Composition and functional characterization of yeast 66S ribosome assembly intermediates.

The pathway and complete collection of factors that orchestrate ribosome assembly are not clear. To address these problems, we affinity purified yeast preribosomal particles containing the nucleolar protein Nop7p and developed means to separate their components. Nop7p is associated primarily with 66S preribosomes containing either 27SB or 25.5S plus 7S pre-rRNAs. Copurifying proteins identified by mass spectrometry include ribosomal proteins, nonribosomal proteins previously implicated in 60S ribosome biogenesis, and proteins not known to be involved in ribosome production. Analysis of strains mutant for eight of these proteins not previously implicated in ribosome biogenesis showed that they do participate in this pathway. These results demonstrate that proteomic approaches in concert with genetic tools provide powerful means to purify and characterize ribosome assembly intermediates.

A national survey of policies on disclosure of conflicts of interest in biomedical research.

BACKGROUND: Conflicts of interest pose a threat to the integrity of scientific research. The current regulations of the U.S. Public Health Service and the National Science Foundation require that medical schools and other research institutions report the existence of conflicts of interest to the funding agency but allow the institutions to manage conflicts internally. The regulations do not specify how to do so. METHODS: We surveyed all medical schools (127) and other research institutions (170) that received more than $5 million in total grants annually from the National Institutes of Health or the National Science Foundation; 48 journals in basic science and clinical medicine; and 17 federal agencies in order to analyze their policies on conflicts of interest. RESULTS: Of the 297 institutions, 250 (84 percent) responded by March 2000, as did 47 of the 48 journals and 16 of the 17 federal agencies. Fifteen of the 250 institutions (6 percent)--5 medical schools and 10 other research institutions--reported that they had no policy on conflicts of interest. Among the institutions that had policies, there was marked variation in the definition and management of conflicts. Ninety-one percent had policies that adhered to the federal threshold for disclosure ($10,000 in annual income or equity in a relevant company or 5 percent ownership), and 9 percent had policies that exceeded the federal guidelines. Only 8 percent had policies requiring disclosure to funding agencies, only 7 percent had such policies regarding journals, and only 1 percent had policies requiring the disclosure of information to the relevant institutional review boards or to research subjects. Twenty journals (43 percent) reported that they had policies requiring disclosure of conflicts of interest. Only four federal agencies had policies that explicitly addressed conflicts of interest in extramural research, and all but one of the agencies relied primarily on institutional discretion. CONCLUSIONS: There is substantial variation among policies on conflicts of interest at medical schools and other research institutions. This variation, combined with the fact that many scientific journals and funding agencies do not require disclosure of conflicts of interest, suggests that the current standards may not be adequate to maintain a high level of scientific integrity.