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At least 649 records · Page 36

Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo

The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.

NASA Discipline Neuroscience↗

Oxidative Stress and Autophagy Responses of Osteocytes Exposed to Spaceflight-like Radiation.

Weightlessness and radiation, two of the unique elements of the space environment, causes a profound decrement in bone mass that mimics aging. This bone loss is thought to result from increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Our current understanding of the signaling factors and mechanisms underlying bone loss is incomplete. However, it is known that oxidative stress, characterized by the excess production of free radicals, is elevated during radiation exposure. The goals of this study is to examine the response of osteocytes to spaceflight-like radiation and to identify signaling processes that may be targeted to mitigate bone loss in scenarios of space exploration, earth-based radiotherapy and accidental radiation exposure. We hypothesize that (1) oxidative stress, as induced by radiation, decreases osteocyte survival and increases pro-osteoclastogenic signals and that (2) autophagy is one of the key cellular defenses against oxidative stress. Autophagy is the process by which cellular components including organelles and proteins are broken down and recycled. To test our hypothesis, we exposed the osteocyte-like cell line, MLO-Y4, to 0.5, 1, and 2 Gy of simulated space radiation (Iron-56 radiation at 600 MeV/n) and assessed cell numbers, cell growth-associated molecules as well as markers of autophagy and oxidative stress at various time points post-irradiation. We observed a reduction in cell numbers in the groups exposed to 1 and 2 Gy of Iron-56 radiation. Collectively, flow cytometry and gene expression analysis revealed that radiation caused a shift in cell cycle distribution consistent with growth arrest. Compared to sham-treatment, 2 Gy of Iron-56 increased FoxO3, SOD1, and RANKL gene expression yet unexpectedly decreased LC3B-II protein levels at 4 and 24 hours post-IR. Taken together, these findings suggest that simulated space radiation invoke antioxidant, pro-osteoclastogenic, and growth arrest responses in osteocytes. The implications of reduced autophagy flux at the time points examined remain to be elucidated.

Biological Sciences↗

Size Exclusion Chromatography Studies of the Initial Self-Association Steps of Chicken Egg White Lysozyme Nucleation

Nucleation is one of the least understood aspects of crystallogenesis. In the case of macromolecule nucleation, this understanding is further hampered by uncertainty over what precisely is being discussed. We define the process of solute self-association (aggregation, oligomerization, interaction, clustering, etc.) whereby n-mers (n > or = 2) having a crystallographic or nascent crystallographic arrangement leading to the critical nucleus reversibly form in the solution, to be part of the nucleation process. This reversible self-association process is a fundamental part of the nucleation process, and occurs as a function of the solute concentration. In the case of chicken egg white lysozyme, a considerable body of experimental evidence leads us to the conclusion that it also forms the crystal growth units. Size exclusion chromatography is a simple and direct method for determining the equilibrium constants for the self-association process. A Pharmacia FPLC system was used to provide accurate solution flow rates. The column, injection valve, and sample loop were all mounted within a temperature-controlled chamber. Chromatographically re-purified lysozyme was first dialyzed against the column equilibration buffer, with injection onto the column after several hours pre-incubation at the running temperature. Preliminary experiments, were carried out using a Toyopearl HW-50F column (1 x 50cm), equilibrated with 0.1 M sodium acetate, 5% sodium chloride, pH 4.6, at 15C. Protein concentrations from 0.1 to 4 mg/ml were employed (C(sub sat) = 1.2 mg/ml). The data from several different protein preparations consistently shows a progressively decreasing elution volume with increasing protein concentration, indicating that reversible self-association is occurring. The dotted line indicates the monomeric lysozyme elution volume. However, lysozyme interacts with the column matrix in these experiments, which complicates data analysis.Accordingly, we are testing silica-based HPLC columns in an effort to eliminate this problem and substantially reduce the column volume and experimental run time. The results and data analysis from these and subsequent experiments will be presented.

