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Muscle wasting remains a feature of many diseases and is counteracted by anabolic supplementation or exercise. Persisting atrophy-inducing conditions can be complicated by skeletal muscle fibrosis, which leads to functional impairment. Identification of early mechanisms that initiate atrophy-induced fibrosis may reveal novel targets for therapy or diagnosis. Therefore, we investigated changes in the expression of genes involved in extracellular matrix homeostasis during glucocorticoid-induced atrophy of myotubes and compared them with insulin-like growth factor-1-induced hypertrophy. Obtained results were verified in rat gastrocnemius muscle that was exposed to microgravity by space flight for 2 weeks. Myostatin and atrogin-1 mRNA levels reflected the magnitude of atrophy. Despite differential induction of these negative muscle mass regulators, no major changes in matrix metalloproteinases-2, -9, and -14 mRNAs or their physiological inhibitors could be detected in either atrophy model. In contrast, transcript levels of plasminogen activator inhibitor type 1 (PAI-1) was dramatically increased in atrophic myotubes and microgravity-exposed rat gastrocnemius muscle, while plasminogen activators remained unaltered. In contrast to atrophy, no increase in PAI-1 mRNA levels could be detected in rat hindlimb that was electrically stimulated for 21 days. Furthermore, a strong increase in PAI-1 mRNA levels was identified in skeletal muscle of patients with neurogenic muscle atrophy. Our study suggests that increased PAI-1 expression in atrophic skeletal muscle may lead to muscle fibrosis by reducing plasmin generation.

There are several motivations for increasing the diameter of melt textured single domain discs. The maximum magnetic field produced by a trapped field magnet is proportional to the radius of the sample. Furthermore, the availability of trapped field magnets with large diameter could enable their use in applications that have traditionally been considered to require wound electromagnets, such as beam bending magnets for particle accelerators and electric propulsion. We have investigated the possibility of using large area epitaxial growth instead of the conventional point nucleation growth mechanism. This process involves the use of large Y123 seeds for the purpose of increasing the maximum achievable Y123 single domain size. The hot seeding technique using large Y-123 seeds was employed to seed Y-123 samples. Trapped field measurements indicate that single domain samples were indeed grown by this technique. Microstructural evaluation indicates that growth can be characterized by a rapid nucleation followed by the usual peritectic grain growth which occurs when large seeds are used. Critical temperature measurements show that no local Tcsuppression occurs in the vicinity of the seed. This work supports the suggestion of using an iterative method for increasing the size of Y-123 single domains that can be grown.

The main purpose of this review is to discuss associations between within-litter variation in birth weight, and preweaning survival and postnatal growth in the pig, as the basis for suggesting that the developmental competence of pigs born, as well as the size of the litter, need critical consideration. Extremes of intrauterine growth retardation (IUGR) occur within a discrete subset of fetuses, substantially smaller than their littermates and commonly described as runt piglets. The lower preweaning growth of runt pigs cannot be entirely explained based on their lower birth weight, nor do they show full postnatal compensatory growth. Interestingly, this more complex reprogramming of development in runt pigs can already be identified by d 27 to 35 of gestation. Recently, we reported more universal IUGR effects in commercial dam-line sows, as an indirect response to selection for increased litter size. High ovulation rates (>30 ovulations) in a proportion of greater parity sows are associated with increased numbers of conceptuses surviving to d 30 of gestation, resulting in detrimental effects on placental development of uterine crowding in the early postimplantation period. In turn, this limits nutrient availability to the embryo during a critical period of myogenesis. Consequently, although a reduction in the number of conceptuses occurs by d 50, placental development in the surviving fetuses remains compromised, resulting in IUGR and reduced numbers of muscle fibers at d 90 and at birth, in all surviving littermates. These effects of uterine crowding on fetal and postnatal development are analogous to the detrimental effects of nutritional restriction in gestating sows on fetal myogenesis, birth weight, and postnatal growth. The incompatibility between increased numbers of conceptuses surviving to the postimplantation period, in the absence of increased uterine capacity, offers a biological explanation for increased variability in birth weight and postnatal growth performance reported in greater parity sows. We conclude that a strategy of introducing hyperprolific females into the breeding nucleus, as a means of increasing the numbers of pigs born, needs to be critically evaluated in the context of the overall efficiency of pork production.

The current-carrying capability of superconducting wires is degraded by stress. Therefore electromechanical properties are one of the key feedback parameters needed for progress in conductor applications. In this work, uniaxial tensile stresses and bending stresses were applied to Fe /MgB2wires at room temperature, followed by measurement of critical current using a transport method at 4.2 K. Basic mechanical properties were calculated from the measured stress-strain characteristics. The irreversible tensile strain at which the critical current density of MgB2wire starts to degrade was found to be 0.5%. In addition, the degradation of Icwith decreasing bending diameters was found to be very rapid for wires that were deformed after the heat treatment that forms the MgB2compound, while not much degradation of Icwas found for wires that were bent before being annealed. SEM observations confirmed that cracks could be healed by post-annealing.

