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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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All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

A data-driven approach to modeling cancer cell mechanics during microcirculatory transport

In order to understand the effect of cellular level features on the transport of circulating cancer cells in the microcirculation, there has been an increasing reliance on high-resolution in silico models. Accurate simulation of cancer cells flowing with blood cells requires resolving cellular-scale interactions in 3D, which is a significant computational undertaking warranting a cancer cell model that is both computationally efficient yet sufficiently complex to capture relevant behavior. Given that the characteristics of metastatic spread are known to depend on cancer type, it is crucial to account for mechanistic behavior representative of a specific cancer’s cells. To address this gap, in the present work we develop and validate a means by which an efficient and popular membrane model-based approach can be used to simulate deformable cancer cells and reproduce experimental data from specific cell lines. Here, cells are modeled using the immersed boundary method (IBM) within a lattice Boltzmann method (LBM) fluid solver, and the finite element method (FEM) is used to model cell membrane resistance to deformation. Through detailed comparisons with experiments, we (i) validate this model to represent cancer cells undergoing large deformation, (ii) outline a systematic approach to parameterize different cell lines to optimally fit experimental data over a range of deformations, and (iii) provide new insight into nucleated vs. non-nucleated cell models and their ability to match experiments. While many works have used the membrane-model based method employed here to model generic cancer cells, no quantitative comparisons with experiments exist in the literature for specific cell lines undergoing large deformation. Here, we describe a phenomenological, data-driven approach that can not only yield good agreement for large deformations, but explicitly detail how it can be used to represent different cancer cell lines. This model is readily incorporated into cell-resolved hemodynamic transport simulations, and thus offers significant potential to complement experiments towards providing new insights into various aspects of cancer progression.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Exposure to multiple ion beams, broadly representative of galactic cosmic rays, causes perivascular cardiac fibrosis in mature male rats

Long-duration space exploratory missions to the Earth’s moon and the planet Mars are actively being planned. Such missions will require humans to live for prolonged periods beyond low earth orbit where astronauts will be continuously exposed to high energy galactic cosmic rays (GCRs). A major unknown is the potential impact of GCRs on the risks of developing degenerative cardiovascular disease, which is a concern to NASA. A ground-based rat model has been used to provide a detailed characterization of the risk of long-term cardiovascular disease from components of GCRs at radiation doses relevant to future human missions beyond low earth orbit. Six month old male WAG/RijCmcr rats were irradiated at a ground-based charged particle accelerator facility with high energy ion beams broadly representative of GCRs: protons, silicon and iron. Irradiation was given either as a single ion beam or as a combination of three ion beams. For the doses used, the single ion beam studies did not show any significant changes in the known cardiac risk factors and no evidence of cardiovascular disease could be demonstrated. In the three ion beam study, the total cholesterol levels in the circulation increased modestly over the 270 day follow up period, and inflammatory cytokines were also increased, transiently, 30 days after irradiation. Perivascular cardiac collagen content, systolic blood pressure and the number of macrophages found in the kidney and in the heart were each increased 270 days after irradiation with 1.5 Gy of the three ion beam grouping. These findings provide evidence for a cardiac vascular pathology and indicate a possible threshold dose for perivascular cardiac fibrosis and increased systemic systolic blood pressure for complex radiation fields during the 9 month follow up period. The development of perivascular cardiac fibrosis and increased systemic systolic blood pressure occurred at a physical dose of the three ion beam grouping (1.5 Gy) that was much lower than that required to show similar outcomes in earlier studies with the same rat strain exposed to photons. Further studies with longer follow up periods may help determine whether humans exposed to lower, mission-relevant doses of GCRs will develop radiation-induced heart disease.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Identification of blood protein biomarkers associated with prostate cancer risk using genetic prediction models: analysis of over 140,000 subjects

Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, the existing findings may be subject to incoherent biases of conventional epidemiologic studies. To better characterize their associations, herein, we evaluated associations of genetically predicted concentrations of plasma proteins with PCa risk. In this study, we developed comprehensive genetic prediction models for protein levels in plasma. After testing 1308 proteins in 79 194 cases and 61 112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL, 24 proteins showed significant associations with PCa risk, including 16 previously reported proteins and eight novel proteins. Of them, 14 proteins showed negative associations and 10 showed positive associations with PCa risk. For 18 of the identified proteins, potential functional somatic changes of encoding genes were detected in PCa patients in The Cancer Genome Atlas (TCGA). Genes encoding these proteins were significantly involved in cancer-related pathways. We further identified drugs targeting the identified proteins, which may serve as candidates for drug repurposing for treating PCa. In conclusion, this study identifies novel protein biomarker candidates for PCa risk, which may provide new perspectives on the etiology of PCa and improve its therapeutic strategies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Circulating levels of micronutrients and risk of osteomyelitis: a Mendelian randomization study

