The ascidian mouth opening is derived from the anterior neuropore: Reassessing the mouth/neural tube relationship in chordate evolution

The relative positions of the brain and mouth are of central importance for models of chordate evolution. The dorsal hollow neural tube and the mouth have often been thought of as developmentally distinct structures that may have followed independent evolutionary paths. In most chordates however, including vertebrates and ascidians, the mouth primordia have been shown to fate to the anterior neural boundary. In ascidians such as Ciona there is a particularly intimate relationship between brain and mouth development, with a thin canal connecting the neural tube lumen to the mouth primordium at larval stages. This so-called neurohypophyseal canal was previously thought to be a secondary connection that formed relatively late, after the independent formation of the mouth primordium and the neural tube. Here we show that the Ciona neurohypophyseal canal is present from the end of neurulation and represents the anteriormost neural tube, and that the future mouth opening is actually derived from the anterior neuropore. The mouth thus forms at the anterior midline transition between neural tube and surface ectoderm. In the vertebrate Xenopus, we find that although the mouth primordium is not topologically continuous with the neural tube lumen, it nonetheless forms at this same transition point. This close association between the mouth primordium and the anterior neural tube in both ascidians and amphibians suggests that the evolution of these two structures may be more closely linked than previously appreciated.     

Functional aberration of myofibrils by cardiomyopathy-causing mutations in the coiled-coil region of the troponin-core domain

Two cardiomyopathy-causing mutations, E244D and K247R, in human cardiac troponin T (TnT) are located in the coiled-coil region of the Tn-core domain. To elucidate effects of mutations in this region on the regulatory function of Tn, we measured Ca²⁺-dependent ATPase activity of myofibrils containing various mutants of TnT at these residues. The results confirmed that the mutant E244D increases the maximum ATPase activity without changing the Ca²⁺-sensitivity. The mutant K247R was shown for the first time to have the effect similar to the mutant E244D. Furthermore, various TnT mutants (E244D, E244M, E244A, E244K, K247R, K247E, and K247A) showed various effects on the maximum ATPase activity while the Ca²⁺-sensitivity was unchanged. Molecular dynamics simulations of the Tn-core containing these TnT mutants suggested that the hydrogen-bond network formed by the side chains of neighboring residues around residues 244 and 247 is important for Tn to function properly.     

Basic characteristics between mechanomyogram and muscle force during twitch and tetanic contractions in rat skeletal muscles

The mechanomyogram (MMG) is a signal measured by various vibration sensors for slight vibrations induced by muscle contraction, and it reflects the muscle force during electrically induced-contraction or until 60%–70% maximum voluntary contraction, so the MMG is considered an alternative and novel measurement tool for muscle strength. We simultaneously measured the MMG and muscle force in the gastrocnemius (GC), vastus intermedius (VI), and soleus (SOL) muscles of rats. The muscle force was measured by attaching a hook to the tendon using a load cell, and the MMG was measured using a charged-coupled device-type displacement sensor at the middle of the target muscle. The MMG-twitch waveform was very similar to that of the muscle force; however, the half relaxation time and relaxation time (10%), which are relaxation parameters, were prolonged compared to those of the muscle force. The MMG amplitude correlated with the muscle force. Since stimulation frequencies that are necessary to evoke tetanic progression have a significant correlation with the twitch parameter, there is a close relationship between twitch and tetanus in the MMG signal. Therefore, we suggest that the MMG, which is electrically induced and detected by a laser displacement sensor, may be an alternative tool for measuring muscle strength.     

