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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.

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At least 649 records · Page 36

Cellular and molecular mechanisms for the bone response to mechanical loading

To define the cellular and molecular mechanisms for the osteogenic response of bone to increased loading, several key steps must be defined: sensing of the mechanical signal by cells in bone, transduction of the mechanical signal to a biochemical one, and transmission of that biochemical signal to effector cells. Osteocytes are likely to serve as sensors of loading, probably via interstitial fluid flow produced during loading. Evidence is presented for the role of integrins, the cell's actin cytoskeleton, G proteins, and various intracellular signaling pathways in transducing that mechanical signal to a biochemical one. Nitric oxide, prostaglandins, and insulin-like growth factors all play important roles in these pathways. There is growing evidence for modulation of these mechanotransduction steps by endocrine factors, particularly parathyroid hormone and estrogen. The efficiency of this process is also impaired in the aged animal, yet what remains undefined is at what step mechanotransduction is affected.

Review↗

The vestibulosympathetic reflex in humans: neural interactions between cardiovascular reflexes

1. Over the past 5 years, there has been emerging evidence that the vestibular system regulates sympathetic nerve activity in humans. We have studied this issue in humans by using head-down rotation (HDR) in the prone position. 2. These studies have clearly demonstrated increases in muscle sympathetic nerve activity (MSNA) and calf vascular resistance during HDR. These responses are mediated by engagement of the otolith organs and not the semicircular canals. 3. However, differential activation of sympathetic nerve activity has been observed during HDR. Unlike MSNA, skin sympathetic nerve activity does not increase with HDR. 4. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes (i.e. barorereflexes and skeletal muscle reflexes) has shown an additive interaction for MSNA. 5. The additive interaction between the baroreflexes and vestibulosympathetic reflex suggests that the vestibular system may assist in defending against orthostatic challenges in humans by elevating MSNA beyond that of the baroreflexes. 6. In addition, the further increase in MSNA via otolith stimulation during isometric handgrip, when arterial pressure is elevated markedly, indicates that the vestibulosympathetic reflex is a powerful activator of MSNA and may contribute to blood pressure and flow regulation during dynamic exercise. 7. Future studies will help evaluate the importance of the vestibulosympathetic reflex in clinical conditions associated with orthostatic hypotension.

Review↗

A genomic regulatory network for development

Development of the body plan is controlled by large networks of regulatory genes. A gene regulatory network that controls the specification of endoderm and mesoderm in the sea urchin embryo is summarized here. The network was derived from large-scale perturbation analyses, in combination with computational methodologies, genomic data, cis-regulatory analysis, and molecular embryology. The network contains over 40 genes at present, and each node can be directly verified at the DNA sequence level by cis-regulatory analysis. Its architecture reveals specific and general aspects of development, such as how given cells generate their ordained fates in the embryo and why the process moves inexorably forward in developmental time.

Non-NASA Center↗

Consequences of contamination of the spacecraft environment: immunologic consequences

Long-term space voyages pose numerous known and unknown health hazards, to the human immune system. Well-studied clinical examples of secondary immunodeficiencies created on Earth, lead one to predict that the conditions of prolonged space flight would weaken the human immune responses that normally hold infection and cancer in check. From evidence gathered from humans flown for prolonged periods in space and from human models of space flight studied on Earth it is reasonable to suspect that space travelers to the planet Mars would experience a weakening of immunity. Subtle defects of immune cell structure and function have been observed in astronauts, such as weakening of specific T-lymphocyte recall of specific antigens. Ground-based models also have demonstrated alterations of immune function, such as the elevation of neuroendocrine immune system messengers, interleukin-6, and soluble tumor necrosis factor-alpha receptor in sleep deprivation. Since severe immune compromise the clinical consequences of reactivation of latent virus infections and the development of cancer, has yet to be seen in space flight or in the Earth models, it is extremely important to begin to quantify early changes in immunity to predict the development of immune system collapse with poor clinical outcomes. This approach is designed to validate a number of surrogate markers that will predict trouble ahead. Inherent in this research is the development of countermeasures to reduce the risks of infection and cancer in the first humans going to Mars.

