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.     

头低位卧床对恒河猴骨代谢、糖脂代谢的抑制效应及其相关性分析

空间失重引起的骨代谢调节失衡是航天员遭受的最严重的危害之一.骨代谢失衡还有可能影响机体的糖脂代谢平衡.本研究利用恒河猴头低位卧床模拟失重效应实验方法,分析头低位卧床过程中恒河猴血清中骨代谢、糖脂代谢指标变化情况及其相关性.卧床组恒河猴血清中BAP在头低位卧床实验开始7天便出现了显著下降（P<0.05）,血清胰岛素、高密度脂肪酸含量在7天显著下降并一直维持在较低水平,血糖含量在7天时显著下降,但在21天时明显回升.分析发现,骨钙素与血糖、皮质醇、高密度脂肪酸含量间均存在相关性,这表明头低位卧床模拟失重效应实验中骨与糖脂代谢之间存在相互调控.      

大鼠后肢去负荷体位调节装置设计与实验研究

通过对大鼠尾吊模型进行改进，研制出一种新型可调节体位的大鼠后肢去负荷悬吊装置，研究模拟微重力效应下体液分布变化对大鼠骨代谢的影响.将36只SD大鼠均分为对照组（CON）、头低位后肢去负荷组（HDT）、水平位后肢去负荷组（HH）和头高位后肢去负荷组（HUT）4组，实验21天后，利用DXA检测大鼠的骨密度（BMD）.模拟微重力效应下的三组大鼠后肢均发生严重骨丢失，其中HH和HUT组后肢BMD显著大于HDT组.实验结果表明，体液分布变化可能在模拟微重力效应导致的骨丢失中起到重要作用，新型大鼠后肢去负荷悬吊装置能够调节大鼠体位（体液）进行模拟微重力效应研究.      

Simulation analysis for effects of bone loss on acceleration tolerance of human lumbar vertebra

The purpose of the present study was to analyze and predict the changes in acceleration tolerance of human vertebra as a result of bone loss caused by long-term space flight. A human L3–L4 vertebra FEM model was constructed, in which the cancellous bone was separated, and surrounding ligaments were also taken into account. The simulation results demonstrated that bone loss has more of an effect on the acceleration tolerance in x-direction. The results serve to aid in the creation of new acceleration tolerance standards, ensuring astronauts return home safely after long-term space flight. This study shows that more attention should be focused on the bone degradation of crew members and to create new protective designs for space capsules in the future.     

飞行员头盔夜视镜系统气流吹袭性能研究

开展飞行员头盔夜视镜系统的高速气流吹袭试验,研究其气动特性和作用在人体颈椎上的力,评价其对弹射救生安全性的影响,为头盔夜视镜系统的设计和使用提供依据。采用高速气流吹袭台（敞开式风洞）吹袭的试验方法,将弹射座椅固定在吹袭台喷口前的台架上,试验假人（HYBRID Ⅱ型假人）端正地放置在弹射座椅上,试验假人穿抗荷服,佩戴头盔、夜视镜、供氧面罩。以850 km/h的吹袭速度作为试验的起点,按照试验设计确定的原则依次调整吹袭速度。夜视镜分下位（工作）和上位（非工作）2个状态进行试验,用高速摄像机记录头盔夜视镜在吹袭时的佩戴状态,测量试验假人颈椎下端的力和力矩。高速摄像机、力和力矩测量系统用高速气流吹袭台设定的时间基准同步测量。共进行了10发试验,其中5发试验夜视镜从头盔上吹脱,5发未吹脱;获得了各次试验中假人颈椎的受力曲线及夜视镜吹脱的时刻和轨迹。按照试验合格判据,吹袭速度均未超过850 km/h。头盔加装夜视镜后,相比头盔不加装夜视镜,气流吹袭性能下降,吹袭速度800 km/h以上颈椎力矩超标,700 km/h为临界点,600 km/h合格。建议将头盔夜视镜系统的气流吹袭性能包线限制在600 km/h以内。      

Summing-up cosmonaut participation in long-term space flights.

The health condition and work capacity of space travellers during many flights remained adequate. Medical examinations performed during and after space flights consistently revealed the following symptom-complexes: space motion sickness, changes in the muscles system, hemodynamics, fluid-electrolyte balance and its regulation, calcium metabolism and bone density, transient erythrocytopenia and immunity decline. This paper presents a detailed discussion of the changes observed in space flight.     

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.     

