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At least 55 records · Page 3

New measurements for hadrontherapy and space radiation: biology

The dual goals of optimizing clinical efficacy of hadrontherapy and determining radiation risk estimates for space research have intersected to a common focus for investigation of the biological effects of charged particles. This paper briefly highlights recent international progress at accelerator facilities engaged in both biological and clinical studies of the effects of particle beams, primarily protons, carbon and iron ions. Basic mechanisms of molecular, cellular and tissue responses continue under investigation for radiations with a range of ionization densities. Late normal tissue effects, including the risk of cancer in particular, are of importance for both research fields. International cooperation has enhanced the rate of progress as evidenced by recent publications. Specific areas of biomedical research related to the biological radiotoxicity of critical organs (especially the central nervous system), individual radiosensitivities to radiation carcinogenesis, and the analysis of effects in mixed radiation fields still require more research. Recommendations for addressing these issues are made.

Review↗

Microbial detection with low molecular weight RNA

The need to monitor microorganisms in the environment has increased interest in assays based on hybridization probes that target nucleic acids (e.g., rRNA). We report the development of liquid-phase assays for specific bacterial 5S rRNA sequences or similarly sized artificial RNAs (aRNAs) using molecular beacon technology. These beacons fluoresce only in the presence of specific target sequences, rendering as much as a 27-fold fluorescence enhancement. The assays can be used with both crude cell lysates and purified total RNA preparations. Minimal sample preparation (e.g., heating to promote leakage from cells) is sufficient to detect many Gram-negative bacteria. Using this approach it was possible to detect an aRNA-labeled Escherichia coli strain in the presence of a large background of an otherwise identical E. coli strain. Finally, by using a longer wavelength carboxytetramethylrhodamine beacon it was possible to reduce the fraction of the signal due to cellular autofluorescence to below 0.5%.

NASA Discipline Life Sciences Technologies↗

Microscopic physical biomarkers in carbonate hot springs: implications in the search for life on Mars

Physical evidence of life (physical biomarkers) from the deposits of carbonate hot springs were documented at the scale of microorganisms--submillimeter to submicrometer. The four moderate-temperature (57 to 72 degrees C), neutral pH springs reported on in this study, support diverse communities of bacteria adapted to specific physical and chemical conditions. Some of the microbes coexist with travertine deposits in endolithic communities. In other cases, the microbes are rapidly coated and destroyed by precipitates but leave distinctive mineral fabrics. Some microbes adapted to carbonate hot springs produce an extracellular polymeric substance which forms a three-dimensional matrix with living cells and cell remains, known as a biofilm. Silicon and iron oxides often coat the biofilm, leading to long-term preservation. Submicrometer mineralized spheres composed of calcium fluoride or silica are common in carbonate hot spring deposits. Sphere formation is biologically mediated, but the spheres themselves are apparently not fossils or microbes. Additionally, some microbes selectively weather mineral surfaces in distinctive patterns. Hot spring deposits have been cited as prime locations for exobiological exploration of Mars. The presence of preserved microscopic physical biomarkers at all four sites supports a strategy of searching for evidence of life in hot spring deposits on Mars.

NASA Center JSC↗

Synthetic spectra of simulated terrestrial atmospheres containing possible biomarker gases

NASA's proposed Terrestrial Planet Finder, a space-based interferometer, will eventually allow spectroscopic analyses of the atmospheres of extrasolar planets. Such analyses would provide information about the existence of life on these planets. One strategy in the search for life is to look for evidence of O3 (and hence O2) in a planet's atmosphere; another is to look for gases that might be present in an atmosphere analogous to that of the inhabited early Earth. In order to investigate these possibilities, we have calculated synthetic spectra for several hypothetical terrestrial-type atmospheres. The model atmospheres represent four different scenarios. The first two, representing inhabited terrestrial planets, are an Earth-like atmosphere containing variable amounts of oxygen and an early Earth-type atmosphere containing methane. In addition, two cases representing Mars-like and early Venus-like atmospheres were evaluated, to provide possible "false positive" spectra. The calculated spectra suggest that ozone could be detected by an instrument like Terrestrial Planet Finder if the O2 concentration in the planet's atmosphere is > or = 200 ppm, or 10(-3) times the present atmospheric level. Methane should be observable on an early-Earth type planet if it is present in concentrations of 100 ppm or more. Methane has both biogenic and abiogenic sources, but concentrations exceeding 1000 ppm, or 0.1% by volume, would be difficult to produce from abiogenic sources alone. High methane concentrations in a planet's atmosphere are therefore another potential indicator for extraterrestrial life.

