Comparing Transcriptomic Points of Departure to Apical Effect Concentrations For Larval Fathead Minnow Exposed to Chemicals with Four Different Modes Of Action.

It is postulated that below a transcriptomic-based point of departure, adverse effects are unlikely to occur, thereby providing a chemical concentration to use in screening level hazard assessment. The present study extends previous work describing a high-throughput fathead minnow assay that can provide full transcriptomic data after exposure to a test chemical. One-day post-hatch fathead minnows were exposed to ten concentrations of three representatives of four chemical modes of action: organophosphates, ecdysone receptor agonists, plant photosystem II inhibitors, and estrogen receptor agonists for 24 h. Concentration response modeling was performed on whole body gene expression data from each exposure, using measured chemical concentrations when available. Transcriptomic points of departure in larval fathead minnow were lower than apical effect concentrations across fish species but not always lower than toxic effect concentrations in other aquatic taxa like crustaceans and insects. The point of departure was highly dependent on measured chemical concentration which were often lower than the nominal concentration. Differentially expressed genes between chemicals within modes of action were compared and often showed statistically significant overlap. In addition, reproducibility between identical exposures using a positive control chemical (CuSO4) and variability associated with the transcriptomic point of departure using in silico sampling were considered. Results extend a transcriptomic-compatible fathead minnow high-throughput assay for possible use in ecological hazard screening.

The Mixoplankton Database (MDB): Diversity of photo-phago-trophic plankton in form, function, and distribution across the global ocean.

Protist plankton are major members of open-water marine food webs. Traditionally divided between phototrophic phytoplankton and phagotrophic zooplankton, recent research shows many actually combine phototrophy and phagotrophy in the one cell; these protists are the "mixoplankton." Under the mixoplankton paradigm, "phytoplankton" are incapable of phagotrophy (diatoms being exemplars), while "zooplankton" are incapable of phototrophy. This revision restructures marine food webs, from regional to global levels. Here, we present the first comprehensive database of marine mixoplankton, bringing together extant knowledge of the identity, allometry, physiology, and trophic interactivity of these organisms. This mixoplankton database (MDB) will aid researchers that confront difficulties in characterizing life traits of protist plankton, and it will benefit modelers needing to better appreciate ecology of these organisms with their complex functional and allometric predator-prey interactions. The MDB also identifies knowledge gaps, including the need to better understand, for different mixoplankton functional types, sources of nutrition (use of nitrate, prey types, and nutritional states), and to obtain vital rates (e.g. growth, photosynthesis, ingestion, factors affecting photo' vs. phago' -trophy). It is now possible to revisit and re-classify protistan "phytoplankton" and "zooplankton" in extant databases of plankton life forms so as to clarify their roles in marine ecosystems.

'Boom-and-busted' dynamics of phytoplankton-virus interactions explain the paradox of the plankton.

Rapid virus proliferation can exert a powerful control on phytoplankton host populations, playing a significant role in marine biogeochemistry and ecology. We explore how marine lytic viruses impact phytoplankton succession, affecting host and nonhost populations. Using an in silico food web we conducted simulation experiments under a range of different abiotic and biotic conditions, exploring virus-host-grazer interactions and manipulating competition, allometry, motility and cyst cycles. Virus-host and predator-prey interactions, and interactions with competitors, generate bloom dynamics with a pronounced 'boom-and-busted' dynamic (BBeD) which leads to the suppression of otherwise potentially successful phytoplankton species. The BBeD is less pronounced at low nutrient loading through distancing of phytoplankton hosts, while high sediment loading and high nonhost biomass decrease the abundance of viruses through adsorption. Larger hosts are inherently more distanced, but motility increases virus attack, while cyst cycles promote spatial and temporal distancing. Virus control of phytoplankton bloom development appears more important than virus-induced termination of those blooms. This affects plankton succession - not only the growth of species infected by the virus, but also those that compete for the same resources and are collectively subjected to common grazer control. The role of viruses in structuring plankton communities via BBeDs can thus provide an explanation for the paradox of the plankton.

Deuterium in marine organic biomarkers: toward a new tool for quantifying aquatic mixotrophy.

