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At least 55 records · Page 3

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NASA NTRS2005

Evaluation of Late Effects of Heavy-Ion Radiation on Mesenchymal Stem Cells

The overall objective of this recently funded study is to utilize well-characterized model test systems to assess the impact of pluripotent stem cell differentiation on biological effects associated with high-energy charged particle radiation. These stem cells, specifically mesenchymal stem cells (MSCs), have the potential for differentiation into bone, cartilage, fat, tendons, and other tissue types. The characterization of the regulation mechanisms of MSC differentiation to the osteoblastic lineage by transcription factors, such as Runx2/Cbfa1 and Osterix, and osteoinductive proteins such as members of the bone morphogenic protein family are well established. More importantly, for late biological effects, MSCs have been shown to contribute to tissue restructuring and repair after tissue injury. The complex regulation of and interactions between inflammation and repair determine the eventual outcome of the responses to tissue injury, for which MSCs play a crucial role. Additionally, MSCs have been shown to respond to reactive oxygen species, a secondary effector of radiation, by differentiating. With this, we hypothesized that differentiation of MSCs can alter or exacerbate the damage initiated by radiation, which can ultimately lead to late biological effects of misrepair/fibrosis which may ultimately lead to carcinogenesis. Currently, studies are underway to examine high-energy X-ray radiation at low and high doses, approximately 20 and 200 Rad, respectively, on cytogenetic damage and gene modulation of isolated MSCs. These cells, positive for MSC surface markers, were obtained from three persons. In vitro cell samples were harvested during cellular proliferation and after both cellular recovery and differentiation. Future work will use established in vitro models of increasing complexity to examine the value of traditional 2D tissue-culture techniques, and utilize 3D in vitro tissue culture techniques that can better assess late effects associated with radiation.

Gonda, S.R.↗

NASA NTRS2000

Spaceflight effects on cultured embryonic chick bone cells

A model calcifying system of primary osteoblast cell cultures derived from normal embryonic chicken calvaria has been flown aboard the shuttle, Endeavour, during the National Aeronautics and Space Administration (NASA) mission STS-59 (April 9-20, 1994) to characterize unloading and other spaceflight effects on the bone cells. Aliquots of cells (approximately 7 x 10(6)) grown in Dulbecco's modified Eagle's medium (DMEM) + 10% fetal bovine serum (FBS) were mixed with microcarrier beads, inoculated into cartridge culture units of artificial hollow fiber capillaries, and carried on the shuttle. To promote cell differentiation, cartridge media were supplemented with 12.5 microg/ml ascorbate and 10 mM beta-glycerophosphate for varying time periods before and during flight. Four cartridges contained cells from 17-day-old embryos grown for 5 days in the presence of ascorbate prior to launch (defined as flight cells committed to the osteoblastic lineage) and four cartridges supported cells from 14-day-old embryos grown for 10 days with ascorbate before launch (uncommitted flight cells). Eight cartridges prepared in the same manner were maintained under normal gravity throughout the flight (control cells) and four additional identical cartridges under normal gravity were terminated on the day of launch (basal cells). From shuttle launch to landing, all cartridges were contained in closed hardware units maintaining 5% CO2, 37 degrees C, and media delivery at a rate of approximately 1.5 ml/6 h. During day 3 and day 5 of flight, duplicate aliquots of conditioned media and accumulated cell products were collected in both the flight and the control hardware units. At the mission end, comparisons among flight, basal, and control samples were made in cell metabolism, gene expression for type I collagen and osteocalcin, and ultrastructure. Both committed and uncommitted flight cells were metabolically active, as measured by glucose uptake and lactate production, at approximately the same statistical levels as control counterparts. Flight cells elaborated a less extensive extracellular matrix, evidenced by a reduced collagen gene expression and collagen protein appearance compared with controls. Osteocalcin was expressed by all cells, a result indicating progressive differentiation of both flight and control osteoblasts, but its message levels also were reduced in flight cells compared with ground samples. This finding suggested that osteoblasts subjected to flight followed a slower progression toward a differentiated function. The summary of data indicates that spaceflight, including microgravity exposure, demonstrably affects bone cells by down-regulating type I collagen and osteocalcin gene expression and thereby inhibiting expression of the osteogenic phenotype notably by committed osteoblasts. The information is important for insight into the response of bone cells to changes of gravity and of force in general.

