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NASA NTRS2001

Physical and biological studies with protons and HZE particles in a NASA supported research center in radiation health

NASA has established and supports a specialized center for research and training (NSCORT) to specifically address the potential deleterious effects of HZE particles on human health. The NSCORT in radiation health is a joint effort between Lawrence Berkeley National Laboratory (LBNL) and Colorado State University (CSU). The overall scope of research encompasses a broad range of subjects from microdosimetric studies to cellular and tissue responses to initial damage produced by highly energetic protons and heavy charged particles of the type found in galactic cosmic rays (GCR) spectrum. The objectives of the microdosimetry studies are to determine the response of Tissue Equivalent Proportional Counter (TEPC) to cosmic rays using ground based accelerators. This includes evaluation of energy loss due to the escape of high-energy delta rays and increased energy deposition due to the enhanced delta ray production in the wall of the detector. In this report major results are presented for 56Fe at 1000, 740, 600 and 400 MeV/nucleon. An assessment of DNA repair and early development of related chromosomal changes is extremely important to our overall understanding of enhanced biological effectiveness of high LET particle radiation. Results are presented with respect to the fidelity of the rejoining of double strand breaks and the implications of misrejoining. The relationship between molecular and cytogenetic measurements is presented by studying damage processing in highly heterochromatic supernumerary (correction of sypernumerary) X chromosomes and the active X-chromosome. One of the important consequences of cell's inability to handle DNA damage can be evaluated through mutation studies. Part of our goal is the assessment of potential radioprotectors to reduce the mutation yield following HZE exposures, and some promising results are presented on one compound. A second goal is the integration of DNA repair and mutation studies. Results are presented on a direct comparison of initial double strand breaks induction, the time course and fidelity of double strand break rejoining, cell killing and mutation induction in the same human model system. In order to understand the carcinogenic potential of protons and HZE particles, the role of damaged microenvironment in this process must be understood. In this project it has been postulated that radiation affects the microenvironment, which then modifies cell interactions in a manner conducive to neoplastic progression. Both TGF-beta and FGF-2 are important components of microenvironment. A recent result on the assessment of the role of FGF-2 and its cross-talk with TGF-beta as a function of radiation quality is presented. Theoretical modeling has so far played a central role in analyzing and integrating experimental data on repair and mutation studies and predicting new phenomena. The integrated NSCORT program also provides a broad training experience for students and postdoctoral fellows in space radiation health.

NASA Discipline Radiation Health↗

NASA NTRS2005

Human Adaptation Genetic Response Suites: Toward New Interventions and Countermeasures for Spaceflight

Genetic response suites in human lymphocytes in response to microgravity are important to identify and further study in order to augment human physiological adaptation to novel environments. Emerging technologies, such as DNA micro array profiling, have the potential to identify novel genes that are involved in mediating adaptation to these environments. These genes may prove to be therapeutically valuable as new targets for countermeasures, or as predictive biomarkers of response to these new environments. Human lymphocytes cultured in lg and microgravity analog culture were analyzed for their differential gene expression response. Different groups of genes related to the immune response, cardiovascular system and stress response were then analyzed. Analysis of cells from multiple donors reveals a small shared set that are likely to be essential to adaptation. These three groups focus on human adaptation to new environments. The shared set contains genes related to T cell activation, immune response and stress response to analog microgravity.

Sundaresan, A.↗

NASA NTRS2010

Multivariate Methods for Prediction of Geologic Sample Composition with Laser-Induced Breakdown Spectroscopy

