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Ergometric evaluation of pathological gait.

At each step of walking, the center of gravity of the body moves up and down and accelerates and decelerates forward with a combined movement that allows an appreciable transfer (R) between gravitational potential energy and kinetic energy, as occurs in a pendulum. The positive work and power to lift the center of gravity, to accelerate it forward, and to maintain its motion in a sagittal plane, the amount of R, the maximal height reached during each step by the center of gravity, and the step length and frequency are all determined by a microcomputer a few minutes after a subject walks on a force platform. This method is applied to the analysis of pathological gait in the attempt to measure quantitatively the alteration of the normal locomotory movement of the center of gravity. The strides of the patient are compared with the strides of normal subjects; in addition, the movement of the center of gravity of the patient during the stance on the affected limb is compared with the movement of the center of gravity during the stance on the unaffected limb, thus giving an index of the asymmetry of locomotion.

Adult↗

Resting energy expenditure of rats acclimated to hypergravity.

BACKGROUND: The use of centrifugation at 1 G has been advocated as a control condition during spaceflight and as a countermeasure to compensate for the adverse effects of spaceflight. Rodents are the primary animal model for the study of the effects of spaceflight and will be used in the evaluation of centrifugation as a countermeasure and means of control at 1 G during flight. HYPOTHESIS: The present study was designed to assess whether resting energy expenditure (EER) of male rats was increased in relation to the magnitude of the level of gravity to which the animals were exposed. The influence of body mass and age on resting energy expenditure (EER) of male rats (n = 42, age 40-400 d) was determined following 2 wk of acclimation to 1, 2.3, or 4.1 G. Hypergravity environments were created by centrifugation. Measurements were made at the gravity level to which the animal was acclimated and during the lights-on period. RESULTS: In rats matched for body mass (approximately 400 g), mean O2 consumption and CO2 production were higher (18% and 27%, respectively) in the 2.3- and 4.1 -G groups than controls. Mean respiratory exchange ratio (RER) increased from 0.80 to 0.87. EER was increased from 47 +/- 0.1 kcal x d(-1) at 1 G, to 57 +/- 1.5 and 58 +/- 2.2 kcal x d(-1) at 2.3 and 4.1 G, respectively. There was no difference in EER between the hypergravity groups. When age differences were considered, EER (kcal x kg(-1) x d(-1)) with increased gravity was 40% higher than at 1 G. The increase in EER was not proportional over gravity levels. CONCLUSION: Acclimation of rats to hypergravity increases their EER, dependent on body mass and age, and may alter substrate metabolism. The increase in EER was not related to the level of gravity increase.

Adaptation, Physiological↗

Gravity-dependent and gravity-independent gain changes during vertical vestibulo-ocular reflex (VOR) adaptation.

The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adaptively increased or decreased with monkeys in a side down position, and the gains were tested with the axis of rotation tilted in 10 degrees increments from left- to right-side-down. Gain changes, expressed as a percentage of the preadapted values, were plotted as a function of head tilt, and fit with a cosine function. The amplitude of the cosine was half of the gravity-dependent component of the gain change and the bias, the gravity independent component. The largest changes in the gain of both components occurred in the first 30 min and continued at a slower rate throughout adaptation. The gravity-dependent and -independent gain changes were larger for gain decreases than for gain increases, but both components had similar dynamics. We conclude that the alteration in gain of the aVOR always occurs in the context of gravity.

Adaptation, Physiological↗

Microgravity and bone cell mechanosensitivity.