Non-NASA Center↗

NASA NTRS1979

Senescent changes in the ribosomes of animal cells in vivo and in vitro

The paper examines RNA-ribosomal changes observed in protozoa and fixed postmitotic cells, as well as the characteristics of intermitotic cells. Attention is given to a discussion of the implications of the reported ribosomal changes as to the senescent deterioration of protein synthesis and physiological functions. A survey of the literature suggests that, while the data on ribosomal change in dividing cells both in vivo and in vitro are inconclusive, there is strong histological and biochemical evidence in favor of some degree of quantitative ribosomal loss in fixed postmitotic cells. Since these decreases in ribosomes are demonstrated in differential cells from nematodes, insects and mammals, they may represent a universal manifestation of cytoplasmic senescence in certain types of fixed postmitotic animal cells. The observed variability in ribosomal loss for cells belonging to the same type suggests that this involution phenomenon is rather related to the wear and tear suffered by a particular cell.

Miquel, J.↗

NASA NTRS2015

Aligned and Electrospun Piezoelectric Polymer Fiber Assembly and Scaffold

A scaffold assembly and related methods of manufacturing and/or using the scaffold for stem cell culture and tissue engineering applications are disclosed which at least partially mimic a native biological environment by providing biochemical, topographical, mechanical and electrical cues by using an electroactive material. The assembly includes at least one layer of substantially aligned, electrospun polymer fiber having an operative connection for individual voltage application. A method of cell tissue engineering and/or stem cell differentiation uses the assembly seeded with a sample of cells suspended in cell culture media, incubates and applies voltage to one or more layers, and thus produces cells and/or a tissue construct. In another aspect, the invention provides a method of manufacturing the assembly including the steps of providing a first pre-electroded substrate surface; electrospinning a first substantially aligned polymer fiber layer onto the first surface; providing a second pre-electroded substrate surface; electrospinning a second substantially aligned polymer fiber layer onto the second surface; and, retaining together the layered surfaces with a clamp and/or an adhesive compound.

Scott-Carnell, Lisa A.↗

NASA NTRS2002

Microgravity modifies protein kinase C isoform translocation in the human monocytic cell line U937 and human peripheral blood T-cells

Individual protein kinase C (PKC) isoforms fulfill distinct roles in the regulation of the commitment to differentiation, cell cycle arrest, and apoptosis in both monocytes and T-cells. The human monocyte like cell line U937 and T-cells were exposed to microgravity, during spaceflight and the translocation (a critical step in PKC signaling) of individual isoforms to cell particulate fraction examined. PKC activating phorbol esters induced a rapid translocation of several PKC isoforms to the particulate fraction of U937 monocytes under terrestrial gravity (1 g) conditions in the laboratory. In microgravity, the translocation of PKC beta II, delta, and epsilon in response to phorbol esters was reduced in microgravity compared to 1 g, but was enhanced in weak hypergravity (1.4 g). All isoforms showed a net increase in particulate PKC following phorbol ester stimulation, except PKC delta which showed a net decrease in microgravity. In T-cells, phorbol ester induced translocation of PKC delta was reduced in microgravity, compared to 1 g, while PKC beta II translocation was not significantly different at the two g-levels. These data show that microgravity differentially alters the translocation of individual PKC isoforms in monocytes and T-cells, thus providing a partial explanation for the modifications previously observed in the activation of these cell types under microgravity.

STS-81 Shuttle Project↗

NASA NTRS2017

Aligned and Electrospun Piezoelectric Polymer Fiber Assembly and Scaffold

A method of manufacturing and/or using a scaffold assembly for stem cell culture and tissue engineering applications is disclosed. The scaffold at least partially mimics a native biological environment by providing biochemical, topographical, mechanical and electrical cues by using an electroactive material. The assembly includes at least one layer of substantially aligned, electrospun polymer fiber having an operative connection for individual voltage application. A method of cell tissue engineering and/or stem cell differentiation that uses the assembly seeded with a sample of cells suspended in cell culture media, incubates and applies voltage to one or more layers, and thus produces cells and/or a tissue construct. In another aspect, the invention provides a method of manufacturing the assembly including the steps of providing a first pre-electroded substrate surface; electrospinning a first substantially aligned polymer fiber layer onto the first surface; providing a second pre-electroded substrate surface; electrospinning a second substantially aligned polymer fiber layer onto the second surface; and, retaining together the layered surfaces with a clamp and/or an adhesive compound.

