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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 829 records · Page 46
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Evidence for lack of direct causality between pain and affective disturbances in a rat peripheral neuropathy model

Chronic pain is frequently accompanied by the manifestation of emotional disturbances and cognitive deficits. While a causality relation between pain and emotional/cognitive disturbances is generally assumed, several observations suggest a temporal dissociation and independent mechanisms. We therefore studied Sprague‐Dawley rats that presented a natural resistance to pain manifestation in a neuropathy model (spared nerve injury [SNI]) and compared their performance in a battery of behavioral paradigms—anxiety, depression and fear memory—with animals that presented a pain phenotype. Afterward, we performed an extensive volumetric analysis across prefrontal, orbitofrontal and insular cortical areas. The majority of SNI animals manifested mechanical allodynia (low threshold [LT]), but 13% were similar to Sham controls (high threshold [HT]). Readouts of spontaneous hypersensivity (paw flinches) were also significantly reduced in HT and correlated with allodynia. To increase the specificity of our findings, we segregated the SNI animals in those with left (SNI‐L) and right (SNI‐R) lesions and the lack of association between pain and behavior still remains. Left‐lesioned animals, independent of the LT or HT phenotype, presented increased anxiety‐like behaviors and decreased well‐being. In contrast, we found that the insular cortex (agranular division) was significantly smaller in HT than in LT. To conclude, pain and emotional disturbances observed following nerve injury are to some extent segregated phenomena. Also, HT and LT SNI presented differences in insular volumes, an area vastly implicated in pain perception, suggesting a supraspinal involvement in the manifestation of these phenotypes.

Guimarães, Marco R.↗
DOE OSTI2020

Molecular Dialogues between Early Divergent Fungi and Bacteria in an Antagonism versus a Mutualism

Animals and plants interact with microbes by engaging specific surveillance systems, regulatory networks, and response modules that allow for accommodation of mutualists and defense against antagonists. Antimicrobial defense responses are mediated in both animals and plants by innate immunity systems that owe their functional similarities to convergent evolution. Like animals and plants, fungi interact with bacteria. However, the principles governing these relations are only now being discovered. In a study system of host and nonhost fungi interacting with a bacterium isolated from the host, we found that bacteria used a common gene repertoire to engage both partners. In contrast, fungal responses to bacteria differed dramatically between the host and nonhost. These findings suggest that as in animals and plants, the genetic makeup of the fungus determines whether bacterial partners are perceived as mutualists or antagonists and what specific regulatory networks and response modules are initiated during each encounter.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Plant GATA Factors: Their Biology, Phylogeny, and Phylogenomics

GATA factors are evolutionarily conserved transcription factors that are found in animals, fungi, and plants. Compared to that of animals, the size of the plant GATA family is increased. In angiosperms, four main GATA classes and seven structural subfamilies can be defined. In recent years, knowledge about the biological role and regulation of plant GATAs has substantially improved. Individual family members have been implicated in the regulation of photomorphogenic growth, chlorophyll biosynthesis, chloroplast development, photosynthesis, and stomata formation, as well as root, leaf, and flower development. In this review, we summarize the current knowledge of plant GATA factors. Using phylogenomic analysis, we trace the evolutionary origin of the GATA classes in the green lineage and examine their relationship to animal and fungal GATAs. Lastly, we speculate about a possible conservation of GATA-regulated functions across the animal, fungal, and plant kingdoms.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Doxorubicin-induced cardiotoxicity is suppressed by estrous-staged treatment and exogenous 17β-estradiol in female tumor-bearing spontaneously hypertensive rats

