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All sourcesNASA NTRSDOE OSTI
NASA NTRS1998

PCR cloning and characterization of multiple ADP-glucose pyrophosphorylase cDNAs from tomato

Four ADP-glucose pyrophosphorylase (AGP) cDNAs were cloned from tomato fruit and leaves by the PCR techniques. Three of them (agp S1, agp S2, and agp S3) encode the large subunit of AGP, the fourth one (agp B) encodes the small subunit. The deduced amino acid sequences of the cDNAs show very high identities (96-98%) to the corresponding potato AGP isoforms, although there are major differences in tissue expression profiles. All four tomato AGP transcripts were detected in fruit and leaves; the predominant ones in fruit are agp B and agp S1, whereas in leaves they are agp B and agp S3. Genomic southern analysis suggests that the four AGP transcripts are encoded by distinct genes.

Non-NASA Center↗
NASA NTRSDate not supplied

Benchmarking Computational Tools for Calling SNPs and Indels in Complex Microbial Populations

The NASA BioNutrients missions seek to understand the suitability of microorganisms for bioproduction during space flight. One topic of interest is the stability of microbial genomes during long-term ambient storage and subsequent rehydration and growth. To address these questions, samples from 8 species were flown to ISS for 5 years of desiccated storage at ambient temperature (Stasis Packs) and 2 species were packaged along with powdered media inside a bioreactor system to allow hydration and growth in microgravity (Production Packs). For both systems, Whole Genome Sequencing (WGS) of the DNA extracted from the returned samples and paired ground controls will be conducted to identify changes in genome stability due to time, storage conditions and growth in space. Across the technical replicates, ground controls, 10 timepoints, and multiple experimental conditions, ~300 samples have been selected for initial analysis with WGS sequencing to 100x coverage. A flexible and resource efficient mutation calling pipeline is needed to process this large dataset and allow for comparisons between species. Many bioinformatics tools for calling Indels and Single Nucleotide Variants (SNVs) are designed for use with pure isolates, where true variations from the reference genome are expected to dominate the reads aligning to the location of mutation. In contrast, DNA from the Stasis Pack (SP) samples was collected directly after recovery from desiccated storage and the Production Pack (PP) samples were collected after fermentation. In this context, reads with mutations are expected to be less frequent than reads that align with the reference genome, as each sample will include multiple lines of cells. Thus, BioNutrients samples are expected to be similar to samples from cancer cell or “pooled” sequencing approaches. In preparation for the analysis of the BioNutrients samples, we have tested three mutation calling tools (GATK for Microbes, BreSeq and DiscoSNP) designed for complex samples. A challenge of validating mutation identification pipelines is a lack of “Ground Truth” datasets, especially for complex samples. To compare these three tools, we sought to identify mutations in pre-existing WGS data collected from populations of Chlamydomonas reinhardtii that were exposed to UV mutagenesis and growth in LEO as part of the Space Algae-1 mission. Here we present a summary of these tools against the analysis originally conducted using the CRISP tool. Critical metrics are compared such as runtime, the number of SNPs, the number and size of Indels, and patterns of transversion and transitions identified by each tool are reported. By sharing these benchmarking results collected in support of the BioNutrients mission, we aim to guide others seeking to identify SNVs in similarly complex microbial samples.

Biology↗
NASA NTRS1994

Heavy ion induced mutations in mammalian cells: Cross sections and molecular analysis

Our investigations of heavy ion-induced mutations in mammalian cells, which had been begun a few years ago, were systematically continued. For the first time, it was possible to cover a large LET range with a few kinds of ions. To do this, both UNILAC and SIS were used to yield comparable data for a large energy range. This is a necessary condition for a comprehensive description of the influence of such ion parameters as energy and LET. In these experiments, the induced resistance against the poison 6-thioguanin (6-TG), which is linked to the HPRT locus on the genome, is being used as mutation system. In addition to the mutation-induction cross-section measurements, the molecular changes of the DNA are being investigated by means of Multiplex PCR ('Polymerase Chain Reaction') gene amplification. From these experiments we expect further elucidation of the mutation-inducing mechanisms composing the biological action of heavy-ion radiation.

