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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↗

SOME GEOLOGIC PROBLEMS OF MARS

Geological and geophysical knowledge and uncertainties concerning the surface and body of Mars are briefly discussed and evaluated. The large number of uncertainties in present data precludes an adequate model of Mars; reliable data are needed. Accurate values for the figure of the planet and the radii, seismic evidence of internal structure, and measurements of the outward heat flux across the surface are important and necessary for a satisfactory description of the body of Mars. Two types of television coverage from an orbiter are required to describe surface features. One type is needed to delineate gross topographic features, such as extensive highlands or basins, with resolution of about one kilometer. The second type is needed to search for evidence of orogenic and volcanic activity, areas of groundwater accumulation, sand dune patterns, etc., with resolution of about 10 meters. Some geological inferences which can be drawn from available photographic and photometric data concerning topography, areas of water accumulation, and biological activity are discussed. The priority of scientific geologic experiments is presented and some present instrumentation capabilities and deficiencies are listed.

Mars surface↗

Growth/reflectance model interface for wheat and corresponding model

The use of modeling to explore the possibility of discovering new and useful crop condition indicators which might be available from the Thematic Mapper and to connect these symptoms to the biological causes in the crop is discussed. A crop growth model was used to predict the day to day growth features of the crop as it responds biologically to the various environmental factors. A reflectance model was used to predict the character of the interaction of daylight with the predicted growth features. An atmospheric path radiance was added to the reflected daylight to simulate the radiance appearing at the sensor. Finally, the digitized data sent to a ground station were calculated. The crop under investigation is wheat.

Suits, G. H.↗

USSR Space Life Sciences Digest, issue 9

This is the ninth issue of NASA's USSR Space Lifes Sciences Digest. It contains abstracts of 46 papers recently published in Russian language periodicals and bound collections and of a new Soviet monograph. Selected abstracts are illustrated with figures and tables from the original. Additional features include reviews of a Russian book on biological rhythms and a description of the papers presented at a conference on space biology and medicine. A special feature describes two paradigms frequently cited in Soviet space life sciences literature. Information about English translations of Soviet materials available to readers is provided. The abstracts included in this issue have been identified as relevant to 28 areas of aerospace medicine and space biology. These areas are: adaptation, biological rhythms, body fluids, botany, cardiovascular and respiratory systems, developmental biology, endocrinology, enzymology, equipment and instrumentation, gastrointestinal system, genetics, habitability and environment effects, hematology, human performance, immunology, life support systems, mathematical modeling, metabolism, microbiology, morphology and cytology, musculoskeletal system, nutrition, neurophysiology, operational medicine, perception, personnel selection, psychology, radiobiology, and space biology and medicine.

Hooke, Lydia Razran↗

Effects of artificial defoliation of pines on the structure and physiology of the soil fungal community of a mixed pine-spruce forest

Loss of photosynthetic area can affect soil microbial communities by altering the availability of fixed carbon. We used denaturing gradient gel electrophoresis (DGGE) and Biolog filamentous-fungus plates to determine the effects of artificial defoliation of pines in a mixed pine-spruce forest on the composition of the fungal community in a forest soil. As measured by DGGE, two fungal species were affected significantly by the defoliation of pines (P < 0.001); the frequency of members of the ectomycorrhizal fungus genus Cenococcum decreased significantly, while the frequency of organisms of an unidentified soil fungus increased. The decrease in the amount of Cenococcum organisms may have occurred because of the formation of extensive hyphal networks by species of this genus, which require more of the carbon fixed by their host, or because this fungus is dependent upon quantitative differences in spruce root exudates. The defoliation of pines did not affect the overall composition of the soil fungal community or fungal-species richness (number of species per core). Biolog filamentous-fungus plate assays indicated a significant increase (P < 0.001) in the number of carbon substrates utilized by the soil fungi and the rate at which these substrates were used, which could indicate an increase in fungal-species richness. Thus, either small changes in the soil fungal community give rise to significant increases in physiological capabilities or PCR bias limits the reliability of the DGGE results. These data indicate that combined genetic and physiological assessments of the soil fungal community are needed to accurately assess the effect of disturbance on indigenous microbial systems.

