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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 397 records · Page 22
All sourcesNASA NTRSDOE OSTI
NASA NTRS1985

Morphologic and histochemical studies of bone cells from SL-3 rats

Previous studies of rat bone following space flight indicate a significant reduction in new bone formation as a result of hypogravity. In the present study of animals from SL-3 flight, the cellular activity of the bone forming cells, the osteoblasts, was investigated. Measurements of alkaline and acid phosphatase, Golgi activity, secretory granule size, and lysosomal activity, all indicated very little difference between flight and flight-simulated controls. However, there was a tendency for osteoblasts in compact bone of flight animals to show a smaller cytoplasmic volume compared to non-flight controls. If, as in previous studies, a significant reduction in bone formation occurred, it could be due to a normal level of procollagen degradation within these smaller osteoblasts, resulting in less collagen secretion per cell.

Doty, S. B.↗
NASA NTRS2000

Convergent properties of vestibular-related brain stem neurons in the gerbil

Three classes of vestibular-related neurons were found in and near the prepositus and medial vestibular nuclei of alert or decerebrate gerbils, those responding to: horizontal translational motion, horizontal head rotation, or both. Their distribution ratios were 1:2:2, respectively. Many cells responsive to translational motion exhibited spatiotemporal characteristics with both response gain and phase varying as a function of the stimulus vector angle. Rotationally sensitive neurons were distributed as Type I, II, or III responses (sensitive to ipsilateral, contralateral, or both directions, respectively) in the ratios of 4:6:1. Four tested factors shaped the response dynamics of the sampled neurons: canal-otolith convergence, oculomotor-related activity, rotational Type (I or II), and the phase of the maximum response. Type I nonconvergent cells displayed increasing gains with increasing rotational stimulus frequency (0.1-2.0 Hz, 60 degrees /s), whereas Type II neurons with convergent inputs had response gains that markedly decreased with increasing translational stimulus frequency (0.25-2.0 Hz, +/-0.1 g). Type I convergent and Type II nonconvergent neurons exhibited essentially flat gains across the stimulus frequency range. Oculomotor-related activity was noted in 30% of the cells across all functional types, appearing as burst/pause discharge patterns related to the fast phase of nystagmus during head rotation. Oculomotor-related activity was correlated with enhanced dynamic range compared with the same category that had no oculomotor-related response. Finally, responses that were in-phase with head velocity during rotation exhibited greater gains with stimulus frequency increments than neurons with out-of-phase responses. In contrast, for translational motion, neurons out of phase with head acceleration exhibited low-pass characteristics, whereas in-phase neurons did not. Data from decerebrate preparations revealed that although similar response types could be detected, the sampled cells generally had lower background discharge rates, on average one-third lower response gains, and convergent properties that differed from those found in the alert animals. On the basis of the dynamic response of identified cell types, we propose a pair of models in which inhibitory input from vestibular-related neurons converges on oculomotor neurons with excitatory inputs from the vestibular nuclei. Simple signal convergence and combinations of different types of vestibular labyrinth information can enrich the dynamic characteristics of the rotational and translational vestibuloocular responses.

Non-NASA Center↗
NASA NTRS1998

Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness

Shortly after the discovery of polonium and radium by Marie Curie and her husband and colleague, Pierre Curie, it was learned that exposure to these alpha-particle emitters produced deleterious biological effects. The mechanisms underlying the increased biological effectiveness of densely ionizing radiations, including alpha particles, neutrons and highly energetic heavy charged particles, remain an active area of investigation. In this paper, we review recent advances in several areas of the radiobiology of these densely ionizing radiations, also known as heavy ions. Advances are described in the areas of DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogenesis in vivo. We focus on technical innovations, including novel applications of pulsed-field gel electrophoresis, fluorescence in situ hybridization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and animal systems, including those with defined DNA repair deficiencies, as well as epithelial cell model systems to assess neoplastic transformation both in vitro and in vivo. The studies reviewed herein have had a substantial impact on our understanding of the genotoxic effects of heavy ions as well as their distinct effects on tissue homeostasis. The use of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several centers around the world, due to their unique energy deposition characteristics that enhance the therapeutic effect and help reduce damage to normal tissue.

Review, Academic↗
NASA NTRS1981

Reissner's membrane and the spiral ligament in normal rats and those treated with ethacrynic acid

A description is presented of recent ultrastructural findings in Reissner's membrane and the spiral ligament in rats treated daily with ethacrynic acid during the 2nd and 3rd weeks of postnatal life, a period of final maturation of the inner ear and its fluids. A distension of Reissner's membrane in every cochlear turn, indicative of mild endolymphatic hydrops, was found to occur in animals that received a higher dose of ethacrynic acid. Ultrastructurally, the cytoplasm of the epithelial cells of Reissner's membrane showed increased electron density after treatment with ethacrynic acid. This increase was most pronounced in animals treated with a greater quantity of the drug. The epithelial cells had similar ultracellular features throughout except that the cells were much thinner in the region of maximal distension.

