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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 1,063 records · Page 59

Neural mechanisms in nitric-oxide-deficient hypertension

Nitric oxide is hypothesized to be an inhibitory modulator of central sympathetic nervous outflow, and deficient neuronal nitric oxide production to cause sympathetic overactivity, which then contributes to nitric-oxide-deficient hypertension. The biochemical and neuroanatomical basis for this concept revolves around nitric oxide modulation of glutamatergic neurotransmission within brainstem vasomotor centers. The functional consequence of neuronal nitric oxide in blood pressure regulation is, however, marked by an apparent conflict in the literature. On one hand, conscious animal studies using sympathetic blockade suggest a significant role for neuronal nitric oxide deficiency in the development of nitric-oxide-deficient hypertension, and on the other hand, there is evidence against such a role derived from 'knock-out' mice lacking nitric-oxide synthase 1, the major source of neuronal nitric oxide.

Review, Tutorial↗

Evolutionary anomalies among the aminoacyl-tRNA synthetases

Unexpected relationships among the various aminoacyl-tRNA synthetases continue to be uncovered. The question arises - is this mainly the result of promiscuous exchange, or is the confusion really a reflection of the differential loss of past duplications? Phylogenetic analysis may yet provide the answer.

Non-NASA Center↗

In search of cellular control: signal transduction in context

The field of molecular cell biology has experienced enormous advances over the last century by reducing the complexity of living cells into simpler molecular components and binding interactions that are amenable to rigorous biochemical analysis. However, as our tools become more powerful, there is a tendency to define mechanisms by what we can measure. The field is currently dominated by efforts to identify the key molecules and sequences that mediate the function of critical receptors, signal transducers, and molecular switches. Unfortunately, these conventional experimental approaches ignore the importance of supramolecular control mechanisms that play a critical role in cellular regulation. Thus, the significance of individual molecular constituents cannot be fully understood when studied in isolation because their function may vary depending on their context within the structural complexity of the living cell. These higher-order regulatory mechanisms are based on the cell's use of a form of solid-state biochemistry in which molecular components that mediate biochemical processing and signal transduction are immobilized on insoluble cytoskeletal scaffolds in the cytoplasm and nucleus. Key to the understanding of this form of cellular regulation is the realization that chemistry is structure and hence, recognition of the the importance of architecture and mechanics for signal integration and biochemical control. Recent work that has unified chemical and mechanical signaling pathways provides a glimpse of how this form of higher-order cellular control may function and where paths may lie in the future.

Non-NASA Center↗

Radiation-induced instability and its relation to radiation carcinogenesis

PURPOSE: A model that identifies radiation-induced genetic instability as the earliest cellular event in the multi-step sequence leading to radiation-induced cancer was previously proposed. In this paper ongoing experiments are discussed which are designed to test this model and its predictions in mouse mammary epithelial cells. RESULTS: Several lines of evidence are presented that appear to support this model: first, the development of delayed mutations in p53 following irradiation in altered growth variants; secondly, the high frequencies for the induction of both instability and transformation following irradiation in mammary epithelial cells; and finally, the demonstration that susceptibility to the induction of cytogenetic instability is a heritable trait that correlates with susceptibility to transformation and radiation-induced mammary cancer. Mice resistant to transformation and mammary cancer development are also resistant to the development of instability after irradiation. In contrast, mice sensitive to transformation and cancer are also sensitive to the development of cytogenetic instability. CONCLUSIONS: Data from this laboratory and from the studies cited above suggest a specific, and perhaps unique, role for radiation-induced instability as a critical early event associated with initiation of the carcinogenic process.

Review↗

The origin of life--a review of facts and speculations

Three popular hypotheses attempt to explain the origin of prebiotic molecules: synthesis in a reducing atmosphere, input in meteorites and synthesis on metal sulfides in deep-sea vents. It is not possible to decide which is correct. It is also unclear whether the RNA world was the first biological world or whether some simpler world preceded it.

