Parathyroid hormone-related protein is a gravisensor in lung and bone cell biology.

Parathyroid Hormone-related Protein (PTHrP) has been shown to be essential for the development and homeostatic regulation of lung and bone. Since both lung and bone structure and function are affected by microgravity, we hypothesized that 0 x g down-regulates PTHrP signaling. To test this hypothesis, we suspended lung and bone cells in the simulated microgravity environment of a Rotating Wall Vessel Bioreactor, which simulates microgravity, for up to 72 hours. During the first 8 hours of exposure to simulated 0 x g, PTHrP expression fell precipitously, decreasing by 80-90%; during the subsequent 64 hours, PTHrP expression remained at this newly established level of expression. PTHrP production decreased from 12 pg/ml/hour to 1 pg/ml/hour in culture medium from microgravity-exposed cells. The cells were then recultured at unit gravity for 24 hours, and PTHrP expression and production returned to normal levels. Based on these findings, we have obtained bones from rats flown in space for 2 weeks (Mission STS-58, SL-2). Analysis of PTHrP expression by femurs and tibias from these animals (n=5) revealed that PTHrP expression was 60% lower than in bones from control ground-based rats. Interestingly, there were no differences in PTHrP expression by parietal bone from space-exposed versus ground-based animals, indicating that the effect of weightlessness on PTHrP expression is due to the unweighting of weight-bearing bones. This finding is consistent with other studies of microgravity-induced osteoporosis. The loss of the PTHrP signaling mechanism may be corrected using chemical agents that up-regulate this pathway. In conclusion, PTHrP represents a stretch-sensitive paracrine signaling mechanism that may sense gravity.     

Global tectonics and metallogeny: Deep roots of some ore-controlling fracture zones. A possible relation to small-scale convective cells at the base of the lithosphere?

Criteria suggest that some of the ore-controlling fracture zones have deep roots, some extending into the upper mantle. The question is analyzed of whether a pattern of deep-seated fracture zones, extending to the base of a continental lithosphere, may be related to, or interact with, the small-scale convective cells (rolls) which originate [1,2] in the mantle beneath a moving lithospheric plate.The analysis follows a previous application of the same concept by others [3,4] who explained the origin of a chain of volcanoes by the movement of an oceanic lithospheric plate over a pattern of small-scale convective cells of the underlying mantle.The Canadian Shield is used to discuss the above question. A correlation has been found between: (1) the direction of two sets of long wavelength gravity anomalies detected by Stephenson and Beaumont, [8] in a study of the isostatic response of the Canadian Shield, and (2) the pattern of N-S and E-W trending trajectories of ore-controlling fracture zones, postulated by the author [5,6] in the southern part of the Canadian Shield. The Hudson Bay Paleolineament [7] correlates very well with the N-S set of gravity anomalies.The above correlation suggests that the ore-controlling lineaments and the long wavelength anomalies of the Canadian Shield are related. If the gravity anomalies reflect, as Stephenson and Beaumont [8] tentatively suggest, a pattern of convective cells beneath the base of the lithosphere, then the volcanic activity and metallogenesis may be related to the boundaries and corners of the cells. The author suggests that the convective cells could, in this case, originate by melting of the mantle material proceeding preferentially along the intersecting deep-seated fracture zones.The pattern of deep-seated fracture zones, compiled for the western United States [9] also shows a relationship of major ore deposits and ore clusters to the corners of rectangular blocks, defined by mutual intersection of the E-W and N-S fracture zones. In this case, the size of the blocks, measured in an E-W direction, is about 530 km, and in a N-S direction about 600 km. These figures are significantly close to the distance from the seismic discontinuity at a depth of 650 km, which is considered by others [2,4] as the lower boundary of the small-scale convection.     

Regional and temporal variability of solar activity and galactic cosmic ray effects on the lower atmosphere circulation

In this work we studied the spatial and temporal structure of long-term effects of solar activity (SA) and galactic cosmic ray (GCR) variations on the lower atmosphere circulation as well as possible reasons for the peculiarities of this structure. The study revealed a strong latitudinal and regional dependence of SA/GCR effects on pressure variations in the lower troposphere which seems to be determined by specific features of baric systems formed in different regions. The temporal structure of SA/GCR effects on the troposphere circulation at high and middle latitudes is characterized by a roughly 60-year periodicity which is apparently due to the epochs of the large-scale atmospheric circulation. It is suggested that a possible mechanism of long-term effects of solar activity and cosmic ray variations on the troposphere circulation involves changes in the evolution of the polar vortex in the stratosphere of high latitudes, as well as planetary frontal zones.     