Background: Doxorubicin (DOX), an anthracycline therapeutic, is widely used to treat a variety of cancer types and known to induce cardiomyopathy in a time and dose-dependent manner. Postmenopausal and hypertensive females are two high-risk groups for developing adverse effects following DOX treatment. This may suggest that endogenous reproductive hormones can in part suppress DOX-induced cardiotoxicity. Here, we investigated if the endogenous fluctuations in 17β-estradiol (E2) and progesterone (P4) can in part suppress DOX-induced cardiomyopathy in SST-2 tumor-bearing spontaneously hypersensitive rats (SHRs) and evaluate if exogenous administration of E2 and P4 can suppress DOX-induced cardiotoxicity in tumor-bearing ovariectomized SHRs (ovaSHRs). Methods: Vaginal cytology was performed on all animals to identify the stage of the estrous cycle. Estrous-staged SHRs received a single injection of saline, DOX, dexrazoxane (DRZ), or DOX combined with DRZ. OvaSHRs were implanted with time-releasing pellets that contained a carrier matrix (control), E2, P4, Tamoxifen (Tam), and combinations of E2 with P4 and Tam. Hormone pellet-implanted ovaSHRs received a single injection of saline or DOX. Cardiac troponin I (cTnI), E2, and P4 serum concentrations were measured before and after treatment in all animals. Cardiac damage and function were further assessed by echocardiography and histopathology. Weight, tumor size, and uterine width were measured for all animals. Results: In SHRs, estrous-staged DOX treatment altered acute estrous cycling that ultimately resulted in prolonged diestrus. Twelve days after DOX administration, all SHRs had comparable endogenous circulating E2. Thirteen days after DOX treatment, SHRs treated during proestrus had decreased cardiac output and increased cTnI as compared to animals treated during estrus and diestrus. DOX-induced tumor reduction was not affected by estrous-staged treatments. In ovaSHRs, exogenous administration of E2 suppressed DOX-induced cardiotoxicity, while P4-implanted ovaSHRs were partly resistant. However, ovaSHRs treated with E2 and P4 did not have cardioprotection against DOXinduced damage. Conclusions: This study demonstrates that estrous-staged treatments can alter the extent of cardiac damage caused by DOX in female SHRs. The study also supports that exogenous E2 can suppress DOX-induced myocardial damage in ovaSHRs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Integrating biomechanics in evolutionary studies, with examples from the amphidromous goby model system

The functional capacities of animals are a primary factor determining survival in nature. In this context, understanding the biomechanical performance of animals can provide insight into diverse aspects of their biology, ranging from ecological distributions across habitat gradients to the evolutionary diversification of lineages. To survive and reproduce in the face of environmental pressures, animals must perform a wide range of tasks, some of which entail tradeoffs between competing demands. Moreover, the demands encountered by animals can change through ontogeny as they grow, sexually mature or migrate across environmental gradients. To understand how mechanisms that underlie functional performance contribute to survival and diversification across challenging and variable habitats, we have pursued diverse studies of the comparative biomechanics of amphidromous goby fishes across functional requirements ranging from prey capture and fast-start swimming to adhesion and waterfall climbing. The pan-tropical distribution of these fishes has provided opportunities for repeated testing of evolutionary hypotheses. By synthesizing data from the lab and field, across approaches spanning high-speed kinematics, selection trials, suction pressure recordings, mechanical property testing, muscle fiber-type measurements and physical modeling of bioinspired designs, we have clarified how multiple axes of variation in biomechanical performance associate with the ecological and evolutionary diversity of these fishes. Here our studies of how these fishes meet both common and extreme functional demands add new, complementary perspectives to frameworks developed from other systems, and illustrate how integrating knowledge of the mechanical underpinnings of diverse aspects of performance can give critical insights into ecological and evolutionary questions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts

Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-andmouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a longterm intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008–2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008–2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Structural basis of glycan specificity of P[19] VP8*: Implications for rotavirus zoonosis and evolution

Recognition of specific cell surface glycans, mediated by the VP8* domain of the spike protein VP4, is the essential first step in rotavirus (RV) infection. Due to lack of direct structural information of virus-ligand interactions, the molecular basis of ligand-controlled host ranges of the major human RVs (P[8] and P[4]) in P[II] genogroup remains unknown. Here, through characterization of a minor P[II] RV (P[19]) that can infect both animals (pigs) and humans, we made an important advance to fill this knowledge gap by solving the crystal structures of the P[19] VP8* in complex with its ligands. Our data showed that P[19] RVs use a novel binding site that differs from the known ones of other genotypes/genogroups. This binding site is capable of interacting with two types of glycans, the mucin core and type 1 histo-blood group antigens (HBGAs) with a common GlcNAc as the central binding saccharide. The binding site is apparently shared by other P[II] RVs and possibly two genotypes (P[10] and P[12]) in P[I] as shown by their highly conserved GlcNAc-interacting residues. These data provide strong evidence of evolutionary connections among these human and animal RVs, pointing to a common ancestor in P[I] with a possible animal host origin. While the binding properties to GlcNAc-containing saccharides are maintained, changes in binding to additional residues, such as those in the polymorphic type 1 HBGAs may occur in the course of RV evolution, explaining the complex P[II] genogroup that mainly causes diseases in humans but also in some animals.

