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At least 91 records · Page 5

Calcium balance in mature male rats with unloaded hindlimbs

BACKGROUND: Calcium balances, regulated by the calcium endocrine system, are negative during spaceflight but have not been reported in flight simulation models using fully mature small animals. METHODS: We conducted two calcium (Ca) balance studies in 6-mo-old male rats exposed to a model that unloads the hindlimbs (HU) for 4 wk. Control (C) and HU rats were fed diets with 0.5% Ca in the first and 0.1% Ca in the second study. Housing in metabolic cages enabled daily food and water intake measurements as well as collections of urine and fecal specimens. At necropsy, blood was obtained for measures of Ca-regulating hormones. RESULTS: Both C and HU rats adjusted to housing and diets with decreases in body weight and negative Ca balances during the first week of each experiment. Thereafter, averages of Ca balances were more negative in the unloaded rats than controls: -8.1 vs. -1.6 mg x d(-1) in rats fed 0.5% (p < 0.05). This difference was not due to urinary Ca excretion since it was lower in HU than C rats (1.27 +/- 0.51 mg x d(-1) vs. 2.35 +/- 0.82 mg x d(-1), p < 0.05). Fecal Ca in HU rats exceeded dietary Ca by 4-7%, Restricting dietary Ca to 0.1% was followed by an increase in serum 1,25-dihydroxyvitamin D (1,25-D) and greater intestinal Ca absorption than in rats fed 0.5% Ca. Ca balances in rats fed 0.1% Ca were also more negative in HU than C rats (-2.4 vs. -0.03 mg x d(-1), p < 0.05). Parathyroid hormone (PTH) was suppressed and 1,25-D increased in HU rats fed 0.5% Ca. C rats fed 0.1% Ca had increased PTH and 1,25-D was the same as in the HU group. CONCLUSION: After adaptation, Ca balances were more negative in mature male rats with unloaded hindlimbs than controls, an effect from increased secretion and loss of endogenous fecal Ca associated with increased 1,25-D in Ca-replete and Ca-restricted rats.

Hindlimb Suspension/physiology↗

Body Unloading Associated with Space Flight and Bed-rest Impacts Functional Performance

The goal of the Functional Task Test study is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. Ultimately this information will be used to assess performance risks and inform the design of countermeasures for exploration class missions. We are currently conducting studies on both ISS crewmembers and on subjects experiencing 70 days of 6 degrees head-down bed-rest as an analog for space flight. Bed-rest provides the opportunity for us to investigate the role of prolonged axial body unloading in isolation from the other physiological effects produced by exposure to the microgravity environment of space flight. This allows us to parse out the contribution of the body unloading component on functional performance. In this on-going study both ISS crewmembers and bed-rest subjects were tested using an interdisciplinary protocol that evaluated functional performance and related physiological changes before and after 6 months in space and 70 days of 6 head-down bed-rest, respectively. Functional tests included ladder climbing, hatch opening, jump down, manual manipulation of objects and tool use, seat egress and obstacle avoidance, recovery from a fall, and object translation tasks. Crewmembers were tested three times before flight, and on 1, 6 and 30 days after landing. Bed-rest subjects were tested three times before bed-rest and immediately after getting up from bed-rest as well as 1, 6 and 12 days after reambulation. A comparison of bed-rest and space flight data showed a significant concordance in performance changes across all functional tests. Tasks requiring a greater demand for dynamic control of postural equilibrium (i.e. fall recovery, seat egress/obstacle avoidance during walking, object translation, jump down) showed the greatest decrement in performance. Functional tests with reduced requirements for postural stability (i.e. hatch opening, ladder climb, manual manipulation of objects and tool use) showed little reduction in performance. Bed-rest results indicate that body support unloading experienced during space flight plays a central role in postflight alteration of functional task performance. These data point to the importance of providing axial body loading as a central component of an inflight training system that will integrate cardiovascular, resistance and sensorimotor adaptability training modalities into a single interdisciplinary countermeasure system.