Ultrastructural changes in osteocytes in microgravity conditions.

We examined the histology and morphometry of biosamples (biopsies) of the iliac crest of monkeys, flown 14 days aboard the "Bion-11", using electron microscopy. We found, that some young osteocytes take part in the activation of collagen protein biosynthesis in the adaptive remodeling process of the bone tissue to microgravity conditions. Osteocyte lacunae filled with collagen fibrils; this correlates with fibrotic osteoblast reorganization in such zones. The osteolytic activity in mature osteocytes is intensified. As a result of osteocyte destruction, the quantity of empty osteocytic lacunae in the bone tissue increases.     

Three-dimensional transgenic cell model to quantify genotoxic effects of space environment.

In this paper we describe a three-dimensional, multicellular tissue-equivalent model, produced in NASA-designed, rotating wall bioreactors using mammalian cells engineered for genomic containment of multiple copies of defined target genes for genotoxic assessment. Rat 2 lambda fibroblasts, genetically engineered to contain high-density target genes for mutagenesis (Stratagene, Inc., Austin, TX), were cocultured with human epithelial cells on Cytodex beads in the High Aspect Ratio Bioreactor (Synthecon, Inc, Houston, TX). Multi-bead aggregates were formed by day 5 following the complete covering of the beads by fibroblasts. Cellular retraction occurred 8-14 days after coculture initiation culminating in spheroids retaining few or no beads. Analysis of the resulting tissue assemblies revealed: multicellular spheroids, fibroblasts synthesized collagen, and cell viability was retained for the 30-day test period after removal from the bioreactor. Quantification of mutation at the LacI gene in Rat 2 lambda fibroblasts in spheroids exposed to 0-2 Gy neon using the Big Blue color assay (Stratagene, Inc.), revealed a linear dose-response for mutation induction. Limited sequencing analysis of mutant clones from 0.25 or 1 Gy exposures revealed a higher frequency of deletions and multiple base sequencing changes with increasing dose. These results suggest that the three-dimensional, multicellular tissue assembly model produced in NASA bioreactors are applicable to a wide variety of studies involving the quantification and identification of genotoxicity including measurement of the inherent damage incurred in Space.     

No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblasts after alpha particle irradiation

A major concern for bystander effects is the probability that normal healthy cells adjacent to the irradiated cells become genomically unstable and undergo further carcinogenesis after therapeutic irradiation or space mission where astronauts are exposed to low dose of heavy ions. Genomic instability is a hallmark of cancer cells. In the present study, two irradiation protocols were performed in order to ensure pure populations of bystander cells and the genomic instability in their progeny were investigated. After irradiation, chromosomal aberrations of cells were analyzed at designated time points using G₂ phase premature chromosome condensation (G₂-PCC) coupled with Giemsa staining and with multiplex fluorescent in situ hybridization (mFISH). Our Giemsa staining assay demonstrated that elevated yields of chromatid breaks were induced in the progeny of pure bystander primary fibroblasts up to 20 days after irradiation. mFISH assay showed no significant level of inheritable interchromosomal aberrations were induced in the progeny of the bystander cell groups, while the fractions of gross aberrations (chromatid breaks or chromosomal breaks) significantly increased in some bystander cell groups. These results suggest that genomic instability occurred in the progeny of the irradiation associated bystander normal fibroblasts exclude the inheritable interchromosomal aberration.     

Remote sensing detection of gold related alteration zones in Um Rus area, Central Eastern Desert of Egypt

Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and Phased Array L-band Synthetic Aperture Radar (PALSAR) images covering the Um Rus area in the Central Eastern Desert of Egypt were evaluated for mapping geologic structure, lithology, and gold-related alteration zones. The study area is covered by Pan-African basement rocks including gabbro and granodiorite intruded into a variable mixture of metavolcanics and metasediments. The first three principal component analyses (PCA1, PCA2, PCA3) in a Red-Green-Blue (RGB) of the visible through shortwave-infrared (VNIR + SWIR) ASTER bands enabled the discrimination between lithological units. The results show that ASTER band ratios ((2 + 4)/3, (5 + 7)/6, (7 + 9)/8) in RGB identifies the lithological units and discriminates the granodiorite very well from the adjacent rock units.The granodiorites are dissected by gold-bearing quartz veins surrounded by alteration zones. The microscopic examination of samples collected from the alteration zones shows sericitic and argillic alteration zones. The Spectral Angle Mapper (SAM) and Spectral Information Divergence (SID) supervised classification methods were applied using the reference spectra of the USGS spectral library. The results show that these classification methods are capable of mapping the alteration zones as indicated by field verification work. The PALSAR image was enhanced for fracture mapping using the second moment co-occurrence filter. Overlying extracted faults and alteration zone classification images show that the N30E and N-S fractures represent potential zones for gold exploration. It is concluded that the proposed methods can be used as a powerful tool for ore deposit exploration.     

