Synchronous Muscle Research Articles

Engineered Heart Tissues for Standard 96-Well Tissue Culture Plates.

Engineered heart tissues (EHTs) have been shown to be a valuable platform for disease investigation and therapeutic testing by increasing human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) maturity and better recreating the native cardiac environment. The protocol detailed in this chapter describes the generation of miniaturized EHTs (mEHTs) incorporating hiPSC-CMs and human stromal cells in a fibrin hydrogel. This platform utilizes an array of silicone posts designed to fit in a standard 96-well tissue culture plate. Stromal cells and hiPSC-CMs are cast in a fibrin matrix suspended between two silicone posts, forming an mEHT that produces synchronous muscle contractions. The platform presented here has the potential to be used for high throughput characterization and screening of disease phenotypes and novel therapeutics through measurements of the myocardial function, including contractile force and calcium handling, and its compatibility withimmunostaining.

Synchronous Muscle Synergy Evaluation of Jaw Muscle Activities during Chewing at Different Speeds, a Preliminary Study.

Human mastication is a complex and rhythmic biomechanical process regulated by the central nervous system (CNS). Muscle synergies are a group of motor primitives that the CNS may combine to simplify motor control in human movement. This study aimed to apply the non-negative matrix factorization approach to examine the coordination of the masticatory muscles on both sides during chewing. Ten healthy individuals were asked to chew gum at different speeds while their muscle activity was measured using surface electromyography of the right and left masseter and temporalis muscles. Regardless of the chewing speed, two main muscle synergies explained most of the muscle activity variation, accounting for over 98% of the changes in muscle patterns (variance accounted for >98%). The first synergy contained the chewing side masseter muscle information, and the second synergy provided information on bilateral temporalis muscles during the jaw closing. Furthermore, there was robust consistency and high degrees of similarity among the sets of muscle synergy information across different rate conditions and participants. These novel findings in healthy participants supported the hypothesis that all participants in various chewing speed conditions apply the same motor control strategies for chewing. Furthermore, these outcomes can be utilized to design rehabilitation approaches such as biofeedback therapy for mastication disorders.

DYNAMICS OF THE EEG SENSORIMOTOR RHYTHM DURING MENTAL REPETITION OF THE OBSERVED MOVEMENT

Mental simulation of one’s own movement, or imagery of movement, as well as observation of other people’s movements are used in neurorehabilitation as methods of stimulation of sensorimotor parts of the brain. The present work tests a new way of representation - mental simulation of movement, synchronous with the movement observed from the first person on a video screen. The objectives of the study were to compare the reactivity of sensorimotor EEG rhythms during voluntary movement representation and representation following a video stimulus, and to identify the relationship between the phases of movement in the video and the dynamics of EEG patterns. The study involved 30 healthy volunteers in whom a 69-channel encephalogram was recorded during their performance and presentation of right thumb movements in two modes: arbitrarily (without an external reference) and synchronously imitating movement on a video clip. During EEG analysis, individual spatial-frequency components with the highest EEG mu-rhythm reactivity (8–14 Hz) were identified in the subjects, followed by quantitative assessment of desynchronization under the studied conditions based on analysis of probability density distributions of mu-rhythm power. A generalized additive model describing the function of responses to single events in the observed movements and their summation during serial execution or presentation of the movements was applied to assess the relationship between the dynamics of mu-rhythm desynchronization and video events. It was shown that the mental kinesthetic simulation of the observed movement did not result in increased desynchronization of sensorimotor rhythms compared to the voluntary representation of the same movement. It was found for the first time that there are perturbations in the temporal course of desynchronization of the mu-rhythm that depend on the phase and speed of the observed movement both during its synchronous muscle repetition and during mental synchronous imitation. The results obtained can be used to optimize movement parameters in individual systems of ideomotor training with EEG control to achieve the greatest sensorimotor activation.

Influence of internal muscle properties on muscle shape change and gearing in the human gastrocnemii.

