Inside this issueCover storiesThe tiniest scale yields the biggest prizeSmilow Cancer Hospital, a 'great achievement,' welcomes patients
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AdvancesHealth and science news from YaleImages help scientists think outside the boxCell structures known as box C/D guide ribonucleoproteins (RNPs) help to maintain the integrity of ribosomes, which synthesize proteins in all forms of life on Earth (see related story). A team in the lab of Susan J. Baserga, M.D., Ph.D., used electron microscopy to discern the structure of the box C/D RNP in Methanocaldococcus jannaschii, a hardy microbe found in Antarctic ice and in boiling vents on the ocean floor. Conventional models have proposed that box C/D RNPs are composed of one RNA molecule and pairs of core proteins. But as reported in the September 11 edition of Science, first author Franziska Bleichert, M.D., and the Yale group found that the M. jannaschii box C/D RNP was instead made up of two RNAs and four copies of each of the three core proteins (see image above). “It looks like a Wheat Thin with feet,” says Baserga, professor of molecular biophysics and biochemistry. “When you can discern structure, you can often figure out function.” Giving a gut punch to Parkinson’s diseaseObesity is a well-known risk factor in diabetes, heart disease, and cancer. Now, scientists are finding links between obesity and neurodegenerative diseases such as Parkinson’s disease (PD) as well. PD is caused when dopamine-producing nerve cells die off in a part of the brain that governs movement. In the November 11 issue of The Journal of Neuroscience, a team led by Tamas L. Horvath, D.V.M., Ph.D., chair and professor in the section of comparative medicine, and also professor of obstetrics, gynecology, and reproductive sciences and of neurobiology, conclude that ghrelin, a hormone produced by the stomach, can protect these neurons from death, and that obesity-related declines in ghrelin may raise the risk of PD. Dopamine cells in mice lacking ghrelin that were exposed to a cell-killing toxin died off in substantially greater numbers than in normal mice; administration of ghrelin reversed this effect. “Because this hormone originates from the stomach, it is circulating normally in the body,” Horvath says, “so it could easiliy be used to boost resistance to Parkinson's or it could be used to slow the development of the disease.” Neurons shouldn’t always stick togetherThe cerebral cortex is organized into contiguous cellular columns—the sort of ordering a dozen pencils takes on if tightly wrapped with a rubber band. These columns form during embryonic development, when neurons shimmy up spoke-like radial glial cells until they reach their proper location in the cortex. However, some neurons in each column shift away from the glial spoke to form interconnections with neurons in neighboring columns, ensuring a proper neuronal “blend” to perform specific functions. Scientists believe that disturbances in this process may cause psychiatric disorders. In the September 24 issue of Nature, a group led by Pasko Rakic, M.D., Ph.D., the Dorys McConnell Duberg Professor of Neurobiology, reports that in mice lacking genes for the receptor EphA, neurons formed tight, even single-file columns, while overexpression of EphA caused too much lateral drift (green in image). In normal mice, appropriate numbers of neurons drifted to neighboring columns to perform their assigned duties. “This so-far unrecognized mechanism … seems to be essential for the proper intermixing of neuronal types in the cortical columns,” the authors write. Can an old antibody learn a new trick?Antibody-based drugs, which harnass and enhance the power of the immune system, have been useful in treating many diseases. However, most are expensive, have unacceptable side effects, or cannot be orally administered. In papers published on the Web on October 19 and November 4 by the Journal of the American Chemical Society, David A. Spiegel, M.D., Ph.D., assistant professor of chemistry, and olleagues describe small molecules that direct antibodies to kill prostate cancer cells or cells infected with the HIV virus. The molecules built by the Spiegel team are “bifunctional”—they have been designed to lock onto diseased cells and also onto anti-DNP, an otherwise passive antibody that is naturally present in many people and can be easily and safely induced in others. “Instead of trying to kill the pathogens directly, these molecules manipulate our immune system to do something it wouldn’t ordinarily do,” says Spiegel. “This is an entirely new approach to treating these two diseases.”  |
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