The traditional separation between primary producers (autotrophs) and consumers (heterotrophs) at the base of the marine food web is being increasingly replaced by the paradigm that mixoplankton, planktonic protists with the nutritional ability to use both phago(hetero)trophy and photo(auto)trophy to access energy are widespread globally. Thus, many 'phytoplankton' eat, while 50% of 'protozooplankton' also perform photosynthesis. Mixotrophy may enhance primary production, biomass transfer to higher trophic levels and the efficiency of the biological pump to sequester atmospheric CO2 into the deep ocean. Although this view is gaining traction, science lacks a tool to quantify the relative contributions of autotrophy and heterotrophy in planktonic protists. This hinders our understanding of their impacts on carbon cycling within marine pelagic ecosystems. It has been shown that the hydrogen (H) isotopic signature of lipids is uniquely sensitive to heterotrophy relative to autotrophy in plants and bacteria. Here, we explored whether it is also sensitive to the trophic status in protists. The new understanding of H isotope signature of lipid biomarkers suggests it offers great potential as a novel tool for quantifying the prevalence of mixotrophy in diverse marine microorganisms and thus for investigating the implications of the 'mixoplankton' paradigm.

The effects of combinations of limited ration and diazinon exposure on acetylcholinesterase activity, growth and reproduction in Oryzias latipes, the Japanese medaka.

Environmental contamination can negatively impact fish populations. In addition to acute toxicity leading to death, toxicants can reduce fish growth and lower reproduction. The potential for adverse population level effects of environmental contaminants are estimated to conduct risk assessments from laboratory toxicity tests that most often measure apical endpoints related to growth, survival and reproduction. The relationships between these effect endpoints are being evaluated to predict shifts in fish population demography better after exposure to environmental toxicants. Environmental contaminants can also affect fish populations indirectly by reducing prey biomass. However, estimating the magnitude of the combined effects of prey reduction and direct toxicity is difficult and rarely attempted. Here we describe a toxicity test designed to estimate the effect on Japanese medaka of both reduced food and chronic exposure to diazinon, an acetylcholinesterase inhibiting organophosphate pesticide. Fish were reared with limited food ration and/or diazinon exposure through a full life cycle to assess possible interactions between the two stressors in their effects on growth and reproduction. Diazinon exposure (10 or 20 µg/L), reduced ration (50% and 25% of ad libitum), or combinations of both lowered growth rates and reproductive output of Japanese medaka. In addition, growth and reproduction alone were modeled, and then various relationships between the two stressors (diazinon and ration) and how they relate to growth and reproduction were modeled.

A Bibliometric Analysis of Microalgae Research in the World, Europe, and the European Atlantic Area.

：A bibliographic database of scientific papers published by authors affiliated worldwide, especially focused in Europe and in the European Atlantic Area, and containing the keywords "microalga(e)" or "phytoplankton" was built. A corpus of 79,020 publications was obtained and analyzed using the Orbit Intellixir software to highlight the evolution of the research domain. Publication rates from 1960 to 2019, organization of the research, collaboration networks between countries and organizations, emerging and fading research concepts, major studied species, and associated concepts, as well as journals publishing microalgae research were considered. As a result, of the 79,020 papers published worldwide, 26,137 included authors from Europe (33% of world production) and 6989 from the European Atlantic Area (AA) (27% of European production, 9% of world production). The main worldwide scientific research topics found in this study were phytoplankton, community, bloom, diatoms, distribution, ecosystem, coastal, chlorophyll, zooplankton, photosynthesis, and primary production. At the European scale, the most studied topics were related to the environment, food, chemicals, pigments, protein, feed, and drugs. The highest scientific trends and market opportunities analysis identified bioplastics and biostimulants as top emerging concepts at the European level and agricultural, animal feed, and blue biotechnology at the European AA level.

Effects of growth rate, cell size, motion, and elemental stoichiometry on nutrient transport kinetics.