Skeletal muscles bulge when they contract. These three-dimensional shape changes, coupled with fiber rotation, influence a muscle's mechanical performance by uncoupling fiber velocity from muscle belly velocity (i.e., gearing). Muscle shape change and gearing are likely mediated by the interaction between internal muscle properties and contractile forces. Muscles with greater stiffness and intermuscular fat, due to aging or disuse, may limit a muscle's ability to bulge in width, subsequently causing higher gearing. The aim of this study was to determine the influence of internal muscle properties on shape change, fiber rotation, and gearing in the medial (MG) and lateral gastrocnemii (LG) during isometric plantar flexion contractions. Multimodal imaging techniques were used to measure muscle shear modulus, intramuscular fat, and fat-corrected physiological cross-sectional area (PCSA) at rest, as well as synchronous muscle architecture changes during submaximal and maximal contractions in the MG and LG of 20 young (24 ± 3 yr) and 13 older (70 ± 4 yr) participants. Fat-corrected PCSA was positively associated with fiber rotation, gearing, and changes in thickness during submaximal contractions, but it was negatively associated with changes in thickness at maximal contractions. Muscle stiffness and intramuscular fat were related to muscle bulging and reduced fiber rotation, respectively, but only at high forces. Furthermore, the MG and LG had varied internal muscle properties, which may relate to the differing shape changes, fiber rotations, and gearing behaviors observed at each contraction level. These results indicate that internal muscle properties may play an important role in mediating in vivo muscle shape change and gearing, especially during high-force contractions.NEW & NOTEWORTHY Here, we measured internal muscle properties in vivo to determine their influence on the varying shape change and gearing behaviors in the synergistic gastrocnemii muscles. These relationships have previously only been hypothesized or examined within isolated muscles during supramaximal contractions. Our results contribute to a more comprehensive understanding of the factors that influence a muscle's mechanical response to force with implications for preventing or treating muscle deficits associated with aging, disease, and disuse.

Physics-informed Deep Learning for Musculoskeletal Modelling: Predicting Muscle Forces and Joint Kinematics from Surface EMG.

Musculoskeletal models have been widely used for detailed biomechanical analysis to characterise various functional impairments given their ability to estimate movement variables (i.e., muscle forces and joint moments) which cannot be readily measured in vivo. Physics-based computational neuromusculoskeletal models can interpret the dynamic interaction between neural drive to muscles, muscle dynamics, body and joint kinematics and kinetics. Still, such set of solutions suffers from slowness, especially for the complex models, hindering the utility in real-time applications. In recent years, data-driven methods have emerged as a promising alternative due to the benefits in speedy and simple implementation, but they cannot reflect the underlying neuromechanical processes. This paper proposes a physics-informed deep learning framework for musculoskeletal modelling, where physics-based domain knowledge is brought into the data-driven model as soft constraints to penalise/regularise the data-driven model. We use the synchronous muscle forces and joint kinematics prediction from surface electromyogram (sEMG) as the exemplar to illustrate the proposed framework. Convolutional neural network (CNN) is employed as the deep neural network to implement the proposed framework. Simultaneously, the physics law between muscle forces and joint kinematics is used the soft constraint. Experimental validations on two groups of data, including one benchmark dataset and one self-collected dataset from six healthy subjects, are performed. The experimental results demonstrate the effectiveness and robustness of the proposed framework.

An early midbrain sensorimotor pathway is involved in the timely initiation and direction of swimming in the hatchling Xenopus laevis tadpole.

Vertebrate locomotion is heavily dependent on descending control originating in the midbrain and subsequently influencing central pattern generators in the spinal cord. However, the midbrain neuronal circuitry and its connections with other brainstem and spinal motor circuits has not been fully elucidated. Vertebrates with very simple nervous system, like the hatchling Xenopus laevis tadpole, have been instrumental in unravelling fundamental principles of locomotion and its suspraspinal control. Here, we use behavioral and electrophysiological approaches in combination with lesions of the midbrain to investigate its contribution to the initiation and control of the tadpole swimming in response to trunk skin stimulation. None of the midbrain lesions studied here blocked the tadpole's sustained swim behavior following trunk skin stimulation. However, we identified that distinct midbrain lesions led to significant changes in the latency and trajectory of swimming. These changes could partly be explained by the increase in synchronous muscle contractions on the opposite sides of the tadpole's body and permanent deflection of the tail from its normal position, respectively. We conclude that the tadpole's embryonic trunk skin sensorimotor pathway involves the midbrain, which harbors essential neuronal circuitry to significantly contribute to the appropriate, timely and coordinated selection and execution of locomotion, imperative to the animal's survival.

