Rational Design of an Orthogonal Pair of Bimolecular RNase P Ribozymes through Heterologous Assembly of Their Modular Domains.

The modular structural domains of multidomain RNA enzymes can often be dissected into separate domain RNAs and their noncovalent assembly can often reconstitute active enzymes. These properties are important to understand their basic characteristics and are useful for their application to RNA-based nanostructures. Bimolecular forms of bacterial RNase P ribozymes consisting of S-domain and C-domain RNAs are attractive as platforms for catalytic RNA nanostructures, but their S-domain/C-domain assembly was not optimized for this purpose. Through analysis and engineering of bimolecular forms of the two bacterial RNase P ribozymes, we constructed a chimeric ribozyme with improved catalytic ability and S-domain/C-domain assembly and developed a pair of bimolecular RNase P ribozymes the assembly of which was considerably orthogonal to each other.

Modular Architecture of Bacterial RNase P Ribozymes as a Structural Platform for RNA Nanostructure Design.

Ribonuclease P (RNase P) is a class of enzymes involved in the processing of precursor tRNAs to remove their 5'-leader sequences. Ribonuclease P enzymes are classified into two completely distinct classes, i.e. an RNA-based enzyme and a protein-only enzyme. The RNA-based enzyme functions as a ribozyme in which the catalytic machinery is supported by its RNA component consisting of a single RNA molecule. Bacterial RNase P RNAs are a classical class of ribozymes and their structures and catalytic mechanisms have been studied extensively. The bacterial RNase P ribozyme has a modular tertiary structure consisting of two large domains, each of which can self-fold without the partner domain. Such modular architecture, identification of which provided important insight into the function of this ribozyme, is attractive as a structural platform to design functional RNA nanostructures. The first section of this article briefly summarizes the diversity of RNase P mainly focusing on RNA-based enzymes. The second section describes the structures of bacterial RNase P ribozymes from the viewpoint of their application as modular tools in RNA nanostructure design. The last section summarizes the current state and next steps in modular engineering of RNase P RNAs, including possible design of RNase P ribozyme-based nanostructures.

Measuring body composition using the bioelectrical impedance method can predict the outcomes of gemcitabine-based chemotherapy in patients with pancreatobiliary tract cancer.

In order to examine the effect on body composition of anticancer drug treatments, the body composition rate in patients being treated with gemcitabine (GEM)-based chemotherapy was measured over time on an outpatient basis with a simple body composition monitor using the bioelectrical impedance (BI) method. The results revealed a significant reduction in the body fat rate (P=0.01) over the course of treatment in patients with pancreatobiliary tract cancer who became unable to continue GEM-based chemotherapy due to progressive disease or a decreased performance status. Meanwhile, no changes were observed in the body composition of control patients with urothelial carcinoma receiving GEM-based chemotherapy. In association with the adverse reactions to GEM and the hematotoxicity profile, a decreased white blood cell count was more likely to occur in body fat-dominant patients (mean fat rate, 25.8%; mean muscle rate, 26.2%), whereas a decreased blood platelet count was more likely to occur in skeletal muscle-dominant patients (mean fat rate, 23.3%; mean muscle rates, 28.7%). The correlation between body composition parameters and the relative dose intensity (RDI) associated with GEM administration was also analyzed. The results revealed a positive correlation between the RDI and basal metabolism amount (P=0.03); however, the RDI did not correlate with the body fat rate, skeletal muscle rate or body mass index (P=0.61, P=0.14 and P=0.20, respectively). In conclusion, the body composition rate measurement using the BI method over time may be useful for predicting the outcome of GEM-based chemotherapy and adverse events in patients with pancreatobiliary tract cancer. In particular, the present findings indicate that the changes in body fat rate may be helpful as an adjunct index for assessing potential continuation of chemotherapy and changes in physical conditions.