Bloomberg, J. J.↗

A Mathematical Model of Oxygen Transport in Skeletal Muscle During Hindlimb Unloading

During hindlimb unloading (HU) dramatic fluid shifts occur within minutes of the suspension, leading to a less precise matching of blood flow to O2 demands of skeletal muscle. Vascular resistance directs blood away from certain muscles, such as the soleus (SOL). The muscle volume gradually reduces in these muscles so that eventually the relative blood flow returns to normal. It is generally believed that muscle volume change is not due to O2 depletion, but a consequence of disuse. However, the volume of the unloaded rat muscle declines over the course of weeks, whereas the redistribution of blood flow occurs immediately. Using a Krogh Cylinder Model, the distribution of O2 was predicted in two skeletal muscles: SOL and gastrocnemius (GAS). Effects of the muscle blood flow, volume, capillary density, and O2 uptake, are included to calculate the pO2 at rest and after 10 min and 15 days of unloading. The model predicts that 32 percent of the SOL muscle tissue has a pO2 1.25 mm Hg within 10 min, whereas the GAS maintains normal O2 levels, and that equilibrium is reached only as the SOL muscle cells degenerate. The results provide evidence that there is an inadequate O2 supply to the mitochondria in the SOL muscle after 10 min HU.

Mathematical models↗

Multi-Omics Analysis of Mouse Retina Following Low Dose Radiation and/or Hindlimb Unloading

Rodent models have been used as analogs for studying the effects of spaceflight. NASA’s GeneLab provides access to omics datasets generated from spaceflight and ground-based experiments allowing for additional retrospective analysis. We used GeneLab’s GLDS-203, a dataset generated by researchers at Loma Linda University to study the impact of prolonged unloading and/or low-dose radiation on mouse retina. The purpose of this study was to understand the effect of gamma radiation and/or hindlimb unloading on mice retinas through a multi-omics analysis. In the experiment that generated the omics data, mice were irradiated with gamma-ray and/or subjected to hindlimb unloading for 21 days and multi-omics analysis was performed at 7 days, 1 month, or 4 months post exposure. In the current study, for each of the three timepoints, we compared epigenomic profiles for retinas from exposed mice against timepoint-matched controls. We identified a total of 5,271 differentially methylated loci (DML) and 321 differentially methylated regions (DMR; using a sliding window and step size of 500 bp) with methylation difference > 10% and q-value < 0.05 (sliding linear model corrected p-value) across the nine exposure groups. Highest correlation in methylation difference was seen for significant DMLs (q-value < 0.05) across different conditions at same post exposure timepoint (Figure 1).The location of DMLs and DMRs were characterized with respect to CpG islands and shores, putative promoters, gene body, and intergenic regions (Table 1). We analyzed RNA-seq counts and performed gene set enrichment analysis using differential expression results from comparing each exposure group to its timepoint-matched control group. Significant pathways (adjusted p-value <0.05) enriched in all three microgravity-only groups were related to morphogenesis of a branching epithelium, skeletal muscle cell differentiation, and response to fibroblast growth factor. Common processes across all timepoints in the radiation-only groups were retina homeostasis, synaptic vesicle exocytosis-endocytosis, and chemotaxis. In the combination groups, regulation of trans-synaptic signaling, and Rho protein signal transduction were enriched at all three timepoints. Processes related to purine nucleotide metabolism were enriched in all nine exposure groups, with activation at 1 month, and suppression at 7 days and 4 months. A total of 14 genes contained at least one DML and were differentially expressed at adjusted p-value < 0.05, including genes implicated in cataract development (Sipa1l3, Crybb3) and those involved in cytoskeletal organization (Plec, Flnb, Eef1a1). This analysis is part of a larger effort to understand the molecular mechanisms following spaceflight exposures that can help translate effects observed in animal models to human impacts.

