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At least 73 records · Page 4

SU-E-T-124: Anthropomorphic Phantoms for Confirmation of Linear Accelerator Based Small Animal Irradiation

Purpose: To document the support of radiobiological small animal research by a modern radiation oncology facility. This study confirms that a standard, human use linear accelerator can cover the range of experiments called for by researchers performing animal irradiation. A number of representative, anthropomorphic murine phantoms were made. The phantoms confirmed the small field photon and electron beams dosimetry validated the use of the linear accelerator for rodents. Methods: Laser scanning a model, CAD design and 3D printing produced the phantoms. The phantoms were weighed and CT scanned to judge their compatibility to real animals. Phantoms were produced to specifically mimic lung, gut, brain, and othotopic lesion irradiations. Each phantom was irradiated with the same protocol as prescribed to the live animals. Delivered dose was measured with small field ion chambers, MOS/FETs or TLDs. Results: The density of the phantom material compared to density range across the real mice showed that the printed material would yield sufficiently accurate measurements when irradiated. The whole body, lung and gut irradiations were measured within 2% of prescribed doses with A1SL ion chamber. MOSFET measurements of electron irradiations for the orthotopic lesions allowed refinement of the measured small field output factor to better than 2% and validated the immunology experiment of irradiating one lesion and sparing another. Conclusion: Linacs are still useful tools in small animal bio-radiation research. This work demonstrated a strong role for the clinical accelerator in small animal research, facilitating standard whole body dosing as well as conformal treatments down to 1cm field. The accuracy of measured dose, was always within 5%. The electron irradiations of the phantom brain and flank tumors needed adjustment; the anthropomorphic phantoms allowed refinement of the initial output factor measurements for these fields which were made in a large block of solid water.

60 APPLIED LIFE SCIENCES↗

WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 of 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work was funded by the Cancer Prevention Research Institute of Texas (CPRIT).

60 APPLIED LIFE SCIENCES↗

Unified many-worlds browsing of arbitrary physics-based animations

Manually tuning physics-based animation parameters to explore a simulation outcome space or achieve desired motion outcomes can be notoriously tedious. This problem has motivated many sophisticated and specialized optimization-based methods for fine-grained (keyframe) control, each of which are typically limited to specific animation phenomena, usually complicated, and, unfortunately, not widely used. In this paper, we propose Unified Many-Worlds Browsing (UMWB), a practical method for sample-level control and exploration of physics-based animations. Our approach supports browsing of large simulation ensembles of arbitrary animation phenomena by using a unified volumetric WORLDPACK representation based on spatiotemporally compressed voxel data associated with geometric occupancy and other low-fidelity animation state. Beyond memory reduction, the WORLDPACK representation also enables unified query support for interactive browsing: it provides fast evaluation of approximate spatiotemporal queries, such as occupancy tests that find ensemble samples ("worlds") where material is either IN or NOT IN a user-specified spacetime region. WORLDPACKS also support real-time hardware-accelerated voxel rendering by exploiting the spatially hierarchical and temporal RLE raster data structure. Our UMWB implementation supports interactive browsing (and offline refinement) of ensembles containing thousands of simulation samples, and fast spatiotemporal queries and ranking. We show UMWB results using a wide variety of physics-based animation phenomena---not just JELL-O ® .

Computer Science↗

Novel reusable animal model for comparative evaluation of in vivo growth and protein-expression of Escherichia coli O157 strains in the bovine rumen

