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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 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Multi-omics Characterization of the Host Response to COVID-19

This project is a multi-disciplinary collaboration between investigators at PNNL with expertise in mass spectrometry (MS)-based omics technology development, omics measurement methods development and application, statistics, machine learning and integration of disparate datasets for a systems-level understanding, and expertise in pathogenic coronaviruses, and investigators at the University of Wisconsin-Madison (UW-Madison) with expertise in pathogenic respiratory viruses (e.g. influenza). The goal of this project is to obtain a comprehensive picture of the human host factors critical for the outcome of SARS-CoV-2 infection. We will generate broad untargeted multi-omics profiles using both state-of-the-art and novel instrumentation and approaches to enable the identification of the molecular mechanisms and host response pathways that impact human COVID-19 outcomes. We anticipate these results will lead to the generation of biomarker panels that are predictive of disease outcomes and mechanistic hypotheses that can be further interrogated in future studies and will provide the basis for vaccine or therapeutic development. To do so, we are obtaining and analyzing blood samples from COVID-19 patients with a range of disease outcomes that were treated at the Center Hospital of the National Center for Global Health and Medicine in Tokyo, Japan and other collaborating hospitals in our network. Specifically, this project will fund proteomics and metabolomics analyses of clinical COVID samples, machine learning-based integration of the data, and pathway-based interpretation of the data. This project was funded in June 2020. In the time span of June to September 2020, the project team developed an analytically and statistically robust analysis plan and made various preparations to facilitate sample receipt from our UW-Madison collaborators. This included blocking and randomization of sample prep orders, ordering of reagents and reference materials, and shipping of materials needed for preparation of the samples under BSL3 conditions to our collaborators at UW-Madison. As of FY21, this project has been picked up via a sponsor, the Naval Medical Research Center, which will cover the remainder of the proposed scope of work.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Asc-Seurat: analytical single-cell Seurat-based web application

Abstract Background Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of transcriptomes, arising as a powerful tool for discovering and characterizing cell types and their developmental trajectories. However, scRNA-seq analysis is complex, requiring a continuous, iterative process to refine the data and uncover relevant biological information. A diversity of tools has been developed to address the multiple aspects of scRNA-seq data analysis. However, an easy-to-use web application capable of conducting all critical steps of scRNA-seq data analysis is still lacking. Summary We present Asc-Seurat, a feature-rich workbench, providing an user-friendly and easy-to-install web application encapsulating tools for an all-encompassing and fluid scRNA-seq data analysis. Asc-Seurat implements functions from the Seurat package for quality control, clustering, and genes differential expression. In addition, Asc-Seurat provides a pseudotime module containing dozens of models for the trajectory inference and a functional annotation module that allows recovering gene annotation and detecting gene ontology enriched terms. We showcase Asc-Seurat’s capabilities by analyzing a peripheral blood mononuclear cell dataset. Conclusions Asc-Seurat is a comprehensive workbench providing an accessible graphical interface for scRNA-seq analysis by biologists. Asc-Seurat significantly reduces the time and effort required to analyze and interpret the information in scRNA-seq datasets.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Effect of Environmental and Socioeconomic Factors on Increased Early Childhood Blood Lead Levels: A Case Study in Chicago

This study analyzes the prevalence of elevated blood lead levels (BLLs) in children across Chicagoland zip codes from 2019 to 2021, linking them to socioeconomic, environmental, and racial factors. Wilcoxon tests and generalized additive model (GAM) regressions identified economic hardship, reflected in per capita income and unemployment rates, as a significant contributor to increased lead poisoning (LP) rates. Additionally, LP rates correlate with the average age of buildings, particularly post the 1978 lead paint ban, illustrating policy impacts on health outcomes. The study further explores the novel area of land surface temperature (LST) effects on LP, finding that higher nighttime LST, indicative of urban heat island effects, correlates with increased LP. This finding gains additional significance in the context of anthropogenic climate change. When these factors are combined with the ongoing expansion of urban territories, a significant risk exists of escalating LP rates on a global scale. Racial disparity analysis revealed that Black and Hispanic/Latino populations face higher LP rates, primarily due to unemployment and older housing. The study underscores the necessity for targeted public health strategies to address these disparities, emphasizing the need for interventions that cater to the unique challenges of these at-risk communities.

