Preliminary Evaluation of a Guideline Classification System

In a previous paper, we presented a proposed expansion of the National Guideline Clearing-house (NGC) classification1. We performed a preliminary evaluation of the classification based on 100 guidelines randomly selected from the NGC collection. We found that 89 of the 100 guidelines could be assigned to a single guideline category. To test inter-observer agreement, twenty guidelines were also categorized by a second investigator. Agreement was found to be 40-90% depending on the axis, which compares favorably with agreement among MeSH indexers (30-60%)2. We conclude that categorization is feasible. Further research is needed to clarify axes with poor inter-observer agreement.

Molecular mechanism by which the nucleoid occlusion factor, SlmA, keeps cytokinesis in check.

In Escherichia coli, cytokinesis is orchestrated by FtsZ, which forms a Z-ring to drive septation. Spatial and temporal control of Z-ring formation is achieved by the Min and nucleoid occlusion (NO) systems. Unlike the well-studied Min system, less is known about the anti-DNA guillotining NO process. Here, we describe studies addressing the molecular mechanism of SlmA (synthetic lethal with a defective Min system)-mediated NO. SlmA contains a TetR-like DNA-binding fold, and chromatin immunoprecipitation analyses show that SlmA-binding sites are dispersed on the chromosome except the Ter region, which segregates immediately before septation. SlmA binds DNA and FtsZ simultaneously, and the SlmA-FtsZ structure reveals that two FtsZ molecules sandwich a SlmA dimer. In this complex, FtsZ can still bind GTP and form protofilaments, but the separated protofilaments are forced into an anti-parallel arrangement. This suggests that SlmA may alter FtsZ polymer assembly. Indeed, electron microscopy data, showing that SlmA-DNA disrupts the formation of normal FtsZ polymers and induces distinct spiral structures, supports this. Thus, the combined data reveal how SlmA derails Z-ring formation at the correct place and time to effect NO.