Drosophila melanogaster, a model system for comparative studies on the responses to real and simulated microgravity

A key requirement to enhance our understanding of the response of biological organisms to different levels of gravity is the availability of experimental systems that can simulate microgravity and hypergravity in ground-based laboratories. This paper compares the results obtained from analysing gene expression profiles of Drosophila in space versus those obtained in a random position machine (RPM) and by centrifugation. The correlation found validates the use of the RPM simulation technique to establish the effects of real microgravity on biological systems. This work is being extended to investigate Drosophila development in another gravity modifying instrument, the levitation magnet.     

Artificial gravity in space and in medical research

The history of manned space flight has repeatedly documented the fact that prolonged sojourn in space causes physiological deconditioning. Physiological deterioration has raised a legitimate concern about man's ability to adequately perform in the course of long missions and even the possibility of leading to circumstances threatening survival. One of the possible countermeasures of physiological deconditioning, theoretically more complete than others presently used since it affects all bodily systems, is artificial gravity. Space stations and spacecrafts can be equipped with artificial gravity, but is artificial gravity necessary? The term "necessary" must be qualified because a meaningful answer to the question depends entirely on further defining the purpose of space travel. If man intends to stay only temporarily in space, then he must keep himself in good physical condition so as to be able to return to earth or to land on any other planetary surface without undue exposure to major physiological problems resulting from transition through variable gravitational fields. Such a situation makes artificial gravity highly desirable, although perhaps not absolutely necessary in the case of relative short exposure to microgravity, but certainly necessary in interplanetary flight and planetary landings. If the intent is to remain indefinitely in space, to colonize space, then artificial gravity may not be necessary, but in this case the consequences of long term effects of adaptation to weightlessness will have to be weighed against the biological evolutionary outcomes that are to be expected. At the moment, plans for establishing permanent colonies in space seem still remote. More likely, the initial phase of exploration of the uncharted solar system will take place through successive, scope limited, research ventures ending with return to earth. This will require man to be ready to operate in gravitational fields of variable intensity. Equipping spacecrafts or space stations with some means of artificial gravity in this initial phase is, therefore, necessary without question. In a strict sense artificial gravity is conceived as a means of replacing natural gravity in space by the centripetal acceleration generated by some sort of rotating device. Rotating devices create an inertial force which has effects on bodies similar to those caused by terrestrial gravity, but artificial gravity by a rotation device is not the same as terrestrial gravity, as we shall see. Present research in artificial gravity for space exploration is projected in two main directions: artificial gravity for whole space stations and artificial gravity produced by short arm centrifuges designed for human use in space.     

A mechanism conjugating cellular and individual adaptations could be produced from space biology]

To know a basic mechanism of biological organism on the earth, we can have a standard point to space. An example is hindlimb suspension model that could induce muscle atrophy. This model mimics adaptational changes under zero gravity; in turn the effect of gravity on the biological system developing on the earth. We can understand gravity is a stress from the specific changes of stress protein induced by mechanical stimuli depending on gravity. Recent development of fluorescent microscopy and time-lapse visual system brought us a possibility of analysis to see visualization of dynamic properties of molecular and cellular events in living cells. Especially dynamic fluctuation of cytoskeleton may include new ideas of biological strategy of living organism on the earth and possibly may suggest subtle changes in space.     

Patch-clamp experiments under micro-gravity

For human based space research it is of high importance to understand the influence of gravity on the properties of single ion channels in biological membranes, as these are involved in about all biological processes. The patch clamp technique is the best established method to investigate electrophysiological properties of single ion channels in detail. Consequently, a patch clamp set-up was designed for the drop tower in Bremen, Germany. Using this set-up among others, successfully leech neurons have been patched under micro-gravity, delivering data about ion channel behaviour, which were compared to results from bilayer experiments in the drop tower and to results from lab controls under 1 g and under higher gravity.     

