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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 973 records · Page 54
All sourcesNASA NTRSDOE OSTI
NASA NTRS1998

Maintenance of myonuclear domain size in rat soleus after overload and growth hormone/IGF-I treatment

The purpose of this study was to determine the effects of functional overload (FO) combined with growth hormone/insulin-like growth factor I (GH/IGF-I) administration on myonuclear number and domain size in rat soleus muscle fibers. Adult female rats underwent bilateral ablation of the plantaris and gastrocnemius muscles and, after 7 days of recovery, were injected three times daily for 14 days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO group). Intact rats receiving saline vehicle served as controls (Con group). Muscle wet weight was 32% greater in the FO than in the Con group: 162 +/- 8 vs. 123 +/- 16 mg. Muscle weight in the FO + GH/IGF-I group (196 +/- 14 mg) was 59 and 21% larger than in the Con and FO groups, respectively. Mean soleus fiber cross-sectional area of the FO + GH/IGF-I group (2,826 +/- 445 microm2) was increased compared with the Con (2,044 +/- 108 microm2) and FO (2,267 +/- 301 microm2) groups. The difference in fiber size between the FO and Con groups was not significant. Mean myonuclear number increased in FO (187 +/- 15 myonuclei/mm) and FO + GH/IGF-I (217 +/- 23 myonuclei/mm) rats compared with Con (155 +/- 12 myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals was not significant. The mean cytoplasmic volume per myonucleus (myonuclear domain) was similar across groups. These results demonstrate that the larger mean muscle weight and fiber cross-sectional area occurred when FO was combined with GH/IGF-I administration and that myonuclear number increased concomitantly with fiber volume. Thus there appears to be some mechanism(s) that maintains the myonuclear domain when a fiber hypertrophies.

NASA Discipline Musculoskeletal↗
NASA NTRS1995

Intramuscular pressure and torque during isometric, concentric and eccentric muscular activity

Intramuscular pressures, electromyography (EMG) and torque generation during isometric, concentric and eccentric maximal isokinetic muscle activity were recorded in 10 healthy volunteers. Pressure and EMG activity were continuously and simultaneously measured side by side in the tibialis anterior and soleus muscles. Ankle joint torque and position were monitored continuously by an isokinetic dynamometer during plantar flexion and dorsiflexion of the foot. The increased force generation during eccentric muscular activity, compared with other muscular activity, was not accompanied by higher intramuscular pressure. Thus, this study demonstrated that eccentric muscular activity generated higher torque values for each increment of intramuscular pressure. Intramuscular pressures during antagonistic co-activation were significantly higher in the tibilis anterior muscle (42-46% of maximal agonistic activity) compared with the soleus muscle (12-29% of maximal agonistic activity) and was largely due to active recruitment of muscle fibers. In summary, eccentric muscular activity creates higher torque values with no additional increase of the intramuscular pressure compared with concentric and isometric muscular activity.

NASA Program Space Physiology and Countermeasures↗
NASA NTRS2005

Transcriptional profile of a myotube starvation model of atrophy

Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

NASA Discipline Musculoskeletal↗
DOE OSTI2025

Phosphoproteomics Modifications in Women with Rheumatoid Arthritis─Application of Web-Based Software to Enhance Data Visualization

Individuals with rheumatoid arthritis (RA) are at increased risk of functional disability, cardiovascular disease, and obesity, all of which are influenced by dysregulated skeletal muscle. Here, this pilot study aims to identify phosphoproteomics changes in RA skeletal muscle and visualize modifications through development of a web-based app designed to promote user-friendly data interpretation and visualization. NanoLC–MS/MS analysis was performed on vastus lateralis biopsies from three women with RA and matched healthy controls. Differential analysis was performed using the Limma R package. Kinase substrate enrichment analysis (KSEA) predicted changes in kinase activity. RA muscle displayed 35 upregulated and 60 downregulated phosphosites, including the cytoskeletal proteins TTN (Ser33201, Ser33013, Ser20925), NEB (Ser2219, Thr254, Ser33013, Ser20925), FLNA (Ser1459), and LASP1 (Ser146). Compared to healthy controls, KSEA predicted decreased activity of several kinases in RA muscle, including PRKACA and CDKs. All such changes were visualized by use of our web-based app. Overall, phosphoproteome analysis reveals signaling alterations in RA skeletal muscle linked to cytoskeletal proteins, representing candidate disease biomarkers; these modifications can be explored through use of our web-based software.

