Translation initiation is poised between global regulation of cell growth and specific regulation of cell division. The mRNA cap-binding protein (eIF4E) is a critical integrator of cell growth and division because it is ratelimiting for translation initiation and is also rate-limiting for G 1 progression. Translation initiation factor eIF4E is also oncogenic and a candidate target of c-myc. Recently, an activated inhibitory 4E-binding protein (4EBP) that blocks eIF4E was used to study its regulation of Drosophila growth. We adopted this approach in mammalian cells after identifying an autosensing mechanism that protects against increased levels of 4EBP1. Increased 4EBP1 induced a quantitative increase in the inactivated phosphorylated form of 4EBP1 in vitro and in vivo. To overcome this protective mechanism, we introduced alanine substitutions at four phosphorylation/ inactivation sites in 4EBP1 to constitutively activate a 4EBP to block eIF4E. Overexpression of activated 4EBP inhibited cell proliferation and completely blocked transformation by both eIF4E and c-myc, although it did not block all tested oncogenes. Surprisingly, expression of the activated 4EBP increased cell size and protein content. Activated 4EBP blocked both cell proliferation and c-myc transformation by inhibiting G 1 progression and increasing apoptosis, without decreasing protein synthesis. Our results identify mammalian eIF4E as rate-limiting for cell cycle progression before it regulates cell growth. It further identifies G 1 control by translation initiation factors as an essential genetic target of c-myc that is necessary for its ability to transform cells.
Laboratory tests were conducted to compare imidacloprid and fipronil foams against various criteria to determine the effect of the deposit conditions, exposure method, and exposure time on the toxicity, repellency, and horizontal transfer of selected foam insecticides. Results of toxicity assays showed that imidacloprid and fipronil foams caused significantly higher mortality than control treatments; however, fipronil foam in fresh or old deposits killed Cryptotermes brevis pseudergates more quickly in the short and continuous exposure tests than foam containing imidacloprid. In brief exposure tests, imidacloprid failed to kill all termites when exposed to fresh deposits and delayed total mortality when exposed to dry residues. The mortality of C. brevis pseudergates was also significantly quicker when the fipronil foam was applied topically compared with the imidacloprid foam. In the repellency test, termites were not repelled from the surface treated with fipronil foam, but more than 90% repellency was observed after 24 h of exposure to imidacloprid-treated surfaces. Moreover, the non-repellent mortality of C. brevis with fipronil was significantly higher than imidacloprid in avoidance tests. Results showed that fipronil was effectively transferred to untreated termites from live or dead donors exposed via residual and topical spray.
Rational, cost‐effective provision of mission‐critical environmental management information remains elusive for almost all large enterprises. Even among the best performing companies—best performing from the perspectives of profitability, quality and/or environmental stewardship—environmental management information systems (EMIS) are usually comprised of dozens to hundreds of individual, isolated applications that require costly data capture, training, and maintenance. This article, the first of two, will discuss ways to coordinate information infrastructures with strategic goals and business processes.
Successful implementation of environmental management information systems (EMIS) has become essential to the success of total quality environmental management (TQEM) programs. Effective TQEM programs will be early indicators of which companies survive and thrive in today's competitive business environment. Highly competitive industries such as chemicals, electronics, and oil and gas are becoming very effective in cooperating to develop metrics, models, and tools that are based on business processes rather than regulatory edicts. Now electric power companies, newly exposed to market competition, are starting to develop and implement these mei.rics, standards, and tools. That industry provides a model for joining TQEM and EMIS. Chris FitzCerald is editorin-chief ofTotal Quality Environmental Management and president of Environmental Management Information Systems in Oakland, California. Mr. FitzGerald consults with industry and service providers on EMIS requirements analysis, design, and implementation, and recently completed a book on EMIS for McGraw-Hill.
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