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NASA NTRS1999

Instrumentation for Non-Invasive Assessment of Cardiovascular Regulation

It is critically important to be able to assess alterations in cardiovascular regulation during and after space flight. We propose to develop an instrument for the non-invasive assessment of such alterations that can be used on the ground and potentially during space flight. This instrumentation would be used by the Cardiovascular Alterations Team at multiple sites for the study of the effects of space flight on the cardiovascular system and the evaluation of countermeasures. In particular, the Cardiovascular Alterations Team will use this instrumentation in conjunction with ground-based human bed-rest studies and during application of acute stresses e.g., tilt, lower body negative pressure, and exercise. In future studies, the Cardiovascular Alterations Team anticipates using this instrumentation to study astronauts before and after space flight and ultimately, during space flight. The instrumentation may also be used by the Bone Demineralization/Calcium Metabolism Team, the Neurovestibular Team and the Human Performance Factors, Sleep and Chronobiology Team to measure changes in autonomic nervous function. The instrumentation will be based on a powerful new technology - cardiovascular system identification (CSI) - which has been developed in our laboratory. CSI provides a non-invasive approach for the study of alterations in cardiovascular regulation. This approach involves the analysis of second-to-second fluctuations in physiologic signals such as heart rate and non-invasively measured arterial blood pressure in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of multiple physiologic mechanisms, CSI provides a closed-loop model of the cardiovascular regulatory state in an individual subject.

Cohen, Richard J.↗

NASA NTRS1981

Variation Principles and Applications in the Study of Cell Structure and Aging

In this report we have attempted to show that "some reality lies concealed in biological variation". This "reality" has its principles, laws, mechanisms, and rules, only a few of which we have sketched. A related idea we pursued was that important information may be lost in the process of ignoring frequency distributions of physiological variables (as is customary in experimental physiology and gerontology). We suggested that it may be advantageous to expand one's "statistical field of vision" beyond simple averages +/- standard deviations. Indeed, frequency distribution analysis may make visible some hidden information not evident from a simple qualitative analysis, particularly when the effect of some external factor or condition (e.g., aging, dietary chemicals) is being investigated. This was clearly illustrated by the application of distribution analysis in the study of variation in mouse liver cellular and fine structure, and may be true of fine structural studies in general. In living systems, structure and function interact in a dynamic way; they are "inseparable," unlike in technological systems or machines. Changes in fine structure therefore reflect changes in function. If such changes do not exceed a certain physiologic range, a quantitative analysis of structure will provide valuable information on quantitative changes in function that may not be possible or easy to measure directly. Because there is a large inherent variation in fine structure of cells in a given organ of an individual and among individuals, changes in fine structure can be analyzed only by studying frequency distribution curves of various structural characteristics (dimensions). Simple averages +/- S.D. do not in general reveal all information on the effect of a certain factor, because often this effect is not uniform; on the contrary, this will be apparent from distribution analysis because the form of the curves will be affected. We have also attempted to show in this chapter that similar general statistical principles and mechanisms may be operative in biological and technological systems. Despite the common belief that most biological and technological characteristics of interest have a symmetric bell-shaped (normal or Gaussian) distribution, we have shown that more often than not, distributions tend to be asymmetric and often resemble a so-called log-normal distribution. We saw that at least three general mechanisms may be operative, i.e., nonadditivity of influencing factors, competition among individuals for a common resource, and existence of an "optimum" value for a studied characteristic; more such mechanisms could exist.

Economos, Angelos C.↗

NASA NTRS1995

Exercise and Human Immunodeficiency Virus (HIV-1) Infection

The human immune system is highly efficient and remarkably protective when functioning properly. Similar to other physiological systems, it functions best when the body is maintained with a balanced diet, sufficient rest and a moderately stress-free lifestyle. It can be disrupted by inappropriate drug use and extreme emotion or exertion. The functioning of normal or compromised immune systems can be enhanced by properly prescribed moderate exercise conditioning regimens in healthy people, and in some human immunodeficiency virus (HIV-1)-infected patients but not in others who unable to complete an interval training program. Regular exercise conditioning in healthy people reduces cardiovascular risk factors, increases stamina, facilitates bodyweight control, and reduces stress by engendering positive feelings of well-being. Certain types of cancer may also be suppressed by appropriate exercise conditioning. Various exercise regimens are being evaluated as adjunct treatments for medicated patients with the HIV-1 syndrome. Limited anecdotal evidence from patients suggests that moderate exercise conditioning is per se responsible for their survival well beyond expectancy. HIV-1-infected patients respond positively, both physiologically and psychologically, to moderate exercise conditioning. However, the effectiveness of any exercise treatment programme depends on its mode, frequency, intensity and duration when prescribed o complement the pathological condition of the patient. The effectiveness of exercise conditioning regimens in patients with HIV-1 infection is reviewed in this article. In addition, we discuss mechanisms and pathways, involving the interplay of psychological and physiological factors, through which the suppressed immune system can be enhanced. The immune modulators discussed are endogenous opioids, cytokines, neurotransmitters and other hormones. Exercise conditioning treatment appears to be more effective when combined with other stress management procedures.

