Yale Alumni Magazine: Findings

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Findings
January/February 2007

A Gene for the Blues
by Marc Wortman

When life hits hard, most people can roll with the punches. Others, less resilient, react to adversity by ruminating over it, often becoming anxious or even depressed. The difference may be genetic.

An international team that included R. Todd Constable, professor of diagnostic radiology, used an innovative combination of genetic and behavioral analysis and brain imaging techniques to examine how genes and stress interact and affect the way the brain works. Their study, published October 24 in the Proceedings of the National Academy of Sciences, compared people with two variants of a receptor gene for serotonin, a neurotransmitter with many functions, including the regulation of mood and anxiety. People who have what’s called the short-variant type of this gene experience a decreased flow of serotonin across neurons; such people may also show more symptoms of depression in response to stressful events. On the other hand, carriers of the long variant tend to take stress in stride.

Constable’s team worked with 48 healthy subjects and studied activation patterns in the amygdala and hippocampus, regions of the brain in which low activation is associated with depression. The subjects were shown images of happy, sad, fearful, and neutral faces. Individuals who carried the short variant of the gene—and who had experienced the worst stress earlier in life—showed less activation relative to other subjects. (People in this short-variant, high-prior-stress group were also more likely to ruminate after stressful events.) But subjects with the short-variant gene and little prior life stress had higher activation patterns.

“This vulnerability is a good example of a gene-environment interaction,” says Constable. The short-variant gene may somehow lead to those brain regions becoming “chronically more sensitive to stressful events. When additional stress occurs, they are likely to react in unhealthy ways.”

Baked Scorpions
by Bruce Fellman

The primary component of a living insect’s tough protective covering is a substance called chitin. Chitin is also found in the shells of crabs and lobsters. Yet in fossils of these crustaceans, especially those more than 25 million years old, chitin is absent. In its place are substances related to kerogens, the long-chain hydrocarbons from which petroleum is derived.

Scientists once thought the chemical transformation took place because, during fossilization, molecules in sediments slowly replace those in an animal’s tissues. But in a paper published in the November 7 issue of the Proceedings of the Royal Society B: Biological Sciences, postdoctoral researcher Neal S. Gupta has shown that an entirely different metamorphosis is at work. His method? Time-lapse fossilization. “You can replicate fossilization in the lab,” explains Gupta, a geochemist who worked with colleagues in England and France to crack the chitin conundrum.

The process of chemical fossilization was developed in part by Derek Briggs, Yale’s Frederick William Beinecke Professor of Geology and Geophysics. Inside a gold vessel about the size of a marking pen, a tiny powdered sample of this organism is subjected to temperatures of more than 650 degrees F and pressures 700 times those found at sea level.

“With this technique, we can age a specimen 25 million years in a day,” Gupta says.

Gupta and his colleagues tested scorpions, shrimp, and hissing cockroaches. They found that the long-chain hydrocarbons come from the
organism itself. Lipids—fat molecules—from living plants and animals are the raw materials from which time, temperature, and pressure eventually recast a fossil’s molecular structure.

Understanding aliphatic chemistry—the chemistry of these relatively simple carbon-based substances—is important for more than scientific reasons, says Gupta: it’s also important for understanding fossil fuels. “It’s this aliphatic component that eventually allows us to drive our cars and heat our homes.”

When Speed is a Savior
by Bruce Fellman

There’s an uncomfortable pressure in your chest. Pain shoots through your neck and arms. You feel faint, anxious, and sick to your stomach.

You may be having a heart attack. Approx-imately 850,000 people in the United States suffered one last year, but about a third of all heart attacks will respond to rapid treatment to open total or near-total blockages in one or more of the coronary arteries. For these people, getting fast treatment is essential.

“The sooner the better,” says Harlan Krumholz '80, the Harold H. Hines Jr. Profes-sor of Medicine. “Heart muscle can’t live long without its supply of blood, and every second the heart is deprived of vital oxygen and nutrients can lead to further and, ultimately, irreversible damage and patient death. And yet across the country we too often squander minutes in the treatment of patients with heart attacks.”

In 2004, Krumholz was a member of an expert panel convened by the American College of Cardiology and the American Heart Association. The panel stated that patients who are referred for an emergency balloon angioplasty for a heart attack should be treated within 90 minutes of their arrival at the hospital. But in recent studies, Krumholz and his colleagues have shown that only about a third of the U.S. hospitals capable of performing the procedure currently achieve that 90-minute “gold standard" with even half their patients. However, in a landmark paper published in the November 30 issue of the New England Journal of Medicine, Krumholz—along with epidemiology professor Elizabeth Bradley and a multidisciplinary research team—showed precisely how hospitals could dramatically reduce their “door-to-balloon" times.