Ewing, Felecia↗

Persistent Ehrlichia chaffeensis infection occurs in the absence of functional major histocompatibility complex class II genes

Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis. We investigated the impact of two genes that control macrophage and T-cell function on murine resistance to E. chaffeensis. Congenic pairs of wild-type and toll-like receptor 4 (tlr4)- or major histocompatibility complex class II (MHC-II)-deficient mice were used for these studies. Wild-type mice cleared the infection within 2 weeks, and the response included macrophage activation and the synthesis of E. chaffeensis-specific Th1-type immunoglobulin G response. The absence of a functional tlr4 gene depressed nitric oxide and interleukin 6 secretion by macrophages and resulted in short-term persistent infections for > or =30 days. In the absence of MHC-II alleles, E. chaffeensis infections persisted throughout the entire 3-month evaluation period. Together, these data suggest that macrophage activation and cell-mediated immunity, orchestrated by CD4(+) T cells, are critical for conferring resistance to E. chaffeensis.

NASA Discipline Cell Biology↗

Building Better Biosensors for Exploration into Deep-Space, Using Humanized Yeast

1.BioSentinel is 1 of 13 secondary payloads hitching a ride beyond Low Earth Orbit on Exploration Mission 1 (EM-1), set to launch from NASAs Space Launch System in 2019. EM-1 is our first opportunity to investigate the effects of the deep space environment on a eukaryotic biological system, the budding yeast S. cerevisiae. Though separated by a billion years of evolution we share hundreds of genes important for basic cell function, including responses to DNA damage. Thus, yeast is an ideal biosensor for detecting typesextent of damage induced by deep-space radiation.We will fly desiccated cells, then rehydrate to wake them up when the automated payload is ready to initiate the experiment. Rehydration solution contains SC (Synthetic Complete) media and alamarBlue, an indicator for changes in growth and metabolism. Telemetry of LED readings will then allow us to detect how cells respond throughout the mission. The desiccation-rehydration process can be extremely damaging to cells, and can severely diminish our ability to accurately measure and model cellular responses to deep-space radiation. The aim of this study is to develop a better biosensor: yeast strains that are more resistant to desiccation stress. We will over-express known cellular protectants, including hydrophilin Sip18, the protein disaggregase Hsp104, and thioredoxin Trx2, a responder to oxidative stress, then measure cell viability after desiccation to determine which factors improve stress tolerance. Over-expression of SIP18 in wine yeast starter cultures was previously reported to increase viability following desiccation stress by up to 70. Thus, we expect similar improvements in our space-yeast strains. By designing better yeast biosensors we can better prepare for and mitigate the potential dangers of deep-space radiation for future missions.This work is funded by NASAs AES program.

biosensor↗

Water as a matrix for life

"Follow the water" is the canonical strategy in searching for life in the universe. Conventionally, discussion of this topic is focused on how solvent supports organic chemistry sufficiently rich to seed life. Perhaps more importantly, solvent must promote self-organization of organic matter into functional structures capable of responding to environmental changes. This process is based on non-covalent interactions. They are constantly formed and broken in response to internal and external stimuli. This requires that their strength must be properly tuned. If they were too weak, the system would exhibit undesired, uncontrolled response to natural fluctuations of physical and chemical parameters. If they were too strong kinetics of biological processes would be slow and energetics costly. Non-covalent interactions are strongly mediated by the solvent. Specifically, high dielectric solvents for life are needed for solubility of polar species and flexibility of biological structures stabilized by electrostatic interactions. Water exhibits a remarkable trait that it promotes solvophobic interactions between non-polar species, which are responsible for self-organization phenomena such as the formation of cellular boundary structures, and protein folding and aggregation. Unusual temperature dependence of hydrophobic interactions - they often become stronger as temperature increases - is a consequence of the temperature insensitivity of properties of the liquid water. This contributes to the existence of robust life over a wide temperature range. Water is not the only liquid with favorable properties for supporting life. Other pure liquids or their mixtures that have high dielectric constants and simultaneously support some level of self-organization will be discussed.