Scott Carnell, Lisa A.↗

NASA NTRS2019

Aligned and Electrospun Piezoelectric Polymer Fiber Assembly and Scaffold

Scott Carnell, Lisa A.↗

NASA NTRS1985

The structure and development of the starch sheath in pea epicotyls

Graviperception in plant stems is thought to occur in endodermal cells differentiated as a starch sheath, but little is known about the ultrastructure of these cells in dicots. The structure of the pea starch sheath was studied with respect to gravity and to development in order to determine whether symplastic or apoplastic blockages exist and to describe any intracellular polarity. Amyloplasts increase in size towards the base of the epicotyl hook but are not consistently sedimented until the cells enter the zone exhibiting gravicurvature below the hook. The starch sheath cells are connected to each other and to cells of the cortex and the stele by plasmodesmata. A casparian strip exists in older endodermal cells but not at the stage that the endodermis is differentiated as a starch sheath. Amyloplasts were frequently observed in apparent contact with endoplasmic reticulum.

Sack, D. F.↗

NASA NTRS2002

Regulation of collagenase-3 and osteocalcin gene expression by collagen and osteopontin in differentiating MC3T3-E1 cells

Both collagenase-3 and osteocalcin mRNAs are expressed maximally during the later stages of osteoblast differentiation. Here, we demonstrate that collagenase-3 mRNA expression in differentiating MC3T3-E1 cells is dependent upon the presence of ascorbic acid, is inhibited in the presence of the collagen synthesis inhibitor, 3,4-dehydroproline, and is stimulated by growth on collagen in the absence of ascorbic acid. Transient transfection studies show that collagenase-3 promoter activity increases during cell differentiation and requires the presence of ascorbic acid. Additionally, we show that, in differentiating MC3T3-E1 cells, collagenase-3 gene expression increases in the presence of an anti-osteopontin monoclonal antibody that binds near the RGD motif of this protein, whereas osteocalcin expression is inhibited. Furthermore, an RGD peptidomimetic compound, designed to block interaction of ligands to the alpha(v) integrin subunit, increases osteocalcin expression and inhibits collagenase-3 expression, suggesting that the RGD peptidomimetic initiates certain alpha(v) integrin signaling in osteoblastic cells. Overall, these studies demonstrate that stimulation of collagenase-3 expression during osteoblast differentiation requires synthesis of a collagenous matrix and that osteopontin and alpha(v) integrins exert divergent regulation of collagenase-3 and osteocalcin expression during osteoblast differentiation.

NASA Discipline Musculoskeletal↗

NASA NTRS1975

Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study

The mechanism of cell proliferation is studied in the lymphoid tissue of the mouse spleen under the stress of continuous irradiation at a dose-rate of 10 roentgens per day for 105 days. Autoradiography and specific labeling with tritiated thymidine were utilized. It was found that at least four compensatory mechanisms maintained a near-steady state of cellular growth: (1) an increase in the proportion of PAS-positive cells which stimulate mitotic activity, (2) maturation arrest of proliferating and differentiating cells which tend to replenish the cells damaged or destroyed by irradiation, (3) an increase in the proportion of cells proliferating, and (4) an increase in the proportion of precursor cells. The results are compared to previous findings observed in the thymus.

Foster, B. R.↗

NASA NTRS2000

Enhanced expression of extracellular calcium sensing receptor in monocyte-differentiated versus undifferentiated HL-60 cells: potential role in regulation of a nonselective cation channel

