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At least 109 records · Page 6

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NASA NTRS1996

Animal models and their importance to human physiological responses in microgravity

Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.

NASA Discipline Cardiopulmonary↗

DOE OSTI2022

An implantable biomechanical energy harvester for animal monitoring devices

Insufficient service life and the resulting need for battery replacements have been a great challenge for implantable electronic devices. This is particularly true for animal tracking applications, because recapturing animals is often unlikely once they are released to the wild. To tackle this problem, we developed a biomechanical energy harvester that uses a Macro Fiber Composite™ (MFC) piezoelectric beam to harvest the mechanical energy from animals’ body bending movements as the power source for implantable and wearable devices. Prototypes of an underwater acoustic transmitter using this technology were subdermally implanted into juvenile white sturgeon and their energy harvesting performance was evaluated through the device’s transmissions. Additionally, the fish successfully recovered from the implantation surgery and freely swam inside a tank. The transmitter prototypes in the fish continually transmitted signals for a period up to 5 weeks. A benchtop test setup was also created to emulate the fish’s body bending, estimate the device’s energy harvesting performance in the live fish, and perform accelerated fatigue testing of the energy harvester by applying test parameters learned from a video study of the fish’s body movement and behavior characteristics. The gradual depolarization of the piezoelectric ceramic material in the MFC under cyclic mechanical loading was the main limiting factor for the life span of the energy harvester. Pathways for improvement are proposed to achieve long-term efficacy of powering implantable and wearable electronic devices.

42 ENGINEERING↗

DOE OSTI2023

Optimal reference genes for RNA tissue analysis in small animal models of hemorrhagic fever viruses

Abstract Reverse-transcription quantitative polymerase chain reaction assays are frequently used to evaluate gene expression in animal model studies. Data analyses depend on normalization using a suitable reference gene (RG) to minimize effects of variation due to sample collection, sample processing, or experimental set-up. Here, we investigated the suitability of nine potential RGs in laboratory animals commonly used to study viral hemorrhagic fever infection. Using tissues (liver, spleen, gonad [ovary or testis], kidney, heart, lung, eye, brain, and blood) collected from naïve animals and those infected with Crimean–Congo hemorrhagic fever (mice), Nipah (hamsters), or Lassa (guinea pigs) viruses, optimal species-specific RGs were identified based on five web-based algorithms to assess RG stability. Notably, the Ppia RG demonstrated stability across all rodent tissues tested. Optimal RG pairs that include Ppia were determined for each rodent species ( Ppia and Gusb for mice; Ppia and Hrpt for hamsters; and Ppia and Gapdh for guinea pigs). These RG pair assays were multiplexed with viral targets to improve assay turnaround time and economize sample usage. Finally, a pan-rodent Ppia assay capable of detecting Ppia across multiple rodent species was developed and successfully used in ecological investigations of field-caught rodents, further supporting its pan-species utility.

Davies, Katherine A.↗

DOE OSTI2025

A Novel Dosimetry Method for Small Animal Irradiators Using 3D-printed Mouse Phantoms and Alanine Dosimeters

Abstract Accurate dosimetry is a crucial component of small animal and preclinical irradiation studies. Various dosimetry options are available but fail to characterize complex geometries and variable energy spectra of modern x-ray irradiators accurately. These options also lack national/international standards of recognition. This paper presents a novel dosimetry system, Dosequate, which uses murine phantoms embedded with alanine dosimeters and paired with x-ray energy spectra corrections to deliver consistent and accurate dosimetry measurements. This study compares Dosequate measurements against a Precision X-RAD 320 internal ion chamber and the treatment planning system of an Xstrahl Small Animal Radiation Research Platform. Results demonstrate the accuracy and reproducibility of the Dosequate system, highlighting its potential for standardizing dosimetry in preclinical research throughout the industry. Results demonstrate the accuracy and reproducibility of the Dosequate system, highlighting its potential for standardizing dosimetry in preclinical research throughout the industry. The Dosequate dosimetry method provides a robust and standardized approach for measuring absorbed dose in small animal irradiators. Its accuracy, reproducibility, and ability to account for complex irradiation geometries make it a valuable tool for preclinical research. This system has the potential to significantly improve the intercomparability of studies across different facilities and enhance the reliability of results.

