Redox, a native modality in biology involving the flow of electrons, energy, and information, is used for energy-harvesting, biosynthesis, immune-defense, and signaling. Because electrons (in contrast Show more
Redox, a native modality in biology involving the flow of electrons, energy, and information, is used for energy-harvesting, biosynthesis, immune-defense, and signaling. Because electrons (in contrast to protons) are not soluble in the medium, electron-flow through the redox modality occurs through redox reactions that are sometimes organized into pathways and networks (e.g., redox interactomes). Redox is also accessible to electrochemistry, which enables electrodes to receive and transmit electrons to exchange energy and information with biology. In this Perspective, efforts to develop electrochemistry as a tool for redox-based bio-information processing: to interconvert redox-based molecular attributes into interpretable electronic signals, are described. Using a series of Case Studies, how the information-content of the measurements can be enriched using: diffusible mediators; tuned electrical input sequences; and cross-modal measurements (e.g., electrical plus spectral), is shown. Also, theory-guided feature engineering approaches to compress the information in the electronic signals into quantitative metrics (i.e., features) that can serve as correlating variables for pattern recognition by data-driven analysis are described. Finally, how redox provides a modality for electrogenetic actuation is illustrated. It is suggested that electrochemistry's capabilities to provide real-time, low-cost, and high-content data in an electronic format allow the feedback-control needed for autonomous learning and deployable sensing/actuation. Show less
Oxidative stress appears to act globally and span body systems (e.g., nervous, immune, and endocrine). Currently, there is no single, generally-accepted measurement of oxidative stress. Many possible Show more
Oxidative stress appears to act globally and span body systems (e.g., nervous, immune, and endocrine). Currently, there is no single, generally-accepted measurement of oxidative stress. Many possible measurement approaches focus on the bottom-up analysis of individual molecules (e.g., reactive species, antioxidants, hormones or signaling molecules) or combinations of molecules (e.g., proteomics or metabolomics). Efforts to develop a global measurement of oxidative stress often detect a sample's ability to reduce a metal-ion (e.g., iron or copper) or quench a free radical. Here, we review results from a recently-developed iridium-reducing capacity assay (Ir-RCA) and suggest that this method offers several key benefits as a potential measurement of oxidative stress. First, the Ir-RCA employs simple optical and/or electrochemical measurements that can be extended to high throughput formats. Second, the Ir-RCA appears to be more sensitive than alternative global antioxidant assays. Third, the Ir-RCA measures stable molecular features of a sample. Fourth, the Ir-RCA has been "validated" by showing statistically significant differences in persons diagnosed with schizophrenia (N = 73) versus healthy controls (N = 45). Fifth, the Ir-RCA measurement of oxidative stress is "movable": psychosocial stressors can increase this measure of oxidative stress, while beneficial dietary interventions can decrease this measure of oxidative stress. Limitations and future directions for the Ir-RCA are discussed. Show less
Abstract TFIIH is a 10âsubunit complex that regulates RNA polymerase II (pol II) transcription but also serves other important biological roles. Although much remains unknown about TFIIH function in Show more
Abstract TFIIH is a 10âsubunit complex that regulates RNA polymerase II (pol II) transcription but also serves other important biological roles. Although much remains unknown about TFIIH function in eukaryotic cells, much progress has been made even in just the past few years, due in part to technological advances (e.g. cryoEM and single molecule methods) and the development of chemical inhibitors of TFIIH enzymes. This review focuses on the major cellular roles for TFIIH, with an emphasis on TFIIH function as a regulator of pol II transcription. We describe the structure of TFIIH and its roles in pol II initiation, promoterâproximal pausing, elongation, and termination. We also discuss cellular roles for TFIIH beyond transcription (e.g. DNA repair, cell cycle regulation) and summarize small molecule inhibitors of TFIIH and diseases associated with defects in TFIIH structure and function. Show less