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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 217 records · Page 12
All sourcesNASA NTRSDOE OSTI
NASA NTRS1992

Decreased heterotopic osteogenesis in vitamin-D-deficient, but normocalcemic guinea pigs

The effect of vitamin D deficiency unhampered by hypocalcemia on de novo bone formation was studied in guinea pigs. Heterotopic induction of osteogenesis was evaluated 4 weeks after intramuscular transplantation of allogenic urinary bladder transitional epithelium from vitamin-D-repleted (+D) donors into +D and -D recipients. In -D recipients the frequency of osteogenesis and the amount of induced bone were significantly diminished; induced bone was less mature, scantly cellular woven bone poorly repopulated with bone marrow. No effect of vitamin D deficiency on orthotopic bone growth and on mineralization of orthotopic and heterotopically induced bone was observed. It is proposed that in addition to inducing factors (BMPs, growth factors) which may be responsible for transformation of mesenchymal cells to osteoprogenitor cells, normal concentrations of 1,25-(OH)2D3 may be required for proliferation and further differentiation of these cells into osteoblasts and for expression of genes engaged in extracellular matrix formation and maturation.

NASA Discipline Musculoskeletal↗
NASA NTRS1994

Hypergravity signal transduction and gene expression in cultured mammalian cells

A number of studies have been conducted during space flight and with clinostats and centrifuges, suggesting that gravity effects the proliferation and differentiation of mammalian cells in vitro. However, little is known about the mechanisms by which mammalian cells respond to changes in gravitational stress. This paper summarizes studies designed to clarify the effects of hypergravity on the cultured human HeLa cells and to investigate the mechanism of hypergravity signal transduction in these cells.

NASA Center JSC↗
NASA NTRS2019

The Omics of Stem Cell Mediated Regeneration: A Pilot Single Cell RNA-Seq Study of Mechanotransduction

Mechanical forces are potent modulators of stem cell based tissue regenerative mechanisms, inducing cell fate decisions and tissue specific commitment. A unique platform for investigating mechanotransduction is spaceflight, where microgravity and altered fluid mechanics provide a loading-null experimental condition. Seminal investigations of regenerative capacity in a wholly regenerative species, the newt model, and in a variety of totipotent and adult stem cell populations have demonstrated the detrimental effects of unloading on maintenance of stem cell based regeneration. Of particular interest is the observation that unloading interferes with the transition of stem cell pools from proliferative state to differentiation commitment. In this work we sought to test the hypothesis that gravity mechanotransduction regulates stem cell tissue regenerative processes by modulating stem cell proliferation and differentiation fates at specific cell cycle stages. To do this, clonally-derived ESCs were plated on a collagen matrix and expanded for 36 hours before re-plating on a non-adherent culture dish in the absence of leukemia inhibitory factor (LIF) to form spheroid aggregate EBs. After formation, the EBs were transferred to a collagen matrix coated culture dishes and given 4 days to allow implantation and outgrowth. In parallel, totipotent ESCs were plated 24 hours before mechanical stimulation on collagen matrix culture dishes in the presence of LIF to maintain totipotency and serve as un-differentiation committed controls. The EBs and ESCs were then subjected to either a 60 minute pulse of gravity (static loading) or 60 minutes of cyclic stretch (dynamic loading) mechanotransduction. Six hours post-stimulation, we used a 10X Genomics Single Cell controller to generate bar-coded single cell Illumina libraries and sequenced expressomes for 5,000 static loaded cells, representative of a change in gravity mechanotransduction, 5,000 dynamic loaded cells, representative of tissue loading associate with physiologic function, and 5,000 unstimulated 1g control cells. The comparison of these 3 libraries by cluster assignment based on like gene expression patterns show substantial alteration in cluster geometry due to mechanical loading. Specifically the mechanically loaded EB outgrowth cells to retain potency markers (PAX6, SOX2, CD34) and suppress early commitment markers (Dhh, VCAN, Igf1). Whereas the EBs cultured under the non-stimulated conditions display clear departure from the ESC expressome with lineage commitment markers upregulated and several tissue specific markers being expressed (BMP "early musculoskeletal development, Mesp1" early cardiovascular cell lineage). These markers are not seen in the mechano-stimulated cultures or the totipotent ESC cultures. Comparison of like clusters between our experimental conditions revealed an array of regenerative and stem cell genes are significantly mechano-regulated. Of particular importance CDKN1a/p21, a gene shown by previous investigation of our research team to be significantly upregulated in unloading, was suppressed in the static and dynamic loaded EBS. In addition to CDKN1a/p21 many genes related to cell cycle and transitory differentiation markers had elevated expression in the mechano-stimulated EBs, but surprisingly these trends were not observed in the ESC cultures. This study is the first of its kind investigating for mechano-signaling and mechano-regulated pathways, and has alre