Environmental Sciences & Ecology↗

DOE OSTI2024

Comparative analysis of SARS-CoV-2 neutralization titers reveals consistency between human and animal model serum and across assays

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires ongoing monitoring to judge the ability of newly arising variants to escape the immune response. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal serum samples. We compared 18 datasets generated using human, hamster, and mouse serum and six different neutralization assays. Datasets using animal model serum samples showed higher titer magnitudes than datasets using human serum samples in this comparison. Fold change in neutralization of variants compared to ancestral SARS-CoV-2, immunodominance patterns, and antigenic maps were similar among serum samples and assays. Most assays yielded consistent results, except for differences in fold change in cytopathic effect assays. Hamster serum samples were a consistent surrogate for human first-infection serum samples. These results inform the transition of surveillance of SARS-CoV-2 antigenic variation from dependence on human first-infection serum samples to the utilization of serum samples from animal models.

Cell Biology↗

DOE OSTI2023

An accurate and interpretable model for antimicrobial resistance in pathogenic Escherichia coli from livestock and companion animal species

Understanding the microbial genomic contributors to antimicrobial resistance (AMR) is essential for early detection of emerging AMR infections, a pressing global health threat in human and veterinary medicine. Here we used whole genome sequencing and antibiotic susceptibility test data from 980 disease causing Escherichia coli isolated from companion and farm animals to model AMR genotypes and phenotypes for 24 antibiotics. We determined the strength of genotype-to-phenotype relationships for 197 AMR genes with elastic net logistic regression. Model predictors were designed to evaluate different potential modes of AMR genotype translation into resistance phenotypes. Our results show a model that considers the presence of individual AMR genes and total number of AMR genes present from a set of genes known to confer resistance was able to accurately predict isolate resistance on average (mean F 1 score = 98.0%, SD = 2.3%, mean accuracy = 98.2%, SD = 2.7%). However, fitted models sometimes varied for antibiotics in the same class and for the same antibiotic across animal hosts, suggesting heterogeneity in the genetic determinants of AMR resistance. We conclude that an interpretable AMR prediction model can be used to accurately predict resistance phenotypes across multiple host species and reveal testable hypotheses about how the mechanism of resistance may vary across antibiotics within the same class and across animal hosts for the same antibiotic.

Chung, Henri C.↗

DOE OSTI2024

Using low volume eDNA methods to sample pelagic marine animal assemblages

Environmental DNA (eDNA) is an increasingly useful method for detecting pelagic animals in the ocean but typically requires large water volumes to sample diverse assemblages. Ship-based pelagic sampling programs that could implement eDNA methods generally have restrictive water budgets. Studies that quantify how eDNA methods perform on low water volumes in the ocean are limited, especially in deep-sea habitats with low animal biomass and poorly described species assemblages. Using 12S rRNA and COI gene primers, we quantified assemblages comprised of micronekton, coastal forage fishes, and zooplankton from low volume eDNA seawater samples (n = 436, 380–1800 mL) collected at depths of 0–2200 m in the southern California Current. We compared diversity in eDNA samples to concurrently collected pelagic trawl samples (n = 27), detecting a higher diversity of vertebrate and invertebrate groups in the eDNA samples. Differences in assemblage composition could be explained by variability in size-selectivity among methods and DNA primer suitability across taxonomic groups. The number of reads and amplicon sequences variants (ASVs) did not vary substantially among shallow (<200 m) and deep samples (>600 m), but the proportion of invertebrate ASVs that could be assigned a species-level identification decreased with sampling depth. Using hierarchical clustering, we resolved horizontal and vertical variability in marine animal assemblages from samples characterized by a relatively low diversity of ecologically important species. Low volume eDNA samples will quantify greater taxonomic diversity as reference libraries, especially for deep-dwelling invertebrate species, continue to expand.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