Investigations onboard the biosatellite Cosmos-1667

The program of the 7-day flight of the biosatellite Cosmos-1667 launched in July 1985 included experiments on two rhesus monkeys, ten Wistar SPF rats, ten newts, Drosophila flies, maize seedlings, lettuce sprouts, and unicellular organisms - Tetrahymena. The primate study demonstrated that transition to orbital flight was accompanied by a greater excitability of the vestibular apparatus and an increased linear blood flow velocity in the common carotid artery. The rat studies showed that atrophy of antigravity muscles and osteoporosis of limb bones developed even during short-term exposure to microgravity. The experiments on other living systems revealed no microgravity effects on the cell division rate, proliferative activity of cells of regenerating tissues and organs, energy metabolism of developing insects, structure or chemical composition of higher plant seedlings.     

Free and membrane-bound calcium in microgravity and microgravity effects at the membrane level.

The changes of [Ca2+]i controlled is known to play a key regulatory role in numerous cellular processes especially associated with membranes. Previous studies from our laboratory have demonstrated an increase in calcium level in root cells of pea seedlings grown aboard orbital station "Salyut 6". These results: 1) indicate that observed Ca(2+)-binding sites of membranes also consist in proteins and phospholipids; 2) suggest that such effects of space flight in membrane Ca-binding might be due to the enhancement of Ca2+ influx through membranes. In model presented, I propose that Ca(2+)-activated channels in plasma membrane in response to microgravity allow the movement of Ca2+ into the root cells, causing a rise in cytoplasmic free Ca2+ levels. The latter, in its turn, may induce the inhibition of a Ca2+ efflux by Ca(2+)-activated ATPases and through a Ca2+/H+ antiport. It is possible that increased cytosolic levels of Ca2+ ions have stimulated hydrolysis and turnover of phosphatidylinositols, with a consequent elevation of cytosolic [Ca2+]i. Plant cell can response to such a Ca2+ rise by an enhancement of membranous Ca(2+)-binding activities to rescue thus a cell from an abundance of a cytotoxin. A Ca(2+)-induced phase separation of membranous lipids assists to appear the structure nonstable zones with high energy level at the boundary of microdomains which are rich by some phospholipid components; there is mixing of molecules of the membranes contacted in these zones, the first stage of membranous fusion, which was found in plants exposed to microgravity. These results support the hypothesis that a target for microgravity effect is the flux mechanism of Ca2+ to plant cell.     

Effect of secondary radiation produced by 70 GeV protons on DNA of mammalian cells.

It is shown that the RBE of the 70 GeV proton secondary radiation for the induction of single-strand break is 1.6-7.6 in Chinese hamster fibroblasts and 1.04-3.8 in limphoid cells and for the lethality of Chinese hamster cells 1.14-1.7. The RBE value increases with decreasing dose of the secondary radiation. On post-irradiation incubation of mammalian cells at 37 degrees C, single-strand breaks induced by the secondary radiation are repaired with the sane time course as those induced by gamma-rays. In our earlier works we have made an attempt to estimate the biological efficiency of radiation generated by the 70 GeV protons on bacteria, phage T4 and Vicia faba beans. The obtained values of the relative biological efficiency (RBE) of this radiation varied between 1.4 and 5.5, depending on the object, criterion of estimation, times of registration and other experimental conditions. The aim of the present work is to estimate the biological efficiency of synchrotron radiation by its effect on mammalian cells.     

A physical and chemical characterization of Martian permafrost as a possible habitat for viable microorganisms.

Data from experiments with model samples show that ion transfer coefficients in the water-rich permafrost on Mars must be three orders of magnitude less than those of terrestrial permafrost. The effects of low temperatures and of carbon dioxide have been accounted for. Exchange between cells and the environment is impeded in Martian permafrost. The microscopic distributional heterogeneity of concentration, pH, Eh, and other physicochemical parameters may be more pronounced in the permafrost of Mars. We present a classification of unfrozen water types in the permafrost that is based on the structures of unfrozen water films and on their functions with respect to cells. Any viable microorganisms on Mars probably exist with minimum metabolism in compact zones with energy carriers and high transfer coefficients. These zones may be microvolumes of unfrozen water in which cells accumulate.     

Cellular parameters for track structure modeling of radiation hazard in space.