Lawless, DeSales↗

NASA NTRS1998

Diurnal Reflectance Changes in Vegetation Observed with AVIRIS

Among the most important short-term dynamic biological processes are diurnal changes in canopy water relations. Plant regulation of water transport through stomatal openings affects other gaseous transport processes, often dramatically decreasing photosynthetic fixation of carbon dioxide during periods of water stress. Water stress reduces stomatal conductance of water vapor through the leaf surface and alters the diurnal timing of stomatal opening. Under non-water stressed conditions, stomates typically open soon after dawn and transpire water vapor throughout the daylight period. During stress periods, stomates may close for part of the day, generally near mid-day. Under prolonged stress conditions, stomatal closure shifts to earlier times during the day; stomates may close by mid-morning and remain closed until the following morning - or remain closed entirely. Under these conditions the relationship between canopy greenness (e.g., measured with a vegetation index or by spectral mixture analysis) and photosynthetic fixation of carbon is lost and the remotely sensed vegetation metric is a poor predictor of gas exchange. Prediction of stomatal regulation and exchange of water and trace gases is critical for ecosystem and climate models to correctly estimate budgets of these gases and understand or predict other processes like gross and net ecosystem primary production. Plant gas exchange has been extensively studied by physiologists at the leaf and whole plant level and by biometeorologists at somewhat larger scales. While these energy driven processes follow a predictable if somewhat asymmetric diurnal cycle dependent on soil water availability and the constraints imposed by the solar energy budget, they are nonetheless difficult to measure at the tree and stand levels using conventional methods. Ecologists have long been interested in the potential of remote sensing for monitoring physiological changes using multi-temporal images. Much of this research has focused on day-to-day changes in water use, especially for agricultural applications. Ustin et al. showed seasonal changes in canopy water content in chaparral shrub could be estimated using optical methods. Vanderbilt et al. followed asymmetric diurnal changes in the reflectance of a walnut orchard, but could not attribute specific reflectance changes to specific changes in canopy architecture or physiology. Forests and shrub lands in California experience prolonged periods of drought, sometimes extending six months without precipitation. The conifer and evergreen chaparral communities common to the foothill region around the central valley of California retain their foliage throughout the summer and have low transpiration rates despite high net radiation and temperature conditions. In contrast, grasslands and drought resistant deciduous species in the same habitat are seasonally dormant in summer. Because of differences in the mechanisms of drought tolerance, rooting depth and physiology between different plant communities in the region, it is likely that they display differences in diurnal water relations. The presence of diverse plant communities provides an opportunity to investigate possible diurnal landscape patterns in water relations that could be observed by an airborne hyperspectral scanner. This investigation of AVIRIS data collected over forest and shrub land represents the continuation of a prior investigation involving spectral mixture analysis of diurnal effects in the same AVIRIS data set.

Vanderbilt, V. C.↗

NASA NTRS2000

NASA Space Technology Can Improve Soldier Health, Performance and Safety

One of the primary goals of NASA Life Sciences research is '... to enable a permanent human presence in space.' To meet this goal, NASA is creating alternative protocols designed to evaluate and test countermeasures that will account for and correct the environmental effects of space flight on crewmembers health, safety, and operational performance. NASA investigators have previously evaluated the effects of long-duration space flight on physiology and performance of cosmonauts aboard the MIR space station. They also initiated tests of a countermeasure, Autogenic-Feedback Training Exercise (AFTE) designed to prevent and/or correct adverse effects, i.e., facilitate adaptation to space and re-adaptation to Earth. AFTE is a six-hour physiological training program that has proven to be a highly efficient and effective method for enabling people to monitor and voluntarily control a range of their own physiological responses, thereby minimizing adverse reactions to environmental stress. However, because of limited opportunities to test this technology with space flight crews, it is essential to find operational or 'real world' environments in which to validate the efficacy of this approach.

