Mature neurons in the central nervous system fail to regen-erate following injury; in fact, this is the main reason that spinal cord injury typically results in permanent paralysis and loss of sensation. A new study shows that small-molecule inhibitors of the epidermal growth factor receptor can coax neurons into growing extensions known as axons, suggesting that such compounds might prove useful as treatments for spinal cord injury (Science 2005, 310, 106). Zhigang He of Harvard Medical School and colleagues demonstrate that inhibiting EGFR with these compounds blocks the activities of myelin inhibitors and chondroitin sulfate proteoglycans—both factors that normally inhibit regeneration of injured axons. Local administration of the small molecules results in significant regeneration of injured optic nerve fibers in mice, they report. He notes that localized administration of Tarceva (shown), an oral EGFR inhibitor marketed by Genentech for cancer treatment, also does the trick. His team is now investigating whether this drug can elicit a similar effect when administered orally.
A new nature-inspired stra-tegy should make it easier to identify the protein targets of bioactive small molecules in living systems (Nat. Biotechnol., published online Oct. 2, dx.doi.org/10.1038/nbt1149). Identifying the protein target of a hit from a chemical genomics screen remains a formidable challenge, particularly in mammalian systems. To overcome this technological hurdle, Benjamin F. Cravatt and coworkers at Scripps Research Institute have created structurally diverse libraries of small molecules (shown) that feature a protein-reactive spiroepoxide electrophile found in a number of natural products. And an alkyne click chemistry handle allows for eventual identification of epoxide-tagged proteins. The researchers compare the proteome reactivity of library members that elicit a desired biological effect in a cell-based screen to identify proteins uniquely labeled by a given bioactive compound. They demonstrated the strategys utility by identifying a library member that inhibits breast cancer cell proliferation and fingering its protein target. Cravatt notes that while the method might not yield good drugs, it provides critical guidance about viable therapeutic targets.
Pheromones—compounds that serve as a means of chemical communication between animals of the same species—are usually, though not always, volatile compounds. Biologist Kazushige Touhara and coworkers at the University of Tokyo have discovered a new nonvolatile sex-specific pheromone secreted from the tear glands of male mice (Nature 2005, 437, 898). The 7-kilodalton peptide, which the researchers call exocrine gland-secreting peptide-1, is secreted from the eyes of male mice and transferred to females through direct contact. The peptide stimulates neurons in the females that are usually associated with pheromone response. The pheromone does not elicit a response in male mice. Through genetic analysis, the researchers found that the gene encoding the peptide is part of a previously unrecognized gene family.
Satellite measurements show that the water vapor content of the upper troposphere increased from 1982 to 2004, according to a study by Brian J. Soden of the University of Miami and his colleagues (Science, published online Oct. 6, dx.doi.org/10.1126/science.1115602). Conventional radiosonde measuring systems had detected an increase in water vapor in the lower troposphere but were unable to detect a rise in the upper troposphere—about 5–12 km above Earths surface. The satellite readings that Soden analyzed, however, show water vapor increasing 6% in the upper troposphere over the past 20 years. Because water vapor is a primary greenhouse gas, the upper tropospheric increase plays a key role in how much the climate warms in response to rising concentrations of CO2. With a doubling of atmospheric CO2 levels from current levels, expected sometime during this century, global temperatures would rise a little over 1 C if there were no moistening in the upper troposphere, Soden says. In contrast, a 3 C rise is predicted with an increase in upper tropospheric water vapor. Previous studies claimed that water vapor in the upper troposphere might decrease in a warmer climate.
Geological evidence has led scientists to hypothesize that between 1.8 billion and 800 million years ago, primordial oceans contained little free oxygen and much sulfur. Now, researchers have found biological evidence that lends further weight to that hypothesis. In 1.6 billion-year-old marine sedimentary rocks from northern Australia, Jochen J. Brocks at Australian National University, Canberra, and colleagues found molecular fossils, including the carotenoid biomarker okenane (shown). These markers are remnants of purple and green sulfur bacteria, anaerobic organisms that produce elemental sulfur and sulfate from hydrogen sulfide (Nature 2005, 437, 866). The study greatly extends the known antiquity of key biomarkers and is a significant contribution to charting the evolution of the mid-Proterozoic biosphere, NASA exobiologist David J. Des Marais notes in a commentary in the same issue of Nature.