Laser-induced breakdown spectroscopy (LIBS) uses pulses of laser light to ablate a material from the surface of a sample and produce an expanding plasma. The optical emission from the plasma produces a spectrum which can be used to classify target materials and estimate their composition. The ChemCam instrument on the Mars Science Laboratory (MSL) mission will use LIBS to rapidly analyze targets remotely, allowing more resource- and time-intensive in-situ analyses to be reserved for targets of particular interest. ChemCam will also be used to analyze samples that are not reachable by the rover's in-situ instruments. Due to these tactical and scientific roles, it is important that ChemCam-derived sample compositions are as accurate as possible. We have compared the results of partial least squares (PLS), multilayer perceptron (MLP) artificial neural networks (ANNs), and cascade correlation (CC) ANNs to determine which technique yields better estimates of quantitative element abundances in rock and mineral samples. The number of hidden nodes in the MLP ANNs was optimized using a genetic algorithm. The influence of two data preprocessing techniques were also investigated: genetic algorithm feature selection and averaging the spectra for each training sample prior to training the PLS and ANN algorithms. We used a ChemCam-like laboratory stand-off LIBS system to collect spectra of 30 pressed powder geostandards and a diverse suite of 196 geologic slab samples of known bulk composition. We tested the performance of PLS and ANNs on a subset of these samples, choosing to focus on silicate rocks and minerals with a loss on ignition of less than 2 percent. This resulted in a set of 22 pressed powder geostandards and 80 geologic samples. Four of the geostandards were used as a validation set and 18 were used as the training set for the algorithms. We found that PLS typically resulted in the lowest average absolute error in its predictions, but that the optimized MLP ANN and the CC ANN often gave results comparable to PLS. Averaging the spectra for each training sample and/or using feature selection to choose a small subset of wavelengths to use for predictions gave mixed results, with degraded performance in some cases and similar or slightly improved performance in other cases. However, training time was significantly reduced for both PLS and ANN methods by implementing feature selection, making this a potentially appealing method for initial, rapid-turn-around analyses necessary for Chemcam's tactical role on MSL. Choice of training samples has a strong influence on the accuracy of predictions. We are currently investigating the use of clustering algorithms (e.g. k-means, neural gas, etc.) to identify training sets that are spectrally similar to the unknown samples that are being predicted, and therefore result in improved predictions

Morris, Richard↗

NASA NTRS2018

Development and Application of a Tool for Optimizing Composite Matrix Viscoplastic Material Parameters

This document describes a recently developed analysis tool that enhances the resident capabilities of the Micromechanics Analysis Code with the Generalized Method of Cells (MAC/GMC) and its application. MAC/GMC is a composite material and laminate analysis software package developed at NASA Glenn Research Center. The primary focus of the current effort is to provide a graphical user interface (GUI) capability that helps users optimize highly nonlinear viscoplastic constitutive law parameters by fitting experimentally observed/measured stress-strain responses under various thermo-mechanical conditions for braided composites. The tool has been developed utilizing the MATrix LABoratory (MATLAB) (The Mathworks, Inc., Natick, MA) programming language. Illustrative examples shown are for a specific braided composite system wherein the matrix viscoplastic behavior is represented by a constitutive law described by seven parameters. The tool is general enough to fit any number of experimentally observed stress-strain responses of the material. The number of parameters to be optimized, as well as the importance given to each stress-strain response, are user choice. Three different optimization algorithms are included: (1) Optimization based on gradient method, (2) Genetic algorithm (GA) based optimization and (3) Particle Swarm Optimization (PSO). The user can mix and match the three algorithms. For example, one can start optimization with either 2 or 3 and then use the optimized solution to further fine tune with approach 1. The secondary focus of this paper is to demonstrate the application of this tool to optimize/calibrate parameters for a nonlinear viscoplastic matrix to predict stress-strain curves (for constituent and composite levels) at different rates, temperatures and/or loading conditions utilizing the Generalized Method of Cells. After preliminary validation of the tool through comparison with experimental results, a detailed virtual parametric study is presented wherein the combined effects of temperature and loading rate on the predicted response of a braided composite is investigated.

thermo-mechanical; MATLAB; GUI-Based Too↗

NASA NTRS2013

Progress Towards an Interdisciplinary Science of Plant Phenology: Building Predictions Across Space, Time and Species Diversity

Climate change has brought renewed interest in the study of plant phenology - the timing of life history events. Data on shifting phenologies with warming have accumulated rapidly, yet research has been comparatively slow to explain the diversity of phenological responses observed across latitudes, growing seasons and species. Here, we outline recent efforts to synthesize perspectives on plant phenology across the fields of ecology, climate science and evolution. We highlight three major axes that vary among these disciplines: relative focus on abiotic versus biotic drivers of phenology, on plastic versus genetic drivers of intraspecific variation, and on cross-species versus autecological approaches. Recent interdisciplinary efforts, building on data covering diverse species and climate space, have found a greater role of temperature in controlling phenology at higher latitudes and for early-flowering species in temperate systems. These efforts have also made progress in understanding the tremendous diversity of responses across species by incorporating evolutionary relatedness, and linking phenological flexibility to invasions and plant performance. Future research with a focus on data collection in areas outside the temperate mid-latitudes and across species' ranges, alongside better integration of how risk and investment shape plant phenology, offers promise for further progress.

