The Determination of the Aqueous Oxidation Potentials of Aniline and Sixteen of its Derivatives via Ultrafast Cyclic Voltammetry to Model the Photocatalyzed Degradation of Organic Pollutants in Natural Bodies of Water

Redox reactions of organic pollutants are important processes to consider when studying the effect of pollutants on the environment. Having accurate aqueous formal oxidation potentials (E0’) for pollutants is essential to understanding their redox chemistry and how they might react with photoactivated dissolved organic matter in natural bodies of water. Aniline and sixteen of its derivatives were studied with cyclic voltammetry and ultrafast cyclic voltammetry in order to determine their aqueous oxidation potentials. Due to the rapid polymerization of aniline upon oxidation, cyclic voltammetry at macroelectrodes is unable to detect reduction, and thus measures an irreversible process. Using a 3.00 mm glassy-carbon macroelectrode and scan rates on the order of 1 Vs-1 the irreversible oxidation of the anilines was observed, and the reversible E0’ was approximated by the inflection points of their oxidation peaks. This data was further analyzed based on the resonance and electron donating / withdrawing effects of the various aniline substituents. In order to study the reversible process, ultrafast cyclic voltammetry was used in an attempt to reduce aniline radical cations before they are consumed by the polymerization reaction. An 11 μm carbon fiber, a 10 μm gold, and a 10 μm platinum microelectrode were employed at scan rates between 200 Vs-1 and 1,000 Vs-1. This technique was successful at measuring a reversible redox couple for some of the anilines; however, further experimentation is required to collect accurate data for all anilines

The development of 2D materials for electrochemical energy applications: A mechanistic approach

Energy production and storage is one of the foremost challenges of the 21st century. Rising energy demands coupled with increasing materials scarcity have motivated the search for new materials for energy technology development. Nanomaterials are an excellent class of materials to drive this innovation due to their emergent properties at the nanoscale. In recent years, two dimensional (2D) layered materials have shown promise in a variety of energy related applications due to van der Waals interlayer bonding, large surface area, and the ability to engineer material properties through heterostructure formation. Despite notable results, their development has largely followed a guess and check approach. To realize the full potential of 2D materials, more efforts must be made towards achieving a mechanistic understanding of the processes that make these 2D systems promising. In this perspective, we bring attention to a series of techniques used to probe fundamental energy related processes in 2D materials, focusing on electrochemical catalysis and energy storage. We highlight studies that have advanced development due to mechanistic insights they uncovered. In doing so, we hope to provide a pathway for advancing our mechanistic understanding of 2D energy materials for further research

Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

N6-methyladenosine (m6A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that, together with depletion of ribosomal RNA and m6A immunoprecipitation, defined thousands of m6A circRNAs with cell-type-specific expression. The presence of m6A circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A circRNAs are frequently derived from exons that are not methylated in mRNAs, whereas mRNAs that are methylated on the same exons that compose m6A circRNAs exhibit less stability in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification

DIGIT Is a Conserved Long Noncoding RNA that Regulates GSC Expression to Control Definitive Endoderm Differentiation of Embryonic Stem Cells

Long noncoding RNAs (lncRNAs) exhibit diverse functions, including regulation of development. Here, we combine genome-wide mapping of SMAD3 occupancy with expression analysis to identify lncRNAs induced by activin signaling during endoderm differentiation of human embryonic stem cells (hESCs). We find that DIGIT is divergent to Goosecoid (GSC) and expressed during endoderm differentiation. Deletion of the SMAD3-occupied enhancer proximal to DIGIT inhibits DIGIT and GSC expression and definitive endoderm differentiation. Disruption of the gene encoding DIGIT and depletion of the DIGIT transcript reveal that DIGIT is required for definitive endoderm differentiation. In addition, we identify the mouse ortholog of DIGIT and show that it is expressed during development and promotes definitive endoderm differentiation of mouse ESCs. DIGIT regulates GSC in trans, and activation of endogenous GSC expression is sufficient to rescue definitive endoderm differentiation in DIGIT-deficient hESCs. Our study defines DIGIT as a conserved noncoding developmental regulator of definitive endoderm

Tricyclic Antidepressants Promote Ceramide Accumulation to Regulate Collagen Production in Human Hepatic Stellate Cells

Activation of hepatic stellate cells (HSCs) in response to injury is a key step in hepatic fibrosis, and is characterized by trans-differentiation of quiescent HSCs to HSC myofibroblasts, which secrete extracellular matrix proteins responsible for the fibrotic scar. There are currently no therapies to directly inhibit hepatic fibrosis. We developed a small molecule screen to identify compounds that inactivate human HSC myofibroblasts through the quantification of lipid droplets. We screened 1600 compounds and identified 21 small molecules that induce HSC inactivation. Four hits were tricyclic antidepressants (TCAs), and they repressed expression of pro-fibrotic factors Alpha-Actin-2 (ACTA2) and Alpha-1 Type I Collagen (COL1A1) in HSCs. RNA sequencing implicated the sphingolipid pathway as a target of the TCAs. Indeed, TCA treatment of HSCs promoted accumulation of ceramide through inhibition of acid ceramidase (aCDase). Depletion of aCDase also promoted accumulation of ceramide and was associated with reduced COL1A1 expression. Treatment with B13, an inhibitor of aCDase, reproduced the antifibrotic phenotype as did the addition of exogenous ceramide. Our results show that detection of lipid droplets provides a robust readout to screen for regulators of hepatic fibrosis and have identified a novel antifibrotic role for ceramide

lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated by the interaction between the long non-coding RNA (lncRNA) DIGIT and the bromodomain and extraterminal domain protein BRD3. BRD3 forms phase-separated condensates of which the formation is promoted by DIGIT, occupies enhancers of endoderm transcription factors and is required for endoderm differentiation. BRD3 binds to histone H3 acetylated at lysine 18 (H3K18ac) in vitro and co-occupies the genome with H3K18ac. DIGIT is also enriched in regions of H3K18ac, and the depletion of DIGIT results in decreased recruitment of BRD3 to these regions. Our findings show that cooperation between DIGIT and BRD3 at regions of H3K18ac regulates the transcription factors that drive endoderm differentiation and suggest that protein–lncRNA phase-separated condensates have a broader role as regulators of transcription