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All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Lassa Virus Replicon Particle Vaccine Protects Strain 13/N Guinea Pigs Against Challenge With Geographically and Genetically Diverse Viral Strains

Abstract Lassa virus (LASV) causes mild to severe hemorrhagic fever disease in humans. Strain 13/N guinea pigs are highly susceptible to infection with LASV strain Josiah (clade IV), providing a critical model system for therapeutics and vaccine development. To develop additional models of disease, we detail the clinical course in guinea pigs infected with 5 geographically and genetically diverse LASV strains. Two of the developed models (LASV clades II and III) were then used to evaluate efficacy of a virus replicon particle vaccine against heterologous LASV challenge, demonstrating complete protection against clinical disease after a single vaccination dose.

Immunology↗
NASA NTRS2010

Global Estimates of Average Ground-Level Fine Particulate Matter Concentrations from Satellite-Based Aerosol Optical Depth

Exposure to airborne particles can cause acute or chronic respiratory disease and can exacerbate heart disease, some cancers, and other conditions in susceptible populations. Ground stations that monitor fine particulate matter in the air (smaller than 2.5 microns, called PM2.5) are positioned primarily to observe severe pollution events in areas of high population density; coverage is very limited, even in developed countries, and is not well designed to capture long-term, lower-level exposure that is increasingly linked to chronic health effects. In many parts of the developing world, air quality observation is absent entirely. Instruments aboard NASA Earth Observing System satellites, such as the MODerate resolution Imaging Spectroradiometer (MODIS) and the Multi-angle Imaging SpectroRadiometer (MISR), monitor aerosols from space, providing once daily and about once-weekly coverage, respectively. However, these data are only rarely used for health applications, in part because the can retrieve the amount of aerosols only summed over the entire atmospheric column, rather than focusing just on the near-surface component, in the airspace humans actually breathe. In addition, air quality monitoring often includes detailed analysis of particle chemical composition, impossible from space. In this paper, near-surface aerosol concentrations are derived globally from the total-column aerosol amounts retrieved by MODIS and MISR. Here a computer aerosol simulation is used to determine how much of the satellite-retrieved total column aerosol amount is near the surface. The five-year average (2001-2006) global near-surface aerosol concentration shows that World Health Organization Air Quality standards are exceeded over parts of central and eastern Asia for nearly half the year.

Van Donkelaar, A.↗
DOE OSTI2023

Differential contagiousness of respiratory disease across the United States

The initial contagiousness of a communicable disease within a given population is quantified by the basic reproduction number, $R_0$. This number depends on both pathogen and population properties. On the basis of compartmental models that reproduce Coronavirus Disease 2019 (COVID-19) surveillance data, we used Bayesian inference and the next-generation matrix approach to estimate region-specific $R_0$ values for 280 of 384 metropolitan statistical areas (MSAs) in the United States (US), which account for 95% of the US population living in urban areas and 82% of the total population. We focused on MSA populations after finding that these populations were more uniformly impacted by COVID-19 than state populations. Our maximum a posteriori (MAP) estimates for $R_0$ range from 1.9 to 7.7 and quantify the relative susceptibilities of regional populations to spread of respiratory diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Copper Reductase Activity and Free Radical Chemistry by Cataract-Associated Human Lens γ-Crystallins

