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Science, Medicine, Technology
  Motor neurons, colored green in this image, attach to muscle fibers.
Motor skills

Columbia physicians recently took skin cells from an 82-year-old victim of Lou Gehrig’s disease and, in collaboration with Harvard researchers, brought about an amazing transformation: They turned the skin cells into nerve cells called motor neurons. Now for the first time medical researchers can observe under a microscope motor neurons from a person who’s afflicted with Lou Gehrig’s disease, which might help them understand and eventually treat the fatal condition.

Motor neurons convey signals from the spinal cord to muscles, telling them when to contract. In a person with Lou Gehrig’s disease, or amyotrophic lateral sclerosis (ALS), the motor neurons slowly degenerate. This eventually paralyzes all of the person’s muscles, including those involved in swallowing and breathing.

Columbia and Harvard teams worked together to reprogram skin cells into a stem-cell-like state in order to generate ALS-afflicted motor neurons. This technique of cellular transformation was first demonstrated last November by researchers in Japan and Wisconsin. It involves turning skin cells into pluripotent stem cells, which can then be prompted to develop into many different types of cells. The technique previously had only been performed using skin cells from healthy people, however.

“Everyone was excited by the potential of this new technology, but it was uncertain that we would be able to obtain the motor neurons from ALS patients’ skin cells,” says Chris Henderson, a coauthor on the study and a Columbia neuroscientist. “Now we can generate hundreds of millions of motor neurons that are genetically identical to a patient’s own neurons.”

The research was published in the August issue of the journal Science. Harvard professor Kevin Eggan was the lead author; Columbia professors Wendy Chung, Hiroshi Mitsumoto, and Hynek Wichterle were coauthors. The Columbia and Harvard research teams are already working together to learn how the cells differ from a healthy person’s motor neurons.
“This will be an immense help,” says Henderson, “as we try to uncover the mechanisms behind this disease and screen for drugs that can prolong life.”

—Alex Lyda

Scientists say the Greenland ice sheet might melt faster than previously predicted.
Laurentide ebbing

The Arctic ice sheets melted a little bit faster this summer than they did last summer. Next year, they’re expected to melt just a little bit faster still.

Some climatologists predict that the rate of melting will continue to increase rather steadily over the course of this century. Other climatologists worry that the ice sheets, because they’re now awash in their own meltwater, might soon begin to break apart violently and disintegrate altogether.

Which scenario is more likely? A recent Columbia study provides insight by retracing the path of the last major ice sheet to vanish. Allegra LeGrande ’07GSAS, a postdoctoral researcher at Columbia’s Center for Climate Systems Research, and Anders Carlson, a glaciologist at the University of Wisconsin, recently mapped and dated the retreat of the Laurentide ice sheet, which once covered the area that is now Canada and the northern United States. It melted sometime between 20,000 and 6500 years ago, but until now scientists didn’t know at what rate.

LeGrande and Carlson say they solved this mystery by examining terrestrial records that indicate when the glacier deposited organic materials in its path and left scars on boulders. Then they analyzed marine records to understand sea-level fluctuation during this era. The scientists plugged this information, along with historical climate data, into a computer program that simulated the Laurentide ice sheet’s demise. LeGrande and Carlson determined that most of the melting occurred in two distinct phases — the first about 9000 years ago and the second 7600 years ago. Each phase lasted roughly 500 to 800 years.

“That’s a very rapid disappearance for an ice sheet this big,” says LeGrande.

The Laurentide’s melting had profound consequences: global sea levels rose an amazing 39 feet, scientists have long known, and Atlantic Ocean currents were disrupted by the fresh-water influx. The Laurentide melted so quickly that at times sea levels rose more than one centimeter per year, the new study found.

Could something similar happen today? LeGrande and Carlson say the temperature increases that melted the Laurentide, which were caused by a natural shift in the earth’s orbit, closely resemble the increases expected by the end of this century from man-made global warming. They say the melting of the ancient ice sheet provides a useful analogue for what could happen to the Greenland ice sheet, which today is losing about 60 cubic miles of ice every year; if the whole thing melts, scientists say global sea levels could rise about 24 feet.

“The geologic record indicates that we could be grossly underestimating how quickly ice sheets could melt during this century,” says Carlson.

—David J. Craig

  CUMC patient Inge Wehrle discusses her fatigue symptoms with Columbia medical researcher Mathew S. Maurer.
Dr. Pep ’er

He’s an old man visiting his doctor on a routine checkup. He doesn’t exercise much anymore, he says, for lack of energy. He spends a lot of time on the couch, which depresses him. That’s normal — a natural part of aging, right?

Mathew S. Maurer recently conducted a study that suggests fatigue is widespread among the elderly but that it should not be considered normal or healthy. The research, which appears in the August issue of the Journal of Gerontology, is based on surveys of 2130 New York City residents between the ages of 65 and 104. Maurer found that 68 percent of respondents felt tired regularly during the day; these subjects also were the most likely to have cardiovascular or respiratory problems, arthritis, sleep disorders, and other health issues. About 18 percent of respondents complained of severe fatigue; nearly all of these subjects had at least one serious medical problem.

How does this help doctors? If fatigue is linked to numerous health problems, does it have any real diagnostic value? “That’s the dilemma,” says Maurer. “What researchers need to do is identify which underlying causes of fatigue are most common.”

Maurer, an assistant professor of medicine, is now investigating the connection between fatigue and heart disease among 61 patients at CUMC. “So far, we’ve found that the worse the fatigue, the worse the person’s heart condition,” he says. Maurer hypothesizes that fatigue associated with heart disease may have certain tell-tale qualities: He thinks it tends to be exacerbated by physical exertion and accompanied by shortness of breath.

Maurer is also trying to develop an objective measure of fatigue. To that end, he’s asked subjects in his heart disease study to wear small, bracelet-like sensor devices that record physical motion around the clock. “This can tell us if the person’s tiredness has a physical correlate, meaning they’re actually less mobile,” Maurer says. “But if they show a normal level of physical activity and feel tired, that might suggest a mood disorder.

“Many older adults feel more comfortable telling their physicians that they’re tired than that they’re in pain or feeling depressed,” says Maurer, who authored the study with fellow CUMC faculty members Huai Cheng and Barry J. Gurland. “Doctors need to recognize that their patients’ self-reported energy level is vital and predictive.”


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