Prachi Kothiyal↗

Phloem unloading via the apoplastic pathway is essential for shoot distribution of root-synthesized cytokinins

Abstract Root-synthesized cytokinins are transported to the shoot and regulate the growth, development, and stress responses of aerial tissues. Previous studies have demonstrated that Arabidopsis (Arabidopsis thaliana) ATP binding cassette (ABC) transporter G family member 14 (AtABCG14) participates in xylem loading of root-synthesized cytokinins. However, the mechanism by which these root-derived cytokinins are distributed in the shoot remains unclear. Here, we revealed that AtABCG14-mediated phloem unloading through the apoplastic pathway is required for the appropriate shoot distribution of root-synthesized cytokinins in Arabidopsis. Wild-type rootstocks grafted to atabcg14 scions successfully restored trans-zeatin xylem loading. However, only low levels of root-synthesized cytokinins and induced shoot signaling were rescued. Reciprocal grafting and tissue-specific genetic complementation demonstrated that AtABCG14 disruption in the shoot considerably increased the retention of root-synthesized cytokinins in the phloem and substantially impaired their distribution in the leaf apoplast. The translocation of root-synthesized cytokinins from the xylem to the phloem and the subsequent unloading from the phloem is required for the shoot distribution and long-distance shootward transport of root-synthesized cytokinins. This study revealed a mechanism by which the phloem regulates systemic signaling of xylem-mediated transport of root-synthesized cytokinins from the root to the shoot.

59 BASIC BIOLOGICAL SCIENCES↗

Effect of Variations in the Gas-Dynamic Unloading on the Laser Initiation of the PETN–Aluminum Composite

Thresholds of explosive decomposition H{sub cr} under irradiation using the first harmonic of a pulsed neodymium laser (14 ns) are experimentally determined for pentaerythritol tetranitrate (PETN) with aluminum nanoparticles (100 nm) at concentrations ranging from 0.05 to 1 wt %. Amplitudes of optoacoustic signals are measured versus concentrations of impurities in the sample at a fixed laser fluence. The experiments are performed in two regimes. In the first one, the irradiated surface of the sample is covered with a finite-weight glass plate that impedes the gas-dynamic unloading. In the second regime, an external pressure of no less than 10{sup 7} Pa is applied to the glass plate to prevent the gas-dynamic unloading. The interpretation of the experimental effects is proven by the results of theoretical simulation.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Feasibility Study For Use Of Commercial Cask Vendor Dry Transfer Systems To Unload Used Fuel Assemblies In L-Area

The purpose of this study is to determine whether a commercial dry transfer system (DTS) could be used for loading or unloading used nuclear fuel (UNF) in L-Basin and to determine if a DTS pool adapter could be made for L-Basin Transfer Pit #2 that could accommodate a variety of DTS casks and fuel baskets or canisters up to 24” diameter.[1, 2] This study outlines the technical feasibility of accommodating different vendor dry transfer systems in the L-Basin Transfer Bay with a general work scope. It identifies equipment needing development, facility modifications, and describes the needed analyses and calculations. After reviewing the L-Basin Transfer Bay area layout and information on the only DTS system currently in use for the Nuclear Assurance Corporation Legal Weight Truck cask (NAC LWT), the authors conclude that use of a dry transfer cask is feasible. AREVA was contacted and acknowledged that they currently do not have a design for a dry transfer cask for their new Transnuclear Long Cask (TN-LC) cask. Nonetheless, this study accounted for a potential future DTS from AREVA to handle fuel baskets up to 18” in diameter. Due to the layout of the Transfer Bay, it was determined that a DTS cask pool adapter designed specifically for spanning Pit #2 and placed just north of the 70 Ton Cask lid lifting superstructure would be needed. The proposed pool adapter could be used to transition a fuel basket up to 24” in diameter and ~11 feet long from a dry transfer cask to the basin. The 18” and 24” applications of the pool adapter are pending vendor development of dry transfer casks that accommodate these diameters. Once a fuel basket has been lowered into Pit #2 through a pool adapter, a basket cart could be used to move the basket out from under the pool adapter for access by the 5 Ton Crane. The cost to install a dry transfer cask handling system in L-Area capable of handling multiple vendor provided transport and dry transfer casks and baskets with different diameters and lengths would likely be on the same order of magnitude as the Basin Modifications project. The cost of a DTS capability is affected by the number of design variations of different vendor transport and dry transfer casks to be considered for design input. Some costs would be incurred for each vendor DTS to be handled. For example, separate analyses would be needed for each dry transfer cask type such as criticality, shielding, dropping a dry transfer cask and basket, handling and auxiliary equipment, procedures, operator training, readiness assessments, and operational readiness reviews. A DTS handling capability in L-Area could serve as a backup to the Shielded Transfer System (STS) for unloading long casks and could support potential future missions such as the Idaho National Laboratory (INL) Exchange or transferring UNF from wet to dry storage.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Orbit-averaged behavior of magnetic control laws for momentum unloading

