Molecular beacons shine light on how cells 'crawl'

"Our premise is that mechanics play a role in almost all biological processes, and with these DNA-based tension probes we’re going to uncover, measure and map those forces,” says biomolecular chemist Khalid Salaita. Graphic by Victor Ma.

By Carol Clark

Adherent cells, the kind that form the architecture of all multi-cellular organisms, are mechanically engineered with precise forces that allow them to move around and stick to things. Proteins called integrin receptors act like little hands and feet to pull these cells across a surface or to anchor them in place. When groups of these cells are put into a petri dish with a variety of substrates they can sense the differences in the surfaces and they will “crawl” toward the stiffest one they can find.

Now chemists have devised a method using DNA-based tension probes to zoom in at the molecular level and measure and map these phenomena: How cells mechanically sense their environments, migrate and adhere to things.

Nature Communications published the research, led by the lab of Khalid Salaita, assistant professor of biomolecular chemistry at Emory University. Co-authors include mechanical and biological engineers from Georgia Tech.

Using their new method, the researchers showed how the forces applied by fibroblast cells are actually distributed at the individual molecule level. “We found that each of the integrin receptors on the perimeter of cells is basically ‘feeling’ the mechanics of its environment,” Salaita says. “If the surface they feel is softer, they will unbind from it and if it’s more rigid, they will bind. They like to plant their stakes in firm ground.”

The integrin receptors on fibroblast cells, above, "are kind of beasts," Salaita says. "They apply relatively high forces in order to adhere to the extracellular matrix." NIH photo.

Each cell has thousands of these integrin receptors that span the cellular membrane. Cell biologists have long been focused on the chemical aspects of how integrin receptors sense the environment and interact with it, while the understanding of the mechanical aspects lagged. Cellular mechanics is a relatively new but growing field, which also involves biophysicists, engineers, chemists and other specialists.

“Lots of good and bad things that happen in the body are mediated by these integrin receptors, everything from wound healing to metastatic cancer, so it’s important to get a more complete picture of how these mechanisms work,” Salaita says.

The Salaita lab previously developed a fluorescent-sensor technique to visualize and measure mechanical forces on the surface of a cell using flexible polymers that act like tiny springs. These springs are chemically modified at both ends. One end gets a fluorescence-based turn-on sensor that will bind to an integrin receptor on the cell surface. The other end is chemically anchored to a microscope slide and a molecule that quenches fluorescence. As force is applied to the polymer spring, it extends. The distance from the quencher increases and the fluorescent signal turns on and grows brighter. Measuring the amount of fluorescent light emitted determines the amount of force being exerted. (Watch a video of the flexible polymer technique.)

Yun Zhang, a co-author of the Nature Communications paper and a graduate student in the Salaita lab, had the idea of using DNA molecular beacons instead of flexible polymers. “She was new to the lab and brought a fresh perspective,” Salaita says.

The molecular beacons are short pieces of lab-synthesized DNA, each consisting of about 20 base pairs, used in clinical diagnostics and research. The beacons are called DNA hairpins because of their shape.

The thermodynamics of DNA, its double-strand helix structure and the energy needed for it to fold are well understood, making the DNA hairpins more refined instruments for measuring force. Another key advantage is the fact that their ends are consistently the same distance apart, Salaita says, unlike the random coils of flexible polymers.

T cells are white blood cells whose receptors are focused not on adhesion, but on activities like identifying various peptides. Electron micrograph of a human T cell by NIAID/NIH.

In experiments, the DNA hairpins turned out to operate more like a toggle switch than a dimmer switch. “The polymer-based tension probes gradually unwind and become brighter as more force is applied,” Salaita says. “In contrast, DNA hairpins don’t budge until you apply a certain amount of force. And once that force is applied, they start unzipping and just keep unraveling.”

In addition, the researchers were able to calibrate the force constant of the DNA hairpins, making them highly tunable, digital instruments for calculating the amount of force applied by a molecule, down to the piconewton level.

“The force of gravity on an apple is about one newton, so we’re talking about a million-millionth of that,” Salaita says. “It’s sort of mind-bogging that that’s how little force you need to unfold a piece of DNA.”

The result is a tension probe that is three times more sensitive than the polymer probes.

In a separate paper, published in Nano Letters, the Salaita lab used the DNA-based probes to experiment with how the density of a substrate affects the force applied.

“Intuitively you might think that a less dense environment, offering fewer anchoring points, would result in more force per anchor,” Salaita said. “We found that it’s actually the opposite: You’re going to see less force per anchor.” The mechanism of sensing ligand spacing and adhering to a substrate appears to be force-mediated, he says. “The integrin receptors need to be closely spaced in order for the engine in the cell that generates force to engage with them and commit the force.”

Now the researchers are using the DNA-based tools they’ve developed to study the forces of more sensitive cellular pathways and receptors.

“Integrin receptors are kind of beasts, they apply relatively high forces in order to adhere to the extracellular matrix,” Salaita says. “There are lots of different cell receptors that apply much weaker forces.”

T cells, for example, are white blood cells whose receptors are focused not on adhesion but on activities like distinguishing a friendly self-peptide from a foreign bacterial peptide.

The Salaita lab is collaborating with medical researchers across Emory to understand the role of cellular mechanics in the immune system, blood clotting and neural patterning of axons. “Basically, our premise is that mechanics play a role in almost all biological processes, and with these DNA-based tension probes we’re going to uncover, measure and map those forces,” Salaita says.

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