NASA Discipline Exobiology↗

A low molecular weight artificial RNA of unique size with multiple probe target regions

Artificial RNAs (aRNAs) containing novel sequence segments embedded in a deletion mutant of Vibrio proteolyticus 5S rRNA have previously been shown to be expressed from a plasmid borne growth rate regulated promoter in E. coli. These aRNAs accumulate to high levels and their detection is a promising tool for studies in molecular microbial ecology and in environmental monitoring. Herein a new construct is described which illustrates the versatility of detection that is possible with aRNAs. This 3xPen aRNA construct carries a 72 nucleotide insert with three copies of a unique 17 base probe target sequence. This aRNA is 160 nucleotides in length and again accumulates to high levels in the E. coli cytoplasm without incorporating into ribosomes. The 3xPen aRNA illustrates two improvements in detection. First, by appropriate selection of insert size, we obtained an aRNA which provides a unique and hence, easily quantifiable peak, on a high resolution gel profile of low molecular weight RNAs. Second, the existence of multiple probe targets results in a nearly commensurate increase in signal when detection is by hybridization. These aRNAs are naturally amplified and carry sequence segments that are not found in known rRNA sequences. It thus may be possible to detect them directly. An experimental step involving RT-PCR or PCR amplification of the gene could therefore be avoided.

Non-NASA Center↗

Multilineage differentiation of rhesus monkey embryonic stem cells in three-dimensional culture systems

In the course of normal embryogenesis, embryonic stem (ES) cells differentiate along different lineages in the context of complex three-dimensional (3D) tissue structures. In order to study this phenomenon in vitro under controlled conditions, 3D culture systems are necessary. Here, we studied in vitro differentiation of rhesus monkey ES cells in 3D collagen matrixes (collagen gels and porous collagen sponges). Differentiation of ES cells in these 3D systems was different from that in monolayers. ES cells differentiated in collagen matrixes into neural, epithelial, and endothelial lineages. The abilities of ES cells to form various structures in two chemically similar but topologically different matrixes were different. In particular, in collagen gels ES cells formed gland-like circular structures, whereas in collagen sponges ES cells were scattered through the matrix or formed aggregates. Soluble factors produced by feeder cells or added to the culture medium facilitated ES cell differentiation into particular lineages. Coculture with fibroblasts in collagen gel facilitated ES cell differentiation into cells of a neural lineage expressing nestin, neural cell adhesion molecule, and class III beta-tubulin. In collagen sponges, keratinocytes facilitated ES cell differentiation into cells of an endothelial lineage expressing factor VIII. Exogenous granulocyte-macrophage colony-stimulating factor further enhanced endothelial differentiation. Thus, both soluble factors and the type of extracellular matrix seem to be critical in directing differentiation of ES cells and the formation of tissue-like structures. Three-dimensional culture systems are a valuable tool for studying the mechanisms of these phenomena.

Pluripotent Stem Cells/cytology/physiology↗

Complex Chromosomal Rearrangements Induced in Vivo by Heavy Ions

It has been suggested that the ratio complex/simple exchanges can be used as a biomarker of exposure to high-LET radiation. We tested this hypothesis in vivo, by considering data from several studies that measured complex exchanges in peripheral blood from humans exposed to mixed fields of low- and high-LET radiation. In particular, we studied data from astronauts involved in long-term missions in low-Earth-orbit, and uterus cancer patients treated with accelerated carbon ions. Data from two studies of chromosomal aberrations in astronauts used blood samples obtained before and after space flight, and a third study used blood samples from patients before and after radiotherapy course. Similar methods were used in each study, where lymphocytes were stimulated to grow in vitro, and collected after incubation in either colcemid or calyculin A. Slides were painted with whole-chromosome DNA fluorescent probes (FISH), and complex and simple chromosome exchanges in the painted genome were classified separately. Complex-type exchanges were observed at low frequencies in control subjects, and in our test subjects before the treatment. No statistically significant increase in the yield of complex-type exchanges was induced by the space flight. Radiation therapy induced a high fraction of complex exchanges, but no significant differences could be detected between patients treated with accelerated carbon ions or X-rays. Complex chromosomal rearrangements do not represent a practical biomarker of radiation quality in our test subjects. Copyright 2003 S. Karger AG, Basel.

