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December 05, 2012

In Research

Researchers discover how rodent wards off cancer

blind mole rat
A blind mole rat is shown on the background of dying necrotic blind mole rat cells.

Rochester biologists have determined how blind mole rats fight off cancer—and the mechanism differs from what they discovered three years ago in another long-lived and cancer-resistant mole rat species, the naked mole rat.

The team of researchers—led by Vera Gorbunova, professor of biology and associate professor of oncology, and Andrei Seluanov, assistant professor of biology—found that abnormally growing cells in blind mole rats secrete the interferon beta protein, which causes those cells to rapidly die. Seluanov and Gorbunova hope the discovery will eventually help lead to new cancer therapies in humans. Their findings are published in the Proceedings of the National Academy of Sciences.

Blind mole rats and naked mole rats—both subterranean rodents with long life spans—are the only mammals never known to develop cancer. Three years ago, Seluanov and Gorbunova determined the anticancer mechanism in the naked mole rat. Their research found that a specific gene, p16, makes the cancerous cells in naked mole rats hypersensitive to overcrowding and stops them from proliferating when too many crowd together.

“We expected blind mole rats to have a similar mechanism for stopping the spread of cancerous cells,” says Seluanov. “Instead, we discovered they’ve evolved their own mechanism.”

Gorbunova and Seluanov say they next want to find out exactly what triggers the secretion of interferon beta after cancerous cells begin proliferating in blind mole rats. Read more at www.rochester.edu/news. A video about the research is also available at www.youtube.com/user/UniversityRochester.

In pregnancy, Type 2 diabetes may pose less risk than Type 1

Pregnant women with Type 2 diabetes have a better chance at good outcomes than those with Type 1, particularly if they receive proper care before and during their pregnancy, according to a Medical Center study published in the Journal of Reproductive Medicine.

“With the rapid rise of Type 2 diabetes in reproductive-age women, it is important to look at it separate from Type 1 so we know how best to support and care for Type 2 diabetics to promote the best possible outcomes in pregnancy,” says study coauthor Eva Pressman, professor of obstetrics and gynecology and head of the division of maternal fetal medicine. Historically, research on diabetes in pregnancy did not differentiate between the two types, Pressman says.

The study indicated that Type 1 diabetics had a higher incidence of complications and of poor outcomes than the Type 2 and nondiabetic women. For example, 20 percent of the Type 1 diabetics had preeclampsia, a condition marked by elevated blood pressure and protein in the urine, compared with 14 percent of Type 2 and 1 percent of nondiabetics. Type 1 mothers who had never had a cesarean delivery had a 50 percent cesarean-section rate, compared with 27 percent for Type 2 and 13 percent for nondiabetics. Babies of Type 2 diabetics in the study had a higher incidence of being large for their gestational age, at 38 percent, versus 23 percent for Type 1 moms and just 3 percent for nondiabetic moms. Eighty-five percent of babies born to Type 1 moms required admission to the neonatal intensive care unit, compared with 71 percent born to Type 2 moms and 11 percent of non-diabetic moms. Read more at www.urmc.rochester.edu/news.

Being neurotic—and conscientious—a good combo for health

Under certain circumstances neuroticism can be good for your health, according to a Medical Center study showing that some self-described neurotics also tended to have the lowest levels of interleukin 6 (IL-6), a biomarker for inflammation and chronic disease.

Researchers made the preliminary discovery while conducting research into how psychosocial factors such as personality traits influence underlying biology to predict harmful conditions like inflammation.

Known as one of the “Big 5” dimensions of personality, neuroticism is usually marked by being moody, nervous, and a worrier and linked to hostility, depression, and excessive drinking and smoking. The scientific literature is rife with findings that extreme anxiety and self-medicating with alcohol and other substances due to neuroticism are detrimental to long-term health. The other four traits are openness (creative, curious, broad-minded), extraversion (outgoing, friendly, talkative), agreeableness (helpful, warm, sympathetic), and conscientiousness (organized, responsible, hardworking).

Exhibiting higher levels of conscientiousness as well as neuroticism points to people who tend to be high functioning in society, very organized, goal-oriented, planners, and more likely to be reflective.

“These people are likely to weigh the consequences of their actions, and therefore their level of neuroticism coupled with conscientiousness probably stops them from engaging in risky behaviors,” says Nicholas Turiano, a postdoctoral fellow in the Department of Psychiatry, whose study is published online by the journal Brain, Behavior, and Immunity. Read more at www.urmc.rochester.edu/news.