Cowings, Patricia S.↗

NASA NTRS2000

NASA SMART Probe: Breast Cancer Application

There is evidence in breast cancer and other malignancies that the physiologic environment within a tumor correlates with clinical outcome. We are developing a unique percutaneous Smart Probe to be used at the time of needle biopsy of the breast. The Smart Probe will simultaneously measure multiple physiologic parameters within a breast tumor. Direct and indirect measurements of tissue oxygen levels, blood flow, pH, and tissue fluid pressure will be analyzed in real-time. These parameters will be interpreted individually and collectively by innovative neural network techniques using advanced intelligent software. The goals are 1) develop a pecutaneous Smart Probe with multiple sensor modalities and applying advanced Information Technologies to provide real time diagnostic information of the tissue at tip of the probe, 2) test the percutaneous Smart Probe in women with benign and malignant breast masses who will be undergoing surgical biopsy, 3) correlate probe sensor data with benign and malignant status of breast masses, 4) determine whether the probe can detect physiologic differences within a breast tumor, and its margins, and in adjacent normal breast tissue, 5) correlate probe sensor data with known prognostic factors for breast caner, including tumor size, tumor grade, axillary lymph node metastases, estrogen receptor and progesterone receptor status.

Mah, Robert W.↗

NASA NTRS1994

Assessment of Psychophysiological Responses During Motion Sickness Testing

The purpose of this investigation is to evaluate a methodology designed to accurately trace the temporal progression of motion sickness and space motion sickness symptoms. With this method, subjects continuously monitor their own motion sickness symptoms during exposure to a provocative stimulus as symptoms occur, in contrast to previous methods during which subjects report symptoms verbally at discrete time intervals. This method not only is comparable to previous methods in the type of symptoms that subjects report, but subjects report symptoms more frequently. Frequent reporting of motion sickness symptoms allows researchers to detail the waxing and waning of motion sickness symptoms for each individual. Previous research has shown that physiological responses to motion sickness stimuli are characterized by unique individual differences in response patterns. By improving our assessment of motion sickness symptoms with continuous monitoring of symptoms, the relationship between specific physiological responses and sickness levels can be more accurately determined for each individual. Results from this study show significant positive relationships between skin conductance levels and symptom levels for ten individuals; a significant positive relationship between temperature and symptom levels for 5 of 10 individuals; and both positive and negative relationships between respiration, heart rate, blood volume pulse and symptom levels. Continuous monitoring of motion sickness symptoms can be used to more accurately assess motion sickness to aid in the evaluation of countermeasures. In addition, recognition of the onset of symptoms that are strongly related to specific physiological responses could be used as cues to initiate procedures (e.g., Autogenic Feedback Training) to prevent the development of severe motion sickness symptoms.

Stoud, Cynthia S.↗

NASA NTRS2001

Organization of P, S, and Fe Inclusions in a Freshwater Magnetococcus

Magnetotactic bacteria are a heterogeneous group of motile, mainly aquatic procaryotes that align and swim along geomagnetic field lines. They are of interest to astrobiologists because of the magnetite crystals found in the Mars meteorite ALH84001 which share many characteristics with the magnetite produced intracellularly by magnetotactic bacteria. These bacteria are diverse morphologically, physiologically and phylogenetically, sharing a few key characteristics: 1) the presence of intracellular membrane-bound magnetic crystals (magnetosomes), usually but not always arranged in chains; 2) motility by means of flagella; and 3) microaerophillic or anaerobic physiology. The bilophotrichous (having two flagella bundles) magnetotactic cocci (MC) are ubiquitous in aquatic habitats but have proven extremely difficult to cultivate. Because only several marine strains have been isolated and grown in axenic culture, little is known about the physiology and the biogeochemical roles of the MC. We studied the composition and distribution of intracellular structures in an uncultured MC, designated ARB-1. To do this, a combination of light microscopy, environmental scanning electron microscopy (ESEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS) were used. Cells of ARB-1 were separated from sediments collected from Baldwin Lake (Los Angeles Arboretum, Arcadia, CA). They are large spherical to oblate spheroidal Gram-negative cells, ranging from 1 to 4 micrometers along the maximum dimension, which is perpendicular to the direction of swimming. Cells have two large phosphorus-containing inclusions that comprise a large percentage of the cell volume. Many smaller sulfur inclusions are located at the convex end of the cell. Most of the cellular Fe is present in the magnetosomes. These may be arranged as a clump at the concave end of the cell, near the two flagella bundles, or as chains, or as both a clump and chains. The magnetosomes were identified as magnetite (Fe3O4) by selected area electron diffraction (SAED) and high resolution TEM. We saw a trend between cell size and organization of the magnetosomes. Smaller, more spherical cells were more likely to have chains than were larger, more oblate cells. This may indicate different populations of cells, or it may be attributed to variations in cell growth cycle. The size distribution (length) of magnetosomes in chains was similar to that of magnetosomes in clusters, except that there was a larger size range for clustered magnetosomes. Magnetosomes from ARB-1 cells average 82 nm in length. If plotted on a graph of length as a function of aspect ratio, they fall within the single domain region of the plot. If compared with the size distributions of magnetite from ALH84001 and magnetosomes from the cultured magnetotactic vibrio MV-1, the magnetites produced by ARB-1 cells are, on average, larger and have a wider range of aspect ratio. ARB-1 cells have a specific organization of the P, S, and Fe inclusions. The P inclusions always occupy the majority of the cell volume and separate the S inclusions from the disorganized clumps of magnetosomes and the flagella bundles. The P inclusions may contain polyphosphate, which could play several roles in motility, adaptation to stress, growth and division, buoyancy, and energy. The S inclusions might be a way to store S, a potential energy source, when the cells move from sulfide to oxygen zones. The consistency of P, S, and Fe organization in ARB-1 cells suggests that these inclusions have some specific and interactive functions.

