Measuring and modeling diel oxygen dynamics in a shallow hypereutrophic estuary: Implications of low oxygen exposure on aquatic life.

Hypoxia, or low dissolved oxygen (DO) is a common outcome of excess nitrogen and phosphorus delivered to coastal waterbodies. Shallow and highly productive estuaries are particularly susceptible to diel-cycling hypoxia, which can exhibit DO excursions between anoxia (DO ≤1 mg L-1) and supersaturated concentrations within a day. Shallow estuaries exhibiting diel-cycling hypoxia are understudied relative to larger and deeper estuaries, with very few mechanistic models that can predict diel oxygen dynamics. We utilized continuous monitoring data and the Coastal Generalized Ecosystem Model (CGEM) coupled with an Environmental Fluid Dynamics Code (EFDC) hydrodynamic model to simulate diel DO dynamics in Weeks Bay, AL. Low oxygen conditions ranging from anoxia to DO ≤4 mg L-1 were consistently observed and simulated in the lower water column for periods of minutes to >11 h. High frequency observations and model simulations also identified significant vertical gradients in near bottom DO that varied as much as 0.8 to 3.1 mg L-1 within 0.4 m from the bottom. This spatiotemporal variability presents unique challenges to adequately quantify DO dynamics and the potential exposure of aquatic life to low oxygen conditions. Our results demonstrate the need for detailed measurements to adequately quantify the complex DO dynamics in shallow estuaries. We also demonstrate that simulation models can be successfully applied to evaluate diel oxygen dynamics in complex estuarine environments when calibrated with fine time scale data and effective parameterization of water column and benthic metabolic processes.

From Protein Sequence to Structure: The Next Frontier in Cross-Species Extrapolation for Chemical Safety Evaluations.

Computational screening for potentially bioactive molecules using advanced molecular modeling approaches including molecular docking and molecular dynamic simulation is mainstream in certain fields like drug discovery. Significant advances in computationally predicting protein structures from sequence information have also expanded the availability of structures for nonmodel species. Therefore, the objective of the present study was to develop an analysis pipeline to harness the power of these bioinformatics approaches for cross-species extrapolation for evaluating chemical safety. The Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool compares protein-sequence similarity across species for conservation of known chemical targets, providing an initial line of evidence for extrapolation of toxicity knowledge. However, with the development of structural models from tools like the Iterative Threading ASSEmbly Refinement (ITASSER), analyses of protein structural conservation can be included to add further lines of evidence and generate protein models across species. Models generated through such a pipeline could then be used for advanced molecular modeling approaches in the context of species extrapolation. Two case examples illustrating this pipeline from SeqAPASS sequences to I-TASSER-generated protein structures were created for human liver fatty acid-binding protein (LFABP) and androgen receptor (AR). Ninety-nine LFABP and 268 AR protein models representing diverse species were generated and analyzed for conservation using template modeling (TM)-align. The results from the structural comparisons were in line with the sequence-based SeqAPASS workflow, adding further evidence of LFABL and AR conservation across vertebrate species. The present study lays the foundation for expanding the capabilities of the web-based SeqAPASS tool to include structural comparisons for species extrapolation, facilitating more rapid and efficient toxicological assessments among species with limited or no existing toxicity data. Environ Toxicol Chem 2023;42:463-474. © 2022 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Inter-model comparison of simulated Gulf of Mexico hypoxia in response to reduced nutrient loads: effects of phytoplankton and organic matter parameterization.

Complex simulation models are a valuable tool to inform nutrient management decisions aimed at reducing hypoxia in the northern Gulf of Mexico, yet simulated hypoxia response to reduced nutrients varies greatly between models. We compared two biogeochemical models driven by the same hydrodynamics, the Coastal Generalized Ecosystem Model (CGEM) and Gulf of Mexico Dissolved Oxygen Model (GoMDOM), to investigate how they differ in simulating hypoxia and their response to reduced nutrients. Different phytoplankton nutrient kinetics produced 2-3 times more hypoxic area and volume on the western shelf in CGEM compared to GoMDOM. Reductions in hypoxic area were greatest in the western shelf, comprising 72% (~4,200 km2) of the total shelfwide hypoxia response. The range of hypoxia responses from multiple models suggests a 60% load reduction may result in a 33% reduction in hypoxic area, leaving an annual hypoxic area of ~9,000 km2 based on the latest 5-yr average (13,928 km2).

Evidence for Cross Species Extrapolation of Mammalian-Based High-Throughput Screening Assay Results.

High-throughput screening (HTS) and computational technologies have emerged as important tools for chemical hazard identification. The US Environmental Protection Agency (EPA) launched the Toxicity ForeCaster (ToxCast) Program, which has screened thousands of chemicals in hundreds of mammalian-based HTS assays for biological activity. The data are being used to prioritize toxicity testing on those chemicals likely to lead to adverse effects. To use HTS assays in predicting hazard to both humans and wildlife, it is necessary to understand how broadly these data may be extrapolated across species. The US EPA Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/ ) tool was used to assess conservation of the 484 protein targets represented in the suite of ToxCast assays and other HTS assays. To demonstrate the utility of the SeqAPASS data for guiding extrapolation, case studies were developed which focused on targets of interest to the US Endocrine Disruptor Screening Program and the Organisation for Economic Cooperation and Development. These case studies provide a line of evidence for conservation of endocrine targets across vertebrate species, with few exceptions, and demonstrate the utility of SeqAPASS for defining the taxonomic domain of applicability for HTS results and identifying organisms for suitable follow-up toxicity tests.