Stoll, U.↗
NASA NTRS2004

Characterization of Two Microbial Isolates from Andean Lakes in Bolivia

We are currently investigating the biological population present in the highest and least explored perennial lakes on earth in the Bolivian and Chilean Andes, including several volcanic crater lakes of more than 6000 m elevation, in combination of microbiological and molecular biological methods. Our samples were collected in saline lakes of the Laguna Blanca Laguna Verde area in the Bolivian Altiplano and in the Licancabur volcano crater (27 deg. 47 min S/67 deg. 47 min. W) in the ongoing project studying high altitude lakes. The main goal of the project is to look for analogies with Martian paleolakes. These Bolivian lakes can be described as Andean lakes following the classification of Chong. We have attempted to isolate pure cultures and phylogenetically characterize prokaryotes that grew under laboratory conditions. Sediment samples taken from the Licancabur crater lake (LC), Laguna Verde (LV), and Laguna Blanca (LB) were analyzed and cultured using enriched liquid media under both aerobic and anaerobic conditions. All cultures were incubated at room temperature (15 to 20 C) and under light exposure. For the reported isolates, 36 hours incubation were necessary for reaching optimal optical densities to consider them viable cultures. Ten serial dilutions starting from 1% inoculum were required to obtain a suitable enriched cell culture to transfer into solid media. Cultures on solid medium were necessary to verify the formation of colonies in order to isolate pure cultures. Different solid media were prepared using several combinations of both trace minerals and carbohydrates sources in order to fit their nutrient requirements. The microorganisms formed individual colonies on solid media enriched with tryptone, yeast extract and sodium chloride. Cells morphology was studied by optical and electronic microscopy. Rodshape morphologies were observed in most cases. Total bacterial genomic DNA was isolated from 50 ml late-exponential phase culture by using the CTAB miniprep protocol. The 16S rRNA genes were amplified by PCR using both Bacteria- and Archaeauniversal primer sets: 27f and 1492r, 21f and 1492r respectively. Sequences of 16S rRNA gene were determined and initially compared with reference sequences contained in the EMBL nucleotide sequence database by using the BLAST program and were subsequently aligned with 16S rRNA reference sequences in the ARB package (http://www.mikro.biologie.tu-muenchen.de). Aligned sequences were inserted within a stable phylogenetic tree by using the ARB parsimony tool. In this work we report the morphology and phylogenetic characterization of two isolates belonged to Laguna Blanca sediments.

Demergasso, C.↗
NASA NTRS1992

Biodiversity: molecular biological domains, symbiosis and kingdom origins

The number of extant species of organisms is estimated to be from fewer than 3 to more than 30 x 10(6) (May, 1992). Molecular biology, comparative genetics and ultrastructural analyses provide new insights into evolutionary relationships between these species, including increasingly precise ideas of how species and higher taxa have evolved from common ancestors. Accumulation of random mutations and large macromolecular sequence change in all organisms since the Proterozoic Eon has been importantly supplemented by acquisition of inherited genomes ('symbiogenesis'). Karyotypic alterations (polyploidization and karyotypic fissioning) have been added to these other mechanisms of species origin in plants and animals during the Phanerozoic Eon. The new evolution concepts (coupled with current rapid rates of species extinction and ignorance of the extent of biodiversity) prompted this analysis of the field of systematic biology and its role in the reorganization of extant species into higher taxa. Two superkingdoms (= Domains: Prokaryotae and Eukaryotae) and five kingdoms (Monera = Procaryotae or Bacteria; Protoctista: algae, amoebae, ciliates, foraminifera, oomycetes, slime molds, etc.; Mychota: 'true' fungi; Plantae: one phylum (division) of bryophytes and nine phyla of tracheophytes; and Animalia) are recognized. Two subkingdoms comprise the monera: the great diverse lineages are Archaebacteria and Eubacteria. The criteria for classification using molecular, ultrastructural and genetic data for this scheme are mentioned. For the first time since the nineteenth century, logical, technical definitions for each group are given with their time of appearance as inferred from the fossil record in the primary scientific literature. This classification scheme, which most closely reflects the evolutionary history, molecular biology, genetics and ultrastructure of extant life, requires changes in social organization of biologists, many of whom as botanists and zoologists, still behave as if there were only two important kingdoms (plants and animals).