phosphoproteomics↗
DOE OSTI2020

Triggering typical nemaline myopathy with compound heterozygous nebulin mutations reveals myofilament structural changes as pathomechanism

Nebulin is a giant protein that winds around the actin filaments in the skeletal muscle sarcomere. Compound-heterozygous mutations in the nebulin gene (NEB) cause typical nemaline myopathy (NM), a muscle disorder characterized by muscle weakness with limited treatment options. We created a mouse model with a missense mutation p.Ser6366Ile and a deletion of NEB exon 55, the Compound-Het model that resembles typical NM. We show that Compound-Het mice are growth-retarded and have muscle weakness. Muscles have a reduced myofibrillar fractional-area and sarcomeres are disorganized, contain rod bodies, and have longer thin filaments. In contrast to nebulin-based severe NM where haplo-insufficiency is the disease driver, Compound-Het mice express normal amounts of nebulin. X-ray diffraction revealed that the actin filament is twisted with a larger radius, that tropomyosin and troponin behavior is altered, and that the myofilament spacing is increased. The unique disease mechanism of nebulin-based typical NM reveals novel therapeutic targets.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

Alterations in protein metabolism during space flight and inactivity

Space flight and the accompanying diminished muscular activity lead to a loss of body nitrogen and muscle function. These losses may affect crew capabilities and health in long-duration missions. Space flight alters protein metabolism such that the body is unable to maintain protein synthetic rates. A concomitant hypocaloric intake and altered anabolic/catabolic hormonal profiles may contribute to or exacerbate this problem. The inactivity associated with bedrest also reduces muscle and whole-body protein synthesis. For this reason, bedrest provides a good model for the investigation of potential exercise and nutritional countermeasures to restore muscle protein synthesis. We have demonstrated that minimal resistance exercise preserves muscle protein synthesis throughout bedrest. In addition, ongoing work indicates that an essential amino acid and carbohydrate supplement may ameliorate the loss of lean body mass and muscle strength associated with 28 d of bedrest. The investigation of inactivity-induced alterations in protein metabolism, during space flight or prolonged bedrest, is applicable to clinical populations and, in a more general sense, to the problems associated with the decreased activity that occur with aging.

Non-NASA Center↗
NASA NTRS2000

Effects of forearm bier block with bretylium on the hemodynamic and metabolic responses to handgrip

We tested the hypothesis that a reduction in sympathetic tone to exercising forearm muscle would increase blood flow, reduce muscle acidosis, and attenuate reflex responses. Subjects performed a progressive, four-stage rhythmic handgrip protocol before and after forearm bier block with bretylium as forearm blood flow (Doppler) and metabolic (venous effluent metabolite concentration and (31)P-NMR indexes) and autonomic reflex responses (heart rate, blood pressure, and sympathetic nerve traffic) were measured. Bretylium inhibits the release of norepinephrine at the neurovascular junction. Bier block increased blood flow as well as oxygen consumption in the exercising forearm (P < 0.03 and P < 0.02, respectively). However, despite this increase in flow, venous K(+) release and H(+) release were both increased during exercise (P < 0.002 for both indexes). Additionally, minimal muscle pH measured during the first minute of recovery with NMR was lower after bier block (6.41 +/- 0.08 vs. 6.20 +/- 0.06; P < 0.036, simple effects). Meanwhile, reflex effects were unaffected by the bretylium bier block. The results support the conclusion that sympathetic stimulation to muscle during exercise not only limits muscle blood flow but also appears to limit anaerobiosis and H(+) release, presumably through a preferential recruitment of oxidative fibers.

