Sensory Perception in Bacterial Cyclic Diguanylate Signal Transduction.

Cyclic diguanylate (c-di-GMP) signal transduction systems provide bacteria with the ability to sense changing cell status or environmental conditions and then execute suitable physiological and social behaviors in response. In this review, we provide a comprehensive census of the stimuli and receptors that are linked to the modulation of intracellular c-di-GMP. Emerging evidence indicates that c-di-GMP networks sense light, surfaces, energy, redox potential, respiratory electron acceptors, temperature, and structurally diverse biotic and abiotic chemicals. Bioinformatic analysis of sensory domains in diguanylate cyclases and c-di-GMP-specific phosphodiesterases as well as the receptor complexes associated with them reveals that these functions are linked to a diverse repertoire of protein domain families. We describe the principles of stimulus perception learned from studying these modular sensory devices, illustrate how they are assembled in varied combinations with output domains, and summarize a system for classifying these sensor proteins based on their complexity. Biological information processing via c-di-GMP signal transduction not only is fundamental to bacterial survival in dynamic environments but also is being used to engineer gene expression circuitry and synthetic proteins with à la carte biochemical functionalities.

Cost analysis and efficacy of recruitment strategies used in a large pragmatic community-based clinical trial targeting low-income seniors: a comparative descriptive analysis.

OBJECTIVE: One of the most challenging parts of running clinical trials is recruiting enough participants. Our objective was to determine which recruitment strategies were effective in reaching specific subgroups. STUDY DESIGN AND SETTING: We assessed the efficacy and costs of the recruitment strategies used in the Assessing Outcomes of Enhanced Chronic Disease Care Through Patient Education and a Value-based Formulary Study (ACCESS) in Alberta, Canada. RESULTS: Twenty percent of the study budget ($354,330 CAD) was spent on recruiting 4013 participants, giving an average cost per enrolled of $88 CAD. Pharmacies recruited the most participants (n = 1217), at a cost of $128/enrolled. "Paid media" had the highest cost ($806/enrolled), whereas "word of mouth" and "unpaid media" had the lowest (~$3/enrolled). Participants enrolled from "seniors outreach" had the lowest baseline quality of life and income, while participants from "word of mouth" had the lowest educational attainment. CONCLUSION: The "health care providers" strategies were especially successful - at a moderate cost per enrolled. The "media" strategies were less effective, short lasting, and more costly. No strategy was singularly effective in recruiting our targeted groups, emphasizing the importance of utilizing a variety of strategies to reach recruitment goals. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579655 . Registered on 19 October 2015.