Nutrient acquisition is a critical determinant for the competitive advantage for auto- and osmohetero- trophs alike. Nutrient limited growth is commonly described on a whole cell basis through reference to a maximum growth rate (Gmax) and a half-saturation constant (KG). This empirical application of a Michaelis-Menten like description ignores the multiple underlying feedbacks between physiology contributing to growth, cell size, elemental stoichiometry and cell motion. Here we explore these relationships with reference to the kinetics of the nutrient transporter protein, the transporter rate density at the cell surface (TRD; potential transport rate per unit plasma-membrane area), and diffusion gradients. While the half saturation value for the limiting nutrient increases rapidly with cell size, significant mitigation is afforded by cell motion (swimming or sedimentation), and by decreasing the cellular carbon density. There is thus potential for high vacuolation and high sedimentation rates in diatoms to significantly decrease KG and increase species competitive advantage. Our results also suggest that Gmax for larger non-diatom protists may be constrained by rates of nutrient transport. For a given carbon density, cell size and TRD, the value of Gmax/KG remains constant. This implies that species or strains with a lower Gmax might coincidentally have a competitive advantage under nutrient limited conditions as they also express lower values of KG. The ability of cells to modulate the TRD according to their nutritional status, and hence change the instantaneous maximum transport rate, has a very marked effect upon transport and growth kinetics. Analyses and dynamic models that do not consider such modulation will inevitably fail to properly reflect competitive advantage in nutrient acquisition. This has important implications for the accurate representation and predictive capabilities of model applications, in particular in a changing environment.

Prevalence of Post-Micturition Incontinence before and after Anterior Urethroplasty.

PURPOSE: In this study we aimed to define the prevalence of preoperative and postoperative post-micturition incontinence or post-void dribbling after anterior urethroplasty for urethral stricture disease. We also sought to determine risk factors for its presence. MATERIALS AND METHODS: We retrospectively reviewed a prospectively maintained, multi-institutional urethral stricture database to evaluate post-micturition incontinence using a single question from a validated questionnaire, "How often have you had a slight wetting of your pants a few minutes after you had finished urinating and had dressed yourself?" Possible answers were never-0 to all the time-3. The presence of post-micturition incontinence was defined as any answer greater than 0. Comparisons were made to stricture type and location, repair type and patient medical comorbidities. RESULTS: Preoperative and postoperative post-micturition incontinence questionnaires were completed by 614 and 331 patients, respectively. Patients without complete data available were excluded from study. Preoperative post-micturition incontinence was present in 73% of patients, of whom 44% stated that this symptom was present most of the time. Overall postoperative post-micturition incontinence was present in 40% of patients and again it was not predicted by stricture location or urethroplasty type. Of the 331 patients with followup questionnaires 60% reported improvement, 32% reported no change and 8% reported worsening symptoms. The overall rate of de novo post-micturition incontinence was low at 6.3%. CONCLUSIONS: The prevalence of preoperative post-micturition incontinence is high and likely under reported. In most patients post-micturition incontinence improves after urethroplasty and the prevalence of de novo post-micturition incontinence is low. The presence of post-micturition incontinence was not predicted by stricture length or location, or urethroplasty repair type.

Accumulation of glucosylceramide in the absence of the beta-glucosidase GBA2 alters cytoskeletal dynamics.

Glycosphingolipids are key elements of cellular membranes, thereby, controlling a variety of cellular functions. Accumulation of the simple glycosphingolipid glucosylceramide results in life-threatening lipid storage-diseases or in male infertility. How glucosylceramide regulates cellular processes is ill defined. Here, we reveal that glucosylceramide accumulation in GBA2 knockout-mice alters cytoskeletal dynamics due to a more ordered lipid organization in the plasma membrane. In dermal fibroblasts, accumulation of glucosylceramide augments actin polymerization and promotes microtubules persistence, resulting in a higher number of filopodia and lamellipodia and longer microtubules. Similar cytoskeletal defects were observed in male germ and Sertoli cells from GBA2 knockout-mice. In particular, the organization of F-actin structures in the ectoplasmic specialization and microtubules in the sperm manchette is affected. Thus, glucosylceramide regulates cytoskeletal dynamics, providing mechanistic insights into how glucosylceramide controls signaling pathways not only during sperm development, but also in other cell types.

The effects of continuous diazinon exposure on growth and reproduction in Japanese medaka using a modified Medaka Extended One Generation Reproduction Test (MEOGRT).

