Assessing the Potential for DNA Quadruplex Formation in the Predatory Bacterium Bdellovibrio bacteriovorus.

During its life cycle, the predatory bacterium Bdellovibrio bacteriovorus switches between an attack and a growth phase, each of which is characterized by a distinct pattern of gene expression. Twenty-one potential G-quadruplex-forming sequences (PQFS) have been identified in the Bdellovibrio genome. These G-rich sequences are prevalent within open reading frames and nearly evenly distributed between the template and the coding strand, suggesting that they could play a role in gene expression and life cycle switching. Published transcriptomic data show that the genes nearest these sequences are not (de)activated together during the same phases of the life cycle. We explored the biophysical properties of three identified PQFS using circular dichroism (CD) spectroscopy and gel electrophoresis and demonstrated that all three sequences fold into stable unimolecular quadruplexes with distinct topologies. In the presence of their complementary strands, each forms an equilibrium mixture of duplex and quadruplex in which quadruplex formation is favored at higher temperatures. Once the quadruplexes are folded, they are slow to form a duplex when the complementary strand is added, with one sequence requiring the equivalent of many Bdellovibrio lifetimes to do so. Using a variety of cosolutes, we showed that molecular crowding mimicking cellular conditions stabilizes the quadruplex structures and induces structural transitions to the parallel topology regardless of the original topology. Taken together, these experiments suggest that Bdellovibrio PQFS are capable of forming quadruplexes in vivo and thereby playing a role in gene expression.

Applying the Digital Health Social Justice Guide.

Introduction: Digital health, the use of apps, text-messaging, and online interventions, can revolutionize healthcare and make care more equitable. Currently, digital health interventions are often not designed for those who could benefit most and may have unintended consequences. In this paper, we explain how privacy vulnerabilities and power imbalances, including racism and sexism, continue to influence health app design and research. We provide guidelines for researchers to design, report and evaluate digital health studies to maximize social justice in health. Methods: From September 2020 to April 2021, we held five discussion and brainstorming sessions with researchers, students, and community partners to develop the guide and the key questions. We additionally conducted an informal literature review, invited experts to review our guide, and identified examples from our own digital health study and other studies. Results: We identified five overarching topics with key questions and subquestions to guide researchers in designing or evaluating a digital health research study. The overarching topics are: 1. Equitable distribution; 2. Equitable design; 3. Privacy and data return; 4. Stereotype and bias; 5. Structural racism. Conclusion: We provide a guide with five key topics and questions for social justice digital health research. Encouraging researchers and practitioners to ask these questions will help to spark a transformation in digital health toward more equitable and ethical research. Future work needs to determine if the quality of studies can improve when researchers use this guide.