Microbiology↗
DOE OSTI2018

Post-Closure Inspection Report for the Tonopah Test Range, Nevada: For Calendar Year 2017, Revision 0

This report provides the results of the annual post-closure inspections conducted at the closed corrective action units (CAUs) located on the Tonopah Test Range (TTR) and the Nevada Test and Training Range (NTTR). This report covers calendar year 2017 and includes visual inspection and repair activities completed at the following CAUs: CAU 400: Bomblet Pit and Five Points Landfill (TTR) CAU 407: Roller Coaster RadSafe Area (TTR) CAU 424: Area 3 Landfill Complexes (TTR) CAU 453: Area 9 UXO Landfill (TTR) CAU 487: Thunderwell Site (TTR) Visual inspections were conducted according to the post-closure plans in the approved closure reports and subsequent correspondence with the Nevada Division of Environmental Protection. The annual post-closure inspections were conducted on May 23, 2017. No maintenance or repair issues were noted at CAU 400 and CAU 487. Maintenance items and subsequent repairs include the following: CAU 407: A large animal burrow was observed in the southeast corner of the cover during the inspection. Two additional animal burrows were discovered during repair actions. All cover defects were repaired on January 9, 2018. CAU 424: CAS 03-08-002-A304 (Landfill Cell A3-4): A new monument was installed and the subsidence area was repaired on January 9, 2018. CAU 424: CAS 03-08-002-A308 (Landfill Cell A3-8): Lava rock, used to mark the two eastern monument locations, was noted as missing during the inspection. The lava rock was replaced on January 9, 2018. CAU 453: Five large animal burrows, located near the east–central portion of cover, was noted during the inspection. Eight additional animal burrows were discovered during repair actions. All cover defects were repaired on January 9, 2018.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

Development of Bio-Compatible Fluorescent Sensor

The development for biocompatible fluorescent sensors is used to understand the movement and fracking of wild boar at SRS. Current fracking methods for wild boar include physical tagging, camera monitoring, and foot tracks in the soil. None of these methods are highly effective in determining the path and habits of the animals as it depends on live imaging, soil consistency (lack of rain), and potentially a gps system is tagged properly. This system allows fracking using an additive digested by the animal and released in the urine that will fluoresce when excited with a particular laser. This method helps determine the actual movements of the animals and even provide a potential prediction model based on their routine. We partnered with Ft. Gordon to utilize their animal testing expertise in determining the best material and pathway for these materials to be excreted.

47 OTHER INSTRUMENTATION↗
DOE OSTI2020

Anthropogenic Markers in Alta Irrigation District Water Supply Wells

In July 2016, LLNL produced a report for the Kings River Watershed Coalition Authority (KRWCA) entitled “Groundwater Age and Nitrate Isotopic Composition in Alta Irrigation District Water Supply Wells” (Esser et al., 2016). That report summarized groundwater age and nitrate isotopic composition data produced by LLNL for Alta Irrigation District (AID) groundwater wells sampled by KRWCA in a pilot project to test the utility of advanced isotopic methods for constraining the timing and source of nitrate in groundwater at selected sites in the Kings River service area. One section of that report made recommendations for follow-on study. The first and strongest recommendation was to measure a wider suite of source tracers including co-contaminants such as herbicides, pesticides, pharmaceuticals, personal care products, and food constituents and additives. KRWCA followed up on this recommendation in Phase II of the pilot study by re-sampling the original set of wells and submitting the samples to a commercial laboratory for analysis of a limited range of co-contaminants (including pharmaceuticals, personal care products , and food constituents and additives, but not including herbicides or pesticides). They have asked that LLNL review and interpret these data in the context of previous LLNL analyses and to evaluate the utility of such co-contaminant analyses in providing additional constraints on the source of groundwater nitrate contamination in Alta Irrigation District water supply wells. The goal of the second phase of this pilot project is to evaluate the utility of co-contaminant occurrence for constraining nitrate source in groundwater at selected sites in the Kings River service area, with special reference to the use of such data in conjunction with advanced isotopic methods such as nitrate isotopic composition and groundwater age. Nitrate isotopic composition alone cannot distinguish nitrate derived from animal manure from nitrate derived from human septic waste. The presence or absence of agricultural chemicals (herbicides, pesticides, veterinary pharmaceuticals) or chemicals associated with people (human pharmaceuticals, artificial sweeteners) can help make this distinction. Co-contaminant analyses using multi-analyte LC-MS-MS protocols are now commercially available and reasonably priced. The feasibility and utility of the using co-contaminants for nitrate source attribution can be evaluated by 1) determining the degree to which co-contaminants occur in distinct and easily attributable groupings (e.g. agricultural chemicals vs personal care products and food additives); 2) determining the degree to which co-contaminant occurrence is consistent with nitrate isotopic composition and groundwater age (e.g. no co-contaminant occurrence in very old groundwater; co-contaminants consistent with animal manure or human septic waste occurring in groundwaters having nitrate isotopic composition also consistent with animal manure or human septic waste); and 3) determining the degree to which co-contaminants provide additional constraint on nitrate source over and beyond nitrate isotopic composition and groundwater age (e.g. distinguishing between animal manure and human septic waste).