Non-NASA Center↗

Psychosocial issues in long-term space flight: overview

Anecdotal evidence of the individual and interpersonal problems that occurred during the Shuttle-Mir Space Program (SMSP) and other long-duration Russian/Soviet missions, and studies of personnel in other isolated and confined extreme (ICE) environments suggest that psychosocial elements of behavior and performance are likely to have a significant impact on the outcome of long-duration missions in space. This impact may range from individual decrements in performance, health and well being, to catastrophic mission failure. This paper reviews our current understanding of the psychosocial issues related to long duration space missions according to three different domains of behavior: the individual domain, the interpersonal domain and the organizational domain. Individual issues include: personality characteristics that predict successful performance, stress due to isolation and confinement and its effect on emotions and cognitive performance, adaptive and maladaptive coping styles and strategies, and requirements for the psychological support of astronauts and their families during the mission. Interpersonal issues include: impact of crew diversity and leadership styles on small group dynamics, adaptive and maladaptive features of ground-crew interactions, and processes of crew cohesion, tension and conflict. Organizational issues include: the influence of organizational culture and mission duration on individual and group performance, and managerial requirements for long duration missions. Improved screening and selection of astronaut candidates, leadership, coping and interpersonal skills training of personnel, and organizational change are key elements in the prevention of performance decrements on long-duration missions.

Review, Tutorial↗

Plants, plant pathogens, and microgravity--a deadly trio

Plants grown in spaceflight conditions are more susceptible to colonization by plant pathogens. The underlying causes for this enhanced susceptibility are not known. Possibly the formation of structural barriers and the activation of plant defense response components are impaired in spaceflight conditions. Either condition would result from altered gene expression of the plant. Because of the tools available, past studies focused on a few physiological responses or biochemical pathways. With recent advances in genomics research, new tools, including microarray technologies, are available to examine the global impact of growth in the spacecraft on the plant's gene expression profile. In ground-based studies, we have developed cDNA subtraction libraries of rice that are enriched for genes induced during pathogen infection and the defense response. Arrays of these genes are being used to dissect plant defense response pathways in a model system involving wild-type rice plants and lesion mimic mutants. The lesion mimic mutants are ideal experimental tools because they erratically develop defense response-like lesions in the absence of pathogens. The gene expression profiles from these ground-based studies will provide the molecular basis for understanding the biochemical and physiological impacts of spaceflight on plant growth, development and disease defense responses. This, in turn, will allow the development of strategies to manage plant disease for life in the space environment.

NASA Discipline Plant Biology↗

Space radiation dosimetry in low-Earth orbit and beyond

Space radiation dosimetry presents one of the greatest challenges in the discipline of radiation protection. This is a result of both the highly complex nature of the radiation fields encountered in low-Earth orbit (LEO) and interplanetary space and of the constraints imposed by spaceflight on instrument design. This paper reviews the sources and composition of the space radiation environment in LEO as well as beyond the Earth's magnetosphere. A review of much of the dosimetric data that have been gathered over the last four decades of human space flight is presented. The different factors affecting the radiation exposures of astronauts and cosmonauts aboard the International Space Station (ISS) are emphasized. Measurements made aboard the Mir Orbital Station have highlighted the importance of both secondary particle production within the structure of spacecraft and the effect of shielding on both crew dose and dose equivalent. Roughly half the dose on ISS is expected to come from trapped protons and half from galactic cosmic rays (GCRs). The dearth of neutron measurements aboard LEO spacecraft and the difficulty inherent in making such measurements have led to large uncertainties in estimates of the neutron contribution to total dose equivalent. Except for a limited number of measurements made aboard the Apollo lunar missions, no crew dosimetry has been conducted beyond the Earth's magnetosphere. At the present time we are forced to rely on model-based estimates of crew dose and dose equivalent when planning for interplanetary missions, such as a mission to Mars. While space crews in LEO are unlikely to exceed the exposure limits recommended by such groups as the NCRP, dose equivalents of the same order as the recommended limits are likely over the course of a human mission to Mars. c2001 Elsevier Science B.V. All rights reserved.

short duration↗

Ageing and water homeostasis

This review outlines current knowledge concerning fluid intake and volume homeostasis in ageing. The physiology of vasopressin is summarized. Studies have been carried out to determine orthostatic changes in plasma volume and to assess the effect of water ingestion in normal subjects, elderly subjects, and patients with dysautonomias. About 14% of plasma volume shifts out of the vasculature within 30 minutes of upright posture. Oral ingestion of water raises blood pressure in individuals with impaired autonomic reflexes and is an important source of noise in blood pressure trials in the elderly. On the average, oral ingestion of 16 ounces (473ml) of water raises blood pressure 11 mmHg in elderly normal subjects. In patients with autonomic impairment, such as multiple system atrophy, strikingly exaggerated pressor effects of water have been seen with blood pressure elevations greater than 75 mmHg not at all uncommon. Ingestion of water is a major determinant of blood pressure in the elderly population. Volume homeostasis is importantly affected by posture and large changes in plasma volume may occur within 30 minutes when upright posture is assumed.