Background Few observational studies have investigated the effect of micronutrients on osteomyelitis, and these findings are limited by confounding and conflicting results. Therefore, we conducted Mendelian randomization (MR) analyses to evaluate the association between blood levels of eight micronutrients (copper, selenium, zinc, vitamin B12, vitamin C, and vitamin D, vitamin B6, vitamin E) and the risk of osteomyelitis. Methods We performed the two-sample and multivariable Mendelian randomization (MVMR) to investigate causation, where instrument variables for the predictor (micronutrients) were derived from the summary data of micronutrients from independent cohorts of European ancestry. The outcome instrumental variables were used from the summary data of European-ancestry individuals ( n = 486,484). The threshold of statistical significance was set at p < 0.00625. Results We found a significant causal association that elevated zinc heightens the risk of developing osteomyelitis in European ancestry individuals OR = 1.23 [95% confidence interval (CI) [1.07, 1.43]; p = 4.26E-03]. Similarly, vitamin B6 showed a similar significant causal effect on osteomyelitis as a risk factor OR = 2.78 (95% CI [1.34, 5.76]; p = 6.04E-03; in the secondary analysis). Post-hoc analysis suggested this result (vitamin B6). However, the multivariable Mendelian randomization (MVMR) provides evidence against the causal association between zinc and osteomyelitis OR = 0.98(95% CI [−0.11, 0.07]; p = 7.20E-1). After searching in PhenoScanner, no SNP with confounding factors was found in the analysis of vitamin B6. There was no evidence of a reverse causal impact of osteomyelitis on zinc and vitamin B6. Conclusion This study supported a strong causal association between vitamin B6 and osteomyelitis while reporting a dubious causal association between zinc and osteomyelitis.

Zhang, Xu↗
DOE OSTI2026

Adverse Neurological Effects of Wildfire Smoke

The respiratory and cardiovascular effects of smoke exposure are well documented from cigarette smoking and particulate matter (PM) associated with air-pollution studies, but epidemiological data also suggests exposure to high levels of woodsmoke correlate with central-nervous-system (CNS) dysfunction, including elevated rates of Alzheimer’s disease (AD) and dementia. Neuro-inflammation is believed to initiate the majority of Alzheimer’s and other neurodegenerative diseases attributed to environmental factors. We investigated whether inhaled PM and specific classes of compounds in wildfire smoke condensate extract (WSE) reach the brain and cause neuro-inflammation that can lead to progressive neurological degeneration, using isotope tracing of labeled particulate matter and major compound classes, biomarkers of blood-brain barrier (BBB) integrity, and biomarkers of neuro-inflammation. This project showed that inhalation exposure to PM and major compound classes present in WSE reached the brain through absorption in the nasal cavity and systemic circulation across the BBB. Twenty-four exposures of WSE to brain endothelial cells that form the main physical barrier of the BBB produced dose-dependent increases in biomarkers of inflammation and decreases in tight junction markers between cells. Intranasal exposure to WSE caused inflammatory disfunction in lung and brain. Biomarkers of inflammation increased and an enzyme inhibiting inflammation decreased. Similar patterns of chemical-induced changes in the lung and brain suggest either: (1) chemicals may act through shared molecular pathways upon entering lung and brain, or (2) that mediators originating in the lung circulate systemically to the brain and drive neuroinflammation. These findings warrant further mechanistic studies to delineate the temporal sequence of events to establish the lung-brain axis.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Full genome sequence for the African swine fever virus outbreak in the Dominican Republic in 1980

