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"As far as we can tell, this is the first time this type of behavior has been reported in cells that are part of a larger organism," says Peter T. Cummings, John R. Hall Professor of Chemical Engineering, who directed the study that is described in the March 10 issue of the Public Library of Science journal PLoS ONE. The discovery was the unanticipated result of a study the Cummings group conducted to test the hypothesis that the freedom with which different cancer cells move - a concept called motility - could be correlated with their aggressiveness: That is, the faster a given type of cancer cell can move through the body the more aggressive it is. "Our results refute that hypothesis—the correlation between motility and aggressiveness that we found among three different types of cancer cells was very weak," Cummings says. "In the process, however, we began noticing that the cell movements were unexpectedly complicated." Then the researchers' interest was piqued by a paper that appeared in the February 2008 issue of the journal Nature titled, "Scaling laws of marine predator search behaviour." The paper contained an analysis of the movements of a variety of radio-tagged marine predators, including sharks, sea turtles and penguins. The authors found that the predators used a foraging strategy very close to a specialized random walk pattern, called a Lévy walk, an optimal method for searching complex landscapes. At the end of the paper's abstract they wrote, "...Lévy-like behaviour seems to be widespread among diverse organisms, from microbes to humans, as a 'rule' that evolved in response to patchy resource distributions." This gave Cummings and his colleagues a new perspective on the cell movements that they were observing in the microscope. They adopted the basic assumption that when mammalian cells migrate they face problems, such as efficiently finding randomly distributed targets like nutrients and growth factors, that are analogous to those faced by single-celled organisms foraging for food. With this perspective in mind, Alka Potdar, now a post-doctoral fellow at Case Western Reserve University and the Cleveland Clinic, cultured cells from three human mammary epithelial cell lines on two-dimensional plastic plates and tracked the cell motions for two-hour periods in a "random migration" environment free of any directional chemical signals. Epithelial cells are found throughout the body lining organs and covering external surfaces. They move relatively slowly, at about a micron per minute which corresponds to two thousandths of an inch per hour. When Potdar carefully analyzed these cell movements, she found that they all followed the same pattern. However, it was not the Lévy walk that they expected, but a closely related search pattern called a bimodal correlated random walk (BCRW). This is a two-phase movement: a run phase in which the cell travels primarily in one direction and a re-orientation phase in which it stays in place and reorganizes itself internally to move in a new direction. In subsequent studies, currently in press, the researchers have found that several other cell types (social amoeba, neutrophils, fibrosarcoma) also follow the same pattern in random migration conditions. They have also found that the cells continue to follow this same basic pattern when a directional chemical signal is added, but the length of their runs are varied and the range of directions they follow are narrowed giving them a net movement in the direction indicated by the signal.

The study authors, led by Rachel Manber, PhD, professor of psychiatry and behavioral sciences, said they hope the results will raise awareness of the problem of depression during pregnancy and provide patients and physicians an alternative to antidepressants. "This standardized acupuncture protocol could be a viable treatment option for depression during pregnancy," they wrote in a paper that will appear in the March issue of Obstetrics & Gynecology. Up to 14 percent of pregnant women may have major depressive disorder, a condition characterized by feelings of dread, gloom and hopelessness, and a loss of interest in normally pleasurable activities. Some women suffer from depression before becoming pregnant, stop taking their medication and then experience a relapse; in other women, pregnancy itself may cause depression.

For this study, the researchers recruited 150 women whose pregnancies were between 12 and 30 weeks gestation and who met the criteria for major depressive disorder. The women were randomized to receive one of three treatments: acupuncture specific for depression; control acupuncture, during which needles were inserted in points not known to help alleviate depressive symptoms; or massage. All of the women received eight weeks of therapy and were assessed for depression at the four- and eight-week marks by an interviewer who was unaware of the treatment each woman received. The researchers found that women who received the depression-specific acupuncture experienced a bigger reduction in depression symptoms than the women in the other groups. The response rate — defined as having a 50 percent or greater reduction in symptoms — was 63 percent for the women receiving depression-specific acupuncture, compared with 44 percent for the women in the other two treatment groups combined. The researchers weren't surprised by what they found — a pilot study yielded similar results, and other studies have shown acupuncture is an effective treatment for depression in the general public — but they were pleased with the results. "I don't think that one-size-fits-all treatments are appropriate for everyone, but acupuncture should be considered as an option," said Lyell. "I hope that people will respect the rigorous methodology used in this blinded, randomized, controlled trial and accept the result: Traditional acupuncture was associated with a significant improvement in depression."