Analytical formulas are derived for orbit-averaged behavior of magnetic control laws for unloading the excess angular momentum of a spacecraft reaction wheel control system in the presence of secular environmental torques. The specific example of an axially symmetric spacecraft with an inertially fixed attitude for which the dominant environmental torque is the gravity-gradient torque is treated in detail, but extensions of the general approach to other inertially fixed and earth-pointing spacecraft are discussed. The analytical formulas are compared to detailed simulations performed for the Solar Maximum Mission spacecraft, and agreement to within 10% is found. The analytical formulas can be used in place of detailed simulations for preliminary studies, and can be used to find selected cases giving the most stringent tests of momentum unloading capability for which detailed simulations may be performed.

Camillo, P. J.↗

Automated Conduit Unloading

Large, cumbersome pipes removed from trailer by one operator. Swiveltruck trailer carries conduit and unloads it. Vertical bins interconnected by web belts that elevate conduit sections for delivery by gravity to unloading point. Trailer loaded with slurry-pipe sections 6 inches (15.2 centimeters) in diameter, but bin width readily changed to hold other sizes. Simple adjustments in bin-partition and web-belt positions needed to adapt system to different conduit cross sections.

Lewis, E. V.↗

Efficient Vent Unloading of Air Compressors

Method for unloading one-and two-stage reciprocating air compressors increases energy efficiency and inhibits deterioration of components. In new unloader configuration, compressor vented to atmosphere on downstream side. Method implemented expeditiously as modification of existing systems.

Muhonen, Alvin J.↗

Insulin effect on amino acid uptake by unloaded rat hindlimb muscles

The effect of insulin on the uptake of alpha-amino-isobutyric acid (AIB) by unloaded rat hindlimb muscles was investigated using soleus and extensor digitorum longus (EDL) muscles from intact and adrenalectomized (ADX) rats that were tail-casted for six days. It was found that, at insulin levels above 0.00001 units/ml, the in vitro rate of AIB uptake by muscles from intact animals was stimulated more in the weight bearing muscles than in unloaded ones. In ADX animals, this differential response to insulin was abolished.

Jaspers, S. R.↗

Transcriptional regulation of decreased protein synthesis during skeletal muscle unloading

The regulatory role of transcriptional alterations in unloaded skeletal muscles was investigated by determining levels of total muscle RNA and mRNA fractions in soleus, gastrocnemius, and extensor digitorum longus (EDL) of rats subjected to whole-body suspension for up to 7 days. After 7 days, total RNA and mRNA contents were lower in soleus and gastrocnemius, compared with controls, but the concentrations of both RNAs per g muscle were unaltered. Alpha-actin mRNA (assessed by dot hybridization) was significantly reduced in soleus after 1, 3, and 7 days of suspension and in gastrocnemius after 3 and 7 days, but was unchanged in EDL. Protein synthesis directed by RNA extracted from soleus and EDL indicated marked alteration in mRNAs coding for several small proteins. Results suggest that altered transcription and availability of specific mRNAs contribute significantly to the regulation of protein synthesis during skeletal muscle unloading.

