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C&EN May 1, 1978
DMBA into the normal cells, to see how they would metabolize it in cell culture. Fve also been looking to see if normal mammary cells contain epoxyhydrase, because this is an important liver enzyme for metabolism of that type of compound. Fve also done a fair amount of synthesis this year. Fve synthesized several DMBA metabolites and in the next few weeks Fm going to put these directly on the mammary glands of the rats to see if the metabolites are more carcinogenic than the parent compound." Meanwhile, the Lucids have also had two more children, bringing the total to three: Kawai, 9; Shandara, 8; and Michael Kermit, 2. Although the older ones are excited and happy about the prospect of having an astronaut for a mother, they're also a little ambivalent about moving. But, their mother says, "I think moving a few times is good. If you get stuck in one place, it's harder to change when you get older." The move also will mean change for husband Michael; the day C&EN interviewed Shannon, Michael was in Houston looking for a new job. Once the Lucids are resettled in Houston, Shannon can look forward to a rigorous training program. "We'll be in classes about four hours a day, in the morning," she says. "Then in the afternoon we'll be working with some of the older astronauts, so we can understand the systems and presumably be useful. We also have to have 15 hours a month flying the T38 trainer. Mission specialists also are supposed to keep up their scientific expertise. At our orientation session in January they were quite emphatic about that, but they were a little vague as to when it was going to be worked in. In our spare time, I guess." According to NASA, mission specialist astronauts will have overall responsibility for the coordination, with the commander and pilot, of space shuttle operations in the areas of crew activity planning, consumables use, and other space shuttle activities affecting experiment operations. They may participate in extravehicular activities ("space walks"), perform special payload handling or maintenance operation using the space shuttle's remote manipulator system, and at the direction of the experiment sponsor, assist in specific experiment operations. The possibilities for experiments in space are almost limitless (C&EN, Feb. 20, page 24). But the experiments won't come cheap. For non-U.S. government users, a "dedicated" space shuttle orbiter flight probably will cost more than $20 million. More typically, however, a number of users will share the orbiter's 18m-long cargo space and 30,000-kg payload capacity. So just how much will Lucid and her fellow mission specialists have to say about the type of work that will be done? "Not very much," she says. "The space shuttle will be open to anyone that is willing to pay to put an experiment aboard, as long as it's reasonable. The mission specialist will be there in large part to make sure that everything's done
right and the customer gets his or her money's worth. But in another way, Fm sure that we'll have quite a bit of say, because we'll be so intimately involved with the whole process and we'll have a lot of ideas on how to get things done." Lucid's final message to C&EN readers: "Get to thinking about how your work could benefit from a zero-gravity, highvacuum environment. Then buy some space on the shuttle and keep me in a job." Ward Worthy, C&EN Chicago
Scientists find uses for pesky proteases "I usually give a talk on Treacher Pringle's Principles' and conclude that 'proteolytic artifacts are pervasive, perplexing, persistent, and pernicious,' " says Dr. John R. Pringle, of the University of Michigan, Ann Arbor. "But I am bored with that talk." So, in a sense, was the group of 60 or more scientists listening to him last month at an international Conference on Limited Proteolysis in Microorganisms: Biological Function, Use in Protein Structural and Functional Studies, held at the National Institutes of Health in Bethesda, Md. But bored isn't really the correct word. These scientists have lost patience with the bad reputation that proteases, enzymes that break down other proteins, have endured. That reputation, matched well with "Pringle's Principles," seems to be waning as proteases are accruing fresh esteem among physiologists and biochemists. The physiologists (including molecular biologists, microbiologists, and the like) are finding that many cellular processes are controlled by proteases. This view is replacing an earlier sense that proteases were like jackhammers in a fine cabinet maker's shop. Fine pieces of furniture—a cell's inner workings—simply could not be subjected to so crude a tool, the former belief had it. But evidence is accumulating that proteases play crucial roles in regulating cellular activity in microorganisms and that these enzymes function with fine control and circumspection. Thus, "jackhammer" is a misnomer for a much finer tool. For example, a phage called T4 specifies and makes a protease during its life cycle. This phage—one of the simplest of viruses that lives by infecting and reproducing within the bacterium Escherichia coli—conjures up its protease to trim and finish off the protein coat that surrounds the DNA of its progeny phage. "The phage first assembles a 'prehead' made up of four structural proteins," explains Dr. Michael K. Showe of Basel, Switzerland. The prehead is very fragile when first put together. But the phage protease, which Showe calls "highly specific," systematically cleaves the proteins in the thick shell of the prehead. "It becomes thinner, wider, and longer," he
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platinum and aluminum. Blades so treated have lasted four times longer in oxidizing tests, and have improved 230% in cyclic corrosion tests. Platinum can also be used to protect against corrosion indirectly. A 31/2 mile train tunnel under San Francisco Bay is protected from corrosion cathodically using leadplatinum bi-electrodes. The steel shell of the train tube is flanked on each side by lead-platinum anode arrays. Rectifiers feed 24 vdc to the anodes with the negative terminal connected to the tube. In effect, the train tube becomes a cathode and acts as the pole of a huge battery that corrodes at an extremely low rate in this highlycorrosive undersea environment. There are other ways platinum can be used to combat corrosion, and to perform other industrial functions, too. Platinum is heat resistant, reclaimable, catalytically active, and possesses highly desirable electrical characteristics. And it is inexpensive because it is virtually indestructible. It can be used, reclaimed, and used again and again. Our "Platinum Packet"
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notes, "and very stable." Once trimmed, the head structure resists strong detergent treatment, rendering the progeny phages very sturdy for the environment they face when they burst free of the bacterium. The phage protease specificity also is limited in time. According to Showe, the protein first is made as a "zymogen" or inactive form that activates itself and gradually inactivates itself. The active protease will cleave its target proteins only after they assemble as a prehead. They then rearrange to prevent further cleavage. The T4 phage protease also is inactive against all other proteins test ed. T4 is a phage that invades and destroys its host bacterium. It uses a protease for a key phage activity and does the task of head assembly without borrowing from the host machinery. Lambda is a very different phage that can integrate its DNA with the host's and the two organisms live in delicate balance. That balance hinges on a host-specified
Proteases hold the key to formation of protein coat of the T4 phage head protease, according to Dr. Jeffrey W. Roberts of Cornell University, Ithaca, N.Y. When lambda is "hibernating" in its host, it makes a protein appropriately called the repressor that shuts off lambda activities. But a host gene, called recA for its role in controlling gene recombination, affects the status of the sleeping lambda. Roberts says that the recA gene product (or possibly a secondary product) is a protease. That protease can knock out the lambda repressor protein, thereby switching on the lethargic phage. Such contorted control is interesting for several reasons. The recA gene by itself has been a puzzle, as it functions in di verse activities such as DNA repair after ultraviolet light damage, recombination, and phage activation. How can one gene product do so many different tasks? The tentative answer, that the product is a protease, seems to fit. Thus, a protease readily can destroy the lambda repressor because the latter is a protein. It might affect DNA repair and recombination by chewing proteins off the DNA, allowing other enzymes access to work there. Yet another phage example helps characterize the role proteases play in
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Transfer RNA:
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the history and the mystery
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An ancient component of biological systems; the agent responsible for many cellular functions; structural features with known functions; structural features with intriguing and mysterious possibilities. All are discussed in a ; collection of papers appearing in the November ^ issue of Accounts of Chemical Research.
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