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NASA NTRS2004

Role of shielding in modulating the effects of solar particle events: Monte Carlo calculation of absorbed dose and DNA complex lesions in different organs

Distributions of absorbed dose and DNA clustered damage yields in various organs and tissues following the October 1989 solar particle event (SPE) were calculated by coupling the FLUKA Monte Carlo transport code with two anthropomorphic phantoms (a mathematical model and a voxel model), with the main aim of quantifying the role of the shielding features in modulating organ doses. The phantoms, which were assumed to be in deep space, were inserted into a shielding box of variable thickness and material and were irradiated with the proton spectra of the October 1989 event. Average numbers of DNA lesions per cell in different organs were calculated by adopting a technique already tested in previous works, consisting of integrating into "condensed-history" Monte Carlo transport codes--such as FLUKA--yields of radiobiological damage, either calculated with "event-by-event" track structure simulations, or taken from experimental works available in the literature. More specifically, the yields of "Complex Lesions" (or "CL", defined and calculated as a clustered DNA damage in a previous work) per unit dose and DNA mass (CL Gy-1 Da-1) due to the various beam components, including those derived from nuclear interactions with the shielding and the human body, were integrated in FLUKA. This provided spatial distributions of CL/cell yields in different organs, as well as distributions of absorbed doses. The contributions of primary protons and secondary hadrons were calculated separately, and the simulations were repeated for values of Al shielding thickness ranging between 1 and 20 g/cm2. Slight differences were found between the two phantom types. Skin and eye lenses were found to receive larger doses with respect to internal organs; however, shielding was more effective for skin and lenses. Secondary particles arising from nuclear interactions were found to have a minor role, although their relative contribution was found to be larger for the Complex Lesions than for the absorbed dose, due to their higher LET and thus higher biological effectiveness. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Non-NASA Center↗

NASA NTRS1996

Characterization of the proteins comprising the integral matrix of Strongylocentrotus purpuratus embryonic spicules

In the present study, we enumerate and characterize the proteins that comprise the integral spicule matrix of the Strongylocentrotus purpuratus embryo. Two-dimensional gel electrophoresis of [35S]methionine radiolabeled spicule matrix proteins reveals that there are 12 strongly radiolabeled spicule matrix proteins and approximately three dozen less strongly radiolabeled spicule matrix proteins. The majority of the proteins have acidic isoelectric points; however, there are several spicule matrix proteins that have more alkaline isoelectric points. Western blotting analysis indicates that SM50 is the spicule matrix protein with the most alkaline isoelectric point. In addition, two distinct SM30 proteins are identified in embryonic spicules, and they have apparent molecular masses of approximately 43 and 46 kDa. Comparisons between embryonic spicule matrix proteins and adult spine integral matrix proteins suggest that the embryonic 43-kDa SM30 protein is an embryonic isoform of SM30. An adult 49-kDa spine matrix protein is also identified as a possible adult isoform of SM30. Analysis of the SM30 amino acid sequences indicates that a portion of SM30 proteins is very similar to the carbohydrate recognition domain of C-type lectin proteins.

Non-NASA Center↗

NASA NTRS1997

The endomembrane sheath: a key structure for understanding the plant cell?

Recent evidence suggests that integrin is abundant in endomembranes of plant cells, and the endomembranes are clad by a sheath of cytoskeleton including F-actin. A role for endomembrane integrin and the endomembrane sheath is proposed: this system might orchestrate metabolic regulation by providing and modulating loci for channelling, and might accelerate channeling as needed by dragging the endoplasmic reticulum (ER) and organelles through the cytoplasm. To accomplish this "streaming", F-actin might lever against the rest of the endomembrane sheath and the ER might also lever against adhesion sites (i.e., plasmodesmata and plasmalemmal control centers). As an important agent in the control of cellular activities, according to this model, the endomembrane sheath would play a major part in responses to diverse signals and stresses, and under extreme stress cell survival would depend on the ability of the system to maintain enough integrity to direct critical syntheses and degradations.