Cataracts are caused by high-molecular weight aggregates of human eye lens proteins that scatter light, causing lens opacity. Metal ions have emerged as important potential players in the etiology of cataract disease, as human lens γ-crystallins are susceptible to metal-induced aggregation. Here, the interaction of Cu 2+ ions with γD-, γC-, and γS- crystallins, the three most abundant γ-crystallins in the lens, has been evaluated. Cu 2+ ions induced non-amyloid aggregation in all three proteins. Solution turbidimetry, SDS-PAGE, circular dichroism and differential scanning calorimetry showed that the mechanism for Cu-induced aggregation involves: i) loss of beta-sheet structure in the N-terminal domain; ii) decreased thermal and kinetic stability; iii) formation of metal-bridged species; and iv) formation of disulfide-bridged dimers. Electron paramagnetic resonance (EPR) revealed two distinct Cu 2+ binding sites in each protein. Spin quantitation demonstrated reduction of γ-crystallin-bound Cu 2+ ions to Cu + under aerobic conditions, while X-ray absorption spectroscopy (XAS) confirmed the presence of linear or trigonal Cu + binding sites in γ-crystallins. Our EPR and XAS studies revealed that γ-crystallins’ Cu 2+ reductase activity yields a protein-based free radical that is likely a Tyr-based species in human γD-crystallin. This unique free radical chemistry carried out by distinct redox-active Cu sites in human lens γ-crystallins likely contributes to the mechanism of copper-induced aggregation. Finally, in the context of an aging human lens, γ-crystallins could be acting, not only as structural proteins, but also as key players for metal and redox homeostasis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Escalation in the host-pathogen arms race: A host resistance response corresponds to a heightened bacterial virulence response

The zig-zag model of host-pathogen interaction describes the relative strength of defense response across a spectrum of pathogen-induced plant phenotypes. A stronger defense response results in increased resistance. Here, we investigate the strength of pathogen virulence during disease and place these findings in the context of the zig-zag model. Xanthomonas vasicola pv. holcicola ( Xvh ) causes sorghum bacterial leaf streak. Despite being widespread, this disease has not been described in detail at the molecular level. We divided diverse sorghum genotypes into three groups based on disease symptoms: water-soaked lesions, red lesions, and resistance. Bacterial growth assays confirmed that these three phenotypes represent a range of resistance and susceptibility. To simultaneously reveal defense and virulence responses across the spectrum of disease phenotypes, we performed dual RNA-seq on Xvh -infected sorghum. Consistent with the zig-zag model, the expression of plant defense-related genes was strongest in the resistance interaction. Surprisingly, bacterial virulence genes related to the type III secretion system (T3SS) and type III effectors (T3Es) were also most highly expressed in the resistance interaction. This expression pattern was observed at multiple time points within the sorghum- Xvh pathosystem. Further, a similar expression pattern was observed in Arabidopsis infected with Pseudomonas syringae for effector-triggered immunity via AvrRps4 but not AvrRpt2. Specific metabolites were able to repress the Xvh virulence response in vitro and in planta suggesting a possible signaling mechanism. Taken together, these findings reveal multiple permutations of the continually evolving host-pathogen arms race from the perspective of host defense and pathogen virulence responses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Contrasting transcriptional responses to Fusarium virguliforme colonization in symptomatic and asymptomatic hosts

The broad host range of Fusarium virguliforme represents a unique comparative system to identify and define differentially induced responses between an asymptomatic monocot host, maize (Zea mays), and a symptomatic eudicot host, soybean (Glycine max). Using a temporal, comparative transcriptome-based approach, we observed that early gene expression profiles of root tissue from infected maize suggest that pathogen tolerance coincides with the rapid induction of senescence dampening transcriptional regulators, including ANACs (Arabidopsis thaliana NAM/ATAF/CUC protein) and Ethylene-Responsive Factors. In contrast, the expression of senescence-associated processes in soybean was coincident with the appearance of disease symptom development, suggesting pathogen-induced senescence as a key pathway driving pathogen susceptibility in soybean. Based on the analyses described herein, we posit that root senescence is a primary contributing factor underlying colonization and disease progression in symptomatic versus asymptomatic host–fungal interactions. This process also supports the lifestyle and virulence of F. virguliforme during biotrophy to necrotrophy transitions. Further support for this hypothesis lies in comprehensive co-expression and comparative transcriptome analyses, and in total, supports the emerging concept of necrotrophy-activated senescence. We propose that F. virguliforme conditions an environment within symptomatic hosts, which favors susceptibility through transcriptomic reprogramming, and as described herein, the induction of pathways associated with senescence during the necrotrophic stage of fungal development.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS2023

Automated Fluidics Device for Extraction and Quantification of miRNA Biomarkers From Blood