African swine fever is a lethal disease of domestic pigs, geographically expanding as a pandemic, that is affecting countries across Eurasia and severely damaging their swine production industry. After more than 40 years of being absent in the Western hemisphere, in 2020 ASF reappeared in the Dominican Republic and Haiti. The recent outbreak strain in the Dominican Republic has been identified as a genotype II ASFV a derivative of the ASF strain circulating in Asia and Europe. However, to date no full-length genome sequence from either the 1978–1980 Here we report the complete genome sequence of an African swine fever virus (ASFV) (DR-1980) that was previously isolated from blood collected in 1980 from the Dominican Republic at the end of the last outbreak, before culling of all swine on the island of Hispaniola and stored in the Plum Island Animal Disease Center ASFV repository. A contig representing the full-length genome (183,687 base pairs) was de novo assembled into a single contig using both Nanopore and Illumina sequences. DR-1980 was determined to belong to genotype I and, as determined by full genome comparison, a close relative to the sequenced Sardinia viruses that were causing outbreaks at this time.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Simulated Night- Shift Schedule Disrupts the Plasma Lipidome and Reveals Early Markers of Cardiovascular Disease Risk

Introduction: The circadian system coordinates daily rhythms in lipid metabolism, storage and utilization. Disruptions of internal circadian rhythms due to altered sleep/wake schedules, such as in night-shift work, have been implicated in increased risk of cardiovascular disease and metabolic disorders. To determine the impact of a night-shift schedule on the human blood plasma lipidome, an in-laboratory simulated shift work study was conducted. Methods: Fourteen healthy young adults were assigned to 3 days of either a simulated day or night-shift schedule, followed by a 24-h constant routine protocol with fixed environmental conditions, hourly isocaloric snacks, and constant wakefulness to investigate endogenous circadian rhythms. Blood plasma samples collected at 3-h intervals were subjected to untargeted lipidomics analysis. Results: More than 400 lipids were identified and quantified across 21 subclasses. Focusing on lipids with low between-subject variation per shift condition, alterations in the circulating plasma lipidome revealed generally increased mean triglyceride levels and decreased mean phospholipid levels after night-shift relative to day-shift. The circadian rhythms of triglycerides containing odd chain fatty acids peaked earlier during constant routine after night-shift. Regardless of shift condition, triglycerides tended to either peak or be depleted at 16:30 h, with chain-specific differences associated with the direction of change. Discussion: The simulated night-shift schedule was associated with altered temporal patterns in the lipidome. This may be premorbid to the elevated cardiovascular risk that has been found epidemiologically in night-shift workers.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Asynchronous aging and turnover of human circulating and tissue-resident memory T cells across sites

Memory T cells are maintained in tissues as circulating effector-memory (T EM ) and tissue-resident (T RM ) populations for protective immunity, though the role of site and subset in memory persistence remains undefined. Here, in this work, we investigated age-associated dynamics of human T cells in lymphoid organs, mucosal sites, and blood over 10 decades of life using retrospective radiocarbon ( 14 C) birth dating, along with cellular, transcriptome, and epigenetic profiling. Memory T cells across peripheral sites exhibited continuous turnover with mean lifespans of 1–2 years, while the spleen contained longer-lived T cells. Over age, T EM cells expressed senescent markers and a GZMK transcriptional signature, while T RM cells maintained site-specific resident phenotypes without exhibiting features of senescence. Both T EM and T RM cells showed age-associated DNA hypomethylation, though T RM cells exhibited more epigenetically regulated genes. Together, our findings reveal asynchronous aging of human memory T cells by subset and site, as well as persistence of T RM cells without immunosenescence.

T cells↗
DOE OSTI2020

Sex Differences in Vagus Nerve Stimulation Effects on Rat Cardiovascular and Immune Systems

Background: Investigations into the benefits of vagus nerve stimulation (VNS) through pre-clinical and clinical research have led to promising findings for treating several disorders. Despite proven effectiveness of VNS on conditions such as epilepsy and depression, understanding of off-target effects and contributing factors such as sex differences can be beneficial to optimize therapy design. New Methods: In this article, we assessed longitudinal effects of VNS on cardiovascular and immune systems, and studied potential sex differences using a rat model of longterm VNS. Rats were implanted with cuff electrodes around the left cervical vagus nerve for VNS, and wireless physiological monitoring devices for continuous monitoring of cardiovascular system using electrocardiogram (ECG) signals. ECG morphology and heart rate variability (HRV) features were extracted to assess cardiovascular changes resulting from VNS in short-term and long-term timescales. We also assessed VNS effects on expression of inflammatory cytokines in blood during the course of the experiment. Statistical analysis was performed to compare results between Treatment and Sham groups, and between male and female animals from Treatment and Sham groups. Results: Considerable differences between male and female rats in cardiovascular effects of VNS were observed in multiple cardiovascular features. However, the effects seemed to be transient with approximately 1-h recovery after VNS. While short-term cardiovascular effects were mainly observed in male rats, females in general showed more significant long-term effects even after VNS stopped. We did not observe notable changes or sex differences in systemic cytokine levels resulting from VNS. Comparison With Existing Methods: Compared to existing methods, our study design incorporated wireless physiological monitoring and systemic blood cytokine level analysis, along with long-term VNS experiments in unanesthetized rats to study sex differences. Conclusion: The contribution of sex differences for long-term VNS off-target effects on cardiovascular and immune systems was assessed using awake behaving rats. Although VNS did not change the concentration of inflammatory biomarkers in systemic circulation for male and female rats, we observed significant differences in cardiovascular effects of VNS characterized using ECG morphology and HRV analyses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