Single cell RNA-sequecing↗
NASA NTRS2006

Three-dimensional Myoblast Aggregates--Effects of Modeled Microgravity

The overall objective of these studies is to elucidate the molecular and cellular alterations that contribute to muscle atrophy in astronauts caused by exposure to microgravity conditions in space. To accomplish this, a three-dimensional model test system was developed using mouse myoblast cells (C2C12). Myoblast cells were grown as three-dimensional aggregates (without scaffolding or other solid support structures) in both modeled microgravity (Rotary Cell Culture System, Synthecon, Inc.) and at unit gravity in coated Petri dishes. Evaluation of H&E stained thin sections of the aggregates revealed the absence of any necrosis. Confocal microscopy evaluations of cells stained with the Live/Dead assay (Molecular Probes) confirmed that viable cells were present throughout the aggregates with an average of only three dead cells observed per aggregate. Preliminary results from gene array analysis (Affymetrix chip U74Av2) showed that approximately 14% of the genes were down regulated (decreased more than 3 fold) and 4% were upregulated in cells exposed to modeled microgravity for 12 hours compared to unit gravity controls. Additional studies using fluorescent phallacidin revealed a decrease in F-actin in the cells exposed to modeled microgravity compared to unit gravity. Myoblast cells grown as aggregates in modeled microgravity exhibited spontaneous differentiation into syncitia while no differentiation was seen in the unit gravity controls. These studies show that 1)the model test system developed is suitable for assessing cellular and molecular alterations in myoblasts; 2) gene expression alterations occur rapidly (within 12 hours) following exposure to modeled microgravity; and 3) modeled microgravity conditions stimulated myoblast cell differentiation. Achieving a greater understanding of the molecular alterations leading to muscle atrophy will eventually enable the development of cell-based countermeasures, which may be valuable for treatment of muscle diseases on Earth and future space explorations.

Byerly, Diane↗
NASA NTRS1993

Studies on the effects of microgravity on the ultrastructure and functions of cultured mammalian cells (L-6)

The human body consists of 10(exp 13) cells. Understanding the mechanisms by which the cells sense and respond to microgravity is very important as the basis for space biology. The cells were originally isolated aseptically from mammalian bodies and cultured in vitro. A set of cell culture vessels was developed to be applied to three kinds of space flight experiments. Experiment 1 is to practice the cell culture technique in a space laboratory and obtain favorable growth of the cells. Aseptic handling in tryspin treatment and medium renewal will be tested. The cells, following space flight, will be returned to the ground and cultured continuously to investigate the effects of space flight on the cellular characteristics. Experiment 2 is to examine the cytoskeletal structure of the cells under microgravity conditions. The cytoskeletal structure plays essential roles in the morphological construction, movements, axonal transport, and differentiation of the cells. The cells fixed during space flight will be returned and the cytoskeleton and ultrastructure observed using electron microscopy and fluorescence microscopy. Experiment 3 is to study the cellular productivity of valuable substances. The waste medium harvested during space flight are returned and quantitated for the cellular products. The effects of microgravity on mammalian cells will be clarified from the various aspects.