Gravitational biology within the German Space Program: goals, achievements, and perspectives

Summary. Gravity plays an important role for the evolution, orientation and development of organisms. Most of us, however, tend to overlook its importance because – due to its constant presence from the beginning of evolution some 4 billion years ago – this environmental parameter is almost hardwired into our interpretation of reality. This negligence of gravity is the more surprising as we all have our strong fights with this factor, especially during the very early and again during the late phases of our lives. On the other hand, scientists have been fascinated to observe the effects of gravity especially on plants and microorganisms for more than a hundred years, since Darwin and Sachs demonstrated the role of the root cap for downward growing plants. Different experimental approaches are nowadays available in order to change the influence of gravity and to study the corresponding influences on the physiology of biological systems. With the advent of spaceflight, a long-term nearly nullification of gravity is possible. Utilisation of this so-called “microgravity” condition for research in life sciences thus became an important asset in the space programs of various space agencies around the world. The German Space Life Sciences Program is managed – like all other space programs and activities in Germany – by the German Aerospace Center (DLR) in its role as space agency for Germany. Within the current space program, approved by the German government in May 2001, the overall goal for its life sciences part was defined as to gain scientific knowledge and to disclose new application potential by research under space conditions, especially by utilising the microgravity environment of the International Space Station. Three main scientific fields have been identified in collaboration with the scientific community: integrative human physiology, biotechnological applications of the microgravity environment, and fundamental biology of gravity and radiation responses (i.e., gravitational and radiation biology). In the present contribution, specific goals as well as achievements and perspectives of research in gravitational biology are given. In addition, some information is provided on spaceflight opportunities available. Correspondence and reprints: German Aerospace Center (DLR), Space Agency, P.O. Box 300364, 53183 Bonn, Federal Republic of Germany.     

Perspective on gravitational biology of amphibians]

We review here the scientific significance of the use of amphibians for research in gravitational biology. Since amphibian eggs are quite large, yet develop rapidly and externally, it is easy to observe their development. Consequently amphibians were the first vertebrates to have their early developmental processes investigated in space. Though several deviations from normal embryonic development occur when amphibians are raised in microgravity, their developmental program is robust enough to return the organisms to an ostensibly normal morphology by the time they hatch. Evolutionally, amphibians were the first vertebrate animal to come out of the water and onto land. Subsequently they diversified and have adaptively radiated to various habitats. They now inhabit aquatic, terrestrial, arboreal and fossorial niches. This diversity can be used to help study the biological effects of gravity at the organismal level, where macroscopic phenomena are associated with gravitational loading. By choosing different amphibian models and using a comparative approach one can effectively identify the action of gravity on biological systems, and the adaptation that vertebrates have made to this loading. Advances in cellular and molecular biology provide powerful tools for the study in many fields, including gravitational biology, and amphibians have proven to be good models for studies at those levels as well. The low metabolic rates of amphibians make them convenient organisms to work with (compared to birds and mammals) in the difficult and confined spaces on orbiting research platforms. We include here a review of what is known about and the potential for further behavioral and physiological researches in space using amphibians.     

Animals and spaceflight: from survival to understanding

Animals have been a critical component of the spaceflight program since its inception. The Russians orbited a dog one month after the Sputnik satellite was launched. The dog mission spurred U.S. interest in animal flights. The animal missions proved that individuals aboard a spacecraft not only could survive, but also could carry out tasks during launch, near-weightlessness, and re-entry; humans were launched into space only after the early animal flights demonstrated that spaceflight was safe and survivable. After these humble beginnings when animals preceded humans in space as pioneers, a dynamic research program was begun using animals as human surrogates aboard manned and unmanned space platforms to understand how the unique environment of space alters life. In this review article, the following questions have been addressed: How did animal research in space evolve? What happened to animal development when gravity decreased? How have animal experiments in space contributed to our understanding of musculoskeletal changes and fracture repair during exposure to reduced gravity?     