Radiation Assessment DuRing Exposure And long-Duration Spaceflight (RADREADS) demonstrates space-compatible point-of-care technology for quantitative biological monitoring of blood miRNA biomarkers in response to long-term low dose radiation exposure. This individualized monitoring approach will inform targeted treatment strategies to maximize medical resource utilization by accounting for individual susceptibility to radiation-related illnesses. As human spaceflight progresses beyond Earth’s magnetic shielding, radiation exposure poses a significant risk to astronaut health and safety. Extended operation in this environment comes with an increased risk of radiation exposure, leading to higher risks of radiation sickness, cancer, central nervous system effects, and degenerative diseases. While conventional physical dosimetry techniques capture radiation dose, individualistic susceptibility to radiation damage is varied. Multiple characteristics, including age, body weight, sex, genetics, and immune status, have been found to influence radiosensitivity (Liu et al. 2011, and Bouffler 2016). This differential response necessitates individualized monitoring and targeted treatment strategies to maximize medical resource utilization; however, a practical diagnostic platform for quantifying long-term, low dose radiation-induced tissue damage does not currently exist. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that regulate gene expression by mediating the degradation of messenger RNA. The levels of particular miRNAs are influenced by biological processes such as inflammation and serve as biomarkers for a variety of conditions including cancer (Singh et al. 2017). MicroRNAs are found in various bodily fluids and are amenable to collection via liquid biopsies, providing a minimally invasive and easily quantifiable readout for a variety of radiosensitive reporters. A preliminary signature of 15 spaceflight sensitive miRNA has been identified in rodent and human studies, including miR-21-5p, miR-24-3p, miR-92a-3p, miR-17-5p, miR-16a-3p, miR-34a-3p, and miR-223-3p. These targets generally increased expression with radiation dose and linear energy transfer, though variation between individuals is not yet described. Current gaps in the field include a lack of understanding of longitudinal biological responses to long-term, low dose radiation exposure and the absence of space-compatible point-of-care technology for quantitative biological monitoring. In this body of work, we aim to develop an automated bleed-to-read system to process whole blood for the detection of miRNA biomarkers in order to monitor individualistic responses to radiation exposure. This will be achieved via separating serum (or plasma) from whole blood, followed by extraction, amplification, and quantification of the miRNA using a RT-qPCR reaction. Previously, the WetLab-2 hardware enabled execution of a RT-qPCR reaction aboard ISS; however, it is a manual system that requires crew manipulation and bulky components (Parra et al. 2017). To address these issues, automated fluid handling hardware was developed for each stage of sample preparation. Extraction of total RNA is achieved by sequentially pumping reagents through an off-the-shelf nucleic acid binding column (miRNeasy Serum/Plasma Advanced Kit, Qiagen). This approach eliminates several manual pipetting and centrifuging steps and limits the use of toxic chemicals commonly found in other sample processing techniques. The resulting elution will then be automatically dispensed for RT-qPCR analysis using a compact rotary qPCR (Mic qPCR Cycler, Bio Molecular Systems) that will improve spaceflight compatibility by removing bubbles from the detection region, another challenge highlighted by WetLab-2 (Parra et al. 2017). Efforts are also being made to simplify the RT-qPCR reaction to a 1-step air-dryable mix to improve long-term reagent stability at room temperature and reduce system complexity. By automating the RT-qPCR processes via microfluidic manipulation, RADREADS will reduce crewmember hands-on time and enable the personalized detection of radiation-induced tissue damage during long duration missions. Minimally invasive, longitudinal monitoring of individual’s response to radiation exposure will inform how the physiological system responds to long-term low dose space radiation and enables development of targeted countermeasures by the medical team. Ultimately, this portable technology will require minimal technical expertise and can also be used to monitor miRNA biomarkers associated with other diseases.

