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Archive - Jun 30, 2009

Long-Lived Bats Show Less Protein Damage

Bats generally live far longer than would be predicted by their size. Scientists have now shown that the relatively long life spans of some bat species, compared to the much shorter life spans of similarly sized mice, may owe to lower levels of protein oxidation and less misfolding of proteins in the bats. In addition, the researchers found that the bats had low levels of protein ubiquitination and reduced proteasome activity, suggesting diminished protein damage and removal in bats. Based on these results, the scientists concluded that long life span in some bat species may be regulated by very efficient maintenance of protein homeostasis. This work was featured as the cover story in the July issue of the FASEB Journal. [Press release] [FASEB abstract]

New Technique Shatters Barriers of Light Microscopy

In what may prove to be a profound advance, researchers have used a combination of light and ultrasound to visualize fluorescent proteins that are several centimeters below the surface of living tissue. In the past, even modern technologies have failed to produce high-resolution fluorescence images from this depth because of the strong scattering of light. Lead author Dr. Daniel Razansky, who played a pivotal role in developing the new method, said that it "opens the door to a whole new universe of research. For the first time, biologists will be able to optically follow the development of organs, cellular function, and genetic expression through several millimeters to centimeters of tissue.” To achieve its feat, the research team made light “audible.” They illuminated adult zebra fish from multiple angles using flashes of laser light that are absorbed by fluorescent pigments in the tissue of the genetically modified fish. The fluorescent pigments absorb the light, a process that causes slight local increases in temperature, which in turn result in tiny local volume expansions. This happens very quickly and creates small shock waves. In effect, the short laser pulse gives rise to an ultrasound wave that the researchers pick up with an ultrasound microphone. The real power of the technique, however, lies in specially developed mathematical formulas used to analyze the resulting acoustic patterns. An attached computer uses these formulas to evaluate and interpret the specific distortions caused by scales, muscles, bones, and internal organs to generate a three-dimensional image. The researchers performed similar successful experiments with fruit fly pupae. The research team included scientists from the Helmholtz Center Munich, Massachusetts General Hospital, and Harvard Medical School.

Three Toll-Like Receptors Implicated in Lupus

Researchers have shown that three particular Toll-like receptors (TLRs) may play a key role in the development of systemic lupus erythematosus (SLE or lupus), an autoimmune disease affecting over 1.5 million Americans. In mouse strains that spontaneously develop human-similar forms of SLE, the authors showed that TRL 3, TRL 7, and TRL 9 appear to be required for the full autoimmune response to take place. These TLRs may thus provide effective targets for the development of new treatments for lupus, as well as other autoimmune diseases. The researchers did their experiments by first engineering lupus-prone mice to have a non-functioning form of the gene (Unc93b1) that is required for transport of the three TRLs from where they are made to the cell’s endolysosome where they do their work. In the endolysosome, TLRs normally detect foreign DNA and RNA and instruct the body’s immune system to make antibodies against these materials. But the production of antibodies against foreign DNA and RNA seems to be particularly prone to error. The most common types of autoantibodies found in lupus patients are ones to the body's own genetic material—the DNA and RNA that resides inside the cell's nucleus. As a result, doctors often test for the presence of "antinuclear" antibodies to diagnose lupus. In their study, the researchers found that compared to the lupus-prone mice with a functioning Unc93b1 gene, the lupus-prone mice with the Unc93b1 mutation produced fewer antinuclear antibodies and had fewer and less severe symptoms of lupus. "It seems like these three TLRs are absolutely required for optimal autoantibody production," said Dr. Dwight Kono, an author of the study.