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At least 163 records · Page 9

Loss of Mitochondrial Tusc2/Fus1 Triggers a Brain Pro-Inflammatory Microenvironment and Early Spatial Memory Impairment

Brain pathological changes impair cognition early in disease etiology. There is an urgent need to understand aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2 is a mitochondrial-resident protein regulating Ca 2+ fluxes to and from mitochondria impacting overall health. We previously reported that Tusc2 –/– female mice develop chronic inflammation and age prematurely, causing age- and sex-dependent spatial memory deficits at 5 months old. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in 4-month-old mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2 –/– female mice demonstrated a pro-inflammatory increase in astrocytes, expression of IFN-γ in CD4 + T cells and Granzyme-B in CD8 + T cells. We also found fewer FOXP3 + T-regulatory cells and Ly49G + NK and Ly49G + NKT cells in female Tusc2 –/– brains, suggesting a dampened anti-inflammatory response. Moreover, Tusc2 –/– hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2 + dynamics. Overall, the data suggest that dysregulation of Ca 2+ -dependent processes and a heightened pro-inflammatory brain microenvironment in Tusc2 –/– mice could underlie cognitive impairment. Thus, strategies to modulate the mitochondrial Tusc2- and Ca 2+ - signaling pathways in the brain should be explored to improve cognitive health.

59 BASIC BIOLOGICAL SCIENCES↗

Experimental investigation of the visual field dependency in the erect and supine positions

The increasing utilization of simulators in many fields, in addition to aeronautics and space, requires the efficient use of these devices. It seemed that personnel highly influenced by the visual scene would make desirable subjects, particularly for those simulators without sufficient motion cues. In order to evaluate this concept, some measure of the degree of influence of the visual field on the subject in necessary. As part of this undertaking, 37 male and female subjects, including eight test pilots, were tested for their visual field dependency or independency. A version of Witkin's rod and frame apparatus was used for the tests. The results showed that nearly all the test subjects exhibited some degree of field dependency, the degree varying from very high field dependency to nearly zero field dependency in a normal distribution. The results for the test pilots were scattered throughout a range similar to the results for the bulk of male subjects. The few female subjects exhibited a higher field dependency than the male subjects. The male subjects exhibited a greater field dependency in the supine position than in the erect position, whereas the field dependency of the female subjects changed only slightly.

Lichtenstein, J. H.↗

Molding apparatus

Apparatus for compression molding of thermosetting plastics compositions including interfitting hollow male and female components is reported. The components are adapted to be compressed to form a rocket nozzle in a cavity. A thermal jacket is provided exteriorly adjacent to the female component for circulating a thermal transfer fluid to effect curing of a thermosetting plastics material being molded. Each of the male and female components is provided with suitable inlets and outlets for circulating a thermal transfer fluid.

Heier, W. C.↗

Bone mineral content in normal US whites

Photon absorptiometry with I-125 was used to measure the bone mineral content and the bone width on 763 children between the ages of 5 and 19 years, on 538 adults between the ages of 20 and 49 years, and on 550 adults over the age of 50 years. Measurements were made on the midshaft and the distal end of the radius and the ulna, and on the humerus midshaft. This has permitted analysis of annual bone growth in children, and the rate of change in elderly adults per decade. Male and female children grew at about the same rate until adolescence. After adolescence females grew at a slow rate until the mid-twenties, while males reached adult mineralization by age 20. Males remained relatively constant until the fifties, and females began their decline in the forties.

Mazess, R. B.↗

Cardiovascular responses of men and women to lower body negative pressure

Changes in blood flow and blood redistribution were measured by impedance plethysmography in the pelvic and leg regions of six male and four female subjects during three 5-min exposures to -20, -40, and -60 mm Hg lower body negative pressure (LBNP). Female subjects demonstrated significantly higher mean heart rate and lower leg blood flow indices than the male subjects during the recumbent control periods. Men had slightly higher mean resting systolic and diastolic blood pressures and higher mean control pelvic blood indices. Women demonstrated significantly less blood pooling in the legs and slightly less in the pelvic region than the men. All of the 18 tests with male subjects at -60 mm Hg were completed without initial signs of syncope, while only two of the tests with women were completed successfully without the subject exhibiting presyncopal conditions. Results indicate that impedance plethysmography can be used to measure segmental cardiovascular responses during LBNP and that females may be less tolerant to -60 mm Hg LBNP than males.

