The conformational landscape of RNA translational regulators and their potential as drug discovery targets

RNA is an underutilized target for drug discovery. Once thought to be a passive carrier of genetic information, RNA is now known to play a critical role in essentially all aspects of biology including signaling, gene regulation, catalysis, and retroviral infection. It is now well-established that RNA does not exist as a single static structure, but instead populates an ensemble of energetic minima along a free-energy landscape. Knowledge of this structural landscape has become an important goal for understanding its diverse biological functions. In this case, NMR spectroscopy has emerged as an important player in the characterization of RNA structural ensembles, with solution-state techniques accounting for almost half of deposited RNA structures in the PDB, yet the rate of RNA structure publication has been stagnant over the past decade. Several bottlenecks limit the pace of RNA structure determination by NMR: the high cost of isotopic labeling, tedious and ambiguous resonance assignment methods, and a limited database of RNA optimized pulse programs. We have addressed some of these challenges to NMR characterization of RNA structure with applications to various RNA-drug targets. These approaches will increasingly become integral to designing new therapeutics targeting RNA.

Quantifying Barriers to Meditation as a Health Behavior: Exploratory and Confirmatory Factor Analysis of the Determinants of Meditation Practice Inventory

Although the benefits of mindfulness meditation practices have been widely documented, research data suggest that there are barriers to regularly engaging in meditation behavior. In order to explore research questions pertaining to meditation initiation and adherence, psychometrically valid scales to assess barriers to meditation practice are necessary. The aim of the present study was to explore the factor structure and construct validity of the Determinants of Meditation Practice Inventory (DMPI) (Williams et al., 2011), a perceived barriers to meditation scale. Exploratory and confirmatory factor analyses along with construct validity tests were performed on data obtained from two large, community samples. Results supported the DMPI as a valid scale assessing perceived barriers with four factors, Lack of Interest, Knowledge Concerns, Pragmatic Concerns and Sociocultural Beliefs. The present study offers a DMPI-revised scale that may be reliably used to assess attitudes and beliefs that might impede meditation behavior.