Sato, Atsushige↗
NASA NTRS2000

T Lymphocyte Activation Threshold is Increased in Reduced Gravity

There have been substantial advances in molecular and cellular biology that have provided new insight into the biochemical and genetic basis of lymphocyte recognition, activation and expression of distinct functional phenotypes. It has now become evident that for both T and B cells, stimuli delivered through their receptors can result in either clonal expansion or apoptosis. In the case of T cells, clonal expansion of helper cells is accompanied by differentiation into two major functional subsets which regulate the immune response. The pathways between the membrane and the nucleus and their molecular components are an area of very active investigation. This meeting will draw together scientists working on diverse aspects of this problem, including receptor ligand interactions, intracellular pathways that transmit receptor mediated signals and the effect of such signal transduction pathways on gene regulation. The aim of this meeting is to integrate the information from these various experimental approaches into a new synthesis and molecular explanation of T cell activation, differentiation and death.

Adams, Charley L.↗
NASA NTRS1994

From neural-based object recognition toward microelectronic eyes

Engineering neural network systems are best known for their abilities to adapt to the changing characteristics of the surrounding environment by adjusting system parameter values during the learning process. Rapid advances in analog current-mode design techniques have made possible the implementation of major neural network functions in custom VLSI chips. An electrically programmable analog synapse cell with large dynamic range can be realized in a compact silicon area. New designs of the synapse cells, neurons, and analog processor are presented. A synapse cell based on Gilbert multiplier structure can perform the linear multiplication for back-propagation networks. A double differential-pair synapse cell can perform the Gaussian function for radial-basis network. The synapse cells can be biased in the strong inversion region for high-speed operation or biased in the subthreshold region for low-power operation. The voltage gain of the sigmoid-function neurons is externally adjustable which greatly facilitates the search of optimal solutions in certain networks. Various building blocks can be intelligently connected to form useful industrial applications. Efficient data communication is a key system-level design issue for large-scale networks. We also present analog neural processors based on perceptron architecture and Hopfield network for communication applications. Biologically inspired neural networks have played an important role towards the creation of powerful intelligent machines. Accuracy, limitations, and prospects of analog current-mode design of the biologically inspired vision processing chips and cellular neural network chips are key design issues.

Sheu, Bing J.↗
NASA NTRS2010

Influence of Ionizing Radiation on Stromal-Epithelial Intercellular Communication in Esophageal Carcinogenesis

Esophageal cancer is the 6th leading cause of cancer death worldwide. Its development is associated with a variety of risk factors including tobacco use, heavy alcohol consumption, human papilloma virus infection, and certain dietary factors such as trace mineral and vitamin deficiencies. An association with ionizing radiation exposure is revealed by the high excess relative risk for squamous cell carcinoma of the esophagus observed in the survivors of the atomic bomb detonations in Japan. It is also seen as a secondary malignancy in patients who received radiotherapy for breast and thoracic cancers; additionally, patients with head/neck and oral squamous cell cancers are at increased risk for metachronous esophageal squamous cell cancers. This malignancy is rapidly fatal, mainly because it remains asymptomatic until late, advanced stages when the disease is rarely curable. The stromal microenvironment plays an essential role in the maintenance and modulation of normal epithelial cell growth and differentiation and cross talk between the epithelial and stromal compartments can influence many aspects of malignant progression, including tumor cell proliferation, migration, invasion and recruitment of new blood vessels. To test the hypothesis that radiation exposure plays a role in esophageal carcinogenesis via non-targeted mechanisms involving stromal-epithelial cell communication, we are studying radiation effects on hTERT-immortalized human esophageal epithelial cells and genetic variants grown in co-culture with human esophageal stromal fibroblasts (Okawa et al., Genes & Dev. 2007. 21: 2788-2803). We examined how radiation treatment of stromal fibroblasts affected epithelial migration and invasion, behaviors associated with cancer promotion and progression. Chemotactic and haptotactic migration of epithelial cells stimulated by conditioned media from irradiated fibroblasts was measured using assays conducted in Transwell cell culture chambers. Our results using low LET radiation showed a dose-dependent increase in migration of epithelial cells when exposed to conditioned media from irradiated vs. non-irradiated fibroblasts. We also observed enhanced invasion through a basement membrane simulant. To identify chemotactic proteins secreted by irradiated stromal fibroblasts, we used antibody capture cytokine arrays and have identified several proteins as candidates. Increased secretion of these factors by irradiated fibroblasts was confirmed using ELISA. We are currently analyzing the contribution of these individual factors on epithelial migration and invasion, as well as their influence on cell survival and DNA repair. Studies using high-LET radiation will help determine radiation quality effects on these processes. These results should further our understanding of the mechanisms by which radiation impacts the tissue microenvironment and how it influences cancer development processes.

