RESEARCH BRIEFS |
Brain Hesitates in Assembling Mosaic of Motion
When interpreting movement in the visual world, the brain must integrate information from many different neurons in the primary visual cortex, each of which has a very tiny receptive field. From all of these localized snapshots the brain must somehow construct the whole picture. But how does it make an interpretation when the snapshots offer conflicting information?
The aperture problem. A vertical bar is shown at five positions as it moves upward and rightward. But when the bar is viewed through a small window, analogous to a single neuron's receptive field, it seems to move only to the right. Model by Jeff Cleary
In the illustration above, a vertical bar is shown at several positions in time as it moves in a diagonal direction upward and to the right. But when viewed through a small window that does not include the end points of the line, it seems to have moved in a perpendicular direction to the right. If the window represented a cell's receptive field, interpreting direction of movement could be misleading because only cells that are positioned at the end points of the line can register the true direction.
Richard Born, HMS assistant professor of neurobiology, and Christopher Pack, a research fellow in his lab, report in the Feb. 22 Nature that the middle temporal (MT) visual area has a dynamic solution to the problem. Using microelectrodes, they measured neuronal responses in alert macaque monkeys who were shown lines moving at different orientations. How the visual part of the brain interpreted the direction of movement could be determined by the firing of direction-selective MT neurons. The team found that the MT initially responded primarily to the perpendicular component of the movement, consistent with the idea that more neurons are registering only this direction. But over a period of about 60 milliseconds, the neurons gradually register the true direction of movement.
"The brain makes a very quick guess," said Born. "It takes time for the right answer to percolate." The monkeys also made initial eye movements that deviated in the direction perpendicular to the lines, suggesting a behavioral correlate of the early neural response.
Measuring Whether New AIDS Therapies Measure Up
One of the challenges for those conducting clinical trials of new AIDS therapies is finding a meaningful measure of success. In the early days when AIDS therapies were less effective, researchers used disease progression or death as benchmarks for evaluating whether or not a drug was successful. But as therapies became better at keeping disease and death at bay, scientists came to rely more on biological measures of success, such as the amount of virus in the bloodstream.
The virologic measure might be sufficient if all subjects in a clinical trial took the drugs every day as prescribed. But people fall off the therapy bandwagon for a variety of reasons. Many of the new AIDS drug regimens are so strong that patients can suffer significant side effects so debilitating that they have to stop treatment. Consequently, their viral load may go up.
To distinguish these noncompliers from patients who are taking treatment but are still not able to suppress viral production, clinical trials often implement a combined measure, called the regimen termination end point. This measure defines treatment failure according to several events: loss of viral suppression, discontinuation of therapy due to drug toxicity, disease progression, or death. In the Feb. 14 Journal of the American Medical Association, Peter Gilbert, assistant professor of biostatistics, and Victor DeGruttola, professor of biostatistics, both at HSPH, and their colleagues evaluate the two methods.
"Each end point is appropriate in some settingsin some trials," said Gilbert. "It all depends on the goals of the trial." If the aim is to measure how drugs affect the durability of suppression, a purely virologic end point may be appropriate.
"But our main point is that it's really important to do both analyses," he said. "There are many studies that don't do both." By doing both it is often possible to tease apart the virtues of a particular drugfor example, whether it is better at suppressing the virus or whether it is less toxic.
Lyme Disease Vaccine Found Cost-effective Only for Those at High Risk
A group of researchers from Brigham and Women's Hospital, HSPH, and HMS have looked at the cost-effectiveness of vaccination against Lyme disease and found it efficient only for people in high-risk areas.
The study, published in the Feb. 26 Archives of Internal Medicine, evaluated the cost-effectiveness of the vaccine in terms of its cost per quality-adjusted life year (QALY), a measure of the impact of illness on quality of life that is useful for quantifying the effects of nonfatal health problems. To be implemented on a large scale, a vaccine must show a reasonable benefit for the additional cost.
Lyme disease, a bacterial infection transmitted through deer tick bites, is rapidly emerging in the U.S. and currently affects about 15,000 people each year. But incidence varies widely according to region, with the highest rates in the Northeast and north central states. A Lyme disease vaccine has been available since 1999, though guidelines on who should receive it have been vague.
The group found that the vaccine has a high cost per QALY compared with other vaccines and only falls into a reasonable cost-effectiveness range for people in areas where the disease is endemic and who have a one percent or greater probability of contracting it. "It still costs more on average to vaccinate a community than not," said senior author Karen Kuntz, HSPH associate professor of decision science and HMS assistant professor of medicine. But she says the extra cost per QALY gained for endemic populations is similar to that of dialysis for patients with kidney failure, an expense covered by Medicare.
The paper is the first to quantify the cost-effectiveness of the vaccine in terms of QALYs and rate of risk. "It allows you to look more closely at the rates of Lyme disease in your area and extrapolate whether getting vaccinated is cost-effective," said Nancy Shadick, HMS assistant professor of medicine and the paper's lead author. Rates vary widely even within a state; many areas of Massachusetts fall well above the one percent risk rate.
Stem Cells Found in Pancreas May Enable Regeneration of Insulin-Producing Cells
All cell types in the endocrine pancreas have been identifiedor so scientists thought. Now Joel Habener, Howard Hughes investigator and HMS professor of medicine at Massachusetts General Hospital, and colleagues report the discovery of stem cells in the pancreatic islets of Langerhans that generate insulin-secreting beta cells. The stem cells have a great proliferative capacity in vitro and can be induced to make insulin. The study appears in the March Diabetes.
Previous work in which rats were given islet-trophic factors, such as glucose or glucagon-like peptide-1, resulted in a doubling of islet cell mass in a few days. The researchers deduced that stem cells were involved. They looked for nestin expression in the islets because nestin, an intermediate filament protein, is a neuronal marker for stem cells. Beta cells have neuronal properties, and developing islet cells resemble mammalian embryonic neuronal stem cells, which express nestin. The researchers found nestin-positive stem cells within the islets as well as the pancreatic ducts.
In work done initially by Henryk Zulewski, a postdoctoral fellow in Habener's lab at the time, and then postdoc Elizabeth Abraham, nestin-positive cells were isolated from rat and human islets and propagated in culture for over eight months.
Because their discovery was hard to believe, Habener says, the team had to demonstrate beyond doubt that these islet stem cells were not any known pancreatic islet cell types. The authors showed that nestin-positive cells in the islets did not express insulin, glucagon, somatostatin, or pancreatic polypeptide. The markers of vascular endothelium or neurons such as collagen IV and galanin were also absent.
These so-called nestin-positive islet-derived progenitor cells, or NIPS, were then differentiated in vitro to cells that express pancreatic endocrine proteins, including insulin, glucose transporter 2, glucagon, and the transcription factor IDX-1. Additionally, the NIPS can differentiate into cells with liver, pancreatic, exocrine, ductal, and endocrine phenotypes.
Habener says that further research into the properties of NIPS may lead to a means to expand NIPs in vitro for transplantation into patients with diabetes mellitus who lack beta cells.
Brief by Delia Cabe