Non-NASA Center↗
NASA NTRS1992

A new animal model for modulating myosin isoform expression by altered mechanical activity

The purpose of this study was to develop a new rodent model that is capable of delineating the importance of mechanical loading on myosin heavy chain (MHC) isoform expression of the plantar and dorsi flexor muscles of the ankle. The essential components of this system include 1) stimulating electrodes that are chronically implanted into a muscle, allowing for the control of the activation pattern of the target muscle(s); 2) a training apparatus that translates the moment of the ankle into a linear force; and 3) a computer-controlled Cambridge 310 ergometer. The isovelocity profile of the ergometer ensured that the medial gastrocnemius (MG) produced forces that were > 90% of maximal isometric force (Po), and the eccentric contractions of the tibialis anterior (TA) were typically 120% of Po. Both the concentric and eccentric training programs produced statistically significant increases in the muscle mass of the MG (approximately 15%) and TA (approximately 7%) as well as a decrease in myofibrillar adenosinetriphosphatase activity. Both the white and red regions of the MG and TA exhibited significant increases in the relative content of the type IIa MHC and concomitant decreases in type IIb MHC expression. Although the red regions of the MG and red TA contained approximately 10% type I MHC, the training programs did not affect this isoform. It appears that when a fast-twitch muscle is stimulated at a high frequency (100 Hz) and required to contract either concentrically or eccentrically under high loading conditions, the expression of the type IIa MHC isoform will be upregulated, whereas that of the type IIb MHC will be concomitantly downregulated.

NASA Discipline Musculoskeletal↗
NASA NTRS1997

Analysis of myosin heavy chain mRNA expression by RT-PCR

An assay was developed for rapid and sensitive analysis of myosin heavy chain (MHC) mRNA expression in rodent skeletal muscle. Only 2 microg of total RNA were necessary for the simultaneous analysis of relative mRNA expression of six different MHC genes. We designed synthetic DNA fragments as internal standards, which contained the relevant primer sequences for the adult MHC mRNAs type I, IIa, IIx, IIb as well as the embryonic and neonatal MHC mRNAs. A known amount of the synthetic fragment was added to each polymerase chain reaction (PCR) and yielded a product of different size than the amplified MHC mRNA fragment. The ratio of amplified MHC fragment to synthetic fragment allowed us to calculate percentages of the gene expression of the different MHC genes in a given muscle sample. Comparison with the traditional Northern blot analysis demonstrated that our reverse transcriptase-PCR-based assay was reliable, fast, and quantitative over a wide range of relative MHC mRNA expression in a spectrum of adult and neonatal rat skeletal muscles. Furthermore, the high sensitivity of the assay made it very useful when only small quantities of tissue were available. Statistical analysis of the signals for each MHC isoform across the analyzed samples showed a highly significant correlation between the PCR and the Northern signals as Pearson correlation coefficients ranged between 0.77 and 0.96 (P < 0.005). This assay has potential use in analyzing small muscle samples such as biopsies and samples from pre- and/or neonatal stages of development.

Non-NASA Center↗
NASA NTRS2000

Single-fiber myosin heavy chain polymorphism during postnatal development: modulation by hypothyroidism

The primary objective of this study was to follow the developmental time course of myosin heavy chain (MHC) isoform transitions in single fibers of the rodent plantaris muscle. Hypothyroidism was used in conjunction with single-fiber analyses to better describe a possible linkage between the neonatal and fast type IIB MHC isoforms during development. In contrast to the general concept that developmental MHC isoform transitions give rise to muscle fibers that express only a single MHC isoform, the single-fiber analyses revealed a very high degree of MHC polymorphism throughout postnatal development. In the adult state, MHC polymorphism was so pervasive that the rodent plantaris muscles contained approximately 12-15 different pools of fibers (i.e., fiber types). The degree of polymorphism observed at the single-fiber level made it difficult to determine specific developmental schemes analogous to those observed previously for the rodent soleus muscle. However, hypothyroidism was useful in that it confirmed a possible link between the developmental regulation of the neonatal and fast type IIB MHC isoforms.