RNA Splicing Events in Circulation Distinguish Individuals With and Without New-onset Type 1 Diabetes

Context: Alterations in RNA splicing may influence protein isoform diversity that contributes to or reflects the pathophysiology of certain diseases. Whereas specific RNA splicing events in pancreatic islets have been investigated in models of inflammation in vitro, how RNA splicing in the circulation correlates with or is reflective of type 1 diabetes (T1D) disease pathophysiology in humans remains unexplored. Objective: To use machine learning to investigate if alternative RNA splicing events differ between individuals with and without new-onset T1D and to determine if these splicing events provide insight into T1D pathophysiology. Methods: RNA deep sequencing was performed on whole blood samples from 2 independent cohorts: a training cohort consisting of 12 individuals with new-onset T1D and 12 age- and sex-matched nondiabetic controls and a validation cohort of the same size and demographics. Machine learning analysis was used to identify specific isoforms that could distinguish individuals with T1D from controls. Results: Distinct patterns of RNA splicing differentiated participants with T1D from unaffected controls. Notably, certain splicing events, particularly involving retained introns, showed significant association with T1D. Machine learning analysis using these splicing events as features from the training cohort demonstrated high accuracy in distinguishing between T1D subjects and controls in the validation cohort. Gene Ontology pathway enrichment analysis of the retained intron category showed evidence for a systemic viral response in T1D subjects. Conclusion: Alternative RNA splicing events in whole blood are significantly enriched in individuals with new-onset T1D and can effectively distinguish these individuals from unaffected controls. Further, our findings also suggest that RNA splicing profiles offer the potential to provide insights into disease pathogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Platelet cloaking of circulating tumour cells in patients with metastatic prostate cancer: Results from ExPeCT, a randomised controlled trial

Background: Circulating tumour cells (CTCs) represent a morphologically distinct subset of cancer cells, which aid the metastatic spread. The ExPeCT trial aimed to examine the effectiveness of a structured exercise programme in modulating levels of CTCs and platelet cloaking in patients with metastatic prostate cancer. Methods: Participants (n = 61) were randomised into either standard care (control) or exercise arms. Whole blood was collected for all participants at baseline (T0), three months (T3) and six months (T6), and analysed for the presence of CTCs, CTC clusters and platelet cloaking. CTC data was correlated with clinico-pathological information. Results: Changes in CTC number were observed within group over time, however no significant difference in CTC number was observed between groups over time. Platelet cloaking was identified in 29.5% of participants. A positive correlation between CTC number and white cell count (WCC) was observed (p = 0.0001), in addition to a positive relationship between CTC clusters and PSA levels (p = 0.0393). Conclusion: The presence of platelet cloaking has been observed in this patient population for the first time, in addition to a significant correlation between CTC number and WCC. Trial registration: ClincalTrials.gov identifier NCT02453139 .

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Challenges and the Evolving Landscape of Assessing Blood-Based PD-L1 Expression as a Biomarker for Anti-PD-(L)1 Immunotherapy

While promising, PD-L1 expression on tumor tissues as assessed by immunohistochemistry has been shown to be an imperfect biomarker that only applies to a limited number of cancers, whereas many patients with PD-L1-negative tumors still respond to anti-PD-(L)1 immunotherapy. Recent studies using patient blood samples to assess immunotherapeutic responsiveness suggests a promising approach to the identification of novel and/or improved biomarkers for anti-PD-(L)1 immunotherapy. In this review, we discuss the advances in our evolving understanding of the regulation and function of PD-L1 expression, which is the foundation for developing blood-based PD-L1 as a biomarker for anti-PD-(L)1 immunotherapy. We further discuss current knowledge and clinical study results for biomarker identification using PD-L1 expression on tumor and immune cells, exosomes, and soluble forms of PD-L1 in the peripheral blood. Finally, we discuss key challenges for the successful development of the potential use of blood-based PD-L1 as a biomarker for anti-PD-(L)1 immunotherapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Establishing reference ranges for circulating biomarkers of drug‐induced liver injury in healthy human volunteers 1