三波长数字相位解调法解调误差及影响因素

介绍了光纤法布里-珀罗(F-P)传感器的传统解调方法,系统地推导了针对非本征法布里-珀罗干涉型(EFPI)传感器解调的三波长数字相位解调法的解调原理,仿真和实验分析了三波长数字相位解调法的解调误差。仿真分析结果表明,相位偏离正交关系是限制解调的最主要因素,要保证解调误差在15 nm以内,腔长变化应小于在正交腔长处2μm的范围。采用3个独立的激光光源进行实验,实验结果表明,在正交腔长附近1μm范围内变化,解调腔长误差小于12 nm,重复性误差小于10 nm,解调具有良好的稳定性。     

Effects of microgravity on bone and calcium homeostasis.

Mechanical function is known to be of crucial importance for the maintenance of bone tissue. Gravity on one hand and muscular effort on the other hand are required for normal skeletal structure. It has been shown by numerous experimental studies that loss of total-body calcium, and marked skeletal changes occur in people who have flown in space. However, most of the pertinent investigations have been conducted on animal models, including rats and non-human primates, and a reasonably clear picture of bone response to spaceflight has emerged during the past few years. Osteopenia induced by microgravity was found to be associated with reduction in both cortical and trabecular bone formation, alteration in mineralization patterns and disorganization of collagen, and non-collagenous protein metabolism. Recently, cell-culture techniques have offered a direct approach of altered gravity effects at the osteoblastic-cell level. But the fundamental mechanisms by which bone and calcium are lost during spaceflight are not yet fully known. Infrequency and high financial cost of flights have created the necessity to develop on-Earth models designed to mimic weightlessness effects. Antiorthostatic suspension devices are now commonly used to obtain hindlimb unloading in rats, with skeletal effects similar to those observed after spaceflight. Therefore, actual and "simulated" spaceflights, with investigations conducted at whole body and cellular levels, are needed to elucidate pathogeny of bone loss in space, to develop effective countermeasures, and to study recovery processes of bone changes after return to Earth.     

Possible nutrient limiting factor in long term operation of closed aquatic ecosystem

To investigate nutrient limitation effect on the community metabolism of closed aquatic ecosystem and possible nutrient limiting factors in the experimental food chains, depletion of inorganic chemicals including carbon, nitrogen and phosphorous was tested. A closed aquatic ecosystem lab module consisting of Chlorella pyrenoidosa and Chlamydomonas reinhardtii, Daphnia magna and associated unidentified microbes was established. Closed ecological systems receive no carbon dioxide; therefore, we presumed carbon as a first limiting factor. The results showed that the algae population in the nutrient saturated group was statistically higher than that in the nutrient limited groups, and that the chlorophyll a content of algae in the phosphorus limited group was the highest among the limited groups. However, the nitrogen limited group supported the most Daphnia, followed by the carbon limited group, the nutrient saturated group and the phosphorus limited group. Redundancy analysis showed that the total phosphorus contents were correlated significantly with the population of algae, and that the amount of soluble carbohydrate as feedback of nutrient depletion was correlated with the number of Daphnia. Thus, these findings suggest that phosphorus is the limiting factor in the operation of closed aquatic ecosystem. The results presented herein have important indications for the future construction of long term closed ecological system.     

Changes of cell-vascular complex in zones of adaptive remodeling of the bone tissue under microgravity conditions.

We examined the peculiarities of the structure of the blood-vascular bed and perivascular cells in zones of osteogenesis in the epiphyses and metaphises of femoral bones of rats, flown aboard the US laboratory SLS-2 for two weeks by electron microscopy and histochemistry. In zones of bone remodeling, there was a tendency for a reduction of sinusoid capillary specific volume. Endotheliocytes preserve the typical structure. In the population of perivascular cells, we discovered differentiating osteogenic cells that contained alkaline phosphomonoesterase as well as cells that don't contain this enzyme and differentiate into fibroblasts. The fibroblasts genesis in zones of adaptive remodeling of spongy bones leads to a further development of fibrous tissue that is not subject to mineralization.     

Study of nucleic acid metabolism in two astronauts.

