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NASA NTRS2015

Gas Supersaturation May Reduce the Survival of Yearling Chinook Salmon in the Lower Columbia River and Ocean Plume

Unusually high flows in the Columbia River in 2011 raised total dissolved gas (TDG) levels in the river above the 120 percent legal limit imposed to prevent harmful impacts to aquatic organisms. This provided a unique opportunity to evaluate the effect on smolt survival. In-river (IR) migrating juvenile yearling Chinook released at Bonneville Dam with acoustic tags during periods when TDG exceeded 120 percent received estimated maximum exposures of 134 TDG. Subsequent daily survival rates in the lower river and plume were reduced by 0.06 per day (SE equals 0.01) and 0.15 per day (SE equals 0.05) relative to IR migrant fish released when TDG was less than 120 percent. Transported smolts (T) released 10-13 kilometers below Bonneville Dam had lower maximum exposure levels (126 percent) and experienced no difference in daily survival rates relative to unexposed smolts. River temperature levels and trends in turbidity and disease prevalence between releases of high and low exposure smolts were not consistent with the observed effects on survival rates. We conclude that smolts may suffer from chronic effects of elevated TDG exposure while migrating through the Columbia River and plume. Consideration should be given to measuring these survival losses in an explicit experimental framework that isolates possible confounding factors.

survival↗

NASA NTRS1990

Corticosterone, but not Glucose, Treatment Enables Fasted Adrenalectomized Rats to Survive Moderate Hemorrhage

Fed adrenalectomized rats survive the stress of hemorrhage and hypovolemia, whereas fasted adrenalectomized rats become hypotensive and hypoglycemic after the first 90 min and die within 4 hours (h). We have studied the effects of glucose and corticosterone (B) infusions after hemorrhage as well as treatment with B at the time of adrenalectomy on the capacity of chronically prepared, conscious, fasted, adrenalectomized rats to survive hemorrhage. We have also measured the magnitudes of vasoactive hormone responses to hemorrhage. Maintenance of plasma glucose concentrations did not sustain life; however, treatment of rats at the time of adrenalectomy with B allowed 100 percent survival, and acute treatment of adrenalectomized rats at the time of hemorrhage allowed about 50 percent survival during the 5-h posthemorrhage observation period. Rats in the acute B infusion group that died exhibited significantly increased plasma B and significantly decreased plasma glucose concentrations by 2 h compared to the rats that lived. Plasma vasopressin, renin, and norepinephrine responses to hemorrhage were markedly augmented in the adrenalectomized rats not treated with B, and plasma vasopressin concentrations were significantly elevated at 1 and 2 h in all of the rats that subsequently died compared to values in those that lived. We conclude that: 1) death after hemorrhage in fasted adrenalectomized rats is not a result of lack of glucose; 2) chronic and, to an extent, acute treatment of fasted adrenalectomized rats with B enables survival; 3) fasted adrenalectomized rats exhibit strong evidence of hepatic insufficiency which is not apparent in either fed adrenalectomized rats or B-treated fasted adrenalectomized rats; 4) death after hemorrhage in fasted adrenalectomized rats may result from hepatic failure as a consequence of marked splanchnic vasoconstriction mediated bv the actions of extraordinarily high levels of vasoactive hormones after hemorrhage; and 5) B appears to act to decrease the magnitude of response of vasoactive hormones after hemorrhage in fasted adrenatectomized rats.

Darlington, Daniel N.↗

NASA NTRS1997

AIAA Survivability Technical Committee Draft

A relatively new area of interest in aerospace systems survivability is the growing threat of spacecraft penetration by orbital debris. Orbital debris, or "space junk", is composed of the man-made remnants of non-functioning spacecraft still orbiting the Earth. NASA estimates that there are currently over 100,000 orbital debris particles 1 centimeter in diameter or larger that cannot be tracked by existing radar, with the population growing at approximately 4% per year in low earth orbits. With an average velocity of over 8.7 km/sec, these projectiles can penetrate and disable many vulnerable spacecraft systems. Since the likelihood of spacecraft penetration increases with spacecraft surface area, large spacecraft (such as the International Space Station) and communication satellite fleets (such as Iridium) have begun to adopt survivability enhancement strategies similar to those employed by combat aircraft. Collision avoidance maneuvers are commonly practiced by the Space Shuttle and are planned by the International Space Station to decrease their susceptibility to impact by trackable orbital debris; likewise, improved shielding, internal equipment placement, and improved crew operations following penetration can reduce the vulnerability of spacecraft to loss following orbital debris impact. Computer simulations such as the Manned Spacecraft and Crew Survivability (MSCSurv) program at the NASA-Marshall Space Flight Center have recently been developed to quantify and reduce the likelihood of crew or spacecraft loss following orbital debris penetration. The AIAA Survivability Technical Committee is working to enable the transfer of military-developed survivability technologies to help the aerospace industry cope with this growing threat.