Non-NASA Center↗
NASA NTRS2021

Application of Whole Genome Sequencing and MALDI-TOF to the Identifcation of Bacillus Species Isolated from Cleanrooms at NASA Johnson Space Center

Astromaterial cleanrooms at NASA Johnson Space Center are built environments that hold samples, such as lunar rocks, from different space exploration missions. Bacillus sp. are frequently detected in routine microbial monitoring of these facilities. Since this, and related genera, can form endospores that can withstand harsh conditions, they could contaminate astromaterials. This could confound searches for extraterrestrial life. Whole genome sequencing (WGS) is widely used for identifying bacterial strains and tracking their source; however, WGS is expensive and time consuming. Matrix-assisted laser desorption ionization– time of flight mass spectrometry (MALDI-TOF) shows promise as a low-cost, rapid method of identifying strains of bacteria, but few studies have compared this proteomics method to WGS. To evaluate a high throughput method of tracking the source of contamination of this built environment, WGS and MALDI-TOF was conducted on 18 bacterial strains isolated from surfaces in astromaterials cleanrooms. WGS identified 14 Bacillus, 2 Paenibacillus, 1 Solibacillus and 1 Alcaligenes strains. These isolates showed similarity to strains commonly observed in spacecraft assembly cleanrooms at other facilities. Cluster analysis of mass spectra generated by MALDI-TOF grouped strains together that were greater than 94% similar to each other in terms of amino acid sequences of single copy core genes, as assessed by WGS. This suggests that MALDI-TOF and WGS results are consistent with each other and MALDI-TOF can rapidly identify strains of Bacillus sp. isolated from cleanroom environments with a resolution comparable to WGS. Based on phylogenomic analysis, these results also suggest the presence of a cosmopolitan class of Bacillus sp. that are more likely to be found in cleanrooms and similar built environments than in natural systems.

Farnaz Mazhari↗
NASA NTRS2007

Testing Prospects for Reliable Diatom Nanotechnology in Microgravity

The worldwide effort to grow nanotechnology, rather than use lithography, focuses on diatoms, single cell eukaryotic algae with ornate silica shells, which can be replaced by oxides and ceramics, or reduced to elemental silicon, to create complex nanostructures with compositions of industrial and electronics importance. Diatoms produce an enormous variety of structures, some of which are microtubule dependent and perhaps sensitive to microgravity. The NASA Single Loop for Cell Culture (SLCC) for culturing and observing microorganisms permits inexpensive, low labor in-space experiments. We propose to send up to the International Space Station diatom cultures of the three diatom species whose genomes are being sequenced, plus the giant diatoms of Antarctica (up to 2 mm diameter for a single cell) and the unique colonial diatom, Bacillaria paradoxa. Bacillaria cells move against each other in partial synchrony, like a sliding deck of cards, by a microfluidics mechanism. Will normal diatoms have aberrant pattern and shape or motility compared to ground controls? The generation time is typically one day, so that many generations may be examined from one flight. Rapid, directed evolution may be possible running the SLCC as a compustat. The shell shapes and patterns are preserved in hard silica, so that the progress of normal and aberrant morphogenesis may be followed by drying samples on a moving filter paper "diatom tape recorder". With a biodiversity of 100,000 distinct species, diatom nanotechnology may offer a compact and portable nanotechnology toolkit for exploration anywhere.

Gordon, Richard↗
NASA NTRSDate not supplied

Simulation of Deployable Composite Structures Based On Mechanics of Structure Genome

In this paper, a simulation method for analyzing deployable composite structures is presented. With a proper material model, effective plate/shell properties of the composites is obtained based on Mechanics of Structure Genome (MSG), and then implemented into a user subroutine UGENS for global structure simulation in ABAQUS. Column bending test (CBT) and composite boom and hub structure are studied for demonstration. A viscoelastic material model with direct integration implementation is adopted in this paper. CBT simulation shows good agreement with experiments during relaxation, while errors are observed when comparing residual deformation. This simulation can be potentially used as a calibration tool for material properties. After CBT simulation, a demonstrative model with a lenticular boom and the hub is created in ABAQUS. Complete process of flattening, coiling, stowage, deploying and recovery is simulated with the viscoelastic material model. Residual deformation of the boom is analyzed.