The Medaka Extended One Generation Reproduction Test (MEOGRT) is a Tier 2 test within U.S. Environmental Protection Agency's (USEPA) Endocrine Disruptor Screening Program (EDSP), designed to characterize the potential adverse effects to fish of exposure to chemical that can cause disruption of the endocrine system. The MEOGRT focuses primarily on adverse effects to reproduction while collecting information regarding effects on growth, survival, and endocrine-related endpoints. However, the risk assessment process for fish, as mandated by legislation such as the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) or the Toxic Substances Control Act (TSCA), could benefit from a more detailed assessment of effects on growth. Typically, fish growth data in support of risk assessment are obtained from full life-cycle tests or early life stage tests using the fathead minnow. As an alternative to these tests, a modified MEOGRT was conducted to assess the effects of diazinon on the various parameters measured in the MEOGRT. Diazinon is an organophosphate insecticide that is detected in the environment, and whose efficacy is a result of inhibition of the acetylcholine esterase enzyme at neuromuscular junctions and synapses of the nervous system. Diazinon (2.9, 5.2, 10.3, 19.8, and 40.2 µg/L) was tested with the MEOGRT protocol, and the lowest observable effect concentrations of 2.9 µg/L for fecundity and 5.2 µg/L for growth were determined. Additional growth measurements were added to the MEOGRT protocol to more robustly define growth rates and to determine the impact size has on reproductive performance. Fish size starting at the first measurement day (i.e. 21 days post-fertilization), and continuing through the duration of the test was reduced with exposure to 5.2 µg/L and higher, and asymptotic size predicted from growth modeling was reduced at 10.3 µg/L and higher. By simply adding non-destructive growth measurements at two additional time points, the MEOGRT provided enough data for the parameterization of growth models, which could be used to characterize the reproductive implications of growth impairment.

The focal adhesion protein PINCH-1 associates with EPLIN at integrin adhesion sites.

PINCH-1 is a LIM-only domain protein that forms a ternary complex with integrin-linked kinase (ILK) and parvin (to form the IPP complex) downstream of integrins. Here, we demonstrate that PINCH-1 (also known as Lims1) gene ablation in the epidermis of mice caused epidermal detachment from the basement membrane, epidermal hyperthickening and progressive hair loss. PINCH-1-deficient keratinocytes also displayed profound adhesion, spreading and migration defects in vitro that were substantially more severe than those of ILK-deficient keratinocytes indicating that PINCH-1 also exerts functions in an ILK-independent manner. By isolating the PINCH-1 interactome, the LIM-domain-containing and actin-binding protein epithelial protein lost in neoplasm (EPLIN, also known as LIMA1) was identified as a new PINCH-1-associated protein. EPLIN localized, in a PINCH-1-dependent manner, to integrin adhesion sites of keratinocytes in vivo and in vitro and its depletion severely attenuated keratinocyte spreading and migration on collagen and fibronectin without affecting PINCH-1 levels in focal adhesions. Given that the low PINCH-1 levels in ILK-deficient keratinocytes were sufficient to recruit EPLIN to integrin adhesions, our findings suggest that PINCH-1 regulates integrin-mediated adhesion of keratinocytes through the interactions with ILK as well as EPLIN.

The influence of control group reproduction on the statistical power of the Environmental Protection Agency's Medaka Extended One Generation Reproduction Test (MEOGRT).

Because of various Congressional mandates to protect the environment from endocrine disrupting chemicals (EDCs), the United States Environmental Protection Agency (USEPA) initiated the Endocrine Disruptor Screening Program. In the context of this framework, the Office of Research and Development within the USEPA developed the Medaka Extended One Generation Reproduction Test (MEOGRT) to characterize the endocrine action of a suspected EDC. One important endpoint of the MEOGRT is fecundity of medaka breeding pairs. Power analyses were conducted to determine the number of replicates needed in proposed test designs and to determine the effects that varying reproductive parameters (e.g. mean fecundity, variance, and days with no egg production) would have on the statistical power of the test. The MEOGRT Reproduction Power Analysis Tool (MRPAT) is a software tool developed to expedite these power analyses by both calculating estimates of the needed reproductive parameters (e.g. population mean and variance) and performing the power analysis under user specified scenarios. Example scenarios are detailed that highlight the importance of the reproductive parameters on statistical power. When control fecundity is increased from 21 to 38 eggs per pair per day and the variance decreased from 49 to 20, the gain in power is equivalent to increasing replication by 2.5 times. On the other hand, if 10% of the breeding pairs, including controls, do not spawn, the power to detect a 40% decrease in fecundity drops to 0.54 from nearly 0.98 when all pairs have some level of egg production. Perhaps most importantly, MRPAT was used to inform the decision making process that lead to the final recommendation of the MEOGRT to have 24 control breeding pairs and 12 breeding pairs in each exposure group.