NASA Discipline Plant Biology↗

NASA NTRS1997

Tensegrity: the architectural basis of cellular mechanotransduction

Physical forces of gravity, hemodynamic stresses, and movement play a critical role in tissue development. Yet, little is known about how cells convert these mechanical signals into a chemical response. This review attempts to place the potential molecular mediators of mechanotransduction (e.g. stretch-sensitive ion channels, signaling molecules, cytoskeleton, integrins) within the context of the structural complexity of living cells. The model presented relies on recent experimental findings, which suggests that cells use tensegrity architecture for their organization. Tensegrity predicts that cells are hard-wired to respond immediately to mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix (e.g. integrins) or to other cells (cadherins, selectins, CAMs). Many signal transducing molecules that are activated by cell binding to growth factors and extracellular matrix associate with cytoskeletal scaffolds within focal adhesion complexes. Mechanical signals, therefore, may be integrated with other environmental signals and transduced into a biochemical response through force-dependent changes in scaffold geometry or molecular mechanics. Tensegrity also provides a mechanism to focus mechanical energy on molecular transducers and to orchestrate and tune the cellular response.

Review↗

NASA NTRS2005

Life in the fast lane for protein crystallization and X-ray crystallography

The common goal for structural genomic centers and consortiums is to decipher as quickly as possible the three-dimensional structures for a multitude of recombinant proteins derived from known genomic sequences. Since X-ray crystallography is the foremost method to acquire atomic resolution for macromolecules, the limiting step is obtaining protein crystals that can be useful of structure determination. High-throughput methods have been developed in recent years to clone, express, purify, crystallize and determine the three-dimensional structure of a protein gene product rapidly using automated devices, commercialized kits and consolidated protocols. However, the average number of protein structures obtained for most structural genomic groups has been very low compared to the total number of proteins purified. As more entire genomic sequences are obtained for different organisms from the three kingdoms of life, only the proteins that can be crystallized and whose structures can be obtained easily are studied. Consequently, an astonishing number of genomic proteins remain unexamined. In the era of high-throughput processes, traditional methods in molecular biology, protein chemistry and crystallization are eclipsed by automation and pipeline practices. The necessity for high-rate production of protein crystals and structures has prevented the usage of more intellectual strategies and creative approaches in experimental executions. Fundamental principles and personal experiences in protein chemistry and crystallization are minimally exploited only to obtain "low-hanging fruit" protein structures. We review the practical aspects of today's high-throughput manipulations and discuss the challenges in fast pace protein crystallization and tools for crystallography. Structural genomic pipelines can be improved with information gained from low-throughput tactics that may help us reach the higher-bearing fruits. Examples of recent developments in this area are reported from the efforts of the Southeast Collaboratory for Structural Genomics (SECSG).

Review↗

NASA NTRSDate not supplied

Selection Factors for Space Crops

NASA is actively researching space crop production to determine its potential to contribute to food system security on long duration missions beyond Low Earth Orbit. Our near-term focus is on nutrient and variety supplementation of prepackaged food with fresh produce that requires little or no processing. The longer-term goal is caloric replacement to become less dependent on Earth, and this will require cultivation of staple crops, processing and cooking equipment, integration with spacecraft air, water, and power systems, and automation. There are numerous technology and knowledge gaps remaining for sustainable space crop production systems, but one high-impact area is in the development of crops specifically customized to meet the needs of controlled environment crop production, astronaut health and well-being, and space-unique environments. Modern crop breeding and genome engineering tools are allowing for rapid development of new genotypes with incredible specificity. Targeted aspects to optimize crops for space have been identified and characterized into five categories: plant growth and development, plant physiology, produce nutrition, produce organoleptic acceptability, and postharvest characteristics. Within each category there are several targets that further the development of crop production systems for spaceflight, such as crop size and harvest index, tolerance to specific environmental stresses, optimizing target nutrients that are low or degrade in the packaged diet, maintenance time requirements, and less indigestible structural material. NASA-funded PIs are already beginning to develop candidate crops, and spaceflight testing and validation of novel space crops is on the horizon. Crops developed for space also have the potential to benefit terrestrial controlled environment agriculture crop production systems. This research was supported by NASA’s Space Biology and Human Research Programs.