Pinus/growth & development/physiology↗

HRP Data Management Plan

The purpose of Human Research Program Data Management Plan (DMP) is to define the processes and activities required for the overall management of the research data collected and managed by HRP throughout their life cycle. New updates to the Data Management Plan in 2023 include 1. CAPABILITIES AND SERVICES Data Repositories. Principal Investigators (PIs) funded by HRP may be asked to submit data to one of several NASA data repositories. HRP archives data in the NASA Life Sciences Portal (NLSP) that it considers to be unique and high value. This includes data from human subjects in space flight (ISS and commercial flights) and ground analogs to spaceflight; spaceflight tech demos involving humans; human omics data including the microbiome; parabolic flight studies; and the NASA Space Radiation Laboratory (NSRL). The Open Science Data Repository (OSDR) includes The Ames Life Sciences Data Archive (ALSDA), used to archive non-human biological data (e.g., animal) generated by the Human Research program, and GeneLab, available to HRP PIs to archive non-human omics data. Catalog for search and retrieval. A catalog of non-human HRP life science experiments, with all associated descriptions (mission, payload, hardware, and personnel related information), and biospecimens is provided on the NLSP public web site for search and retrieval. 2. IRB ROLE IN RETURN OF INDIVIDUAL RESEARCH RESULTS The NASA IRB manages the process for incidental findings and for returning results to subjects for studies for which NASA IRB is the IRB of record. Omics data, especially genomics data, may generate information significant to the health of or risk to a research subject. These data potentially hold the keys to understand lifetime risks of chronic diseases, such as cancer, as well as risks associated with exposures common in space flight. 3. UPDATE OF TERMS – IDENTIFIABLE AND ATTRIBUTABLE DATA HRP now follows Federal and NASA policy by using “identifiable” instead of “attributable” for Personally Identifiable Information (PII). 4. POLICY ABOUT INTERNAL NON-RESEARCH USE OF DATA The HRP Chief Scientist grants access to data from HRP-funded research for non-research internal use that includes program management, customer facilitation, strategic planning, and risk research planning. Typical HRP personnel granted access to HRP research data for internal use include the Element Scientist, Subject Matter Experts (SME), and Data/bioinformatics Scientists. If data accessed for Internal Use is provided to an intramural or extramural scientist for hypothesis driven research, all Federal and NASA regulations (e.g., IRB review) regarding human subject research apply.

Data Management Plan↗

Activation and proliferation of lymphocytes and other mammalian cells in microgravity

The experimental findings reviewed in this chapter support the following conclusions: Proliferation. Human T-lymphocytes, associated with monocytes as accessory cells, show dramatic changes in the centrifuge, in the clinostat and in space. In free-floating cells the mitogenic response is depressed by 90% in microgravity, whereas in cells attached to a substratum activation is enhanced by 100% compared to 1-G ground and inflight controls. The duration of phase G1 of the mitotic cycle of HeLa cells is reduced in hypergravity, resulting in an increased proliferation rate. Other systems like Friend cells and WI38 human embryonic lung cells do not show significant changes. Genetic expression and signal transduction. T-lymphocytes and monocytes show important changes in the expression of cytokines like interleukin-1, interleukin-2, interferon-gamma and tumor necrosis factor. The data from space experiments in Spacelab, Space Shuttle mid-deck, and Biokosmos have helped to clarify certain aspects of the mechanism of T-cell activation. Epidermoid A431 cells show changes in the genetic expression of the proto-oncogenes c-fos and c-jun in the clinostat and in sounding rockets. Membrane function, in particular the binding of ligates as first messengers of a signal, is not changed in most of the cell systems in microgravity. Morphology and Mortility. Free cells, lymphocytes in particular, are able to move and form aggregates in microgravity, indicating that cell-cell contacts and cell communications do take place in microgravity. Dramatic morphological and ultrastructural changes are not detected in cells cultured in microgravity. Important experiments with single mammalian cells, including immune cells, were carried out recently in three Spacelab flights, (SL-J, D-2, and IML-2 in 1992, 1993, and 1994, respectively). The results of the D-2 mission have been published in ref. 75; those of the IML-2 mission in ref. 76. Finally, many cell biology experiments in space have suffered in the past from a lack of adequate controls (like 1-G centrifuges) and of proper experimental conditions (like well-controlled temperature). In this respect the availability of Biorack, outfitted with proper incubators with 1-G control centrifuge as well as a glovebox with a microscope, is a great advantage. It is also desirable that cell biology experiments in space are accompanied or even preceded by a program of ground-based investigations in the fast rotating clinostat and in the centrifuge, and that preparatory experiments be done in parabolic flights and sounding rockets, whenever possible. Proper publication of the results of space experiments is another important need. A great number of data have been published in proceedings and reports that are not available to the broad scientific community. To guarantee the credibility and the international recognition of space biology it is important that the results be published in international, peer reviewed journals.