58 GEOSCIENCES↗
DOE OSTI2021

Biota Modeling in EPA’s Preliminary Remediation Goal and Dose Compliance Concentration Calculators for Use in EPA Superfund Risk Assessment: Explanation of Intake Rate Derivation, Transfer Factor Compilation, and Mass Loading Factor Sources

The Preliminary Remediation Goal (PRG) and Dose Compliance Concentration (DCC) calculators are screening level risk assessment tools that set forth the Environmental Protection Agency’s (EPA) recommended approaches and currently available risk assessment guidance for response actions at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) sites, commonly known as Superfund. The environmental screening levels derived by the PRG and DCC calculators are used to identify isotopes contributing the highest risk and dose as well as establish preliminary remediation goals. Each calculator has residential gardening and subsistence farmer exposure scenarios that model transfer of contaminants from soil and water into various types of biota (crops and animal products). New publications of human intake rates of biota; farm animal intakes of water, soil, and fodder; and soil to plant interactions require updates be implemented into the PRG and DCC calculators. Recent improvements in the biota modeling for these calculators include newly derived biota intake rates, enhanced soil mass loading factors (MLFs), and more comprehensive soil to plant transfer factors (BV’s) and soil to tissue transfer factors (TFs) for animals. New biota have been added in both the produce and animal products categories that greatly improve the accuracy and utility of the PRG and DCC calculators and encompass greater geographic diversity on a national and international scale.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

2024 OES-Environmental 2024 State of the Science Report, Chapter 9: Beyond Single Marine Renewable Energy Devices: A System-wide Effects Approach

Global expansion of renewable energy, including marine renewable energy (MRE) technology development is necessary to mitigate the effects of climate change, facilitate a sustainable transition from carbon-based energy sources, and satisfy national energy security needs using locally produced electricity (European Commission 2022; IPCC 2023; IRENA 2020). As MRE engineering and research continue to focus on designing devices for deployment in nearshore and offshore waters around the world, researchers are also examining potential environmental effects on marine animals, habitats, and ecosystem processes. To date, the focus has been on interactions between small numbers of MRE devices (1-6) and the environment, such as collisions between animals and turbine blades, the effects of underwater noise and electromagnetic field (EMF) emissions, changes in habitats and oceanographic processes, risk of entanglement of animals, and displacement of animals (Boehlert & Gill 2010; Copping & Hemery 2020) (see Chapter 3).