Lee, Jangho (ORCID:0000000289421092)↗
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 OSTI2022

Expanding Structural Space for Immunomodulatory Nucleic Acid Nanoparticles via Spatial Arrangement of Their Therapeutic Moieties

Different therapeutic nucleic acids (TNAs) can be unified in a single structure by their elongation with short oligonucleotides designed to self-assemble into nucleic acid nanoparticles (NANPs). With this approach, therapeutic cocktails with precisely controlled composition and stoichiometry of active ingredients can be delivered to the same diseased cells for enhancing pharmaceutical action. In this study, an additional nanotechnology-based therapeutic option that enlists a biocompatible NANP-encoded platform for their controlled patient-specific immunorecognition is explored. For this, a set of representative functional NANPs is extensively characterized in vitro, ex vivo, and in vivo and then further analyzed for immunostimulation of human peripheral blood mononuclear cells freshly collected from healthy donor volunteers. The results of the study present the advancement of the current TNA approach toward personalized medicine and offer a new strategy to potentially address top public health challenges related to drug overdose and safety through the biodegradable nature of the functional platform with immunostimulatory regulation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Trace metal transfer to passerines inhabiting wastewater treatment wetlands

Wastewater treatment wetlands are cost-effective strategies for remediating trace metals in industrial effluent. However, biogeochemical exchange between wastewater treatment wetlands and adjacent environments provides opportunities for trace metals to cycle in surrounding ecosystems. The transfer of trace metals to wildlife inhabiting treatment wetlands must be considered when evaluating wetland success. Using passerine birds as bioindicators, we conducted a multi-tissue analysis to investigate the mobilization of zinc, copper, and lead derived from wastewater to terrestrial wildlife in treatment wetlands and surrounding habitat. In addition, we evaluate the strength of relationships between metal concentrations in non-lethal (blood and feathers) and lethal (muscle and liver) sample types for estimation of toxicity risk. From July 2020 to August 2021, 177 passerines of seven species were captured at two wetlands constructed to treat industrial wastewater and two reference wetlands in the coastal plain of South Carolina. Feather, blood, liver, and muscle samples from each bird were analyzed for fourteen metals using inductively coupled plasma mass spectrometry and direct mercury analysis. Passerines inhabiting wastewater treatment wetlands accumulated higher concentrations of zinc in liver, copper in blood, and lead in feathers than passerines in reference wetlands, but neither blood nor feather concentrations were correlated with internal tissue concentrations. Of all the detected metals, only mercury in the blood showed a strong predictive relationship with mercury in internal tissues. This study indicates that trace metals derived from wastewater are bioavailable and exported to terrestrial wildlife and that passerine biomonitoring is a valuable tool for assessing metal transfer from treatment wetlands. Furthermore, regular blood sampling can reveal proximate trace metal exposure but cannot predict internal body burdens for most metals.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2022

A Generalizable Evaluated Approach, Applying Advanced Geospatial Statistical Methods, to Identify High Lead Exposure Locations at Census Tract Scale: Michigan Case Study

BACKGROUND: Despite great progress in reducing environmental lead (Pb) levels, many children in the United States are still being exposed. OBJECTIVE: Our aim was to develop a generalizable approach for systematically identifying, verifying, and analyzing locations with high prevalence of children’s elevated blood Pb levels (EBLLs) and to assess available Pb models/indices as surrogates, using a Michigan case study. METHODS: We obtained ~1:9 million BLL test results of children <6 years of age in Michigan from 2006–2016; we then evaluated them for data representativeness by comparing two percentage EBLL (%EBLL) rates (number of children tested with EBLL divided by both number of children tested and total population). We analyzed %EBLLs across census tracts over three time periods and between two EBLL reference values (≥5 vs. ≥10 μg/dL) to evaluate consistency. Locations with high %EBLLs were identified by a top 20 percentile method and a Getis-Ord Gi* geospatial cluster “hotspot” analysis. For the locations identified, we analyzed convergences with three available Pb exposure models/indices based on old housing and sociodemographics. RESULTS: Analyses of 2014–2016 %EBLL data identified 11 Michigan locations via cluster analysis and 80 additional locations via the top 20 percentile method and their associated census tracts. Data representativeness and consistency were supported by a 0.93 correlation coefficient between the two EBLL rates over 11 y, and a Kappa score of ~0:8 of %EBLL hotspots across the time periods (2014–2016) and reference values. Many EBLL hotspot locations converge with current Pb exposure models/indices; others diverge, suggesting additional Pb sources for targeted interventions. DISCUSSION: This analysis confirmed known Pb hotspot locations and revealed new ones at a finer geographic resolution than previously available, using advanced geospatial statistical methods and mapping/visualization. It also assessed the utility of surrogates in the absence of blood Pb data. This approach could be applied to other states to inform Pb mitigation and prevention efforts. https://doi.org/10.1289/EHP9705

