SEARCH · Search NASA
Results for “Review, Tutorial”
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Mechanosensitive channels of Escherichia coli: the MscL gene, protein, and activities
Although mechanosensory responses are ubiquitous and diverse, the molecular bases of mechanosensation in most cases remain mysterious MscL, a mechanosensitive channel of large conductance of Escherichia coli and its bacterial homologues are the first and currently only channel molecules shown to directly sense mechanical stretch of the membrane. In response to the tension conveyed via the lipid bilayer, MscL increases its open probability by several orders of magnitude. In the present review we describe the identification, cloning, and first sets of biophysical and structural data on this simplest mechanosensory molecule. We discovered a 2.5-ns mechanosensitive conductance in giant E. coli spheroplasts. Using chromatographies to enrich the target and patch clamp to assay the channel activity in liposome-reconstituted fractions, we identified the MscL protein and cloned the mscL gene. MscL comprises 136 amino acid residues (15 kDa), with two highly hydrophobic regions, and resides in the inner membrane of the bacterium. PhoA-fusion experiments indicate that the protein spans the membrane twice with both termini in the cytoplasm. Spectroscopic techniques show that it is highly helical. Expression of MscL tandems and covalent cross-linking suggest that the active channel complex is a homo-hexamer. We have identified several residues, which when deleted or substituted, affect channel kinetics or mechanosensitivity. Although unique when discovered, highly conserved MscL homologues in both gram-negative and gram-positive bacteria have been found, suggesting their ubiquitous importance among bacteria.
Tensegrity: the architectural basis of cellular mechanotransduction
Physical forces of gravity, hemodynamic stresses, and movement play a critical role in tissue development. Yet, little is known about how cells convert these mechanical signals into a chemical response. This review attempts to place the potential molecular mediators of mechanotransduction (e.g. stretch-sensitive ion channels, signaling molecules, cytoskeleton, integrins) within the context of the structural complexity of living cells. The model presented relies on recent experimental findings, which suggests that cells use tensegrity architecture for their organization. Tensegrity predicts that cells are hard-wired to respond immediately to mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix (e.g. integrins) or to other cells (cadherins, selectins, CAMs). Many signal transducing molecules that are activated by cell binding to growth factors and extracellular matrix associate with cytoskeletal scaffolds within focal adhesion complexes. Mechanical signals, therefore, may be integrated with other environmental signals and transduced into a biochemical response through force-dependent changes in scaffold geometry or molecular mechanics. Tensegrity also provides a mechanism to focus mechanical energy on molecular transducers and to orchestrate and tune the cellular response.
Psychosocial value of space simulation for extended spaceflight
There have been over 60 studies of Earth-bound activities that can be viewed as simulations of manned spaceflight. These analogs have involved Antarctic and Arctic expeditions, submarines and submersible simulators, land-based simulators, and hypodynamia environments. None of these analogs has accounted for all the variables related to extended spaceflight (e.g., microgravity, long-duration, heterogeneous crews), and some of the stimulation conditions have been found to be more representative of space conditions than others. A number of psychosocial factors have emerged from the simulation literature that correspond to important issues that have been reported from space. Psychological factors include sleep disorders, alterations in time sense, transcendent experiences, demographic issues, career motivation, homesickness, and increased perceptual sensitivities. Psychiatric factors include anxiety, depression, psychosis, psychosomatic symptoms, emotional reactions related to mission stage, asthenia, and postflight personality, and marital problems. Finally, interpersonal factors include tension resulting from crew heterogeneity, decreased cohesion over time, need for privacy, and issues involving leadership roles and lines of authority. Since future space missions will usually involve heterogeneous crews working on complicated objectives over long periods of time, these features require further study. Socio-cultural factors affecting confined crews (e.g., language and dialect, cultural differences, gender biases) should be explored in order to minimize tension and sustain performance. Career motivation also needs to be examined for the purpose of improving crew cohesion and preventing subgrouping, scapegoating, and territorial behavior. Periods of monotony and reduced activity should be addressed in order to maintain morale, provide meaningful use of leisure time, and prevent negative consequences of low stimulation, such as asthenia and crew member withdrawal. Leadership roles and lines of authority need to be studied further to understand the factors leading to status leveling, leadership competition, and role confusion. Finally, the relationship between crews and ground personnel should be characterized in order to minimize the displacement of anger and tension to the outside, to counter the effects of inter-group miscommunications, and to develop support strategies that can help to counter in-group/out-group conflicts. Ground-based space simulations still have a role to play in terms of understanding the impact of these factors and ways of dealing with them. In particular, issues involving language, cultural differences, gender biases, career motivation, monotonous conditions, use of free time, leadership, lines of authority, and the relationship between crews and outside monitoring personnel need to be further characterized and examined under controlled conditions. Until such time as these factors can be studied directly in space, simulations provide an opportunity to learn more about these psychosocial issues and to plan ways of minimizing their negative consequences during actual space missions.