Patel, Zarana S.↗
NASA NTRS1998

BIGEL analysis of gene expression in HL60 cells exposed to X rays or 60 Hz magnetic fields

We screened a panel of 1,920 randomly selected cDNAs to discover genes that are differentially expressed in HL60 cells exposed to 60 Hz magnetic fields (2 mT) or X rays (5 Gy) compared to unexposed cells. Identification of these clones was accomplished using our two-gel cDNA library screening method (BIGEL). Eighteen cDNAs differentially expressed in X-irradiated compared to control HL60 cells were recovered from a panel of 1,920 clones. Differential expression in experimental compared to control cells was confirmed independently by Northern blotting of paired total RNA samples hybridized to each of the 18 clone-specific cDNA probes. DNA sequencing revealed that 15 of the 18 cDNA clones produced matches with the database for genes related to cell growth, protein synthesis, energy metabolism, oxidative stress or apoptosis (including MYC, neuroleukin, copper zinc-dependent superoxide dismutase, TC4 RAS-like protein, peptide elongation factor 1alpha, BNIP3, GATA3, NF45, cytochrome c oxidase II and triosephosphate isomerase mRNAs). In contrast, BIGEL analysis of the same 1,920 cDNAs revealed no differences greater than 1.5-fold in expression levels in magnetic-field compared to sham-exposed cells. Magnetic-field-exposed and control samples were analyzed further for the presence of mRNA encoding X-ray-responsive genes by hybridization of the 18 specific cDNA probes to RNA from exposed and control HL60 cells. Our results suggest that differential gene expression is induced in approximately 1% of a random pool of cDNAs by ionizing radiation but not by 60 Hz magnetic fields under the present experimental conditions.

Non-NASA Center↗
NASA NTRS2019

The Role of Gravity Mechanotransduction in Regulating Stem Cell Tissue Regenerative Potential at the Single Cell Expressome Level

Gravity is an omnipresent force on Earth, and all living organisms have evolved under the influence of constant gravity. Mechanical forces generated by gravity are potent modulators of stem cell based tissue regenerative mechanisms, inducing cell fate decisions and tissue specific commitment. A novel mechanical unloading investigation assessed the formation, morphology, and gene expression of embryoid bodies (EB), a transitory cell model of early differentiation. After 15 days of spaceflight, the mechanotransduction-null EB cells showed upregulated proliferative mechanisms while differentiation cues were silenced.

Juran, Cassandra M.↗
NASA NTRS2015

Transient Gene and miRNA Expression Profile Changes of Confluent Human Fibroblast Cells in Space

Microgravity or an altered gravity environment from the static 1 gravitational constant has been shown to influence global gene expression patterns and protein levels in cultured cells. However, most of the reported studies conducted in space or using simulated microgravity on the ground have focused on the growth or differentiation of the cells. Whether non-dividing cultured cells will sense the presence of microgravity in space has not been specifically addressed. In an experiment conducted on the International Space Station, confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 days for investigations of gene and miRNA (microRNA) expression profile changes in these cells. A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for tissues, and plays a critical role in wound healing and other functions. Results of the experiment showed that on Day 3, both the flown and ground cells were still proliferating slowly even though they were confluent, as measured by the expression of the protein Ki-67 positive cells, and the cells in space grew slightly faster. Gene and miRNA expression data indicated activation of NF(sub kappa)B (nuclear factor kappa-light-chain-enhancer of activated B cells) and other growth related pathways involving HGF and VEGF in the flown cells. On Day 14 when the cells were mostly non-dividing, the gene and miRNA expression profiles between the flight and ground samples were indistinguishable. Comparison of gene and miRNA expressions in the Day 3 samples in respect to Day 14 revealed that most of the changes observed on Day 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeleton changes by immunohistochemistry staining of the cells with antibodies for alpha-tubulin showed no difference between the flight and ground samples. Results of our study suggest that in true non-dividing human fibroblast cells, microgravity in space has little effect on the gene and miRNA expression. Gene and miRNA expression changes were observed in cells that were confluent, but still proliferating slowly. The faster growth in the flown cells was associated with the activation of NF(sub kappa)B pathways which triggers the expression of several growth factors and the suppression of the cell cycle checkpoint.

