Saturday, October 30, 2010

MOLECULAR SWITCH CONTROLS MELANIN PRODUCTION, MAY ALLOW TRUE SUNLESS TANNING

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Discovery of a molecular switch that turns off the natural process of skin pigmentation may lead to a novel way of protecting the skin – activating the tanning process without exposure to cancer-causing UV radiation. In their report in the journal Genes & Development, researchers from the Massachusetts General Hospital (MGH) Cutaneous Biology Research Center (CBRC) describe how blocking the action of this switch – an enzyme called PDE-4D3 – in the skin of mice led to a significant increase in melanin production.

"The primary goal of inducing melanin production in human skin would be prevention of skin cancer, since all the common forms are known to be associated with UV exposure, " explains David Fisher, MD, PhD, director of the hospital's Department of Dermatology and an investigator at the MGH CBRC, who led the study. "Not only would increased melanin directly block UV radiation, but an alternative way to activate the tanning response could help dissuade people from sun tanning or indoor tanning, both of which are known to raise skin cancer risk."

In 2006 Fisher's group showed that the metabolic pathway leading to UV-induced pigmentation is controlled by cyclic AMP (cAMP), a molecule known to regulate many important cellular processes by carrying messages from the cell surface to internal target molecules. Using a strain of transgenic mice with red hair and melanocytes in their epidermis – common mice have none of these melanin-producing cells in the outer skin layer – they found that inducing cAMP production in the animals' skin led to significant pigmentation. But since the drug used in that study cannot penetrate human skin, they needed to investigate an alternative approach.

Because most drugs act by blocking rather than stimulating their target molecules, better defining the pathway leading from UV exposure to melanin production could identify a step limiting melanin expression that, if suppressed, would increase production of the pigment. The strength and duration of the signals carried by cAMP are controlled by PDE enzymes, which break down the molecule after its message is delivered. Detailed analysis of the melanin expression pathway identified PDE-4D3 as the regulator of cAMP activity in melanocytes. The transcription factor activated by cAMP induces production of both melanin and PDE-4D3, and the enzyme in turn modulates the pigmentation process by breaking down cAMP.

The researchers confirmed role of PDE-4D3 in controlling melanin expression by applying several agents that block PDE production to the skin of the transgenic mice with epidermal melanocytes. After five days of treatment, the animals' skin had darkened significantly, while treatment of control mice with no epidemal melanocytes produced no effect.

"Although PDE enzymes degrade cAMP within all cells, different members of this enzyme family are active in different types of cells," Fisher explains. "We showed that PDE-4D3 is particularly important within melanocytes, and while the enzyme may have a role in other cells, a blocking drug that is applied directly to the skin would probably have limited effects in other tissues." Additional research is needed to identify drugs that penetrate human skin and safely block PDE-4D3, he notes, and his team has already starting searching for such agents.

Massachusetts General Hospital

HOW TO WEIGH A STAR USING A MOON

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How do astronomers weigh a star that's trillions of miles away and way too big to fit on a bathroom scale? In most cases they can't, although they can get a best estimate using computer models of stellar structure.

New work by astrophysicist David Kipping says that in special cases, we can weigh a star directly. If the star has a planet, and that planet has a moon, and both of them cross in front of their star, then we can measure their sizes and orbits to learn about the star.

"I often get asked how astronomers weigh stars. We've just added a new technique to our toolbox for that purpose," said Kipping, a predoctoral fellow at the Harvard-Smithsonian Center for Astrophysics.

Astronomers have found more than 90 planets that cross in front of, or transit, their stars. By measuring the amount of starlight that's blocked, they can calculate how big the planet is relative to the star. But they can't know exactly how big the planet is unless they know the actual size of the star. Computer models give a very good estimate but in science, real measurements are best.

Kipping realized that if a transiting planet has a moon big enough for us to see (by also blocking starlight), then the planet-moon-star system could be measured in a way that lets us calculate exactly how large and massive all three bodies are.

"Basically, we measure the orbits of the planet around the star and the moon around the planet. Then through Kepler's Laws of Motion, it's possible to calculate the mass of the star," explained Kipping.

The process isn't easy and requires several steps. By measuring how the star's light dims when planet and moon transit, astronomers learn three key numbers: 1) the orbital periods of the moon and planet, 2) the size of their orbits relative to the star, and 3) the size of planet and moon relative to the star.

Plugging those numbers into Kepler's Third Law yields the density of the star and planet. Since density is mass divided by volume, the relative densities and relative sizes gives the relative masses. Finally, scientists measure the star's wobble due to the planet's gravitational tug, known as the radial velocity. Combining the measured velocity with the relative masses, they can calculate the mass of the star directly.

"If there was no moon, this whole exercise would be impossible," stated Kipping. "No moon means we can't work out the density of the planet, so the whole thing grinds to a halt."

Kipping hasn't put his method into practice yet, since no star is known to have both a planet and moon that transit. However, NASA's Kepler spacecraft should discover several such systems.

"When they're found, we'll be ready to weigh them," said Kipping.

(Photo: David A. Aguilar (CfA))

CfA

U OF A RESEARCH STUDIES WHY SOME BRAND NAMES ARE MUSIC TO OUR EARS

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If you're having a bad day, you may want to stay away from listening to commercials for Lululemon or Coca Cola. Or from any retailer or merchandise whose name bears a similarly repetitive phonetic sound.

University of Alberta marketing professor Jennifer Argo recently published a study in the Journal of Marketing indicating that hearing the names of brands containing these types of repetitive sounds can influence our mood and thus our decision-making ability when it comes to choosing whether or not we frequent that establishment or buy those items.

Argo, along with her colleagues, conducted a number of studies testing brand names, including identical samples of ice cream that were given two different names: one for which the name contained a repetitive sound and one where there was none. The researchers introduced the identical products to test subjects one at a time, citing the name for each sample aloud during the product description. Despite the same ice cream being used, the majority of respondents chose the brand with the repetitive-sounding name.

In other studies, giving people choices over everything from types of desserts in one or cell phone options in another, the researchers found similar results from the respondents' selections. In these cases, they chose based on an affective (emotional) response. Argo says that an audible repetition needs to be present—findings that are key for marketers, advertisers and store managers.

"Based on the results, it would say that tv and radio advertisements are critical to this strategy," Argo said. "But the employees are also critical. Before customers order, a server can remind the name of the restaurant they're at. Sales people can talk with customers and mention the brand name."

In all of the six trials Argo's group conducted, each invented brand name underwent only minute changes in variations, such as "zanozan" versus "zanovum". Argo noted that, in all cases, such small variations, even as much as a single letter, had a huge impact as to the person's choice and how they responded.

Alas, too much sound repetition can also be a bad thing, as can developing a name that does not follow a natural linguistic sound, for example, "ranthfanth". In these cases, she says, respondents displayed negative affect when these conditions were present.

"You can't deviate too much from our language, otherwise it will backfire on you," said Argo.

Argo, whose studies often deal with subjects related to consumer awareness, notes that there is one loophole to the brand/sound strategy: the device is less effective if the person is already positively affected. Argo's advice for someone practising retail therapy would be to "plug your ears; don't let anyone talk to you." Overall, Argo notes that people need to be aware of the influence that a brand name may have on mood and choice and that marketing strategists have gone to great lengths in choosing the moniker for their product.

"The companies have spent millions of dollars choosing their brands and their brand names and they've been picked explicitly to have an influence on consumers," she said. "We show that it can get you at the affective level."

University of Alberta

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