Shipman, Jim↗

NASA NTRS2010

Introduction of the Space Shuttle Columbia Accident, Investigation Details, Findings and Crew Survival Investigation Report

As the Space Shuttle Program comes to an end, it is important that the lessons learned from the Columbia accident be captured and understood by those who will be developing future aerospace programs and supporting current programs. Aeromedical lessons learned from the Accident were presented at AsMA in 2005. This Panel will update that information, closeout the lessons learned, provide additional information on the accident and provide suggestions for the future. To set the stage, an overview of the accident is required. The Space Shuttle Columbia was returning to Earth with a crew of seven astronauts on 1Feb, 2003. It disintegrated along a track extending from California to Louisiana and observers along part of the track filmed the breakup of Columbia. Debris was recovered from Littlefield, Texas to Fort Polk, Louisiana, along a 567 statute mile track; the largest ever recorded debris field. The Columbia Accident Investigation Board (CAIB) concluded its investigation in August 2003, and released their findings in a report published in February 2004. NASA recognized the importance of capturing the lessons learned from the loss of Columbia and her crew and the Space Shuttle Program managers commissioned the Spacecraft Crew Survival Integrated Investigation Team (SCSIIT) to accomplish this. Their task was to perform a comprehensive analysis of the accident, focusing on factors and events affecting crew survival, and to develop recommendations for improving crew survival, including the design features, equipment, training and procedures intended to protect the crew. NASA released the Columbia Crew Survival Investigation Report in December 2008. Key personnel have been assembled to give you an overview of the Space Shuttle Columbia accident, the medical response, the medico-legal issues, the SCSIIT findings and recommendations and future NASA flight surgeon spacecraft accident response training. Educational Objectives: Set the stage for the Panel to address the investigation, medico-legal issues, the Spacecraft Crew Survival Integrated Investigation Team report and training for accident response.

Chandler, Michael↗

NASA NTRS2014

Towards a General Equation for the Survival of Microbes Transferred between Solar System Bodies

It should be possible to construct a general equation describing the survival of microbes transferred between Solar System bodies. Such an equation will be useful for constraining the likelihood of transfer of viable organisms between bodies throughout the lifetime of the Solar System, and for refining Planetary Protection constraints placed on future missions. We will discuss the construction of such an equation, present a plan for definition of pertinent factors, and will describe what research will be necessary to quantify those factors. Description: We will examine the case of microbes transferred between Solar System bodies as residents in meteorite material ejected from one body (the "intial body") and deposited on another (the "target body"). Any microbes transferred in this fashion will experience four distinct phases between their initial state on the initial body, up to the point where they colonize the target body. Each of these phases features phenomena capable of reducing or exterminating the initial microbial population. They are: 1) Ejection: Material is ejected from the initial body, imparting shock followed by rapid desiccation and cooling. 2) Transport: Material travels through interplanetary space to the target body, exposing a hypothetical microbial population to extended desiccation, irradiation, and temperature extremes. 3) Infall: Material is deposited on the target body, diminishing the microbial population through shock, mass loss, and heating. 4) Adaptation: Any microbes which survive the previous three phases must then adapt to new chemophysical conditions of the target body. Differences in habitability between the initial and target bodies dominate this phase. A suitable general-form equation can be assembled from the above factors by defining the initial number of microbes in an ejected mass and applying multiplicitive factors based on the physical phenomena inherent to each phase. It should be possible to present the resulting equation in terms of initial ejection mass, ejection shock magnitude, transfer time, initial microbial load and/or other terms and generate graphs defining the number of surviving microbes. The general form of the equation is: x(sub f) = x(sub i) f(sub1) f(sub 2) f(sub 3) f(sub 4) Where x(sub f) is the final number of microbes to survive transfer, x(sub i) is the initial population prior to ejection, and f(sub 1-4) are mortality factors for the four phases described above. Among other considerations, f(sub 1) will vary with respect to impact shock magnitude and f(sub 2) will be time-dependent. Considerable research has been performed to date to quantify the survival rates of various microbes in response to portions of these four phases, both as vegetative cells and/or spores. Results indicate that many species tend to respond differently to the pertinent mortality factors, especially in the case of extremophiles. Therefore, a complete equation will include species-specific responses to the mortality factors.