Ions/adverse effects/therapeutic use↗

Cancer Risk-Assessment of Radiation Damage in Ataxia Telangiectasia Heterozygous Human Breast Epithelial Cell Cultures

This paper describes the study of the markers of cellular changes that are found during the onset of carcinogenesis. Several of the biological factors are markers of stress response, oncoprotein expression, and differentiation factors. Oxidative stress response agents such as heat shock proteins (HSPs) protect cells from oxidative stresses such as ionizing radiation. The onocoprotein HER-2/neu, a specific breast cancer marker, indicates early onset of cancer. Additional structural and morphogenetic markers of differentiation were considered in order to determine initial cellular changes at the initial onset of cancer. As an additional consideration, all-trans retinoic acid (RA), a differentiation agent, was considered because of its known role in regulating normal differentiation and inhibiting tumor proliferation via specific nuclear receptors. This paper discusses study and results of the preliminary analyses of gamma irradiation of AT heterozygous human breast epithelial cells (WH). Comparisons are also made of the effects various RA concentrations post-irradiation.

Lisa C. Applewhite↗

NSCOR for Evaluating Risk Factors and Biomarkers for Adaptation and Resilience to Spaceflight: Emotional Valence and Social Processes in ICC/ICE Environments

Space exploration class missions, such as a mission to Mars, will require optimization of human performance, adaptability, and resilience. This NASA Specialized Center of Research (NSCOR) utilizes the NIMH Research Domain Criteria (RDoC) framework to identify biological and behavioral markers of individual social adaptation and emotional resilience (as well as vulnerability) to spaceflight-relevant stressors such as living in extended isolation. The overarching goal of this NSCOR is to obtain novel information to help identify biomarkers of individuals who are resilient and/or adaptable to the stressors of isolated, confined, and controlled (ICC) and isolated, confined, and extreme (ICE) environments.A total of N=90 healthy adult astronaut surrogates are being studied in three spaceflight-analog environments: (1) n=40 healthy adults in the Isolation and Confinement Analog Research Unit (ICARUS), an ICC at the University of Pennsylvania, during 7-day missions, for a target total of 280 subject days; (2) n=32 healthy adult astronaut surrogates studied in NASA’s Human Exploration Research Analog (HERA), an ICC at Johnson Space Center during 45-day missions, for a target total of 2,112 subject days; and (3) n=18 healthy adults in the Alfred-Wegener-Institute’s Neumayer Station III, an ICE in Antarctica, during 14-month missions, for a target total of 7,560 subject days. Dr. Nindl’s Laboratory at the University of Pittsburgh is analyzing a priori selected protein biomarkers in blood, saliva, and urine. Complementary rodent models of exposure to early life stressors, confinement, and isolation are being evaluated at Dr. Hensch’s Laboratory to further validate the neurobehavioral and biological findings from the human studies.Given the inconsistency and varied definition of resilience/adaptation in the scientific literature, the NSCOR team developed a composite resilience/adaptation measure that reflects the most relevant outcomes to resilience/adaptation across psychosocial and neurobehavioral functions, as well as neurocognitive and spaceflight-relevant operational performance. To achieve this, group consensus was attained from subject matter experts to produce a rank-order of importance for each input variable. The final resilience/adaptation score included 36 variables that were collected across spaceflight analogs. As of 10/1/2021, the NSCOR project acquired data on n=27 subjects at ICARUS, n=16 at HERA, and n=18 at Neumayer. The COVID-19 pandemic delayed data acquisition at ICARUS and HERA.Among subjects studied to date, 99% of neural and neurobehavioral data (e.g., neuroimaging for structure and function, behavioral measures) as well as blood, saliva, and urine for biochemical assays have been acquired. For rodent models, Dr. Hensch’s laboratory has established biochemical and behavioral parameters reflecting confinement stress in social networks of mice for comparison to stress responses in the human spaceflight analog environments.Group social behaviors were measured with a Social Network Analysis (SNA) approach to define objective parameters associated with sociability and its plasticity by sex. This analytic approach may help identify a network of individuals who are more effective teammates or more likely to generate new social relationships. Data acquisition, biomarker assessment, and data quality control will continue through September 2022.