Previously, we had demonstrated that Escherichia coli O157:H7 (O157) strain 86–24 expresses proteins involved in survival rather than virulence in vitro in rumen fluid from dairy cattle limit fed a maintenance diet. Here, we verified if this observation would be true for different O157 strains grown in vitro in rumen fluid from, and in vivo in the rumen of, animals on contrasting maintenance (high fiber) and lactation (high energy-protein) diets usually limit fed to dairy cattle. For the in vivo studies, an economical, novel, reusable and non-terminal rumen-fistulated animal model permitting simultaneous evaluation of multiple bacterial strains in the bovine rumen was developed. All experiments were conducted in duplicate using different animals to account for host-related variations. The O157 strains included, 86–24, EDL933 and the super shed SS-17. E. coli Nal R (#5735), derived from a bovine intestinal commensal E. coli, was included as a control. As expected, diet influenced ruminal pH and volatile fatty acid (VFA) composition. The pH ranged from 6.2–7.0 and total VFA concentrations from 109–141 μM/ml, in animals fed the maintenance diet. In comparison, animals fed the lactation diet had a ruminal pH ranging between 5.18–6.0, and total VFA of 125–219 μM/ml. Strain dependent differences in O157 recovery from the rumen fluid of cattle fed either diet was observed, both in vitro and in vivo, with O157 strains 86–24 and EDL933 demonstrating similar survival patterns. Analysis of the O157 proteomes expressed in the rumen fluid/rumen verified previous observations of adaptive responses. Any difference in the adaptive response was mainly influenced by the animal’s diet and growth conditions (in vitro and in vivo) and not the O157 strain. These new insights into the O157 responses could help formulate modalities to control O157 across strains in cattle at all stages of husbandry.

59 BASIC BIOLOGICAL SCIENCES↗

Dissemination of blaNDM-5 and mcr-8.1 in carbapenem-resistant Klebsiella pneumoniae and Klebsiella quasipneumoniae in an animal breeding area in Eastern China

Animal farms have become one of the most important reservoirs of carbapenem-resistant Klebsiella spp. (CRK) owing to the wide usage of veterinary antibiotics. “One Health”-studies observing animals, the environment, and humans are necessary to understand the dissemination of CRK in animal breeding areas. Based on the concept of “One-Health,” 263 samples of animal feces, wastewater, well water, and human feces from 60 livestock and poultry farms in Shandong province, China were screened for CRK. Five carbapenem-resistant Klebsiella pneumoniae (CRKP) and three carbapenem-resistant Klebsiella quasipneumoniae (CRKQ) strains were isolated from animal feces, human feces, and well water. The eight strains were characterized by antimicrobial susceptibility testing, plasmid conjugation assays, whole-genome sequencing, and bioinformatics analysis. All strains carried the carbapenemase-encoding gene bla NDM-5 , which was flanked by the same core genetic structure (IS 5 - bla NDM-5 - ble MBL - trpF - dsbD -IS 26 -IS Kox3 ) and was located on highly related conjugative IncX3 plasmids. The colistin resistance gene mcr-8.1 was carried by three CRKP and located on self-transmissible IncFII(K)/IncFIA(HI1) and IncFII(pKP91)/IncFIA(HI1) plasmids. The genetic context of mcr-8.1 consisted of IS 903 - orf - mcr-8.1-copR-baeS-dgkA - orf -IS 903 in three strains. Single nucleotide polymorphism (SNP) analysis confirmed the clonal spread of CRKP carrying- bla NDM-5 and mcr-8.1 between two human workers in the same chicken farm. Additionally, the SNP analysis showed clonal expansion of CRKP and CRKQ strains from well water in different farms, and the clonal CRKP was clonally related to isolates from animal farms and a wastewater treatment plant collected in other studies in the same province. These findings suggest that CRKP and CRKQ are capable of disseminating via horizontal gene transfer and clonal expansion and may pose a significant threat to public health unless preventative measures are taken.

Yang, Chengxia↗

Biological Consequences of Marine Energy Development on Marine Animals

Marine energy devices harness power from attributes of ocean water to form a sustainable energy source. Knowledge gaps remain about whether marine energy systems can affect the environment, adding another threat to animal populations and habitats already under pressure from climate change and anthropogenic activities. To date, potential environmental effects have been studied under the scope of stressor–receptor interactions, where moving parts of, or emissions from, a system could harm the animals, habitats, and natural processes. While crucial for understanding effects and identifying knowledge gaps, this approach misses a holistic view of what animals may experience in the presence of marine energy systems. We look at six biological consequences and forces that drive the health of an animal population and the effects expected from marine energy development: success of early life stages; changes in competitive capabilities; growth and survival based on food availability; susceptibility to predators; injury or death; and reproductive success. We use case studies to develop this approach, focusing on a variety of marine animals. An approximate level of risk is assigned for each interaction based on the biological consequences. This work highlights the need to examine the effects of marine energy development on animal populations within their natural habitats.