phenology↗

NASA NTRS2005

Tow-Steered Panels With Holes Subjected to Compression or Shear Loads

Tailoring composite laminates to vary the fiber orientations within a fiber layer of a laminate to address non-uniform stress states and provide structural advantages such as the alteration of principal load paths has potential application to future low-cost, light-weight structures for commercial transport aircraft. Evaluation of this approach requires the determination of the effectiveness of stiffness tailoring through the use of curvilinear fiber paths in flat panels including the reduction of stress concentrations around the holes and the increase in load carrying capability. Panels were designed through the use of an optimization code using a genetic algorithm and fabricated using a tow-steering approach. Manufacturing limitations, such as the radius of curvature of tows the machine could support, avoidance of wrinkling of fibers and minimization of gaps between fibers were considered in the design process. Variable stiffness tow-steered panels constructed with curvilinear fiber paths were fabricated so that the design methodology could be verified through experimentation. Finite element analysis where each element s stacking sequence was accurately defined is used to verify the behavior predicted based on the design code. Experiments on variable stiffness flat panels with central circular holes were conducted with the panels loaded in axial compression or shear. Tape and tow-steered panels are used to demonstrate the buckling, post-buckling and failure behavior of elastically tailored panels. The experimental results presented establish the buckling performance improvements attainable by elastic tailoring of composite laminates.

Jegley, Dawn C.↗

NASA NTRS2011

Markov Chain Monte Carlo Bayesian Learning for Neural Networks

Conventional training methods for neural networks involve starting al a random location in the solution space of the network weights, navigating an error hyper surface to reach a minimum, and sometime stochastic based techniques (e.g., genetic algorithms) to avoid entrapment in a local minimum. It is further typically necessary to preprocess the data (e.g., normalization) to keep the training algorithm on course. Conversely, Bayesian based learning is an epistemological approach concerned with formally updating the plausibility of competing candidate hypotheses thereby obtaining a posterior distribution for the network weights conditioned on the available data and a prior distribution. In this paper, we developed a powerful methodology for estimating the full residual uncertainty in network weights and therefore network predictions by using a modified Jeffery's prior combined with a Metropolis Markov Chain Monte Carlo method.

Goodrich, Michael S.↗

NASA NTRS2003

Adaptation of SUBSTOR for controlled-environment potato production with elevated carbon dioxide

The SUBSTOR crop growth model was adapted for controlled-environment hydroponic production of potato (Solanum tuberosum L. cv. Norland) under elevated atmospheric carbon dioxide concentration. Adaptations included adjustment of input files to account for cultural differences between the field and controlled environments, calibration of genetic coefficients, and adjustment of crop parameters including radiation use efficiency. Source code modifications were also performed to account for the absorption of light reflected from the surface below the crop canopy, an increased leaf senescence rate, a carbon (mass) balance to the model, and to modify the response of crop growth rate to elevated atmospheric carbon dioxide concentration. Adaptations were primarily based on growth and phenological data obtained from growth chamber experiments at Rutgers University (New Brunswick, N.J.) and from the modeling literature. Modified-SUBSTOR predictions were compared with data from Kennedy Space Center's Biomass Production Chamber for verification. Results show that, with further development, modified-SUBSTOR will be a useful tool for analysis and optimization of potato growth in controlled environments.