Multi-scale modeling↗
NASA NTRS1998

Taxane recovery from cells of Taxus in micro- and hypergravity

Cell suspension cultures of Taxus cuspidata produce taxanes that are released from the outer surface of cells into the culture medium as free and bound alkaloids. Paclitaxel (Taxol (TM)), is an anti-cancer drug in short supply. It has a taxane ring derived from baccatin III and a C-13 phenylisoserine side-chain. This drug is produced over a wide range of gravitational forces. Monoclonal and polyclonal antibodies to paclitaxel, baccatin III, and the C-13 phenylisoserine side chain were combined in multiple-labeling studies to localize taxanes and paclitaxel on cell surfaces or on particles released into the culture medium. Bioreactor vessel design altered the composition of taxanes recovered from cells in simulated microgravity. At 10(-2) and 2x10(-4)g, taxane recovery was reduced but biomass growth and percent paclitaxel was significantly increased. At 1 to 24g, growth was reduced with a significant recovery of total taxanes with low percent paclitaxel. Bound paclitaxel was also localized in endonuclease-rich fragmenting nuclei of individual apoptotic cells. A model is presented comprising TCH (touch) genes encoding enzymes that modify taxane-bearing xylan residues in cell walls, the calcium-sensing of gravitational forces by the cytoplasm, and the predisposition of nuclei to apoptosis. This integrates the adaptive physiological and biochemical responses of drug-producing genomes with gravitational forces.

Plants, Medicinal/chemistry/cytology↗
NASA NTRS2016

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

BACKGROUND: Astronauts participating in long duration space missions are at an increased risk of physiological disruptions. The development of visual impairment and intracranial pressure (VIIP) syndrome is one of the leading health concerns for crew members on long-duration space missions; microgravity-induced fluid shifts and chronic elevated cabin CO2 may be contributing factors. By studying physiological and molecular changes in one identical twin during his 1-year ISS mission and his ground-based co-twin, this work extends a current NASA-funded investigation to assess space flight induced "Fluid Shifts" in association with the development of VIIP. This twin study uniquely integrates physiological and -omic signatures to further our understanding of the molecular mechanisms underlying space flight-induced VIIP. We are: (i) conducting longitudinal proteomic assessments of plasma to identify fluid regulation-related molecular pathways altered by long-term space flight; and (ii) integrating physiological and proteomic data with genomic data to understand the genomic mechanism by which these proteomic signatures are regulated. PURPOSE: We are exploring proteomic signatures and genomic mechanisms underlying space flight-induced VIIP symptoms with the future goal of developing early biomarkers to detect and monitor the progression of VIIP. This study is first to employ a male monozygous twin pair to systematically determine the impact of fluid distribution in microgravity, integrating a comprehensive set of structural and functional measures with proteomic, metabolomic and genomic data. This project has a broader impact on Earth-based clinical areas, such as traumatic brain injury-induced elevations of intracranial pressure, hydrocephalus, and glaucoma. HYPOTHESIS: We predict that the space-flown twin will experience a space flight-induced alteration in proteins and peptides related to fluid balance, fluid control and brain injury as compared to his pre-flight protein/peptide signatures. Conversely, the trajectory of these protein signatures will remain relatively constant in his ground based co-twin. METHODS: We are using proteomic and standard immunoelectrophoresis techniques to delineate the change in protein signatures throughout the course of a long duration space flight in relation to the development of VIIP. We are also applying a novel cell-based metaboloic organ system assay ("Organs on a Plate") to address how these circulating biomarkers affect physiological processes at the cellular and organ level which could result in VIIP symptoms. These molecular data will be correlated with physiological measures (eg. extra and intracellular fluid volume, vascular filling/flow patterns, MRI, and Optic Coherence Tomography. DISCUSSION: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Biosamples will be batch processed when received from ISS after the conclusion of the 1-year mission. Omic and Physiological measures from the twin astronauts will be compared to similar data being collected on twin subjects who participated in simulated microgravity study. bed rest study.