Motor function in microgravity: movement in weightlessness
Microgravity provides unique, though experimentally challenging, opportunities to study motor control. A traditional research focus has been the effects of linear acceleration on vestibular responses to angular acceleration. Evidence is accumulating that the high-frequency vestibulo-ocular reflex (VOR) is not affected by transitions from a 1 g linear force field to microgravity (<1 g); however, it appears that the three-dimensional organization of the VOR is dependent on gravitoinertial force levels. Some of the observed effects of microgravity on head and arm movement control appear to depend on the previously undetected inputs of cervical and brachial proprioception, which change almost immediately in response to alterations in background force levels. Recent studies of post-flight disturbances of posture and locomotion are revealing sensorimotor mechanisms that adjust over periods ranging from hours to weeks.
Human physiology in space
The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.
Regulation of the systemic circulation at microgravity and during readaptation to 1G
No abstract available
Effect of spaceflight on the functional, biochemical, and metabolic properties of skeletal muscle
This paper summarizes the effects of spaceflight on the functional, morphological, and biochemical properties of human and rodent skeletal muscle. The findings suggest that following as little as 5-6 in space there are deficits in both human and rodent motor capacity, strength, and endurance properties of skeletal muscle. The reduced strength is associated, in part, with a reduction in muscle mass as reflected in smaller cross-sectional areas of both fast- and slow-twitch fibers. Available evidence in animal models suggests that slow-twitch fibers are more sensitive to the atrophying process. Accompanying the atrophy is a transformation of slow to fast protein phenotype involving myosin heavy chain and sarcoplasmic reticulum protein isoforms. These transformations appear to be regulated, in part, by pretranslational processes. Data on the oxidative capacity of rodent skeletal muscle suggest a bias toward preferential utilization of carbohydrate as the primary substrate. These collective findings suggest that skeletal muscles comprised chiefly of slow fibers are highly dependent on gravity for the normal expression of protein mass and slow phenotype. Future studies need to focus on elucidating the mechanisms associated with the atrophy response, as well as identifying suitable exercise and other countermeasures capable of preserving the structural and functional integrity of skeletal muscle.
Life sciences space missions. Overview
It has been known for many years that weightlessness induces changes in numerous physiological systems: the cardiovascular system declines in both aerobic capacity and orthostatic tolerance; there is a reduction in fluid and electrolyte balance, hematocrit, and certain immune parameters; bone and muscle mass and strength are reduced; various neurological responses include space motion sickness and posture and gate alterations. These responses are caused by the hypokinesia of weightlessness, the cephalic fluid shift, the unloading of the vestibular system, stress, and the altered temporal environment.
The origin and early evolution of life: prebiotic chemistry, the pre-RNA world, and time
No abstract available
The cerebellum: a neuronal learning machine?
Comparison of two seemingly quite different behaviors yields a surprisingly consistent picture of the role of the cerebellum in motor learning. Behavioral and physiological data about classical conditioning of the eyelid response and motor learning in the vestibulo-ocular reflex suggests that (i) plasticity is distributed between the cerebellar cortex and the deep cerebellar nuclei; (ii) the cerebellar cortex plays a special role in learning the timing of movement; and (iii) the cerebellar cortex guides learning in the deep nuclei, which may allow learning to be transferred from the cortex to the deep nuclei. Because many of the similarities in the data from the two systems typify general features of cerebellar organization, the cerebellar mechanisms of learning in these two systems may represent principles that apply to many motor systems.