Montgomery, L. D.↗

Femoral development in chronically centrifuged rats

Groups of 30-d-old male and female rats were centrifuged at 2.00 G (RE, Rotation Experimental), 1.05 G (RC, Rotation Control) or exposed to the noise and wind of the centrifuge at 1.00 G (EC, Earth Control) for periods of 1, 2, 4, 8, and 16 weeks. Measurements of their femurs indicated that exposure to centrifugation a) decreased femoral length in RE animals, b) increased femoral length in RC animals, c) reduced femoral diameter in RE and RC animals, d) increased L/D ratios in RC animals, e) decreased L/D ratios in RE animals, f) increased femur length/body weight in RE animals, g) decreased cortical thickness (CT) in RE animals, h) increased relative CT in RE animals, and decreased it in RC animals, i) accelerated ossification in RC femoral heads, j) thinned and distorted RE epiphyseal plates, and k) thickened condylar cartilage in RE females. The effects tended to be strongly sexually dimorphic, with females more severely affected by the stress than males.

Smith, S. D.↗

Experiment K-313: Rat and quail ontogenesis

The potential effects of spaceflight on the processes of mammalian fertilizaton, implantation and embryonic development are investigated. Five female and two male rats were placed together on Day 2 of the flight. By R+17, it was determined that both flight and synchronous females were not carrying normal pregnancies and three of the flight animals were laparotomized. The uterus and ovaries were processed for microscopic analyses. The two remaining flight females were allowed to recover from the exploratory operation, rebred with flight males and delivered normal litters. As a control for potential transplacental effects that might be interpreted as direct spaceflight effects, a series of fertilized Japanese quail (Coturnix japonica) eggs was flown on Cosmos 1129. Although all of the eggs were adversely impacted by an inflight failure of the incubator humidifier on flight Day 13, several embryos were able to progress to a developmental stage equivalent to that of a control 10-12 Day embryo.

Keefe, J. R.↗

Effects of age and sex on hormonal responses to weightlessness simulation

The effects of horizontal bedrest on the excretion of catecholamines, aldosterone, and cortisol by human subjects grouped by age and sex are examined. The responses are assessed by assays of 24-hr urine samples collected throughout the studies. In 36-45-yr-olds, the excretion of epinephrine increases, whereas it decreases in the 46-55- and 56-65-yr-old groups. Norepinephrine excretion decreases (5-27%) in all groups during bedrest. Aldosterone excretion increases in the younger two groups of both males (19 and 6%) and females (47 and 9%). A slight decrease is observed in 56-65-yr-old males (6%), whereas excretion in females is unchanged. Cortisol excretion increases in the youngest groups of both men (12%) and women (13%) but decreases in the 56-65-yr-old groups (6 and 5%). For the two groups of intermediate age (46-55 yr), excretion in females decreases (15%), whereas in males it increases (19%). It is believed that hormone measurements may be of value in explaining variation in stress tolerance due to age and/or sex during space flight.

Larochelle, F.↗

Comparison of voice types for helicopter voice warning systems

Three related studies were conducted to compare different types of human voice warnings. In the first study, a comparison of three LPC-encoded voices, human female, human male, and phoneme-synthesized, by the criteria of pilot flight task performance showed no differences due to the voice type. In the second study, pilots' preferences were investigated, by comparing preference for direct synthesized speech to the LPC-encoded human female speech and to LPC-encoded synthesized speech. Most pilots were found to prefer direct synthesized speech over both LPC-encoded human female speech and the LPC-encoded synthesized speech. In the third study, phonetically balanced (PB) words heard in simulated helicopter noise were used to compare the intelligibility of direct synthesized and LPC-encoded phoneme-synthesized speech types. PB word intelligibility was found to be better for direct synthesized speech than for the LPC-encodes synthesized speech.

