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GeneLab: A Systems Biology Platform for Spaceflight Omics Data

NASA's mission includes expanding our understanding of biological systems to improve life on Earth and to enable long-duration human exploration of space. Resources to support large numbers of spaceflight investigations are limited. NASA's GeneLab project is maximizing the science output from these experiments by: (1) developing a unique public bioinformatics database that includes space bioscience relevant "omics" data (genomics, transcriptomics, proteomics, and metabolomics) and experimental metadata; (2) partnering with NASA-funded flight experiments through bio-sample sharing or sample augmentation to expedite omics data input to the GeneLab database; and (3) developing community-driven reference flight experiments. The first database, GeneLab Data System Version 1.0, went online in April 2015. V1.0 contains numerous flight datasets and has search and download capabilities. Version 2.0 will be released in 2016 and will link to analytic tools. In 2015 Genelab partnered with two Biological Research in Canisters experiments (BBRIC-19 and BRIC-20) which examine responses of Arabidopsis thaliana to spaceflight. GeneLab also partnered with Rodent Research-1 (RR1), the maiden flight to test the newly developed rodent habitat. GeneLab developed protocols for maxiumum yield of RNA, DNA and protein from precious RR-1 tissues harvested and preserved during the SpaceX-4 mission, as well as from tissues from mice that were frozen intact during spaceflight and later dissected. GeneLab is establishing partnerships with at least three planned flights for 2016. Organism-specific nationwide Science Definition Teams (SDTs) will define future GeneLab dedicated missions and ensure the broader scientific impact of the GeneLab missions. GeneLab ensures prompt release and open access to all high-throughput omics data from spaceflight and ground-based simulations of microgravity and radiation. Overall, GeneLab will facilitate the generation and query of parallel multi-omics data, and deep curation of metadata for integrative analysis, allowing researchers to uncover cellular networks as observed in systems biology platforms. Consequently, the scientific community will have access to a more complete picture of functional and regulatory networks responsive to the spaceflight environment.. Analysis of GeneLab data will contribute fundamental knowledge of how the space environment affects biological systems, and enable emerging terrestrial benefits resulting from mitigation strategies to prevent effects observed during exposure to space. As a result, open access to the data will foster new hypothesis-driven research for future spaceflight studies spanning basic science to translational science.

proteomics↗

The Effect of Surface Chemical Functionality Upon Ice Adhesion

In nature, anti-freeze proteins present in fish utilize specific organic functionalities to disrupt ice crystal formation and propagation. Based on these structures, surfaces with controlled chemical functionality and chain length were evaluated both experimentally and computationally to assess the effect of both parameters in mitigating ice formation. Linear aliphatic dimethylethoxysilanes terminated with methyl or hydroxyl groups were prepared, characterized, and used to coat aluminum. The effect upon icing using a microdroplet freezing apparatus and the Adverse Environment Rotor Test Stand found hydroxyl-terminated materials exhibited a greater propensity for ice formation and adhesion. Molecular dynamics simulations of a silica substrate bearing functionalized species of similar composition were brought into contact with a pre-equilibrated ice crystal. Several parameters including chain mobility were monitored to ascertain the size of a quasi-liquid layer. The studies suggested that chain mobility affected the interface between ice and the surface more than terminal group chemical composition.

Smith, Joseph G., Jr.↗

Epigenetics Research on the International Space Station

The International Space Station (ISS) is a state-of-the orbiting laboratory focused on advancing science and technology research. Experiments being conducted on the ISS include investigations in the emerging field of Epigenetics. Epigenetics refers to stably heritable changes in gene expression or cellular phenotype (the transcriptional potential of a cell) resulting from changes in a chromosome without alterations to the underlying DNA nucleotide sequence (the genetic code), which are caused by external or environmental factors, such as spaceflight microgravity. Molecular mechanisms associated with epigenetic alterations regulating gene expression patterns include covalent chemical modifications of DNA (e.g., methylation) or histone proteins (e.g., acetylation, phorphorylation, or ubiquitination). For example, Epigenetics ("Epigenetics in Spaceflown C. elegans") is a recent JAXA investigation examining whether adaptations to microgravity transmit from one cell generation to another without changing the basic DNA of the organism. Mouse Epigenetics ("Transcriptome Analysis and Germ-Cell Development Analysis of Mice in Space") investigates molecular alterations in organ-specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight, as well as assessing changes in offspring DNA. NASA's first foray into human Omics research, the Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), includes investigations evaluating differential epigenetic effects via comprehensive whole genome analysis, the landscape of DNA and RNA methylation, and biomolecular changes by means of longitudinal integrated multi-omics research. And the inaugural Genes in Space student challenge experiment (Genes in Space-1) is aimed at understanding how epigenetics plays a role in immune system dysregulation by assaying DNA methylation in immune cells directly in space using miniPCR technology. In addition, NASA's geneLAB campaign covers the epigenome as part of the "expressome", by employing an innovative open source science platform for multi-investigator high throughput utilization of the ISS. Earth benefits of Epigenetics research onboard the ISS range from contributions to the fundamental understanding of epigenetic phenomena with applications in countermeasure development for biomedical conditions, to the generation of integrated strategies for personalized medicine based on unique physiological responses.

