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At least 271 records · Page 15

A dual-mode disturbance-accommodating controller for the Hubble Space Telescope

Cyclic thermal expansions and mechanical stiction effects in the Solar Arrays on the Hubble Space Telescope (HST) are triggering repeated occurrences of damped, relaxation-type flex-body vibrations of the solar arrays. Those solar array vibrations are, in turn, causing unwanted, oscillating disturbance torques on the HST main body, which cause unwanted deviations of the telescope from its specified pointing direction. In this paper we propose two strategies one can adopt in designing a telescope-pointing controller to cope with the aforementioned disturbances: (1) a `total isolation' (TI) control strategy whereby the HST controller torques are designed to adaptively counteract and cancel-out the persistent disturbing torques that are causing the unwanted telescope motions, and (2) an `array damping' (AD) control strategy whereby the HST controller torques are used to actively augment the natural dampening of the solar array vibrations and the attendant telescope motions, between triggerings of the stiction-related flex-body relaxation oscillations. Using the principles of Disturbance-Accommodating Control (DAC) Theory a dual-mode controller for a generic, planar-motion (single-axis) model of the HST is proposed. This controller incorporates both the TI and AD modes of disturbance-accommodation. Simulation studies of the closed-loop system using generic parameter values clearly indicate, qualitatively, the enhanced pointing-performance such a controller can achieve.

Addington, Stewart↗

Thermal/structural analyses of several hydrogen-cooled leading-edge concepts for hypersonic flight vehicles

The aerodynamic heating at high flight Mach numbers, when shock interference heating is included, can be extremely high and can exceed the capability of most conventional metallic and potential ceramic materials available. Numerical analyses of the heat transfer and thermal stresses are performed on three actively cooled leading-edge geometries (models) made of three different materials to address the issue of survivability in a hostile environment. These analyses show a mixture of results from one configuration to the next. Results for each configuration are presented and discussed. Combinations of enhanced internal film coefficients and high material thermal conductivity of copper and tungsten are predicted to maintain the maximum wall temperature for each concept within acceptable operating limits. The exception is the TD nickel material which is predicted to melt for most cases. The wide range of internal impingement film coefficients (based on correlations) for these conditions can lead to a significant uncertainty in expected leading-edge wall temperatures. The equivalent plastic strain, inherent in each configuration which results from the high thermal gradients, indicates a need for further cyclic analysis to determine component life.

Gladden, Herbert J.↗

Thermal/structural analyses of several hydrogen-cooled leading-edge concepts for hypersonic flight vehicles

The aerodynamic heating at high flight Mach numbers, when shock interference heating is included, can be extremely high and can exceed the capability of most conventional metallic and potential ceramic materials available. Numerical analyses of the heat transfer and thermal stresses are performed on three actively cooled leading-edge geometries (models) made of three different materials to address the issue of survivability in a hostile environment. These analyses show a mixture of results from one configuration to the next. Results for each configuration are presented and discussed. Combinations of enhanced internal film coefficients and high material thermal conductivity of copper and tungsten are predicted to maintain the maximum wall temperature for each concept within acceptable operating limits. The exception is the TD nickel material which is predicted to melt for most cases. The wide range of internal impingement film coefficients (based on correlations) for these conditions can lead to a significant uncertainty in expected leading-edge wall temperatures. The equivalent plastic strain, inherent in each configuration which results from the high thermal gradients, indicates a need for further cyclic analysis to determine component life.

Gladden, Herbert J.↗

Development of a Deep-Penetrating, Compact Geothermal Heat Flow System for Robotic Lunar Geophysical Missions