Howard, G.↗

Age effects on rat hindlimb muscle atrophy during suspension unloading

The effects of hindlimb unloading on muscle mass and biochemical responses were examined and compared in adult (450-g) and juvenile (200-g) rats after 1, 7, or 14 days of whole-body suspension. Quantitatively and qualitatively the soleus, gastrocnemius, plantaris, and extensor digitorum longus (EDL) muscles of the hindlimb exhibited a differential sensitivity to suspension and weightlessness unloading in both adults and juveniles. The red slow-twitch soleus exhibited the most pronounced atrophy under both conditions, with juvenile responses being greater than adult. In contrast, the fast-twitch EDL hypertrophied during suspension and atrophied during weightlessness, with no significant difference between adults and juveniles. Determination of biochemical parameters (total protein, RNA, and DNA) indicates a less rapid rate of response in adult muscles.

Steffen, Joseph M.↗

Rat limb unloading - Soleus histochemistry, ultrastructure, and electromyography

The effects of hindlimb unloading on rat-soleus histochemisty, ultrastructure, and electromyogram (EMG) activity were investigated. It was found that, after 14 days of tail suspension, the area of type I and type IIa muscle fibers decreased by 63 and 47 percent, respectively, mainly due to the degradation of subsarcolemmal mitochondria and myofibrils. After 10 days, 3 percent of type IIa fibers exhibited segmental necrosis. After four days, video monitoring revealed abnormal plantar flexion of the hindfeet, which shortened the soleus working range. The EMG activity shifted from tonic to phasic, and aggregate activity decreased drastically after only seven days. The results indictate that the pathological changes in the soleus resulted from unloaded contractions, reduced use, compromised blood flow, and shortened working length.

Riley, D. A.↗

TDRSS momentum unload planning

A knowledge-based system is described which monitors TDRSS telemetry for problems in the momentum unload procedure. The system displays TDRSS telemetry and commands in real time via X-windows. The system constructs a momentum unload plan which agrees with the preferences of the attitude control specialists and the momentum growth characteristics of the individual spacecraft. During the execution of the plan, the system monitors the progress of the procedure and watches for unexpected problems.

Cross, George R.↗

Patterns of global gene expression in rat skeletal muscle during unloading and low-intensity ambulatory activity

Physical inactivity and unloading lead to diverse skeletal muscle alterations. Our goal was to identify the genes in skeletal muscle whose expression is most sensitive to periods of unloading/reduced physical activity and that may be involved in triggering initial responses before phenotypic changes are evident. The ability of short periods of physical activity/loading as an effective countermeasure against changes in gene expression mediated by inactivity was also tested. Affymetrix microarrays were used to compare mRNA levels in the soleus muscle under three experimental treatments (n = 20-29 rats each): 12-h hindlimb unloading (HU), 12-h HU followed by 4 h of intermittent low-intensity ambulatory and postural activity (4-h reloading), and control (with ambulatory and postural activity). Using a combination of criteria, we identified a small set of genes (approximately 1% of 8,738 genes on the array or 4% of significant expressed genes) with the most reproducible and largest responses to altered activity. Analysis revealed a coordinated regulation of transcription for a large number of key signaling proteins and transcription factors involved in protein synthesis/degradation and energy metabolism. Most (21 of 25) of the gene expression changes that were downregulated during HU returned at least to control levels during the reloading. In surprising contrast, 27 of 38 of the genes upregulated during HU remained significantly above control, but most showed trends toward reversal. This introduces a new concept that, in general, genes that are upregulated during unloading/inactivity will be more resistant to periodic reloading than those genes that are downregulated. This study reveals genes that are the most sensitive to loading/activity in rat skeletal muscle and indicates new targets that may initiate muscle alterations during inactivity.

NASA Discipline Musculoskeletal↗