During the last years data have evidenced that alteration in nucleic acid metabolism, expecially increased urinary excretion of modified nucleosides reflects physiological changes in living organism. In relation with the Soyuz-36-Salyut-6-Soyuz-35 mission in 1980 urinary nucleoside excretion of two astronauts /B.F., V.K./ were traced. Individual daily urine samples were collected for 4 days before starting and 6 days after landing and were analysed with improved analytical procedures /affinity chromatography, high Performance liquid chromatography/. Levels of 1-methylinosine, 1-methylguanosine and N,2,2-dimethylguanosine in urine were determined. Thus recorded changes differ considerably at two astronauts. One of the /V.K./ excreted nucleosides normally, another /B.F./ showed increase to 200-400 % levels excretion of above nucleosides on the second day after landing. The peak values disappeared on the 3-6 days after. To interpret this phenomenon extreme factors of space-flight /weightlessness, stress, radiations, etc./ have to be taken into consideration. However, we attach importance to training of astronauts. During the last decade data have evidenced that alterations in the metabolism of nucleic acids especial increased urinary excretion of modified nucleosides reflects physiological and in some cases pathological changes in living organism. In relation with the Soyuz-36-Salyut-6-Soyuz 35 mission urinary excretion of certain modified nucleosides of two astronauts /B.F. and V.K./ were measured. The aim of the measurements was: how the metabolism of transfer ribonucleic acids /tRNAs/ referring to cosmic flight, how it is reflected in urinary excretions of modified nucleosides. For these purposes we studied the excretion of methylguanosine, dimethylguanosine and methylinosine. These nucleosides are the normal minor components of tRNA.     

Function of the cytoskeleton in gravisensing during spaceflight.

Since astronauts and cosmonauts have significant bone loss in microgravity we hypothesized that there would be physiological changes in cellular bone growth and cytoskeleton in the absence of gravity. Investigators from around the world have studied a multitude of bone cells in microgravity including Ros 17/2.8, Mc3T3-E1, MG-63, hFOB and primary chicken calvaria. Changes in cytoskeleton and extracellular matrix (ECM) have been noted in many of these studies. Investigators have noted changes in shape of cells exposed to as little as 20 seconds of microgravity in parabolic flight. Our laboratory reported that quiescent osteoblasts activated by sera under microgravity conditions had a significant 60% reduction in growth (p<0.001) but a paradoxical 2-fold increase in release of the osteoblast autocrine factor PGE2 when compared to ground controls. In addition, a collapse of the osteoblast actin cytoskeleton and loss of focal adhesions has been noted after 4 days in microgravity. Later studies in Biorack on STS-76, 81 and 84 confirmed the increased release of PGE2 and collapse of the actin cytoskeleton in cells grown in microgravity conditions, however flown cells under 1 g conditions maintained normal actin cytoskeleton and fibronectin matrix. The changes seen in the cytoskeleton are probably not due to alterations in fibronectin message or protein synthesis since no differences have been noted in microgravity. Multiple investigators have observed actin and microtubule cytoskeletal modifications in microgravity, suggesting a common root cause for the change in cell architecture. The inability of the O g grown osteoblast to respond to sera activation suggests that there is a major alteration in anabolic signal transduction under microgravity conditions, most probably through the growth factor receptors and/or the associated kinase pathways that are connected to the cytoskeleton. Cell cycle is dependent on the cytoskeleton. Alterations in cytoskeletal structure can block cell growth either in G1 (F-actin microfilament collapse), or in G2/M (inhibition of microtubule polymerization during G2/M-phase). We therefore hypothesize that microgravity would inhibit growth in either G1, or G2/M.     

小型铯原子钟微波腔调谐过程的仿真研究

通过建立模型,利用Ansoft HFSS 12.0对小型铯原子钟内微波腔的调谐过程进行了仿真,得到了调谐棒半径、在调配器内长度与微波腔谐振频率之间的关系曲线。结果表明,调谐棒半径一定时,调谐棒长度在一定范围内,微波腔谐振频率随着长度的增加逐渐下降;随着半径的增大,微波腔谐振频率的变化范围逐渐增大,在铯原子跃迁中心频率处,调谐棒长度对微波腔谐振频率的影响变大。根据仿真结果,给出了调谐棒半径的取值范围,为微波腔的设计、加工和调谐提供了理论指导。     

The white blood cell line: changes induced in mice by hypergravity.

The effect of hypergravity on the white blood cell (WBC) line of mice was investigated by use of horizontal centrifuge. Several sets of experiments were performed, in which the parameters measured were the WBC and differential cell count in the peripheral blood. In another experiment, lymphocyte counts from the spleen, lymph nodes, and the thymus were measured. The needed samples were taken from the mice during a stay of 7-40 days under a hypergravity of 1.6G. The test groups that were placed on the arms of the centrifuge (1.6G) were compared with stationary control groups (1G) and a rotating control group located at the center of the centrifuge (1G). Such a comparison revealed the test animals to be deficient on all counts, to wit, showing a decrease in total number of WBC's, a decrease in lymphocyte number in the peripheral blood and a decrease in the number of lymphocyte in the spleen and thymus. The decrease of lymphocytes in peripheral blood was characterized by two different slopes--an early and temporary decrease at the first days of the experiment evident in both test and rotating control groups followed by a temporary increase, and a later persistent decrease, evident only in the test group, while in the rotating control lymphocyte counts reverted to normal. There were no significant differences in monocyte or neutrophil counts, except for a temporary increase in the number of neutrophils which peaked on the seventh day. In order to evaluate the effect of hypergravity on restoration of hematopoiesis following hematopoietic suppression, 5-fluoro-uracil (5-FU) was administered i.v. to both the experimental and control mice. Suppression of bone marrow was observed in all groups injected with 5-FU, but while there was later an increase in cell counts in the control groups, there was no such increase in the test group subjected to hypergravity.     