16 TIDAL AND WAVE POWER↗

The development of a Space Shuttle Research Animal Holding Facility

The ability to maintain the well being of experiment animals is of primary importance to the successful attainment of life sciences flight experiment goals. To assist scientists in the conduct of life sciences flight experiments, a highly versatile Research Animal Holding Facility (RAHF) is being developed for use on Space Shuttle/Spacelab missions. This paper describes the design of the RAHF system, which in addition to providing general housing for various animal species, approximating the environment found in ground based facilities, is designed to minimize disturbances of the specimens by vehicle and mission operations. Life-sustaining capabilities such as metabolic support and environmental control are provided. RAHF is reusable and is a modular concept to accommodate animals of different sizes. The basic RAHF system will accommodate a combination of 24 500-g rats or 144 mice or a mixed number of rats and mice. An alternative design accommodates four squirrel monkeys. The entire RAHF system is housed in a single ESA rack. The animal cages are in drawers which are removable for easy access to the animals. Each cage contains a waste management system, a feeding system and a watering system all of which will operate in zero or one gravity.

Jagow, R. B.↗

Animation of multi-flexible body systems and its use in control system design

Animation can greatly assist the structural dynamicist and control system analyst with better understanding of how multi-flexible body systems behave. For multi-flexible body systems, the structural characteristics (mode frequencies, mode shapes, and damping) change, sometimes dramatically with large angles of rotation between bodies. With computer animation, the analyst can visualize these changes and how the system responds to active control forces and torques. A characterization of the type of system we wish to animate is presented. The lack of clear understanding of the above effects was a key element leading to the development of a multi-flexible body animation software package. The resulting animation software is described in some detail here, followed by its application to the control system analyst. Other applications of this software can be determined on an individual need basis. A number of software products are currently available that make the high-speed rendering of rigid body mechanical system simulation possible. However, such options are not available for use in rendering flexible body mechanical system simulations. The desire for a high-speed flexible body visualization tool led to the development of the Flexible Or Rigid Mechanical System (FORMS) software. This software was developed at the Center for Simulation and Design Optimization of Mechanical Systems at the University of Iowa. FORMS provides interactive high-speed rendering of flexible and/or rigid body mechanical system simulations, and combines geometry and motion information to produce animated output. FORMS is designed to be both portable and flexible, and supports a number of different user interfaces and graphical display devices. Additional features have been added to FORMS that allow special visualization results related to the nature of the flexible body geometric representations.

Juengst, Carl↗

Dynamic Analysis With Stress Mode Animation by the Integrated Force Method

Dynamic animation of stresses and displacements, which complement each other, can be a useful tool in the analysis and design of structural components. At the present time only displacement-mode animation is available through the popular stiffness formulation. This paper attempts to complete this valuable visualization tool by augmenting the existing art with stress mode animation. The reformulated method of forces, which in the literature is known as the integrated force method (IFM), became the analyzer of choice for the development of stress mode animation because stresses are the primary unknowns of its dynamic analysis. Animation of stresses and displacements, which have been developed successfully through the IFM analyzers, is illustrated in several examples along with a brief introduction to IFM dynamic analysis. The usefulness of animation in design optimization is illustrated considering the spacer structure component of the International Space Station as an example. An overview of the integrated force method analysis code (IFM/ANALYZERS) is provided in the appendix.

Patnaik, Surya N.↗

History of the Animal Care Program at Johnson Space Center

NASA has a rich history of scientific research that has been conducted throughout our numerous manned spaceflight programs. This scientific research has included animal test subjects participating in various spaceflight missions, including most recently, Space Shuttle mission STS-131. The Animal Care Program at Johnson Space Center (JSC) in Houston, Texas is multi-faceted and unique in scope compared to other centers within the agency. The animal care program at JSC has evolved from strictly research to include a Longhorn facility and the Houston Zoo's Attwater Prairie Chicken refuge, which is used to help repopulate this endangered species. JSC is home to more than 300 species of animals including home of hundreds of white-tailed deer that roam freely throughout the center which pose unique issues in regards to population control and safety of NASA workers, visitors and tourists. We will give a broad overview of our day to day operations, animal research, community outreach and protection of animals at NASA Johnson Space Center.