Love, John↗

A Review and Comparison of Mouse and Rat Responses to Micro Gravity, Hyper Gravity and Simulated Models of Partial Gravity; Species Differences, Gaps in the Available Data, and Consideration of the Advantages and Caveats of Each Model for Spaceflight

Laboratory strains of mice and rat are widely used to study mammalian responses to stimulus, and both have been studied under a variety of gravity conditions, including space flight. We compared results obtained from exposure to spaceflight and microgravity, hyper gravity via centrifugation, earth gravity, and models of simulated partial gravity (hind-limb unloading and partial weight bearing treatments). We examined the reported changes in survival, body mass, circadian rhythm (body temperature and activity levels), behavior, bone, muscle, immune, cardio-vasculature, vestibular, reproduction and neonate survival, microbiome, and the visual system. Not all categories have published data for both species, some have limited data, and there are variations in experiment design that allow for only relative comparisons to be considered. The data reveal species differences in both the level of gravity required to obtain a response, degree of response, and in temporal expression of responses. Examination of the data across the gravity levels allows consideration of the hypothesis that gravitational responses follow a continuum, and organ specific differences are noted. In summary, we present advantages and caveats of each model system as pertains to gravitational biology research and identify gaps in our knowledge of how these mammals respond to gravity.

mouse rat gravity↗

Chimeric Mouse Models for Space Radiation Risk Investigations

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. For instance, mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, can be used for quantification of space radiation damage. A chimeric brain model, which was shown to perform superiorly in memory and cognitive tests, can also be a candidate for studying the CNS effects of radiation. It has also been reported that mice engrafted with human hematopoietic progenitor cells were exposed to X-rays and high-LET Si ions to investigate the radiation effects in the immune system. In a pilot study, we use PXB mice whose livers contain >90% human cells. These mice are exposed to gamma rays for investigations of DNA damage and transcriptomics changes in the humanized livers. Results obtained from PXB mice will be compared non-engrafted control animals from the same background strain that are exposed to identical conditions. The aim of the study is to determine whether chimeric mouse models are suitable for investigations of space radiation risks.

Honglu Wu↗

Chimeric Mouse Models for Space Radiation Risk Investigations

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. For instance, mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, can be used for quantification of space radiation damage. A chimeric brain model, which was shown to perform superiorly in memory and cognitive tests, can also be a candidate for studying the CNS effects of radiation. It has also been reported that mice engrafted with human hematopoietic progenitor cells were exposed to X-rays and high-LET Si ions to investigate the radiation effects in the immune system. In a pilot study, we use PXB mice whose livers contain >90% human cells. These mice are exposed to gamma rays for investigations of DNA damage and transcriptomics changes in the humanized livers. Results obtained from PXB mice will be compared non-engrafted control animals from the same background strain that are exposed to identical conditions. The aim of the study is to determine whether chimeric mouse models are suitable for investigations of space radiation risks.

Honglu Wu↗

Chimeric Mouse Models for Space Radiation Risk Investigations

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. Here we investigate use of mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, for assessment of space radiation damage. In a pilot study, we use PXB mice whose livers contain >90% human cells and have been found to function nearly identically to human liver tissues. These mice were exposed to gamma rays for investigations of DNA damage, transcriptomics, and histopathological changes in the humanized livers. Results obtained from PXB mice were compared non-engrafted control animals from the same background strain that are exposed to identical conditions. Preliminary data from histopathological analysis suggest chimeric mouse models are suitable for investigations of space radiation risks, as the humanized liver tissue exhibited changes induced by radiation and was markedly distinct from the liver tissue from the control animals (Fox Chase SCID mice).

Radiation effects↗

Comparison of Radiation-induced Damage Between Livers from Control and Chimeric Mice

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. In this pilot study, we use PXB mice whose livers contain >90% human cells. These mice are exposed to gamma rays for investigations of DNA damage and transcriptomics changes in the humanized livers. Results obtained from PXB mice were compared non-engrafted control animals from the same background strain that are exposed to identical conditions. Staining of the liver tissues with H&E indicated that the human liver tissue in chimeric mice responds differently than the mouse liver tissue to gamma radiation on the cellular level, as evidenced by differences in inflammation and cellular damage seen on histopathology. The gene expression data collected from the liver samples will also be presented, which potentially offers an explanation for the differential responses.