Cox, Lea↗

NASA NTRS1995

Sensor Systems for Space Life Sciences

Sensors 2000! (S2K!) is a NASA Ames Research Center engineering initiative designed to provide biosensor and bio-instrumentation systems technology expertise to NASA's life sciences spaceflight programs. S2K! covers the full spectrum of sensor technology applications, ranging from spaceflight hardware design and fabrication to advanced technology development, transfer and commercialization. S2K! is currently developing sensor systems for space biomedical applications on BION (a Russian biosatellite focused on Rhesus Monkey physiology) and NEUROLAB (a Space Shuttle flight devoted to neuroscience). It's Advanced Technology Development-Biosensors (ATD-B) project focuses efforts in five principle areas: biotelemetry Systems, chemical and biological sensors, physiological sensors, advanced instrumentation architectures, and data and information management. Technologies already developed and tested included, application-specific sensors, preamplifier hybrids, modular programmable signal conditioners, power conditioning and distribution systems, and a fully implantable dual channel biotelemeter. Systems currently under development include a portable receiver system compatible with an off-the-shelf analog biotelemeter, a 4 channel digital biotelemetry system which monitors pH, a multichannel, g-processor based PCM biotelemetry system, and hand-held personal monitoring systems. S2K! technology easily lends itself to telescience and telemedicine applications as a front-end measurement and data acquisition device, suitable for obtaining and configuring physiological information, and processing that information under control from a remote location.

Somps, Chris J.↗

NASA NTRS1996

Telemetric Sensors for the Space Life Sciences

Telemetric sensors for monitoring physiological changes in animal models in space are being developed by NASA's Sensors 2000! program. The sensors measure a variety of physiological measurands, including temperature, biopotentials, pressure, flow, acceleration, and chemical levels, and transmit these signals from the animals to a remote receiver via a wireless link. Thus physiologic information can be obtained continuously and automatically without animal handling, tethers, or percutaneous leads. We report here on NASA's development and testing of advanced wireless sensor systems for space life sciences research.

Hines, John W.↗

NASA NTRS1997

Research on the Effects of Fatigue within the Corporate/Business Aircraft Environment