The role of coccolithophore calcification in bioengineering their environment.

Coccolithophorids are enigmatic plankton that produce calcium carbonate coccoliths, which over geological time have buried atmospheric CO2 into limestone, changing both the atmosphere and geology of the Earth. However, the role of coccoliths for the proliferation of these organisms remains unclear; suggestions include roles in anti-predation, enhanced photosynthesis and sun-screening. Here we test the hypothesis that calcification stabilizes the pH of the seawater proximate to the organisms, providing a level of acidification countering the detrimental basification that occurs during net photosynthesis. Such bioengineering provides a more stable pH environment for growth and fits the empirical evidence for changes in rates of calcification under different environmental conditions. Under this scenario, simulations suggest that the optimal production ratio of inorganic to organic particulate C (PIC : POCprod) will be lower (by approx. 20%) with ocean acidification and that overproduction of coccoliths in a future acidified ocean, where pH buffering is weaker, presents a risk to calcifying cells.

Ocean acidification with (de)eutrophication will alter future phytoplankton growth and succession.

Human activity causes ocean acidification (OA) though the dissolution of anthropogenically generated CO2 into seawater, and eutrophication through the addition of inorganic nutrients. Eutrophication increases the phytoplankton biomass that can be supported during a bloom, and the resultant uptake of dissolved inorganic carbon during photosynthesis increases water-column pH (bloom-induced basification). This increased pH can adversely affect plankton growth. With OA, basification commences at a lower pH. Using experimental analyses of the growth of three contrasting phytoplankton under different pH scenarios, coupled with mathematical models describing growth and death as functions of pH and nutrient status, we show how different conditions of pH modify the scope for competitive interactions between phytoplankton species. We then use the models previously configured against experimental data to explore how the commencement of bloom-induced basification at lower pH with OA, and operating against a background of changing patterns in nutrient loads, may modify phytoplankton growth and competition. We conclude that OA and changed nutrient supply into shelf seas with eutrophication or de-eutrophication (the latter owing to pollution control) has clear scope to alter phytoplankton succession, thus affecting future trophic dynamics and impacting both biogeochemical cycling and fisheries.

Primary renal extra-osseous osteosarcoma.

Primary renal extra-osseous osteosarcoma is an exceedingly rare and deadly kidney neoplasm with only 27 reported cases to date. Extra-osseous osteosarcoma is a mesenchymal sarcoma that produces osteoid, but has no skeletal or periosteal involvement and most commonly arises in the lower extremities. Yet, it can arise in other locations such as the kidney. Extra-osseous osteosarcoma behaves as a separate entity from osseous osteosarcoma and should be treated as such. The treatment is surgical resection. Five year overall survival is 46% for local and 10% for metastatic disease. Additionally, 45%-50% of patients experience disease recurrence. We present a 77-year-old woman who underwent work up for recurrent gross hematuria and subsequently underwent radical nephroureterectomy for presumed upper tract urothelial cell carcinoma. However, pathologic analysis revealed a diagnosis of primary renal extra-osseous osteosarcoma. She is alive with no evidence of disease 30 months after surgery.

Serum Response Factor (SRF)-cofilin-actin signaling axis modulates mitochondrial dynamics.

Aberrant mitochondrial function, morphology, and transport are main features of neurodegenerative diseases. To date, mitochondrial transport within neurons is thought to rely mainly on microtubules, whereas actin might mediate short-range movements and mitochondrial anchoring. Here, we analyzed the impact of actin on neuronal mitochondrial size and localization. F-actin enhanced mitochondrial size and mitochondrial number in neurites and growth cones. In contrast, raising G-actin resulted in mitochondrial fragmentation and decreased mitochondrial abundance. Cellular F-actin/G-actin levels also regulate serum response factor (SRF)-mediated gene regulation, suggesting a possible link between SRF and mitochondrial dynamics. Indeed, SRF-deficient neurons display neurodegenerative hallmarks of mitochondria, including disrupted morphology, fragmentation, and impaired mitochondrial motility, as well as ATP energy metabolism. Conversely, constitutively active SRF-VP16 induced formation of mitochondrial networks and rescued huntingtin (HTT)-impaired mitochondrial dynamics. Finally, SRF and actin dynamics are connected via the actin severing protein cofilin and its slingshot phosphatase to modulate neuronal mitochondrial dynamics. In summary, our data suggest that the SRF-cofilin-actin signaling axis modulates neuronal mitochondrial function.