The capacity of bone tissue to alter its mass and structure in response to mechanical demands has long been recognized but the cellular mechanisms involved remained poorly understood. Bone not only develops as a structure designed specifically for mechanical tasks, but it can adapt during life toward more efficient mechanical performance. Mechanical adaptation of bone is a cellular process and needs a biological system that senses the mechanical loading. The loading information must then be communicated to the effector cells that form new bone or destroy old bone. The in vivo operating cell stress derived from bone loading is likely the flow of interstitial fluid along the surface of osteocytes and lining cells. The response of bone cells in culture to fluid flow includes prostaglandin (PG) synthesis and expression of prostaglandin G/H synthase inducible cyclooxygenase (COX-2). Cultured bone cells also rapidly produce nitric oxide (NO) in response to fluid flow as a result of activation of endothelial nitric oxide synthase (ecNOS), which enzyme also mediates the adaptive response of bone tissue to mechanical loading. Earlier studies have shown that the disruption of the actin-cytoskeleton abolishes the response to stress, suggesting that the cytoskeleton is involved in cellular mechanotransduction. Microgravity, or better near weightlessness, is associated with the loss of bone in astronauts, and has catabolic effects on mineral metabolism in bone organ cultures. This might be explained as resulting from an exceptional form of disuse under near weightlessness conditions. However, under near weightlessness conditions the assembly of cytoskeletal elements may be altered since it has been shown that the direction of the gravity vector determines microtubular pattern formation in vivo. We found earlier that the transduction of mechanical signals in bone cells also involves the cytoskeleton and is related to PGE2 production. Therefore it is possible that the mechanosensitivity of bone cells is altered under near weightlessness conditions, and that this abnormal mechanosensation contributes to disturbed bone metabolism observed in astronauts. In our current project for the International Space Station, we wish to test this hypothesis experimentally using an in vitro model. The specific aim of our research project is to test whether near weightlessness decreases the sensitivity of bone cells for mechanical stress through a decrease in early signaling molecules (NO, PGs) that are involved in the mechanical loading-induced osteogenic response. Bone cells are cultured with or without gravity prior to and during mechanical loading, using our modified in vitro oscillating fluid flow apparatus. In this "FlowSpace" project we are developing a cell culture module that is used to provide further insight in the mechanism of mechanotransduction in bone.

Animals↗

Gravity and light effects on the circadian clock of a desert beetle, Trigonoscelis gigas.

Circadian function is affected by exposure to altered ambient force environments. Under non-earth gravitational fields, both basic features of circadian rhythms and the expression of the clock responsible for these rhythms are altered. We examined the activity rhythm of the tenebrionid beetle, Trigonoscelis gigas, in conditions of microgravity (microG; spaceflight), earth's gravity (1 G) and 2 G (centrifugation). Data were recorded under a light-dark cycle (LD), constant light (LL), and constant darkness (DD). Free-running period (tau) was significantly affected by both the gravitational field and ambient light intensity. In DD, tau was longer under 2 G than under either 1 G or microG. In addition, tauLL was significantly different from tauDD under microG and 1 G, but not under 2 G.

Animals↗

Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat).

Alteration in cytoskeletal organization appears to underlie mechanisms of gravity sensitivity in space-flown cells. Human T lymphoblastoid cells (Jurkat) were flown on the Space Shuttle to test the hypothesis that growth responsiveness is associated with microtubule anomalies and mediated by apoptosis. Cell growth was stimulated in microgravity by increasing serum concentration. After 4 and 48 h, cells filtered from medium were fixed with formalin. Post-flight, confocal microscopy revealed diffuse, shortened microtubules extending from poorly defined microtubule organizing centers (MTOCs). In comparable ground controls, discrete microtubule filaments radiated from organized MTOCs and branched toward the cell membrane. At 4 h, 30% of flown, compared to 17% of ground, cells showed DNA condensation characteristic of apoptosis. Time-dependent increase of the apoptosis-associated Fas/ APO-1 protein in static flown, but not the in-flight 1 g centrifuged or ground controls, confirmed microgravity-associated apoptosis. By 48 h, ground cultures had increased by 40%. Flown populations did not increase, though some cells were cycling and actively metabolizing glucose. We conclude that cytoskeletal alteration, growth retardation, and metabolic changes in space-flown lymphocytes are concomitant with increased apoptosis and time-dependent elevation of Fas/APO-1 protein. We suggest that reduced growth response in lymphocytes during spaceflight is linked to apoptosis.

Apoptosis↗

Defects in root development and gravity response in the aem1 mutant of rice are associated with reduced auxin efflux.