Geothermal heat flow measurements are a high priority for the future lunar geophysical network missions recommended by the latest Decadal Survey of the National Academy. Geothermal heat flow is obtained as a product of two separate measurements of geothermal gradient and thermal conductivity of the regolith/soil interval penetrated by the instrument. The Apollo 15 and 17 astronauts deployed their heat flow probes down to 1.4-m and 2.3-m depths, respectively, using a rotary-percussive drill. However, recent studies show that the heat flow instrument for a lunar mission should be capable of excavating a ~3-m deep hole to avoid the effect of potential long-term changes of the surface thermal environment. For a future robotic geophysical mission, a system that utilizes a rotary/percussive drill would far exceed the limited payload and power capacities of the lander/rover. Therefore, we are currently developing a more compact heat flow system that is capable of 3-m penetration. Because the grains of lunar regolith are cohesive and densely packed, the previously proposed lightweight, internal hammering systems (the so-called moles ) are not likely to achieve the desired deep penetration. The excavation system for our new heat flow instrumentation utilizes a stem which winds out of a pneumatically driven reel and pushes its conical tip into the regolith. Simultaneously, gas jets, emitted from the cone tip, loosen and blow away the soil. Lab tests have demonstrated that this proboscis system has much greater excavation capability than a mole-based heat flow system, while it weighs about the same. Thermal sensors are attached along the stem and at the tip of the penetrating cone. Thermal conductivity is measured at the cone tip with a short (1- to 1.5-cm long) needle sensor containing a resistance temperature detector (RTD) and a heater wire. When it is inserted into the soil, the heater is activated. Thermal conductivity of the soil is obtained from the rate of temperature increase during the heating. By stopping during the excavation, it is possible to measure thermal conductivities at different depths. The gas jets are turned off when the penetrating cone reaches the target depth. Then, the stem pushes the needle sensor into the undisturbed soil at the bottom of the hole and carries out a thermal conductivity measurement. When the measurement is complete, the system resumes excavation. RTDs, placed along the stem at short (approx 30 cm) intervals, will monitor long-term temperature stability of the subsurface. Temperature in the shallow subsurface would fluctuate with the diurnal, annual, and precession cycles of the Moon. These thermal waves penetrate to different depths into the regolith. Longterm monitoring of the subsurface temperature would allow us to accurately delineate these cyclic signals and separate them from the signal associated with the outward flow of the Moon s endogenic heat. Further, temperature toward bottom of the 3-m hole should be fairly stable after the heat generated during the excavation dissipates into the surrounding soil. The geothermal gradient may be determined reliably from temperature measurements at the RTDs near the bottom. In order to minimize the heat conduction along the stem from affecting the geothermal gradient measurements, we plan to use low-conductive materials for the stem and develop a mechanism to achieve close coupling between the RTDs and the wall of the excavated hole.

Nagihara, Seiichi↗

Solar flare gamma-ray and hard x ray imaging with the GRID-on-a-balloon

A primary scientific objective for solar flare research during the rapidly approaching maximum in solar activity is the imaging of gamma-ray and hard x ray sources of solar flare emissions. These goals will be pursued by the Gamma Ray Imaging Device (GRID) instrument, one of three instruments recently selected for NASA's Max '91 Solar Balloon Program. The GRID instrument is based on the technique of Fourier transform imaging and utilizes scanning modulation grid collimator optics to provide full-Sun imaging with 1.9-arcsecond resolution over the energy range from 20 to 700 keV at time resolutions from 0.1 to 2 s. The GRID telescope will employ 32 subcollimators, each composed of a matched pair of high-Z collimator grids separated by 5.2 meters and a phoswich scintillation spectrometer detector having no spatial resolution. The subcollimators and integrally-mounted fine aspect system are contained within a telescope canister which will be pointed to 0.1 degree accuracy and cyclically scanned to produce source modulation. The 32 subcollimators provide a uniform distribution of grid slit orientations and a logarithmic distribution of slit spacings corresponding to angular dimensions of 1.9 arcseconds to several arcminutes. The instrument is several orders of magnitude more sensitive than the HXIS instrument on the Solar Maximum Mission (SMM) and nearly 10 times more sensitive than any similar instrument scheduled to fly during the next solar maximum. The payload, designed for long-duration high-altitude balloon capability, is scheduled for its first science flight (8 to 14 days duration) from the Antarctic in January of 1992.

Orwig, Larry E.↗

Membrane association of sucrose synthase: changes during the graviresponse and possible control by protein phosphorylation

Sucrose synthase (SuSy) plays an important role in sucrose degradation and occurs both as a soluble and as a membrane-associated enzyme in higher plants. We show that membrane association can vary in vivo in response to gravistimulation, apparently involving SuSy dephosphorylation, and is a reversible process in vitro. Phosphorylation of SuSy has little effect on its activity but decreases its surface hydrophobicity as reported with the fluorescent probe bis-ANS. We postulate that phosphorylation of SuSy (and perhaps other membrane proteins) is involved in the release of the membrane-bound enzyme in part as a result of decreased surface hydrophobicity.

