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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Chronic arsenic increases cell migration in BEAS-2B cells by increasing cell speed, cell persistence, and cell protrusion length

Highlights: • Chronic arsenic exposure primes lung epithelial cells for enhanced cell migration. • Chronic arsenic increases cell motility in an EGFR-dependent manner. • Chronic arsenic increases cell persistence in an EGFR-independent manner. • EGFR is sufficient, but not necessary for increasing cell protrusion length in chronic arsenic treated cells. There is a strong association between arsenic exposure and lung cancer development, however, the mechanism by which arsenic exposure leads to carcinogenesis is not clear. In our previous study, we observed that when BEAS-2B cells are chronically exposed to arsenic, there is an increase in secreted TGFα, as well as an increase in EGFR expression and activity. Further, these changes were broadly accompanied with an increase in cell migration. The overarching goal of this study was to acquire finer resolution of the arsenic-dependent changes in cell migration, as well as to understand the role of increased EGFR expression and activity levels in the underlying mechanisms of cell migration. To do this, we used a combination of biochemical and single cell assays, and observed chronic arsenic treatment enhancing cell migration by increasing cell speed, cell persistence and cell protrusion length. All three parameters were further increased by the addition of TGFα, indicating EGFR activity is sufficient to enhance those aspects of cell migration. In contrast, EGFR activity was necessary for the increase in cell speed, as it was reversed with an EGFR inhibitor, AG1478, but was not necessary to enhance persistence and protrusion length. From these data, we were able to isolate both EGFR-dependent and –independent features of cell migration that were enhanced by chronic arsenic exposure.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Manganese and Vanadium Co-Exposure Induces Severe Neurotoxicity in the Olfactory System: Relevance to Metal-Induced Parkinsonism

Chronic environmental exposure to toxic heavy metals, which often occurs as a mixture through occupational and industrial sources, has been implicated in various neurological disorders, including Parkinsonism. Vanadium pentoxide (V 2 O 5 ) typically presents along with manganese (Mn), especially in welding rods and high-capacity batteries, including electric vehicle batteries; however, the neurotoxic effects of vanadium (V) and Mn co-exposure are largely unknown. In this study, we investigated the neurotoxic impact of MnCl 2 , V 2 O 5 , and MnCl 2 -V 2 O 5 co-exposure in an animal model. C57BL/6 mice were intranasally administered either de-ionized water (vehicle), MnCl 2 (252 µg) alone, V 2 O 5 (182 µg) alone, or a mixture of MnCl 2 (252 µg) and V 2 O 5 (182 µg) three times a week for up to one month. Following exposure, we performed behavioral, neurochemical, and histological studies. Our results revealed dramatic decreases in olfactory bulb (OB) weight and levels of tyrosine hydroxylase, dopamine, and 3,4-dihydroxyphenylacetic acid in the treatment groups compared to the control group, with the Mn/V co-treatment group producing the most significant changes. Interestingly, increased levels of α-synuclein expression were observed in the substantia nigra (SN) of treated animals. Additionally, treatment groups exhibited locomotor deficits and olfactory dysfunction, with the co-treatment group producing the most severe deficits. The treatment groups exhibited increased levels of the oxidative stress marker 4-hydroxynonenal in the striatum and SN, as well as the upregulation of the pro-apoptotic protein PKCδ and accumulation of glomerular astroglia in the OB. The co-exposure of animals to Mn/V resulted in higher levels of these metals compared to other treatment groups. Taken together, our results suggest that co-exposure to Mn/V can adversely affect the olfactory and nigral systems. These results highlight the possible role of environmental metal mixtures in the etiology of Parkinsonism.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Empirical evidence that mean soil contaminant concentration is not a conservative indicator of external exposure to wildlife