Tristen Head↗
DOE OSTI2020

Autoclave treatment of the classical scrapie agent US No. 13-7 and experimental inoculation to susceptible VRQ/ARQ sheep via the oral route results in decreased transmission efficiency

Scrapie, a prion disease of sheep, is highly resistant to conventional deactivation. Numerous methods to deactivate scrapie have been tested in laboratory animal models, and adequate autoclave treatment can reduce or remove the infectivity of some classical scrapie strains depending on the heating parameters used. In this study, we autoclaved brain homogenate from a sheep with US scrapie strain 13–7 for 30 minutes at 121°C. Genetically susceptible VRQ/ARQ sheep were orally inoculated with 3 grams of the autoclaved brain homogenate. For comparison, a second group of sheep was inoculated with a non-autoclaved brain homogenate. Rectal biopsies were used to assess antemortem scrapie disease progression throughout the study. Five out of ten (5/10) sheep that received autoclaved inoculum ultimately developed scrapie after an experimental endpoint of 72 months. These sheep had a mean incubation period of 26.99 months. Two out of five (2/5) positive sheep had detectable PrP Sc in antemortem rectal biopsies, and two (2/5) other sheep had PrP Sc in postmortem rectal tissue. A single sheep (1/5) was positive for scrapie in the CNS, small intestine, and retropharyngeal lymph node but had negative rectal tissue. All of the sheep (10/10) that received non-autoclaved inoculum developed scrapie with a mean incubation period of 20.2 months and had positive rectal biopsies at the earliest timepoint (14.7 months post-inoculation). These results demonstrate that sheep are orally susceptible to US derived classical scrapie strain 13–7 after autoclave treatment at 121°C for 30 minutes. Differences in incubation periods and time interval to first positive rectal biopsies indicate a partial reduction in infectivity titers for the autoclaved inoculum group.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Transcriptomic and functional analyses uncover a conserved effector driving genotype-dependent virulence in the Sphaerulina musiva-Populus trichocarpa interaction

The introduction of invasive microbes compromises the structure, biodiversity, and function of naïve ecosystems. Sphaerulina musiva, a hemibiotrophic pathogen that causes leaf spot and stem cankers in Populus species, exemplifies an invasive fungal pathogen spread by human activities. However, the genetic mechanisms of pathogenicity and virulence are poorly understood, impeding mitigation strategies. We utilized RNA sequencing to identify fungal effectors linked to stem canker formation, informing the development of future strategies for effective disease management. Our analysis revealed 70 genes differentially expressed at 2 weeks and 110 genes at 3 weeks between inoculated trees and controls. Notably, the gene with the highest expression at 2 weeks and the second highest at 3 weeks was homologous to Extracellular protein 2 (Ecp2). Complementary genome-wide association studies linked sequence polymorphisms in this locus to phenotypic variation in disease severity. Infiltration of S. musiva Ecp2 into Populus trichocarpa leaves induced necrosis in susceptible genotypes. Gene disruption using a CRISPR-Cas9 RNP system resulted in a genotype-dependent reduction of stem canker and disease severity. Tracing the evolutionary history of this effector across the fungal kingdom, we uncovered clade-specific gene-family expansions and orthologs in new species. These findings raise questions about the function and adaptive significance of these gene families in fungal lifestyles. Our study provides the first tractable target for breeding resistant poplar genotypes, addressing the challenges of managing S. musiva and uncovering mechanisms that drive its virulence, and provides deeper insights into the evolutionary dynamics of a conserved small-secreted protein with a diversity of functions.

Sondreli, Kelsey L [Oregon State University]↗
DOE OSTI2022

Characterization of Classical Sheep Scrapie in White-tailed Deer after Experimental Oronasal Exposure