D F Dinges↗

BAW and SAW sensors for in-situ analysis

In-situ analysis is a major goal in current and future NASA exploration missions. In general in-situ analysis experiments are designed to investigate chmical, biological or geological markers or properties to determine the complex history of the body being studied. In order to expand the number of applicable sensor schemes an investigation into piezoelectric bulk acoustic wave (BAW) and surface acoustic wave (SAW) resonators has been initiated.

robotics EAP artificial muscles biomimetics↗

Comprehensive Investigation of Mars Methane and Organics with ExoMars/NOMAD

Methane (CH4) on Mars has attracted a great deal of attention since it was first detected in January 2003. As methane is considered a potential marker for past/present biological or geological activity, any possible detection would require evidence with strong statistical significance. Ethane (C2H6) and ethylene (C2H4) are also relevant chemical species as their shorter lifetimes in the Martian atmosphere make them excellent tracers for recent and ongoing releases. If detected, a CH4/C2Hn ratio could aid in constraining the potential source of organic production. Here we present the results of an extensive search for hydrocarbons in the Martian atmosphere in 240,000 solar occultation measurements performed by the ExoMars Trace Gas Orbiter/NOMAD instrument from April 2018 to April 2019. The observations are global, covering all longitudes and latitudes from 85°N to 85°S, and sampled from 6-100 km altitude with a typical vertical resolution of 2km. There were no statistically significant detections of organics and new stringent upper limits for global ethane and ethylene were set at 0.1 ppbv and 130.7 ppbv, respectively. No global background level of methane was observed, obtaining an upper limit of 0.06 ppbv, in agreement with early results from ExoMars (Korablev et al., 2019). Dedicated searches for localized plumes at more than 2000 locations provided no positive detections, implying that if methane were released in strong and rapid events, the process would have to be sporadic.

Elise W Knutsen↗

Biomarkers of exposure, sensitivity and disease

PURPOSE: This review is to evaluate the use of biomarkers as an indication of past exposure to radiation or other environmental insults, individual sensitivity and risk for the development of late occurring disease. OVERVIEW: Biomarkers can be subdivided depending on their applications. Markers of exposure and dose can be used to reconstruct and predict past accidental or occupational exposures when limited or no physical measurements were available. Markers of risk or susceptibility can help identify sensitivity individuals that are at increased risk for development of spontaneous disease and may help predict the increased risk in sensitive individuals associated with environmental or therapeutic radiation exposures. Markers of disease represent the initial cellular or molecular changes that occur during disease development. Each of these types of biomarkers serves a unique purpose. OUTLINE: This paper concentrates on biomarkers of dose and exposure and provides a brief review of biomarkers of sensitivity and disease. The review of biomarkers of dose and exposure will demonstrate the usefulness of biomarkers in evaluation of physical factors associated with radiation exposure, such as LET, doserate and dose distribution. It will also evaluate the use of biomarkers to establish relationships that exist between exposure parameters such as energy deposition, environmental concentration of radioactive materials, alpha traversals and dose. In addition, the importance of biological factors on the magnitude of the biomarker response will be reviewed. Some of the factors evaluated will be the influence of species, tissue, cell types and genetic background. The review will demonstrate that markers of sensitivity and disease often have little usefulness in dose-reconstruction and, by the same token, many markers of dose or exposure may not be applicable for prediction of sensitivity or risk.

Non-NASA Center↗

Pyrolysis-gas chromatography/mass spectrometry analyses of biological particulates collected during recent space shuttle missions

Biological particulates collected on air filters during shuttle missions (STS-40 and STS-42) were identified using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). A method was developed for identifying the atmospheric particles and their sources through the analysis of standard materials and the selection of "marker" compounds specific to the particle type. Pyrolysis spectra of biological standards were compared with those of airborne particles collected during two space shuttle missions; marker compounds present in the shuttle particle spectra were matched with those of the standards to identify the source of particles. Particles of 0,5--1-mm diameter and weighing as little as 40 micrograms could be identified using this technique. The Py-GC/MS method identified rat food and soilless plant-growth media as two sources of particles collected from the shuttle atmosphere during flight.

NASA Program Environmental Health↗

National Aeronautics and Space Administration Biological Specimen Repository

The National Aeronautics and Space Administration Biological Specimen Repository (Repository) is a storage bank that is used to maintain biological specimens over extended periods of time and under well-controlled conditions. Samples from the International Space Station (ISS), including blood and urine, will be collected, processed and archived during the preflight, inflight and postflight phases of ISS missions. This investigation has been developed to archive biosamples for use as a resource for future space flight related research. The International Space Station (ISS) provides a platform to investigate the effects of microgravity on human physiology prior to lunar and exploration class missions. The storage of crewmember samples from many different ISS flights in a single repository will be a valuable resource with which researchers can study space flight related changes and investigate physiological markers. The development of the National Aeronautics and Space Administration Biological Specimen Repository will allow for the collection, processing, storage, maintenance, and ethical distribution of biosamples to meet goals of scientific and programmatic relevance to the space program. Archiving of the biosamples will provide future research opportunities including investigating patterns of physiological changes, analysis of components unknown at this time or analyses performed by new methodologies.