The phytohormone auxin is involved in the regulation of a variety of developmental processes. In this report, we describe how the processes of lateral root and root hair formations and root gravity response in rice are controlled by auxin. We use a rice mutant aem1 (auxin efflux mutant) because the mutant is defective in these characters. The aem1 line was originally isolated as a short lateral root mutant, but we found that the mutant has a defect in auxin efflux in roots. The acropetal and basipetal indole-3-acetic acid (IAA) transports were reduced in aem1 roots compared to wild type (WT). Furthermore, gravitropic bending as well as efflux of radioactive IAA was impaired in the mutant roots. We also propose a unique distribution of endogenous IAA in aem1 roots. An immunoassay revealed a 4-fold-endogenous IAA content in the aem1 roots compared to WT, and the application of IAA to the shoot of WT seedlings mimicked the short lateral root phenotype of aem1, suggesting that the high content of IAA in aem1 roots impaired the elongation of lateral roots. However, the high level of IAA in aem1 roots contradicts the auxin requirement for root hair formation in the epidermis of mutant roots. Since the reduced development in root hairs of aem1 roots was rescued by exogenous auxin, the auxin level in the epidermis is likely to be sub-optimum in aem1 roots. This discrepancy can be solved by the ideas that IAA level is higher in the stele and lower in the epidermis of aem1 roots compared to WT and that the unique distribution of IAA in aem1 roots is induced by the defect in auxin efflux. All these results suggest that AEM1 may encode a component of auxin efflux carrier in rice and that the defects in lateral roots, root hair formation and root gravity response in aem1 mutant are due to the altered auxin efflux in roots.

Biological Transport↗

Gravity in a lattice Boltzmann model

In this paper we consider the introduction of a body force, in the incompressible limit, into the lattice Boltzmann model. A number of methods are considered and their suitability to our objectives determined. When there is no density variation across the fluid, gravity can be introduced in the form of an altered pressure gradient. This method correctly satisfies the Navier-Stokes equation; however, if there is a non-negligible density variation present (produced by the body force or otherwise) this method becomes less accurate as the density variation increases and the constant density approximation becomes less valid. Three other methods are also considered for application when there is a non-negligible density variation. The equations of motion satisfied by these models are found up to second order in the Knudsen number and it is seen that only one of these methods satisfies the true Navier-Stokes equation. Numerical simulations are performed to compare the different models and to assess the range of application of each.

Journal Article↗

Altered TNF-alpha, glucose, insulin, and amino acids in islets of Langerhans cultured in a microgravity model system.

The present studies were designed to determine effects of a microgravity model system upon lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) activity and indexes of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1,726 +/- 117, 150 islet equivalent units) from Wistar-Furth rats were treated as 1) high aspect ratio vessel (HARV) cell culture, 2) HARV plus LPS, 3) static culture, and 4) static culture plus LPS. TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures; yet the increase was more pronounced in the static culture group (P < 0.05). A decrease in insulin concentration was demonstrated in the LPS-stimulated HARV culture (P < 0.05). We observed a greater glucose concentration and increased disappearance of arginine in islets cultured in HARVs. Although nitrogenous compound analysis indicated a ubiquitous reliance on glutamine in all experimental groups, arginine was converted to ornithine at a twofold greater rate in the islets cultured in the HARV microgravity model system (P < 0.05). These studies demonstrate alterations in LPS-induced TNF-alpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV. These alterations in fuel homeostasis may be promulgated by gravity-averaged cell culture methods or by three-dimensional cell assembly.

Amino Acids↗

Mammalian cell cultivation in space.

In order to study the effect of microgravity on mammalian cell growth, proliferation and biosynthesis, the human T leukemia cells, human lung adenocarcinoma cells, EVI-H1 hybridoma cells and genetic engineering cells producing human growth hormone were flown on re-entry Scientific Satellite 90105 for a duration of eight days. The preliminary results indicate that the mammalian cells are sensitive to gravity. They might adapt to microgravity conditions leading to altered growth rate and subsequently, to altered biosynthesis and molecular secretion. In addition, their morphology may be affected in microgravity.

Adenocarcinoma↗

Critical path plan for food and nutrition research required for planetary exploration missions.

In preparation for future planetary exploration, NASA-Johnson Space Center has developed a critical path plan for food and nutrition research needs. The plan highlights the risk factors pertaining to food and nutrition associated with exposure to the space flight environment as well as the possible consequences if no corrective measures are implemented. Included in the plan are the initiating events such as microgravity, remote environment and mission duration, which obviously impact the risk factors. The plan includes points of intervention where mitigating factors can be implemented to avoid outcomes such as malnutrition and unsafe foods. Physiological changes induced by lack of gravity, as well as increased exposure to radiation, may alter nutrient bio-availability, and/or nutrient requirements. An inadequate food system, whether due to technical limitations or nutritional shortcomings, can result in serious consequences. Additionally, microbial and chemical food contamination or psychological factors such as depression may lead to insufficient food intake. Critical questions define areas where further research is required to eliminate or ameliorate the risk from each of those factors. These questions delineate priorities for NASA food and nutrition research for planetary exploration missions.