NASA Discipline Life Support Systems↗

NASA NTRS1997

Equally parsimonious pathways through an RNA sequence space are not equally likely

An experimental system for determining the potential ability of sequences resembling 5S ribosomal RNA (rRNA) to perform as functional 5S rRNAs in vivo in the Escherichia coli cellular environment was devised previously. Presumably, the only 5S rRNA sequences that would have been fixed by ancestral populations are ones that were functionally valid, and hence the actual historical paths taken through RNA sequence space during 5S rRNA evolution would have most likely utilized valid sequences. Herein, we examine the potential validity of all sequence intermediates along alternative equally parsimonious trajectories through RNA sequence space which connect two pairs of sequences that had previously been shown to behave as valid 5S rRNAs in E. coli. The first trajectory requires a total of four changes. The 14 sequence intermediates provide 24 apparently equally parsimonious paths by which the transition could occur. The second trajectory involves three changes, six intermediate sequences, and six potentially equally parsimonious paths. In total, only eight of the 20 sequence intermediates were found to be clearly invalid. As a consequence of the position of these invalid intermediates in the sequence space, seven of the 30 possible paths consisted of exclusively valid sequences. In several cases, the apparent validity/invalidity of the intermediate sequences could not be anticipated on the basis of current knowledge of the 5S rRNA structure. This suggests that the interdependencies in RNA sequence space may be more complex than currently appreciated. If ancestral sequences predicted by parsimony are to be regarded as actual historical sequences, then the present results would suggest that they should also satisfy a validity requirement and that, in at least limited cases, this conjecture can be tested experimentally.

NASA Discipline Exobiology↗

NASA NTRS2016

Characterization of Aircraft Structural Damage Using Guided Wave Based Finite Element Analysis for In-Flight Structural Health Management

The development of multidisciplinary Integrated Vehicle Health Management (IVHM) tools will enable accurate detection, diagnosis and prognosis of damage under normal and adverse conditions during flight. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and structural damage conditions. A major concern is the growth of undetected damage/cracks due to fatigue and low velocity foreign object impact that can reach a critical size during flight, resulting in loss of control of the aircraft. To avoid unstable catastrophic propagation of damage during a flight, load levels must be maintained that are below the load-carrying capacity for damaged aircraft structures. Hence, a capability is needed for accurate real-time predictions of safe load carrying capacity for aircraft structures with complex damage configurations. In the present work, a procedure is developed that uses guided wave responses to interrogate damage. As the guided wave interacts with damage, the signal attenuates in some directions and reflects in others. This results in a difference in signal magnitude as well as phase shifts between signal responses for damaged and undamaged structures. Accurate estimation of damage size and location is made by evaluating the cumulative signal responses at various pre-selected sensor locations using a genetic algorithm (GA) based optimization procedure. The damage size and location is obtained by minimizing the difference between the reference responses and the responses obtained by wave propagation finite element analysis of different representative cracks, geometries and sizes.

Seshadri, Banavara R.↗

NASA NTRS1997

W Photoprotection in Tropical Marine Organisms

Increasing levels of ultraviolet (UV) radiation reaching the earth's surface which results from stratospheric ozone depletions could have serious implications for terrestrial plants and for aquatic organisms within the euphotic zone. A documented 9% decline in ozone at mid-latitudes is considered to produce a 12% increase in harmful UV radiation. The biologically damaging effects of higher UV levels, particularly W-B (280-320 rim), could manifest earlier in the tropics because of the relative thinness of the earth's equatorial ozone layer. Tropical marine organisms are also living close to their upper tolerance levels of water temperature, However, despite the large potential effects on plants and animals, little is known about UV effects on tropical ecosystems. Long-term ecological studies are needed to quantify the effects of increased UV radiation on terrestrial and marine ecosystems and to produce reliable data for prediction. Plants have developed several mechanisms to protect themselves from harmful UV radiation, one of which is the production of secondary leaf pigments that absorb W-B radiation (screening pigments). A higher concentration of screening pigments (e.g. flavonoids) in leaves may be interpreted as a natural response to increased W radiation. If higher concentrations of flavonoids filter out the excessive W radiation, no damage will occur, as suggested by Caldwell et al. (1989) and Tevini (1993). Failure to screen all W-B may result in deleterious effects on photosynthesis, plant genetic material, and plant and leaf morphology and growth. Eventually this will have an impact on ecosystem processes, structure, species composition, and productivity. This paper describes an ongoing project that is assessing the responses of mangroves, seagrasses and corals to W radiation by studying pigment concentrations, biophysical parameters, and variations in spectral reflectance in the field and in W-reduction experiments. Preliminary results on the distribution of W-absorbing flavonoid compounds in red mangroves (Rhizophora mangle) and the seagrass Thalassia testudinum, are presented. This research also provides, for the first time, a permanent record of daily W irradiance measurements at a tropical -location.