Based on irradiation with 45 MeV/u N and B ions and with Co-60 gamma rays, cellular parameters of Katz's track structure model have been fitted for the survival of V79-379A Chinese hamster lung fibroblasts. Cellular parameters representing neoplastic transformations in C3H10T/1/2 cells after their irradiation with heavy ion beams, taken from earlier work, were also used to model the radiation hazard in deep space, following the system for evaluating, summing and reporting occupational exposures proposed in 1967 by a subcommittee of NCRP. We have performed model calculations of the number of transformations in surviving cells, after a given fluence of heavy charged particles of initial energy 500 MeV/u, penetrating thick layers of cells. We take the product of cell transformation and survival probabilities, calculated along the path lengths of charged particles using cellular survival and transformation parameters, to represent a quantity proportional to the "radiation risk factor" discussed in the NCRP document. The "synergistic" effect of simultaneous charged particle transfers is accounted for by the "track overlap" mode inherent in the model of Katz.     

Effects of lunar and mars dust simulants on HaCaT keratinocytes and CHO-K1 fibroblasts

Exposure to lunar dust during Apollo missions resulted in occasional reports of ocular, respiratory and dermal irritations which showed that lunar dust has a risk potential for human health. This is caused by its high reactivity as well as its small size, leading to a wide distribution also inside habitats. Hence, detailed information regarding effects of extraterrestrial lunar dusts on human health is required to best support future missions to moon, mars or other destinations. In this study, we used several methods to assess the specific effects of extraterrestrial dusts onto mammalian skin by exposing HaCaT keratinocytes and CHO-K1 fibroblasts to dusts simulating lunar or mars soils. These particular cell types were chosen because the skin protects the human body from potentially harmful substances and because a well orchestrated program ensures proper wound healing. Keratinocytes and fibroblasts were exposed to the dusts for different durations of time and their effects on morphology and viability of the cells were determined. Cytotoxicity was measured using the MTT assay and by monitoring culture impedance, while phalloidin staining of the actin cytoskeleton was performed to address structural integrity of the cells which was also investigated by propidium iodide intake. It was found that the effects of the two types of dust simulants on the different features of both cell lines varied to a considerable extent. Moreover, proliferation of HaCaT keratinocytes, as analyzed by Ki67 labeling, was suppressed in sub-confluent cultures exposed to lunar dust simulant. Furthermore, experimental evidence is provided for a delay in regeneration of keratinocyte monolayers from scratch-wounding when exposed to lunar dust simulant. The obtained results will facilitate further investigations of dust exposure during wound healing and will ease risk assessment studies e.g., for lunar lander approaches. The investigations will help to determine safety measures to be taken during extraterrestrial expeditions in order to minimize risks to human health associated with exposure of human skin to dust contaminants.     

Mechano-sensing and mechano-reaction of soft connective tissue cells.

One main function of the connective tissues is to provide cells with a mechanically resistant attachment support required for survival, division and differentiation. All cells contain membrane-anchored attachment proteins able to recognize specific chemical motifs in the extracellular macromolecules forming the supporting scaffold, made of various types of collagen, adhesive glycoproteins, elastin, proteoglycans, etc... These cell-matrix interactions are mainly mediated by receptors of the integrins family, heterodimeric molecules made of an extracellular domain connected through a transmembrane sequence to an intracytoplasmic tail. Upon recognition of the extracellular ligand, the clustering and activation of the integrins result in the recruitment of a complex of proteins and formation of the focal adhesion plaque, containing both cytoskeletal and catalytic signaling molecules. Activation results in polymerization of actin and formation of stress fibers. These structures establish a physical link between the extracellular matrix components and the cytoskeleton through the integrins providing a continuous path acting as a mechanotransducer. This connection is used by the cells to perform their mechanical functions as adhesion, migration and traction. In vitro experimental models using fibroblasts in a collagen gel demonstrate that cells are in mechanical equilibrium with their support which regulates their replicative and biosynthetic phenotype. The present review discusses the molecular structures operating in the transmission of the mechanical messages from the support to the connective tissue cells, and their effect on the cellular machinery. We present arguments for investigating these mechanisms in understanding the perception of reduced gravity and the resulting reaction leading to microgravity induced pathologies.     

DNA fragmentation by charged particle tracks.