Fries, M.↗

NASA NTRS2014

The Affect of the Space Environment on the Survival of Halorubrum Chaoviator and Synechococcus (Nageli): Data from the Space Experiment OSMO on EXPOSE-R

We have shown using ESA's Biopan facility flown in Earth orbit that when exposed to the space environment for 2 weeks the survival rate of Synechococcus (Nageli), a halophilic cyanobacterium isolated from the evaporitic gypsum-halite crusts that form along the marine intertidal, and Halorubrum chaoviator a member of the Halobacteriaceae isolated from an evaporitic NaCl crystal obtained from a salt evaporation pond, were higher than all other test organisms except Bacillus spores. These results led to the EXPOSE-R mission to extend and refine these experiments as part of the experimental package for the external platform space exposure facility on the ISS. The experiment was flown in February 2009 and the organisms were exposed to low-Earth orbit for nearly 2 years. Samples were either exposed to solar ultraviolet (UV)-radiation (lambda is greater than 110 nm or lambda is greater than 200 nm, cosmic radiation (dosage range 225-320 mGy), or kept in darkness shielded from solar UV-radiation. Half of each of the UV-radiation exposed samples and dark samples were exposed to space vacuum and half kept at 105 pascals in argon. Duplicate samples were kept in the laboratory to serve as unexposed controls. Ground simulation control experiments were also performed. After retrieval, organism viability was tested using Molecular Probes Live-Dead Bac-Lite stain and by their reproduction capability. Samples kept in the dark, but exposed to space vacuum had a 90 +/- 5% survival rate compared to the ground controls. Samples exposed to full UV-radiation for over a year were bleached and although results from Molecular Probes Live-Dead stain suggested approximately 10% survival, the data indicate that no survival was detected using cell growth and division using the most probable number method. Those samples exposed to attenuated UV-radiation exhibited limited survival. Results from of this study are relevant to understanding adaptation and evolution of life, the future of life beyond earth, the potential for interplanetary transfer of viable microbes via meteorites and dust particles as well as spacecraft, and the physiology of halophiles.

space flight↗

NASA NTRS2016

Design for Survivability: An Approach to Assured Autonomy

Rapidly expanding unmanned air traffic includes and will continue to include non-cooperative participants. Non-cooperative behavior may be due to technical failure, a lack of appropriate equipment, a careless or malicious operator. Regardless of the cause, the outcome remains: growing density of non-cooperative traffic will increase the risk of collision between unmanned vehicles and aircraft carrying humans. As a result, the degraded safety of airspace may limit access to airspace, with adverse consequences for the traveling public and the economy. Because encounters with small non-cooperative objects, such as birds or wayward drones, can happen too rapidly for an external control system to mitigate them, it is imperative that the aircraft that carry humans survive encounters with non-cooperative vehicles. To-date, design for survivability has been practiced explicitly in the military domain. Survivability against collisions in civil aviation has been limited to tolerances against bird strikes; and these tolerances have proved inadequate on occasion. The growing risk of collision with unmanned vehicles now requires the development of survivability discipline for civilian transport aircraft. The new discipline must be infused into multidisciplinary design methods, on par with traditional disciplines. In this paper, we report on a preliminary study of survivability considerations for the civil aviation domain.

Alexandrov, Natalia M.↗

NASA NTRS2017

Technology Considerations for Inclusion of Survivability in MDAO

Rising traffic density, along with autonomy and diversity of vehicles in the air, will fundamentally change the safety environment of the future air transportation system. The change in risk is two-fold: increasing chances of mid-air collisions with non-cooperative objects and increasing chances of crashes over highly populated areas. The changing nature of the vehicles populating the airspace means that civilian aircraft design must now explicitly include considerations of survivability in the event of collision with other vehicles, as well as prevention of damage to people, animals and property on the ground, to a much greater extent than today. This paper offers a preliminary perspective on how MDAO could contribute toward these goals. One of the conclusions is that, in contrast to traditional vehicle design, to accommodate the complexity of the future airspace safely and efficiently, vehicle design requirements, modeling, and design optimization must be closely connected to the properties of the airspace, including those of other vehicles in the air. Thus, the total measure of a vehicle's survivability should include the traditional survivability in malfunction scenarios, combined with new considerations of survivability in collisions and survivability of the public on the ground.