Armstrong, Roy A.↗

NASA NTRS2007

NASA Strategy to Safely Live and Work in the Space Radiation Environment

In space, astronauts are constantly bombarded with energetic particles. The goal of the National Aeronautics and Space Agency and the NASA Space Radiation Project is to ensure that astronauts can safely live and work in the space radiation environment. The space radiation environment poses both acute and chronic risks to crew health and safety, but unlike some other aspects of space travel, space radiation exposure has clinically relevant implications for the lifetime of the crew. Among the identified radiation risks are cancer, acute and late CNS damage, chronic and degenerative tissue decease, and acute radiation syndrome. The term "safely" means that risks are sufficiently understood such that acceptable limits on mission, post-mission and multi-mission consequences can be defined. The NASA Space Radiation Project strategy has several elements. The first element is to use a peer-reviewed research program to increase our mechanistic knowledge and genetic capabilities to develop tools for individual risk projection, thereby reducing our dependency on epidemiological data and population-based risk assessment. The second element is to use the NASA Space Radiation Laboratory to provide a ground-based facility to study the health effects/mechanisms of damage from space radiation exposure and the development and validation of biological models of risk, as well as methods for extrapolation to human risk. The third element is a risk modeling effort that integrates the results from research efforts into models of human risk to reduce uncertainties in predicting the identified radiation risks. To understand the biological basis for risk, we must also understand the physical aspects of the crew environment. Thus, the fourth element develops computer algorithms to predict radiation transport properties, evaluate integrated shielding technologies and provide design optimization recommendations for the design of human space systems. Understanding the risks and determining methods to mitigate the risks are keys to a successful radiation protection strategy.

Cucinotta, Francis A.↗

NASA NTRS2017

Structural Health Management of Damaged Aircraft Structures Using the Digital Twin Concept

The development of multidisciplinary integrated Structural Health Management (SHM) tools will enable accurate detection, and prognosis of damaged aircraft under normal and adverse conditions during flight. As part of the digital twin concept, methodologies are developed by using integrated multiphysics models, sensor information and input data from an in-service vehicle to mirror and predict the life of its corresponding physical twin. SHM tools are necessary for both damage diagnostics and prognostics for continued safe operation of damaged aircraft structures. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and structural damage conditions. A major concern in these structures is the growth of undetected damage/cracks due to fatigue and low velocity foreign object impact that can reach a critical size during flight, resulting in loss of control of the aircraft. To avoid unstable, catastrophic propagation of damage during a flight, load levels must be maintained that are below a reduced load-carrying capacity for continued safe operation of an aircraft. Hence, a capability is needed for accurate real-time predictions of damage size and safe load carrying capacity for structures with complex damage configurations. In the present work, a procedure is developed that uses guided wave responses to interrogate damage. As the guided wave interacts with damage, the signal attenuates in some directions and reflects in others. This results in a difference in signal magnitude as well as phase shifts between signal responses for damaged and undamaged structures. Accurate estimation of damage size, location, and orientation is made by evaluating the cumulative signal responses at various pre-selected sensor locations using a genetic algorithm (GA) based optimization procedure. The damage size, location, and orientation is obtained by minimizing the difference between the reference responses and the responses obtained by wave propagation finite element analysis of different representative cracks, geometries, and sizes.