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Defining blood hematology reference values in female pig-tailed macaques ( Macaca nemestrina ) using the Isolation Forest algorithm

Background: Pig-tailed macaques (PTMs) are commonly used as preclinical models to assess antiretroviral drugs for HIV prevention research. Drug toxicities and disease pathologies are often preceded by changes in blood hematology. To better assess the safety profile of pharmaceuticals, we defined normal ranges of hematological values in PTMs using an Isolation Forest (iForest) algorithm. Methods: Eighteen female PTMs were evaluated. Blood was collected 1–24 times per animal for a total of 159 samples. Complete blood counts were performed, and iForest was used to analyze the hematology data to detect outliers. Results: Median, IQR, and ranges were calculated for 13 hematology parameters. From all samples, 22 outliers were detected. These outliers were excluded from the reference index. Conclusions: Using iForest, we defined a normal range for hematology parameters in female PTMs. This reference index can be a valuable tool for future studies evaluating drug toxicities in PTMs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Emerging Role of Exosomal Long Non-coding RNAs in Spaceflight-Associated Risks in Astronauts

During spaceflight, astronauts are exposed to multiple unique environmental factors, particularly microgravity and ionizing radiation, that can cause a range of harmful health consequences. Over the past decades, increasing evidence demonstrates that the space environment can induce changes in gene expression and RNA processing. Long non-coding RNA (lncRNA) represent an emerging area of focus in molecular biology as they modulate chromatin structure and function, the transcription of neighboring genes, and affect RNA splicing, stability, and translation. They have been implicated in cancer development and associated with diverse cardiovascular conditions and associated risk factors. However, their role on astronauts’ health after spaceflight remains poorly understood. In this perspective article, we provide new insights into the potential role of exosomal lncRNA after spaceflight. We analyzed the transcriptional profile of exosomes isolated from peripheral blood plasma of three astronauts who flew on various Shuttle missions between 1998–2001 by RNA-sequencing. Computational analysis of the transcriptome of these exosomes identified 27 differentially expressed lncRNAs with a Log 2 fold change, with molecular, cellular, and clinical implications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Assessment of the Utility of the Oral Fluid and Plasma Proteome for Hydrocodone Usage

Non-medical use and abuse of prescription opioids is a growing problem in both the civilian and military communities, with minimal technologies for detecting hydrocodone use. This study explored the proteomic changes that occur in the oral fluid and blood plasma following controlled hydrocodone administration in twenty subjects. The global proteomic profile was determined for samples taken at four time points per subject of pre-exposure and 4, 6, or 168 hours post-exposure. The oral fluid samples analyzed herein provided greater differentiation between “baseline” and “response” time points than was observed with blood plasma, at least partially due to significant person-to-person variability in the plasma proteome. A total of 399 proteins were identified from oral fluid samples, and the abundance of 102 of those proteins was determined to be significantly different upon metabolism of hydrocodone (4 and 6 hour time points) as compared to baseline levels in the oral fluid (pre-dose and 168 hour). This is the first, to our knowledge, assessment of the oral fluid and blood plasma proteome following hydrocodone administration, which demonstrates the potential of oral fluid as a non-invasive sample that may reveal features of hydrocodone or other opioid use and/or misuse.