Ground-based methods reproduce space-flight experiments and show that weak vibrations trigger microtubule self-organisation

The effect of weightlessness on physical and biological systems is frequently studied by experiments in space. However, on the ground, gravity effects may also be strongly attenuated using methods such as magnetic levitation and clinorotation. Under suitable conditions, in vitro preparations of microtubules, a major element of the cytoskeleton, self-organise by a process of reaction–diffusion: self-organisation is triggered by gravity and samples prepared in space do not self-organise. Here, we report experiments carried out with ground-based methods of clinorotation and magnetic levitation. The behaviour observed closely resembles that of the space-flight experiment and suggests that many space experiments could be carried out equally well on the ground. Using clinorotation, we find that weak vibrations also trigger microtubule self-organisation and have an effect similar to gravity. Thus, in some in vitro biological systems, vibrations are a countermeasure to weightlessness.     

Models to study gravitational biology of Mammalian reproduction

Mammalian reproduction evolved within Earth's 1-g gravitational field. As we move closer to the reality of space habitation, there is growing scientific interest in how different gravitational states influence reproduction in mammals. Habitation of space and extended spaceflight missions require prolonged exposure to decreased gravity (hypogravity, i.e., weightlessness). Lift-off and re-entry of the spacecraft are associated with exposure to increased gravity (hypergravity). Existing data suggest that spaceflight is associated with a constellation of changes in reproductive physiology and function. However, limited spaceflight opportunities and confounding effects of various nongravitational factors associated with spaceflight (i.e., radiation, stress) have led to the development of ground-based models for studying the effects of altered gravity on biological systems. Human bed rest and rodent hindlimb unloading paradigms are used to study exposure to hypogravity. Centrifugation is used to study hypergravity. Here, we review the results of spaceflight and ground-based models of altered gravity on reproductive physiology. Studies utilizing ground-based models that simulate hyper- and hypogravity have produced reproductive results similar to those obtained from spaceflight and are contributing new information on biological responses across the gravity continuum, thereby confirming the appropriateness of these models for studying reproductive responses to altered gravity and the underlying mechanisms of these responses. Together, these unique tools are yielding new insights into the gravitational biology of reproduction in mammals.     

Gravitational biology of integrative organisms and ecological system--the road map of space activities]

History of the International Space Station, ISS, and planning of its scientific use are described in this essay. Fundamental gravitational biology and its facility on the ISS have been identified to have the highest priority to conduct scientific experiments with variable G environment in orbit. The road map of space activities is clearly directing the efforts toward manned Mars exploration. The Centrifuge is a core element of the facilities dedicated to this endeavor. Several research subjects are discussed with the results obtained from the past space experiments. Direct effects of gravity on the biological system at the level of integrative organisms are major subjects of study that will be conducted on the large scaled centrifuge.     

Signal transduction in cells of the immune system in microgravity

Life on Earth developed in the presence and under the constant influence of gravity. Gravity has been present during the entire evolution, from the first organic molecule to mammals and humans. Modern research revealed clearly that gravity is important, probably indispensable for the function of living systems, from unicellular organisms to men. Thus, gravity research is no more or less a fundamental question about the conditions of life on Earth. Since the first space missions and supported thereafter by a multitude of space and ground-based experiments, it is well known that immune cell function is severely suppressed in microgravity, which renders the cells of the immune system an ideal model organism to investigate the influence of gravity on the cellular and molecular level. Here we review the current knowledge about the question, if and how cellular signal transduction depends on the existence of gravity, with special focus on cells of the immune system. Since immune cell function is fundamental to keep the organism under imnological surveillance during the defence against pathogens, to investigate the effects and possible molecular mechanisms of altered gravity is indispensable for long-term space flights to Earth Moon or Mars. Thus, understanding the impact of gravity on cellular functions on Earth will provide not only important informations about the development of life on Earth, but also for therapeutic and preventive strategies to cope successfully with medical problems during space exploration.     

Strategies of cell biology experimentation in space

The purpose of this article is to inform newcomers on the most important aspects of experimentation with living cells and tissues in space laboratories and platforms. There are strong arguments that justify the efforts and investments in such activity. Experimentation in space is subject to safety and technological constraints that require considerable attention to the development of the flight protocols and of the flight instrumentation. Nevertheless to fly an experiment in space is a unique opportunity to study living systems under conditions not reproducible on Earth and it is also a contribution to human exploration of space. Thereby important progress in basic and applied science can be expected. Parallel investigations on ground with devices averaging the exposure to the gravity vector but not reproducing microgravity shall always be part of a space flight project.     