Aims The potential of mechanistic biomarkers to improve prediction of drug‐induced liver injury (DILI) and hepatic regeneration is widely acknowledged. We sought to determine reference intervals for new biomarkers of DILI and regeneration, as well as to characterize their natural variability and impact of diurnal variation. Methods Serum samples from 227 healthy volunteers were recruited as part of a cross‐sectional study; of these, 25 subjects had weekly serial sampling over 3 weeks, while 23 had intensive blood sampling over a 24h period. Alanine aminotransferase (ALT), MicroRNA‐122 (miR‐122), High Mobility Group Box‐1 (HMGB1), total Keratin‐18 (K18), caspase‐cleaved Keratin‐18 (ccK18), Glutamate Dehydrogenase (GLDH) and Macrophage Colony‐Stimulating Factor‐1 (CSF‐1) were assayed. Results Reference intervals were established for each biomarker based on the 97.5% quantile (90% CI) following the assessment of fixed effects in univariate and multivariable models. Intra‐individual variability was found to be non‐significant, and there was no significant impact of diurnal variation. Conclusion Reference intervals for novel DILI biomarkers have been described. An upper limit of a reference range might represent the most appropriate mechanism to utilize these data. These data can now be used to interpret data from exploratory clinical DILI studies and to assist their further qualification as required by regulatory authorities.

Jorgensen, Andrea L. [Department of Health Data Sc↗
DOE OSTI2022

A Highly Effective African Swine Fever Virus Vaccine Elicits a Memory T Cell Response in Vaccinated Swine

African Swine Fever Virus (ASFV) is the causative agent of a highly contagious and lethal vector-borne disease in suids. Recently, a live attenuated virus strain, developed using the currently circulating, virulent Georgia strain (ASFV-G) with a single gene deletion (ASFV-G-ΔI177L), resulted in an effective vaccine. Nevertheless, protective immune response mechanisms induced by this candidate are poorly understood. In this study, Yorkshire crossbred swine intramuscularly vaccinated with 10 6 50% hemadsorption dose (HAD 50 ) of ASFV-G-ΔI177L or a vehicle control were challenged at 28 days post-inoculation (dpi) with 10 2 HAD 50 of ASFV-G. Analysis of purified peripheral blood mononuclear cells following inoculation and challenge revealed that CD4+, CD8+ and CD4+CD8+ central memory T cells (CD44+CD25–CD27–CD62L+CCR7+, T cm ) decreased significantly by 28 dpi in ASFV-G-ΔI177L-vaccinated swine compared to baseline and time-matched controls. Conversely, CD4+, CD8+ and CD4+CD8+ effector memory T cells (CD44+CD25–CD27–CD62–CCR7–, T em ) increased significantly among ASFV-G-ΔI177L-vaccined swine by 28 dpi compared to baseline and time-matched controls. Additionally, the percentage of natural killer (NK), CD4+ and CD4+CD8+ T em and CD8+ T cm and T em positive for IFNγ increased significantly following inoculation, surpassing that of controls by 28 dpi or earlier. These results suggest that NK and memory T cells play a role in prote

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

SARS-CoV-2 Omicron (B.1.1.529) Infection of Wild White-Tailed Deer in New York City

