Publications by authors named "Thomas J Burkholder"

Previous studies established strong links between morphological characteristics of mammalian hindlimb muscles and their sensorimotor functions during locomotion. Less is known about the role of forelimb morphology in motor outputs and generation of sensory signals. Here, we measured morphological characteristics of 46 forelimb muscles from six cats.

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Previous studies established strong links between morphological characteristics of mammalian hindlimb muscles and their sensorimotor functions during locomotion. Less is known about the role of forelimb morphology in motor outputs and generation of sensory signals. Here, we measured morphological characteristics of 46 forelimb muscles from 6 cats.

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The balance of ATP production and consumption is reflected in adenosine monophosphate (AMP) and nicotinamide adenine dinucleotide (NAD) content and has been associated with phenotypic plasticity in striated muscle. Some studies have suggested that AMPK-dependent plasticity may be an indirect consequence of increased NAD synthesis and SIRT1 activity. The primary goal of this study was to assess the interaction of AMP- and NAD-dependent signaling in adaptation of C2C12 myotubes.

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Background: Abnormal branched myofibers within skeletal muscles are commonly found in diverse animal models of muscular dystrophy as well as in patients. Branched myofibers from dystrophic mice are more susceptible to break than unbranched myofibers suggesting that muscles containing a high percentage of these myofibers are more prone to injury. Previous studies showed ubiquitous over-expression of mouse olfactory receptor 23 (mOR23), a G protein-coupled receptor, in wild type mice decreased myofiber branching.

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Muscle cells adjust their glucose metabolism in response to myriad stimuli, and particular attention has been paid to glucose metabolism after contraction, ATP depletion, and insulin stimulation. Each of these requires translocation of GLUT4 to the cell membrane, and may require activation of glucose transporters by p38. In contrast, AICAR stimulates glucose transport without activation of p38, suggesting that p38 activation may be an indirect consequence of accelerated glucose transport or metabolism.

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High-frequency electrical stimulation (HFES) leads to muscle hypertrophy, and attention has been drawn to the high forces involved. However, both mechanical and metabolic stresses occur simultaneously, and both stimuli influence signaling cascades related to protein synthesis. This study aimed to identify the immediate signaling correlates of contraction-induced force and metabolic stresses under the hypothesis that HFES induces growth-related signaling through mechanical stimulation.

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Statistical decomposition, including non-negative matrix factorization (NMF), is a convenient tool for identifying patterns of structured variability within behavioral motor programs, but it is unclear how the resolved factors relate to actual neural structures. Factors can be extracted from a uniformly sampled, low-dimension command space. In practical application, the command space is limited, either to those activations that perform some task(s) successfully or to activations induced in response to specific perturbations.

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Neuromusculoskeletal models solve the basic problem of determining how the body moves under the influence of external and internal forces. Existing biomechanical modeling programs often emphasize dynamics with the goal of finding a feed-forward neural program to replicate experimental data or of estimating force contributions or individual muscles. The computation of rigid-body dynamics, muscle forces, and activation of the muscles are often performed separately.

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Sarcopenia coincides with declines in several systemic processes that signal through the MAP kinase and Akt-mTOR-p70S6k cascades typically associated with muscle growth. Effects of aging on these pathways have primarily been examined in limb muscles, which experience substantial activity and neural changes in addition to systemic hormonal and metabolic changes. Head and neck muscles are reported to undergo reduced sarcopenia and disuse with age relative to limb muscles, suggesting muscle activity may contribute to maintaining mass with age.

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Postural control requires the coordination of force production at the limb endpoints to apply an appropriate force to the body. Subjected to horizontal plane perturbations, quadruped limbs stereotypically produce force constrained along a line that passes near the center of mass. This phenomenon, referred to as the force constraint strategy, may reflect mechanical constraints on the limb or body, a specific neural control strategy or an interaction among neural controls and mechanical constraints.

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Expression of developmental and unconventional myosin heavy chain (MHC) isoforms in some adult head and neck muscles is thought to reflect specific contractile demands of muscle fibers active during kinematically complex movements. Mammalian tongue muscles are active during oromotor behaviors that encompass a wide range of tongue movement speeds and tongue shape changes (e.g.

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Mechanical stretch rapidly activates multiple signaling cascades, including phospholipases and kinases, to stimulate protein synthesis and growth. The purpose of this study was to determine whether PLA2 activation contributes to stretch-induced phosphorylation of ERK2 in skeletal muscle myotubes. Myotubes derived from neonatal C57 mice were cultured on silicone membranes and subjected to brief cyclic stretch.

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Postural control requires the coordination of multiple muscles to achieve both endpoint force production and postural stability. Multiple muscle activation patterns can produce the required force for standing, but the mechanical stability associated with any given pattern may vary, and has implications for the degree of delayed neural feedback necessary for postural stability. We hypothesized that muscular redundancy is reduced when muscle activation patterns are chosen with respect to intrinsic musculoskeletal stability as well as endpoint force production.