Honglu Wu↗

Chimeric Mouse Models for Space Radiation Risk Investigations

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. Here we investigate use of mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, for assessment of space radiation damage. In a pilot study, we use PXB mice whose livers contain >90% human cells and have been found to function nearly identically to human liver tissues. These mice were exposed to gamma rays for investigations of DNA damage, transcriptomics, and histopathological changes in the humanized livers. Results obtained from PXB mice were compared non-engrafted control animals from the same background strain that are exposed to identical conditions. Preliminary data from histopathological analysis suggest chimeric mouse models are suitable for investigations of space radiation risks, as the humanized liver tissue exhibited changes induced by radiation and was markedly distinct from the liver tissue from the control animals (Fox Chase SCID mice).

Radiation effects↗

Comparison of Radiation-Induced Damage Between Livers From Control and Chimeric Mice

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge gained from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. In this pilot study, we used PXB mice whose livers contain >90% human cells. These mice were exposed to gamma rays to investigate DNA damage and transcriptomics changes in the chimeric livers. Results obtained from PXB mice were compared to non-engrafted control animals from the same background strain that were exposed to identical conditions. Staining of the liver tissues with H&E indicated that the human liver tissue in chimeric mice responded differently than the mouse liver tissue to gamma radiation on the cellular level, as evidenced by differences in inflammation and cellular damage seen on histopathology. The gene expression data collected from the liver samples will also be presented, which potentially offers an explanation for the differential responses.

Honglu Wu↗

Comparison of Radiation-Induced Damage Between Livers From Control and Chimeric Mice

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge gained from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. In this pilot study, we used PXB mice whose livers contain >90% human cells. These mice were exposed to gamma rays to investigate DNA damage and transcriptomics changes in the chimeric livers. Results obtained from PXB mice were compared to non-engrafted control animals from the same background strain that were exposed to identical conditions. Staining of the liver tissues with H&E indicated that the human liver tissue in chimeric mice responded differently than the mouse liver tissue to gamma radiation on the cellular level, as evidenced by differences in inflammation and cellular damage seen on histopathology. The gene expression data collected from the liver samples will also be presented, which potentially offers an explanation for the differential responses.

Honglu Wu↗

Comparison of Radiation-Induced Damage Between Livers From Control and Chimeric Mice

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge gained from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. In this pilot study, we used PXB mice whose livers contain >90% human cells. These mice were exposed to gamma rays to investigate DNA damage and transcriptomics changes in the chimeric livers. Results obtained from PXB mice were compared to non-engrafted control animals from the same background strain that were exposed to identical conditions. Staining of the liver tissues with H&E indicated that the human liver tissue in chimeric mice responded differently than the mouse liver tissue to gamma radiation on the cellular level, as evidenced by differences in inflammation and cellular damage seen on histopathology. The gene expression data collected from the liver samples will also be presented, which potentially offers an explanation for the differential responses.

Honglu Wu↗

Plant-microbial interplay for organic nitrogen mediated by functional specificity of root compartments

The organic form of nitrogen (N) is a critical intermediate in mutualistic and competitive root-microbial interactions, mediated by extracellular enzymes. Visualization of the hotspots of organic N and proteolytic activity might be valuable for revealing root functional specificity in N acquisition and transformation at the level of individual roots and compartments. For the first time, we used time-lapse amino-mapping and zymography to co-localize and map the spatial distribution of amino-N and leucine aminopeptidase (LAP) activity in the soil and different root parts of maize (Zea mays L.). Amino-N distribution was mainly associated with seminal roots and root tips, where it overlapped with LAP activity hotspots. In the lateral roots and bulk soil, however, LAP activity was decoupled from amino-N. Distinct functional traits revealed themselves as the highest amino-N content and LAP activity in seminal root tips and as the largest relative extent of the rhizosphere in lateral root tips. Co-localized amino-N and LAP activities highlighted different nutrient acquisition strategies mediated by root-microbe interactions, depending on the root compartment. Seminal roots and their tips appeared to adopt mutualistic strategies, potentially attracting root-associated microorganisms through releasing oligo- and polypeptides. In contrast, lateral roots, with amino-N detected only at their tips, demonstrated stronger N competition, relying on the enzyme activity of the rhizosphere microbial community for N acquisition. These insights emphasized the role of root functional specialization in shaping plant-microbe interactions, offering pathways to enhance nutrient use efficiency.