Are there neuromuscular differences on proximal and distal joints in patellofemoral pain people? A systematic review and meta-analysis

We aim to determine the neuromuscular differences in proximal and distal joints between patellofemoral pain (PFP) and healthy participants. Relevant articles were selected through seven databases. Studies comparing electromyography (EMG) or morphology parameters of trunk, hip, ankle/foot joints in PFP people compared to a healthy control group (CG) were included. 1458 studies were identified, from which 36 were included in the systematic review [PFP, n = 655; CG, n = 649] (31 involving EMG) and 32 in the meta-analysis (27 involving EMG). 75% of studies presented moderate to high methodological quality. The meta-analysis demonstrated that, compared to CG, PFP have: (i) similar transversus abdominis/internal oblique and erector spinae muscle onset, independently of sex; (ii) similar EMG amplitude of gluteus medius and gluteus maximus, independently of sex or task performed; (iii) similar gluteus medius muscle onset, independently of sex or task performed; (iv) similar gluteus maximus muscle onset, independently of sex; (v) a small effect for a shorter activation duration of gluteus medius (0.50; 95% CI [0.07; 0.93]; p = 0.02); (vi) a medium effect for a shorter activation duration of gluteus medius during stair/step down task (0.81; 95% CI [0.18; 1.45]; p = 0.01); (vii) similar external oblique, gluteus maximus, tensor fascia latae, tibialis anterior and fibularis muscle thickness and (viii) a small effect for a smaller gluteus medius muscle thickness (0.52; 95% CI [0.22; 0.82]; p = 0.007). We were not able to perform meta-analysis for EMG at distal joints. Neuromuscular differences in PFP seems to occur only in the gluteus medius muscle. Due to high heterogeneity and several methodological concerns observed, mainly in EMG studies, the interpretation of these results needs caution.     

Estimation of muscle fiber conduction velocity from two-dimensional surface EMG recordings in dynamic tasks

The aims of this study are (1) to demonstrate that multi-channel surface electromyographic (EMG) signals can be detected with negligible artifacts during fast dynamic movements with an adhesive two-dimensional (2D) grid of 64 electrodes and (2) to propose a new method for the estimation of muscle fiber conduction velocity from short epochs of 2D EMG recordings during dynamic tasks. Surface EMG signals were collected from the biceps brachii muscle of four subjects with a grid of 13 × 5 electrodes during horizontal elbow flexion/extension movements (range 120–170°) at the maximum speed, repeated cyclically for 2 min. Action potentials propagating between the innervation zone and tendon regions could be detected during the dynamic task. A maximum likelihood method for conduction velocity estimation from the 2D grid using short time intervals was developed and applied to the experimental signals. The accuracy of conduction velocity estimation, assessed from the standard deviation of the residual of the regression line with respect to time, decreased from (range) 0.20–0.33 m/s using one column to 0.02–0.15 m/s when combining five columns of the electrode grid. This novel method for estimation of muscle fiber conduction velocity from 2D EMG recordings provides an estimate which is global in space and local in time, thus representative of the entire muscle yet able to track fast changes over the execution of a task, as is required for assessing muscle properties during fast movements.     

Genes required for embryonic muscle development in Drosophila melanogaster A survey of the X chromosome

We have begun a genetic analysis to dissect the process of myogenesis by surveying the X chromosome of Drosophila melanogaster for mutations that affect embryonic muscle development. Using polarised light microscopy and antibody staining techniques we analysed embryos hemizygous for a series of 67 deletion mutations that together cover an estimated 85% of the X chromosome, or 16.5% of the genome. Whereas the mature wild type embryo has a regular array of contractile muscles that insert into the epidermis, 31 of the deletion mutants have defects in muscle pattern, contractility or both, that cannot be attributed simply to epidermal defects and identify functions required for wild type muscle development. We have defined mutant pattern phenotypes that can be described in terms of muscle absences, incomplete myoblast fusion, failure of attachment of the muscle to the epidermis or mispositioning of attachment sites. Thus muscle development can be mutationally disrupted in characteristic and interpretable ways. The areas of overlap of the 31 deletions define 19 regions of the X chromosome that include genes whose products are essential for various aspects of myogenesis. We conclude that our screen can usefully identify loci coding for gene products essential in muscle development.     