Kaiser, Brooke LD↗
DOE OSTI2022

Large-Scale Interlaboratory DI-FT-ICR MS Comparability Study Employing Various Systems

We report ultra-high resolution mass spectrometry (UHR-MS) coupled with direct infusion (DI) electrospray ionization offers a fast solution for accurate untargeted profiling. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers have been shown to produce a wealth of insights into complex chemical systems because they enable unambiguous molecular formula assignment even if the vast majority of signals is of unknown identity. Inter-laboratory comparisons are required to apply this type of instrumentation in quality control (for food industry or pharmaceutics), large-scale environmental studies or clinical diagnostics. Extended comparisons employing different FT-ICR MS instruments with qualitative direct infusion analysis are scarce since the majority of detected compounds cannot be quantified. The extent to which observations can be reproduced by different laboratories remains unknown. We set up a preliminary study which encompassed a set of seventeen laboratories around the globe, diverse in instrumental characteristics and applications, to analyze the same sets of extracts from commercially available standard human blood plasma and Standard Reference Material (SRM) for blood plasma (SRM1950), which were delivered at different dilutions or spiked with different concentrations of pesticides. The aim of this study was to assess the extent to which the outputs of differently tuned FTICR mass spectrometers, with different technical specifications, are comparable for setting the frames of a future DI-FT-ICR MS ring trial. We concluded that a cluster of five laboratories, with diverse instrumental characteristics showed comparable and representative performance across all experiments, setting a reference to be used in a future ring trial on blood plasma.

47 OTHER INSTRUMENTATION↗
DOE OSTI2023

One Health Assessment of Bacillus anthracis Incidence and Detection in Anthrax-Endemic Areas of Pakistan

Anthrax, a severe zoonotic disease, is infrequently reported in anthrax-endemic regions of Pakistan. Despite clinical reports indicating its presence, particularly cutaneous anthrax, there is insufficient laboratory evidence regarding disease occurrence and environmental persistence. The present study aimed to confirm Bacillus anthracis presence, accountable for animal mortality and human infection, while exploring environmental transmission factors. Between March 2019 and July 2021, a total of 19 outbreaks were documented. Of these, 11 affected sheep/goats in Zhob district and 8 affected cattle/sheep in Bajour Agency. Clinical signs suggestive of Bacillus anthracis outbreak were observed in 11 animals. Blood and swab samples were collected for confirmation. The study followed a One Health approach, analyzing animal, environmental (soil/plant), and human samples. Of the 19 outbreaks, 11 were confirmed positive for anthrax based on growth characteristics, colony morphology, and PCR. Soil and plant root samples from the outbreak areas were collected and analyzed microscopically and molecularly. Cutaneous anthrax was observed in six humans, and swab samples were taken from the lesions. Human serum samples (n = 156) were tested for IgG antibodies against PA toxin and quantitative analysis of anthrax toxin receptor 1 (ANTXR1). Bacillus anthracis was detected in 65 out of 570 (11.40%) soil samples and 19 out of 190 (10%) plant root samples from the outbreak areas. Four out of six human samples from cutaneous anthrax lesions tested positive for Bacillus anthracis. Human anthrax seroprevalence was found to be 11% and 9% in two districts, with the highest rates among butchers and meat consumers. The highest ANTXR1 levels were observed in butchers, followed by meat consumers, farm employees, meat vendors, veterinarians, and farm owners. These findings highlight the persistence of anthrax in the region and emphasize the potential public health risks.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Interpreting Morphological Adaptations Associated with Viviparity in the Tsetse Fly Glossina morsitans (Westwood) by Three-Dimensional Analysis

Tsetse flies (genus Glossina), the sole vectors of African trypanosomiasis, are distinct from most other insects, due to dramatic morphological and physiological adaptations required to support their unique biology. These adaptations are driven by demands associated with obligate hematophagy and viviparous reproduction. Obligate viviparity entails intrauterine larval development and the provision of maternal nutrients for the developing larvae. The reduced reproductive capacity/rate associated with this biology results in increased inter- and intra-sexual competition. Here, we use phase contrast microcomputed tomography (pcMicroCT) to analyze morphological adaptations associated with viviparous biology. These include (1) modifications facilitating abdominal distention required during blood feeding and pregnancy, (2) abdominal and uterine musculature adaptations for gestation and parturition of developed larvae, (3) reduced ovarian structure and capacity, (4) structural features of the male-derived spermatophore optimizing semen/sperm delivery and inhibition of insemination by competing males and (5) structural features of the milk gland facilitating nutrient incorporation and transfer into the uterus. Three-dimensional analysis of these features provides unprecedented opportunities for examination and discovery of internal morphological features not possible with traditional microscopy techniques and provides new opportunities for comparative morphological analyses over time and between species.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

