In an effort to identify sets of yeast genes that are coregulated across various cellular transitions, gene expression data sets derived from yeast cells progressing through the cell cycle, sporulation, and diauxic shift were analyzed. A partitioning algorithm was used to divide each data set into 24 clusters of similar expression profiles, and the membership of the clusters was compared across the three experiments. A single cluster of 189 genes from the cell cycle experiment was found to share 65 genes with a cluster of 159 genes from the sporulation data set. Many of these genes were found to be clustered in the diauxic-shift experiment as well. The overlapping set was enriched for genes required for rRNA biosynthesis and included genes encoding RNA helicases, subunits of RNA polymerases I and III, and rRNA processing factors. A subset of the 65 genes was tested for expression by a quantitative-relative reverse transcriptase PCR technique, and they were found to be coregulated after release from alpha factor arrest, heat shock, and tunicamycin treatment. Promoter scanning analysis revealed that the 65 genes within this ribosome and rRNA biosynthesis (RRB) regulon were enriched for two motifs: the 13-base GCGATGAGATGAG and the 11-base TGAAAAATTTT consensus sequences. Both motifs were found to be important for promoting gene expression after release from alpha factor arrest in a test rRNA processing gene (EBP2), which suggests that these consensus sequences may function broadly in the regulation of a set of genes required for ribosome and rRNA biosynthesis.Ribosome biosynthesis is a complex and demanding process that depends directly upon multiple metabolic pathways, including the activities of three different RNA polymerases (reviewed in references 21 and 27). In Saccharomyces cerevisiae there are 137 ribosomal protein genes (RP genes), and they are transcribed by RNA polymerase II to yield 78 ribosomal proteins. Because the RP genes are transcribed at such a high level, together they account for nearly 50% of the total RNA polymerase II-mediated transcription initiation events (18). The 25S, 18S, and 5.8S rRNAs are synthesized by RNA polymerase I, first as a large 35S transcript that subsequently gets processed into the three smaller, mature species. Synthesis of the 5S rRNA is distinct from the other rRNAs and is carried out by RNA polymerase III. In order to achieve the high levels of rRNA production that are required during rapid cell division, yeast cells contain roughly 150 repeats of the rRNA genes in a tandem array on chromosome XII. Together, these repeats represent 10% of the genome, and rRNA production alone accounts for some 60% of the total cellular transcription.Ribosome biogenesis also depends upon the activities of a large number of protein and RNA molecules that are not themselves components of the final ribosome. The complex processing pathway that converts the 35S precursor rRNA into the mature 25S, 18S, and 5.8S rRNA species requires a multitude of factors, including RNA endonucleases, exon...

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The incidence of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome is higher than previously reported but does not appear to be rising. Apparent international differences in incidence could be the result of imprecision in identifying thrombotic thrombocytopenia purpura and hemolytic uremic syndrome in large research databases.

IM862 given as intranasal drops is well tolerated and has antitumor activity in patients with AIDS-KS. A randomized double-blinded study to define the activity of IM862 in patients with AIDS-KS is in progress.