16 TIDAL AND WAVE POWER↗
DOE OSTI2025

Bioaccumulation Factor for Radium in Rio Grande Biota

The Los Alamos National Laboratory (LANL or Laboratory) Environmental Protection and Compliance Division’s Environmental Stewardship Group (EPC-ES) performs the radiological analysis portion of biota dose assessments using the computer program RESRAD-Biota (DOE 2004, DOE 2020). RESRAD-Biota uses a default bioaccumulation factor, B iv , for radium in aquatic animals. This bioaccumulation factor, also listed in Department of Energy (DOE) Standard, DOE-STD-1153-2019, is the ratio of a radionuclide concentration in fresh weight biota to the environment in which it resides, which for aquatic animals is water. DOE-STD-1153-2019 offers conservative values for these ratios that are specific to the radiological contaminant, the biota, and the environment. The B iv in RESRAD-Biota can be used for general screening (Level 1 screening). If the factor proves to be too conservative, then a site-specific B iv may be used. The biota dose assessment of fish from the northern New Mexico region of the Rio Grande fail the general screen, which indicates that further analysis is necessary. Level 2 analysis is site-specific but still has conservative limitations. Level 3 analysis is a more realistic and representative, sitespecific analysis. The purpose of this paper is to use data specific to the Rio Grande to calculate a new aquatic animal radium B iv . This B iv can then be used for Level 3 analysis of aquatic animals specifically in the northern New Mexico region of the Rio Grande. The calculated radium B iv is a useful value for performing detailed, accurate biota dose assessments and calculating dose to fish using RESRAD-Biota when only sediment data are available.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

A Perspective Around Cephalopods and Their Parasites, and Suggestions on How to Increase Knowledge in the Field

Although interest in several areas of cephalopod research has emerged over the last decades (e.g., neurobiology, aquaculture, genetics, and welfare), especially following their 2010 inclusion in the EU Directive on the use of animals for experimental purposes, knowledge regarding the parasites of cephalopods is lacking. Cephalopods can be intermediate, paratenic, or definitive hosts to a range of parasites with a wide variety of life cycle strategies. Here, we briefly review the current knowledge in cephalopod parasitological research, summarizing the main parasite groups that affect these animals. We also emphasize some topics that, in our view, should be addressed in future research, including: (i) better understanding of life cycles and transmission pathways of common cephalopod parasites; (ii) improve knowledge of all phases of the life cycle (i.e., paralarvae, juveniles, adults and senescent animals) and on species from polar deep sea regions; (iii) exploration of the potential of using cephalopod-parasite specificity to assess population boundaries of both, hosts and parasites; (iv) risk evaluation of the potential of standard aquacultural practices to result in parasite outbreaks; (v) evaluation and description of the physiological and behavioral effects of parasites on their cephalopod hosts; (vi) standardization of the methods for accurate parasite sampling and identification; (vii) implementation of the latest molecular methods to facilitate and enable research in above mentioned areas; (viii) sharing of information and samples among researchers and aquaculturists. In our view, addressing these topics would allow us to better understand complex host-parasite interactions, yield insights into cephalopod life history, and help improve the rearing and welfare of these animals in captivity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

A scoping review of zoonotic parasites and pathogens associated with abattoirs in Eastern Africa and recommendations for abattoirs as disease surveillance sites

Abattoirs are facilities where livestock are slaughtered and are an important aspect in the food production chain. There are several types of abattoirs, which differ in infrastructure and facilities, sanitation and PPE practices, and adherence to regulations. In each abattoir facility, worker exposure to animals and animal products increases their risk of infection from zoonotic pathogens. Backyard abattoirs and slaughter slabs have the highest risk of pathogen transmission because of substandard hygiene practices and minimal infrastructure. These abattoir conditions can often contribute to environmental contamination and may play a significant role in disease outbreaks within communities. To assess further the risk of disease, we conducted a scoping review of parasites and pathogens among livestock and human workers in abattoirs across 13 Eastern African countries, which are hotspots for zoonoses. Our search results (n = 104 articles) showed the presence of bacteria, viruses, fungi, and macroparasites (nematodes, cestodes, etc.) in cattle, goats, sheep, pigs, camels, and poultry. Most articles reported results from cattle, and the most frequent pathogen detected was Mycobacterium bovis, which causes bovine tuberculosis. Some articles included worker survey and questionnaires that suggested how the use of PPE along with proper worker training and safe animal handling practices could reduce disease risk. Based on these findings, we discuss ways to improve abattoir biosafety and increase biosurveillance for disease control and mitigation. Abattoirs are a ‘catch all’ for pathogens, and by surveying animals at abattoirs, health officials can determine which diseases are prevalent in different regions and which pathogens are most likely transmitted from wildlife to livestock. We suggest a regional approach to biosurveillance, which will improve testing and data gathering for enhanced disease risk mapping and forecasting. Next generation sequencing will be key in identifying a wide range of pathogens, rather than a targeted approach.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