In 1980, responding to a Congressional request, NASA Ames Research Center created a program to examine whether 'there is a safety problem of uncertain magnitude, due to transmeridian flying and a potential problem due to fatigue in association with various factors found in air transport operations.' The NASA Ames Fatigue/Jet Lag Program was created to collect systematic, scientific information on fatigue, sleep, circadian rhythms, and performance in flight operations. Three Program goals were established and continue to guide research efforts to: (1) determine the extent of fatigue, sleep loss, and circadian disruption in flight operations; (2) determine the impact of these factors on flight crew performance; (3) develop and evaluate countermeasures to mitigate the adverse effects of these factors and maximize flight crew performance and alertness. Since 1980, studies have been conducted in a variety of aviation environments, in controlled laboratory environments, as well as in a full-mission flight simulation. Early studies included investigations of short-haul, long-haul, and overnight cargo flight crews. In 1991, the name of the program was changed to the Fatigue Countermeasures Program to provide a greater emphasis on the development and evaluation of countermeasures. More recent work has examined the effects of planned cockpit rest as an operational countermeasure and provided analyses of the pertinent sleep/duty factors preceding an aviation accident at Guantanamo Bay, Cuba. The Short-Haul study examined the extent of sleep loss, circadian disruption, and fatigue engendered by flying commercial short-haul air transport operations (flight legs less than eight hours). This was one of the first field studies conducted by the NASA program and provided unique insight into the physiological and subjective effects of flying commercial short-haul operations. It demonstrated that a range of measures could be obtained in an operational environment without disturbing the regular performance of duties. The Long-Haul study examined how long-haul flight crews organized their sleep during a variety of international trip patterns and examined how duty requirements, local time, and the circadian system affected the timing, duration, and quality of sleep. Duty requirements and local time can be viewed as external/environmental constraints on time available for sleep, while the internal circadian system is a major physiological modulator of sleep duration and quality. The Overnight Cargo study documented the psychophysiological effects of flying overnight cargo operations. The data collected clearly demonstrated that overnight cargo operations, like other night work, involve physiological disruption not found in comparable daytime operations.

Neri, David F.↗

NASA NTRS1997

Space Biosensor Systems: Implications for Technology Transfer

To meet the need for continuous, automated monitoring of animal subjects, including; humans, during space flight, NASA is developing advanced physiologic sensor and biotelemetry system technologies. The ability to continuously track basic physiological parameters, such as heart rate, blood pH, and body temperature, in untethered subjects in space is a challenging task. At NASA's Ames Research Center, where a key focus is gravitational biology research, engineers have teamed with life scientists to develop wireless sensor systems for automated physiologic monitoring of animal models as small as the rat. This technology is also being adapted, in collaboration with medical professionals, to meet human clinical monitoring needs both in space and on the ground. Thus, these advanced monitoring technologies have important dual-use functions; they meet space flight data collection requirements and constraints, while concurrently addressing a number of monitoring and data acquisition challenges on the ground in areas of clinical monitoring and biomedical research. Additional applications for these and related technologies are being sought and additional partnerships established that enhance development efforts, reduce costs and facilitate technology infusion between the public and private sectors. This paper describes technology transfer and co-development projects that have evolved out of NASA's miniaturized, implantable chemical sensor development efforts.

Hines, J. W.↗

NASA NTRS2001

Crew Factors in Flight Operations X: Alertness Management in Flight Operations

In response to a 1980 congressional request, NASA Ames Research Center initiated a Fatigue/Jet Lag Program to examine fatigue, sleep loss, and circadian disruption in aviation. Research has examined fatigue in a variety of flight environments using a range of measures (from self-report to performance to physiological). In 1991, the program evolved into the Fatigue Countermeasures Program, emphasizing the development and evaluation of strategies to maintain alertness and performance in operational settings. Over the years, the Federal Aviation Administration (FAA) has become a collaborative partner in support of fatigue research and other Program activities. From the inception of the Program, a principal goal was to return the information learned from research and other Program activities to the operational community. The objectives of this Education and Training Module are to explain what has been learned about the physiological mechanisms that underlie fatigue, demonstrate the application of this information in flight operations, and offer some specific fatigue countermeasure recommendations. It is intended for all segments of the aeronautics industry, including pilots, flight attendants, managers, schedulers, safety and policy personnel, maintenance crews, and others involved in an operational environment that challenges human physiological capabilities because of fatigue, sleep loss, and circadian disruption.

Rosekind, Mark R.↗

NASA NTRS2002

The Efficacy of Using Synthetic Vision Terrain-Textured Images to Improve Pilot Situation Awareness