Ross, M. D.↗
NASA NTRS2004

Effects of heavy ion to the primary culture of mouse brain cells

To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions by HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05 Gy up to 2.0 Gy. The subsequent biological effects were evaluated by an induction of apoptosis and neuron survival focusing on the dependencies of the animal strains, SCID, B6, B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to particle radiation as evaluated by 10% apoptotic criterion. The LET dependency was compared with using SCID and B6 cells exposing to different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency was observed in the high LET (55-200 keV/micrometers) and low dose (<0.5 Gy) regions. The survivability profiles of the neurons were different in the mouse strains and ions. In this report, a result of memory and learning function to adult mice after whole-body and brain local irradiation at carbon ion and iron ion.

NASA Discipline Radiation Health↗
NASA NTRS1993

Association of actin with alpha crystallins

The alpha crystallins are cytosolic proteins that co-localize and co-purify with actin-containing microfilaments. Affinity column chromatography employing both covalently-coupled actin or alpha crystallin was used to demonstrate specific and saturable binding of actin with alpha crystallin. This conclusion was confirmed by direct visualization of alpha aggregates bound to actin polymerized in vitro. The significance of this interaction in relation to the functional properties of these two polypeptides will be discussed.

NASA Program NSCORT↗
NASA NTRS2002

Inhibition of caspases prevents ototoxic and ongoing hair cell death

Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal transduction pathways that mediate hair cell death are not known. Here we identify several important signaling events that regulate the death of vestibular hair cells. Chick utricles were cultured in media supplemented with the ototoxic antibiotic neomycin and selected pharmacological agents that influence signaling molecules in cell death pathways. Hair cells that were treated with neomycin exhibited classically defined apoptotic morphologies such as condensed nuclei and fragmented DNA. Inhibition of protein synthesis (via treatment with cycloheximide) increased hair cell survival after treatment with neomycin, suggesting that hair cell death requires de novo protein synthesis. Finally, the inhibition of caspases promoted hair cell survival after neomycin treatment. Sensory hair cells in avian vestibular organs also undergo continual cell death and replacement throughout mature life. It is unclear whether the loss of hair cells stimulates the proliferation of supporting cells or whether the production of new cells triggers the death of hair cells. We examined the effects of caspase inhibition on spontaneous hair cell death in the chick utricle. Caspase inhibitors reduced the amount of ongoing hair cell death and ongoing supporting cell proliferation in a dose-dependent manner. In isolated sensory epithelia, however, caspase inhibitors did not affect supporting cell proliferation directly. Our data indicate that ongoing hair cell death stimulates supporting cell proliferation in the mature utricle.

Non-NASA Center↗
NASA NTRS2002

Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns

The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

NASA Discipline Evolutionary Biology↗
NASA NTRS1992

Proliferation and performance of hybridoma cells in microgravity (7-IML-1)

The purpose of this experiment is to study how cell performance (biosynthesis and secretion) is altered by altered gravity conditions. Hybridoma cells are obtained by fusion of an activated B-lymphocyte with a myeloma cell. Activated B-lymphocytes, derived from a human or an animal, carry the information required to produce antibodies of a certain specificity and can survive only a few days in culture. Myeloma cells are tumor cells which can grow indefinitely in culture. Therefore, the product of the fusion is an immortal cell line capable of producing homogeneous antibodies (monoclonal antibodies). Experimental procedures are explained in some detail.

Cogoli, Augusto↗
NASA NTRS1995

Lipopolysaccharide modulation of a CD14-like molecule on porcine alveolar macrophages

Cluster of differentiation antigen 14 (CD14) functions as a receptor for lipopolysaccharide (LPS) LPS-binding protein (LBP) complexes. Because LPS has varying effects on CD14 expression in vitro, we evaluated CD14 expression in response to LPS with a fully differentiated macrophage phenotype, the alveolar macrophage. By using flow microfluorometric analysis and a radioimmunoassay with an anti-human CD14 monoclonal antibody (My4) that cross-reacts with porcine CD14, we found that macrophages stimulated with LPS for 24 h exhibited a two- to fivefold increase in CD14-like antigen compared with unstimulated cells. At low concentrations of LPS, up-regulation of the CD14-like antigen was dependent on serum; at higher concentrations of LPS, serum was not required. In the absence of serum a 10-fold higher dose of LPS (10 ng/ml) was required to increase CD14-like expression. In addition, LPS-induced CD14-like up-regulation correlated with secretion of tumor necrosis factor-alpha, regardless of serum concentration. Blockade with My4 antibody significantly inhibited LPS-induced tumor necrosis factor-alpha secretion at 1 ng/ml of LPS. However, inhibition decreased as we increased the LPS concentration, suggesting the existence of CD14-independent pathways of macrophage activation in response to LPS. Alternatively, My4 may have a lower affinity for the porcine CD14 antigen than LPS, which may have only partially blocked the LPS-LBP binding site at high concentrations of LPS. Therefore, these data suggest that LPS activation of porcine alveolar macrophages for 24 h increased CD14-like receptor expression. The degree of CD14-like up-regulation was related to LPS concentration, however, activation did not require the presence of serum at high concentrations of LPS.