Alexandrov, Natalia M.↗

NASA NTRS2019

Development and Analysis of the Automated Object Reentry Survival Analysis Tool Parametric Study Wrapper

The NASA Orbital Debris Program Office (ODPO) Safety Group at the Johnson Space Center analyzes reentering spacecraft at the end of life. The program primarily used by ODPO in this effort is the Object Reentry Survival Analysis Tool (ORSAT). ORSAT utilizes shape primitives as well as a variety of other parameters (material, size, thickness, aerodynamic mass, orbit inclination, etc.) to simulate the reentry process and ultimately, to determine if a spacecraft could be hazardous to the population on the ground. The NASA ODPO plans to automate the ORSAT process to run multiple ORSAT input files either concurrently or consecutively. This type of automation program will provide several benefits. First, there is a need to run large parametric studies for ORSAT analysts to gain a greater understanding of reentering object’s sensitivity to certain input variables. Secondly, a database of pre-run ORSAT cases will be used to develop a survivability model, which could be made available to spacecraft developers as a design for demise (D4D) tool. The recently completed Automated Object Reentry Survival Analysis Tool (AutoORSAT) Wrapper is currently being used to build a survivability database, the first step in developing a survivability model. Already, the data that AutoORSAT has produced provides a greater understanding of the sensitivity of variables such as the initial temperature of the spacecraft, spacecraft breakup altitude, and the aerodynamic mass of spacecraft.

Smith, Andrew N.↗

NASA NTRS1998

Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular arrhythmias.

Non-NASA Center↗

NASA NTRSDate not supplied

Dust Mitigation Technology to Enable Survive the Night Capabilities

Introduction: As we return to the Moon, the lunar regolith (i.e. lunar dust) covering the surface will be an obstacle to nominal operations. Accounts from Apollo astronauts and analysis of hardware returned from the surface illustrate just how deleterious the dust can be [1]. During Apollo missions, the lunar dust adhered to hardware mechanically and electrostatically [2]. Surviving the Night: Mitigating the lunar dust will be critical to surviving the night. Going hand-in-hand with other extreme environment considerations, dust mitigation is critical to mission success. Dust Impacts on Other Systems: The lunar dust can have negative implications for power, thermal, mechanisms, and several other systems or sub-systems. For example, Apollo encountered marked degradation of performance in heat rejection systems for the lunar roving vehicle, science packages, and other components because of the lunar dust [1]. For power alone, dust can cause internal clogging for power connectors, heat rejection issues, excessive dust on reflective surfaces, reduced power output for solar arrays, and so on. Dust Mitigation Strategy: In addition to considering technology solutions, it is important for hardware, systems, and or components to have a dust mitigation strategy. At a high level, hardware that will encounter the lunar dust should consider these things when defining a dust mitigation strategy: • Understand Natural Environment • Understand Induced Environment • Understand Tolerance to Dust • Write Dust Requirements • Select Dust Mitigation Solutions • Test Hardware in Dusty Environment More information on each of these can be provided to hardware owners. Dust Mitigation Technology Development: NASA has a series of technologies that may be available for hardware that needs to survive the lunar night. Many of these solutions are leveraging dust mitigation technology development efforts from NASA’s Space Technology Mission Directorate (STMD), as well as efforts from ESDMD programs, industry, and academia. Through a series of STMD programs (both internal to NASA and through partnerships), there are several technologies in development as considerations as dust mitigation solutions for hardware. Within STMD, the Game Changing Development Program (GCD) has funded several internal dust mitigation projects including low to mid TRL development, demonstrations on CLPS landers of high TRL solutions, and creating standards and best practices for dust mitigation. STMD dust mitigation efforts also include a series of partnerships for developing technologies and advancing the state of dust mitigation at NASA. This includes the Lunar Surface Innovation Consortium (LSIC), Small Business Innovation Research, Early Stage Innovations (ESI), Space Technology Research Grants (STRG), Announcement of Collaboration Opportunities (ACOs) and Tipping Points (TPs), and Challenges and Crowdsourcing, among others. There are also a series of dust mitigation solutions that have been widely used terrestrially, or during Apollo. In recent years, several studies have produced more data on the efficacy of these potential solutions in the lunar environment. Dust Mitigation Solutions: Dust mitigation solutions generally fall into four categories: • Dust Tolerant Mechanisms • Passive Dust Mitigation Capabilities • Active Dust Mitigation Capabilities • Dust Measurement Capabilities There are a series of solutions that may prove beneficial for hardware that needs to survive the lunar night, including new technology development as well as proven, terrestrial solutions. This presentation will discuss in more detail what some of these solutions are for payloads going to the surface. References: [1] J. R. Gaier, NASA/TM—2005-213610, The Effects of Lunar Dust on EVA Systems During the Apollo Missions [2] T. J. Stubbs, et al. Impact of Dust on Lunar Exploration, 2005