Review, Tutorial↗

Crystal growth and crystallography

Selected topics that may be of interest for both crystal-structure and crystal-growth communities are overviewed. The growth of protein crystals, along with that of some other compounds, is one of the topics, and recent insights into related phenomena are considered as examples of applications of general principles. The relationship between crystal growth shape and structure is reviewed and an attempt to introduce semiquantitative characterization of binding for proteins is made. The concept of kinks for complex structures is briefly discussed. Even at sufficiently low supersaturations, the fluctuation of steps may not be sufficient to implement the Gibbs-Thomson law if the kink density is low enough. Subsurface ordering of liquids and growth of rough interfaces from melts is discussed. Crystals growing in microgravity from solution should be more perfect if they preferentially trap stress-inducing impurities, thus creating an impurity-depleted zone around themselves. Evidently, such a zone is developed only around the crystals growing in the absence of convection. Under terrestrial conditions, the self-purified depleted zone is destroyed by convection, the crystal traps more impurity and grows stressed. The stress relief causes mosaicity. In systems containing stress-inducing but poorly trapped impurities, the crystals grown in the absence of convection should be worse than those of their terrestrial counterparts.

Review, Tutorial↗

Autonomic neuropathies

A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

Non-NASA Center↗

How do tissues respond to damage at the cellular level? The role of cytokines in irradiated tissues

The capacity of ionizing radiation to affect tissue function, control tumor growth and elicit pathological sequelae has been attributed in great part to its effects on cellular DNA, which, as the transmitter of genetic information, can both register damage and perpetuate it. Nonetheless, multicellular organisms function as the result of the cooperation of many cell types. What then occurs when individual cells are damaged by ionizing radiation? Is tissue response a sum of cellular effects such as cell death and DNA damage? Or does the tissue respond as a coherent unit to the damage of its parts? In this paper, data in support of the latter model that indicate a role for cytokines, in particular transforming growth factor beta1, as critical components of extracellular signaling pathways that mediate tissue response to radiation will be reviewed. The key to manipulating the consequences of radiation exposure lies in understanding the complex interplay of events initiated at the cellular level, but acting on the tissue.

Review↗

The molecular basis of ethylene signalling in Arabidopsis

The simple gas ethylene profoundly influences plants at nearly every stage of growth and development. In the past ten years, the use of a genetic approach, based on the triple response phenotype, has been a powerful tool for investigating the molecular events that underlie these effects. Several fundamental elements of the pathway have been described: a receptor with homology to bacterial two-component histidine kinases (ETR1), elements of a MAP kinase cascade (CTR1) and a putative transcription factor (EIN3). Taken together, these elements can be assembled into a simple, linear model for ethylene signalling that accounts for most of the well-characterized ethylene mediated responses.

Non-NASA Center↗

Adaptation in a rotating artificial gravity environment

The centripetal force generated by a rotating space vehicle is a potential source of artificial gravity. Minimizing the cost of such a vehicle dictates using the smallest radius and highest rotation rate possible, but head movements made at high rotation rates generate disorienting, nauseogenic cross-coupled semicircular canal stimulation. Early studies suggested 3 or 4 rpm as the highest rate at which humans could adapt to this vestibular stimulus. These studies neglected the concomitant Coriolis force actions on the head/neck system. We assessed non-vestibular Coriolis effects by measuring arm and leg movements made in the center of a rotating room turning at 10 rpm and found that movement endpoints and trajectories are initially deviated; however, subjects readily adapt with 10-20 additional movements, even without seeing their errors. Equilibrium point theories of motor control errantly predict that Coriolis forces will not cause movement endpoint errors so that subjects will not have to adapt their reaching movements during rotation. Adaptation of movement trajectory acquired during Coriolis force perturbations of one arm transfers to the unexposed arm but there is no intermanual transfer of endpoint adaptation indicating that neuromotor representations of movement endpoint and trajectory are separable and can adapt independently, also contradictory to equilibrium point theories. Touching a surface at the end of reaching movements is required for complete endpoint adaptation in darkness but trajectory adapts completely with or without terminal contact. We have also made the first kinematic measurements of unconstrained head movements during rotation, these movements show rapid adaptation to Coriolis force perturbations. Our results point to methods for achieving full compensation for rotation up to 10 rpm. Copyright 1998 Published by Elsevier Science B.V.