Human promyelocytic leukemia cells (HL-60) have been used widely as a model for studying the differentiation of hematopoietic progenitor cells in vitro. After treatment with phorbol-12-myristate-13-acetate (PMA) or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], HL-60 cells differentiate into cells with the phenotype of monocytes/macrophages. We previously showed that peripheral blood monocytes and the murine J774 monocytic cell line express the CaR, and myeloid progenitors in the bone marrow and myeloid cells in peripheral blood other than monocytes express lower levels of the CaR. Therefore, we investigated whether undifferentiated HL-60 cells express a functional G protein-coupled, extracellular calcium (Ca(2+)(o))-sensing receptor (CaR) and if the expression of the CaR increases as these cells differentiate along the monocytic lineage. The use of reverse transcription-polymerase chain reaction (RT-PCR) with CaR-specific primers, followed by sequencing of the amplified products, identified an authentic CaR transcript in undifferentiated HL-60 cells. Both immunocytochemistry and Western blot analysis using a CaR-specific antiserum detected low levels of CaR protein expression in undifferentiated HL-60 cells. The levels of CaR protein increased considerably following treatment of the cells with PMA (50 nM) or 1,25(OH)(2)D(3) (100 nM) for 5 days. Northern analysis using a CaR-specific riboprobe identified CaR transcripts in undifferentiated HL-60 cells, but CaR mRNA levels did not change appreciably after treatment with either agent, suggesting that upregulation of CaR protein occurs at a translational level. PMA-treated HL-60 cells expressed a nonselective cation channel (NCC), and the calcimimetic CaR activator, NPS R-467, but not its less active stereoisomer, NPS S-467, as well as the polycationic CaR agonist, neomycin, activated this NCC, demonstrating that the CaR expressed in these cells is functionally active. Therefore, HL-60 cells exhibit an increase in CaR protein expression, occurring at a translational level during their differentiation into cells with a monocyte/macrophage phenotype in response to treatment with PMA or 1, 25(OH)(2)D(3), which is functionally linked to activation of a nonselective cation channel.

NASA Discipline Musculoskeletal↗

NASA NTRSDate not supplied

Microgravity Effect on Bacterial Growth: A Literature Review

Gravity is a well-known, but little understood, physical force. It interacts with other physical environmental factors to impact the formation of today’s Earth, and to contribute to biological variations between water and land species. It is also involved with cell differentiation process, and is responsible for setting the boundaries for life and keeping cells small. With their simple structures and small sizes, microbes are expected to be less gravity sensitive than larger species. Nevertheless, various effects of spaceflight on bacterial growth have been reported, but the reports have been sometime inconsistent, and the underlying mechanism remains unclear to many. This paper summarizes the systematic efforts to evaluate the spaceflight effect on microbial growth, highlighting the extracellular mass transfer mechanism. It also provides a critical literature review on the topic to resolve the discrepancy in experimental observations and to further clarify the underlying mechanisms.

Wenyan Li↗

DOE OSTI2026

Small Signaling Peptides in Sorghum bicolor : Integrating Phylogeny and Gene Expression to Characterize Roles in Stem Development

Small signaling peptides (SSPs) are important regulators of plant growth, development, and responses to biotic and abiotic stress, yet their role in the C4 grass Sorghum bicolor is largely uncharacterized. To help fill this knowledge gap, 219 sorghum genes that encode SSPs were identified based on SSP sequences previously identified in Arabidopsis thaliana, Zea mays, Oryza sativa, Triticum aestivum , and Brachypodium distachyon . The 219 sorghum SSP-encoding genes were assigned to 19 gene families, analyzed for the presence of motifs, and aligned with genes that encode SSPs in other plants using phylogenetic analysis. Sorghum genes in 12 of the 19 SSP gene families had not been previously characterized. Expression of the 219 SSP-encoding genes in sorghum organs, during stem development, and in stem tissues and cell types revealed distinct spatial, temporal, and developmental patterns of expression. Genes associated with the SbCEP and SbRGF families were preferentially expressed in roots, whereas SbEPF genes were expressed in stem epidermal and pith parenchyma cells and panicles. The expression of genes during bioenergy sorghum stem growth and development was investigated because stems account for ~80% of harvested biomass and serve as conduits for water and nutrient transport between leaves and roots. During stem development, 28 SSP genes in several families ( CLE, EPF, CEP, GASS, PSY, ES, PSK, CAPE, POE ) were expressed at higher levels in zones of cell proliferation. For example, the TDIF homologs SbCLE41 and SbCLE42 were expressed at high levels in nascent stem nodes where they may regulate vascular bundle cambial activity and cell differentiation. A different set of 15 genes in the CIF, POE, CAPE, PSY, CEP, RALF , and CLE families were expressed at higher levels in zones of stem tissue differentiation highlighted by elevated expression of five SbRALFR s in the stem nodal plexus. Cell type–specific expression of many sorghum genes that encode SSPs was observed in fully elongated internodes indicating gene expression is regulated with high spatial resolution. Overall, the results provide a foundation of information for analysis of SSP function in sorghum that can be integrated with knowledge of sorghum gene regulatory networks to modulate traits important for production of sorghum crops.