Pohorille, Andrew↗

GeneLab: A Systems Biology Platform for Spaceflight Omics Data

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

proteomics↗

Nutritional Status in Self-Neglecting Elderly

Elder self-neglect is the most common, and most compelling form of elder mistreatment. Individuals who cannot provide the basic needs for themselves may develop social, functional, and physical deficits. The CREST project has the goal of systematically characterizing these individuals, and the objective of the study reported here is to characterize aspects of their nutritional status. Self-neglect (SN) subjects referred from Adult Protective Services were recruited and consented. Control (CN) subjects were matched for age, gender, race, and socio-economic status when possible. Reported here are data on 47 SN subjects (age 77 +/- 7, mean +/- SD; body weight 76 kg +/- 26) and 40 CN subjects (77 +/- 7, 79 kg +/- 20). Blood samples were analyzed for indices of nutritional status. SN subjects had higher serum concentrations of homocysteine (p < 0.01) and methylmalonic acid (p < 0.05). Red blood cell folate levels were lower (p < 0.01) in the SN subjects and serum folate levels tended (p < 0.07) to be lower, also. C-reactive protein concentrations were higher than 10 mg/dL in 36% of SN subjects and 18% of CN subjects. Total cholesterol and triglyceride concentrations were similar in the two groups. These data demonstrate that the self-neglecting elderly population is at risk with respect to several markers of nutritional status.

Oliver, S. Mathews↗

Otx1 null mutant mice show partial segregation of sensory epithelia comparable to lamprey ears

We investigated the development of inner ear innervation in Otx1 null mutants, which lack a horizontal canal, between embryonic day 12 (E12) and postnatal day 7 (P7) with DiI and immunostaining for acetylated tubulin. Comparable to control animals, horizontal crista-like fibers were found to cross over the utricle in Otx1 null mice. In mutants these fibers extend toward an area near the endolymphatic duct, not to a horizontal crista. Most Otx1 null mutants had a small patch of sensory hair cells at this position. Measurement of the area of the utricular macula suggested it to be enlarged in Otx1 null mutants. We suggest that parts of the horizontal canal crista remain incorporated in the utricular sensory epithelium in Otx1 null mutants. Other parts of the horizontal crista appear to be variably segregated to form the isolated patch of hair cells identifiable by the unique fiber trajectory as representing the horizontal canal crista. Comparison with lamprey ear innervation reveals similarities in the pattern of innervation with the dorsal macula, a sensory patch of unknown function. SEM data confirm that all foramina are less constricted in Otx1 null mutants. We propose that Otx1 is not directly involved in sensory hair cell formation of the horizontal canal but affects the segregation of the horizontal canal crista from the utricle. It also affects constriction of the two main foramina in the ear, but not their initial formation. Otx1 is thus causally related to horizontal canal morphogenesis as well as morphogenesis of these foramina.

NASA Discipline Developmental Biology↗

Notes on Interface Growth Kinetics 50 Years after Burton, Cabrera and Frank

This overview is devoted to some unresolved basic problems in crystal growth kinetics. The density wave approach to propagation of a spatially diffuse interface between a growing crystal and its simple (e.g., metallic) melt is discussed is Section 2. This approach allows for the calculation of kinetic coefficients and is an alternative to the localized interface concept in which each atom belongs to either a solid or a liquid. Sections 3 and 4 deals mainly with layer growth from solution. Mutual retardation of the growth steps via their bulk and d a c e diffusion fields is the major subject. The influence of solution flow on step bunching (Section 4) suggests the essential influence of bulk diffusion on the surface morphology. The flow within the solution boundary layer enhances step-step interaction, influences the step bunching process and the resulting step pattern morphology on the growing surface. Recent experiments on the rates at which strongly polygonized steps on protein and small molecule crystals propagate during growth from solution are analyzed in Section 5 . We have shown that the step segments may be "singular" and that "one-dimensional nucleation" may be the rate limiting stage for the segments that are shorter or comparable in length to the thermodynamically equilibrium interlink distance. In this case, the reciprocal dependence of the segment propagation rate on the segment length that follow from the Gibbs-Thompson law, should be replaced by an abrupt switch from zero to a finite constant velocity. Until recently, the Kossel crystal remained the only model used in crystal growth theory. In such Kossel Gibbs-Thomson law, should be replaced by an abrupt switch &om zero to a finite constant velocity. crystals, all kinks at the steps are identical and the kink rate is a linear function of the supersaturation. In the non-Kossel crystals, there may be several kink configurations characterized by different geometries and energies. These configurations should appear in a specific sequence when each new lattice unit cell is filled. As a result of such a cooperative interaction within the unit cell, a non-linear dependence of the kink rate on the vapor pressure or solution concentration in excess over the equilibrium value should be expected.