Hydrothermal systems on Mars: an assessment of present evidence
Hydrothermal processes have been suggested to explain a number of observations for Mars, including D/H ratios of water extracted from Martian meteorites, as a means for removing CO2 from the Martian atmosphere and sequestering it in the crust as carbonates, and as a possible origin for iron oxide-rich spectral units on the floors of some rifted basins (chasmata). There are numerous examples of Martian channels formed by discharges of subsurface water near potential magmatic heat sources, and hydrothermal processes have also been proposed as a mechanism for aquifer recharge needed to sustain long term erosion of sapping channels. The following geological settings have been identified as targets for ancient hydrothermal systems on Mars: channels located along the margins of impact crater melt sheets and on the slopes of ancient volcanoes; chaotic and fretted terranes where shallow subsurface heat sources are thought to have interacted with ground ice; and the floors of calderas and rifted basins (e.g. chasmata). On Earth, such geological environments are often a locus for hydrothermal mineralization. But we presently lack the mineralogical information needed for a definitive evaluation of hypotheses. A preferred tool for identifying minerals by remote sensing methods on Earth is high spatial resolution, hyperspectral, near-infrared spectroscopy, a technique that has been extensively developed by mineral explorationists. Future efforts to explore Mars for ancient hydrothermal systems would benefit from the application of methods developed by the mining industry to look for similar deposits on Earth. But Earth-based exploration models must be adapted to account for the large differences in the climatic and geological history of Mars. For example, it is likely that the early surface environment of Mars was cool, perhaps consistently below freezing, with the shallow portions of hydrothermal systems being dominated by magma-cryosphere interactions. Given the smaller gravitational field, declining atmospheric pressure, and widespread, permeable megaregolith on Mars, volatile outgassing and magmatic cooling would have been more effective than on Earth. Thus, hydrothermal systems are likely to have had much lower average surface temperatures than comparable geological settings on Earth. The likely predominance of basaltic crust on Mars suggests that hydrothermal fluids and associated deposits should be enriched in Fe, Mg, Si and Ca, with surficial deposits being dominated by lower temperature, mixed iron oxide and carbonate mineralogies.
The limits of palaeontological knowledge: finding the gold among the dross
Palaeontological interpretation rests on two interwoven sets of comparisons with the modern world. Palaeobiological interpretation relies on the placement of fossils within a phylogenetic and functional framework based primarily on the comparative biology of living organisms. Analogy to currently observable chemical, physical and taphonomic processes enables palaeoenvironmental inferences to be drawn from geological data. In older rocks, comparisons with the modern Earth can become tenuous, limiting palaeontological interpretation. The problem reaches its apogee in Archaean successions, yet pursuit of multiple lines of evidence establishes that complex microbial communities, fuelled by autotrophy and, likely, photoautotrophy, existed 3500 million years ago. Although Archaean palaeontology has to date focused on silicified coastal sediments, improved understanding of Earth's earliest biosphere may depend on the development of alternative environmental and taphonomic analogies. Spring precipitates and hydrothermal metal deposits are promising candidates. Terrestrial organisms may be of limited value in interpreting such fossils as may be found on Mars, although some points of comparison could prove general. Given limited opportunities for exploration, proper choice of environmental analogy is critical. Spring precipitates constitute excellent deposits for addressing questions of biology on another planet.
Lipid biomarkers for bacterial ecosystems: studies of cultured organisms, hydrothermal environments and ancient sediments
This paper forms part of our long-term goal of using molecular structure and carbon isotopic signals preserved as hydrocarbons in ancient sediments to improve understanding of the early evolution of Earth's surface environment. We are particularly concerned with biomarkers which are informative about aerobiosis. Here, we combine bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems to construct models for the nature, behaviour and preservation potential of primitive microbial communities. We use a combined molecular and isotopic approach to characterize lipids produced by cultured bacteria and test a variety of culture conditions which affect their biosynthesis. This information is then compared with lipid mixtures isolated from contemporary hot springs and evaluated for the kinds of chemical change that would accompany burial and incorporation into the sedimentary record. In this study we have shown that growth temperature does not appear to alter isotopic fractionation within the lipid classes produced by a methanotropic bacterium. We also found that cultured cyanobacteria biosynthesize diagnostic methylalkanes and dimethylalkanes with the latter only made when growing under low pCO2. In an examination of a microbial mat sample from Octopus Spring, Yellowstone National Park (USA), we could readily identify chemical structures with 13C contents which were diagnostic for the phototrophic organisms such as cyanobacteria and Chloroflexus. We could not, however, find molecular evidence for operation of a methane cycle in the particular mat samples we studied.
Towards an understanding of the structural and functional properties of MscL, a mechanosensitive channel in bacteria
Whether it be to sense a touch, arterial pressure, or an osmotic gradient across a cell membrane, essentially all living organisms require the capability of detecting mechanical force. Electrophysiological evidence has suggested that mechanosensitive ion channels play a major role in many systems where mechanical force is detected. But, despite their biological importance, determination of the most basic structural and functional features of mechanosensitive channels has only recently become possible. A gene called mscL, which was isolated from Escherichia coli, was the first gene shown to encode a mechanosensitive channel activity. This channel directly responds to tension in the membrane; no other proteins are required. MscL appears to be a homohexamer of a 136 amino acid polypeptide that is highly alpha helical, contains two transmembrane domains, and has both the amino and carboxyl termini in the cytoplasm. The study of the MscL protein remains, to date, one of the most viable options for understanding the structural and functional characteristics of a mechanosensitive channel.