Adequate information on external exposure is often a limiting factor in ecological risk assessments because of a lack of exposure data for free-ranging animals as they interact with a heterogeneous distribution of contaminants. Instead, most wildlife exposure data are estimated from model simulations. However, empirical exposure data are rarely available to verify model results, or to test fundamental assumptions inherent in exposure assessments. We used novel, GPS-coupled radiation dosimeters on reindeer (Rangifer tarandus) to quantify their external exposure for five months in a Chernobyl fallout affected mountainous area of Norway. The exposure data were then used to test a fundamental assumption in screening-level risk assessments: Mean soil contaminant concentrations can be used to conservatively estimate chronic external exposures to representative animals. External exposure and GPS coordinates were obtained hourly and compared to model simulations of exposure based on airborne surveys of 137 Cs soil contamination. Our objectives were to determine 1) if modelled dose estimates based on mean 137 Cs soil concentrations were conservative, and 2) if modelled dose estimates could be improved by adjusting for spatial–temporal heterogeneity of contaminants using 137 Cs concentrations within reindeers’ GPS-defined home ranges and core areas. We found that external exposure modelled from mean soil contaminant concentrations underestimated exposure by 70% compared to empirical measurements from GPS-dosimeter collars worn on individual animals. Using area-weighted mean contaminant levels within the animals’ home range improved the model estimates, but still underestimated the field dosimeter data by 53%. The best estimate of external exposure was obtained when high-use areas within their home range, along with spatial heterogeneity of the contaminant, was accounted for by using area-weighted mean soil contaminant levels within GPS-derived core areas. Accounting for temporal use of core areas within animals’ home range provided a 24% improvement. Here, a comparison of our analyses to similar work performed on Chernobyl wolves found the two studies concur that risk assessors should be cautious in relying on the paradigm of using averaged soil contaminant levels to provide conservative estimates of external exposure to representative individuals. Results of modelled external exposure based on mean soil contaminant concentrations could misguide assessors and cause inappropriate management decisions.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2023

Salinity exposure affects lower-canopy specific leaf area of upland trees in a coastal deciduous forest

Sea level rise and increasing storm surges are likely to affect the canopy physiology, ecology, and structure of coastal forests, even well in advance of tree mortality. Laboratory and greenhouse studies have documented that saltwater exposure can trigger changes in leaf-level physiology and morphology, but few in situ studies have examined how tree-specific leaf area (SLA), the ratio of leaf area to mass and a crucial trait and model parameter, is affected by saline soils. We conducted an observational study of SLA in a mid-Atlantic (USA) coastal deciduous forest, taking advantage of a natural gradient in salinity along a tidal creek. Measured SLA of the 239 trees and seven species sampled ranged from Carya glabra (N = 6 trees, mean SLA = 277.9±36.3cm 2 /g) to Fagus grandifolia (N=60, 321.9±62.9cm 2 g); as expected, trees species and canopy position (sun versus shade) significantly affected SLA. For trees (N=100) directly exposed to the tidal creek, salinity was highly significant after accounting for species (P<0.001), with trees in the lower reaches of the creek having lower SLA. Leaf area index (LAI), computed from SLA and litter traps, ranged from 4.8 to 15.8 and was inversely related to salinity exposure; the spatial variability in leaf litter production contributed much more to LAI uncertainty than did SLA variability. These in situ results are correlative but consistent with the hypothesis, based on previous greenhouse studies, that the stress of chronic salinity exposure changes species’ leaf morphology. Our findings are useful for understanding the growing effects of saltwater intrusion into upland forests, as well as parameterizing and testing ecosystem-scale models simulating forest stressors and disturbances at the terrestrial-aquatic interface.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Year-around survey and manipulation experiments reveal differential sensitivities of soil prokaryotic and fungal communities to saltwater intrusion in Florida Everglades wetlands

Global sea-level rise is transforming coastal ecosystems, especially freshwater wetlands, in part due to increased episodic or chronic saltwater exposure, leading to shifts in biogeochemistry, plant- and microbial communities, as well as ecological services. Yet, it is still difficult to predict how soil microbial communities respond to the saltwater exposure because of poorly understood microbial sensitivity within complex wetland soil microbial communities, as well as the high spatial and temporal heterogeneity of wetland soils and saltwater exposure. To address this, we first conducted a two-year survey of microbial community structure and bottom water chemistry in submerged surface soils from 14 wetland sites across the Florida Everglades. We identified ecosystem-specific microbial biomarker taxa primarily associated with variation in salinity. Bacterial, archaeal and fungal community composition differed between freshwater, mangrove, and marine seagrass meadow sites, irrespective of soil type or season. Especially, methanogens, putative denitrifying methanotrophs and sulfate reducers shifted in relative abundance and/or composition between wetland types. Methanogens and putative denitrifying methanotrophs declined in relative abundance from freshwater to marine wetlands, whereas sulfate reducers showed the opposite trend. A four-year experimental simulation of salt-water intrusion in a pristine freshwater site and a previously saltwater-impacted site corroborated the highest sensitivity and relative increase of sulfate reducers, as well as taxon-specific sensitivity of methanogens, in response to continuously pulsing of saltwater treatment. Collectively, these results suggest that besides increased salinity, saltwater-mediated increased sulfate availability leads to displacement of methanogens by sulfate reducers even at low or temporal salt exposure. In conclusion, these changes of microbial composition could affect organic matter degradation pathways in coastal freshwater wetlands exposed to sea-level rise, with potential consequences, such as loss of stored soil organic carbon.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Psychosocial experiences are associated with human brain mitochondrial biology

Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal brain function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position mitochondria both as targets and drivers of psychosocial experiences. On the one hand, chronic stress exposure and mood states may alter multiple aspects of mitochondrial biology; on the other hand, functional variations in mitochondrial OxPhos capacity may alter social behavior, stress reactivity, and mood. But are psychosocial exposures and subjective experiences linked to mitochondrial biology in the human brain? By combining longitudinal antemortem assessments of psychosocial factors with postmortem brain (dorsolateral prefrontal cortex) proteomics in older adults, we find that higher well-being is linked to greater abundance of the mitochondrial OxPhos machinery, whereas higher negative mood is linked to lower OxPhos protein content. Combined, positive and negative psychosocial factors explained 18 to 25% of the variance in the abundance of OxPhos complex I, the primary biochemical entry point that energizes brain mitochondria. Moreover, interrogating mitochondrial psychobiological associations in specific neuronal and nonneuronal brain cells with single-nucleus RNA sequencing (RNA-seq) revealed strong cell-type-specific associations for positive psychosocial experiences and mitochondria in glia but opposite associations in neurons. As a result, these “mind-mitochondria” associations were masked in bulk RNA-seq, highlighting the likely underestimation of true psychobiological effect sizes in bulk brain tissues. Thus, self-reported psychosocial experiences are linked to human brain mitochondrial phenotypes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Community response of soil microorganisms to combined contamination of polycyclic aromatic hydrocarbons and potentially toxic elements in a typical coking plant

Both polycyclic aromatic hydrocarbons (PAHs) and potentially toxic elements (PTEs) of coking industries impose negative effects on the stability of soil ecosystem. Soil microbes are regarded as an essential moderator of biochemical processes and soil remediation, while their responses to PAHs-PTEs combined contamination are largely unknown. In the present study, soil microbial diversity and community composition in the typical coking plant under the chronic co-exposure of PAHs and PTEs were investigated and microbial interaction networks were built to reveal microbial co-occurrence patterns. The results indicated that the concentrations of PAHs in the soil inside the coking plant were significantly higher than those outside the plant. The mean concentration of ∑16PAHs was 2894.4 ng·g −1 , which is 5.58 times higher than that outside the plant. The average Hg concentration inside the coking plant was 22 times higher than the background value of Hebei province. The soil fungal community inside the coking plant showed lower richness compared with that of outside community, and there are significant difference in the bacterial and fungal community composition between inside and outside of coking plant ( p < 0.01). Predicted contribution of different environmental factors to each dominant species based on random forest identified 20 and 25 biomarkers in bacteria and fungi, respectively, that were highly sensitive to coking plant soil in operation, such as Betaproteobacteria，Sordariomycetes and Dothideomycetes . Bacterial and fungal communities were shaped by the soil chemical properties (pH), PTEs (Hg), and PAHs together in the coking plant soils. Furthermore, the bacterial and fungal interaction patterns were investigated separately or jointly by intradomain and interdomain networks. Competition is the main strategy based on the co-exclusion pattern in fungal community, and the competitive relationship inside the coking plant is more complex than that outside the plant. In contrast, cooperation is the dominant strategy in bacterial networks based on the co-occurrence pattern. The present study provided insights into microbial response strategies and the interactions between bacteria and fungi under long-term combined contamination.