Rana, Brinda K.↗
NASA NTRS1989

X ray sensitivity of diploid skin fibroblasts from patients with Fanconi's anemia

Experiments were performed on Fanconi's anemia and normal human fibroblast cell lines growing in culture in an attempt to correlate cell cycle kinetics with genomic damage and determine their bearing on the mechanism of chromosome aberration induction. FA fibroblasts showed a significantly increased susceptibility to chromosomal breakage by x rays in the G2 phase of the cell cycle. No such response was observed in fibroblasts irradiated in the G0 phase. The observed increases in achromatic lesions and in chromatid deletions in FA cells as compared with normal cells appear to indicate that FA cells are deficient in strand break repair and also possibly in base damage excision repair. Experiments are now in progress to further elucidate the mechanisms involved.

Kale, Ranjini↗
NASA NTRS2012

The Origins of Transmembrane Ion Channels

Even though membrane proteins that mediate transport of ions and small molecules across cell walls are among the largest and least understood biopolymers in contemporary cells, it is still possible to shed light on their origins and early evolution. The central observation is that transmembrane portions of most ion channels are simply bundles of -helices. By combining results of experimental and computer simulation studies on synthetic models and natural channels, mostly of non-genomic origin, we show that the emergence of -helical channels was protobiologically plausible, and did not require highly specific amino acid sequences. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. Specifically, we explain how the antiamoebin channels, which are made of identical helices, 16 amino acids in length, achieve efficiency comparable to that of highly evolved channels. We further show that antiamoebin channels are extremely flexible, compared to modern, genetically coded channels. On the basis of our results, we propose that channels evolved further towards high structural complexity because they needed to acquire stable rigid structures and mechanisms for precise regulation rather than improve efficiency. In general, even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

Pohorille, Andrew↗
NASA NTRS2011

Introduction of structural affinity handles as a tool in selective nucleic acid separations

The method is used for separating nucleic acids and other similar constructs. It involves selective introduction, enhancement, or stabilization of affinity handles such as single-strandedness in the undesired (or desired) nucleic acids as compared to the usual structure (e.g., double-strandedness) of the desired (or undesired) nucleic acids. The undesired (or desired) nucleic acids are separated from the desired (or undesired) nucleic acids due to capture by methods including but not limited to immobilized metal affinity chromatography, immobilized single-stranded DNA binding (SSB) protein, and immobilized oligonucleotides. The invention is useful to: remove contaminating genomic DNA from plasmid DNA; remove genomic DNA from plasmids, BACs, and similar constructs; selectively separate oligonucleotides and similar DNA fragments from their partner strands; purification of aptamers, (deoxy)-ribozymes and other highly structured nucleic acids; Separation of restriction fragments without using agarose gels; manufacture recombinant Taq polymerase or similar products that are sensitive to host genomic DNA contamination; and other applications.

Willson, III, Richard Coale↗
NASA NTRSDate not supplied

Spaceflight Environmental-Telemetry Data for Biological Science

There is a critical need for better access and visualization of spaceflight environmental telemetry and mission hardware data from sensors including relative humidity, carbon dioxide, oxygen, radiation, airflow, temperature, acceleration, and acoustics. Under the stewardship of the Ames Life Sciences Data Archive (ALSDA) and GeneLab, an effort is underway to consolidate, normalize and provide accessibility of archived mission environmental data and hardware information, with the purpose of providing important context to biological data. This effort is necessary to provide scientific context of its impact upon biological and biomedical data from spaceflight missions and experiments (genomic, metagenomic, gene expression, proteomic, metabolomic, physiological, phenomics, behavioral; tabular, imaging, video). Environmental spaceflight data is derived from dozens of sources, with various formats, and in the past year a pipeline is in development to collect, curate and present this data efficiently. In the upcoming year, a new Data Visualization Portal will utilize the standardized pipeline data to provide easy user access to compare parameters and environmental conditions between missions, locations, subjects, and durations. Environmental and hardware data enables broad accessibility and analytics, without the need for advanced data informatic expertise. Familiarity with the capabilities and limitations of a variety of existing hardware/tools is a strength that could be applied to creation of improved hardware for future ecosystems on the Moon and Mars. The intention is to make biological and environmental telemetry data maximally open-access and FAIR (findable, accessible, interoperable, reusable) for data mining-informatic approaches to support knowledge discovery necessary for low Earth orbit, cis-Lunar, Mars transit, and Mars surface missions.