NASA Program Biomedical Research and Countermeasur↗
DOE OSTI2023

The mitochondrially targeted peptide elamipretide (SS-31) improves ADP sensitivity in aged mitochondria by increasing uptake through the adenine nucleotide translocator (ANT)

Aging muscle experiences functional decline in part mediated by impaired mitochondrial ADP sensitivity. Elamipretide (ELAM) rapidly improves physiological and mitochondrial function in aging and binds directly to the mitochondrial ADP transporter ANT. We hypothesized that ELAM improves ADP sensitivity in aging leading to rescued physiological function. We measured the response to ADP stimulation in young and old muscle mitochondria with ELAM treatment, in vivo heart and muscle function, and compared protein abundance, phosphorylation, and S-glutathionylation of ADP/ATP pathway proteins. ELAM treatment increased ADP sensitivity in old muscle mitochondria by increasing uptake of ADP through the ANT and rescued muscle force and heart systolic function. Protein abundance in the ADP/ATP transport and synthesis pathway was unchanged, but ELAM treatment decreased protein s-glutathionylation incuding of ANT. Mitochondrial ADP sensitivity is rapidly modifiable. This research supports the hypothesis that ELAM improves ANT function in aging and links mitochondrial ADP sensitivity to physiological function.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1974

Power spectral density analysis of the electromyogram from a work task performed in a full pressure suit

Surface electromyograms (EMG) taken from three upper torso muscles during a push-pull task were analyzed by a power spectral density technique to determine the utility of the spectral analysis for identifying changes in the EMG caused by muscular fatigue. The results confirmed the value of the frequency analysis for identifying fatigue producing muscular performance. Data revealed reliable differences between muscles in fatigue induced responses to various locations in the reach envelope at which the subjects were required to perform the push-pull exercise, and the differential sensitivity of individual muscles to the various reach positions; i.e., certain reach positions imposed more fatigue related shifts in EMG power than did others. It was found that a pressurized space suit changed the pattern of normal shirtsleeve muscle fatigue responses in all three of the muscles.

Lafevers, E. V.↗
NASA NTRS1973

Blood flow and oxygen uptake during exercise

A model is developed for predicting oxygen uptake, muscle blood flow, and blood chemistry changes under exercise conditions. In this model, the working muscle mass system is analyzed. The conservation of matter principle is applied to the oxygen in a unit mass of working muscle under transient exercise conditions. This principle is used to relate the inflow of oxygen carried with the blood to the outflow carried with blood, the rate of change of oxygen stored in the muscle myoglobin, and the uptake by the muscle. Standard blood chemistry relations are incorporated to evaluate venous levels of oxygen, pH, and carbon dioxide.

Mitchell, J. W.↗
NASA NTRS1975

EMGAN: A computer program for time and frequency domain reduction of electromyographic data

An experiment in electromyography utilizing surface electrode techniques was developed for the Apollo-Soyuz test project. This report describes the computer program, EMGAN, which was written to provide first order data reduction for the experiment. EMG signals are produced by the membrane depolarization of muscle fibers during a muscle contraction. Surface electrodes detect a spatially summated signal from a large number of muscle fibers commonly called an interference pattern. An interference pattern is usually so complex that analysis through signal morphology is extremely difficult if not impossible. It has become common to process EMG interference patterns in the frequency domain. Muscle fatigue and certain myopathic conditions are recognized through changes in muscle frequency spectra.