Simpson, C. A.↗

Amphibian fertilization and development in microgravity

During the year before launch, female frogs will be tested every 3 months for the quantity and quality of eggs produced. Two weeks or more prior to launch, male and female frogs will be transported to the John F. Kennedy Space Center (KSC). During the few weeks before launch, groups will be periodically tested for egg quality to assure that the frogs have adapted to the KSC laboratory environment. About 27 hours before launch, four females will be placed in a damp foam-lined box, called the Adult Frog Box (AFB), through which 100 cc/min of air wil be circulated. The AFB will be lowered into the Spacelab and loaded into the Frog Environmental Unit (FEU) during the final pre-launch preparations. A sperm suspension, for use in flight to fertilize the eggs, will also be prepared and loaded during the pre-launch period. The sperm suspension, together with a kit of syringes containing Human Chorionic Gonadotropin (HCG), will be stored in a refrigerator aboard the shuttle until needed in flight. On the first day of flight, the AFB will be transferred from the FEU to the General Purpose Work Station (GPWS), which is a type of glove box specially designed to allow the crew to use chemicals and biological materials during the flight without contaminating the shuttle/Spacelab environment. Inside the GPWS the four adult frogs will be injected with the HCG hormone and returned to the FEU. Approximately 16 hours after injection, ovulation should have taken place and 15 to 20 eggs from each frog will be placed on each of two egg baskets and covered with sperm for 10 minutes. The egg baskets are inserted into acrylic egg chambers and 50 ml of 'pond water' (20 percent strength Modified Ringers solution (is added. One of the chambers from each frog will be placed on a centrifuge within the FEU and rotated to simulate normal terrestrial gravity (1 g). The remaining chambers are incubated under microgravity conditions within the FEU. Forty minutes after fertilization, the four chambers exposed to 1 g will be removed and observed within the GPWS using a dissecting microscope and camera system. On the basis of egg rotation and egg appearance, the 'best' and 'second best' frogs will be selected to contribute additional eggs. Using the two best frogs, 22 egg chambers will be loaded with eggs and fertilized. Eleven chambers wil be incubated at microgravity and eleven will be incubated on the centrifuge. At various times during the flight, chambers will be removed from the FEU and transferred to the GPWS where a formaldehyde-based fixative will be injected in order to preserve important developmental stages for in depth study following the flight. Five of the 22 chambers plus the eight fertilization test chambers will be returned to Earth with live tadpoles. The swimming behavior of these free swimming tadpoles will be examined within several hours of landing and some will be fixed for a detailed analysis of their inner ear, the otolity, the animals 'balance system.' Lychakov and Vinikov reported an increase in otolith size in tadpoles that developed (but were not fertilized) in space. Live tadpoles from the SL-J flight will be raised through metamorphsis for studies of maturation including an analysis of the effects of space flight on their ability to produce normal progency. Following the flight, the fixed embryos will be serially sectioned and stained using procedures that were developed for this experiment. The embroys fixed at the 2-4 cell stage will be examined for the distribution of cytoplasmic contents, including the various classes of yolk platelets, and the location and shape of the cleavage furrows. The gastrulae will be assessed for the normality of the complex cellular rearrangements that constitute blastopore formation and involution, i.e., the differentiation of the embryo into its specialized body parts. Using a new procedure, the gastrulae will be bleached which will enable the initial sperm entry point (SEP) to be located. The correlation between the SEP and the dorsal lip of the blastopore will be determined. Under normal terrestrial conditions it was shown that the SEP typically is located on the side of the egg opposite the future dorsal side of the embryo. The neurulae will be examined for the normality and completeness of the neural plate and archenteron expansion. The tadpole stages will be used to study the allometry and morphology of the various organ systems.