Abstract Background Classic scrapie is a prion disease of sheep and goats that is associated with accumulation of abnormal prion protein (PrPSc) in the central nervous and lymphoid tissues. Chronic wasting disease (CWD) is the prion disease of cervids. This study was conducted to determine the susceptibility of white-tailed deer (WTD) to the classic scrapie agent. Methods We inoculated WTD (n = 5) by means of a concurrent oral/intranasal exposure with the classic scrapie agent from sheep or oronasally with the classic scrapie agent from goats (n = 6). Results All deer exposed to the agent of classic scrapie from sheep accumulated PrPSc. PrPSc was detected in lymphoid tissues at preclinical time points, and necropsies in deer 28 months after inoculation showed clinical signs, spongiform lesions, and widespread PrPSc in neural and lymphoid tissues. Western blots on samples from the brainstem, cerebellum, and lymph nodes of scrapie-infected WTD have a molecular profile similar to CWD and distinct from samples from the cerebral cortex, retina, or the original classic scrapie inoculum. There was no evidence of PrPSc in any of the WTD inoculated with classic scrapie prions from goats. Conclusions WTD are susceptible to the agent of classic scrapie from sheep, and differentiation from CWD may be difficult.

Immunology↗
DOE OSTI2023

Micro–Global Positioning Systems for Identifying Nightly Opportunities for Marburg Virus Spillover to Humans by Egyptian Rousette Bats

Marburg virus disease, caused by Marburg and Ravn orthomarburgviruses, emerges sporadically in sub-Saharan Africa and is often fatal in humans. The natural reservoir is the Egyptian rousette bat (ERB), which sheds virus in saliva, urine, and feces. Frugivorous ERBs discard test-bitten and partially eaten fruit, potentially leaving infectious virus behind that could be consumed by other susceptible animals or humans. Historically, 8 of 17 known Marburg virus disease outbreaks have been linked to human encroachment on ERB habitats, but no linkage exists for the other 9 outbreaks, raising the question of how bats and humans might intersect, leading to virus spillover. We used micro–global positioning systems to identify nightly ERB foraging locations. ERBs from a known Marburg virus–infected population traveled long distances to feed in cultivated fruit trees near homes. Our results show that ERB foraging behavior represents a Marburg virus spillover risk to humans and plausibly explains the origins of some past outbreaks.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

The relatively young and rural population may limit the spread and severity of COVID-19 in Africa: a modelling study

A novel coronavirus disease 2019 (COVID-19) has spread to all regions of the world. There is great uncertainty regarding how countries’ characteristics will affect the spread of the epidemic; to date, there are few studies that attempt to predict the spread of the epidemic in African countries. In this paper, we investigate the role of demographic patterns, urbanisation and comorbidities on the possible trajectories of COVID-19 in Ghana, Kenya and Senegal. We use an augmented deterministic Susceptible-Infected-Recovered model to predict the true spread of the disease, under the containment measures taken so far. We disaggregate the infected compartment into asymptomatic, mildly symptomatic and severely symptomatic to match observed clinical development of COVID-19. We also account for age structures, urbanisation and comorbidities (HIV, tuberculosis, anaemia). In our baseline model, we project that the peak of active cases will occur in July, subject to the effectiveness of policy measures. When accounting for the urbanisation, and factoring in comorbidities, the peak may occur between 2 June and 17 June (Ghana), 22 July and 29 August (Kenya) and, finally, 28 May and 15 June (Senegal). Successful containment policies could lead to lower rates of severe infections. While most cases will be mild, we project in the absence of policies further containing the spread, that between 0.78% and 1.03%, 0.61% and 1.22%, and 0.60% and 0.84% of individuals in Ghana, Kenya and Senegal, respectively, may develop severe symptoms at the time of the peak of the epidemic. Compared with Europe, Africa’s younger and rural population may modify the severity of the epidemic. The large youth population may lead to more infections but most of these infections will be asymptomatic or mild, and will probably go undetected. The higher prevalence of underlying conditions must be considered.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Evaluation of Cross-Protection of African Swine Fever Vaccine ASFV-G-ΔI177L Between ASFV Biotypes