Hursta, W. N.↗
NASA NTRS1983

Cardiovascular responses to exercise as functions of absolute and relative work load

The roles of absolute and relative oxygen uptake (VO2 and percent of muscle group specific VO2-max) as determinants of the cardiovascular and ventilatory responses to exercise over a wide range of active muscle mass are investigated. Experiments were conducted using four types of dynamic exercise: one-arm curl, one-arm cranking, and one and two-leg cycling at four different relative work loads (25, 50, 75, and 100 percent of VO2-max) for the corresponding muscle group. Results show that VO2 during maximal one-arm curl, one-arm cranking, and one-leg cycling averaged 20, 50, and 75 percent, respectively, of that for maximal two-leg cycling. Cardiac output was determined to be linearly related to VO2 with a similar slope and intercept for each type of exercise, and the heart rate at a given percent VO2-max was higher with larger active muscle mass. It is concluded that the cardiovascular responses to exercise was determined to a large extent by the active muscle mass and the absolute oxygen uptake, with the principal feature appearing to be the tight linkage between systematic oxygen transport and utilization.

Lewis, S. F.↗
NASA NTRS1984

Appropriateness of the small-cage-reared rat as a model for the study of altered-activity effects

Within genetically imposed limits, the fatigue-resistance capability of muscle varies according to the chronic demands of usage imposed on the muscle. Given the fiber-type distribution within a muscle, its fatigue-resistance can be utilized as an indicant of its physiological status. It is suggested that the hindlimb musculature of rats raised in cages constructed to minimum DFA specifications are physiologically inappropriate for the study of altered-activity effects. This proposition is based upon two observations from the medial gastrocnemius muscle (n = 7) of Sprague-Dawley rats (500 g, 100 d); first, a substantial disparity in the peak forces (twitch and tetanic) elicited by neural and direct-muscle stimulation, and second, a reduction in force during the fatigue test (2 min of 1 Hz trains with each train lasting 330 ms and including 13 stimuli) that was greater (79%) than theoretically expected (62%). Both of these observations are critically assessed.

Enoka, R. M.↗
NASA NTRS1983

The validity of an animal model for experiments related to weightlessness

Animal evolution has witnessed morphological and physiological adaptations to gravitational forces. In the rat, hind limb muscles can be used to illustrate a range of load bearing functions: soleus - gastrocnemius = plantaris - extensor digitorum longus (EDL). A harness suspension apparatus is used to induce hypokinesia and hypodynamia (H&H) and to simulate responses comparable to those seen in weightlessness (i.e., COSMOS experiments). After one and two weeks of suspension H&H, there is muscle atrophy with a loss in muscle mass; the result of loss in muscle protein. Concommitantly, there is a decrease in RNA, but not in DNA content. The effects are greatest in the soleus and least in the EDL. These recent findings, in concert with earlier reports of increased nitrogenous excretion, suggest that both decreased protein synthesis and increased protein catabolism are characteristic of muscle atrophy. Recovery is seen in terms of reversal of these effects after removal from suspension.

Musacchia, X. J.↗
NASA NTRS1986

Models of disuse - A comparison of hindlimb suspension and immobilization

The effects of 1 and 2 weeks of hindlimb suspension (HS) on the contractile properties of fast- and slow-twitch skeletal muscles of male Sprague Dawley rats are studied and compared with hindlimb immobilization (HI) data. The optimal length and contractile properties of the slow-twitch soleus, fast-twitch extensor digitorum longus, and the vastus lateralis are measured. It is observed that HS and HI affect slow-twitch muscles; isometric twitch duration in the slow-twitch soleus is decreased. Soleus muscle mass and peak tetanic tension declines with disuse. A major difference in the influence of HS and HI on the maximal speed of soleus muscle shortening, V(max) is detected; HS produced a twofold increase in V(max) compared to control data and HI had no significant effect on V(max). The relation between V(max) and myosin concentration is analyzed. The data reveal that HS modifies slow-twitch muscle yielding hybrid fibers with elevated shortening velocities and this change may be dependent on the elimination of load-bearing contractions.

Fitts, R. H.↗