Souza, Kenneth A.↗

Split spline screw

A split spline screw type payload fastener assembly, including three identical male and female type split spline sections, is discussed. The male spline sections are formed on the head of a male type spline driver. Each of the split male type spline sections has an outwardly projecting load baring segment including a convex upper surface which is adapted to engage a complementary concave surface of a female spline receptor in the form of a hollow bolt head. Additionally, the male spline section also includes a horizontal spline releasing segment and a spline tightening segment below each load bearing segment. The spline tightening segment consists of a vertical web of constant thickness. The web has at least one flat vertical wall surface which is designed to contact a generally flat vertically extending wall surface tab of the bolt head. Mutual interlocking and unlocking of the male and female splines results upon clockwise and counter clockwise turning of the driver element.

John M Vranish↗

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

The purpose of this study was to determine if human parathyroid hormone-(1-38) (PTH) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses (PTM) of female rats. The right hindlimbs of six-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization (RHLI), the rats were subcutaneously injected with 200 microgram hPTH(1-38)/kg/day for 15 (short-term) or 75 (longer-term) days. Static bone histomorphometry was performed on the primary spongiosa, while both static and dynamic histomorphometry were performed on the secondary spongiosa of the right PTM. Immobilization for 30 days without treatment decreased trabecular bone area, number and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate (BFR/TV) in the secondary spongios. These changes reached a new steady state thereafter. Treatment with 200 microgram hPTH(1-38)/kg/day for 15 days, beginning at 30 days post immobilization (IM), significantly increased trabecular bone area, thickness and number in both primary and secondary spongiosa despite continuous IM when compared to the age-related and IM controls. The short-term (15 days) PTH treatment significantly increased labeling perimeter, mineral apposition rate and BFR/TV in the secondary spongiosa and stimulated longitudinal bone growth as compared to the age-related and IM controls. PTH treatment for longer-term (75 days) further increased trabecular bone area, thickness and number as compared to aging and IM controls and short-term (15 days) PTH treated groups. The bone formation indices in the secondary spongiosa of these longer-term treated rats were lower than that of short-term (15 days) PTH treated group, but they were still higher than those of IM and age-related controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of continuously RHLI female rats. These results suggest that PTH may be a useful agent in treatment disuse-induced osteoporosis in humans.

Ma, Y. F.↗

Solar particle dose rate buildup and distribution in critical body organs

Human body organs have varying degrees of radiosensitivity as evidenced by radioepidemiologic tables. The major critical organs for both the male and female that have been identified include the lung, thyroid, stomach, and breast (female). Using computerized anatomical models of the 50th percentile United States Air Force male and female, we present the self-shielding effects of these various body organs and how the shielding effects change as the location (dose point) in the body varies. Several major solar proton events from previous solar cycles and several events from the current 22nd solar cycle have been analyzed. The solar particle event rise time, peak intensity, and decay time vary considerably from event to event. Absorbed dose and dose equivalent rate calculations and organ risk assessment data are presented for each critical body organ. These data are compared with the current NASA astronaut dose limits as recommended by the National Council on Radiation Protection and Measurements.

Atwell, William↗

Prostaglandin E2 Restores Cancellous Bone to Immobilized Limb and Adds Bone to Overloaded Limb in Right Hindlimb Immobilization Rats