A predictive model of moment-angle characteristics in human skeletal muscle: application and validation in muscles across the ankle joint

In the present work, a generic model for the prediction of moment-angle characteristics in individual human skeletal muscles is presented. The model's prediction is based on the equation M = V x Lo(-1)sigma c cos phi x d, where M, V, and Lo are the moment-generating potential of the muscle, the muscle volume and the optimal muscle fibre length, respectively, and sigma, phi and d are the stress-generating potential of the muscle fibres, their pennation angle and the tendon moment arm length, respectively, at any given joint angle. The input parameters V, Lo, sigma, phi and d can be measured or derived mechanistically. This eliminates the common problem of the necessity to estimate one or more of the input parameters in the model by fitting its outcome to experimental results often inappropriate for the function modelled. The model's output was validated by comparisons with the moment-angle characteristics of the gastrocnemius (GS) and tibialis anterior (TA) muscles in six men, determined experimentally using voluntary contractions at several combinations of ankle and knee joint angles for the GS muscle and electrical stimulation for the TA muscle. Although the model predicted realistically the pattern of moment-angle relationship in both muscles, it consistently overestimated the GS muscle M and consistently underestimated the TA muscle M, with the difference gradually increasing from dorsiflexion to plantarflexion in both cases. The average difference between predicted and measured M was 14% for the GS muscle and 10% for the TA muscle. Approximating the muscle fibres as a single sarcomere in both muscles and failing to achieve complete TA muscle activation by electrical stimulation may largely explain the differences between theory and experiment.     

Suppressor of cytokine signaling 1 suppresses muscle differentiation through modulation of IGF-I receptor signal transduction

Suppressor of cytokine signaling (SOCS) 1 was initially identified as an intracellular negative feedback regulator of the JAK-STAT signal pathway. Recently, it has been suggested that SOCS1 affects signals of growth factors and hormones. One of them, SOCS1, is also known to be involved in auto-regulation of IRS-1-mediated signaling. However, the mechanism(s) of SOCS1 induction by insulin-like growth factor (IGF)-I and a role of SOCS1 on IGF-I receptor-mediated signaling are not clarified. Here, we investigate SOCS1 on muscle differentiation. We found that muscle differentiation was suppressed in SOCS1 stable transformant C2C12 myoblasts, while it was promoted in SOCS1-deficient myoblasts. Additionally, SOCS1 augmented MEK phosphorylation and reduced Akt phosphorylation induced by IGF-I. Then, SOCS1 stable transformant C2C12 myoblasts, infected with adenovirus bearing constitutively active Akt, have the ability to differentiate again. Collectively, these findings suggest that SOCS1 suppresses muscle differentiation through negative feedback regulation of IGF-I receptor-mediated signaling.     

Effects of NS1608 on MaxiK Channels in Smooth Muscle Cells from Urinary Bladder

Using the patch-clamp technique, we have characterized membrane currents in single detrusor smooth muscle cells from rat and human urinary bladder. From the voltage- and Ca²⁺-dependence of the current as well as the single channel conductance we conclude that rat and human urinary bladder smooth muscle cells express MaxiK channels. In smooth muscle cells from rat urinary bladder we tested the action of NS1608 on current through these MaxiK channels. Application of 10 μm NS1608 increased the amplitude of the current and this increase could be explained by a shift in the activation voltage of the MaxiK channels ∼100 mV towards more negative potentials. Charybdotoxin as well as paxilline, well known blockers of MaxiK channels, were able to reduce current through MaxiK channels in our cell preparation. In addition, application of 10 μm NS1608 hyperpolarized the membrane potential of the investigated cells. This hyperpolarization could be antagonized by the application of paxilline. We conclude that application of NS1608 results in the opening of MaxiK channels under physiological conditions that leads to a hyperpolarization of the cells. This hyperpolarization in turn could relax urinary bladder smooth muscle cells. MaxiK channels in these cells could therefore play a role in directly controlling muscle tone by regulating the membrane potential. This opens up the possibility of MaxiK channels being targets for the treatment of urge incontinence. Received: 19 July/Revised: 20 September 1999