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Aliquots ó Research highlights from VUMC laboratories

3/30/2007 - Vitamin A at the root

Vitamin A and its derivatives (retinoids) have long been staples of skin care products like Retin A. But retinoids may also be involved in hair development and maintenance. Enzymes involved in the synthesis of retinoic acid (RA), the active form of vitamin A, have been found within the hair follicle, suggesting that the follicle is able to synthesize its own RA for use in hair growth.

In the advance online edition of the Journal of Investigative Dermatology, Helen Everts, Ph.D., David Ong, Ph.D., and colleagues report the localization of all components — enzymes, binding proteins and RA receptors — of the RA biosynthesis pathway within mouse hair follicles during different stages of the hair cycle. The study also revealed sites where exogenous RA (like that in cosmetics or skin care products) could disrupt the hair cycle and lead to skin fragility and hair loss.

Understanding this pathway, the researchers write, could lead to better skin treatments that lack the unwanted side effects.

— Melissa Marino

Bad diet inflames fat

That “spare tire” from eating too many donuts may be the key factor driving an inflammatory condition in the body's white fat, a recent study suggests.

In obese animals and humans, macrophages infiltrate the body's white adipose tissue, an encroachment associated with increased inflammation, insulin resistance and predisposition to diabetes. But how do other diet-related factors, such as elevated plasma lipids, affect this inflammatory state?

Kimberly Coenen, M.S., Marnie Gruen, M.S. and Alyssa Hasty, Ph.D., examined the abdominal fat of mice genetically predisposed to obesity and elevated plasma lipid levels and fed either a standard chow diet or a high-fat, “Western” diet. Contrary to expectations, the researchers found that macrophage infiltration correlated only with the degree of diet-induced obesity, not hyperlipidemia. The results, published in the March issue of Diabetes, sound a warning that a high-fat diet, even if it doesn't result in plasma lipid abnormalities, could increase diabetes risk through its actions on white fat.

— Melissa Marino

Neutralizing a toxic threat

Through the actions of its epsilon-toxin, the anaerobic bacterium Clostridium perfringens can be just as lethal — at least to farm animals — as its more well known relatives that cause botulism and tetanus. While its potential to cause human illness is unclear, epsilon-toxin is considered a “category B” agent by the U.S. government. A vaccine and an antitoxin are available to protect livestock against this toxin, but neither is acceptable for human use.

In the April issue of Infection and Immunity, Mark McClain, Ph.D., and Timothy Cover, M.D., identify the regions in the toxin's protein sequence to which two neutralizing antibodies can bind and inhibit the toxin's deadly effects in cultured cells. The antibodies, which block the toxin's ability to form pores in the cell membrane, bind to a short sequence of amino acids (epitope) that appear to control the toxin's insertion into the cell membrane. Such epitopes may be useful in guiding the development of therapeutic agents to counter the effects of epsilon-toxin in humans.

— Melissa Marino

Partners in movement

Wiggle your fingers. You just activated motor neurons — through a chain of highly specific neuronal connections. What makes a motor neuron choose one input in the chain over another? Stephen Von Stetina, Ph.D., Rebecca Fox, Ph.D., David Miller, Ph.D., and colleagues are probing this question of “synaptic choice” in the motor system of the nematode C. elegans. They knew that C. elegans “VA” and “VB” motor neurons choose different neuronal inputs and that in “uncoordinated” worms with a deletion in the unc-4 transcription factor, VA neurons are miswired with VB inputs. The researchers used a neuron-specific microarray strategy to understand how unc-4 controls synaptic choice.

They report in the Feb. 1 Genes & Development that UNC-4, with its co-repressor UNC-37/Groucho, turns off expression of another transcription factor, CEH-12/HB9, and that this developmental switch controls the selection of synaptic inputs in motor neurons. All three factors are conserved in the vertebrate motor circuit, suggesting that similar mechanisms may regulate synaptic choice in the spinal cord.

— Leigh MacMillan

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012
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