Khan-Mayberry, Noreen↗

Vegetation and vantage point influence visibility across diverse ecosystems: Implications for animal ecology

Visual information can influence animal behavior and habitat use in diverse ways. Visibility is the property that relates 3D habitat structure to accessibility of visual information. Despite the importance of visibility in animal ecology, this property remains largely unstudied. Our objective was to assess how habitat structure from diverse environments and animal position within that structure can influence visibility. We gathered terrestrial lidar data (1 cm at 10 m) in four ecosystems (forest, shrub-steppe, prairie, and desert) to characterize viewsheds (i.e., estimates of visibility based on spatially explicit sightlines) from multiple vantage points. Both ecosystem-specific structure and animal position influenced potential viewsheds. Generally, as height of the vantage point above the ground increased, viewshed extent also increased, but the relationships were not linear. In low-structure ecosystems (prairie, shrub-steppe, and desert), variability in viewsheds decreased as vantage points increased to heights above the vegetation canopy. In the forest, however, variation in viewsheds was highest at intermediate heights, and markedly lower at the lowest and highest vantage points. These patterns are likely linked to the amount, heterogeneity, and distribution of vegetation structure occluding sightlines. Our work is the first to apply a new method that can be used to estimate viewshed properties relevant to animals (i.e., viewshed extent and variability). We demonstrate that these properties differ across terrestrial landscapes in complex ways that likely influence many facets of animal ecology and behavior.

Rachel Stein↗

A miniaturized long-life acoustic transmitter for animal tracking in marine environments

Marine and hydrokinetic (MHK) energy devices are early-stage technologies and their impacts to ocean life and environment are largely unknown, which consequently limits the progress of deploying these devices at commercial scale. Optical and acoustic imaging have been the primary technologies for monitoring marine animals’ behavior at existing or potential MHK sites. However, these technologies lack the ability to identify individual animals, which makes them less useful in identifying protected species as well as studying the animals’ long-term behavior. Implantable acoustic transmitters with unique identification codes could be used as a complementary technology. To minimize the tag burden on the tagged animal (and hence the resulting bias) and to satisfy the long-term monitoring needs, it is desired that the implanted transmitter be as small and light as possible and can last for as long as possible. To date, the smallest acoustic transmitters suitable for marine animal tracking have relatively short service life and detection range (up to 200 m). In this report, we introduce a new miniaturized acoustic transmitter which operates at 208.3 kHz. It offers a smaller dry weight (0.45 g), a significantly longer service life (140 days at a 5-second ping rate) as well as a greater detection range than the existing commercial counterparts, which will help obtain more comprehensive movement and behavioral information of animals around MHK energy devices.

Li, Huidong↗

Animal models for osteoporosis

Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.

