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Scholarship & Creative Work
Knee injuries may start with strain on the brain, not the muscles

New research shows that training your brain may be just as effective as training your muscles in preventing ACL knee injuries, and suggests a shift from performance-based to prevention-based athletic training programs.

The ACL, or anterior cruciate ligament, is one of the four major ligaments of the knee, and ACL injuries pose a rising public health problem as well as an economic strain on the medical system.

U-M researchers studying ACL injuries had subjects perform one-legged squats to fatigue, then tested the reactions to various jumping and movement commands. Researchers found that both legs — not just the fatigued leg — showed equally dangerous and potentially injurious responses, says Scott McLean, assistant professor with the School of Kinesiology. The fatigued subjects showed significant potentially harmful changes in lower body movements that, when preformed improperly, can cause ACL tears.

"These findings suggest that training the central control process — the brain and reflexive responses — may be necessary to counter the fatigue induced ACL injury risk," says McLean, who also has an appointment with the Bone & Joint Injury Prevention Center.

McLean says that most research and prevention of ACL injuries focuses below the waist in a controlled lab setting, but the U-M approach looks a bit north and attempts to untangle the brain's role in movements in a random, realistic and complex sports environments.

The findings could have big implications for training programs, McLean says. Mental imagery or virtual reality technology can immerse athletes in very complex athletic scenarios, thus teaching rapid decision making. It might also be possible to train "hard wired" spinal control mechanisms to combat fatigue fallout.

The paper, "Fatigue Induced ACL Injury Risk Stems from a Degradation in Central Control," appears in the August issue of Medicine and Science in Sports and Exercise.e

Climate caused biodiversity booms and busts in ancient plants, mammals

A period of global warming from 53 million to 47 million years ago strongly influenced plants and animals, spurring a biodiversity boom in western North America, researchers from three research museums report.

"Today, the middle of Wyoming is a vast desert, and a few antelope and deer are all you see," says lead author Michael Woodburne, honorary curator of geology at the Museum of Northern Arizona. "But 50 million years ago, when temperatures were at their highest, that area was a tropical rainforest teeming with lemur-like primates, small dawn horses and a number of small forest rodents and other mammals. In fact, there were more species of mammals living in the western part of North America at that time than at any other time."

The paper appears online in the Proceedings of the National Academy of Sciences.

Woodburne and co-authors Gregg Gunnell of the U-M Museum of Paleontology and Richard Stucky of the Denver Museum of Nature & Science examined the records of ancient temperatures and information on the fossil plants and mammals that inhabited North America during the Eocene epoch and found that diversity increased and declined with rising and falling temperatures.

Until this research, the consensus among paleontologists who study North American vertebrates was that climate played only a background role in supporting the evolution of mammals during the Paleocene and Eocene (65 million to 35 million years ago) and that only at the end of the Eocene, when Antarctic glaciations began, did Earth's climate deteriorate enough to cause observable changes in land mammal diversity.

"Our paper documents the fact that global change affected plants and animals on a wide scale," says Gunnell, an associate research scientist and vertebrate collection coordinator at the Museum of Paleontology. "Some plants and animals flourished while others suffered."

Protein complex key in avoiding DNA repair mistakes, cancer

As the body creates antibodies to fight invaders, a three-protein DNA repair complex called MRN is crucial for a normal gene-shuffling process to proceed properly, U-M research shows.

The discoveries in mice, published online in Nature Structural and Molecular Biology, advance understanding of the immune system and shed light on how B-cell lymphoma and some other cancers may begin.

U-M scientists found that:

• When one protein in the MRN complex, Mre11, is absent, mistakes occur in a risky DNA break-and-repair process that routinely occurs in immune system B cells. The process is known as immunoglobulin class switch recombination.

• Incorrectly repaired DNA can alter the normal action of B lymphocytes and their offspring, whose job is to make antibodies to combat and protect against specific disease-causing microbes and other foreign agents.