A Probabilistic Methodology for Determining Collision Risk of Marine Animals with Tidal Energy Turbines

Commercial development of tidal stream energy is hampered by technical and financial challenges, and impeded by uncertainty about potential environmental effects that drive environmental risk assessments and permitting (consenting) processes. The effect of greatest concern for operational tidal stream energy devices is the potential for marine animals to collide with turbine blades, resulting in injury or death. Due to the turbulent and often turbid waters that frequently characterize tidal turbine sites, there is an absence of empirical evidence about collisions with marine animals. This paucity of observations often leads to risk-averse permitting decisions that further restrict the deployment of tidal energy devices that are needed to collect this evidence. This paper relies on the framework of stressors and receptors that is widely used in marine energy studies and outlines a stepwise probabilistic methodology that applies existing knowledge to further elucidate the risk to marine animals from operational tidal turbines. A case study using striped bass from the Bay of Fundy, Canada, accompanies the methodology, to partially demonstrate its application.

16 TIDAL AND WAVE POWER↗

NASA NTRS1974

Automatic real-time pair-feeding system for animals

A pair feeding method and apparatus are provided for experimental animals wherein the amount of food consumed is immediately delivered to a normal or control animal so that there is a qualitative, quantitative and chronological correctness in the pair feeding of the two animals. This feeding mechanism delivers precisely measured amounts of food to a feeder. Circuitry is provided between master and slave feeders so that there is virtually no chance of a malfunction of the feeding apparatus, causing erratic results. Recording equipment is also provided so that an hourly record is kept of food delivery.

Leon, H. A.↗

NASA NTRS1975

Selection of artificial gravity by animals during suborbital rocket flights

White rats selected preferred artificial gravity levels by locomotion in centrifuges consisting of two runways mounted in the nose of sounding rockets. Roll rate of the Aerobee 150A rocket was designed to produce an angular velocity of 45 rpm during 5 min of free-fall, providing a gravity range from 0.3 to 1.5 G depending on a subject's runway position. One animal was released at the high and one at the low gravity position in each flight. Animal positions were continuously recorded. Locomotion patterns during these flights were similar. All four animals explored the entire available G-range. One rat settled at 0.4 G after 2 min; the others crossed the 1-G location in progressively narrower excursions and were near earth gravity at the end of the test period. Tentatively, the data suggest that normal earth-reared rats select earth gravity when available magnitudes include values above and below 1 G. Modification of gravity preference by prolonged exposure to higher or lower levels remains a possibility.

Lange, K. O.↗

NASA NTRS1976

Animal exposure during burn tests

An animal exposure test system has been designed and fabricated for the purpose of collecting physiological and environmental (temperature) data from animal subjects exposed to combustion gases in large scale fire tests. The AETS consists of an open wire mesh, two-compartment cage, one containing an exercise wheel for small rodents, and the other containing one rat instrumented externally for electrocardiogram and respiration. The ECG and respiration sensors are located in a belt placed around the torso of the subject, electrode wires forming an umbilical to a connector in the top of the compartment. A cable extends from the connector to the power supply and signal conditioning electronics. These are connected to a dual-beam oscilloscope for real time monitoring and a magnetic tape recorder having three or more channels. Endpoints observed are bradycardia, cardiac arrhythmias, changes in respiratory pattern, respiratory arrest and cardiac arrest. The ECG record also appears to be a good method of monitoring animal activity as indicated by an increase in EMG noise superimposed on the record during increased activity of the torso musculature. Examples of the recordings are presented and discussed as to their significance regarding toxicity of fire gases.