The purpose of this study was to determine whether prostaglandin E2 (PGE2) can restore cancellous bone mass and architecture to osteopenic, continuously immobilized (IM), proximal tibial metaphysis (PTM) in female rats. The right hindlimb of three and one-half-month-old Sprague-Dawley female rats were immobilized by right hindlimb immobilization (RHLI) in which the right hindlimb was underloaded and the contralateral left limb was overloaded during ambulation. After 4 or 12 weeks of RHLI, the rats were treated with 3 or 6 mg PGE2/kg/day and RHLI for 8 or 16 weeks. Bone histomorphometry was performed on microradiographs of PTM. Immobilization (IM) induced a transient cancellous bone loss and decreased trabecular thickness, number and node density, and increased free end density that established a new steady state after 4 weeks of IM. Three or 6 mg PGE2/kg/d for 8 weeks beginning at 4 or 12 weeks of IM completely restored cancellous bone mass (+127 to +188 percent) and structure to the age-related control levels in spite of continuous IM. Another 8 weeks of treatment maintained bone mass and architecture at these levels. No differences in cancellous bone mass and architecture were found between the overloaded PTM or RHLI rats and the age-related controls. However, 3 and 6 mg/kg/d of PGE2 treatment started at 4 or 12 weeks for 8 weeks significantly increased cancellous bone mass in the overloaded PTM (+45 to +74% of untreated controls), and another 8 weeks of treatment maintained bone mass at these levels. Our findings indicate that daily 3 or 6 mg PGE2/kg/d treatment restores and maintains PTM cancellous bone mass in continuously immobilized (right) tibiae, and adds and maintains extra bone to slightly overloaded PTM cancellous bone in female rats.

Li, M.↗

Applying Space Technology to Enhance Control of an Artificial Arm for Children and Adults With Amputations

The first single function myoelectric prosthetic hand was introduced in the 1960's. This hand was controlled by the electric fields generated by muscle contractions in the residual limb of the amputee user. Electrodes and amplifiers, embedded in the prosthetic socket, measured these electric fields across the skin, which increase in amplitude as the individual contracts their muscle. When the myoelectric signal reached a certain threshold amplitude, the control unit activated a motor which opened or closed a hand-like prosthetic terminal device with a pincher grip. Late in the 1990's, little has changed. Most current myoelectric prostheses still operate in this same, single-function way. To better understand the limitations of the current single-function myoelectric hand and the needs of those who use them, The Institute for Rehabilitation and Research (TIRR), sponsored by the National Institutes of Health (NUH), surveyed approximately 2,500 individuals with upper limb loss [1]. When asked to identify specific features of their current myoelectric prostheses that needed improvement, the survey respondents overwhelmingly identified the lack of wrist and finger movement, as well as poor control capability. However, simply building a mechanism with individual finger and wrist motion is not enough. In the 1960's and 1970's, engineers built a number of more dexterous prosthetic hands. Unfortunately, these were rejected during clinical trials due to a difficult and distracting control interface. The goal of this project, "Applying Space Technology to Enhance Control of an Artificial Arm for Children and Adults with Amputations," was to lay the foundation for a multi-function, intuitive myoelectric control system which requires no conscious thought to move the hand. We built an extensive myoelectric signal database for six motions from ten amputee volunteers, We also tested a control system based on new artificial intelligence techniques on the data from two of these subjects. This data is available to anyone doing myoelectric control research. Its availability is an important contribution to the prosthetics research community, as many researchers do not have access to amputee subjects. Since we collected myoelectric data from subjects' sound arms as well as their residual arms, this database will also prove useful to virtual reality and robotics researchers who want to explore myoelectric-based interfaces between any user and a machine. Currently, one small company (Intelligenta, Inc.) and one university (University of New Brunswick, Canada) are using this myoelectric database under other funding to develop multifunction control systems for prostheses. A prosthetics manufacturer (Liberty Technology, Inc.) is making plans to incorporate the results of their work into an artificial hand capable of several different movements to provide functionality only dreamed of by current myoelectric users. Methods Six adults and four children, all with unilateral, below-elbow amputations served as subjects. Five of the adults (3 male, 2 female, average age 34 years) had amputations due to traumatic injury, while one adult (female, age 32 years) and the four children (3 male, 1 female, average age 13 years) had congenital (i.e. from birth) limb deficiencies.