Maize (Zea mays L.)↗

Mass-Specific Power at the Organism and Biosphere Level

The concept of mass-specific power (MSP) quantitatively relates energy flux to the biomass that flux can sustain. We sought to assess the range and distribution of MSP as expressed at both the organism and biosphere level. The former serves to establish what is possible, and what predominates, in physiological terms; the latter reflects the expression of that physiological potential in an environmental context. To assess the potential range of MSP across a diversity of organisms and physiological states, we compiled a data set of more than 10,000 individual MSP measurements, encompassing more than 2900 unique species and spanning 22 orders of magnitude in body mass. Across the data set, MSP varies over six orders of magnitude, from 3 x 10-5 to 49 Watts per gram biomass carbon (W/gC), but the majority of measured values fall within a relatively narrow range of 0.018 ± 6.4-fold W/gC. It is well documented, and clearly expressed in the data set, that MSP exhibits a strong mass dependence within specific taxa (e.g., birds, mammals, and many others); however, MSP exhibits no mass dependence when considering the data set overall. To assess the expression of MSP in environmental context, we estimated energy utilization rates within eight distinct components of the global biosphere, and for the biosphere overall, and used recently published estimates of biomass within those components to compute MSP. We estimate MSP of 0.005 W/gC for the global biosphere as a whole. The close agreement with the organism-level all-species mean (within 4-fold) is noteworthy because the organism-level data set is dominated in statistical terms by animals, while the global biosphere is dominated in mass terms by trees and microorganisms. The various components of the microbe-dominated marine biosphere exhibit a systematic 5 order of magnitude decrease in MSP from the top of the water column (marine primary producers: 0.9 W/gC) to the depths of the sediment column (> 1m sediment biota: 3 x 10-6 W/gC). Biomass turnover rates, combined with the microbial capacity for both high specific growth rates and low maintenance rates, appear to underlie this large range in MSP, which is not expressed to the same extent in the terrestrial biosphere.

Tori M Hoehler↗

Characterizing the Influence of Organic Polymers on the Specific Reactivity of Particulate Remedial Amendments

Commercially available particulate amendments demonstrate high reactivity for effective treatment of water soluble organic and inorganic contaminants in laboratory studies; however, transport of these particles is constrained in the subsurface. In many field applications, particulate amendments are mixed with organic polymers to enhance mobility for direct push applications or stabilize suspensions for high mass loadings. As such, the interactions between particulate amendments, organic polymers and contaminant species need to be systematically investigated to properly understand mechanistic processes that facilitate predictive performance metrics for specific applications in situ . In this study, batch experiments were conducted to quantify the effects of organic polymers (xanthan gum, guar gum, and sodium alginate), polymer concentration (800 and 4,000 mg/L), and aging (up to 28 days) on chromate treatment rate and capacity by two classes of amendments: reductants [granular zero-valent iron (gZVI), micron-ZVI (mZVI), sulfur modified iron (SMI)], and an adsorbent (bismuth sub-nitrate). When particulate amendments were suspended in polymer solutions, reductants retained between 84–100% of the amendment treatment capacity. Conversely, the adsorbent maintained 63–97% relative treatment capacity of the no-polymer control. Polymer solutions had a more pronounced impact on the rate of chromate removal; first order rates of chemical reduction decreased by as much as 70% and adsorption by up to 81% relative to the no-polymer controls. Polymer–amendment aging experiments also showed decreased Cr(VI) treatment capacity; reductants decreased by as much as 24% and adsorption decreased by as much as 44% after 28 days of incubation. While polymer suspensions are needed to aid the injection of particulate amendments into the subsurface, the results from this study indicate potential losses of treatment capacity and a decrease in the rate of remedial performance due to the physical and chemical interactions between polymer suspensions and reactive particulate amendments. Simple batch systems provide baseline characterization of tripartite interactions for the removal of Cr(VI). Additional work is needed to quantify the full impact of polymers on remedial outcomes under site relevant conditions at field scale.

54 ENVIRONMENTAL SCIENCES↗

HAL/S-FC compiler system functional specification

Compiler organization is discussed, including overall compiler structure, internal data transfer, compiler development, and code optimization. The user, system, and SDL interfaces are described, along with compiler system requirements. Run-time software support package and restrictions and dependencies are also considered of the HAL/S-FC system.

Source record↗

Exciton-blocking treatments for buffer layers in organic photovoltaics

Disclosed herein are exciton-blocking treatments for buffer layers used in organic photosensitive optoelectronic devices. More specifically, the organic photosensitive optoelectronic devices described herein include at least one self-assembled monolayer disposed on the surface of an anode buffer layer. Methods of preparing these devices are also disclosed. The present disclosure further relates to methods of forming at least one self-assembled monolayer on a substrate.

Forrest, Stephen R.↗