Non-NASA Center↗

Opioid agonists binding and responses in SH-SY5Y cells

SH-SY5Y (human neuroblastoma) cultured cells, known to have mu-opioid receptors, have been used to assess and compare the ability of eight representative mu-selective compounds from diverse opioid families to recognize and activate these receptors. A wide range of receptor affinities spanning a factor of 10,000 was found between the highest affinity fentanyl analogs (Ki = 0.1nM) and the lowest affinity analog, meperidine (Ki = 1 microM). A similar range was found for inhibition of PGE1-stimulated cAMP accumulation with a rank order of activities that closely paralleled binding affinities. Maximum inhibition of cAMP accumulation by each compound was about 80%. Maximum stimulation of GTPase activity (approximately 50%) was also similar for all compounds except the lowest affinity meperidine. Both effects were naloxone reversible. These results provide further evidence that mu-receptors are coupled to inhibition of adenylate cyclase and that the SH-SY5Y cell line is a good system for assessment of mu-agonists functional responses.

Non-NASA Center↗

Human osteoblast-like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation

Exposure of osteosarcoma cell lines to chronic intermittent strain increases the activity of mechano-sensitive cation (SA-cat) channels. The impact of mechano-transduction on osteoblast function has not been well studied. We analyzed the expression and production of bone matrix proteins in human osteoblast-like osteosarcoma cells, OHS-4, in response to chronic intermittent mechanical strain. The OHS-4 cells exhibit type I collagen production, 1,25-Dihydroxyvitamin D-inducible osteocalcin, and mineralization of the extracellular matrix. The matrix protein message level was determined from total RNA isolated from cells exposed to 1-4 days of chronic intermittent strain. Northern analysis for type I collagen indicated that strain increased collagen message after 48 h. Immunofluorescent labeling of type I collagen demonstrated that secretion was also enhanced with mechanical strain. Osteopontin message levels were increased several-fold by the application of mechanical load in the absence of vitamin D, and the two stimuli together produced an additive effect. Osteocalcin secretion was also increased with cyclic strain. Osteocalcin levels were not detectable in vitamin D-untreated control cells. However, after 4 days of induced load, significant levels of osteocalcin were observed in the medium. With vitamin D present, osteocalcin levels were 4 times higher in the medium of strained cells compared to nonstrained controls. We conclude that mechanical strain of osteoblast-like cells is sufficient to increase the transcription and secretion of matrix proteins via mechano-transduction without hormonal induction.

NASA Discipline Number 40-40↗

Identification of Methanotrophic Biomarker Lipids in the Symbiont-Containing Gills of Seep Mussels

Mussels collected from hydrocarbon seeps in the Gulf of Mexico grow with methane as sole carbon and energy source due to a symbiotic association with methane-oxidizing bacteria. Transmission electron micrographs of mussel gills show cells with stacked intracytoplasmic membranes similar to type I methanotrophic bacteria. Methanotrophs are known to synthesize several types of cyclic triterpenes, hopanoids and methyl sterols, as well as unique monounsaturated fatty acid, double bond positional isomers that serve as biomarkers for this group. Lipid analysis of dissected mussels demonstrated the presence of these biomarkers predominantly in the gill tissue with much smaller amounts in mantle and remaining body tissues. Gill tissue contained 1150 micrograms/g dry wt. of hopanepolyol derivatives and diplopterol while the mantle tissue contained only 17 micrograms/g. The C16 monounsaturated fatty acids (16:1) characteristic of type I methanotrophic membranes dominated the gill tissue making up 53% of the total while only 5% 16:1 was present in the mantle tissue. The methyl sterol distribution was more dispersed. The predominant sterol in all tissues was cholesterol with lesser amounts of other desmethyl and 4-methyl sterols. The gill and mantle tissues contained 3461 micrograms (17% methyl) and 2750 micrograms (5% methyl) sterol per gm dry wt., respectively. Methyl sterol accounted for 44% of the sterol esters isolated from the gill, suggesting active demethylation of the methanotrophic sterols in this tissue. The use of lipid biomarkers could provide an effective means for identifying host-symbiont relationships.