Aerospace Medicine↗

[Lymphangion in health and in lymphedema].

Comparative analysis of lymphangion construction in different organs and sites of human body is performed. Quantitative parameters of lymphangions (length, width, volume) are found to have age and site peculiarities. Myo-myocyte contacts of the nexus type and fascicular-reticular organizational principle of the cells underly myocyte association into functional syncytium. The valve consists of a muscleless fold and valvular bolster containing muscles. Restructuring of lymphangions in lower limb lymphedema are observed. In the course of the disease progression myocyte atrophy occurs which is followed by lymphangion wall collagenization. The alterations in lower limb lymphangions are proportional to the gravity of the disease.

Aging↗

Protein composition in human plasma after long-term orbital missions and in rodent plasma after spaceflights on biosatellites "Cosmos-1887" and "Cosmos-2044".

The two-dimensional plasma protein map of crewmembers of long-duration "Mir" expeditions obtained the day after the recovery shows a manifold increase in the content of several proteins normally seen in trace amounts. The emergence of several unusual protein spots occurs as well, some of them probably due to charge shifts provided by the events influencing posttranslational modification processes. By the 8 postflight day these phenomena were disappeared. In the "Cosmos-1887" biosatellite experiment, the plasma samples obtained two days after the landing as well as plasma of synchronous animals exhibited the higher fibrinogen levels when compared to those of vivarium animals. The protein consisting of a number of fractions with molecular weight of 50 to 60 kD and pI 5 to 6 had protein spots of similar size in flight and synchronous animals while in vivarium rats one of the spots was larger in size as opposed to the others. The plasma protein spectrum of flight and synchronous groups of animals in "Cosmos-1887" experiment where plasma samples were prepared in the period of time from 5 to 10 hours after spaceflight coincided with the pattern of vivarium animals. The data suggest that the protein changes described above develop during postflight period and accelerations, vibrations, readaptation to 1 G gravity, emotional stress could be the cause of these alterations.

Animals↗

[Evaluation of the cephalometric structure of the upper airway on the configuration of the obstructive sleep apnea syndrome].

Thirty aleatory patients polysomnographically diagnosed as sleep apnea syndrome (SAOS) with an apnea-hypoapnea index (AHI) accounting for 61.3 +/- 31.1 were, bipedal and in decubitus, cephalometrically explored, aiming at establish the correlation between the cephalometric quantum of the upper airway and the anthropomorphic and polysomnographic parameters clearly establishing the syndrome. The weak correlation confirmed among the AHI and the back passage in decubitus (PASDEC), even between the nocturnal oxymetric nadir and the length of the palate, advice against considering the gravity of the OSAS as sole function of the altered cephalometric degree checked in the test.

Adult↗

Mutations in the SGR4, SGR5 and SGR6 loci of Arabidopsis thaliana alter the shoot gravitropism.

Shoots of higher plants grow upward in response to gravity. To elucidate the molecular mechanism of this response, we have isolated shoot gravitropism (sgr) mutants in Arabidopsis thaliana. In this report, we describe three novel mutants, sgr4-1, sgr5-1 and sgr6-1 whose inflorescence stems showed abnormal gravitropic responses as previously reported for sgr1, sgr2 and sgr3. These new sgr mutations were recessive and occurred at three independent genetic loci. The sgr4-1 mutant showed severe defect in gravitropism of both inflorescence stem and hypocotyl but were normal in root gravitropism as were sgr1 and sgr2. The sgr5-1 and sgr6-1 mutants showed reduced gravitropism only in inflorescence stems but normal in both hypocotyls and roots as sgr3. These results support the hypothesis that some mechanisms of gravitropism are genetically different in these three organs in A. thaliana. In addition, these mutants showed normal phototropic responses, suggesting that SGR4, SGR5 and SGR6 genes are specifically involved in gravity perception and/or gravity signal transduction for the shoot gravitropic response.