Chernov, A. A.↗

The estimation of genetic divergence

Consideration is given to the criticism of Nei and Tateno (1978) of the REH (random evolutionary hits) theory of genetic divergence in nucleic acids and proteins, and to their proposed alternative estimator of total fixed mutations designated X2. It is argued that the assumption of nonuniform amino acid or nucleotide substitution will necessarily increase REH estimates relative to those made for a model where each locus has an equal likelihood of fixing mutations, thus the resulting value will not be an overestimation. The relative values of X2 and measures calculated on the basis of the PAM and REH theories for the number of nucleotide substitutions necessary to explain a given number of observed amino acid differences between two homologous proteins are compared, and the smaller values of X2 are attributed to (1) a mathematical model based on the incorrect assumption that an entire structural gene is free to fix mutations and (2) the assumptions of different numbers of variable codons for the X2 and REH calculations. Results of a repeat of the computer simulations of Nei and Tateno are presented which, in contrast to the original results, confirm the REH theory. It is pointed out that while a negative correlation is observed between estimations of the fixation intensity per varion and the number of varions for a given pair of sequences, the correlation between the two fixation intensities and varion numbers of two different pairs of sequences need not be negative. Finally, REH theory is used to resolve a paradox concerning the high rate of covarion turnover and the nature of general function sites as permanent covarions.

Holmquist, R.↗

Physiology of a microgravity environment invited review: microgravity and skeletal muscle

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

short duration↗

Biomaterials Out of Thin Air: in Situ, On-Demand Printing of Advanced Biocomposites

Upmass is the single most significant limitation of our current space mission capability. Although biomaterials and biocomposites have mass, strength, flexibility, and self-healing properties that could significantly reduce upmass, their use is limited by the following drawbacks: Expensive, specific production. Many biomaterials can only be produced as part of significant support ecosystem; Inaccessible functional customization. The grain of wood, the porosity of bone, and so on are an integral part of the materials' desired mechanical properties, but are not deterministic when the material is naturally grown; Limited compositions. Most biomaterials (unlike metal, plastic, etc.) cannot be easily combined or modified to produce new materials. This project builds on recent advances in: Synthetic biology. Libraries of standardized genetic parts which can be used for controlled cellular material production, delivery, and binding; 3D printing. Commercial off-the-shelf components which can be used to make of a pico- to nanoliter cell deposition system; Tissue engineering. Proven cell-compatible support hydrogels and scaffolds can be modified to bind the deposited biomaterials of interest. Objectives: Feasibility and benefit analysis. Two mission contexts span the concept's scope (see below); Proof-of-concept demonstration. A simple grid of two proteins, fluorescent for easy detection, to validate the core technology concept; Proposed implementations for follow-on work. Avenues for future work on each core component (host cell, production control, material delivery, material binding, etc.); Complementary studies exploration. A survey of other emerging areas (in situ resource utilization, protein engineering, etc.) with the potential to multiply our technology's impact. Potential Impacts: This application could dramatically expand manufacturing capabilities on Earth and in space: In situ resource utilization. A far greater range of materials and products will be available from the limited palette offered by in situ resource extraction techniques; Reduced equipment and material upmass for off-Earth habitats. Ready- to-use highly specialized construction materials (radiation hardened, compressive/tensile, light or dense) from an extremely low starting mass; Structured biomaterial production. New ready-to-use macro, micro, and molecular manufacturing techniques for traditional biomaterials such as wood, bone and shell; New and novel biocomposite creation. The ability to create completely novel material composites from any base material that cells can be engineered to produce. Suggested Mission Contexts: ISS part manufacturing. A 'minimal working example' making a finished biomaterial part aboard the International Space Station; A long-term Mars habitat. 'Cradle-to-grave' use at a hypothetical Mars habitat, covering everything from tools to construction materials. Alternate Abstract: Imagine being able to print anything from tools and composite building materials to food and human tissues. Imagine being on Mars with the ability to replace any broken part, whether it's a part of your spacesuit, your habitat, or your own body. We propose a technique that would allow just that. By printing 3D arrays of cells engineered to secrete the necessary materials, the abundant in situ resources of atmosphere and regolith become organic, inorganic, or organic-inorganic composite materials. Such materials include novel, biologically derived materials not previously possible to fabricate.