bioenergy sorghum↗

NASA NTRS1992

Glucocorticoids promote development of the osteoblast phenotype by selectively modulating expression of cell growth and differentiation associated genes

To understand the mechanisms by which glucocorticoids promote differentiation of fetal rat calvaria derived osteoblasts to produce bone-like mineralized nodules in vitro, a panel of osteoblast growth and differentiation related genes that characterize development of the osteoblast phenotype has been quantitated in glucocorticoid-treated cultures. We compared the mRNA levels of osteoblast expressed genes in control cultures of subcultivated cells where nodule formation is diminished, to cells continuously (35 days) exposed to 10(-7) M dexamethasone, a synthetic glucocorticoid, which promotes nodule formation to levels usually the extent observed in primary cultures. Tritiated thymidine labelling revealed a selective inhibition of internodule cell proliferation and promotion of proliferation and differentiation of cells forming bone nodules. Fibronectin, osteopontin, and c-fos expression were increased in the nodule forming period. Alkaline phosphatase and type I collagen expression were initially inhibited in proliferating cells, then increased after nodule formation to support further growth and mineralization of the nodule. Expression of osteocalcin was 1,000-fold elevated in glucocorticoid-differentiated cultures in relation to nodule formation. Collagenase gene expression was also greater than controls (fivefold) with the highest levels observed in mature cultures (day 35). At this time, a rise in collagen and TGF beta was also observed suggesting turnover of the matrix. Short term (48 h) effects of glucocorticoid on histone H4 (reflecting cell proliferation), alkaline phosphatase, osteopontin, and osteocalcin mRNA levels reveal both up or down regulation as a function of the developmental stage of the osteoblast phenotype. A comparison of transcriptional levels of these genes by nuclear run-on assays to mRNA levels indicates that glucocorticoids exert both transcriptional and post-transcriptional effects. Further, the presence of glucocorticoids enhances the vitamin D3 effect on gene expression. Those genes which are upregulated by 1,25(OH)2D3 are transcribed at an increased rate by dexamethasone, while those genes which are inhibited by vitamin D3 remain inhibited in the presence of dexamethasone and D3. We propose that the glucocorticoids promote changes in gene expression involved in cell-cell and cell-extracellular matrix signaling mechanisms that support the growth and differentiation of cells capable of osteoblast phenotype development and bone tissue-like organization, while inhibiting the growth of cells that cannot progress to the mature osteoblast phenotype in fetal rat calvarial cultures.

NASA Discipline Musculoskeletal↗

NASA NTRS2011

Hydrofocusing Bioreactor Produces Anti-Cancer Alkaloids

A methodology for growing three-dimensional plant tissue models in a hydrodynamic focusing bioreactor (HFB) has been developed. The methodology is expected to be widely applicable, both on Earth and in outer space, as a means of growing plant cells and aggregates thereof under controlled conditions for diverse purposes, including research on effects of gravitation and other environmental factors upon plant growth and utilization of plant tissue cultures to produce drugs in quantities greater and at costs lower than those of conventional methodologies. The HFB was described in Hydro focus - ing Bioreactor for Three-Dimensional Cell Culture (MSC-22358), NASA Tech Briefs, Vol. 27, No. 3 (March 2003), page 66. To recapitulate: The HFB offers a unique hydrofocusing capability that enables the creation of a low-shear liquid culture environment simultaneously with the herding of suspended cells and tissue assemblies and removal of unwanted air bubbles. The HFB includes a rotating cell-culture vessel with a centrally located sampling port and an internal rotating viscous spinner attached to a rotating base. The vessel and viscous spinner can be made to rotate at the same speed and direction or different speeds and directions to tailor the flow field and the associated hydrodynamic forces in the vessel in order to obtain low-shear suspension of cells and control of the locations of cells and air bubbles. For research and pharmaceutical-production applications, the HFB offers two major benefits: low shear stress, which promotes the assembly of cells into tissue-like three-dimensional constructs; and randomization of gravitational vectors relative to cells, which affects production of medicinal compounds. Presumably, apposition of plant cells in the absence of shear forces promotes cell-cell contacts, cell aggregation, and cell differentiation. Only gentle mixing is necessary for distributing nutrients and oxygen. It has been postulated that inasmuch as cells in the simulated microgravitation of an HFB do not need to maintain the same surface forces as in normal Earth gravitation, they can divert more energy sources to growth and differentiation and, perhaps, to biosynthesis of greater quantities of desired medicinal compounds. Because one can adjust the HFB to vary effective gravitation, one can also test the effects of intermediate levels of gravitation on biosynthesis of various products. The potential utility of this methodology for producing drugs was demonstrated in experiments in which sandalwood and Madagascar periwinkle cells were grown in an HFB. The conditions in the HFB were chosen to induce the cells to form into aggregate cultures that produced anti-cancer indole alkaloids in amounts greater than do comparable numbers of cells of the same species cultured according to previously known methodologies. The observations made in these experiments were interpreted as suggesting that the aggregation of the cells might be responsible for the enhancement of production of alkaloids.