Inter-muscular networks of synchronous muscle fiber activation.

Skeletal muscles continuously coordinate to facilitate a wide range of movements. Muscle fiber composition and timing of activation account for distinct muscle functions and dynamics necessary to fine tune muscle coordination and generate movements. Here we address the fundamental question of how distinct muscle fiber types dynamically synchronize and integrate as a network across muscles with different functions. We uncover that physiological states are characterized by unique inter-muscular network of muscle fiber cross-frequency interactions with hierarchical organization of distinct sub-networks and modules, and a stratification profile of links strength specific for each state. We establish how this network reorganizes with transition from rest to exercise and fatigue-a complex process where network modules follow distinct phase-space trajectories reflecting their functional role in movements and adaptation to fatigue. This opens a new area of research, Network Physiology of Exercise, leading to novel network-based biomarkers of health, fitness and clinical conditions.

The flying insect thoracic cuticle is heterogenous in structure and in thickness-dependent modulus gradation

The thorax is a specialized structure central to insect flight. In the thorax, flight muscles are surrounded by a thin layer of cuticle. The structure, composition, and material properties of this chitinous structure may influence the efficiency of the thorax in flight. However, these properties, as well as their variation throughout the thorax and between insect taxa, are not known. We provide a multi-faceted assessment of thorax cuticle for fliers with asynchronous (honey bee; Apis mellifera) and synchronous (hawkmoth; Manduca sexta) muscles. These muscle types are defined by the relationship between their activation frequency and the insect's wingbeat frequency. We investigated cuticle structure using histology, resilin distribution through confocal laser scanning microscopy, and modulus gradation with nanoindentation. Our results suggest that thorax cuticle properties are highly dependent on anatomical region and species. Modulus gradation, but not mean modulus, differed between the two types of fliers. In some regions, A. mellifera had a positive linear modulus gradient from cuticle interior to exterior of about 2 GPa. In M. sexta, modulus values through cuticle thickness were not well represented by linear fits. We utilized finite element modeling to assess how measured modulus gradients influenced maximum stress in cuticle. Stress was reduced when cuticle with a linear gradient was compressed from the high modulus side. These results support the protective role of the A. mellifera thorax cuticle. Our multi-faceted assessment advances our understanding of thorax cuticle structural and material heterogeneity and the potential benefits of material gradation to flying insects. Statement of significanceThe insect thorax is essential for efficient flight but questions remain about the contribution of the exoskeletal cuticle. We investigated the microscale properties of the thorax cuticle, a crucial step to determine its role in flight. Techniques including histology, nanoindentation, and confocal laser scanning microscopy revealed that cuticle properties vary through cuticle thickness, by thorax region, and between species with asynchronous (honey bee; Apis mellifera) and synchronous (hawkmoth; Manduca sexta) muscles. This variation highlights the importance of high resolution cuticle assessment for flying insect lineages and points to factors that may (modulus gradation) and may not (mean modulus) contribute to different flight forms. Understanding material variation in the thorax may inform design of technologies inspired by insects, such as mobile micro robots.

Differential Expression of Drosophila Transgelins Throughout Development.

Transgelins are a conserved family of actin-binding proteins involved in cytoskeletal remodeling, cell contractility, and cell shape. In both mammals and Drosophila, three genes encode transgelin proteins. Transgelins exhibit a broad and overlapping expression pattern, which has obscured the precise identification of their role in development. Here, we report the first systematic developmental analysis of all Drosophila transgelin proteins, namely, Mp20, CG5023, and Chd64 in the living organism. Drosophila transgelins display overall higher sequence identity with mammalian TAGLN-3 and TAGLN-2 than with TAGLN. Detailed examination in different developmental stages revealed that Mp20 and CG5023 are predominantly expressed in mesodermal tissues with the onset of myogenesis and accumulate in the cytoplasm of all somatic muscles and heart in the late embryo. Notably, at postembryonic developmental stages, Mp20 and CG5023 are detected in the gut’s circumferential muscles with distinct subcellular localization: Z-lines for Mp20 and sarcomere and nucleus for CG5023. Only CG5023 is strongly detected in the adult fly in the abdominal, leg, and synchronous thoracic muscles. Chd64 protein is primarily expressed in endodermal and ectodermal tissues and has a dual subcellular localization in the cytoplasm and the nucleus. During the larval–pupae transition, Chd64 is expressed in the brain, eye, legs, halteres, and wings. In contrast, in the adult fly, Chd64 is expressed in epithelia, including the alimentary tract and genitalia. Based on the non-overlapping tissue expression, we predict that Mp20 and CG5023 mostly cooperate to modulate muscle function, whereas Chd64 has distinct roles in epithelial, neuronal, and endodermal tissues.