Shen, Qihui↗
DOE OSTI2021

Mastering Medaka Culture: Improved Techniques for Increasing Egg and Fry Production in Japanese Rice Fish ( Oryzias latipes )

Aquatic systems are integral to ecosystem function and human health. By trapping sediments and retaining nutrients, wetlands protect our water quality. However, a wetland’s capacity to trap sediments and nutrients also means they can capture many contaminants (e.g., heavy metals and radionuclides) released into the environment due to anthropogenic activities. Both heavy metals and radionuclides have detrimental effects on wildlife at acute dosages. However, little is known regarding underlying biological responses associated with chronic low dose exposure to both ionizing radiation and heavy metals. Our long-term research goal is to work to fill this knowledge gap using Medaka (Oryzias latipes), small fish amenable to experimental manipulation. However, the current study focused on altering the husbandry protocol of a laboratory colony of Medaka in a way that would increase colony size to at least 400 individual fish over a six-week period. At the beginning of our work, we followed a strict cleaning, feeding and egg harvesting protocol. Two weeks into our work, we suspected that food limitations may be negatively impacting egg production and noticed fungal growth on eggs. Thus, we altered the feeding regime and egg harvesting protocol. The altered protocol more than tripled egg production and almost doubled of fry production. By the end of our study the colony had 673 individuals: 191 adults and 482 fry. Furthermore, our protocol changes resulted in growth of the colony at sufficient numbers to begin experiments related to investigating sub-lethal impacts of heavy metals and radionuclides on Medaka.

Thompson, Melissa↗
DOE OSTI2021

Weather responsive smart ventilation system using multiple optimization parameters

A smart ventilation system which uses outdoor temperature and moisture to optimize control of the system. The main principle is to shift ventilation from time periods that have large indoor-outdoor temperature and moisture differences to periods when these differences are smaller, and their energy and comfort impacts are expected to be less. Fan flow rates are reduced when the outside temperature and moisture falls outside of optimum levels, yet overall air exchange is maintained to ensure chronic and acute exposure to pollutants remains relative to best practice. Online weather and smart thermostat data can be used as control inputs, so no specific measurement devices are needed to control ventilation fans.

Parker, Danny↗
DOE OSTI2021

Efficacy of Hair Total Mercury Content as a Biomarker of Methylmercury Exposure to Communities in the Area of Artisanal and Small-Scale Gold Mining in Madre de Dios, Peru

Total mercury content (THg) in hair is an accepted biomarker for chronic dietary methylmercury (MeHg) exposure. In artisanal and small-scale gold mining (ASGM) communities, the validity of this biomarker is questioned because of the potential for contamination from inorganic mercury. As mining communities may have both inorganic and organic mercury exposures, the efficacy of the hair-THg biomarker needs to be evaluated, particularly as nations begin population exposure assessments under their commitments to the Minamata Convention. We sought to validate the efficacy of hair THg for public health monitoring of MeHg exposures for populations living in ASGM communities. We quantified both THg and MeHg contents in hair from a representative subset of participants (N = 287) in a large, population-level mercury exposure assessment in the ASGM region in Madre de Dios (MDD), Peru. We compared population MeHg-THg correlations and %MeHg values with demographic variables including community location, sex, occupation, and nativity. We observed that hair MeHg-THg correlations were high (r > 0.7) for all communities, regardless of location or nativity. Specifically, for individuals within ASGM communities, 81% (121 of 150 total) had hair THg predominantly in the form of MeHg (i.e., >66% of THg) and reflective of dietary exposure to mercury. Furthermore, for individuals with hair THg exceeding the U.S. EPA threshold (1.0 μg/g), 88 out of 106 (83%) had MeHg as the predominant form. As a result, had urine THg solely been used for mercury exposure monitoring, approximately 59% of the ASGM population would have been misclassified as having low mercury exposure. Our results support the use of hair THg for monitoring of MeHg exposure of populations in ASGM settings where alternative biomarkers of MeHg exposure are not feasible.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2020

DNA Methylation Patterns of Chronic Explosive Breaching in U.S. Military Warfighters