Atkins, Diane J.↗

Operational Characteristics of Four Commercially Available Personal Cooling Vests

Personal thermoregulatory systems which provide chest cooling are used in the industrial and aerospace environments to alleviate thermal stress. However, little information is available regarding the physiologic and circulatory changes produced by routine operation of these systems. The objectives of this study were to compare the effectiveness of two passive and two active cooling vests, and to measure the body temperature and circulatory changes produced by each cooling vest configuration. The MicroClimate Systems and the Life Enhancement Tech(LET) lightweight liquid cooling vests, the Steele Vest and LET's Zipper Front Garment were used to cool the chest region of 11 male and 10 female subjects (25 to 55 yr.) in this study. Calf, forearm and finger blood flows were measured using a tetrapolar impedance rheograph. The subjects, seated in an upright position at normal room temperature (approx.21 C), were tested for 60 min. with the cooling system operated at its maximum cooling capacity. Blood flows were recorded continuously using a computer data acquisition system with a sampling frequency of 250 Hz. Oral, right and left ear temperatures and cooling system parameters were logged manually every 5 min. Arm, leg, chest and rectal temperatures; heart rate; respiration; and an activity index were recorded continuously on a URI Inc. Biolog ambulatory monitor. In general, the male and female subjects' rectal and ear temperature responses to cooling were similar for all vest configurations tested. Oral temperatures during the recovery period were significantly (P<0.05) lower than during the control period, approx.0.2 - 0.5 C, for both men and women wearing any of the four different garments. The corresponding car temperatures were significantly (P<0.05) decreased approx.0.2 - 0.3 C by the end of the recovery period. Compared to the control period, no significant differences were found in rectal temperatures during cooling and recovery periods. These results show that all vest configurations elicit a similar thermal response in both male and female subject groups. However, subject population variance was rather large and may have masked differences between the vests. One vest may prove more effective than another for a given individual, and experience is the only means of determining this.

Ku, Yu-Tsuan E.↗

Decreased Estrogen May Contribute to Osteopenia in Unloaded Bones

Progressive loss of weight-bearing bone in astronauts is one of the most serious impediments to long-duration spaceflight. Estrogen deficiency in women is an established factor in bone loss. Reduced sex hormone levels have been reported in male astronauts, but no data is available regarding spaceflight effects on female sex hormones. The objective of our study was to determine the role of estrogen in disuse osteopenia. The NASA developed hindlimb suspension (HLS) model was used to simulate the unloading disuse of weight-bearing bones experienced in space. Female Sprague-Dawley rats (age 77d; n = 20/group) were HLS or kept ambulatory (AMB) for 38 d and endocrine and bone indices determined. HLS of rats resulted in lower (p less than 0.01) bone mass (9%0), bone mineral content (BMC 13%) and mechanical strength (28%) compared to AMB animals. Plasma estradiol (E2) was lower (p = 0.03) in HLS (10.1 +/- 1.4 pg/ml) compared to AMB rats (16.7 +/- 2.6 pg/ml). E2 was positively correlated to BMC r(sup 2) = 0.67 and mechanical strength r(sup 2) = 0.61. These results suggest that reduced E2 plays a role in disuse osteopenia induced by HLS. Plasma or pituitary lutenizing hormone (LH) and follicle stimulating hormone (FSH) levels were not different in HLS versus AMB rats. However, pituitary LH was correlated to E2 (r(sup 2) = 0.57), suggesting changes in E2 were exerted at the level of the hypothalamus-pituitary axis. Understanding the role of estrogen in disuse osteopenia is necessary to the development of efficacious therapies for female astronauts, bed rest patients and the increasing number of individuals in our sedentary population suffering bone loss.

Tou, Janet↗

High Salt Intake Promotes Urinary Loss of Vitamin D Metabolites by Dahl Salt-Sensitive Rats in a Space Flight Model

Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have demonstrated that female S rats are more vulnerable than female R rats to decreases in plasma 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations during hind limb unloading (a space flight model). We report here on the response of the vitamin D endocrine system of S and R rats to hind limb unloading during high salt intake. Dahl female rats (9.7-week-old) were tail-suspended (hind limb unloaded) for 28 days, while fed a diet containing twice the salt in standard rat chow (2 % sodium chloride). Control rats were fed the same diet, but were not hind limb unloaded. Vitamin D metabolites were analyzed by HPLC and radioimmunoassay kits from Diasorin.

Thierry-Palmer, M.↗