3,3’-Diindolylmethane Exhibits Significant Metabolism After Oral Dosing in Humans

3,3’-Diindolylmethane (DIM), a major phytochemical derived from ingestion of cruciferous vegetables such as Brussels sprouts, is also a dietary supplement. In preclinical models, DIM is an effective cancer chemopreventive agent and has been studied in a number of clinical trials. Previous pharmacokinetic studies in preclinical and clinical models have not reported DIM metabolites in plasma or urine following oral dosing and the pharmacological actions of DIM on target tissues is assumed to be solely via the parent compound. Seven subjects (6 males and 1 female) ranging from 26-65 years of age, on a cruciferous vegetable-restricted diet prior to and during the study, took 2 BioResponse-DIM® 150 mg capsules (45.3 mg DIM/capsule) in the evening for one week with a final dose the morning of the first blood draw. A complete time course was performed with plasma and urine collected over 48 hours and analyzed by UPLC-MS/MS. In addition to parent DIM, two mono-hydroxylated (2-ox- and 3-methylenehydroxy-DIM) and 1 dihydroxylated (3-methylenehydroxy-2-ox-DIM) metabolites, along with their sulfate and glucuronide conjugates, were present in both plasma and urine. The results reported here are indicative of significant phase 1 and phase 2 metabolism and differ from previous pharmacokinetic studies in rodents and humans which reported only parent DIM present following oral administration.

Vermillion-Maier, Monica↗
DOE OSTI2022

Colorectal Cancer Metastases in the Liver Establish Immunosuppressive Spatial Networking between Tumor-Associated SPP1 + Macrophages and Fibroblasts

Abstract Purpose: The liver is the most frequent metastatic site for colorectal cancer. Its microenvironment is modified to provide a niche that is conducive for colorectal cancer cell growth. This study focused on characterizing the cellular changes in the metastatic colorectal cancer (mCRC) liver tumor microenvironment (TME). Experimental Design: We analyzed a series of microsatellite stable (MSS) mCRCs to the liver, paired normal liver tissue, and peripheral blood mononuclear cells using single-cell RNA sequencing (scRNA-seq). We validated our findings using multiplexed spatial imaging and bulk gene expression with cell deconvolution. Results: We identified TME-specific SPP1-expressing macrophages with altered metabolism features, foam cell characteristics, and increased activity in extracellular matrix (ECM) organization. SPP1+ macrophages and fibroblasts expressed complementary ligand–receptor pairs with the potential to mutually influence their gene-expression programs. TME lacked dysfunctional CD8 T cells and contained regulatory T cells, indicative of immunosuppression. Spatial imaging validated these cell states in the TME. Moreover, TME macrophages and fibroblasts had close spatial proximity, which is a requirement for intercellular communication and networking. In an independent cohort of mCRCs in the liver, we confirmed the presence of SPP1+ macrophages and fibroblasts using gene-expression data. An increased proportion of TME fibroblasts was associated with the worst prognosis in these patients. Conclusions: We demonstrated that mCRC in the liver is characterized by transcriptional alterations of macrophages in the TME. Intercellular networking between macrophages and fibroblasts supports colorectal cancer growth in the immunosuppressed metastatic niche in the liver. These features can be used to target immune-checkpoint–resistant MSS tumors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Large-scale survey of prion protein genetic variability in scrapie disease-free goats from the United States