There is mounting evidence of SARS-CoV-2 spillover from humans into many domestic, companion, and wild animal species. Research indicates that humans have infected white-tailed deer, and that deer-to-deer transmission has occurred, indicating that deer could be a wildlife reservoir and a source of novel SARS-CoV-2 variants. We examined the hypothesis that the Omicron variant is actively and asymptomatically infecting the free-ranging deer of New York City. Between December 2021 and February 2022, 155 deer on Staten Island, New York, were anesthetized and examined for gross abnormalities and illnesses. Paired nasopharyngeal swabs and blood samples were collected and analyzed for the presence of SARS-CoV-2 RNA and antibodies. Of 135 serum samples, 19 (14.1%) indicated SARS-CoV-2 exposure, and 11 reacted most strongly to the wild-type B.1 lineage. Of the 71 swabs, 8 were positive for SARS-CoV-2 RNA (4 Omicron and 4 Delta). Two of the animals had active infections and robust neutralizing antibodies, revealing evidence of reinfection or early seroconversion in deer. Variants of concern continue to circulate among and may reinfect US deer populations, and establish enzootic transmission cycles in the wild: this warrants a coordinated One Health response, to proactively surveil, identify, and curtail variants of concern before they can spill back into humans.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Interaction of amphiphilic lipoarabinomannan with host carrier lipoproteins in tuberculosis patients: Implications for blood-based diagnostics

Lipoarabinomannan (LAM), an amphiphilic lipoglycan of the Mycobacterium tuberculosis cell wall, is a diagnostic target for tuberculosis. Previous work from our laboratory and others suggests that LAM is associated with host serum lipoproteins, which may in turn have implications for diagnostic assays. Our team has developed two serum assays for amphiphile detection: lipoprotein capture and membrane insertion. The lipoprotein capture assay relies on capture of the host lipoproteins, exploiting the biological association of host lipoprotein with microbial amphiphilic biomarkers to “concentrate” LAM. In contrast, the membrane insertion assay is independent of the association between pathogen amphiphiles and host lipoprotein association, and directly captures LAM based on its thermodynamic propensity for association with a supported lipid membrane, which forms the functional surface of an optical biosensor. In this manuscript, we explored the use of these assays for the detection of LAM in sera from adults whose tuberculosis status had been well-characterized using conventional microbiological tests, and endemic controls. Using the lipoprotein capture assay, LAM signal/noise ratios were >1.0 in 29/35 (83%) individuals with culture-confirmed active tuberculosis, 8/13 (62%) individuals with tuberculosis symptoms, but no positive culture for M . tuberculosis , and 0/6 (0%) symptom-free endemic controls. To evaluate serum LAM levels without bias associated with potential differences in circulating host lipoprotein concentrations between individuals, we subsequently processed available samples to liberate LAM from associated host lipoprotein assemblies followed by direct detection of the pathogen biomarker using the membrane insertion approach. Using the membrane insertion assay, signal/noise for detection of serum LAM was greater than that observed using the lipoprotein capture method for culture-confirmed TB patients (6/6), yet remained negative for controls (2/2). Taken together, these results suggest that detection of serum LAM is a promising TB diagnostic approach, but that further work is required to optimize assay performance and to decipher the implications of LAM/host lipoprotein associations for diagnostic assay performance and TB pathogenesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Stress Drivers of Glucose Dynamics during Ozone Exposure Measured Using Radiotelemetry in Rats

Inhaled irritant air pollutants may trigger stress-related metabolic dysfunction associated with altered circulating adrenal-derived hormones. We used implantable telemetry in rats to assess real-time changes in circulating glucose during and after exposure to ozone and mechanistically linked responses to neuroendocrine stress hormones. First, using a cross-over design, we monitored glucose during ozone exposures (0.0, 0.2, 0.4, and 0.8 ppm) and nonexposure periods in male Wistar Kyoto rats implanted with glucose telemeters. A second cohort of unimplanted rats was exposed to ozone (0.0, 0.4 or 0.8 ppm) for 30 min, 1 h, 2 h, or 4 h with hormones measured immediately post exposure. We assessed glucose metabolism in sham and adrenalectomized rats, with or without supplementation of adrenergic/glucocorticoid receptor agonists, and in a separate cohort, antagonists. Ozone (0.8 ppm) was associated with significantly higher blood glucose and lower core body temperature beginning 90 min into exposure, with reversal of effects 4–6 h post exposure. Glucose monitoring during four daily 4-h ozone exposures revealed duration of glucose increases, adaptation, and diurnal variations. Ozone-induced glucose changes were preceded by higher levels of adrenocorticotropic hormone, corticosterone, and epinephrine but lower levels of thyroid-stimulating hormone, prolactin, and luteinizing hormones. Higher glucose and glucose intolerance were inhibited in rats that were adrenalectomized or treated with adrenergic plus glucocorticoid receptor antagonists but exacerbated by agonists. We demonstrated the temporality of neuroendocrine-stress–mediated biological sequalae responsible for ozone-induced glucose metabolic dysfunction and mechanism in a rodent model.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