Localization of the Elastic Proteins in the Flight Muscle of Manduca sexta.

The flight muscle of Manduca sexta (DLM1) is an emerging model system for biophysical studies of muscle contraction. Unlike the well-studied indirect flight muscle of Lethocerus and Drosophila, the DLM1 of Manduca is a synchronous muscle, as are the vertebrate cardiac and skeletal muscles. Very little has been published regarding the ultrastructure and protein composition of this muscle. Previous studies have demonstrated that DLM1 express two projectin isoform, two kettin isoforms, and two large Salimus (Sls) isoforms. Such large Sls isoforms have not been observed in the asynchronous flight muscles of Lethocerus and Drosophila. The spatial localization of these proteins was unknown. Here, immuno-localization was used to show that the N-termini of projectin and Salimus are inserted into the Z-band. Projectin spans across the I-band, and the C-terminus is attached to the thick filament in the A-band. The C-terminus of Sls was also located in the A-band. Using confocal microscopy and experimental force-length curves, thin filament lengths were estimated as ~1.5 µm and thick filament lengths were measured as ~2.5 µm. This structural information may help provide an interpretive framework for future studies using this muscle system.

F167. Usefulness of combined surface polymyographic and back averaging techniques as essential tools in the evaluation of axial myoclonus of propriospinal origin: Two case presentation

Introduction Propriospinal Myoclonus (PSM) was first described as flexion or extension nonrhythmic repetitive myoclonic jerks arising in axial muscles, spreading to more caudal and rostral segments. Electrophysiologic features include a fixed pattern of muscle activation, slow conduction velocity, EMG burst duration of less than 1.000 ms, synchronous activation of agonist and antagonist muscles, and no facial involvement. The purpose of our study is to describe the usefulness of surface polymyography (sPMG) and jerk-lock techniques in the diagnosis of PSM. Methods Two patients with an involuntary periodic movement disorder were examined. Case 1: Patient underwent sPMG, back averaging and SSEPs testing. For jerk lock averaging, EMG with parallel EEG was registered from tibialis anterior (TA) muscle. SPMG activity was recorded with electrodes placed on paraspinalis dorsalis (PD) and lumbaris (PL), rectus femoris (RF), TA, and gastrocnemius (GM) muscles. The activity was scored for order of muscle recruitment, consistency of activation of the first muscle, consistency of pattern of spread of muscles involved, burst duration, and synchronous co-contraction muscle activation. Case 2: Back averaging, sPMG and SSEPs recordings were performed. For back averaging, sPMG was recorded from masseter, deltoideus, rectus abdominis (RA), PD, PL, RF and TA muscles. Triggers were set at burst onset of the initial muscle. SPMG recording muscles and study parameters were alike to the previous case, except that rectus abdominis rostral (RARA) and caudal aspect (RACA) muscles were added. Results Case 1: A 55-years old male presented with persistent jerks and involuntary lower limbs twitching. Awake and daytime sleep EEG did not show time-locked cortical correlate activity. SSEPs recordings were normal. During sPMG, burst activity started at PL muscle spreading upward to PD muscles and downward to right RF, TA and GM muscles. EMG burst occurred irregularly every 20–60 s, with duration of 100–800 ms. Case 2: A 60-years old male presented with excessive daytime sleepiness due to an acute onset of sudden abdominal jerks at the sleep- wake transition time. All jerks occurred at the transition from wake to sleep, and there were not Bereitschaftspotential preceding spontaneous activity. Burst started in RACA with rostro-caudal propagation. SPMG confirmed activation of the first muscle and consistency of pattern of spread. Jerks occurred irregularly every 20–60 s, with 100–800 ms duration. Co-contraction was evident. The latency of jerks recorded from RACA to RARA and from PD to TA was 55 ms and 95 ms, allowing calculation of spinal conduction velocity, found to be 9.1 ms−1 and 8.6 ms−1. SSEPs recordings were normal. Conclusion PMS is a rare movement disorder that arises from a spinal generator, with rostro-caudal propagation, which shows a typical electrophysiological pattern. We praise the using of sPMG to assess recruitment variability, combined with back averaging recordings to help to establish the diagnosis.