Hypergravity suppresses bone resorption in ovariectomized rats

The effects of gravity on bone metabolism are unclear, and little has been reported about the effects of hypergravity on the mature skeleton. Since low gravity has been shown to decrease bone volume, we hypothesized that hypergravity increases bone volume. To clarify this hypothesis, adult female rats were ovariectomized and exposed to hypergravity (2.9G) using a centrifugation system. The rats were killed 28 days after the start of loading, and the distal femoral metaphysis of the rats was studied. Bone architecture was assessed by micro-computed tomography (micro-CT) and bone mineral density was measured using peripheral quantitative CT (pQCT). Hypergravity increased the trabecular bone volume of ovariectomized rats. Histomorphometric analyses revealed that hypergravity suppressed both bone formation and resorption and increased bone volume in ovariectomized rats.     

Microgravity and bone cell mechanosensitivity.

The capacity of bone tissue to alter its mass and structure in response to mechanical demands has long been recognized but the cellular mechanisms involved remained poorly understood. Bone not only develops as a structure designed specifically for mechanical tasks, but it can adapt during life toward more efficient mechanical performance. Mechanical adaptation of bone is a cellular process and needs a biological system that senses the mechanical loading. The loading information must then be communicated to the effector cells that form new bone or destroy old bone. The in vivo operating cell stress derived from bone loading is likely the flow of interstitial fluid along the surface of osteocytes and lining cells. The response of bone cells in culture to fluid flow includes prostaglandin (PG) synthesis and expression of prostaglandin G/H synthase inducible cyclooxygenase (COX-2). Cultured bone cells also rapidly produce nitric oxide (NO) in response to fluid flow as a result of activation of endothelial nitric oxide synthase (ecNOS), which enzyme also mediates the adaptive response of bone tissue to mechanical loading. Earlier studies have shown that the disruption of the actin-cytoskeleton abolishes the response to stress, suggesting that the cytoskeleton is involved in cellular mechanotransduction. Microgravity, or better near weightlessness, is associated with the loss of bone in astronauts, and has catabolic effects on mineral metabolism in bone organ cultures. This might be explained as resulting from an exceptional form of disuse under near weightlessness conditions. However, under near weightlessness conditions the assembly of cytoskeletal elements may be altered since it has been shown that the direction of the gravity vector determines microtubular pattern formation in vivo. We found earlier that the transduction of mechanical signals in bone cells also involves the cytoskeleton and is related to PGE2 production. Therefore it is possible that the mechanosensitivity of bone cells is altered under near weightlessness conditions, and that this abnormal mechanosensation contributes to disturbed bone metabolism observed in astronauts. In our current project for the International Space Station, we wish to test this hypothesis experimentally using an in vitro model. The specific aim of our research project is to test whether near weightlessness decreases the sensitivity of bone cells for mechanical stress through a decrease in early signaling molecules (NO, PGs) that are involved in the mechanical loading-induced osteogenic response. Bone cells are cultured with or without gravity prior to and during mechanical loading, using our modified in vitro oscillating fluid flow apparatus. In this "FlowSpace" project we are developing a cell culture module that is used to provide further insight in the mechanism of mechanotransduction in bone.     

Phosphorus as a potential guide in the search for extinct life on Mars.

In contrast to the search for extant organisms, the quest for fossil remains of life on Mars need not be guided by the presence of water and organic compounds on the present surface. An appropriate tracer might be the element phosphorus which is a common constituent of living systems. Utilizing terrestrial analogues, it should preferentially exist in the form of sedimentary calcium phosphate (phosphorites), which would have readily resisted changing conditions on Mars. Moreover, higher ratios of P/Th in phosphorites in comparison to calcium phosphates from magmatic rocks give us the possibility to distinguish them from inorganically formed phosphorus deposits at or close to the Martian surface. Identification of anomalous phosphorus enrichments by remote sensing or in situ analysis could be promising approaches for selecting areas preferentially composed of rocks with remains of extinct life.     

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.