Gaume, J. G.↗

NASA NTRS1977

Systems for animal exposure in full-scale fire tests

Two systems for exposing animals in full-scale fire tests are described. Both systems involve the simultaneous exposure of two animal species, mice and rats, in modular units; determination of mortality, morbidity, and behavioral response; and analysis of the blood for carboxyhemoglobin. The systems described represent two of many possible options for obtaining bioassay data from full-scale fire tests. In situations where the temperatures to which the test animals are exposed can not be controlled, analytical techniques may be more appropriate than bioassay techniques.

Hilado, C. J.↗

NASA NTRS1978

Animal Exposure During Burn Tests

An animal exposure test system (AETS) was designed and fabricated for the purpose of collecting physiological and environmental (temperature) data from animal subjects exposed to combustion gases in large scale fire tests. The AETS consisted of an open wire mesh, two-compartment cage, one containing an exercise wheel for small rodents, and the other containing one rat instrumented externally for electrocardiogram (ECG) and respiration. Cage temperature is measured by a thermistor located in the upper portion of the rat compartment. Animal activity is monitored by the ECG and the records indicate an increase in EMG (electromyograph) noise super-imposed by the increased activity of the torso musculature. Examples of the recordings are presented and discussed as to their significance regarding toxicity of fire gases and specific events occurring during the test. The AETS was shown to be a useful tool in screening materials for the relative toxicity of their outgassing products during pyrolysis and combustion.

Gaume, J. G.↗

NASA NTRS1981

Development of an Animal Holding Facility for Space Shuttle studies

The modular Research Animal Holding Facility (RAHF) developed by NASA is described. Besides providing general housing for various animal species, the RAHF is designed to minimize disturbance of the specimens caused by vehicle and mission operations. The RAHF system offers life-sustaining capabilities, such as food, water, and waste removal, as well as environmental control. Modularity of construction to accommodate a variety of small animals and associated instrumentation ensures continued use of RAHF as the sophistication of experiments increases on subsequent missions.

Berry, W. E.↗

NASA NTRS1986

Flutter and Vibration Animation Program

Flutter and Vibration Animation (FLUVIAN) program produces animated picture of structure as it vibrates at constant amplitude. Permits visual observation of fluttering motion of components as they oscillate in combination of modes. Animated display provides insight into local deflection patterns induced in structure, overlooked if modal deflection patterns were separately examined and combined mentally. FLUVIAN program written in FORTRAN 77 for interactive execution.

Tischner, R. L.↗

NASA NTRS1986

Animal studies on Spacelab-3

The flight of two squirrel monkeys and 24 rates on Spacelab-3 was the first mission to provide hand-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity-dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space-adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferon production by spleen cells, defective release of growth hormone by somatotrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythopoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

Schatte, C.↗

NASA NTRS1986

NASA Workshop on Animal Gravity-Sensing Systems

The opportunity for space flight has brought about the need for well-planned research programs that recognize the significance of space flight as a scientific research tool for advancing knowledge of life on Earth, and that utilize each flight opportunity to its fullest. For the first time in history, gravity can be almost completely eliminated. Thus, studies can be undertaken that will help to elucidate the importance of gravity to the normal functioning of living organisms, and to determine the effects microgravity may have on an organism. This workshop was convened to organize a plan for space research on animal gravity-sensing systems and the role that gravity plays in the development and normal functioning of these systems. Scientists working in the field of animal gravity-sensing systems use a wide variety of organisms in their research. The workshop presentations dealt with topics which ranged from the indirect gravity receptor of the water flea, Daphnia (whose antennal setae apparently act as current-sensing receptors as the animal moves up and down in water), through specialized statocyst structures found in jellyfish and gastropods, to the more complex vestibular systems that are characteristic of amphibians, avians, and mammals.

Corcoran, M. L.↗

NASA NTRS1987

Animal studies on Spacelab-3

The flight of two squirrel monkeys and 24 rats on Spacelab-3 was the first mission to provide hands-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferom production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

Schatte, C.↗