manned↗

Geological Factors Impacted Cadmium Availability and use as an Alternative Cofactor for Zinc in the Carbon Fixation Pathways of Marine Diatoms

Transition metal cofactors are crucial for many biological processes. Despite being primarily considered to be toxic, the transition metal cadmium (Cd) was discovered to be a substitute cofactor for zinc (Zn) in photosynthetic carbon fixation pathways of marine diatoms. However, it is not known how conditions in the geosphere impacted Cd availability and its incorporation as an alternative metal cofactor for phytoplankton. We employed mineral chemistry network analysis to investigate which geochemical factors may have influenced the availability of Cd and Zn during the putative time period that the alternative Cd-based pathway evolved. Our results show that Zn minerals are more chemically diverse than are Cd minerals, but Zn- and Cd-containing minerals have similar network centrality values when specifically considering sulfur (S)-containing species. Cadmium and Zn sulfides are the most common Cd- and Zn-containing mineral species over the past 500 million years. In particular, the Cd and Zn sulfides, respectively greenockite and sphalerite, were highly abundant during this time period. Furthermore, S-containing Cd and Zn minerals are commonly co-located in geologic time, allowing them to be weathered and transported to the ocean in tandem, rather than from separate sources. We suggest that the simultaneous weathering of Cd and Zn sulfides allowed for Cd to be a bioavailable direct substitute for Zn in protein complexes during periods of Zn depletion. The biogeochemical cycles of Zn and Cd exemplify the importance of the coevolution of the geosphere and biosphere in shaping primary production in the modern ocean.

Naman Srivastava↗

Free-flyer biostack experiment

The free-flyer biostack experiment is part of a radiobiological space research program that includes experiments in space as well as in accelerators on Earth. The program has been specially designed to increase knowledge concerning the importance, effectiveness, and hazards of the structured components of cosmic radiation to man and to any biological specimen in space. Up to now, our understanding of the ways in which HZE particles might affect biological matter is based on a few spaceflight experiments from the last Apollo missions and on the limited data available from heavy-ion irradiation from accelerators. In the near future, accelerators capable of accelerating particles up to higher atomic numbers and higher energies will promote increased activity in ground-based studies on biological effects of HZE particles. Comparison of data from such irradiation experiments on Earth with those from an actual spaceflight experiment will show any potential influence of the inevitably attendant spaceflight factors (e.g., weightlessness) on the radiobiological events.

Buecker, H.↗

Mars Field Geology, Biology, and Paleontology Workshop: Summary and Recommendations

Current NASA planning envisions human missions to Mars as early as 2013, on a mission that would send six crew members for a 500-day stay on the surface of Mars. While our understanding of how we would get there and back is fairly mature, the planning for what the crew would do to explore while on the surface for 500 days is less detailed. Mission objectives are to understand the composition and geo- morphology of the martian surface, and to continue to investigate and sample the geologic history of Mars. Special emphasis will focus on exploring for possible biogenic signatures, past or present, and on analyzing pre-biotic chemistry. The purpose of this workshop was to explore the strategies, desired capabilities, skills, and operational realities required to lend success to the first human missions to Mars. Current mission planning dictates that there will be considerable mobility, sampling and analytical capability available to human crews, at a site warranting long-term geologic and possibly biological interest. However, the details of specific capabilities are not yet clearly defined.