dust mitigation↗

NASA NTRS1975

Impact survival conditions for very large meteorites, with special reference to the legendary Chinguetti meteorite

Contrary to popular belief, very large meteorites can be sufficiently slowed by aerodynamic drag to survive impact with the earth's surface provided that they enter the atmosphere at very low angles. This is a stringent requirement and survival probabilities for large, unguided objects are low; but they are not zero. Based on high-velocity impact experiments and published tabulations of the parameters of shallow angle entry trajectories, we estimate the probability of survival for an iron meteorite approximately the size and shape of the legendary Chinguetti meteorite (100 x 40 x 20-40 m) to be between 0.1 and 1 percent. Together with a limiting estimate of the flux of such bodies encountering the earth, this leads to an expected survival rate of one per (0.1-1.0) billion years on the earth's land surface.

Fudali, R. F.↗

NASA NTRS1985

Can spores survive in interstellar space?

Experimental evidence is presented for the effects of very low temperature and UV radiation, characteristic of the interstellar medium, on the survival of bacteria. In the most general space environment, 10 percent survival times are only of the order of hundreds of years, too short for panspermia to work. In a substantial fraction of space within dark clouds, however, it is shown that, even with conservative figures, survival times as long as millions to tens of millions of years are attainable. In such conditions, clouds could transport organisms from one solar system to another in times significantly shorter than the mean survival time. This occurs with significant probability.

Weber, P.↗

NASA NTRS1992

Survival of falling robots

As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

Cameron, Jonathan M.↗

NASA NTRS1992

Advanced wing design survivability testing and results

Composite wings on current operational aircraft are conservatively designed to account for stress/strain concentrations, and to assure specified damage tolerance. The technology that can lead to improved composite wing structures and associated structural efficiency is to increase design ultimate strain levels beyond their current limit of 3500 to 4000 micro-in/in to 6000 micro-in/in without sacrificing structural integrity, durability, damage tolerance, or survivability. Grumman, under the sponsorship of the Naval Air Development Center (NADC), has developed a high-strain composite wing design for a subsonic aircraft wing using novel and innovative design concepts and manufacturing methods, while maintaining a state-of-the-art fiber/resin system. The current advanced wing design effort addressed a tactical subsonic aircraft wing using previously developed, high-strain wing design concepts in conjunction with newer/emerging fiber and polymer matrix composite (PMC) materials to achieve the same goals, while reducing complexity. Two categories of advanced PMC materials were evaluated: toughened thermosets; and engineered thermoplastics. Advanced PMC materials offer the technological opportunity to take maximum advantage of improved material properties, physical characteristics, and tailorability to increase performance and survivability over current composite structure. Damage tolerance and survivability to various threats, in addition to structural integrity and durability, were key technical issues addressed during this study, and evaluated through test. This paper focuses on the live-fire testing, and the results performed to experimentally evaluate the survivability of the advanced wing design.

Bruno, J.↗

NASA NTRS1994

Survival and Recovery of Methanotrophic Bacteria Starved Under Oxic and Anoxic Conditions