Arabidopsis↗

Choroidal readaptation to gravity in rats after spaceflight and head-down tilt.

To determine when choroidal structures were restored after readaptation to Earth gravity or orthostatic position, fine structure and protein distribution were studied in rat choroid plexus dissected either 6 h [Space Life Sciences-2 (SLS-2) experiments] or 2 days [National Institutes of Health-Rodent 1 (NIH-R1) experiments] after a spaceflight, or 6 h after head-down tilt (HDT) experiments. Apical alterations were noted in choroidal cells from SLS-2 and HDT animals, confirming that weightlessness impaired choroidal structures and functions. However, the presence of small apical microvilli and kinocilia and the absence of vesicle accumulations showed that the apical organization began to be restored rapidly after landing. Very enlarged apical microvilli appeared after 2 days on Earth, suggesting increased choroidal activity. However, as distributions of ezrin and carbonic anhydrase II remained altered in both flight and suspended animals after readaptation to Earth gravity, it was concluded that choroidal structures and functions were not completely restored, even after 2 days in Earth's gravity.

Adaptation, Physiological↗

Shifts in blood volume alter the perception of posture.

Recent experiments have shown that somatic graviceptors exist in humans. Traditionally, extravestibular gravity information has been thought to originate from mechanoreceptors in the joints, muscles and skin. Experiments with normal, paraplegic and nephrectomized subjects revealed that the kidneys and the cardiovascular system are involved in providing truncal gravity information. The present study intends to determine the influence of shifts in body fluid, especially of the distribution of blood along the subjects' spinal (Z-) axis, on the perception of posture. To this end, the distribution of body fluids was altered by means of the technique of lower body negative and positive pressure (LBNP and LBPP). LBNP leads to venous pooling of blood in the legs, whereas LBPP prevents venous blood from pooling, increasing central volume. Changes in blood distribution were measured by segmental impedance cardiography for four body segments: the upper torso (thoracic cavity), lower torso (abdominal and pelvic region), thigh and calf. Seventeen healthy subjects (mean age: 27.3 years) participated in the experiment. They were positioned on the side (right-ear-down head position) on a tilt table which the subjects and the experimenter could tilt via remote control around an axis parallel to the subjects' visual (X-) axis. The experimenter set the initial tilt in total darkness to arbitrary angles while strictly alternating between head-up and head-down tilts. Subjects were then asked to rotate the board until they felt they were in a horizontal posture. Means and variances of eight pairs of settings were taken as a measure of the subjective horizontal posture (SHP). During LBNP (-30 mmHg), subjects perceived being tilted head-up, whereas LBPP (+30 mmHg) led them to feel tilted head-down. The results corroborate the hypothesis of an effect of the blood's mass on graviception and also indicate supplementary contributions of other visceral afferences.

Adult↗

Knee loads in the standard and recumbent cycling positions.

The recumbent cycling position (RCP) has become increasingly popular in recent years as a mode of exercise and rehabilitation. However, subtle, but important, differences are expected to exist between the RCP and the standard, upright cycling position (SCP). The differences are due primarily to the altered orientation of the rider's lower extremities relative to gravity. In order to determine if one cycling position may be preferential to another for certain types of rehabilitation, knee loads from a planar, inverse-dynamics model were examined. Nineteen recreational cyclists (24.6 +/- 4.2 yrs) were acclimated to recumbent cycling prior to measuring kinetics and kinematics in both a RCP and SCP (90 rpm; 250 W; max hip-to-pedal distance = 105% leg length). Significance was set at p [symbol: see text] 0.01. Lower-extremity kinematics were not different between the two positions, suggesting that muscle, ligament, and supporting structures travel through the same ranges of motion in both forms of cycling. However, the anterior/posterior forces were altered in such a way that the magnitude of the forces tending to displace the tibia anterior relative to the femur were significantly reduced in the RCP, suggesting that less load may be placed on the anterior cruciate ligament (ACL) while recumbent cycling. No changes in the tension/compression forces were observed at the knee, suggesting no differences in knee stability resulting from compressive forces between the tibia and femur. These findings indicate that the RCP may be beneficial when attempting to minimize ACL loads while utilizing cycling as an exercise and rehabilitative modality.

Adult↗