Jahnke, L. L.↗

Iridium profile for 10 million years across the Cretaceous-Tertiary boundary at Gubbio (Italy)

The iridium anomaly at the Cretaceous-Tertiary (KT) boundary was discovered in the pelagic limestone sequence at Gubbio on the basis of 12 samples analyzed by neutron activation analysis (NAA) and was interpreted as indicating impact of a large extraterrestrial object at exactly the time of the KT mass extinction. Continuing controversy over the shape of the Ir profile at the Gubbio KT boundary and its interpretation called for a more detailed follow-up study. Analysis of a 57-meter-thick, 10-million-year-old part of the Gubbio sequence using improved NAA techniques revealed that there is only one Ir anomaly at the KT boundary, but this anomaly shows an intricate fine structure, the origin of which cannot yet be entirely explained. The KT Ir anomaly peaks in a 1-centimeter-thick clay layer, where the average Ir concentration is 3000 parts per trillion (ppt); this peak is flanked by tails with Ir concentrations of 20 to 80 ppt that rise above a background of 12 to 13 ppt. The fine structure of the tails is probably due in part to lateral reworking, diffusion, burrowing, and perhaps Milankovitch cyclicity.

Alvarez, Walter↗

Mechanotransduction and the functional response of bone to mechanical strain

Mechanotransduction plays a crucial role in the physiology of many tissues including bone. Mechanical loading can inhibit bone resorption and increase bone formation in vivo. In bone, the process of mechanotransduction can be divided into four distinct steps: (1) mechanocoupling, (2) biochemical coupling, (3) transmission of signal, and (4) effector cell response. In mechanocoupling, mechanical loads in vivo cause deformations in bone that stretch bone cells within and lining the bone matrix and create fluid movement within the canaliculae of bone. Dynamic loading, which is associated with extracellular fluid flow and the creation of streaming potentials within bone, is most effective for stimulating new bone formation in vivo. Bone cells in vitro are stimulated to produce second messengers when exposed to fluid flow or mechanical stretch. In biochemical coupling, the possible mechanisms for the coupling of cell-level mechanical signals into intracellular biochemical signals include force transduction through the integrin-cytoskeleton-nuclear matrix structure, stretch-activated cation channels within the cell membrane, G protein-dependent pathways, and linkage between the cytoskeleton and the phospholipase C or phospholipase A pathways. The tight interaction of each of these pathways would suggest that the entire cell is a mechanosensor and there are many different pathways available for the transduction of a mechanical signal. In the transmission of signal, osteoblasts, osteocytes, and bone lining cells may act as sensors of mechanical signals and may communicate the signal through cell processes connected by gap junctions. These cells also produce paracrine factors that may signal osteoprogenitors to differentiate into osteoblasts and attach to the bone surface. Insulin-like growth factors and prostaglandins are possible candidates for intermediaries in signal transduction. In the effector cell response, the effects of mechanical loading are dependent upon the magnitude, duration, and rate of the applied load. Longer duration, lower amplitude loading has the same effect on bone formation as loads with short duration and high amplitude. Loading must be cyclic to stimulate new bone formation. Aging greatly reduces the osteogenic effects of mechanical loading in vivo. Also, some hormones may interact with local mechanical signals to change the sensitivity of the sensor or effector cells to mechanical load.

Non-NASA Center↗

Non-Invasive Investigation of Bone Adaptation in Humans to Mechanical Loading

Experimental studies have identified peak cyclic forces, number of loading cycles, and loading rate as contributors to the regulation of bone metabolism. We have proposed a theoretical model that relates bone density to a mechanical stimulus derived from average daily cumulative peak cyclic 'effective' tissue stresses. In order to develop a non-invasive experimental model to test the theoretical model we need to: (1) monitor daily cumulative loading on a bone, (2) compute the internal stress state(s) resulting from the imposed loading, and (3) image volumetric bone density accurately, precisely, and reproducibly within small contiguous volumes throughout the bone. We have chosen the calcaneus (heel) as an experimental model bone site because it is loaded by ligament, tendon and joint contact forces in equilibrium with daily ground reaction forces that we can measure; it is a peripheral bone site and therefore more easily and accurately imaged with computed tomography; it is composed primarily of cancellous bone; and it is a relevant site for monitoring bone loss and adaptation in astronauts and the general population. This paper presents an overview of our recent advances in the areas of monitoring daily ground reaction forces, biomechanical modeling of the forces on the calcaneus during gait, mathematical modeling of calcaneal bone adaptation in response to cumulative daily activity, accurate and precise imaging of the calcaneus with quantitative computed tomography (QCT), and application to long duration space flight.