Non-NASA Center↗

Posture, locomotion, spatial orientation, and motion sickness as a function of space flight

This article summarizes a variety of newly published findings obtained by the Neuroscience Laboratory, Johnson Space Center, and attempts to place this work within a historical framework of previous results on posture, locomotion, motion sickness, and perceptual responses that have been observed in conjunction with space flight. In this context, we have taken the view that correct transduction and integration of signals from all sensory systems is essential to maintaining stable vision, postural and locomotor control, and eye-hand coordination as components of spatial orientation. The plasticity of the human central nervous system allows individuals to adapt to altered stimulus conditions encountered in a microgravity environment. However, until some level of adaptation is achieved, astronauts and cosmonauts often experience space motion sickness, disturbances in motion control and eye-hand coordination, unstable vision, and illusory motion of the self, the visual scene, or both. Many of the same types of disturbances encountered in space flight reappear immediately after crew members return to earth. The magnitude of these neurosensory, sensory-motor and perceptual disturbances, and the time needed to recover from them, tend to vary as a function of mission duration and the space travelers prior experience with the stimulus rearrangement of space flight. To adequately chart the development of neurosensory changes associated with space flight, we recommend development of enhanced eye movement systems and body position measurement. We also advocate the use of a human small radius centrifuge as both a research tool and as a means of providing on-orbit countermeasures that will lessen the impact of living for long periods of time with out exposure to altering gravito-inertial forces. Copyright 1998 Elsevier Science B.V.

Flight Experiment↗

Post-spaceflight orthostatic intolerance: possible relationship to microgravity-induced plasticity in the vestibular system

Even after short spaceflights, most astronauts experience at least some postflight reduction of orthostatic tolerance; this problem is severe in some subjects. The mechanisms leading to postflight orthostatic intolerance are not well-established, but have traditionally been thought to include the following: changes in leg hemodynamics, alterations in baroreceptor reflex gain, decreases in exercise tolerance and aerobic fitness, hypovolemia, and altered sensitivity of beta-adrenergic receptors in the periphery. Recent studies have demonstrated that signals from vestibular otolith organs play an important role in regulating blood pressure during changes in posture in a 1-g environment. Because spaceflight results in plastic changes in the vestibular otolith organs and in the processing of inputs from otolith receptors, it is possible that another contributing factor to postflight orthostatic hypotension is alterations in the gain of vestibular influences on cardiovascular control. Preliminary data support this hypothesis, although controlled studies will be required to determine the relationship between changes in the vestibular system and orthostatic hypotension following exposure to microgravity. Copyright 1998 Elsevier Science B.V.

NASA Discipline Neuroscience↗

Neuronal plasticity: adaptation and readaptation to the environment of space

While there have been few documented permanent neurological changes resulting from space travel, there is a growing literature which suggests that neural plasticity sometimes occurs within peripheral and central vestibular pathways during and following spaceflight. This plasticity probably has adaptive value within the context of the space environment, but it can be maladaptive upon return to the terrestrial environment. Fortunately, the maladaptive responses resulting from neuronal plasticity diminish following return to earth. However, the literature suggests that the longer the space travel, the more difficult the readaptation. With the possibility of extended space voyages and extended stays on board the international space station, it seems worthwhile to review examples of plastic vestibular responses and changes in the underlying neural substrates. Studies and facilities needed for space station investigation of plastic changes in the neural substrates are suggested. Copyright 1998 Elsevier Science B.V.

unmanned↗

Effect of gravity on vestibular neural development

The timing, molecular basis, and morphophysiological and behavioral consequences of the interaction between external environment and the internal genetic pool that shapes the nervous system over a lifetime remain important questions in basic neuroscientific research. Space station offers the opportunity to study this interaction over several life cycles in a variety of organisms. This short review considers past work in altered gravity, particularly on the vestibular system, as the basis for proposing future research on space station, and discusses the equipment necessary to achieve goals. It is stressed that, in keeping with the international investment being made in this research endeavor, both the questions asked and the technologies to be developed should be bold. Advantage must be taken of this unique research environment to expand the frontiers of neuroscience. Copyright 1998 Published by Elsevier Science B.V.