Melt-textured YBCO superconductors are capable of carrying higher current densities than comparable copper conductors, and can therefore be used in electromechanical devices requiring high power densities. The advantage of textured YBCO superconductors is most pronounced in large systems such as electromagnetic launchers for aircraft carriers. In general, an electromagnetic launcher consists of a series of stationary pulsed electromagnets (the primary), which attract and/or repel a carriage carrying one or more magnets (the secondary). Several possibilities exist for the incorporation of HTSs into EM launchers, with the most direct being upgrading the magnets in the secondary to melt-textured YBCO. A system was developed to study propulsive force in a coaxial-type launcher. Results from this study are presented and their implications for launcher development discussed. A second type of launcher was also studied, with a power supply integrated into the launcher primary, so that the primary serves as a superconducting magnetic energy storage system. A method of optimizing energy conversion in a system of this type has been found. The time dependence of the magnetic field in this type of launcher is presented.

A sharp cube textured Ni overlayer on Cu substrates has been developed for the manufacturing of long-length RABiTS-based coated conductor tapes. Using a low-cost, non-vacuum and easily scalable technique of electroplating, smooth, crack-free and continuous Ni overlayers were deposited on cube textured Cu substrates without any intermediate layers. In addition, sharp cube textured Sm-doped CeO2buffer layers have been grown on the Ni-plated Cu substrates using pulsed laser deposition and found to exhibit in-plane and out-of-plane FWHM values of 6.50° and 5.25°, respectively. This electroplating process promises an efficient route for manufacturing Cu-based HTS coated conductors.

The present study examined the effect of chronic activation of 5′‐AMP‐activated protein kinase (AMPK) on the metabolic profile, including uncoupling protein‐3 (UCP‐3) and myosin heavy chain (MHC)‐based fibre phenotype of rodent fast‐twitch tibialis anterior muscle. Sprague‐Dawley rats were given daily injections of 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR), a known activator of AMPK, or vehicle (control) for 28 days. After AICAR treatment, UCP‐3 expression at the mRNA level was elevated 1.6 ± 0.1‐fold (P< 0.006) and corresponded to a 3.3 ± 0.2‐fold increase in UCP‐3 protein content (P< 0.0001). In addition, the activities of the mitochondrial reference enzymes citrate synthase (EC 4.1.3.7) and 3‐hydroxyacyl‐CoA‐dehydrogenase (EC 1.1.1.35), which are known to increase in proportion to mitochondrial volume density, were elevated 1.6‐fold (P< 0.006), while the activity of lactate dehydrogenase (EC 1.1.1.27) was reduced to 80 % of control (P< 0.02). No differences were detected after AICAR treatment in the activities of the glycolytic reference enzymes glyceraldehydephosphate dehydrogenase (EC 1.2.1.12) or phosphofructokinase (EC 2.7.1.11), nor were MHC‐based fibre‐type transitions observed, using immunohistochemical or electrophoretic analytical methods. These changes could not be attributed to variations in inter‐organ signalling by metabolic substrates or insulin. We conclude that an AMPK‐dependent pathway of signal transduction does mimic some of the metabolic changes associated with chronic exercise training, but does not affect expression of the MHC‐based structural phenotype. Thus, the metabolic and MHC‐based fibre types do not appear to be regulated in a co‐ordinated way, but may be independently modified by different signalling pathways.

The present study examined the effect of short‐term submaximal training on plasma acid‐base balance during exercise. The influence of water and ion exchange between plasma, active muscles and erythrocytes in the response to training were also studied. The contributions of independent physicochemical variables (i.e. strong ion difference ([SID]), total concentration of weak acids ([Atot]) and PO2) to changes in arterial (a) and femoral venous (v) plasma [H+] were examined in six subjects (age 24 ± 1.5 years; maximum oxygen consumption rate (V̇O2,max), 3.67 ± 0.24 l min−1) during steady‐state cycling for 15 min at each of 30, 65 and 75 % of V̇O2,maxbefore (pre) and after (post) training for 7 days on a cycle ergometer (2 h daily at 60 % V̇O2,max). The rise in [H+]aduring exercise was attenuated post‐training by 3 and 5 nequiv l−1(P< 0.05) at 65 and 75 % V̇O2,max, respectively, due first to less decrease in [SID]a, secondary to lower [Cl−]aand [Lac−]a; and second, to a reduction in [Atot]a, due to greater plasma volume and less plasma water flux (Jv) into leg muscle (P< 0.05). The rise in [H+]vwas also less in post‐training by 4.5 and 6 nequiv l−1(P< 0.05) at 65 and 75 % V̇O2,max, respectively, and attributed solely to lower [Atot]v(P< 0.05). Attenuation of exercise induced decreases in plasma [SID]aand [SID]vfrom rest to 75 % V̇O2,maxwas accompanied by reductions in erythrocyte Lac−and Cl−uptake (P< 0.05), and smaller increases in erythrocyte K+release (P< 0.05). We conclude that the training‐induced attenuation of the rise in plasma [H+]aand [H+]vduring incremental exercise resulted from adaptive changes within muscles (less Lac−production and less water uptake) and erythrocytes (less uptake of Lac−, Cl−and K+), leading to greater [SID] and lower [Atot] in both arterial and femoral venous plasma.