Space Crop Production↗

NASA NTRSDate not supplied

Selection Factors for Space Crops

Space Crop Production↗

NASA NTRS2003

NASA Virtual Glovebox (VBX): Emerging Simulation Technology for Space Station Experiment Design, Development, Training and Troubleshooting

The International Space Station demonstrates the greatest capabilities of human ingenuity, international cooperation and technology development. The complexity of this space structure is unprecedented; and training astronaut crews to maintain all its systems, as well as perform a multitude of research experiments, requires the most advanced training tools and techniques. Computer simulation and virtual environments are currently used by astronauts to train for robotic arm manipulations and extravehicular activities; but now, with the latest computer technologies and recent successes in areas of medical simulation, the capability exists to train astronauts for more hands-on research tasks using immersive virtual environments. We have developed a new technology, the Virtual Glovebox (VGX), for simulation of experimental tasks that astronauts will perform aboard the Space Station. The VGX may also be used by crew support teams for design of experiments, testing equipment integration capability and optimizing the procedures astronauts will use. This is done through the 3D, desk-top sized, reach-in virtual environment that can simulate the microgravity environment in space. Additional features of the VGX allow for networking multiple users over the internet and operation of tele-robotic devices through an intuitive user interface. Although the system was developed for astronaut training and assisting support crews, Earth-bound applications, many emphasizing homeland security, have also been identified. Examples include training experts to handle hazardous biological and/or chemical agents in a safe simulation, operation of tele-robotic systems for assessing and diffusing threats such as bombs, and providing remote medical assistance to field personnel through a collaborative virtual environment. Thus, the emerging VGX simulation technology, while developed for space- based applications, can serve a dual use facilitating homeland security here on Earth.

Smith, Jeffrey D.↗

NASA NTRS2015

Omics Research on the International Space Station

The International Space Station (ISS) is an orbiting laboratory whose goals include advancing science and technology research. Completion of ISS assembly ushered a new era focused on utilization, encompassing multiple disciplines such as Biology and Biotechnology, Physical Sciences, Technology Development and Demonstration, Human Research, Earth and Space Sciences, and Educational Activities. The research complement planned for upcoming ISS Expeditions 45&46 includes several investigations in the new field of omics, which aims to collectively characterize sets of biomolecules (e.g., genomic, epigenomic, transcriptomic, proteomic, and metabolomic products) that translate into organismic structure and function. For example, Multi‐Omics is a JAXA investigation that analyzes human microbial metabolic cross‐talk in the space ecosystem by evaluating data from immune dysregulation biomarkers, metabolic profiles, and microbiota composition. The NASA OsteoOmics investigation studies gravitational regulation of osteoblast genomics and metabolism. Tissue Regeneration uses pan‐omics approaches with cells cultured in bioreactors to characterize factors involved in mammalian bone tissue regeneration in microgravity. Rodent Research‐3 includes an experiment that implements pan‐omics to evaluate therapeutically significant molecular circuits, markers, and biomaterials associated with microgravity wound healing and tissue regeneration in bone defective rodents. The JAXA Mouse Epigenetics investigation examines molecular alterations in organ specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight. Lastly, Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), NASA's first foray into human omics research, applies integrated analyses to assess biomolecular responses to physical, physiological, and environmental stressors associated with spaceflight.

Love, John↗

NASA NTRS2011

Differential Processing of Low and High LET Radiation Induced DNA Damage: Investigation of Switch from ATM to ATR Signaling