NASA Discipline Neuroscience↗

Postnatal development under conditions of simulated weightlessness and space flight

The adaptability of the developing nervous system to environmental influences and the mechanisms underlying this plasticity has recently become a subject of interest in space neuroscience. Ground studies on neonatal rats using the tail suspension model of weightlessness have shown that the force of gravity clearly influences the events underlying the postnatal development of motor function. These effects depend on the age of the animal, duration of the perturbation and the motor function studied. A nine-day flight study has shown that a dam and neonates can develop under conditions of space flight. The motor function of the flight animals after landing was consistent with that seen in the tail suspension studies, being marked by limb joint extension. However, there were expected differences due to: (1) the unloading of the vestibular system in flight, which did not occur in the ground-based experiments; (2) differences between flight and suspension durations; and (3) the inability to evaluate motor function during the flight. The next step is to conduct experiments in space with the flexibility and rigor that is now limited to ground studies: an opportunity offered by the International Space Station. Copyright 1998 Published by Elsevier Science B.V.

Non-NASA Center↗

Life and death in the microcirculation: a role for angiotensin II

OBJECTIVE: Angiotensin II (ANGII) plays a critical role in the maintenance of the microcirculation and in the anatomical loss of microvessels (rarefaction) that occurs in low renin forms of hypertension and in animals fed a high-salt diet. Elevations in sodium intake can trigger a series of hemodynamic and hormonal responses culminating in a substantial rarefaction of small arterioles and capillaries in both normal and reduced renal mass hypertensive rats. METHODS: Immunohistochemistry, Northern blot, and reverse transcription-polymerase chain reaction (RT-PCR) analysis of microdissected blood vessels were used to localize ANGII receptors in the microcirculation. Chronic infusion of ANGII and other physiologic and pharmacologic manipulations of the reninangiotensin system in rats was combined with morphologic and mathematical analysis of the network architecture. RESULTS: We have shown that rarefaction of the microcirculation can cause an increase in total peripheral resistance, reduced tissue perfusion, decreased oxygen delivery, and impaired organ function. Although the mechanisms by which this occurs are not well understood, a number of key observations point to a role for the renin-angiotensin system in this effect. First, ANGII infused systemically at subpressor levels, or locally into the skeletal muscle interstitium, can induce significant microvessel growth. Second, localization of ANGII receptor proteins by immunohistochemistry and Western blotting and RNA localization by RT-PCR confirm the presence of AT1 receptors, which are growth-stimulatory, and AT2 receptors, which are growth-inhibitory in the microcirculation. Third, maintenance of ANGII at normal levels during periods of hypertension or high-salt diet completely eliminates rarefaction. CONCLUSIONS: Taken together, these results support the hypothesis that ANGII acting through AT1- and AT2-receptor mechanisms modulate vessel density during high-salt diet and hypertension.

Review↗

Of mice and genes: evolution of vertebrate brain development

In this review the current understanding of genetic and molecular evolution of development, in particular the formation of the major axis of bilateral animals, is critically evaluated, and the early pattern formation in the hindbrain is related as much as possible to these processes. On the genetic level it is proposed that the exuberant multiplication of regulatory genes compared to that of structural genes relates to the increased flexibility of early vertebrate development. In comparisons to fruit flies, many conserved genes are found to be expressed very differently, while many others seem to reflect a comparable pattern and thus suggest a conservation of function. Even genes with a largely conserved pattern of expression may change the level at which they are expressed and the mechanisms by which they are regulated in their expression. Evolution and development of hindbrain motoneurons is reviewed, and it is concluded that both comparative data as well as more recent experimental data suggest a limited importance for the rhombomeres. Clearly, many cell fate-specifying processes work below the level of rhombomeres or in the absence of rhombomeres. It is suggested that more comparative developmental data are needed to establish firmly the relationship between homeobox genes and rhombomere specification in vertebrates other than a few model species.

NASA Discipline Developmental Biology↗