Review↗

Neutron dosimetry in low-earth orbit using passive detectors

This paper summarizes neutron dosimetry measurements made by the USF Physics Research Laboratory aboard US and Russian LEO spacecraft over the past 20 years using two types of passive detector. Thermal/resonance neutron detectors exploiting the 6Li(n,T) alpha reaction were used to measure neutrons of energies <1 MeV. Fission foil neutron detectors were used to measure neutrons of energies above 1 MeV. While originally analysed in terms of dose equivalent using the NCRP-38 definition of quality factor, for the purposes of this paper the measured neutron data have been reanalyzed and are presented in terms of ambient dose equivalent. Dose equivalent rate for neutrons <1 MeV ranged from 0.80 microSv/d on the low altitude, low inclination STS-41B mission to 22.0 microSv/d measured in the Shuttle's cargo bay on the highly inclined STS-51F Spacelab-2 mission. In one particular instance a detector embedded within a large hydrogenous mass on STS-61 (in the ECT experiment) measured 34.6 microSv/d. Dose equivalent rate measurements of neutrons >1 MeV ranged from 4.5 microSv/d on the low altitude STS-3 mission to 172 microSv/d on the ~6 year LDEF mission. Thermal neutrons (<0.3 eV) were observed to make a negligible contribution to neutron dose equivalent in all cases. The major fraction of neutron dose equivalent was found to be from neutrons >1 MeV and, on LDEF, neutrons >1 MeV are responsible for over 98% of the total neutron dose equivalent. Estimates of the neutron contribution to the total dose equivalent are somewhat lower than model estimates, ranging from 5.7% at a location under low shielding on LDEF to 18.4% on the highly inclined (82.3 degrees) Biocosmos-2044 mission. c2001 Elsevier Science Ltd. All rights reserved.

Flight Experiment↗

Neutron measurements onboard the space shuttle

The radiation environment inside a shielded volume is highly complex, consisting of both charged and neutral particles. Since the inception of human space flights, the charged particle component has received virtually all of the attention. There is however, a significant production of secondary neutrons, particularly from the aluminum structure in low earth orbiting spacecrafts. The interactions of galactic cosmic rays (GCR), and solar energetic particles with the earth's atmosphere produce a non-isotropic distribution of albedo neutrons. Inside any reasonable habitable module, the average radiation quality factor of neutrons is about 4-5 times larger than the corresponding average quality factor of charged particles. The measurement of neutrons and their energy spectra is a difficult problem due the intense sources of charged particles. This paper reviews the results of Shuttle flight experiments (made during both solar maximum and solar minimum) to measure the contribution of neutrons to the dose equivalent, as well as theoretical calculations to estimate the appropriate range of neutron energies that contribute most to the dose equivalent. Published by Elsevier Science Ltd.

short duration↗

Flexible substrata for the detection of cellular traction forces

By modulating adhesion signaling and cytoskeletal organization, mechanical forces play an important role in various cellular functions, from propelling cell migration to mediating communication between cells. Recent developments have resulted in several new approaches for the detection, analysis and visualization of mechanical forces generated by cultured cells. Combining these methods with other approaches, such as green-fluorescent protein (GFP) imaging and gene manipulation, proves to be particularly powerful for analyzing the interplay between extracellular physical forces and intracellular chemical events.

Review, Tutorial↗

Skeletal adaptation to external loads optimizes mechanical properties: fact or fiction

The skeleton adapts to a changing mechanical environment but the widely held concept that bone cells are programmed to respond to local mechanical loads to produce an optimal mechanical structure is not consistent with the high frequency of bone fractures. Instead, the author suggests that other important functions of bone compete with mechanical adaptation to determine structure. As a consequence of competing demands, bone architecture never achieves an optimal mechanical structure. c2001 Lippincott Williams & Wilkins, Inc.

Review, Tutorial↗

Do no harm--normal tissue effects

Radiation therapy confers enormous benefits that must be balanced against the possibilities for harm including late toxicity in normal tissues and radiation-induced second malignancies. A small percentage of patients experience severe late complications. The question is, do these late sequelae occur randomly, or are they confined to individuals who are genetically predisposed to radiosensitivity. Experiments with knockout mice and with patients demonstrate that individuals heterozygous for a number of genes appear to be radiosensitive. If radiosensitive patients were identified prospectively by genetic analysis, they could be spared the trauma of late sequelae. Several large studies have shown a statistically significant excess of radiation-induced malignancies in radiotherapy patients. Most second cancers are carcinomas, developing in the lining cells of the body often remote from the treatment site. Radiation-induced sarcomas appear only in the heavily irradiated areas. These are small in number but appear with a very high relative risk.