The members of the phosphatidylinositol kinase-like kinase family of proteins namely ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are directly responsible for the maintenance of genomic integrity by mounting DDR through signaling and facilitating the recruitment of repair factors at the sites of DNA damage along with coordinating the deployment of cell cycle checkpoints to permit repair by phosphorylating Checkpoint kinase Chk1, Chk2 and p53. High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of protons and high energy and charged (HZE) particles from SPE (Solar Particle Event) pose a major health risk for astronauts on their space flight missions. The determination of these risks and the design of potential safeguards require sound knowledge of the biological consequences of lesion induction and the capability of the cells to counter them. We here strive to determine the coordination of ATM and ATR kinases at the break sites directly affecting checkpoint signaling and DNA repair and whether differential processing of breaks induced by low and high LET radiation leads to possible augmentation of swap of these damage sensors at the sites of DNA damage. Exposure of cells to IR triggers rapid autophosphorylation of serine-1981 that causes dimer dissociation and initiates monomer formation of ATM. ATM kinase activity depends on the disruption of the dimer, which allows access and phosphorylation of downstream ATM substrates like Chk2. Evidence suggests that ATM is activated by the alterations in higher-order chromatin structure although direct binding of ATM to DSB ends may be a crucial step in its activation. On the other hand, in case of ATR, RPA (replication protein A)-coated ssDNA (single-stranded DNA) generated as a result of stalled DNA replication or during processing of chromosomal lesions is crucial for the localization of ATR to sites of DNA damage in association with ATR-interacting protein (ATRIP). Although the majority of RPA-coated ssDNA is generally present only during DNA replication, ATR activation in G1 and G2-phase might still require formation of RPA-coated ssDNA, probably initiated by the MRN-CtIP complex and then extended by the Exo1- or BLM-dependent mechanisms at the sites of DSBs. Evidence accumulates that activation of ATM and ATR are oppositely regulated by the length of single stranded overhangs generated at the break sites by processes mentioned above and these stretches of single stranded overhangs hold the clue for ATM to ATR switch at broken DNA ends. We irradiated 82-6hTERT human fibroblast cells with low LET gamma-rays and high LET Fe and Si particles. Preliminary results with cells exposed to 1Gy gamma-rays show that the kinetics of pChk2-pT68 foci formation is comparable to that of gamma-H2AX although they appear to recede quicker. The number and intensity of observed foci reaches a maximum at 30 min and 60 min post IR for Chk2-pT68 and gamma-H2AX foci respectively and all Chk2-pT68 foci colocalize with gamma-H2AX foci. The kinetics of Chk1-pS345 and ATRIP are being determined. Results of Chk2-pT68 foci kinetics was also corroborated by western blot experiments, although phosphorylation was detected as early as 10 min and started receding 30 min post IR with 2Gy of gamma-rays. On the other hand, level of ATR-pS428 reached its maximum between 60 and 120 min and was maintained until the last measured time point of 4 hours post IR as determined by western blotting. Experiments performed with high LET Fe and Si particles will be reported.

Saha, Janapriya↗

NASA NTRS2018

Satellite Radiation Products for Ocean Biology and Biogeochemistry: Needs, State-Of-The-Art, Gaps, Development Priorities, and Opportunities

Knowing the spatial and temporal distribution of the underwater light field, i.e., the spectral and angular structure of the radiant intensity at any point in the water column, is essential to understanding the biogeochemical processes that control the composition and evolution of aquatic ecosystems and their impact on climate and reaction to climate change. At present, only a few properties are reliably retrieved from space, either directly or via water-leaving radiance. Existing satellite products are limited to planar photosynthetically available radiation (PAR) and ultraviolet (UV) irradiance above the surface and diffuse attenuation coefficient. Examples of operational products are provided, and their advantages and drawbacks are examined. The usefulness and convenience of these products notwithstanding, there is a need, as expressed by the user community, for other products, i.e., sub-surface planar and scalar fluxes, average cosine, spectral fluxes (UV to visible), diurnal fluxes, absorbed fraction of PAR by live algae (APAR), surface albedo, vertical attenuation, and heating rate, and for associating uncertainties to any product on a pixel-by-pixel basis. Methodologies to obtain the new products are qualitatively discussed in view of most recent scientific knowledge and current and future satellite missions, and specific algorithms are presented for some new products, namely sub-surface fluxes and average cosine. A strategy and roadmap (short, medium, and long term) for usage and development priorities is provided, taking into account needs and readiness level. Combining observations from satellites overpassing at different times and geostationary satellites should be pursued to improve the quality of daily-integrated radiation fields, and products should be generated without gaps to provide boundary conditions for general circulation and biogeochemical models. Examples of new products, i.e., daily scalar PAR below the surface, daily average cosine for PAR, and sub-surface spectral scalar fluxes are presented. A procedure to estimate algorithm uncertainties in the total uncertainty budget for above-surface daily PAR, based on radiative simulations for expected situations, is described. In the future, space-borne lidars with ocean profiling capability offer the best hope for improving our knowledge of sub-surface fields. To maximize temporal coverage, space agencies should consider placing ocean-color instruments in L1 orbit, where the sunlit part of the Earth can be frequently observed.