Background: Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigation of blast-related neurotrauma. We have undertaken human studies involving military “breachers” —exposed to controlled, low-level blast during a 3-days explosive breaching course. Methods: We screened epigenetic profiles in peripheral blood samples from 59 subjects (in two separate U.S. Military training sessions) using Infinium MethylationEPIC BeadChips. Participants had varying numbers of exposures to blast over their military careers (empirically defined as high ≥ 40, and conversely, low < 39 breaching exposures). Daily self-reported physiological symptoms were recorded. Tinnitus, memory problems, headaches, and sleep disturbances are most frequently reported. Results: We identified 14 significantly differentially methylated regions (DMRs) within genes associated with cumulative blast exposure in participants with high relative to low cumulative blast exposure. Notably, NTSR1 and SPON1 were significantly differentially methylated in high relative to low blast exposed groups, suggesting that sleep dysregulation may be altered in response to chronic cumulative blast exposure. In comparing lifetime blast exposure at baseline (prior to exposure in current training), and top associated symptoms, we identified significant DMRs associated with tinnitus, sleep difficulties, and headache. Notably, we identified KCNN3, SOD3, MUC4, GALR1, and WDR45B, which are implicated in auditory function, as differentially methylated associated with self-reported tinnitus. These findings suggest neurobiological mechanisms behind auditory injuries in our military warfighters and are particularly relevant given tinnitus is not only a primary disability among veterans, but has also been demonstrated in active duty medical records for populations exposed to blast in training. Additionally, we found that differentially methylated regions associated with the genes CCDC68 and COMT track with sleep difficulties, and those within FMOD and TNXB track with pain and headache. Conclusion: Sleep disturbances, as well as tinnitus and chronic pain, are widely reported in U.S. military service members and veterans. As we have previously demonstrated, DNA methylation encapsulates lifetime exposure to blast. The current data support previous findings and recapitulate transcriptional regulatory alterations in genes involved in sleep, auditory function, and pain. These data uncovered novel epigenetic and transcriptional regulatory mechanism underlying the etiological basis of these symptoms.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

On the Determination of the Radiation Doses at Hiroshima [Slides]

Essentially all knowledge regarding the chronic effects of radiation exposure is derived from statistical analyses of the survivors of Hiroshima and Nagasaki. However, we were then, and are now, uncertain about the exposures. That is: We know the effects through observations and statistical analyses, but we can only estimate the doses. Other complications include the fact that Little Boy was truly unique. It was never tested, measurements of yield were ambiguous, calculations of yield were not consistent, and calibration measurements were not made, could not be made.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2024

Repeated exposure to eucalyptus wood smoke alters pulmonary gene and metabolic profiles in male Long-Evans rats

Abstract Exposure to wildfire smoke is associated with both acute and chronic cardiopulmonary illnesses, which are of special concern for wildland firefighters who experience repeated exposure to wood smoke. It is necessary to better understand the underlying pathophysiology by which wood smoke exposure increases pulmonary disease burdens in this population. We hypothesize that wood smoke exposure produces pulmonary dysfunction, lung inflammation, and gene expression profiles associated with future pulmonary complications. Male Long-Evans rats were intermittently exposed to smoldering eucalyptus wood smoke at 2 concentrations, low (11.0 ± 1.89 mg/m3) and high (23.7 ± 0.077 mg/m3), over a 2-week period. Whole-body plethysmography was measured intermittently throughout. Lung tissue and lavage fluid were collected 24 h after the final exposure for transcriptomics and metabolomics. Increasing smoke exposure upregulated neutrophils and select cytokines in the bronchoalveolar lavage fluid. In total, 3446 genes were differentially expressed in the lungs of rats in the high smoke exposure and only 1 gene in the low smoke exposure (Cd151). Genes altered in the high smoke group reflected changes to the Eukaryotic Initiation Factor 2 stress and oxidative stress responses, which mirrored metabolomics analyses. xMWAS-integrated analysis revealed that smoke exposure significantly altered pathways associated with oxidative stress, lung morphogenesis, and tumor proliferation pathways. These results indicate that intermittent, 2-week exposure to eucalyptus wood smoke leads to transcriptomic and metabolic changes in the lung that may predict future lung disease development. Collectively, these findings provide insight into cellular signaling pathways that may contribute to the chronic pulmonary conditions observed in wildland firefighters.