Have we been underestimating the effects of ocean acidification in zooplankton?

Understanding how copepods may respond to ocean acidification (OA) is critical for risk assessments of ocean ecology and biogeochemistry. The perception that copepods are insensitive to OA is largely based on experiments with adult females. Their apparent resilience to increased carbon dioxide (pCO2 ) concentrations has supported the view that copepods are 'winners' under OA. Here, we show that this conclusion is not robust, that sensitivity across different life stages is significantly misrepresented by studies solely using adult females. Stage-specific responses to pCO2 (385-6000 µatm) were studied across different life stages of a calanoid copepod, monitoring for lethal and sublethal responses. Mortality rates varied significantly across the different life stages, with nauplii showing the highest lethal effects; nauplii mortality rates increased threefold when pCO2 concentrations reached 1000 µatm (year 2100 scenario) with LC50 at 1084 µatm pCO2 . In comparison, eggs, early copepodite stages, and adult males and females were not affected lethally until pCO2 concentrations ≥3000 µatm. Adverse effects on reproduction were found, with >35% decline in nauplii recruitment at 1000 µatm pCO2 . This suppression of reproductive scope, coupled with the decreased survival of early stage progeny at this pCO2 concentration, has clear potential to damage population growth dynamics in this species. The disparity in responses seen across the different developmental stages emphasizes the need for a holistic life-cycle approach to make species-level projections to climate change. Significant misrepresentation and error propagation can develop from studies which attempt to project outcomes to future OA conditions solely based on single life history stage exposures.

Variation in elemental stoichiometry of the marine diatom Thalassiosira weissflogii (Bacillariophyceae) in response to combined nutrient stress and changes in carbonate chemistry.

The combined consequences of the multi-stressors of pH and nutrient availability upon the growth of a marine diatom were investigated. Thalassiosira weissflogii was grown in N- or P-limited batch culture in sealed systems, with pH commencing at 8.2 ("extant" conditions) or 7.6 ("ocean acidification" [OA] conditions), and then pH was allowed to either drift with growth, or was held fixed. Results indicated that within the pH range tested, the stability of environmental pH rather than its value (i.e., OA vs. extant) fundamentally influenced biomass accumul-ation and C:N:P stoichiometry. Despite large changes in total alkalinity in the fixed pH systems, final biomass production was consistently greater in these systems than that in drifting pH systems. In drift systems, pH increased to exceed pH 9.5, a level of alkalinity that was inhibitory to growth. No statis-tically significant differences between pH treatments were measured for N:C, P:C or N:P ratios during nutrient-replete growth, although the diatom expre-ssed greater plasticity in P:C and N:P ratios than in N:C during this growth phase. During nutrient-deplete conditions, the capacity for uncoupled carbon fixa-tion at fixed pH was considerably greater than that measured in drift pH systems, leading to strong contrasts in C:N:P stoichiometry between these treatments. Whether environmental pH was stable or drifted directly influenced the extent of physiological stress. In contrast, few distinctions could be drawn between "extant" versus "OA" conditions for cell physiology.

Derivation of Transcriptomics-Based Points of Departure for 20 Per- or Polyfluoroalkyl Substances Using a Larval Fathead Minnow (Pimephales promelas) Reduced Transcriptome Assay.

Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that ecological hazards of most PFAS remain uncharacterized. The present study employed a high-throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response (termed a transcriptomics-based point of departure [tPOD]) in larval fathead minnows (Pimephales promelas; 5-6 days postfertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole-body expression of 1832 genes, the median tPOD for the 20 PFAS tested was 10 µM. Longer-chain carboxylic acids (12-13 C-F); an eight-C-F dialcohol, N-alkyl sulfonamide; and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations <1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole-transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sublethal effects have been reported in fish (available for 10 PFAS). Nonetheless, fathead minnow tPODs were orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes, suggesting a substantial margin of safety. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening-level potency estimates for use in ecological risk-based prioritization. Environ Toxicol Chem 2024;00:1-16. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.