Frouin, Robert↗

NASA NTRSDate not supplied

NASA’s NextGen Remote Sensing Instruments Have Arrived: Data Products For Studying Disease Vectors

Remote sensing can be used to measure, evaluate or estimate both the environment (state functions) and interfaces (processfunctions) defining vector habitats. The products of remote sensing can be integrated directly into the epidemiological equationsto significantly enhance our understanding of disease vector’s life cycles and habitats. The next generation of NASA’s remotesensing instruments which have become recently operational will provide a significant enhancement in our ability to studydisease vector’s life cycles and habitats. These instruments are on the International Space Station (ISS) and includeECOSTRESS, DESIS, and GEDI. ECOSTRESS is a 5 channel, thermal IR instrument with 70 m resolution and approximately1-5 day repeat cycle of day/night pairs. DESIS jointly developed by German Aerospace Center and Teledyne Brown Engineeringis a hyperspectral sensor system of 235 channels and 30 m resolution. DESIS data is only being acquired on demand. GEDI is ahigh-resolution laser ranger used for observing Earth’s forests and topography. NASA’s current ISS instrument configuration provides measurements of the critical environmental measures of environmentalstate functions important to vector & disease life cycles. Remote sensing data provide a spatial context and time series oflandscape scale process functions represented by land use mapping and measurements of ecological functions. Global publichealth is entering a new information age through the use of spatial models of disease vector/host ecologies driven by the use ofremotely sensed data to measure environmental and structural factors critical in determining disease vector habitats. In 2018, NASA initiated a new study for the Surface Biology and Geology (SBG) Designated Observable, identified in the 2018National Academies’ Decadal Survey entitled, “Thriving on Our Changing Planet: A Decadal Strategy for Earth Observationfrom Space.” (https://www.nap.edu/catalog/24938/thriving-on-our-changing-planet-a-decadal-strategy-for-earth) . The SBG isplanned to collect global remote sensing measurements using a hyperspectral spectrometer and multispectral thermal data. Thesedata sets will provide a significant enhancement in our ability to study disease vector’s life cycles and habitats globally. The 3sensors on the ISS provide precursor data to prepare the community for the application of future SBG data toward diseasestudies.

Disease Vectors↗

NASA NTRS1997

Assembly and enlargement of the primary cell wall in plants

Growing plant cells are shaped by an extensible wall that is a complex amalgam of cellulose microfibrils bonded noncovalently to a matrix of hemicelluloses, pectins, and structural proteins. Cellulose is synthesized by complexes in the plasma membrane and is extruded as a self-assembling microfibril, whereas the matrix polymers are secreted by the Golgi apparatus and become integrated into the wall network by poorly understood mechanisms. The growing wall is under high tensile stress from cell turgor and is able to enlarge by a combination of stress relaxation and polymer creep. A pH-dependent mechanism of wall loosening, known as acid growth, is characteristic of growing walls and is mediated by a group of unusual wall proteins called expansins. Expansins appear to disrupt the noncovalent bonding of matrix hemicelluloses to the microfibril, thereby allowing the wall to yield to the mechanical forces generated by cell turgor. Other wall enzymes, such as (1-->4) beta-glucanases and pectinases, may make the wall more responsive to expansin-mediated wall creep whereas pectin methylesterases and peroxidases may alter the wall so as to make it resistant to expansin-mediated creep.

NASA Discipline Plant Biology↗

NASA NTRS2012

Technical Evaluation of the NASA Model for Cancer Risk to Astronauts Due to Space Radiation