NASA Discipline Radiation Health↗

Mechanotransduction: all signals point to cytoskeleton, matrix, and integrins

Mechanical stresses modulate cell function by either activating or tuning signal transduction pathways. Mechanotransduction, the process by which cells convert mechanical stimuli into a chemical response, occurs both in cells specialized for sensing mechanical cues and in parenchymal cells whose primary function is not mechanosensory. However, common among the various responses to mechanical stress is the importance of direct or indirect connections between the internal cytoskeleton, the extracellular matrix (ECM), and traditional signal transducing molecules. In many instances, these elements converge at focal adhesions, sites of structural attachment between the cytoskeleton and ECM that are anchored by cell surface integrin receptors. Alenghat and Ingber discuss the accumulating evidence for the central role of cytoskeleton, ECM, and integrin-anchored focal adhesions in several mechanotransduction pathways.

Review, Tutorial↗

Artificial cells: prospects for biotechnology

A variety of techniques can now be used to alter the genome of a cell. Although these techniques are very powerful, they have limitations related to cost and efficiency of scale. Artificial cells designed for specific applications combine properties of biological systems such as nanoscale efficiency, self-organization and adaptability at relatively low cost. Individual components needed for such structures have already been developed, and now the main challenge is to integrate them in functional microscopic compartments. It will then become possible to design and construct communities of artificial cells that can perform different tasks related to therapeutic and diagnostic applications.

Review↗

Getting through to circadian oscillators: why use constant routines?

Overt 24-h rhythmicity is composed of both exogenous and endogenous components, reflecting the product of multiple (periodic) feedback loops with a core pacemaker at their center. Researchers attempting to reveal the endogenous circadian (near 24-h) component of rhythms commonly conduct their experiments under constant environmental conditions. However, even under constant environmental conditions, rhythmic changes in behavior, such as food intake or the sleep-wake cycle, can contribute to observed rhythmicity in many physiological and endocrine variables. Assessment of characteristics of the core circadian pacemaker and its direct contribution to rhythmicity in different variables, including rhythmicity in gene expression, may be more reliable when such periodic behaviors are eliminated or kept constant across all circadian phases. This is relevant for the assessment of the status of the circadian pacemaker in situations in which the sleep-wake cycle or food intake regimes are altered because of external conditions, such as in shift work or jet lag. It is also relevant for situations in which differences in overt rhythmicity could be due to changes in either sleep oscillatory processes or circadian rhythmicity, such as advanced or delayed sleep phase syndromes, in aging, or in particular clinical conditions. Researchers studying human circadian rhythms have developed constant routine protocols to assess the status of the circadian pacemaker in constant behavioral and environmental conditions, whereas this technique is often thought to be unnecessary in the study of animal rhythms. In this short review, the authors summarize constant routine methodology and what has been learned from constant routines and argue that animal and human circadian rhythm researchers should (continue to) use constant routines as a step on the road to getting through to central and peripheral circadian oscillators in the intact organism.

Non-NASA Center↗

Parathyroid hormone-dependent signaling pathways regulating genes in bone cells

Parathyroid hormone (PTH) is an 84-amino-acid polypeptide hormone functioning as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. PTH and PTH-related protein (PTHrP) indirectly activate osteoclasts resulting in increased bone resorption. During this process, PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone resorption. In addition to these catabolic effects, PTH has been demonstrated to be an anabolic factor in skeletal tissue and in vitro. As a result, PTH has potential medical application to the treatment of osteoporosis, since intermittent administration of PTH stimulates bone formation. Activation of osteoblasts by PTH results in expression of genes important for the degradation of the extracellular matrix, production of growth factors, and stimulation and recruitment of osteoclasts. The ability of PTH to drive changes in gene expression is dependent upon activation of transcription factors such as the activator protein-1 family, RUNX2, and cAMP response element binding protein (CREB). Much of the regulation of these processes by PTH is protein kinase A (PKA)-dependent. However, while PKA is linked to many of the changes in gene expression directed by PTH, PKA activation has been shown to inhibit mitogen-activated protein kinase (MAPK) and proliferation of osteoblasts. It is now known that stimulation of MAPK and proliferation by PTH at low concentrations is protein kinase C (PKC)-dependent in both osteoblastic and kidney cells. Furthermore, PTH has been demonstrated to regulate components of the cell cycle. However, whether this regulation requires PKC and/or extracellular signal-regulated kinases or whether PTH is able to stimulate other components of the cell cycle is unknown. It is possible that stimulation of this signaling pathway by PTH mediates a unique pattern of gene expression resulting in proliferation in osteoblastic and kidney cells; however, specific examples of this are still unknown. This review will focus on what is known about PTH-mediated cell signaling, and discuss the established or putative PTH-regulated pattern of gene expression in osteoblastic cells following treatment with catabolic (high) or anabolic (low) concentrations of the hormone.

NASA Discipline Musculoskeletal↗