Change in defibrillator therapy leads to huge benefits for heart patients

A new study shows that defibrillators—devices designed to detect and correct dangerous heart rhythms—can help people with heart disease live longer, and with a much better quality of life, than they do now.

defibrillatorA small, very simple change in the way physicians set or programmed the device led to a dramatic 80 to 90 percent reduction in inappropriate therapies—potentially painful and anxiety-provoking shocks delivered for rhythms that aren’t dangerous or life threatening. And, to the authors’ surprise, the new programming also significantly increased survival, lowering the risk of death by 55 percent compared to patients whose devices used traditional programming. The reduction is above and beyond the usual decrease in mortality associated with defibrillator therapy, leading to an overall 70 percent reduction in death.

The MADIT-RIT trial, published in the New England Journal of Medicine and presented at the American Heart Association’s Scientific Sessions in Los Angeles, was led by Arthur Moss, professor of cardiology. Moss’s team found that simply raising the heart rate at which the device is set to fire—deliver therapy—made all the difference.

“The way we’ve been using implantable defibrillators for the last 20 years has really been less than optimal,” says Moss. “The extent to which the new programming reduced death and inappropriate therapies was quite striking and has the potential to beneficially affect a wide spectrum of patients who are at risk for sudden death or rhythm disorders.”

Currently, most defibrillators are set to initiate therapy when the heart rate exceeds around 170 beats per minute, but rates of 180 or 190 are not always dangerous, are usually short lived, and could be related to increased activity or exercise. The study showed that setting the device to fire at a higher rate of 200 beats per minute reduced the risk of experiencing a first inappropriate therapy by 79 percent compared to standard programming. Fewer shocks also corresponded with less energy delivered to the heart, which study authors believe contributed to the reduced risk of death. Read more and watch a video at urmc.rochester.edu/news.

Medical Center scientists create 'endless supply' of myelin-forming cells

In a new study appearing in the Journal of Neuroscience, researchers have unlocked the complex cellular mechanics that instruct specific brain cells to continue to divide. The discovery overcomes a significant technical hurdle to potential human stem cell therapies; ensuring that an abundant supply of cells is available to study and ultimately treat people with diseases.

“One of the major factors that will determine the viability of stem cell therapies is access to a safe and reliable supply of cells,” says Steve Goldman, the Edward A. and Alma Vollertsen Rykenboer Chair in Neurophysiology and lead author of the study. “This study demonstrates that—in the case of certain populations of brain cells—we now understand the cell biology and the mechanisms necessary to control cell division and generate an almost endless supply of cells.”

The study focuses on cells called glial progenitor cells (GPCs) that are found in the white matter of the human brain. The stem cells give rise to two cells found in the central nervous system: oligodendrocytes, which produce myelin, the fatty tissue that insulates the connections between cells; and astrocytes, cells that are critical to the health and signaling function of oligodendrocytes as well as neurons.

Damage to myelin lies at the root of a long list of diseases, such as multiple sclerosis, cerebral palsy, and a family of deadly childhood diseases called pediatric leukodystrophies. The scientific community believes that regenerative medicine—in the form of cell transplantation—holds great promise for treating myelin disorders. Goldman and his colleagues, for example, have demonstrated in numerous animal model studies that transplanted GPCs can proliferate in the brain and repair damaged myelin. Read more at urmc.rochester.edu/news.

Rare meteorites created in violent celestial collision

slide of meteorite, showing gold/brown crystal network
A slice of the Esquel meteorite, discovered in central Argentina.

A tiny fraction of meteorites on earth contain strikingly beautiful, translucent, olive-green crystals embedded in an iron-nickel matrix. Called pallasites, the “space gems” have fascinated scientists since they were first identified as originating from outer space more than 200 years ago.

A new study published in Science shows that their origins were more dramatic than first thought. Using a carbon dioxide laser, a magnetic field, and a sophisticated recording device, a team led by John Tarduno, professor of geophysics, has shown that the pallasites were likely formed when a smaller asteroid crashed into a planet-like body about one 30th the size of earth, resulting in a mix of materials that make up the distinctive meteorites.

“The findings by John Tarduno and his team turn the original pallasite formation model on its head,” says Joshua Feinberg, assistant professor of earth sciences at the University of Minnesota, who was not involved in the study. “Their analysis of the pallasites has helped to significantly redefine our understanding of how these objects formed during the early history of our solar system.”

Pallasites are made of iron-nickel and the translucent, gem-like mineral olivine, leading many scientists to assume they were formed where those two materials typically come together—at the boundary of the iron core and rocky mantle in an asteroid or other planetary body. Tarduno discovered that tiny metal grains in the olivine were magnetized in a common direction, a revelation that led the researchers to conclude that the pallasites must have been formed much farther from the core. Read more at www.rochester.edu/news.