The effects of carbon deprivation on survival of methanotrophic bacteria were compared in cultures incubated in the presence and absence of oxygen in the starvation medium. Survival and recovery of the examined methanotrophs were generally highest for cultures starved under anoxic conditions as indicated by poststarvation measurements of methane oxidation, tetrazolium salt reduction, plate counts, and protein synthesis. Methylosinus trichosporium OB3b survived up to 6 weeks of carbon deprivation under anoxic conditions while maintaining a physiological state that allowed relatively rapid (hours) methane oxidation after substrate addition. A small fraction of cells starved under oxic and anoxic conditions (4 and 10%, respectively) survived more than 10 weeks but required several days for recovery on plates and in liquid medium. A non-spore-forming methanotroph, strain WP 12, displayed 36 to 118% of its initial methane oxidation capacity after 5 days of carbon deprivation. Oxidation rates varied with growth history prior to the experiments as well as with starvation conditions. Strain WP 12 starved under anoxic conditions showed up to 90% higher methane oxidation activity and 46% higher protein production after starvation than did cultures starved under oxic conditions. Only minor changes in biomass and niorpholow were seen for methanotrophic bacteria starved tinder anoxic conditions. In contrast, starvation under oxic conditions resulted in morphology changes and an initial 28 to 35% loss of cell protein. These data suggest that methanotrophic bacteria can survin,e carbon deprivation under anoxic conditions by using maintenance energy derived Solelyr from an anaerobic endogenous metabolism. This capability could partly explain a significant potential for methane oxidation in environments not continuously, supporting aerobic methanotrophic growth.

Roslev, Peter↗

NASA NTRS2000

Regulation of Osteoblast Survival by the Extracellular Matrix and Gravity

Spaceflight adversely affects the skeleton, posing a substantial risk to astronaut's health during long duration missions. The reduced bone mass observed in growing animals following spaceflight is due at least in part to inadequate bone formation by osteoblasts. Thus, it is of central importance to identify basic cellular mechanisms underlying normal bone formation. The fundamental ideas underlying our research are that interactions between extracellular matrix proteins, integrin adhesion receptors, cytoplasmic signaling and cytoskeletal proteins are key ingredients for the proper functioning of osteoblasts, and that gravity impacts these interactions. As an in vitro model system we used primary fetal rat calvarial cells which faithfully recapitulate osteoblast differentiation characteristically observed in vivo. We showed that specific integrin receptors ((alpha)3(beta)1), ((alpha)5(beta)1), ((alpha)8(betal)1) and extracellular matrix proteins (fibronectin, laminin) were needed for the differentiation of immature osteoblasts. In the course of maturation, cultured osteoblasts switched from depending on fibronectin and laminin for differentiation to depending on these proteins for their very survival. Furthermore, we found that manipulating the gravity vector using ground-based models resulted in activation of key intracellular survival signals generated by integrin/extracellular matrix interactions. We are currently testing the in vivo relevance of some of these observations using targeted transgenic technology. In conclusion, mechanical factors including gravity may participate in regulating survival via cellular interactions with the extracellular matrix. This leads us to speculate that microgravity adversely affects the survival of osteoblasts and contributes to spaceflight-induced osteoporosis.

Globus. Ruth K.↗

NASA NTRS2000

Development of utricular otoliths, but not saccular otoliths, is necessary for vestibular function and survival in zebrafish

We have been studying the consequences of embryonic vestibular dysfunction caused by the monolith (mnl) mutation in zebrafish. mnl is a dominant mutation that specifically inhibits formation of utricular otoliths. However, briefly immobilizing mnl/mnl embryos in agarose with the otic vesicle orientated at certain angles selectively induces or prevents formation of utricular and/or saccular otoliths. With this noninvasive technique, we generated six phenotypic classes of mnl/mnl mutants, designated S-S, U-U, U-S, S-US, U-US, and US-US, depending on which otoliths are present on each side (U, utricular otolith; S, saccular otolith). All mnl/mnl larvae survived through day 10 of development. Thereafter, S-S larvae showed a rapid decline, probably because of starvation, and none survived to adulthood. Survival rates in all other classes of mnl/mnl larvae (those having at least one utricular otolith) were close to normal. The presence or absence of utricular otoliths also correlated with vestibular function during early larval development, as measured by three criteria: First, unlike wild-type larvae, S-S mutant larvae showed almost no detectable counter-rotation of the eyes when tilted tail up or tail down. Second, 95% of S-S mutant larvae never acquired the ability to maintain a balanced dorsal-up posture. Third, although most wild-type larvae responded to gentle prodding by swimming in a straight line, S-S larvae responded by swimming in rapid circles, showing sudden and frequent changes in direction ("zigzagging"), and/or rolling and spiraling. All other phenotypic classes of mnl/mnl larvae behaved normally in these assays. These data demonstrate that bilateral loss of utricular otoliths disrupts the ability to sense gravity, severely impairs balance and motor coordination, and is invariably lethal. The presence of a utricular otolith in at least one inner ear is necessary and sufficient for vestibular function and survival. In contrast, saccular otoliths are dispensable for these functions. Copyright 2000 John Wiley & Sons, Inc.

Non-NASA Center↗