Zhang, Ye↗
NASA NTRS2000

Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

Hair cells in many nonmammalian vertebrates are regenerated by the mitotic division of supporting cell progenitors and the differentiation of the resulting progeny into new hair cells and supporting cells. Recent studies have shown that nonmitotic hair cell recovery after aminoglycoside-induced damage can also occur in the vestibular organs. Using hair cell and supporting cell immunocytochemical markers, we have used confocal and electron microscopy to examine the fate of damaged hair cells and the origin of immature hair cells after gentamicin treatment in mitotically blocked cultures of the bullfrog saccule. Extruding and fragmenting hair cells, which undergo apoptotic cell death, are replaced by scar formations. After losing their bundles, sublethally damaged hair cells remain in the sensory epithelium for prolonged periods, acquiring supporting cell-like morphology and immunoreactivity. These modes of damage appear to be mutually exclusive, implying that sublethally damaged hair cells repair their bundles. Transitional cells, coexpressing hair cell and supporting cell markers, are seen near scar formations created by the expansion of neighboring supporting cells. Most of these cells have morphology and immunoreactivity similar to that of sublethally damaged hair cells. Ultrastructural analysis also reveals that most immature hair cells had autophagic vacuoles, implying that they originated from damaged hair cells rather than supporting cells. Some transitional cells are supporting cells participating in scar formations. Supporting cells also decrease in number during hair cell recovery, supporting the conclusion that some supporting cells undergo phenotypic conversion into hair cells without an intervening mitotic event.

Non-NASA Center↗
NASA NTRS1997

Plant and Animal Gravitational Biology

Session TA2 includes short reports covering: (1) The Interaction of Microgravity and Ethylene on Soybean Growth and Metabolism; (2) Structure and G-Sensitivity of Root Statocytes under Different Mass Acceleration; (3) Extracellular Production of Taxanes on Cell Surfaces in Simulated Microgravity and Hypergravity; (4) Current Problems of Space Cell Phytobiology; (5) Biological Consequences of Microgravity-Induced Alterations in Water Metabolism of Plant Cells; (6) Localization of Calcium Ions in Chlorella Cells Under Clinorotation; (7) Changes of Fatty Acids Content of Plant Cell Plasma Membranes under Altered Gravity; (8) Simulation of Gravity by Non-Symmetrical Vibrations and Ultrasound; and (9) Response to Simulated weightlessness of In Vitro Cultures of Differentiated Epithelial Follicular Cells from Thyroid.

Source record↗
NASA NTRS1997

Signal transduction in T lymphocytes in microgravity

More than 120 experiments conducted in space in the last 15 years have shown that dramatic changes are occurring in several types of single cells during their exposure to microgravity. One focus of today's research on cells in space is on signal transduction, especially those steps involving the cytoskeleton and cell-cell interactions. Signal transduction is often altered in microgravity as well as in hypergravity. This leads to changes in cell proliferation, genetic expression and differentiation. Interesting examples are leukocytes, HeLa cells, epidermoid cells and osteoblastic cells. Signalling pathways were studied in T lymphocytes in microgravity by several investigators after the discovery that mitogenic activation in vitro is virtually nil at 0g. T cells are a good model to study signal transduction because three extracellular signals (mitogen, IL-1 and IL-2) are required for full activation, and two classical pathways (via proteins G and PKC) are activated within the cell. In addition, low molecular weight GTP-binding proteins (Ras and Rap) are interacting with the cytoskeleton. The data at 0g support the notion that the expression of IL-2 receptor is inhibited at 0g, while mitogen binding and the transmission of IL-1 by accessory cells occur normally. In addition, alterations of the cytoskeleton suggest that the interaction with Rap proteins is disturbed. Data obtained with phorbol esters indicate that the function of PKC is changed in microgravity. Similar conclusions are drawn from the results with epidermoid cells A431.