McMonigal, Kathleen A.↗

The use of mineral crystals as bio-markers in the search for life on Mars

It is proposed that minerals resulting from biologically controlled mineralization processes be utilized as biomarkers because of their favorable qualities. Universal signatures of life (biomarkers) are discussed in terms of their terrestrial forms and hypothetical Martian counterparts including organics, suites of specific inorganic and organic compounds, and isotopic ratios. It is emphasized that minerals produced under biologic control have morphological and isotopic compositions that are not found in their abiotic counterparts. Other biomarkers are not necessarily indicative of biological origin and are therefore unreliable resources for scientific study. Mineral crystals are also stable over long geological periods, and the minerals from Martian fluvial features can therefore be employed to search for fossils and biomarkers of early biological activity.

Schwartz, D. E.↗

Vitamin D Supplementation and Immune Response to Antarctic Winter

Maintaining vitamin D status without sunlight exposure is difficult without supplementation. This study was designed to better understand interrelationships between periodic cholecalciferol(vitamin D3) supplementation and immune function in Antarctic workers. The effect of 2 oral dosing regimens of vitamin D3 supplementation on vitamin D status and markers of immune function were evaluated in people in Antarctica with no ultraviolet light exposure for 6 mo. Participants were given a 2,000-IU (50 g) daily (n=15) or 10,000-IU (250 g) weekly (n=14) vitamin D3 supplement for 6 mo during a winter in Antarctica. Biological samples were collected at baseline and at 3 and 6 mo. Vitamin D intake, markers of vitamin D and bone metabolism, and latent virus reactivation were determined. After 6 mo the mean (SD) serum 25-hydroxyvitamin D3 concentration increased from 56 plus or minus 17 to 79 plus or minus 16 nmol/L and 52 plus or minus 10 to 69 plus or minus 9 nmol/L in the 2,000-IU/d and 10,000-IU/wk groups (main effect over time P less than 0.001). Participants with a greater BMI (participant BMI range = 19-43 grams per square meter) had a smaller increase in 25-hydroxyvitamin D3 after 6 mo supplementation (P less than 0.05). Participants with high serum cortisoland higher serum 25-hydroxyvitamin D3 were less likely to shed Epstein-Barr virus in saliva (P less than 0.05). The doses given raised vitamin D status in participants not exposed to sunlight for 6 mo, and the efficacy was influenced by baseline vitamin D status and BMI. The data also provide evidence that vitamin D, interacting with stress, can reduce risk of latent virus reactivation during the winter in Antarctica.

Zwart, S. R.↗

Radiation Effect on Human Tissue

Predicting the occurrence of human cancer following exposure of an epidemiologic population to any agent causing genetic damage is a difficult task. To an approximation, this is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within clinically normal individuals. This situation begs the need for alternate controlled experimental models that are predictive for the development of human cancer following exposures to agents causing genetic damage. Such models historically have not been of substantial proven value. It is more recently encouraging, however, that developments in molecular and cell biology have led to an expanded knowledge of human carcinogenesis, and of molecular markers associated with that process. It is therefore appropriate to consider new laboratory models developed to accomodate that expanded knowledge in order to assess the cancer risks associated with exposures to genotoxic agents. When ionizing radiation of space is the genotoxic agent, then a series of additional considerations for human cancer risk assessment must also be applied. These include the dose of radiation absorbed by tissue at different locations in the body, the quality of the absorbed radiation, the rate at which absorbed dose accumulates in tissue, the way in which absorbed dose is measured and calculated, and the alterations in incident radiation caused by shielding materials. It is clear that human cancer risk assessment for damage caused by ionizing radiation is a multidisciplinary responsibility, and that within this responsibility no single discipline can hold disproportionate sway if a risk assessment model of radiation-induced human cancer is to be developed that has proven value. Biomolecular and cellular markers from the work reported here are considered for use in assessing human cancer risk related to exposure to space radiation. This potential use must be integrated within the specified multidisciplinary context in order to create a new tool of molecular epidemiology that can hopefully then realistically assess this cancer risk.

Richmond, Robert C.↗