Seshadri, Banavara R.↗

NASA NTRS1999

A Quantitative Study of Oxygen as a Metabolic Regulator

An acute reduction in oxygen (O2) delivery to a tissue is generally associated with a decrease in phosphocreatine, increases in ADP, NADH/NAD, and inorganic phosphate, increased rates of glycolysis and lactate production, and reduced rates of pyruvate and fatty acid oxidation. However, given the complexity of the human bioenergetic system and its components, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in tissue O2 availability affect the pathways of ATP synthesis and the metabolites that control these pathways. In this study, we extend a previously developed mathematical model of human bioenergetics to provide a physicochemical framework that permits quantitative understanding of O2 as a metabolic regulator. Specifically, the enhancement permits studying the effects of variations in tissue oxygenation and in parameters controlling the rate of cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The whole body is described as a bioenergetic system consisting of metabolically distinct tissue/organ subsystems that exchange materials with the blood. In order to study the dynamic response of each subsystem to stimuli, we solve the ordinary differential equations describing the temporal evolution of metabolite levels, given the initial concentrations. The solver used in the present study is the packaged code LSODE, as implemented in the NASA Lewis kinetics and sensitivity analysis code, LSENS. A major advantage of LSENS is the efficient procedures supporting systematic sensitivity analysis, which provides the basic methods for studying parameter sensitivities (i.e., changes in model behavior due to parameter variation). Sensitivity analysis establishes relationships between model predictions and problem parameters (i.e., initial concentrations, rate coefficients, etc). It helps determine the effects of uncertainties or changes in these input parameters on the predictions, which ultimately are compared with experimental observations in order to validate the model. Sensitivity analysis can identify parameters that must be determined accurately because of their large effect on the model predictions and parameters that need not be known with great precision because they have little or no effect on the solution. This capability may prove to be important in optimizing the design of experiments, thereby reducing the use of animals. This approach can be applied to study the metabolic effects of reduced oxygen delivery to cardiac muscle due to local myocardial ischemia and the effects of acute hypoxia on brain metabolism. Other important applications of sensitivity analysis include identification of quantitatively relevant pathways and biochemical species within an overall mechanism, when examining the effects of a genetic anomaly or pathological state on energetic system components and whole system behavior.

Radhakrishnan, Krishnan↗

NASA NTRS2006

A Strategy to Safely Live and Work in the Space Radiation Environment

The goal of the National Aeronautics and Space Agency and the Space Radiation Project is to ensure that astronauts can safely live and work in the space radiation environment. The space radiation environment poses both acute and chronic risks to crew health and safety, but unlike some other aspects of space travel, space radiation exposure has clinically relevant implications for the lifetime of the crew. The term safely means that risks are sufficiently understood such that acceptable limits on mission, post-mission and multi-mission consequences (for example, excess lifetime fatal cancer risk) can be defined. The Space Radiation Project strategy has several elements. The first element is to use a peer-reviewed research program to increase our mechanistic knowledge and genetic capabilities to develop tools for individual risk projection, thereby reducing our dependency on epidemiological data and population-based risk assessment. The second element is to use the NASA Space Radiation Laboratory to provide a ground-based facility to study the understanding of health effects/mechanisms of damage from space radiation exposure and the development and validation of biological models of risk, as well as methods for extrapolation to human risk. The third element is a risk modeling effort that integrates the results from research efforts into models of human risk to reduce uncertainties in predicting risk of carcinogenesis, central nervous system damage, degenerative tissue disease, and acute radiation effects. To understand the biological basis for risk, we must also understand the physical aspects of the crew environment. Thus the fourth element develops computer codes to predict radiation transport properties, evaluate integrated shielding technologies and provide design optimization recommendations for the design of human space systems. Understanding the risks and determining methods to mitigate the risks are keys to a successful radiation protection strategy.

Corbin, Barbara J.↗

NASA NTRS1998

A natural view of microbial biodiversity within hot spring cyanobacterial mat communities

This review summarizes a decade of research in which we have used molecular methods, in conjunction with more traditional approaches, to study hot spring cyanobacterial mats as models for understanding principles of microbial community ecology. Molecular methods reveal that the composition of these communities is grossly oversimplified by microscopic and cultivation methods. For example, none of 31 unique 16S rRNA sequences detected in the Octopus Spring mat, Yellowstone National Park, matches that of any prokaryote previously cultivated from geothermal systems; 11 are contributed by genetically diverse cyanobacteria, even though a single cyanobacterial species was suspected based on morphologic and culture analysis. By studying the basis for the incongruity between culture and molecular samplings of community composition, we are beginning to cultivate isolates whose 16S rRNA sequences are readily detected. By placing the genetic diversity detected in context with the well-defined natural environmental gradients typical of hot spring mat systems, the relationship between gene and species diversity is clarified and ecological patterns of species occurrence emerge. By combining these ecological patterns with the evolutionary patterns inherently revealed by phylogenetic analysis of gene sequence data, we find that it may be possible to understand microbial biodiversity within these systems by using principles similar to those developed by evolutionary ecologists to understand biodiversity of larger species. We hope that such an approach guides microbial ecologists to a more realistic and predictive understanding of microbial species occurrence and responsiveness in both natural and disturbed habitats.