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Maintaining the postural configuration of a limb such as an arm or leg is a fundamental neural control task that involves the coordination of multiple linked body segments. Biological systems are known to use a complex network of inter- and intra-joint feedback mechanisms arising from muscles, spinal reflexes and higher neuronal structures to stabilize the limbs. While previous work has shown that a small amount of asymmetric heterogenic feedback contributes to the behavior of these systems, a satisfactory functional explanation for this non-conservative feedback structure has not been put forth.

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The biomechanical principles underlying the organization of muscle activation patterns during standing balance are poorly understood. The goal of this study was to understand the influence of biomechanical inter-joint coupling on endpoint forces and accelerations induced by the activation of individual muscles during postural tasks. We calculated induced endpoint forces and accelerations of 31 muscles in a 7 degree-of-freedom, three-dimensional model of the cat hindlimb.

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Recent reports of slow tonic myosin heavy chain (MHCst) in human masticatory and laryngeal muscles suggest that MHCst may have a wider distribution in humans than previously thought. Because of the novelty of this finding, we sought to confirm the presence of MHCst in human masticatory and laryngeal muscles by reacting tissue from these muscles and controls from extraocular, intrafusal, cardiac, appendicular, and developmental muscle with antibodies (Abs) ALD-58 and S46, considered highly specific for MHCst. At Ab dilutions producing minimal reaction to muscle fibers positive for MHCI, only extraocular, intrafusal, and fetal tongue tissue reacted with Ab S46 had strong immunoreaction in an appreciable number of muscle fibers.

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Objective: Muscle fibre contractile diversity is thought to be increased by the hybridization of multiple myosin heavy chain (MHC) isoforms in single muscle fibres. Reports of hybrid fibres composed of MHCI and MHCII isoforms in human, but not macaque, tongue muscles, suggest a human adaptation for increased tongue muscle contractile diversity. Here we test whether hybrid fibres composed of MHCI and MHCII are unique to human tongue muscles or are present as well in the macaque.

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During postural responses to perturbations, horizontal plane forces generated by the cat hindlimb are stereotypically directed either towards or away from the animal's center of mass, independent of perturbation direction. We used a static, three-dimensional musculoskeletal model of the hindlimb to investigate possible biomechanical determinants of this "force constraint strategy." We hypothesized that directions in which the hindlimb can produce large forces are preferentially used in postural control.

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Mechanical signals are critical to the development and maintenance of skeletal muscle, but the mechanisms that convert these shape changes to biochemical signals is not known. When a deformation is imposed on a muscle, changes in cellular and molecular conformations link the mechanical forces with biochemical signals, and the close integration of mechanical signals with electrical, metabolic, and hormonal signaling may disguise the aspect of the response that is specific to the mechanical forces. The mechanically induced conformational change may directly activate downstream signaling and may trigger messenger systems to activate signaling indirectly.

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Skeletal muscle increases in size due to weight bearing loads or passive stretch. This growth response is dependent in part upon myoblast proliferation. Although skeletal muscles are responsive to mechanical forces, the effect on myoblast proliferation remains unknown.

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Mechanotransduction is critical to the maintenance and growth of skeletal muscle, but the mechanism by which cellular deformations are converted to biochemical signals remains unclear. Among the earliest and most ubiquitous responses to mechanical stimulation is the phosphorylation and activation of mitogen-activated protein kinases, in particular ERK2. Caveolin-3 (CAV-3) binds ERK2 and its upstream activators in inactive states on the caveolae of resting muscle.

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Several lines of evidence suggest that muscle cells can distinguish between specific mechanical stimuli. To test this concept, we subjected C(2)C(12) myotubes to cyclic uniaxial or multiaxial stretch. Both types of stretch induced an increase in extracellular signal-regulated kinase (ERK) and protein kinase B (PKB/Akt) phosphorylation, but only multiaxial stretch induced ribosomal S6 kinase (p70(S6k)) phosphorylation.

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This article describes a three-dimensional musculoskeletal model of the feline hindlimb based on digitized musculoskeletal anatomy. The model consists of seven degrees of freedom: three at the hip and two each at the knee and ankle. Lines of action and via points for 32 major muscles of the limb are described.

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Mechanical signals are critical to the growth and maintenance of skeletal muscle, but the mechanism by which these signals are transduced by the cell remains unknown. This work examined the hypothesis that stretch conditions influence membrane permeability consistent with a role for membrane permeability in mechanotransduction. C2C12 myotubes were grown in conditions that encourage uniform alignment and subjected to uniform mechanical deformation in the presence of fluorescein labeled dextran to evaluate membrane permeability as a function of stretch amplitude and velocity.

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