High-LET (linear energy transfer) charged particles induce DNA double-strand breaks (DSB) in a non-random fashion in mammalian cells. The clustering of DSB, probably determined by track structure as well as chromatin conformation, results in an excess of small- and intermediate-sized DNA fragments. DNA fragmentation in normal human fibroblasts (GM5758) was analyzed by pulsed-field gel electrophoresis after irradiation with photons (60Co) or 125 keV/micrometers nitrogen ions. Compared to conventional DSB analysis, i.e. assays only measuring the fraction of DNA smaller than a single threshold, the relative biological effectiveness (RBE) for DSB induction increased with 100%. Further, the size distribution of DNA fragments showed a significant dependence on radiation quality, with an excess of fragments up to 1 Mbp. Irradiation of naked genomic DNA without histone proteins increased the DSB yields 25 and 13 times for photons and nitrogen ions, respectively. The results suggest possible roles of both track structure and chromatin organization in the distribution of DNA double-strand breaks along the chromosome.     

Changes in the numbers of osteoclasts in newts under conditions of microgravity.

Intensity of osteoclastic resorption and calcium content were investigated in intact limb bones of the newts flown on board of a biosatellite Cosmos-2229 after amputation of their forelimbs and tail. Using X-ray microanalysis it was shown an increase in calcium content in the bones on 20th day after operation. Histological study revealed an activation of osteoclastic resorption on endosteal surface of long bones. The newts exposed after surgery on a biosatellite had the same level of bone mineralisation as operated ground control ones, but the increase in number of polynuclear osteoclasts was lower.     

压电网络板的机电耦合动力学特性

借鉴复合材料结构建模中的均匀化处理方法建立了压电网络板机电耦合动力学方程并对其进行求解,获得了耦合系统的频率特征方程;通过求解频率特征方程发现压电网络板的固有模态以耦合模态对的形式存在;在此基础上对耦合系统的频率特性进行了分析,表明耦合模态对的特征频率值随着电感的变化会出现频率转向现象.进一步通过对系统在频率转向区能量转换规律的研究,揭示了压电网络板中频率转向的意义.最后,分析了压电网络板设计参数对频率转向区特性的影响,为压电网络板的合理设计提供了理论参考.     

Microgravity and musculoskeletal system of mammals.

This review surveys data in the literature and our own findings concerning the effects of weightlessness on bones and muscles of white rats flown on Cosmos biosatellites and Spacelab-3. It has been shown that the magnitude and sign of functional changes in muscles depend on their biomechanical profile. Structural and metabolic foundations of functional adaptation and its dynamics have been identified: in 5-7 day flights muscle contractility changes are mainly associated with a diminished activity of excitation-contraction coupling, in longer-term flights they are produced by changes in myosin populations specific for myofibers of different functional profile. At early flight stages (up to 1 week) osteoporosis and bone demineralization are very mild; therefore decrease in bone mechanical strength may be caused by changes in physico-chemical parameters of the collagen-crystal system. In flights of up to 3 weeks noticeable osteoporosis develops which is primarily produced by osteogenesis inhibition and which is responsible for a marked decrease of bone strength. These changes may result from uncoupling of bone resorption and remodelling processes. This uncoupling is characterized as incomplete osteogenesis and may be caused by changes in the collagen composition of the organic bone matrix. The above-mentioned adaptive changes in muscle functions of specific skeletal compartments may play a role in different responses of various bones to weightlessness.     

Landsat model for groundwater exploration in Nuba Mountains,Sudan

The region of Nuba Mountains is largely dominated by Precambrian crystalline basement rocks, and often experiences acute shortage of water for domestic and irrigation purposes especially during the dry season (February – May). A Landsat model essentially based on lineament and drainage analysis is proposed to delineate potential target zones for groundwater prospecting. Target zones are indicated by the overlap of the high-intensity lineament contours and the low-intensity drainage contours, and by intersection of a stream channel and lineament structure. Most wells lying within the defined targets are successful.     

Potential vascular damage from radiation in the space environment.

Cultured endothelial cells of blood vessels have a Do of 2 Gy for X-rays. A dose of 0.5 Gy of X-rays has an acute effect on vessel diameter. The vessels may show other acute effects such as change in permeability including a change in the blood brain barrier. Changes occurring from late effects of chronic exposure in vascular architecture include telangiectasia and decrease in vascular density. Changes in the perivascular connective tissue particularly collagen may play a role in these changes. After charged particle exposure of 15 and 30 Gy, radiation changes in the blood brain barrier and vascular changes are noted in the nervous system. These long term changes are recorded by PET, MRI, and CT imaging. Chronic exposure to alpha particles causes vascular damage in compact bone resulting in bone infarcts. Using tandem scanning confocal microscopy in-situ imaging of the capillaries and collagen of the papillary dermis provides a non-invasive method of serial recording of changes in irradiated microvasculature.