Review↗

NASA NTRS2023

Exploring the ARNTL and RORc Genes' Impact on Lipid Accumulation in the Liver via the Circadian Rhythm

The objective of our proposed experiment is to prove the significance of the upregulation of the ARNTL gene and down regulation of the RORc gene in space, highlighting their crucial roles in causing circadian rhythm misalignment during spaceflight, ultimately resulting in liver lipid accumulation. This experiment was created by thoroughly analyzing the genetic data (UseGalaxy) in OSD-245, Transcriptional analysis of liver from mice flown on the RR-6 mission (NASA GeneLab), and making a comparison between the Flight ISS Terminal and the Ground Control ISS Terminal groups. In our study, we intend to establish experimental groups of Mus musculus (lab mice), with 4 of these groups designated for space travel, while the remaining groups will serve as ground control samples on Earth. Both the space and ground conditions are categorized into four groups according to the genetic makeup of the mice. Within each condition, there will be a control group representing the wild type genes, and the experimental groups will involve knockout mice for ARNTL and RORc. We will then compare the lipid accumulation between the ground control mice and FLT mice to understand whether or not spaceflight causes lipid accumulation, due to a misaligned circadian rhythm. The experiment is anticipated to yield two main outcomes. Firstly, the upregulation of ARNTL is expected to rectify the circadian rhythm misalignment in space, consequently heightening lipid accumulation within the liver. Secondly, the downregulation of RORc is predicted to result in a diminished immune response in the liver, thereby facilitating lipid accumulation. Our space research is expected to aid in lipid buildup countermeasures, informing scientists regarding astronaut protection and providing insights into obesity and non-alcoholic fatty liver disease.

GL4HS↗

NASA NTRS2019

A Multi-Omics Approach Demonstrates that Spaceflight Leads to Lipid Accumulation in Mouse Livers

Spaceflight has several detrimental effects on the physiology of astronauts, many of which are recapitulated in rodent models. We analyzed liver transcriptomic and proteomic data from three mouse spaceflight experiments flown aboard the International Space Station (Rodent Research-1 NASA (RR-1 NASA), Rodent Research-1 CASIS (RR-1 CASIS), Rodent Research-3 (RR-3)), and one mouse experiment flown on the Space Shuttle (Commercial Biomedical Testing Module-3 (CBTM-3) aboard STS-135). Despite the differences in genetic background and time of exposure to microgravity it was shown through Oil Red staining and histology that increased lipid accumulation was occurring in the liver of all mice flown in space compared to the ground controls. This led to further pursue the existing GeneLab datasets related to liver omics data from these mice. We were able to discover key conserved pathways across all the mice independent of the flight conditions that were related to increased lipid metabolism, fatty acid metabolism, both lipid and fatty acid processing, lipid catabolic processing, and lipid localization. In addition, key upstream regulators were predicted to be commonly regulated across all conditions which include ESR1, GCG, and NR1I2 being inhibited and INS being activated. Interestingly, estrogen receptor alpha (ESR1) expression has been known to be heavily involved with lipoprotein metabolism. In addition, insulin (INS) is the primary driver for fat metabolism and increased INS has been associated with increased fatty acids in the liver. Through additional proteomic analysis we were able to identify the majority of the key proteins related to lipids for both the RR-1 and RR-3 rodents were being up-regulated in the livers when comparing flight to ground controls. This additional confirmation of the lipid associated activity also showed that the lipid related proteins are heavily involved with lipid metabolism, cholesterol binding, and cholesterol metabolism. Lastly, the analysis also revealed that the circadian clock related pathways in the liver are commonly being increased across all space flight conditions which has also been reported in the literature to potentially cause increased liver damage. The combination of the very strong lipid uptake in the liver and the transcriptomic/proteomic signatures (including the circadian clock pathways) following spaceflight are consistent with early onset of liver disease. Taken together, these data indicate that, activation of lipotoxic pathways could persist during longer duration spaceflight which might result in the development of liver disease

Lipids↗