基于“三生空间”的土地利用功能演变及生态环境响应——以桂西资源富集区为例

分析土地利用功能演变及生态环境响应是区域"三生空间"划定和管控以及生态环境保护的重要依据。以桂西资源富集区为例,基于1995年、2000年、2005年、2010年和2015年5期遥感数据,构建"三生空间"土地利用主导功能分类体系,运用转移矩阵、重心转移和生态环境响应模型分析研究区20年土地利用功能演变特征及生态环境响应情况,结果表明:(1)研究区生态生产空间和生活生产空间面积呈上升趋势,生产生态空间和生态空间面积呈下降趋势。(2)生态生产空间重心转移距离最大,其次是生活生产空间重心,生产生态空间和生态空间重心转移距离较小。(3)研究区生态环境质量指数从1995年的0.6337持续降至2015年的0.6323,整体质量有所下降。(4)以林草地为主要地类的县域生态环境质量较高,重点矿产资源型县域和农产品生产基地生态环境质量较低,城镇化重点县域生态环境质量最低。     

The microgravity environment for experiments on the International Space Station

Experiments are sent to space laboratories in order to take advantage of the low-gravity environment. However, it is crucial to appreciate the distinction between the real microgravity environment and "weightlessness" or "simulated microgravity". The microgravity in space laboratories may be of much smaller magnitude than the gravitational acceleration on earth. However, it is not zero, nor even one microg (defined as 1e-6 earth gravity). Moreover, the orientation is not uniaxial, as on earth. The net acceleration that acts on a space experiment arises from, e.g., orbital mechanics, atmospheric drag, and thruster firings, and it can act on the experiments in gravity-like ways. In essence, a well-defined, stable 1 g acceleration on the earth's surface is substituted for a complex array of dynamically changing accelerations with ever-changing frequency content, magnitude and direction. This paper will show measured accelerations on the Shuttle from launch to orbit, as well as the latest measurements on the International Space Station (ISS). The ISS data presented here represent over 34,790 hours of data obtained from June 2002 to April 2003 during Increments 5 and 6 of the ISS construction cycle. The quasisteady acceleration level on the ISS has been measured to be on the order of a few microg during time allotted to microgravity mode. The vibratory acceleration environment spans a rich spectrum from 0.01-300 Hz.     

A model for studying the baroreflex in microgravity and hypergravity

The study on development in altered gravity has been investigated in a wide range of animal species from a molecular level or cell culture to mammalian bodies. However development of the baroreflex has been studied in limited mammalian species even on the ground except the turtle to study diving reflex. The rat or mouse has been selectively used for studying the relationship between development of various functions and gravity especially microgravity, because of the limited body size for the loading space on the space ship, an experimental-animal most often used, and other biological characteristics. We have used the rat and rabbit for investigating the effect of microgravity on the development of the aortic baroflex. In the present paper a few results of our experiments using the rat will be shown and the appropriateness of the rat as a model system for studying the baroflex development in altered gravity will be discussed.     

Quality assurance of biological monitoring in occupational and environmental medicine

Biological monitoring of chemical exposure in the workplace has become increasingly important in the assessment of health risk as an integral part of the overall occupational health and safety strategy. In environmental medicine biological monitoring plays also an important role in the assessment of excessive, acute or chronic exposure to chemical agents. To guarantee that the results obtained in biological monitoring are comparable with threshold limit values and results from other laboratories, the analysis must be carried out with tested and reliable analytical methods and accompanied by a quality assurance scheme. Confounding influences and interferences during the pre-analytical phase can be minimised by recommendations from experienced laboratories. For internal quality control commercially available control samples with an assigned concentration are used. External quality control programs for biological monitoring are offered by several institutions. The external quality control program of the German Society of Occupational and Environmental Medicine has been organised since 1982. In the meantime the 27th program has been carried out offering 96 analytes in urine, blood and plasma for 47 substances. This program covers most of the parameters relevant to occupational and environmental medicine. About 350 laboratories take part in these intercomparison programs. At present, ten German and 14 international laboratories are commissioned to determine the assigned values. The data evaluated from the results of the intercomparison programs give a good overview of the current quality of the determination of analytes assessed in occupational and environmental toxicological laboratories. For the analysis of inorganic substances in blood and urine the tolerable variation ranges from 7.5 to 43.5%. For organic substances in urine the tolerable variation ranges from 12 to 48%. The highest variations (36-60%) were found for the analysis of organochlorine compounds in plasma. The tolerable variations for the determination of solvents in blood by head space gas chromatography range from 26 to 57%. If the recommendations for the pre-analytical phase, the selection of reliable analytical methods by the laboratory and the carrying out of adequate quality control are observed, the pre-requisites for reliable findings during biological monitoring are fulfilled     