Background/Objectives: Vaccine development for the prevention of ASF has been very challenging due to the extensive genetic and largely unknown antigenic diversity. Inactivated vaccines, using different inactivation methods and a variety of adjuvants, have been consistently inefficacious. Historically, animals recovering from an infection with an attenuated virus became protected from the development of a clinical disease caused by an antigenically related strain. Therefore, immunization of susceptible animals with attenuathe ted virus strains has become a common method of vaccination with the first two commercially available vaccines based on recombinant live-attenuated viruses (LAVs). An important limitation is that the efficacy of the LAV is restricted to those strains that are antigenically related and, in most cases, only provide protection against homologous strains. Due to the unknown antigenic heterogeneity among all ASFV field isolates, the development of broad-spectrum vaccines is a challenge. Besides the anecdotal data, there is not a large amount of information describing patterns of cross-protection between different ASFV strains. Methods: We evaluated the cross-protection induced by the ASFV live-attenuated vaccine ASFV-G-ΔI177L against different biotypes of ASFV and compared their genomic sequences to determine potential genetic mutations that could cause the lack of cross-protection. Results: Results presented here demonstrate different patterns of protection when ASFV-G-ΔI177L vaccinated pigs were challenged with six different ASFV field isolates belonging to different biotypes. Conclusions: The presence of cross-protection cannot be predicted solely by the classical methodology for genotyping-based B646L ORF only. Biotyping, considering the entire virus proteome, appears to be a more promising prediction tool, although additional gathering of experimental data will be necessary to fully validate it; until then, the presence of cross-protection needs to be confirmed in efficacy trials challenging vaccinated animals.

Immunology↗
DOE OSTI2020

Xylella fastidiosa causes transcriptional shifts that precede tylose formation and starch depletion in xylem

Abstract Pierce's disease (PD) in grapevine ( Vitis vinifera ) is caused by the bacterial pathogen Xylella fastidiosa . X. fastidiosa is limited to the xylem tissue and following infection induces extensive plant‐derived xylem blockages, primarily in the form of tyloses. Tylose‐mediated vessel occlusions are a hallmark of PD, particularly in susceptible V. vinifera . We temporally monitored tylose development over the course of the disease to link symptom severity to the level of tylose occlusion and the presence/absence of the bacterial pathogen at fine‐scale resolution. The majority of vessels containing tyloses were devoid of bacterial cells, indicating that direct, localized perception of X. fastidiosa was not a primary cause of tylose formation. In addition, we used X‐ray computed microtomography and machine‐learning to determine that X. fastidiosa induces significant starch depletion in xylem ray parenchyma cells. This suggests that a signalling mechanism emanating from the vessels colonized by bacteria enables a systemic response to X. fastidiosa infection. To understand the transcriptional changes underlying these phenotypes, we integrated global transcriptomics into the phenotypes we tracked over the disease spectrum. Differential gene expression analysis revealed that considerable transcriptomic reprogramming occurred during early PD before symptom appearance. Specifically, we determined that many genes associated with tylose formation (ethylene signalling and cell wall biogenesis) and drought stress were up‐regulated during both Phase I and Phase II of PD. On the contrary, several genes related to photosynthesis and carbon fixation were down‐regulated during both phases. These responses correlate with significant starch depletion observed in ray cells and tylose synthesis in vessels.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2012

Abiotic Versus Biotic Pathogens: Replicative Growth in Host Tissues Key to Discriminating Between Biotoxic Injury and Active Pathogenesis

Life can be defined as a self-sustaining chemical system capable of undergoing Darwinian evolution; a self-bounded, self-replicating, and self-perpetuating entity [1]. This definition should hold for terrestrial as well as extraterrestrial life-forms. Although, it is reasonable to expect that a Mars life-form would be more adaptable to Mars-like conditions than to Earth-like environments, it remains possible that negative ecological or host interactions might occur if Mars microbiota were to be inadvertently released into the terrestrial environment. A biogenic infectious agent can be defined as a self-sustaining chemical system capable of undergoing Darwinian evolution and derives its sustenance from a living cell or from the by-products of cell death. Disease can be de-fined as the detrimental alteration of one or more ordered metabolic processes in a living host caused by the continued irritation of a primary causal factor or factors; disease is a dynamic process [2]. In contrast, an injury is due to an instantaneous event; injury is not a dynamic process [2]. A causal agent of disease is defined as a pathogen, and can be either abiotic or biotic in nature. Diseases incited by biotic pathogens are the exceptions, not the norms, in terrestrial host-microbe interactions. Disease induction in a plant host can be conceptually characterized using the Disease Triangle (Fig. 1) in which disease occurs only when all host, pathogen, and environ-mental factors that contribute to the development of disease are within conducive ranges for a necessary minimum period of time. For example, plant infection and disease caused by the wheat leaf rust fungus, Puccinia recondita, occur only if virulent spores adhere to genetically susceptible host tissues for at least 4-6 hours under favorable conditions of temperature and moisture [3]. As long as one or more conditions required for disease initiation are not available, disease symptoms will not develop.