Whalen, R.↗

Preference for internucleotide linkages as a function of the number of constituents in a mixture

Phosphoimidazolide-activated ribomononucleotides (*pN; see Scheme I) are useful substrates for the nonenzymatic synthesis of oligonucleotides. In the presence of metal ions dilute neutral aqueous solutions of *pN (0.01 M) typically yield only small amounts of dimers and traces of oligomers; most of *pN hydrolyzes to yield nucleoside 5'-monophosphate (5'NMP). An earlier investigation of *pN reactions in highly concentrated aqueous solutions (up to 1.4 M) showed, as expected, that the percentage yield of the condensation products increases and the yield of the hydrolysis product correspondingly decreases with *pN concentration (Kanavarioti 1997). Here we report product distributions in reactions with one, two, or three reactive components at the same total nucleotide concentration. *pN used as substrates were the nucleoside 5'-phosphate 2-methylimidazolides, 2-MeImpN, with N = cytidine (C), uridine (U), or guanosine (G). Reactions were conducted as self-condensations, i. e., one nucleotide only, with two components in the three binary U,C, U,G, and C,G mixtures, and with three components in the ternary U,C, G mixture. The products are 5'NMP, 5',5'-pyrophosphate-, 2',5'-, 3', 5'-linked dimers, cyclic dimers, and a small percentage of longer oligomers. The surprising finding was that, under identical conditions, including the same total monomer concentration, the product distribution differs substantially from one reaction to another, most likely due to changing intermolecular interactions depending on the constituents. Even more unexpected was the observed trend according to which reactions of the U,C,G mixture produce the highest yield of internucleotide-linked dimers, whereas the self-condensations produce the least and the reactions with the binary mixtures produce yields that fall in between. What is remarkable is that the approximately two-fold increase in the percentage yield of internucleotide-linked dimers is not due to a concentration effect or a catalyst, but to the increased complexity of the system from a single to two and three components. These observations, perhaps, provide an example of how increased complexity in relatively simple chemical systems leads to organization of the material and consequently to chemical evolution. A possible link between prebiotic chemistry and the postulated RNA world is discussed.

NASA Discipline Exobiology↗

Rapid tachyphylaxis to hemodynamic effects of PACAP-27 after inhibition of nitric oxide synthesis

The vasodilator effects of pituitary adenylate cyclase-activating polypeptide (PACAP)-27 are subject to tachyphylaxis in rats treated with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). We examined whether this tachyphylaxis could be prevented by administration of the putative endothelium-derived nitrosyl factor S-nitroso-L-cysteine (L-SNC) and whether L-SNC may exert its effects via increases in cGMP levels in vascular smooth muscle. Five doses of PACAP-27 (2 nmol/kg iv) produced pronounced vasodilator responses in saline-treated rats. These responses were not subject to tachyphylaxis. The first injection of PACAP-27 (2 nmol/kg iv) in L-NAME-treated (50 micromol/kg iv) rats produced vasodilator responses similar to those in saline-treated rats, whereas subsequent injections produced progressively smaller responses. The injection of L-SNC (1,200 nmol/kg iv) before each injection of PACAP-27 prevented tachyphylaxis to the Gs protein-coupled receptor agonist in L-NAME-treated rats, whereas equihypotensive doses of the NO donor sodium nitroprusside (100 micrograms/kg iv) did not. The injection of the membrane-permeant cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-CPT-cGMP; 30 micromol/kg iv) to L-NAME-treated rats restored resting hemodynamic values to pre-L-NAME levels but did not prevent the development of tachyphylaxis to PACAP-27. These results suggest that nitrosyl factors prevent the development of tachyphylaxis to the hemodynamic actions of PACAP-27. These nitrosyl factors may act independently of their ability to generate cGMP in vascular smooth muscle.