The regulation and regulatory role of collagenase in bone
Interstitial collagenase plays an important role in both the normal and pathological remodeling of collagenous extracellular matrices, including skeletal tissues. The enzyme is a member of the family of matrix metalloproteinases. Only one rodent interstitial collagenase has been found but there are two human enzymes, human collagenase-1 and -3, the latter being the homologue of the rat enzyme. In developing rat and mouse bone, collagenase is expressed by hypertrophic chondrocytes, osteoblasts, and osteocytes, a situation that is replicated in a fracture callus. Cultured osteoblasts derived from neonatal rat calvariae show greater amounts of collagenase transcripts late in differentiation. These levels can be regulated by parathyroid hormone (PTH), retinoic acid, and insulin-like growth factors, as well as the degree of matrix mineralization. Much of the work on collagenase in bone has been derived from studies on the rat osteosarcoma cell line, UMR 106-01. All bone-resorbing agents stimulate these cells to produce collagenase mRNA and protein, with PTH being the most potent stimulator. Determination of secreted levels of collagenase has been difficult because UMR cells, normal rat osteoblasts, and rat fibroblasts possess a scavenger receptor that removes the enzyme from the extracellular space, internalizes and degrades it, thus imposing another level of control. PTH can also regulate the abundance of the receptor as well as the expression and synthesis of the enzyme. Regulation of the collagenase gene by PTH appears to involve the cAMP pathway as well as a primary response gene, possibly Fos, which then contributes to induction of the collagenase gene. The rat collagenase gene contains an activator protein-1 sequence that is necessary for basal expression, but other promoter regions may also participate in PTH regulation. Thus, there are many levels of regulation of collagenase in bone perhaps constraining what would otherwise be a rampant enzyme.
Response of the neuromuscular unit to spaceflight: what has been learned from the rat model
Despite the inherent limitations placed on spaceflight investigations, much has been learned about the adaptations of the neuromuscular system to weightlessness from studies of rats flown for relatively short periods (approximately 4-22 days). Below is a summary of the major effects of spaceflight observed in muscles of rats that are not in their rapid growth stage: 1. Skeletal muscles atrophy rapidly during spaceflight; significant atrophy is observed as early as after 4 days of flight. 2. The atrophic response appears to be related to the primary function of the muscle. In the hindlimb, the relative amount of atrophy can be characterized as slow extensors > fast extensors > fast flexors. This pattern of relative atrophy does not appear to be occurring in the forelimb; however, not enough data are available to draw any definitive conclusions at this time. 3. Both slow and fast fibers atrophy during spaceflight, with the largest fibers within an individual muscle generally showing the greatest atrophic response. Interestingly, the amount of fiber atrophy appears to reach a plateau after about 14 days of flight. 4. Adaptations have been observed in the concentration and content of all muscle proteins pools, with the protein pools in slow muscles the most affected. 5. Some slow and fast fibers in predominantly slow and fast muscles show shifts in their histochemical and biochemical properties, toward those observed in a "faster" phenotype. 6. Some fibers, presumably expressing slow MHC isoforms before flight, begin to express fast MHC isoforms during flight. 7. The oxidative capacity of the muscles or fibers is relatively unaffected by spaceflight, particularly in the slow muscles. Any change in whole-body fatigability associated with spaceflight most likely reflects the loss in muscle and fiber mass. 8. The glycolytic capacity of the muscles and muscle fibers is enhanced after spaceflight. This metabolic adaptation seems to be related to the shift in the contractile proteins towards "faster" isoforms. 9. The vascularity of muscles appears to be maintained after flight, based, at least, on histological observations of capillarity. 10. The force capabilities of the muscles and fibers appear to decrease in parallel with the decreases in size, i.e., the specific tension is not significantly affected after flight. 11. Changes in the speed-related properties of the slow muscles are consistent with the adaptations in the myosin molecule, i.e., the slow muscles and some fibers in the slow muscles become "faster." 12. Some muscle fiber and neuromuscular junction damage has been observed after flight, particularly in the slow muscles. The extent of damage may be related to the amount of time that the muscles are allowed to reload before removal, i.e., in general, shorter intervals result in less fiber damage. 13. Adaptations in the motor (ventral horn) and sensory (spinal ganglia) neurons have been quite variable, but this may be related to the amount of time that the muscles are allowed to reload before removal. Morphological adaptations after relatively short periods of reloading may reflect a decrease in the activation of the neural elements during flight.
Managing fatigue in operational settings 2: An integrated approach
The six domains that must be addressed in managing fatigue in operational settings are identified, and examples of how the aviation industry is dealing with the problems in each domain are given. Challenges facing healthcare providers in managing fatigue are also discussed.