Schuerger, Andrew C.↗
NASA NTRS1999

Biomarkers of exposure, sensitivity and disease

PURPOSE: This review is to evaluate the use of biomarkers as an indication of past exposure to radiation or other environmental insults, individual sensitivity and risk for the development of late occurring disease. OVERVIEW: Biomarkers can be subdivided depending on their applications. Markers of exposure and dose can be used to reconstruct and predict past accidental or occupational exposures when limited or no physical measurements were available. Markers of risk or susceptibility can help identify sensitivity individuals that are at increased risk for development of spontaneous disease and may help predict the increased risk in sensitive individuals associated with environmental or therapeutic radiation exposures. Markers of disease represent the initial cellular or molecular changes that occur during disease development. Each of these types of biomarkers serves a unique purpose. OUTLINE: This paper concentrates on biomarkers of dose and exposure and provides a brief review of biomarkers of sensitivity and disease. The review of biomarkers of dose and exposure will demonstrate the usefulness of biomarkers in evaluation of physical factors associated with radiation exposure, such as LET, doserate and dose distribution. It will also evaluate the use of biomarkers to establish relationships that exist between exposure parameters such as energy deposition, environmental concentration of radioactive materials, alpha traversals and dose. In addition, the importance of biological factors on the magnitude of the biomarker response will be reviewed. Some of the factors evaluated will be the influence of species, tissue, cell types and genetic background. The review will demonstrate that markers of sensitivity and disease often have little usefulness in dose-reconstruction and, by the same token, many markers of dose or exposure may not be applicable for prediction of sensitivity or risk.

Non-NASA Center↗
DOE OSTI2024

Emergency department visits in California associated with wildfire PM 2.5 : differing risk across individuals and communities

The threats to human health from wildfires and wildfire smoke (WFS) in the United States (US) are increasing due to continued climate change. A growing body of literature has documented important adverse health effects of WFS exposure, but there is insufficient evidence regarding how risk related to WFS exposure varies across individual or community level characteristics. To address this evidence gap, we utilized a large nationwide database of healthcare utilization claims for emergency department (ED) visits in California across multiple wildfire seasons (May through November, 2012–2019) and quantified the health impacts of fine particulate matter <2.5 μm (PM 2.5 ) air pollution attributable to WFS, overall and among subgroups of the population. We aggregated daily counts of ED visits to the level of the Zip Code Tabulation Area (ZCTA) and used a time-stratified case-crossover design and distributed lag non-linear models to estimate the association between WFS and relative risk of ED visits. We further assessed how the association with WFS varied across subgroups defined by age, race, social vulnerability, and residential air conditioning (AC) prevalence. Over a 7 day period, PM 2.5 from WFS was associated with elevated risk of ED visits for all causes (1.04% (0.32%, 1.71%)), non-accidental causes (2.93% (2.16%, 3.70%)), and respiratory disease (15.17% (12.86%, 17.52%)), but not with ED visits for cardiovascular diseases (1.06% (–1.88%, 4.08%)). Analysis across subgroups revealed potential differences in susceptibility by age, race, and AC prevalence, but not across subgroups defined by ZCTA-level Social Vulnerability Index scores. These results suggest that PM 2.5 from WFS is associated with higher rates of all cause, non-accidental, and respiratory ED visits with important heterogeneity across certain subgroups. Notably, lower availability of residential AC was associated with higher health risks related to wildfire activity.

54 ENVIRONMENTAL SCIENCES↗