NASA Discipline Regulatory Physiology↗

The Effects of Spaceflight on the Rat Circadian Timing System

Two fundamental environmental influences that have shaped the evolution of life on Earth are gravity and the cyclic changes occurring over the 24-hour day. Light levels, temperature, and humidity fluctuate over the course of a day, and organisms have adapted to cope with these variations. The primary adaptation has been the evolution of a biological timing system. Previous studies have suggested that this system, named the circadian (circa - about; dies - a day) timing system (CTS), may be sensitive to changes in gravity. The NASA Neurolab spaceflight provided a unique opportunity to evaluate the effects of microgravity on the mammalian CTS. Our experiment tested the hypotheses that microgravity would affect the period, phasing, and light sensitivity of the CTS. Twenty-four Fisher 344 rats were exposed to 16 days of microgravity on the Neurolab STS-90 mission, and 24 Fisher 344 rats were also studied on Earth as one-G controls. Rats were equipped with biotelemetry transmitters to record body temperature (T(sub b)) and heart rate (HR) continuously while the rats moved freely. In each group, 18 rats were exposed to a 24-hour light-dark (LD 12:12) cycle, and six rats were exposed to constant dim red-light (LL). The ability of light to induce a neuronal activity marker (c-fos) in the circadian pacemaker of the brain, the suprachiasmatic nucleus (SCN), was examined in rats studied on flight days two (FD2) and 14 (FD14), and postflight days two (R+1) and 14 (R+13). The flight rats in LD remained synchronized with the LD cycle. However, their T(sub b), rhythm was markedly phase-delayed relative to the LD cycle. The LD flight rats also had a decreased T(sub b) and a change in the waveform of the T(sub b) rhythm compared to controls. Rats in LL exhibited free-running rhythms of T(sub b), and HR; however, the periods were longer in microgravity. Circadian period returned to preflight values after landing. The internal phase angle between rhythms was different in flight than in one-G. Compared with control rats, the flight rats exhibited no change in HR. Finally, the LD FD2 flight rats demonstrated a reduced sensitivity to light as shown by significantly reduced c-fos expression in the SCN in comparison with controls. These findings constitute the first demonstration that microgravity affects the fundamental properties of the mammalian circadian timing system, specifically by influencing the clock's period, and its ability to maintain temporal organization and phase angle of synchronization to an external LD cycle.

Fuller, Charles A.↗

A Comparison of Potential IM-CW Lidar Modulation Techniques for ASCENDS CO2 Column Measurements From Space

Global atmospheric carbon dioxide (CO2) measurements through the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) Decadal Survey recommended space mission are critical for improving our understanding of CO2 sources and sinks. IM-CW (Intensity Modulated Continuous Wave) lidar techniques are investigated as a means of facilitating CO2 measurements from space to meet the ASCENDS science requirements. In previous laboratory and flight experiments we have successfully used linear swept frequency modulation to discriminate surface lidar returns from intermediate aerosol and cloud contamination. Furthermore, high accuracy and precision ranging to the surface as well as to the top of intermediate clouds, which is a requirement for the inversion of the CO2 column-mixing ratio from the instrument optical depth measurements, has been demonstrated with the linear swept frequency modulation technique. We are concurrently investigating advanced techniques to help improve the auto-correlation properties of the transmitted waveform implemented through physical hardware to make cloud rejection more robust in special restricted scenarios. Several different carrier based modulation techniques are compared including orthogonal linear swept, orthogonal non-linear swept, and Binary Phase Shift Keying (BPSK). Techniques are investigated that reduce or eliminate sidelobes. These techniques have excellent auto-correlation properties while possessing a finite bandwidth (by way of a new cyclic digital filter), which will reduce bias error in the presence of multiple scatterers. Our analyses show that the studied modulation techniques can increase the accuracy of CO2 column measurements from space. A comparison of various properties such as signal to noise ratio (SNR) and time-bandwidth product are discussed.

Campbell, Joel F.↗

Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in treating neurodegenerative disorders.

Sroufe, Angela E.↗

Fertilization of sea urchin eggs and sperm motility are negatively impacted under low hypergravitational forces significant to space flight

Sperm and other flagellates swim faster in microgravity (microG) than in 1 G, raising the question of whether fertilization is altered under conditions of space travel. Such alterations have implications for reproduction of plant and animal food and for long-term space habitation by man. We previously demonstrated that microG accelerates protein phosphorylation during initiation of sperm motility but delays the sperm response to the egg chemotactic factor, speract. Thus sperm are sensitive to changes in gravitational force. New experiments using the NiZeMi centrifugal microscope examined whether low hypergravity (hyperG) causes effects opposite to microG on sperm motility, signal transduction, and fertilization. Sperm % motility and straight-line velocity were significantly inhibited by as little as 1.3 G. The phosphorylation states of FP130, an axonemal phosphoprotein, and FP160, a cAMP-dependent salt-extractable flagellar protein, both coupled to motility activation, showed a more rapid decline in hyperG. Most critically, hyperG caused an approximately 50% reduction in both the rate of sperm-egg binding and fertilization. The similar extent of inhibition of both fertilization parameters in hyperG suggests that the primary effect is on sperm rather than eggs. These results not only support our earlier microG data demonstrating that sperm are sensitive to small changes in gravitational forces but more importantly now show that this sensitivity affects the ability of sperm to fertilize eggs. Thus, more detailed studies on the impact of space flight on development should include studies of sperm function and fertilization.

NASA Discipline Developmental Biology↗