Budden, Nancy Ann↗

Mars Field Geology, Biology. and Paleontology Workshop: Summary and Recommendations

Current NASA planning envisions human missions to Mars as early as 2013, on a mission that would send six crew members for a 500-day stay on the surface of Mars. While our understanding of how we would get there and back is fairly mature, the planning for what the crew would do to explore while on the surface for 500 days is less detailed. Mission objectives are to understand the composition and geo- morphology of the martian surface, and to continue to investigate and sample the geologic history of Mars. Special emphasis will focus on exploring for possible biogenic signatures, past or present, and on analyzing pre-biotic chemistry. The purpose of this workshop was to explore the strategies, desired capabilities, skills, and operational realities required to lend success to the first human missions to Mars. Current mission planning dictates that there will be considerable mobility, sampling and analytical capability available to human crews, at a site warranting long-term geologic and possibly biological interest. However, the details of specific capabilities are not yet clearly defined.

Budden, Nancy Ann↗

Evaluation of class 2 biological cabinets

Basic investigations, consisting primarily of airflow measurements and visual smoke tests, were made on four commercially available units. The results indicated that performance varied considerably between units. Therefore, it was decided to outline the performance desired and to include in the overall equipment specifications a set of performance tests to assure a clean air safety cabinet with respect to chemical usage. The evaluation was to be based on aerodynamic performance under the various modes of operation.

Chamberlin, R. E.↗

Mutagenic effects of a single and an exact number of alpha particles in mammalian cells

One of the main uncertainties in risk estimation for environmental radon exposure using lung cancer data from underground miners is the extrapolation from high- to low-dose exposure where multiple traversal is extremely rare. The biological effects of a single alpha particle are currently unknown. Using the recently available microbeam source at the Radiological Research Accelerator Facility at Columbia University, we examined the frequencies and molecular spectrum of S1- mutants induced in human-hamster hybrid (A(L)) cells by either a single or an exact number of alpha particles. Exponentially growing cells were stained briefly with a nontoxic concentration of Hoechst dye for image analysis, and the location of individual cells was computer-monitored. The nucleus of each cell was irradiated with either 1,2,4, or 8 alpha particles at a linear energy transfer of 90 keV/microm consistent with the energy spectrum of domestic radon exposure. Although single-particle traversal was only slightly cytotoxic to A(L) cells (survival fraction approximately 0.82), it was highly mutagenic, and the induced mutant fraction averaged 110 mutants per 10(5) survivors. In addition, both toxicity and mutant induction were dose-dependent. Multiplex PCR analysis of mutant DNA showed that the proportion of mutants with multilocus deletions increased with the number of particle traversals. These data provide direct evidence that a single a particle traversing a nucleus will have a high probability of resulting in a mutation and highlight the need for radiation protection at low doses.

NASA Discipline Radiation Health↗

A Quasi-Laue Neutron Crystallographic Study of D-Xylose Isomerase

Hydrogen atom location and hydrogen bonding interaction determination are often critical to explain enzymatic mechanism. Whilst it is difficult to determine the position of hydrogen atoms using X-ray crystallography even with subatomic (less than 1.0 Angstrom) resolution data available, neutron crystallography provides an experimental tool to directly localise hydrogeddeuteriwn atoms in biological macromolecules at resolution of 1.5-2.0 Angstroms. Linearisation and isomerisation of xylose at the active site of D-xylose isomerase rely upon a complex hydrogen transfer. Neutron quasi-Laue data were collected on Streptomyces rubiginosus D-xylose isomerase crystal using the LADI instrument at ILL with the objective to provide insight into the enzymatic mechanism (Myles et al. 1998). The neutron structure unambiguously reveals the protonation state of His 53 in the active site, identifying the model for the enzymatic pathway.

Meilleur, Flora↗