NASA Discipline Regulatory Physiology↗

RENEWABLE ENERGY AND ENVIRONMENTAL SUSTAINABILITY USING BIOMASS FROM DAIRY AND BEEF ANIMAL PRODUCTION

The Texas Panhandle is regarded as the "Cattle Feeding Capital of the World", producing 42% of the fed beef cattle in the United States within a 200-mile radius of Amarillo generating more than 5 million tons of feedlot manure /year. Apart from feedlots, the Bosque River Region in Erath County, just north of Waco, Texas with about 110,000 dairy cattle in over 250 dairies, produces 1.8 million tons of manure biomass (excreted plus bedding) per year. While the feedlot manure has been used extensively for irrigated and dry land crop production, most dairies, as well as other concentrated animal feeding operations (CAFO's), the dairy farms utilize large lagoon areas to store wet animal biomass. Water runoff from these lagoons has been held responsible for the increased concentration of phosphorus and other contaminates in the Bosque River which drains into Lake Waco—the primary source of potable water for Waco's 108,500 people. The concentrated animal feeding operations may lead to land, water, and air pollution if waste handling systems and storage and treatment structures are not properly managed. Manure-based biomass (MBB) has the potential to be a source of green energy at large coal-fired power plants and on smaller-scale combustion systems at or near confined animal feeding operations. Although MBB particularly cattle biomass (CB) is a low quality fuel with an inferior heat value compared to coal and other fossil fuels, the concentration of it at large animal feeding operations can make it a viable source of fuel. The overall objective of this interdisciplinary proposal is to develop environmentally benign technologies to convert low-value inventories of dairy and beef cattle biomass into renewable energy. Current research expands the suite of technologies by which cattle biomass (CB: manure, and premature mortalities) could serve as a renewable alternative to fossil fuel. The work falls into two broad categories of research and development. Category 1 – Renewable Energy Conversion. This category addressed mostly in volume I involves developing. Thermo-chemical conversion technologies including cofiring with coal, reburn to reduce nitrogen oxide (NO, N2O, NOx, etc.) and Hg emissions and gasification to produce low-BTU gas for on-site power production in order to extract energy from waste streams or renewable resources. Category 2 – Biomass Resource Technology. This category, addressed mostly in Volume II, deals with the efficient and cost-effective use of CB as a renewable energy source (e.g. through and via aqueous-phase, anaerobic digestion or biological gasification). The investigators formed an industrial advisory panel consisting fuel producers (feedlots and dairy farms) and fuel users (utilities), periodically met with them, and presented the research results; apart from serving as dissemination forum, the PIs used their critique to red-direct the research within the scope of the tasks. The final report for the 5 to 7 year project performed by an interdisciplinary team of 9 professors is arranged in three volumes: Vol. I (edited by Kalyan Annamalai) addressing thermo-chemical conversion and direct combustion under Category 1 and Vol. II and Vol. III ( edited by J M Sweeten) addressing biomass resource Technology under Category 2. Various tasks and sub-tasks addressed in Volume I were performed by the Department of Mechanical Engineering (a part of TEES; see Volume I), while other tasks and sub-tasks addressed in Volume II and IIII were conducted by Texas AgriLife Research at Amarillo; the TAMU Biological & Agricultural Engineering Department (BAEN) College Station; and West Texas A&M University (WTAMU) (Volumes II and III). The three volume report covers the following results: fuel properties of low ash and high ash CB (particularly DB) and MB (mortality biomass and coals, non-intrusive visible infrared (NVIR) spectroscopy techniques for ash determination, dairy energy use surveys at 14 dairies in Texas and California, cofiring of low quality CB with high quality coal, emission results and ash fouling behavior, using CB as reburn fuel for NOx and Hg reduction, gasification of fuels to produce low quality gases, modeling of reburn, pilot scale test results, synthesis of engineering characterization, geographical mapping, a transportation cost study to determine potential handling and transportation systems for co-firing with coal at regional coal-fired power plants, software analyses for the design of off-site manure, pre-processing and storage systems for a typical dairy farm or beef cattle feedlot, recursive production functions/systems models for both cattle feedlots, systems modeling, stocks and flows of energy involved in the CAFO system, feedback from an Industry Advisory Committee (IAC) to the investigators on project direction and task emphasis and economics of using CB as cofiring and reburn fuel.

09 BIOMASS FUELS↗

A Frequency-Programmable Miniaturized Radio Frequency Transmitter for Animal Tracking

In animal tracking applications, smaller transmitters can reduce the impact of the transmitter on the tagged animal and thus provide more accurate data about animal behavior. By combining a novel circuit design and a newly developed micro-battery, we developed frequency-programmable and more powerful radio frequency transmitters that are about 40% smaller and lighter in weight than the smallest commercial counterpart for animal monitoring at the time of development. The new radio frequency transmitter has a miniaturized form factor for studying small animals. Designs of two coding schemes were developed: one transmits unmodulated signals (weight: 152 mg; dimensions: Ø 2.95 mm × 11.22 mm), and the other transmits modulated signals (weight: 160 mg; dimensions: Ø 2.95 mm × 11.85 mm). To accommodate different transmitter life requirements, each design can be configured to transmit in high or low signal strength. Prototypes of these transmitters were evaluated in the laboratory and exhibited comparable or longer service life and higher signal strength compared to their smallest commercial counterparts.