At the request of NASA, the National Research Council's (NRC's) Committee for Evaluation of Space Radiation Cancer Risk Model reviewed a number of changes that NASA proposes to make to its model for estimating the risk of radiation-induced cancer in astronauts. The NASA model in current use was last updated in 2005, and the proposed model would incorporate recent research directed at improving the quantification and understanding of the health risks posed by the space radiation environment. NASA's proposed model is defined by the 2011 NASA report Space Radiation Cancer Risk Projections and Uncertainties 2010 (Cucinotta et al., 2011). The committee's evaluation is based primarily on this source, which is referred to hereafter as the 2011 NASA report, with mention of specific sections or tables cited more formally as Cucinotta et al. (2011). The overall process for estimating cancer risks due to low linear energy transfer (LET) radiation exposure has been fully described in reports by a number of organizations. They include, more recently: (1) The "BEIR VII Phase 2" report from the NRC's Committee on Biological Effects of Ionizing Radiation (BEIR) (NRC, 2006); (2) Studies of Radiation and Cancer from the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR, 2006), (3) The 2007 Recommendations of the International Commission on Radiological Protection (ICRP), ICRP Publication 103 (ICRP, 2007); and (4) The Environmental Protection Agency s (EPA s) report EPA Radiogenic Cancer Risk Models and Projections for the U.S. Population (EPA, 2011). The approaches described in the reports from all of these expert groups are quite similar. NASA's proposed space radiation cancer risk assessment model calculates, as its main output, age- and gender-specific risk of exposure-induced death (REID) for use in the estimation of mission and astronaut-specific cancer risk. The model also calculates the associated uncertainties in REID. The general approach for estimating risk and uncertainty in the proposed model is broadly similar to that used for the current (2005) NASA model and is based on recommendations by the National Council on Radiation Protection and Measurements (NCRP, 2000, 2006). However, NASA's proposed model has significant changes with respect to the following: the integration of new findings and methods into its components by taking into account newer epidemiological data and analyses, new radiobiological data indicating that quality factors differ for leukemia and solid cancers, an improved method for specifying quality factors in terms of radiation track structure concepts as opposed to the previous approach based on linear energy transfer, the development of a new solar particle event (SPE) model, and the updates to galactic cosmic ray (GCR) and shielding transport models. The newer epidemiological information includes updates to the cancer incidence rates from the life span study (LSS) of the Japanese atomic bomb survivors (Preston et al., 2007), transferred to the U.S. population and converted to cancer mortality rates from U.S. population statistics. In addition, the proposed model provides an alternative analysis applicable to lifetime never-smokers (NSs). Details of the uncertainty analysis in the model have also been updated and revised. NASA's proposed model and associated uncertainties are complex in their formulation and as such require a very clear and precise set of descriptions. The committee found the 2011 NASA report challenging to review largely because of the lack of clarity in the model descriptions and derivation of the various parameters used. The committee requested some clarifications from NASA throughout its review and was able to resolve many, but not all, of the ambiguities in the written description.

Source record↗

NASA NTRS1993

Mutations in the putative calcium-binding domain of polyomavirus VP1 affect capsid assembly

Calcium ions appear to play a major role in maintaining the structural integrity of the polyomavirus and are likely involved in the processes of viral uncoating and assembly. Previous studies demonstrated that a VP1 fragment extending from Pro-232 to Asp-364 has calcium-binding capabilities. This fragment contains an amino acid stretch from Asp-266 to Glu-277 which is quite similar in sequence to the amino acids that make up the calcium-binding EF hand structures found in many proteins. To assess the contribution of this domain to polyomavirus structural integrity, the effects of mutations in this region were examined by transfecting mutated viral DNA into susceptible cells. Immunofluorescence studies indicated that although viral protein synthesis occurred normally, infective viral progeny were not produced in cells transfected with polyomavirus genomes encoding either a VP1 molecule lacking amino acids Thr-262 through Gly-276 or a VP1 molecule containing a mutation of Asp-266 to Ala. VP1 molecules containing the deletion mutation were unable to bind 45Ca in an in vitro assay. Upon expression in Escherichia coli and purification by immunoaffinity chromatography, wild-type VP1 was isolated as pentameric, capsomere-like structures which could be induced to form capsid-like structures upon addition of CaCl2, consistent with previous studies. However, although VP1 containing the point mutation was isolated as pentamers which were indistinguishable from wild-type VP1 pentamers, addition of CaCl2 did not result in their assembly into capsid-like structures. Immunogold labeling and electron microscopy studies of transfected mammalian cells provided in vivo evidence that a mutation in this region affects the process of viral assembly.

Non-NASA Center↗

NASA NTRSDate not supplied

NASA's Planetary Protection Program to Assure Mission Safety and Success

NASA's planetary protection program seeks to understand and control harmful contamination of solar systems targets of exploration by terrestrial contamination and prevent harmful biological contamination of the Earth-Moon system by extraterrestrial life, should it exist. To accomplish these objective's NASA has developed a balanced safety and mission assurance strategy that leverages COSPAR Policy guidelines, workshops, scientific consensus, partnerships and international working groups to develop policy and implementation guidelines. Upcoming crewed missions to the Moon and Mars, as well as robotic missions to small solar system bodies, Europa, Titan and Mars are some of the driving activities of astrobiological interest that continue to emphasize the importance of planetary protection throughout the project life cycle.Development of a responsive and updated agency planetary protection policy has been a focus area in supporting upcoming mission opportunities for exploration to include Mars sample return and crewed mission concepts. An extensive update of this policy is underway which encompasses crewed and robotic procedural polices, a general technical requirements standard, and an implementation handbook. During this timeframe NASA has been working with the international community to develop scientific consensus, and to identify and fill in knowledge gaps for developing balanced policy guidelines, incorporation of risk informed decision making and quantitative technical standards. NASA has developed a planetary protection roadmap as a technology management strategy to track and monitor the development of each knowledge gaps. The Committee of Space Research (COSPAR) Policy on Planetary Protection and the National Academies of Science, Engineering, and Medicine's Committee of Planetary Protection are used to inform updates to the planetary protection polices and guidelines. This integrated strategy for planetary protection seeks to provide a transparent, structured approach for enabling missions, providing guidance for NASA and NASA partnered missions, and being responsive to the increased interest and activities in space exploration whilst maintaining an understanding and control of harmful contamination.