This study compares effects of chronic electrical stimulation on the expression levels of FGF-1, FGF-2 and their receptors (FGFR1, FGFR4) in rat tibialis anterior (TA) muscle of hypothyroid rat, as well as in satellite cell cultures derived from normal rat TA and soleus (SOL) muscles. In 5-day (5-d)-stimulated hypothyroid TA muscle, FGF-1 and FGF-2 mRNA levels were threefold elevated over control. FGFR1 and FGFR4 mRNAs were twofold and 1.5-fold elevated, respectively. In longer stimulated muscles, FGF-1 and FGFR4 mRNAs returned to basal levels, whereas FGF-2 mRNA remained elevated. FGFR1 mRNA decreased to control levels in 10-d stimulated muscles, but increased again after 20 days of stimulation. SOL- and TA-derived satellite cell cultures were stimulated for 5 days. At this time point, changes in myosin heavy chain isoforms were detectable consisting of increases in MHCI mRNA and decreases in MHCIIb and MHCIId mRNA. The comparison between 5-d-stimulated hypothyroid TA muscle and 5-d-stimulated TA- and SOL-derived satellite cell cultures revealed differences in the expression of FGF-1 and FGF-2, but similar expression levels of FGFR1 and FGFR4. Even though FGF-1 and FGF-2 mRNAs were elevated in the satellite cell cultures, their increases were less pronounced than in the stimulated hypothyroid muscle. Taking into consideration that skeletal muscle contains muscle fibres and various non-muscle tissues, e.g. blood vessels, these results suggest that the latter contribute to the observed increases in FGF-1 and FGF-2 expression in stimulated muscle.

Respiratory impairment in myasthenia gravis is usually attributed to weakness of the diaphragm and thoracic chest wall muscles, and is rarely attributed to upper airway obstruction. Myasthenia gravis is characterized by weakness of the striated muscles and usually affects those innervated by the bulbar cranial nerves. Weakness of these bulbar and upper airway muscles can lead to upper airway obstruction. To our knowledge, there are only five case reports in the literature associating upper airway obstruction with myasthenia gravis. Therefore, we attempted to further define its occurrence in myasthenia gravis patients by reviewing their flow volume loops. We present a case of upper airway obstruction causing respiratory symptoms in a myasthenia gravis patient. We then surveyed a total of 61 patients with myasthenia gravis who were tested in our pulmonary function laboratory between February 1990 and August 1993. Of these 61 patients, 12 had flow volume loops and 7 of these 12 disclosed a pattern of extrathoracic upper airway obstruction. The FVC was 80% or more in five of seven patients. Our data suggest that upper airway obstruction is much more common in patients with myasthenia gravis than previously recognized. In conclusion, we recommend the performance of flow volume loops in patients with myasthenia gravis to evaluate their respiratory impairment.

Chronic low-frequency stimulation was used to study the effects of enhanced contractile activity on satellite cell content and myosin isoform expression in extensor digitorum longus muscles from hypothyroid rats. As verified by immunohistochemical staining for desmin, vimentin, and myosin heavy chain (MHC) isoforms and by histological analysis, stimulation induced a transformation of existing fast fibers toward slower fibers without signs of fiber deterioration or regeneration. Immunohistochemically detected increases in MHC I and MHC IIa isoforms, as well as reduced numbers of fibers expressing the faster MHC isoforms, mirrored the rearrangement of the thick-filament composition. These changes, especially the upregulation of MHC IIa, were accompanied by an induction of developmental MHC isoforms in the transforming adult fibers. Satellite cell content rose 2.6-, 3.0-, and 3.7-fold over that of corresponding controls (P< 0.05 in all cases) in 5-, 10-, and 20-day-stimulated muscles, respectively. Hypothyroidism alone had no effect on satellite cell content but resulted in a significant reduction in fiber size. The relative satellite cell contents increased (P< 0.05) from 3.8% in euthyroid control muscles to 7.9, 11.5, and 13.8% in the 5-, 10-, and 20-day-stimulated hypothyroid muscles, respectively. In 20-day-stimulated muscles, the relative satellite cell content reached an almost twofold higher level than that of normal slow-twitch soleus muscle. This increase occurred concomitantly with a rise in myonuclear density, most probably because of the fusion of satellite cells with existing fibers.