"Class switch recombination represents a double-edged sword, being necessary for immune system function, but known to cause cancer when mistakes are made. We now understand that Mre11 and the MRN complex as a whole lie in the middle of this delicate balance," says Dr. David Ferguson, the study's senior author and assistant professor of pathology at the Medical School.

In further research in mice, Ferguson and his team are now searching for specific evidence that double strand breaks get "misrepaired" in ways that lead to B-cell lymphoma. The research may eventually lead to human trials of new strategies in cancer diagnosis and treatment.

Additional authors include: Maria Dinkelmann, Elizabeth Spehalski, Trina Stoneham, Jeffrey Buis and Yipin Wu, Department of Pathology; and JoAnn Sekiguchi, Department of Internal Medicine and Department of Human Genetics.

Game utilizes human intuition to help computers solve complex problems

A new computer game prototype combines work and play to help solve a fundamental problem underlying many computer hardware design tasks.

The online logic puzzle is called FunSAT, and it could help integrated circuit designers select and arrange transistors and their connections on silicon microchips, among other applications.

Designing chip architecture for the best performance and smallest size is an exceedingly difficult task that's outsourced to computers these days. But computers simply flip through possible arrangements in their search. They lack the human capacities for intuition and visual pattern recognition that could yield a better or even optimal design. That's where FunSAT comes in.

Developed by computer science researchers Valeria Bertacco and Andrew DeOrio, FunSAT is designed to harness humans' abilities to strategize, visualize and understand complex systems.

"Computer games can be more than a fun diversion," says Bertacco, an associate professor in computer science and engineering. "Humans are good at playing games and they enjoy dedicating time to it. We hope that we can use their strengths to improve chip designs, databases and even robotics."

DeOrio, a doctoral student in computer science and engineering, will present a paper on the research on July 30 at the Design Automation Conference in San Francisco. The paper is called "Human Computing for EDA."

A single-player prototype exists at, implemented in Java by undergraduate Erica Christensen. Bertacco and DeOrio are working on growing it to a multi-player game, which would allow more complicated problems to be solved.

By solving challenging problems on the FunSAT board, players can contribute to the design of complex computer systems, but you don't have to be a computer scientist to play. The game is a sort of puzzle that might appeal to Sudoku fans.

Teens cite multiple motives for using nonprescribed pain medication

Many high school seniors who take pain medications without a prescription do so for reasons besides relieving pain, a new study finds.

From a list of 17 motives for nonmedical use of prescription opioids, the leading motives were "to relax or relieve tension" (56.4 percent), "to feel good or get high" (53.5 percent), "to experiment, see what it's like" (52.4 percent) and "to relieve physical pain" (44.8 percent).

The study sought to assess motives for nonmedical use of prescription opioids among high school seniors, as well as examine motives for nonmedical use and other substance use behaviors. Examples of prescription opioids — medications prescribed to manage pain — include hydrocodone, oxycodone, hydromorphone, meperidine, morphine, opium or codeine.

"The results of this study provide compelling evidence that adolescents have a wide range of motives for using prescription opioids nonmedically and these motives should be carefully considered in efforts to reduce this behavior," says Sean Esteban McCabe, the study's lead author and a research associate professor at the Substance Abuse Research Center and the Institute for Research on Women and Gender.

Data were collected from 12,441 seniors in public and private high schools in the United States between 2002 and 2006.

More than one in 10 students — or 12.3 percent — reported lifetime nonmedical use, including 8 percent who used during the past year.

Screening efforts should be used to differentiate between adolescents who need help with pain management and those who need a more comprehensive assessment for substance use disorders, the researchers conclude.

The findings appear in the August issue of the Archives of Pediatrics & Adolescent Medicine.

McCabe collaborated on the study with Carol Boyd, director, Institute for Research on Women and Gender; and James Cranford, research assistant professor, Addiction Research Center.

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