A Review of African Swine Fever and the Potential for Introduction into the United States and the Possibility of Subsequent Establishment in Feral Swine and Native Ticks

African swine fever (ASF) is caused by African swine fever virus (ASFV), which can cause substantial morbidity and mortality events in swine. The virus can be transmitted via direct and indirect contacts with infected swine, their products, or competent vector species, especially Ornithodoros ticks. Africa and much of Eastern Europe are endemic for ASF; a viral introduction to countries that are currently ASF free could have severe economic consequences due to the loss of production from infected animals and the trade restrictions that would likely be imposed as a result of an outbreak. We identified vulnerabilities that could lead to ASFV introduction or persistence in the United States or other ASF-free regions. Both legal and illegal movements of live animals, as well as the importation of animal products, byproducts, and animal feed, pose a risk of virus introduction. Each route is described, and current regulations designed to prevent ASFV and other pathogens from entering the United States are outlined. Furthermore, existing ASFV research gaps are highlighted. Laboratory experiments to evaluate multiple species of Ornithodoros ticks that have yet to be characterized would be useful to understand vector competence, host preferences, and distribution of competent soft tick vectors in relation to high pig production areas as well as regions with high feral swine (wild boar or similar) densities. Knowledge relative to antigenic viral proteins that contribute to host response and determination of immune mechanisms that lead to protection are foundational in the quest for a vaccine. Finally, sampling of illegally imported and confiscated wild suid products for ASFV could shed light on the types of products being imported and provide a more informed perspective relative to the risk of ASFV importation.

Veterinary Sciences↗
DOE OSTI2021

ASFV-G-ΔI177L as an Effective Oral Nasal Vaccine against the Eurasia Strain of Africa Swine Fever

The African swine fever virus (ASFV) is currently causing a pandemic affecting wild and domestic swine from Western Europe to Asia. No commercial vaccines are available to prevent African swine fever (ASF), resulting in overwhelming economic losses to the swine industry. We recently developed a recombinant vaccine candidate, ASFVG-ΔI177L, by deleting the I177L gene from the genome of the highly virulent ASFV strain Georgia (ASFV-G). ASFV-G-ΔI177L has been proven safe and highly efficacious in challenge studies using parental ASFV-G. Here, we present data demonstrating that ASFV-G-ΔI177L can be administered by the oronasal (ON) route to achieve a similar efficacy to that of intramuscular (IM) administration. Animals receiving ON ASFV-G-ΔI177L were completely protected against virulent ASFV-G challenge. As previously described, similar results were obtained when ASFV-G-ΔI177L was given intramuscularly. Interestingly, viremias induced in animals inoculated oronasally were lower than those measured in IM-inoculated animals. ASFV-specific antibody responses, mediated by IgG1, IgG2 and IgM, do not differ in animals inoculated by the ON route from that had IM inoculations. Therefore, the ASFV-G-ΔI177L vaccine candidate can be administered oronasally, a critical attribute for potential vaccination of wild swine populations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Modeling Within-Host Dynamics of SARS-CoV-2 Infection: A Case Study in Ferrets

The pre-clinical development of antiviral agents involves experimental trials in animals and ferrets as an animal model for the study of SARS-CoV-2. Here, we used mathematical models and experimental data to characterize the within-host infection dynamics of SARS-CoV-2 in ferrets. We also performed a global sensitivity analysis of model parameters impacting the characteristics of the viral infection. We provide estimates of the viral dynamic parameters in ferrets, such as the infection rate, the virus production rate, the infectious virus proportion, the infected cell death rate, the virus clearance rate, as well as other related characteristics, including the basic reproduction number, pre-peak infectious viral growth rate, post-peak infectious viral decay rate, pre-peak infectious viral doubling time, post-peak infectious virus half-life, and the target cell loss in the respiratory tract. These parameters and indices are not significantly different between animals infected with viral strains isolated from the environment and isolated from human hosts, indicating a potential for transmission from fomites. While the infection period in ferrets is relatively short, the similarity observed between our results and previous results in humans supports that ferrets can be an appropriate animal model for SARS-CoV-2 dynamics-related studies, and our estimates provide helpful information for such studies.

59 BASIC BIOLOGICAL SCIENCES↗