Gonda, Steve R.↗

NASA NTRS1987

Hematological measurements in rats flown on Spacelab shuttle, SL-3

Previous studies have shown that a decrease in red cell mass occurs in astronauts, and some studies indicate a leukocytosis occurs. A life science module housing young and mature rats was flown on shuttle mission Spacelab 3 (SL-3), and the results of hematology studies of flight and control rats are presented. Statistically significant increases in the hematocrit, red blood cell counts, and hemoglobin determinations, together with a mild neutrophilia and lymphopenia, were found in flight animals. No significant changes were found in bone marrow and spleen cell differentials or erythropoietin determinations. Clonal assays demonstrated an increased erythroid colony formation of flight animal bone marrow cells at erythropoietin doses of 0.02 and 1.0 U/ml but not 0.20 U/ml. These results agree with some but vary from other previously published studies. Erythropoietin assays and clonal studies were performed for the first time.

NASA Experiment Number SL3-26↗

NASA NTRS1997

Calbindin and parvalbumin are early markers of non-mitotically regenerating hair cells in the bullfrog vestibular otolith organs

Earlier studies have demonstrated hair cell regeneration in the absence of cell proliferation, and suggested that supporting cells could phenotypically convert into hair cells following hair cell loss. Because calcium-binding proteins are involved in gene up-regulation, cell growth, and cell differentiation, we wished to determine if these proteins were up-regulated in scar formations and regenerating hair cells following gentamicin treatment. Calbindin and parvalbumin immunolabeling was examined in control or gentamicin-treated (GT) bullfrog saccular and utricular explants cultured for 3 days in amphibian culture medium or amphibian culture medium supplemented with aphidicolin, a blocker of nuclear DNA replication in eukaryotic cells. In control cultures, calbindin and parvalbumin immunolabeled the hair bundles and, less intensely, the cell bodies of mature hair cells. In GT or mitotically-blocked GT (MBGT) cultures, calbindin and parvalbumin immunolabeling was also seen in the hair bundles, cuticular plates, and cell bodies of hair cells with immature hair bundles. Thus, these antigens were useful markers for both normal and regenerating hair cells. Supporting cell immunolabeling was not seen in control cultures nor in the majority of supporting cells in GT cultures. In MBGT cultures, calbindin and parvalbumin immunolabeling was up-regulated in the cytosol of single supporting cells participating in scar formations and in supporting cells with hair cell-like characteristics. These data provide further evidence that non-mitotic hair cell regeneration in cultures can be accomplished by the conversion of supporting cells into hair cells.

Non-NASA Center↗

NASA NTRS2004

Lessons from Immune 1-3: what did we learn and what do we need to do in the future?

Sprague-Dawley rats were subjected to three 8-to-10 day space flights on the Space Shuttle. Housed in NASA's Animal Enclosure Modules, rats were flown to test the hypotheses that therapy with pegylated interleukin-2 or insulin-like growth factor-1 would ameliorate some of the effects of space flight on the immune system. As part of these experiments, we measured body and organ weights, blood cell differentials, plasma corticosterone, macrophage colony forming units, lymphocyte mitogenic, super-antigenic and interferon-gamma responses, bone marrow cell and peritoneal macrophage cytokine secretion and bone strength and mass. This paper compares some of the immunophysiological parameters of the control animals used in the Immune1-3 flight series and presents data from an animal infection model for use during space flight.

short duration↗