habitats↗

Biomaterials Out of Thin Air: in Situ, On-demand Printing of Advanced Biocomposites

Upmass is the single most significant limitation of our current space mission capability. Although biomaterials and biocomposites have mass, strength, flexibility, and self-healing properties that could significantly reduce upmass, their use is limited by the following drawbacks: Expensive, specific production. Many biomaterials can only be produced as part of significant support ecosystem; Inaccessible functional customization. The grain of wood, the porosity of bone, and so on are an integral part of the materials' desired mechanical properties, but are not deterministic when the material is naturally grown; Limited compositions. Most biomaterials (unlike metal, plastic, etc.) cannot be easily combined or modified to produce new materials. This project builds on recent advances in: Synthetic biology. Libraries of standardized genetic parts which can be used for controlled cellular material production, delivery, and binding; 3D printing. Commercial off-the-shelf components which can be used to make of a pico- to nanoliter cell deposition system; Tissue engineering. Proven cell-compatible support hydrogels and scaffolds can be modified to bind the deposited biomaterials of interest. Objectives: Feasibility and benefit analysis. Two mission contexts span the concept's scope (see below); Proof-of-concept demonstration. A simple grid of two proteins, fluorescent for easy detection, to validate the core technology concept; Proposed implementations for follow-on work. Avenues for future work on each core component (host cell, production control, material delivery, material binding, etc.); Complementary studies exploration. A survey of other emerging areas (in situ resource utilization, protein engineering, etc.) with the potential to multiply our technology's impact. Potential Impacts: This application could dramatically expand manufacturing capabilities on Earth and in space: In situ resource utilization. A far greater range of materials and products will be available from the limited palette offered by in situ resource extraction techniques; Reduced equipment and material upmass for off-Earth habitats. Ready- to-use highly specialized construction materials (radiation hardened, compressive/tensile, light or dense) from an extremely low starting mass; Structured biomaterial production. New ready-to-use macro, micro, and molecular manufacturing techniques for traditional biomaterials such as wood, bone and shell; New and novel biocomposite creation. The ability to create completely novel material composites from any base material that cells can be engineered to produce. Suggested Mission Contexts: ISS part manufacturing. A 'minimal working example' making a finished biomaterial part aboard the International Space Station; A long-term Mars habitat. 'Cradle-to-grave' use at a hypothetical Mars habitat, covering everything from tools to construction materials. Alternate Abstract: Imagine being able to print anything from tools and composite building materials to food and human tissues. Imagine being on Mars with the ability to replace any broken part, whether it's a part of your spacesuit, your habitat, or your own body. We propose a technique that would allow just that. By printing 3D arrays of cells engineered to secrete the necessary materials, the abundant in situ resources of atmosphere and regolith become organic, inorganic, or organic-inorganic composite materials. Such materials include novel, biologically derived materials not previously possible to fabricate.

habitats↗

Variability in Galactic Cosmic Radiation- Induced DNA Damage Response in Inbred Mice Is Modulated by Genetics

In radiation biology, the ability to predict cancer risk associated with exposure to low doses of high-LET (Linear Energy Transfer) ionizing radiation remains a challenge. Epidemiological methods lack the sensitivity and power to provide detailed risk estimates for cancer and ignore individual sensitivity. We have hypothesized that DNA repair capacity is the primary factor differentiating peoples radiation sensitivity. We previously showed in immortalized human cell lines that characterizing the dose and time dependence of p53-binding protein 1 (53BP1) foci formation in the nucleus following X-rays exposure is sufficient to predict DNA repair response to any other LET in the same cell line. We now tested this hypothesis across a population of mice with different genetic background. Fibroblast cells were extracted and cultivated from 76 individual mice from 15 different strains and exposed to HZE (high (H) atomic number (Z) and energy (E) galactic cosmic ray particles) particles and X-rays. Individual radiation sensitivities were investigated by high throughput measurement of DNA repair kinetics that evaluated 53bp1 foci numbers as a surrogate for DNA double-strand breaks at various times post-irradiation. Instead of just counting foci which can be hard to distinguish for high-LET or high doses, we also took into account the track structure of high-LET particles to compute the remaining number of unrepaired tracks as a function of time post-irradiation. As expected, the percentage of unrepaired track over a 48 hours follow-up period increased with LET. In addition, repair rate was modulated by genetics, with animals from the same strain showing small variance while large rate differences were observed between strains. Radiation strain sensitivity ranking was estimated based on repair rates from exposure to each LET evaluated in this work, and ranking for high-LET correlated better with ranking from high dose of X-ray, not low dose. At the in-vivo level, drops in T-cells and B-cells number measured 24 hours after 0.1 Gy (Gray) X-ray exposure, correlated with slower DNA repair kinetic in fibroblast cells of the same strains of mice. At the genomic level, mouse genome wide association (GWA) analysis identified seven significant genetic loci on chromosomes 2, 3, 7, 10, 11, 13 and 19 with different significance depending on the LET. Interestingly, for the two highest LET, a common locus on Chromosome 10 was identified with high enrichment for DNA repair associated genes.Overall, this work suggests that repair kinetics of primary skin fibroblasts is a good surrogate marker for in-vivo radiation sensitivities in other tissues and that this response is modulated by genetics. Our study also confirms that DNA repair kinetics following high doses of X-ray can be used to predict radiation sensitivity to high-LET.