The General Aviation Element of the Aviation Safety Program's Synthetic Vision Systems (SVS) Project is developing technology to eliminate low visibility induced General Aviation (GA) accidents. SVS displays present computer generated 3-dimensional imagery of the surrounding terrain on the Primary Flight Display (PFD) to greatly enhance pilot's situation awareness (SA), reducing or eliminating Controlled Flight into Terrain, as well as Low-Visibility Loss of Control accidents. SVS-conducted research is facilitating development of display concepts that provide the pilot with an unobstructed view of the outside terrain, regardless of weather conditions and time of day. A critical component of SVS displays is the appropriate presentation of terrain to the pilot. An experimental study is being conducted at NASA Langley Research Center (LaRC) to explore and quantify the relationship between the realism of the terrain presentation and resulting enhancements of pilot SA and performance. Composed of complementary simulation and flight test efforts, Terrain Portrayal for Head-Down Displays (TP-HDD) experiments will help researchers evaluate critical terrain portrayal concepts. The experimental effort is to provide data to enable design trades that optimize SVS applications, as well as develop requirements and recommendations to facilitate the certification process. In this part of the experiment a fixed based flight simulator was equipped with various types of Head Down flight displays, ranging from conventional round dials (typical of most GA aircraft) to glass cockpit style PFD's. The variations of the PFD included an assortment of texturing and Digital Elevation Model (DEM) resolution combinations. A test matrix of 10 terrain display configurations (in addition to the baseline displays) were evaluated by 27 pilots of various backgrounds and experience levels. Qualitative (questionnaires) and quantitative (pilot performance and physiological) data were collected during the experimental runs. This paper focuses on the experimental set-up and final physiological results of the TP-HDD simulation experiment. The physiological measures of skin temperature, heart rate, and muscle response, show a decreased engagement (while using the synthetic vision displays as compared to the baseline conventional display) of the sympathetic and somatic nervous system responses which, in turn, indicates a reduced level of mental workload. This decreased level of workload is expected to enable improvement in the pilot's situation and terrain awareness.

Uenking, Michael D.↗

NASA NTRS2001

Helping Video Games Rewire "Our Minds"

Biofeedback-modulated video games are games that respond to physiological signals as well as mouse, joystick or game controller input; they embody the concept of improving physiological functioning by rewarding specific healthy body signals with success at playing a video game. The NASA patented biofeedback-modulated game method blends biofeedback into popular off-the- shelf video games in such a way that the games do not lose their entertainment value. This method uses physiological signals (e.g., electroencephalogram frequency band ratio) not simply to drive a biofeedback display directly, or periodically modify a task as in other systems, but to continuously modulate parameters (e.g., game character speed and mobility) of a game task in real time while the game task is being performed by other means (e.g., a game controller). Biofeedback-modulated video games represent a new generation of computer and video game environments that train valuable mental skills beyond eye-hand coordination. These psychophysiological training technologies are poised to exploit the revolution in interactive multimedia home entertainment for the personal improvement, not just the diversion, of the user.

Pope, Alan T.↗

NASA NTRS2004

Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats

Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.

Estrous Cycle/physiology↗

NASA NTRS2003

An in silico assessment of gene function and organization of the phenylpropanoid pathway metabolic networks in Arabidopsis thaliana and limitations thereof

The Arabidopsis genome sequencing in 2000 gave to science the first blueprint of a vascular plant. Its successful completion also prompted the US National Science Foundation to launch the Arabidopsis 2010 initiative, the goal of which is to identify the function of each gene by 2010. In this study, an exhaustive analysis of The Institute for Genomic Research (TIGR) and The Arabidopsis Information Resource (TAIR) databases, together with all currently compiled EST sequence data, was carried out in order to determine to what extent the various metabolic networks from phenylalanine ammonia lyase (PAL) to the monolignols were organized and/or could be predicted. In these databases, there are some 65 genes which have been annotated as encoding putative enzymatic steps in monolignol biosynthesis, although many of them have only very low homology to monolignol pathway genes of known function in other plant systems. Our detailed analysis revealed that presently only 13 genes (two PALs, a cinnamate-4-hydroxylase, a p-coumarate-3-hydroxylase, a ferulate-5-hydroxylase, three 4-coumarate-CoA ligases, a cinnamic acid O-methyl transferase, two cinnamoyl-CoA reductases) and two cinnamyl alcohol dehydrogenases can be classified as having a bona fide (definitive) function; the remaining 52 genes currently have undetermined physiological roles. The EST database entries for this particular set of genes also provided little new insight into how the monolignol pathway was organized in the different tissues and organs, this being perhaps a consequence of both limitations in how tissue samples were collected and in the incomplete nature of the EST collections. This analysis thus underscores the fact that even with genomic sequencing, presumed to provide the entire suite of putative genes in the monolignol-forming pathway, a very large effort needs to be conducted to establish actual catalytic roles (including enzyme versatility), as well as the physiological function(s) for each member of the (multi)gene families present and the metabolic networks that are operative. Additionally, one key to identifying physiological functions for many of these (and other) unknown genes, and their corresponding metabolic networks, awaits the development of technologies to comprehensively study molecular processes at the single cell level in particular tissues and organs, in order to establish the actual metabolic context.

NASA Program Fundamental Space Biology↗

NASA NTRS2002

Evidence for vestibular regulation of autonomic functions in a mouse genetic model

Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

Non-NASA Center↗