short duration↗
NASA NTRS1993

Use of microgravity bioreactors for development of an in vitro rat salivary gland cell culture model

During development, salivary gland (SG) cells both secrete factors which modulate cellular behavior and express specific hormone receptors. Whether SG cell growth is modulated by an autocrine epidermal growth factor (EGF) receptor-mediated signal transduction pathway is not clearly understood. SG tissue is the synthesis site for functionally distinct products including growth factors, digestive enzymes, and homeostasis maintaining factors. Historically, SG cells have proven difficult to grow and may be only maintained as limited three-dimensional ductal-type structures in collagen gels or on reconstituted basement membrane gels. A novel approach to establishing primary rat SG cultures is use of microgravity bioreactors originally designed by NASA as low-shear culture systems for predicting cell growth and differentiation in the microgravity environment of space. These completely fluid-filled bioreactors, which are oriented horizontally and rotate, have proven advantageous for Earth-based culture of three-dimensional cell assemblies, tissue-like aggregates, and glandular structures. Use of microgravity bioreactors for establishing in vitro models to investigate steroid-mediated secretion of EGF by normal SG cells may also prove useful for the investigation of cancer and other salivary gland disorders. These microgravity bioreactors promise challenging opportunities for future applications in basic and applied cell research.

NASA Program Space Biology↗
NASA NTRS1985

Polyamine levels as related to growth, differentiation and senescence in protoplast-derived cultures of Vigna aconitifolia and Avena sativa

We have previously reported that aseptically cultured mesophyll protoplasts of Vigna divide rapidly and regenerate into complete plants, while mesophyll protoplasts of Avena divide only sporadically and senesce rapidly after isolation. We measured polyamine titers in such cultures of Vigna and Avena, to study possible correlations between polyamines and cellular behavior. We also deliberately altered polyamine titer by the use of selective inhibitors of polyamine biosynthesis, noting the effects on internal polyamine titer, cell division activity and regenerative events. In Vigna cultures, levels of free and bound putrescine and spermidine increased dramatically as cell division and differentiation progressed. The increase in bound polyamines was largest in embryoid-forming callus tissue while free polyamine titer was highest in root-forming callus. In Avena cultures, the levels of total polyamines decreased as the protoplast senesced. The presence of the inhibitors alpha-difluoromethyl-arginine (specific inhibitor of arginine decarboxylase), alpha-difluoromethylornithine (specific inhibitor of ornithine decarboxylase) and dicyclohexylamine (inhibitor of spermidine synthase) reduced cell division and organogenesis in Vigna cultures. Addition of low concentration of polyamines to such cultures containing inhibitors or removal of inhibitors from the culture medium restored the progress of growth and differentiation with concomitant increase in polyamine levels.

NASA Program Space Biology↗
NASA NTRS2018

Stem Cell-Based Regenerative Health in Microgravity

The research of Dr. Almeida's Lab at NASA Ames focuses on the effects of microgravity mechanical unloading on stem-cell-based tissue regeneration. The research focuses on testing the broad hypothesis that mechanical load from gravity at 1 g is required for normal adult stem cell proliferation and differentiation during tissue regeneration. Research from the lab has provides evidence supporting the hypothesis in various biological models, including newt tail regeneration, mouse bone and bone marrow in whole animals, and mouse embryonic stem cells all exposed to microgravity during spaceflight. Using these models, the lab has identified overexpression of the cell cycle inhibitor p21/CDKN1a as a candidate molecular mediator mechanism of bone marrow mesenchymal and hematopoietic lineage tissue regenerative arrest in microgravity. The labis currently focused on using p21/CDKN1a null mouse and cell culture approaches in microgravity to test the gravity tissue regeneration hypothesis.

stem cells microgravity regeneration↗