Scrapie is a slowly progressive neurodegenerative disease of small ruminants caused by an accumulation of an abnormal isoform of prion protein in the central nervous system. Polymorphisms of the prion protein gene (PRNP) strongly modulate scrapie resistance and incubation period in goats. The aim of this study was to identify PRNP genetic variability in goats across the United States. Blood from a total of 6,029 apparent scrapie disease-free goats from 654 operations and 19 breeds were analyzed. Sequencing of PRNP revealed 26 genotypes with different rates based on eight codons. The GG127, RR154, and QQ222 genotypes were predominant and showed a remarkably high rate across all goats. The QK222 and NS146 genotypes, known to be protective against scrapie, were found in 0.6% [with 95% CI = (0.3, 1.2)] and 22.0% [95% CI = (19.1, 25.2)] of goats, respectively. The QK222 genotype was found in 23.1% of Oberhasli goats tested, with 95%CI = (3.9, 68.7)] and 22.0% of Toggenburg goats tested with 95%CI = (9.7, 42.5)], while NS146 was found in 65.5% of Savannah goats tested, with 95%CI = (30.8, 89.9), 36.7% of Boer goats tested, with 95%CI = (33.1, 40.4), 36.3% of Nubian goats tested, with 95%CI = (27.0, 46.7)], and 35.6% of LaMancha goats tested, with 95%CI = (22.8, 50.8%). The MM142 and IM142 genotypes were found more frequently in goats on dairy operations, while the HR143, NS146, and ND146 genotypes were found more frequently in goats on meat operations. Goats in the east region had a higher percentage of goats with RH154, RQ211, and QK222 genotypes than goats in the west region. The results of this study showed high genetic variability of PRNP among the U.S. goat population, with differences by location and breed, and may serve as a rationale for development of goat breeding programs at the national level to mitigate the risk of scrapie.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Temporal serum neurofilament light chain concentrations in sheep inoculated with the agent of classical scrapie

Objective: Neurofilament light chain (Nf-L) has been used to detect neuroaxonal damage in the brain caused by physical injury or disease. The purpose of this study was to determine if serum Nf-L could be used as a biomarker for pre-symptomatic detection of scrapie in sheep. Methods: Four sheep with prion protein genotype AVQQ were intranasally inoculated with the classical scrapie strain x124. Blood was collected every 4 weeks until 44 weeks post-inoculation, at which point weekly collection commenced. Serum was analyzed using single molecule array (Quanterix SR-X) to evaluate Nf-L concentrations. Results: Scrapie was confirmed in each sheep by testing homogenized brainstem at the level of the obex with a commercially available enzyme immunoassay. Increased serum Nf-L concentrations were identified above the determined cutoff during the last tenth of the respective incubation period for each sheep. Throughout the time course study, PrP Sc accumulation was not detected antemortem by immunohistochemistry in rectal tissue at any timepoint for any sheep. RT-QuIC results were inconsistently positive throughout the timepoints tested for each sheep; however, each sheep had at least one timepoint detected positive. When assessing serum Nf-L utility using receiver operator characteristic curves against different clinical parameters, such as asymptomatic and symptomatic (pruritus or neurologic signs), results showed that Nf-L was most useful at being an indicator of disease only late in disease progression when neurologic signs were present. Conclusion: Serum Nf-L concentrations in the cohort of sheep increased as disease progressed; however, serum Nf-L did not increase during the presymptomatic window. The levels increased substantially throughout the final 10% of the animals’ scrapie incubation period when other clinical signs were present. Serum Nf-L is not a reliable biomarker for pre-clinical detection of scrapie.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Wintertime Brine Discharge at the Surface of a Cold Polar Glacier and the Unexpected Absence of Associated Seismicity

A subglacial groundwater system beneath Taylor Glacier, Antarctica, discharges hypersaline, iron-rich brine episodically at the glacier surface to create Blood Falls. However, the triggering mechanism for these brine release events is not yet understood. Identifying which fracture processes are observed seismically can help us better characterize the hydrological system at Taylor Glacier, and more generally, provide us with a broader understanding of englacial hydrologic activity in cold glaciers. We document wintertime brine discharge using time-lapse photography. Subfreezing air temperatures during the brine discharge indicate that surface melt-induced hydrofracture is an unlikely trigger for brine release. Further, we analyze local seismic data to test a hypothesis that fracturing generates elevated surface wave energy preceding and/or coinciding with brine release events. Our results show no discernible elevated Rayleigh wave activity prior to or during Blood Falls brine release. Instead, we find a pattern of seismic events dominated by a seasonal signal, with more Rayleigh events occurring in the summer than the winter from the Blood Falls source area. We calculate that the volumetric opening of cracks that would generate Rayleigh waves at our detection limits are of similar size to myriad cracks in glacier ice, lake ice, and frozen sediment in the terminus area. We therefore propose that any fracturing coincident with brine release activity likely consists of a series of smaller opening events that are masked by other seismicity in the local environment.

58 GEOSCIENCES↗