Non-NASA Center↗
NASA NTRS2015

Dietary Supplement Attenuates Radiation-Induced Osteoclastogenic and Oxidative Stress-Related Responses and Protects Adult Mice from Radiation-Induced Bone Loss

Our central hypothesis is that oxidative stress plays a key role in cell dysfunction and progressive bone loss caused by radiation exposure during spaceflight. In animal studies, excess free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. We previously reported that exposure to low or high-LET radiation rapidly increases expression levels of pro-osteoclastogenic and oxidative stress-related genes in bone and marrow, followed by pathological changes in skeletal structure. To screen various antioxidants for radioprotective effects on bone, 4 month old, male C57Bl6/J mice were treated with a dietary antioxidant cocktail, injectable alpha-lipoic acid, or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs total body radiation and one day later marrow cells were collected and the relevant genes analyzed for expression levels. Of the candidates tested, DP was most effective in reducing bone resorption-related gene expression. Microcomputed tomography revealed that DP also prevented the radiation-induced deterioration of skeletal microarchitecture, as indicated by percent bone volume, trabecular spacing and trabecular number. DP had similar protective effects on skeletal structure after sequential exposure to protons (0.5 Gy, 150MeV/n) and 56Fe 0.5Gy, 600 MeV/n). When cultured ex vivo under osteogenic conditions, bone marrow-derived cells from DP-fed animals exhibited increased colony numbers compared to control diet-fed animals. These findings suggest that DP exerted pro-osteogenic effects apart from previously identified anti-resorptive actions, which may contribute to radioprotection of skeletal tissue. In conclusion, a diet enriched in certain types of antioxidants and polyphenols such as DP may be useful as an intervention to protect tissues from degenerative effects of ionizing radiation.

Globus, Ruth↗
NASA NTRS2003

Dual reporter transgene driven by 2.3Col1a1 promoter is active in differentiated osteoblasts

AIM: As quantitative and spatial analyses of promoter reporter constructs are not easily performed in intact bone, we designed a reporter gene specific to bone, which could be analyzed both visually and quantitatively by using chloramphenicol acetyltransferase (CAT) and a cyan version of green fluorescent protein (GFPcyan), driven by a 2.3-kb fragment of the rat collagen promoter (Col2.3). METHODS: The construct Col2.3CATiresGFPcyan was used for generating transgenic mice. Quantitative measurement of promoter activity was performed by CAT analysis of different tissues derived from transgenic animals; localization was performed by visualized GFP in frozen bone sections. To assess transgene expression during in vitro differentiation, marrow stromal cell and neonatal calvarial osteoblast cultures were analyzed for CAT and GFP activity. RESULTS: In mice, CAT activity was detected in the calvaria, long bone, teeth, and tendon, whereas histology showed that GFP expression was limited to osteoblasts and osteocytes. In cell culture, increased activity of CAT correlated with increased differentiation, and GFP activity was restricted to mineralized nodules. CONCLUSION: The concept of a dual reporter allows a simultaneous visual and quantitative analysis of transgene activity in bone.

Non-NASA Center↗
NASA NTRS2000

Role of founder cell deficit and delayed neuronogenesis in microencephaly of the trisomy 16 mouse

Development of the neocortex of the trisomy 16 (Ts16) mouse, an animal model of Down syndrome (DS), is characterized by a transient delay in the radial expansion of the cortical wall and a persistent reduction in cortical volume. Here we show that at each cell cycle during neuronogenesis, a smaller proportion of Ts16 progenitors exit the cell cycle than do control, euploid progenitors. In addition, the cell cycle duration was found to be longer in Ts16 than in euploid progenitors, the Ts16 growth fraction was reduced, and an increase in apoptosis was observed in both proliferative and postmitotic zones of the developing Ts16 neocortical wall. Incorporation of these changes into a model of neuronogenesis indicates that they are sufficient to account for the observed delay in radial expansion. In addition, the number of neocortical founder cells, i.e., precursors present just before neuronogenesis begins, is reduced by 26% in Ts16 mice, leading to a reduction in overall cortical size at the end of Ts16 neuronogenesis. Thus, altered proliferative characteristics during Ts16 neuronogenesis result in a delay in the generation of neocortical neurons, whereas the founder cell deficit leads to a proportional reduction in the overall number of neurons. Such prenatal perturbations in either the timing of neuron generation or the final number of neurons produced may lead to significant neocortical abnormalities such as those found in DS.