Danielle K. Lopez↗
NASA NTRS2019

GeneLab: A Systems Biology Platform for Omics Analysis

NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). The GeneLab Data Systems (GLDS) version 4.0 will be available on October 1st 2019, and will provide the latest in terms of professional state-of-the-art bioinformatics platform for the space biology and radiation community to upload their data into an omics data commons, to process their data with vetted standard workflows and to compare to existing analyses. Started in 2015 as a repository designed to archive omics data from space experiments, GeneLab has expanded its scope to all ionizing radiation omics experiments conducted on the ground and has put considerable effort in providing carefully characterized radiation metadata on all dataset. GeneLab is also providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome) to help users explore important questions: 1) Which genes or proteins are expressed differently in space for various living organisms? 2) What specific DNA mutations or epigenetic changes happen in space or after exposure to ionizing radiation? and 3) How does genetics affect these responses? Processed data available on GeneLab are derived by standard data analysis workflows vetted by hundreds of scientists who volunteered to join one of the four GeneLab Analysis Working Groups (Animal AWG, Plant AWG, Microbe AWG, Multi-Omics AWG). In this presentation, we will discuss how to bridge the gap between irradiation studies performed on earth and biological experiments conducted in space since the early 1990's. We will discuss how radiation dosimetry was estimated for datasets derived from samples collected during the Space Shuttle era or on the International Space Station. Finally, we will address future strategies regarding dose monitoring in future missions into space, inter-agency efforts to unify data under one umbrella, and knowledge dissemination across the radiation research community and the space biology community.

open-science↗
NASA NTRS2019

NASA GeneLab Space Omics Database: Expanding from Space to Ionizing Radiation Data on the Ground

NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or ground experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). The GeneLab Data Systems (GLDS) version 4.0 will be available on October 1st 2019, and will provide a state-of-the-art bioinformatics platform for the space biology and radiation communities to upload their data into an omics data commons, to process their data with vetted standard workflows and to compare with existing analyses. Started in 2015 as a repository designed to archive omics data from space experiments, GeneLab has expanded its scope to all ionizing radiation omics experiments conducted on the ground and has put considerable effort in providing carefully characterized radiation metadata on all datasets. GeneLab is also providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome) to help users explore important questions: 1) Which genes or proteins are expressed differently in space for various living organisms? 2) What specific DNA mutations or epigenetic changes happen in space or after exposure to ionizing radiation? and 3) How does genetics affect these responses? Processed data available on GeneLab are derived by standard data analysis workflows vetted by hundreds of scientists who volunteered to join one of the four GeneLab Analysis Working Groups (Animal AWG, Plant AWG, Microbe AWG, Multi-Omics AWG). In this presentation, we will discuss how to bridge the gap between irradiation studies performed on earth and biological experiments conducted in space since the early 1990's. We will discuss how radiation dosimetry was estimated for datasets derived from samples collected during the Space Shuttle era on the International Space Station and on other orbiting platforms. Finally, we will address future strategies regarding dose monitoring in future missions into space, inter-agency efforts to unify data under one umbrella, and knowledge dissemination across the radiation research community and the space biology community.

open-science↗
NASA NTRS2017

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗
NASA NTRS2002

Characteristics of genomic instability in clones of TK6 human lymphoblasts surviving exposure to 56Fe ions

Genomic instability in the human lymphoblast cell line TK6 was studied in clones surviving 36 generations after exposure to accelerated 56Fe ions. Clones were assayed for 20 characteristics, including chromosome aberrations, plating efficiency, apoptosis, cell cycle distribution, response to a second irradiation, and mutant frequency at two loci. The primary effect of the 56Fe-ion exposure on the surviving clones was a significant increase in the frequency of unstable chromosome aberrations compared to the very low spontaneous frequency, along with an increase in the phenotypic complexity of the unstable clones. The radiation-induced increase in the frequency of unstable chromosome aberrations was much greater than that observed previously in clones of the related cell line, WTK1, which in comparison to the TK6 cell line expresses an increased radiation resistance, a mutant TP53 protein, and an increased frequency of spontaneous unstable chromosome aberrations. The characteristics of the unstable clones of the two cell lines also differed. Most of the TK6 clones surviving exposure to 56Fe ions showed unstable cytogenetic abnormalities, while the phenotype of the WTK1 clones was more diverse. The results underscore the importance of genotype in the characteristics of instability after radiation exposure.

NASA Discipline Radiation Health↗