Repurposing Waste Chemicals for Sustainable and Durable Molecular Data Storage.

Molecular data storage offers the intriguing possibility of higher theoretical density and longer lifetimes than today's electronic memory devices. Some demonstrations have used deoxyribonucleic acid (DNA), but bottlenecks in nucleic acid synthesis continue to make DNA data storage orders of magnitude more expensive than electronic storage media. Additionally, despite its potential for long-term storage, DNA faces durability challenges from environmental degradation. In this work, we demonstrate nongenomic molecular data storage using molecular libraries redirected from chemical waste streams. This approach requires no synthetic effort and can be implemented by using molecules that have a minimal associated cost. While the technique is agnostic about the exact molecular content of its inputs, we confirmed that some sources contained poly fluoroalkyl substances (PFAS), which persist for long periods in the natural environment and could offer extremely durable information storage as well as environmental benefits. These demonstrations provide a perspective on some of the valuable possibilities for nongenomic molecular information systems.

Assessing CaMPARI as new approach methodology for evaluating neurotoxicity.

Developmental exposure to environmental toxicants has been linked to the onset of neurological disorders and diseases. Despite substantial advances in the field of neurotoxicology, there remain significant knowledge gaps in our understanding of cellular targets and molecular mechanisms that mediate the neurotoxicological endpoints associated with exposure to both legacy contaminants and emerging contaminants of concern. Zebrafish are a powerful neurotoxicological model given their high degree sequence conservation with humans and the similarities they share with mammals in micro- and macro-level brain structures. Many zebrafish studies have effectively utilized behavioral assays to predict the neurotoxic potential of different compounds, but behavioral phenotypes are rarely able to predict the brain structures, cell types, or mechanisms affected by chemical exposures. Calcium-modulated photoactivatable ratiometric integrator (CaMPARI), a recently developed genetically-encoded calcium indicator, undergoes a permanent green to red switch in the presence of elevated intracellular Ca2+ concentrations and 405-nm light, which allows for a "snapshot" of brain activity in freely-swimming larvae. To determine whether behavioral results are predictive of patterns of neuronal activity, we assessed the effects of three common neurotoxicants, ethanol, 2,2',3,5',6-pentachlorobiphenyl (PCB 95), and monoethylhexyl phthalate (MEHP), on both brain activity and behavior by combining the behavioral light/dark assay with CaMPARI imaging. We demonstrate that brain activity profiles and behavioral phenotypes are not always concordant and, therefore, behavior alone is not sufficient to understand how toxicant exposure affects neural development and network dynamics. We conclude that pairing behavioral assays with functional neuroimaging tools such as CaMPARI provides a more comprehensive understanding of the neurotoxic endpoints of compounds while still offering a relatively high throughput approach to toxicity testing.

Obstacles and opportunities for base excision repair in chromatin.

Most eukaryotic DNA is packaged into chromatin, which is made up of tandemly repeating nucleosomes. This packaging of DNA poses a significant barrier to the various enzymes that must act on DNA, including DNA damage response enzymes that interact intimately with DNA to prevent mutations and cell death. To regulate access to certain DNA regions, chromatin remodeling, variant histone exchange, and histone post-translational modifications have been shown to assist several DNA repair pathways including nucleotide excision repair, single strand break repair, and double strand break repair. While these chromatin-level responses have been directly linked to various DNA repair pathways, how they modulate the base excision repair (BER) pathway remains elusive. This review highlights recent findings that demonstrate how BER is regulated by the packaging of DNA into nucleosome core particles (NCPs) and higher orders of chromatin structures. We also summarize the available data that indicate BER may be enabled by chromatin modifications and remodeling.