ABSTRACT
Cyclic di-guanosine monophosphate (di-GMP) is a circular RNA dinucleotide that functions as a second messenger in diverse species of bacteria to trigger wide-ranging physiological changes, including cell differentiation, conversion between motile and biofilm lifestyles, and virulence gene expression. However, the mechanisms by which cyclic di-GMP regulates gene expression have remained a mystery. We found that cyclic di-GMP in many bacterial species is sensed by a riboswitch class in messenger RNA that controls the expression of genes involved in numerous fundamental cellular processes. A variety of cyclic di-GMP regulons are revealed, including some riboswitches associated with virulence gene expression, pilus formation, and flagellum biosynthesis. In addition, sequences matching the consensus for cyclic di-GMP riboswitches are present in the genome of a bacteriophage.
Subject(s)
Aptamers, Nucleotide/metabolism , Bacteria/genetics , Cyclic GMP/analogs & derivatives , Gene Expression Regulation, Bacterial , RNA, Bacterial/metabolism , RNA, Messenger/metabolism , Second Messenger Systems , Bacillus cereus/genetics , Bacillus cereus/metabolism , Bacteria/metabolism , Bacteriophages/genetics , Base Sequence , Clostridioides difficile/genetics , Clostridioides difficile/metabolism , Cyclic GMP/metabolism , Genes, Bacterial , Ligands , Molecular Sequence Data , Nucleic Acid Conformation , RNA, Bacterial/chemistry , RNA, Messenger/chemistry , Regulon , Vibrio cholerae/genetics , Vibrio cholerae/metabolismABSTRACT
Written examinations are widely used for assessment in clinical clerkships and for licensure and specialty board certification, as opposed to assessment based on actual performance with patients. This reliance on written examinations is due to their ease of use and perceived objectivity and occurs despite the fact that the examinations assess few components of clinical competence. Simulated patients can standardize the presentation of a patient problem; and, if the patients are employed in an assessment in a manner parallel to the design of written test items, the assessment can have an objectivity similar to that enjoyed by written tests. Such an assessment allows the major components of clinical competence to be tested. The results and feasibility of using simulated patients in a multiple-station assessment of an entire senior class in January 1986 are described. A second assessment was administered to a different senior class in December 1986. This latter assessment was designed in collaboration with another medical school that administered the same assessment to its senior students in March 1987.