47 OTHER INSTRUMENTATION↗

Altered microRNA expression in animal models of Huntington’s disease and potential therapeutic strategies

A review of recent animal models of Huntington’s disease showed many microRNAs had altered expression levels in the striatum and cerebral cortex, and which were mostly downregulated. Among the altered microRNAs were miR-9/9*, miR-29b, miR-124a, miR-132, miR-128, miR-139, miR-122, miR-138, miR-23b, miR-135b, miR-181 (all downregulated) and miR-448 (upregulated), and similar changes had been previously found in Huntington’s disease patients. In the animal cell studies, the altered microRNAs included miR-9, miR-9*, miR-135b, miR-222 (all downregulated) and miR-214 (upregulated). In the animal models, overexpression of miR-155 and miR-196a caused a decrease in mutant huntingtin mRNA and protein level, lowered the mutant huntingtin aggregates in striatum and cortex, and improved performance in behavioral tests. Improved performance in behavioral tests also occurred with overexpression of miR-132 and miR-124. In the animal cell models, overexpression of miR-22 increased the viability of rat primary cortical and striatal neurons infected with mutant huntingtin and decreased huntingtin -enriched foci of ≥ 2 µm. Also, overexpression of miR-22 enhanced the survival of rat primary striatal neurons treated with 3-nitropropionic acid. Exogenous expression of miR-214, miR-146a, miR-150, and miR-125b decreased endogenous expression of huntingtin mRNA and protein in Hdh Q111 /Hdh Q111 cells. Further studies with animal models of Huntington’s disease are warranted to validate these findings and identify specific microRNAs whose overexpression inhibits the production of mutant huntingtin protein and other harmful processes and may provide a more effective means of treating Huntington’s disease in patients and slowing its progression.

59 BASIC BIOLOGICAL SCIENCES↗

MicroRNA expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches

A review of recent animal models of amyotrophic lateral sclerosis showed a large number of miRNAs had altered levels of expression in the brain and spinal cord, motor neurons of spinal cord and brainstem, and hypoglossal, facial, and red motor nuclei and were mostly upregulated. Among the miRNAs found to be upregulated in two of the studies were miR-21, miR-155, miR-125b, miR-146a, miR-124, miR-9, and miR-19b, while those downregulated in two of the studies included miR-146a, miR-29, miR-9, and miR-125b. A change of direction in miRNA expression occurred in some tissues when compared (e.g., miR-29b-3p in cerebellum and spinal cord of wobbler mice at 40 days), or at different disease stages (e.g., miR-200a in spinal cord of SOD1(G93A) mice at 95 days vs. 108 and 112 days). In the animal models, suppression of miR-129-5p resulted in increased lifespan, improved muscle strength, reduced neuromuscular junction degeneration, and tended to improve motor neuron survival in the SOD1(G93A) mouse model. Suppression of miR-155 was also associated with increased lifespan, while lowering of miR-29a tended to improve lifespan in males and increase muscle strength in SOD1(G93A) mice. Overexpression of members of miR-17~92 cluster improved motor neuron survival in SOD1(G93A) mice. Treatment with an artificial miRNA designed to target hSOD1 increased lifespan and improved muscle strength in SOD1(G93A) animals. Further studies with animal models of amyotrophic lateral sclerosis are warranted to validate these findings and identify specific miRNAs whose suppression or directed against hSOD1 results in increased lifespan, improved muscle strength, reduced neuromuscular junction degeneration, and improved motor neuron survival in SOD1(G93A) animals.

59 BASIC BIOLOGICAL SCIENCES↗

Evaluation of Rodent Spaceflight in the NASA Animal Enclosure Module for an Extended Operational Period (up to 35 days)

The National Aeronautics and Space Administration Animal Enclosure Module (AEM) was developed as a self-contained rodent habitat for shuttle flight missions that provides inhabitants with living space, food, water, ventilation, and lighting for shuttle flight missions, and this study reports whether, after minimal hardware modification, the AEM could support an extended term up to 35 days for Sprague-Dawley rats and C57BL/6 female mice for use on the International Space Station. Success was evaluated based on comparison of AEM housed animals to that of vivarium housed and to normal biological ranges through various measures of animal health and well-being, including animal health evaluations, animal growth and body masses, organ masses, rodent food bar consumption, water consumption, and analysis of blood contents. The results of this study confirmed that the AEMs could support 12 adult female C57BL/6 mice for up to 35 days with self-contained RFB and water, and the AEMs could also support 5 adult male Sprague-Dawley rats for 35 days with external replenishment of diet and water. This study has demonstrated the capability and flexibility of the AEM to operate for up to 35 days with minor hardware modification. Therefore, with modifications, it is possible to utilize this hardware on the International Space Station or other operational platforms to extend the space life science research use of mice and rats.

Animal enclosure module↗