High-LET Radiation↗

Nutrition in Space: Benefits on Earth

History has often proven the criticality for adequate nutrition to ensure expedition success. Space exploration will be no different, with the exception of the certainty that food will not be found along the journey. Ensuring the health and safety of astronauts is critical and nutrition will serve several functions to that end. Nutritional assessment of International Space Station (ISS) crewmembers not only serves to evaluate the nutritional health of individuals, but also allows a better understanding of how space flight affects nutritional requirements, and how nutrition can serve in mitigating the negative effects of weightlessness on the human. Available data suggest that the nutritional status of astronauts is compromised during and after flight. Inadequate dietary intake and subsequent weight loss are often considered hallmarks of space flight, although exceptions to this do exist, and provide hope. However, beyond energy intake, specific nutrient issues also exist. Several vitamins, including D and folate, are affected in space travelers. Hematological and antioxidant defense systems are impacted, with increased iron storage, and increased markers of oxidative damage. Bone loss during space flight remains a critical challenge. Ground-based studies have proven that nutrition is a potent modulator of the bone response to simulated weightlessness. Protein and sodium are two nutrients which tend to exacerbate bone resorption and loss, likely mediated through acid base balance. Defining nutrient requirements, and being able to provide and maintain those nutrients on exploration missions, will be critical for maintaining crew member health. Both flight and ground-based research provide a unique situation, one where healthy individuals are put in a unique and challenging environment. A full understanding of the role of nutrition during space flight will not only enhance crew health and safety during flight, but will also expand our understanding of the role of nutrition in health of those remaining on Earth.

Smith, Scott M.↗

Relationships between pigment composition variation and reflectance for plant species from a coastal savannah in California

Advances in imaging spectroscopy have indicated that remotely sensed reflectance measurements of the plant canopy may be used to identify and qualify some classes of canopy biochemicals; however, the manner in which differences in biochemical compositions translate into differences is not well understood. Most frequently, multiple linear regression routines have been used to correlate narrow band reflectance values with measured biochemical concentrations. Although some success has been achieved with such methods for given data sets, the bands selected by multiple regression are not consistent between data sets, nor is it always clear what physical or biological basis underlies the correlation. To examine the relationship between biochemical concentration and leaf reflectance signal we chose to focus on the visible spectrum where the primary biochemical absorbances are due to photosynthetic pigments. Pigments provide a range of absorbance features, occur over a range of concentrations in natural samples, and are ecophysiologically important. Concentrations of chlorophyll, for example, have been strongly correlated to foliar nitrogen levels within a species and to photosynthetic capacity across many species. In addition pigments effectively absorb most of the photosynthetically active radiation between 400-700 nm, a spectral region for which silicon detectors have good signal/noise characteristics. Our strategy has been to sample a variety of naturally occurring species to measure leaf reflectance and pigment compositions. We hope to extend our understanding of pigment reflectance effects to interpret small overlapping absorbances of other biochemicals in the infrared region. For this reason, selected samples were also tested to determine total nitrogen, crude protein, cellulose, and lignin levels. Leaf reflectance spectra measured with AVIRIS bandwidths and wavelengths were compared between species and within species and for differences between seasons, for changes in the the shape of the spectra. We attempt to statistically correlate these shape changes with differences in pigment compositions. In parallel with our comparisons of pigment composition and leaf reflectance, we have modified the PROSPECT leaf reflectance model to test the contributions of pigments or pigment group concentrations. PROSPECT considers a leaf as a multi-layer dielectric plane with an uneven surface. Jacquemoud adapted the basic analysis of Allen for surface effects, a leaf thickness factor, and the absorption of water and chlorophyll (actually all pigments) and the plant matrix. Our modifications to PROSPECT in the forward direction include breaking out the pigment concentration parameter into separate components for chlorophyll a and b and a number of xanthophylls and carotenes, and introducing a shift and convolution function to model the spread and shift from their in vitro measurements to their in vivo state. Further, we have considered how the matrix elements (i.e., all biochemicals and structural effects not modeled explicity) vary with species.