Toxicology↗
DOE OSTI2025

Catecholamine exposure and the gut microbiota in obstructive sleep apnea

Patients with obstructive sleep apnea (OSA) have increased mortality from chronic inflammatory and cardiovascular diseases. Excess catecholamine exposure contributes to the disease associations of OSA, but the underlying mechanism is unknown. This study tested the hypothesis that increased catecholamine exposure is associated with Enterobacteriaceae abundance in OSA. We compared urinary norepinephrine and the fecal microbiota in 24 patients with OSA and 23 controls. Urinary norepinephrine was elevated in OSA patients, consistent with increased sympathetic activation in those patients. OSA patients did not show changes in the community structure of the microbiome or in Enterobacteriaceae abundance compared to controls. Longitudinal changes in Enterobacteriaceae abundance in OSA patients were significantly associated with within-subject changes in norepinephrine, but this association was absent in controls. These results provide a preliminary association between norepinephrine exposure and Enterobacteriaceae in patients with disordered sleep.

Science & Technology - Other Topics↗
DOE OSTI2025

Building hypotheses to understand the synergistic effects of heat and pollution exposure in a changing climate

The increasing intensity, frequency, and duration of extreme weather events due to climate change poses a broad range of health risks, and the synergistic effects of extreme temperature co-occurring with other hazardous exposures such as air pollution may result in higher risks of all-cause mortality and cardiovascular and respiratory morbidity than exposure to either event alone. There are a number of hypothesized mechanisms for this interaction effect, including increased susceptibility to heat effects on chronic conditions affected by air pollution exposure, exacerbation of pollution effects due to temperature-induced stress, and shared pathophysiological pathways (e.g., systemic inflammation), but specific physiological mechanisms are not well understood. In this editorial, the authors discuss this aspect of a recently published study examining ambient formaldehyde combined with high temperature exposure and respiratory disease admissions among children. Here, the observation that the health effects of pollutants such as formaldehyde are amplified following periods of high temperature can help inform risk warning systems even without knowledge of the underlying physiological mechanisms, but a deeper biological understanding of the interaction effects of heat and ambient air pollution may better inform interventions. This is even more important in view of increases in both extreme temperature and pollution events tied to climate change.

Chambliss, Sarah [University of Texas at Austin, T↗
DOE OSTI2024

Biphasic response of human iPSC-derived neural network activity following exposure to a sarin-surrogate nerve agent

Organophosphorus nerve agents (OPNA) are hazardous environmental exposures to the civilian population and have been historically weaponized as chemical warfare agents (CWA). OPNA exposure can lead to several neurological, sensory, and motor symptoms that can manifest into chronic neurological illnesses later in life. There is still a large need for technological advancement to better understand changes in brain function following OPNA exposure. The human-relevant in vitro multi-electrode array (MEA) system, which combines the MEA technology with human stem cell technology, has the potential to monitor the acute, sub-chronic, and chronic consequences of OPNA exposure on brain activity. However, the application of this system to assess OPNA hazards and risks to human brain function remains to be investigated. In a concentration-response study, we have employed a human-relevant MEA system to monitor and detect changes in the electrical activity of engineered neural networks to increasing concentrations of the sarin surrogate 4-nitrophenyl isopropyl methylphosphonate (NIMP). We report a biphasic response in the spiking (but not bursting) activity of neurons exposed to low (i.e., 0.4 and 4 μM) versus high concentrations (i.e., 40 and 100 μM) of NIMP, which was monitored during the exposure period and up to 6 days post-exposure. Regardless of the NIMP concentration, at a network level, communication or coordination of neuronal activity decreased as early as 60 min and persisted at 24 h of NIMP exposure. Once NIMP was removed, coordinated activity was no different than control (0 μM of NIMP). Interestingly, only in the high concentration of NIMP did coordination of activity at a network level begin to decrease again at 2 days post-exposure and persisted on day 6 post-exposure. Notably, cell viability was not affected during or after NIMP exposure. Also, while the catalytic activity of AChE decreased during NIMP exposure, its activity recovered once NIMP was removed. Gene expression analysis suggests that human iPSC-derived neurons and primary human astrocytes resulted in altered genes related to the cell’s interaction with the extracellular environment, its intracellular calcium signaling pathways, and inflammation, which could have contributed to how neurons communicated at a network level.

59 BASIC BIOLOGICAL SCIENCES↗