The short history of research in a marine climate change hotspot: from anecdote to adaptation in south-east Australia

Climate change is not being felt equally around the world. Regions where warming is most rapid will be among those to experience impacts first, will need to develop early responses to these impacts and can provide a guide for management elsewhere. We describe the research history in one such global marine hotspot—south-east Australia—where a number of contentions about the value of hotspots as natural laboratories have been supported, including (1) early reporting of changes (2) early documentation of impacts, and (3) earlier development and promotion of adaptation options. We illustrate a transition from single discipline impacts-focused research to an inter-disciplinary systems view of adaptation research. This transition occurred against a background of change in the political position around climate change and was facilitated by four preconditioning factors. These were: (1) early observations of rapid oceanic change that coincided with (2) biological change which together provided a focus for action, (3) the strong marine orientation and history of management in the region, and (4) the presence of well developed networks. Three case studies collectively show the critical role of inter-disciplinary engagement and stakeholder participation in supporting industry and government adaptation planning.     

Exploration of plant growth and development using the European Modular Cultivation System facility on the International Space Station

Space experiments provide a unique opportunity to advance our knowledge of how plants respond to the space environment, and specifically to the absence of gravity. The European Modular Cultivation System (EMCS) has been designed as a dedicated facility to improve and standardise plant growth in the International Space Station (ISS). The EMCS is equipped with two centrifuges to perform experiments in microgravity and with variable gravity levels up to 2.0 g. Seven experiments have been performed since the EMCS was operational on the ISS. The objectives of these experiments aimed to elucidate phototropic responses (experiments TROPI‐1 and ‐2), root gravitropic sensing (GRAVI‐1), circumnutation (MULTIGEN‐1), cell wall dynamics and gravity resistance (Cell wall/Resist wall), proteomic identification of signalling players (GENARA‐A) and mechanism of InsP₃ signalling (Plant signalling). The role of light in cell proliferation and plant development in the absence of gravity is being analysed in an on‐going experiment (Seedling growth). Based on the lessons learned from the acquired experience, three preselected ISS experiments have been merged and implemented as a single project (Plant development) to study early phases of seedling development. A Topical Team initiated by European Space Agency (ESA), involving experienced scientists on Arabidopsis space research experiments, aims at establishing a coordinated, long‐term scientific strategy to understand the role of gravity in Arabidopsis growth and development using already existing or planned new hardware.     

Mechanisms of the Early Phases of Plant Gravitropism

Gravitropism is directed growth of a plant or plant organ in response to gravity and can be divided into the following temporal sequence: perception, transduction, and response. This article is a review of the research on the early events of gravitropism (i.e., phenomena associated with the perception and transduction phases). The two major hypotheses for graviperception are the protoplast-pressure and starch-statolith models. While most researchers support the concept of statoliths, there are suggestions that plants have multiple mechanisms of perception. Evidence supports the hypothesis that the actin cytoskeleton is involved in graviperception/ transduction, but the details of these mechanisms remain elusive. A number of recent developments, such as increased use of the molecular genetic approach, magnetophoresis, and laser ablation, have facilitated research in graviperception and have allowed for refinement of the current models. In addition, the entire continuum of acceleration forces from hypo- to hyper-gravity have been useful in studying perception mechanisms. Future interdisciplinary molecular approaches and the availability of sophisticated laboratories on the International Space Station should help to develop new insights into mechanisms of gravitropism in plants.