Ustin, Susan L.↗

Journal of Gravitational Physiology, Volume 12, Number 1

The following topics were covered: System Specificity in Responsiveness to Intermittent -Gx Gravitation during Simulated Microgravity in Rats; A Brief Overview of Animal Hypergravity Studies; Neurovestibular Adaptation to Short Radius Centrifugation; Effect of Artificial Gravity with Exercise Load by Using Short-Arm Centrifuge with Bicycle Ergometer as a Countermeasure Against Disused Osteoporosis; Perception of Body Vertical in Microgravity during Parabolic Flight; Virtual Environment a Behavioral and Countermeasure Tool for Assisted Gesture in Weightlessness: Experiments during Parabolic Flight; Artificial Gravity: Physiological Perspectives for Long-Term Space Exploration; Comparison of the Effects of DL-threo-Beta-Benzyloxyaspartate on the Glutamate Release from Synaptosomes before and after Exposure of Rats to Artificial Gravity; Do Perception and Postrotatory Vestibulo-Ocular Reflex Share the Same Gravity Reference?; Vestibular Adaptation to Changing Gravity Levels and the Orientation of Listing's Plane; Compound Mechanism Hypothesis on +Gz - Induced Brain Injury and Dysfunction of Learning and Memory; Environmental Challenge Impairs Prefrontal Brain Functions; Effect of 6-Days of Support Withdrawal on Characteristics of Balance Function; Hypergravity-Induced Changes of Neuronal Activities in CA1 Region of Rat Hippocampus; Audiological Findings in Antiorthostatic Position Modelling Microgravitation; Investigating Human Cognitive Performance during Spaceflight; The Relevance of the Minimization of Torque Exchange with the Environment in Weightlessness is Confirmed by Asimulation Study; Characteristics of the Eyes Pursuit Function during Readaptation to Terrestrial Gravity after Prolonged Flights Aboard the International Space Station; Comparison of Cognitive Performance Tests for Promethazine Pharmacodynamics in Human Subjects; Structural Reappraisal of Dendritic Tree of Cerebellar Purkinje Cell for Novel Functional Modeling of Elementary Sensorimotor Adaptive Processes; Orpheus 0 G or Ear in Microgravity to Establish Symptoms Concomittant of Inner and Middle Ear and Osteoporosis in Microgravity; Understanding Visual Perception in the Perspective of Gravity; Cortical Regions Associated with Orthostatic Stress in Conscious Humans; Restoration of Central Blood Volume: Application of a Simple Concept and Simple Device to Counteract Cardiovascular Instability in Syncope and Hemorrhage; WISE-2005: Integrative Cardiovascular Responses with LBNP during 60-Day Bed Rest in Women; Intracranial Pressure Increases during Weightlessness. A Parabolic Flights Study; Lower Limb & Portal Veins Echography for Predicting Risk of Thrombosis during a 90-D Bed Rest; Calf Tissue Liquid Stowage and Muscular and Deep Vein Distension in Orthostatic Tests after a 90-Day Head Down Bed Rest; Morphology of Brain Vessels in the Tail Suspended Rats Exposed to Intermittent 2 G; Alterations in Vasoreactivity of Femoral Artery Induced by Hindlimb Unweighting are Related to the Changes of Contractile Protein in Rats; and Respiratory Sinus Arrhythmia: A Marker of Decreased Parasympathetic Modulation after Short Duration.

Fuller, Charles A.↗