The research team had earlier visited 11 hospitals with some of the nation’s fastest times for an in-depth investigation of the secrets to their success. For the NEJM study, Krumholz, Bradley, and colleagues, building on this qualitative research, conducted a Web-based survey of 365 hospitals on their approach to emergency angioplasty.

The team then correlated these survey responses with the times the hospitals achieved. (The responses were based on data hospitals submit to the federal government as part of a national public reporting program that Krumholz helped develop.)

Among their findings: letting emergency room doctors activate the catheterization lab—instead of waiting for a cardiologist to order the activation—saves an average of 8.2 minutes. Establishing a one-call paging system to assemble the angioplasty team saves 13.8 minutes. And expecting the staff to be in the lab within 20 minutes saves 19.3 minutes.

“The door-to-balloon time is about a very special choreography between different hospital services,” says Krumholz. “Our study emphasizes not a single action but a sequence of steps to improve communication, coordination, and collaboration. What is notable is that each of the strategies associated with faster times was utilized by only a minority of the hospitals.”

Krumholz and a group of cardiologists, emergency room physicians, nurses, and administrators have already put these strategies into practice at Yale–New Haven Hospital. As a result, YNHH has become one of the few facilities in the country to meet the 90-minute standard consistently. “Five years ago, door-to-balloon times averaged over two hours at YNHH,” says Krumholz. “But, now they’re exemplary.”

The time-saving strategies outlined in the NEJM paper have been adopted by the American College of Cardiology, along with the American Heart Association and other prominent organizations, as part of a campaign designed and led by Krumholz to lower door-to-balloon times nationwide. “Most of these strategies can be implemented right away without significant cost,” says Krumholz. “If we are successful, we could save 1,000 people a year.”

Appearances Deceive
by Bruce Fellman

When biologists try to distinguish one species from another, the first task is always to look for obvious physical differences. But looks can lead even a scientist astray.

Consider the pair of mouse lemurs at left. Mouse lemurs are the world’s smallest living primates, found only in Madagascar; these two are part of a group of nearly 200 collected from 2003 to 2005 at a wildlife refuge on the island. Scientists found such a wide variation in fur color that they suspected there might be several different species.

But when Kellie Heckman, a postdoctoral researcher in ecology and evolutionary biology, compared a gene sequence taken from 70 lemurs’s ear tissue, she got a surprise. “The sequences were absolutely identical,” says Heckman. “They’re all the same species.” (Her paper appeared in BMC Evolutionary Biology in November.)

Fur color may not, in fact, have any influence on evolutionary trends among mouse lemurs. They are strictly nocturnal animals with limited nighttime color vision, relying mostly on smell and sound to tell each other apart. But even a species with excellent color sensitivity may display wide color variations (Homo sapiens springs to mind). Ultimately, says Heckman, in identifying different species “you can’t rely on just one kind of information.”

Noted

Paleontologist Derek Briggs and his colleagues have discovered a biological treasure in an unusually well-preserved cache of fossils in England: 425-million-year-old eggs. The oldest known eggs, and what appear to be juveniles, were found inside a tiny shrimp the team named Nymphatelina gravida. The discovery, published in the November 21 online edition of the Proceedings of the Royal Society B, provides evidence for the evolution of egg brooding.

For those whose knees are afflicted with osteoarthritis, massage therapy combined with conventional drug treatments delivers better pain relief and joint function improvement than can be achieved by medication alone. This finding, by David L. Katz, director of the Yale Prevention Research Center, and his colleagues, appears in the December 11 issue of the Archives of Internal Medicine.

Beware bicycle seats. Prolonged sitting on them has led to erectile dysfunction in male bicyclists, the result of compression of the arteries and nerves of the perineum. Now a team led by Professor Marsha Guess has shown that women can also experience compression-related problems. In a study published in the November issue of the Journal of Sexual Medicine, the researchers found that almost two-thirds of 48 competitive female bicyclists reported a significant decrease in genital sensation.

Inactive senior citizens can reduce their chances of becoming disabled by participating in a structured exercise program. Medical school researcher Thomas M. Gill showed that seniors who exercised regularly were nearly one-third more likely to remain able to walk a quarter-mile than those who were given health education alone. The results appeared in the November Journal of Gerontology: Medical Sciences.




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