Planetary Protection↗

NASA NTRS2001

Three-dimensional tissue assemblies: novel models for the study of Salmonella enterica serovar Typhimurium pathogenesis

The lack of readily available experimental systems has limited knowledge pertaining to the development of Salmonella-induced gastroenteritis and diarrheal disease in humans. We used a novel low-shear stress cell culture system developed at the National Aeronautics and Space Administration in conjunction with cultivation of three-dimensional (3-D) aggregates of human intestinal tissue to study the infectivity of Salmonella enterica serovar Typhimurium for human intestinal epithelium. Immunohistochemical characterization and microscopic analysis of 3-D aggregates of the human intestinal epithelial cell line Int-407 revealed that the 3-D cells more accurately modeled human in vivo differentiated tissues than did conventional monolayer cultures of the same cells. Results from infectivity studies showed that Salmonella established infection of the 3-D cells in a much different manner than that observed for monolayers. Following the same time course of infection with Salmonella, 3-D Int-407 cells displayed minimal loss of structural integrity compared to that of Int-407 monolayers. Furthermore, Salmonella exhibited significantly lower abilities to adhere to, invade, and induce apoptosis of 3-D Int-407 cells than it did for infected Int-407 monolayers. Analysis of cytokine expression profiles of 3-D Int-407 cells and monolayers following infection with Salmonella revealed significant differences in expression of interleukin 1alpha (IL-1alpha), IL-1beta, IL-6, IL-1Ra, and tumor necrosis factor alpha mRNAs between the two cultures. In addition, uninfected 3-D Int-407 cells constitutively expressed higher levels of transforming growth factor beta1 mRNA and prostaglandin E2 than did uninfected Int-407 monolayers. By more accurately modeling many aspects of human in vivo tissues, the 3-D intestinal cell model generated in this study offers a novel approach for studying microbial infectivity from the perspective of the host-pathogen interaction.

NASA Discipline Environmental Health↗

NASA NTRSDate not supplied

NASA’s Planetary Protection Program to Assure Mission Safety and Success

NASA’s planetary protection program seeks to understand and control harmful contamination of solar systems targets of exploration by terrestrial contamination and prevent harmful biological contamination of the Earth-Moon system by extraterrestrial life, should it exist. To accomplish these objective’s NASA has developed a balanced safety and mission assurance strategy that leverages COSPAR Policy guidelines, workshops, scientiﬁc consensus, partnerships and international working groups to develop policy and implementation guidelines. Upcoming crewed missions to the Moon and Mars, as well as robotic missions to small solar system bodies, Europa, Titan and Mars are some of the driving activities of astrobiological interest that continue to emphasize the importance of planetary protection throughout the project life cycle. Development of a responsive and updated agency planetary protection policy has been a focus area in supporting upcoming mission opportunities for exploration to include Mars sample return and crewed mission concepts. An extensive update of this policy is underway which encompasses crewed and robotic procedural polices, a general technical requirements standard, and an implementation handbook. During this timeframe NASA has been working with the international community to develop scientiﬁc consensus, and to identify and ﬁll in knowledge gaps for developing balanced policy guidelines, incorporation of risk informed decision making and quantitative technical standards. NASA has developed a planetary protection roadmap as a technology management strategy to track and monitor the development of each knowledge gaps. The Committee of Space Research (COSPAR) Policy on Planetary Protection and the National Academies of Science, Engineering, and Medicine’s Committee of Planetary Protection are used to inform updates to the planetary protection polices and guidelines. This integrated strategy for planetary protection seeks to provide a transparent, structured approach for enabling missions, providing guidance for NASA and NASA partnered missions, and being responsive to the increased interest and activities in space exploration whilst maintaining an understanding and control of harmful contamination.

James Benardini↗