Non-NASA Center↗
NASA NTRS2002

Transcriptional profiling reveals regulated genes in the hippocampus during memory formation

Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real-time polymerase chain reaction. These genes were growth hormone (GH), c-kit receptor tyrosine kinase (c-kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor-beta (NGF-beta), Jun oncogene (c-Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal-dependent associative memories.

Non-NASA Center↗
NASA NTRS1992

Microtubules as key cytoskeletal elements in cellular transport and shape changes: their expected responses to space environments

Application of reference standard reagents to alternatively depolymerize or stabilize microtubules in a cell that undergoes very regular cytoskeleton-dependent shape changes provides a model system in which some expected components of the environments of spacecraft and space can be tested on Earth for their effects on the cytoskeleton. The fertilized eggs of Ilyanassa obsoleta undergo polar lobe formation by repeated, dramatic, constriction and relaxation of a microfilamentous band localized in the cortical cytoplasm and activated by microtubules.

NASA Discipline Number 93-10↗
NASA NTRS1995

Satellite cell proliferation in adult skeletal muscle

Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

Booth, Frank W.↗
NASA NTRS2002

Functional Characterization of G12, a Gene Required for Mitotic Progression during Gastrulation in Zebrafish

In a differential RNA display screen we have isolated a zebrafish gene, G12, for which homologs can only be found in DNA databases for vertebrates, but not invertebrates. This suggests that this is a gene required specifically in vertebrates. G12 expression is upregulated at mid-blastula transition (MBT). Morpholino inactivation of this gene by injection into 1-cell embryos results in mitotic defects and apoptosis shortly after MBT. Nuclei in morpholino treated embryos also display segregation defects. We have characterized the localization of this gene as a GFP fusion in live and fixed embryos. Overexpression of G12-GFP is non-toxic. Animals retain GFP expression for at least 7 days with no developmental defects, Interestingly in these animals G12-GFP is never detectable in blood cells though blood is present. In the deep cells of early embryos, G 12GFP is localized to nuclei and cytoskeletal elements in interphase and to the centrosome and spindle apparatus during mitosis. In the EVL, G12-GFP shows additional localization to the cell periphery, especially in mitosis. In the yolk syncytium, G12-GFP again localizes to nuclei and strongly to cytoplasmic microtubules of migrating nuclei at the YSL margin. Morpholinc, injection specifically into the YSL after cellularization blocks epiboly and nuclei of the YSL show mitotic defects while deep cells show no mitotic defects and continue to divide. Rescue experiments in which morpholino and G12-GFP RNA are co-injected indicate partial rescue by the G12-GFP. The rescue is cell autonomous; that is, regions of the embryo with higher G12-GFP expression show fewer mitotic defects. Spot 14, the human bomolog of G12, has been shown to be amplified in aggressive breast tumors. This finding, along with our functional and morphological data suggest that G12 and spot 14 are vertebrate-specific and may function either as mitotic checkpoints or as structural components of the spindle apparatus.

Reinsch, Sigrid↗
NASA NTRS2001

Osteoblasts respond to pulsatile fluid flow with short-term increases in PGE(2) but no change in mineralization

Although there is no consensus as to the precise nature of the mechanostimulatory signals imparted to the bone cells during remodeling, it has been postulated that deformation-induced fluid flow plays a role in the mechanotransduction pathway. In vitro, osteoblasts respond to fluid shear stress with an increase in PGE(2) production; however, the long-term effects of fluid shear stress on cell proliferation and differentiation have not been examined. The goal of this study was to apply continuous pulsatile fluid shear stresses to osteoblasts and determine whether the initial production of PGE(2) is associated with long-term biochemical changes. The acute response of bone cells to a pulsatile fluid shear stress (0.6 +/- 0.5 Pa, 3.0 Hz) was characterized by a transient fourfold increase in PGE(2) production. After 7 days of static culture (0 dyn/cm(2)) or low (0.06 +/- 0.05 Pa, 0.3 Hz) or high (0.6 +/- 0.5 Pa, 3.0 Hz) levels of pulsatile fluid shear stress, the bone cells responded with an 83% average increase in cell number, but no statistical difference (P > 0.53) between the groups was observed. Alkaline phosphatase activity per cell decreased in the static cultures but not in the low- or high-flow groups. Mineralization was also unaffected by the different levels of applied shear stress. Our results indicate that short-term changes in PGE(2) levels caused by pulsatile fluid flow are not associated with long-term changes in proliferation or mineralization of bone cells.

NASA Discipline Musculoskeletal↗