Fundamental constraints in synchronous muscle limit superfast motor control in vertebrates.

Superfast muscles (SFMs) are extremely fast synchronous muscles capable of contraction rates up to 250 Hz, enabling precise motor execution at the millisecond time scale. SFM phenotypes have been discovered in most major vertebrate lineages, but it remains unknown whether all SFMs share excitation-contraction coupling pathway adaptations for speed, and if SFMs arose once, or from independent evolutionary events. Here, we demonstrate that to achieve rapid actomyosin crossbridge kinetics bat and songbird SFM express myosin heavy chain genes that are evolutionarily and ontologically distinct. Furthermore, we show that all known SFMs share multiple functional adaptations that minimize excitation-contraction coupling transduction times. Our results suggest that SFM evolved independently in sound-producing organs in ray-finned fish, birds, and mammals, and that SFM phenotypes operate at a maximum operational speed set by fundamental constraints in synchronous muscle. Consequentially, these constraints set a fundamental limit to the maximum speed of fine motor control.

Efficient Flight Control via Mechanical Impedance Manipulation: Energy Analyses for Hummingbird-Inspired MAVs

Within the growing family of unmanned aerial vehicles (UAV), flapping-wing micro aerial vehicles (MAV) are a relatively new field of research. Inspired by small size and agile flight of insects and birds, these systems offer a great potential for applications such as reconnaissance, surveillance, search and rescue, mapping, etc. Nevertheless, practicality of these vehicles depends on how we address various challenges ranging from control methodology to morphological construction and power supply design. A reasonable approach to resolving such problems is to acquire further inspiration from solutions in nature. Through modeling synchronous muscles in insects, we have shown that manipulation of mechanical impedance properties at wing joints can be a very efficient method for controlling lift and thrust production in flapping-wing MAVs. In the present work, we describe how this approach can be used to decouple lift/thrust regulation, thus reducing the complexity of flight controller. Although of simple design, this controller is still capable of demonstrating a high degree of precision and maneuverability throughout various simulated flight experiments with different types of trajectories. Furthermore, we use these flight simulations to investigate the power requirements of our control approach. The results indicate that these characteristics are considerably lower compared to when conventional control strategies--methods that often rely on manipulating stroke properties such as frequency or magnitude of the flapping motion--are employed. With less power demands, we believe our proposed control strategy is able to significantly improve flight time in future flapping-wing MAVs.

Long-term plasticity may be manifested as reduction or expansion of cortical representations of actively used muscles in motor skill specialists

Our aim was to study long-term plasticity in the organization of cortical muscle representations due to extensive motor training for different skills. We were especially interested in whether skill-specific demands on independent hand muscle movements and synchronous leg muscle movements are reflected differently in the reorganization of muscle representations. We used navigated transcranial magnetic stimulation to estimate the size of cortical representations of opponens pollicis, abductor digiti minimi, and tibialis anterior muscles in five string instrument players, five figure skaters, and five controls. The extent of the representation area was presented as an amplitude-area curve showing the spatial distribution of motor evoked potentials. The size of representation areas was compared between the dominant and nondominant hemispheres and between the groups. The representation area of the left abductor digiti minimi (critical for reaching right tones) in the right, nondominant hemisphere was smaller in string players and the representation area of the tibialis anterior in the dominant hemisphere (critical for jumps) was larger in figure skaters when compared with controls. Reorganization in the motor cortex may differ depending upon the skill and an individual muscle's role in the skill. A smaller representation area of the independently used hand muscle in masters of fine motor skills may reflect long-term plasticity toward more focused representation, which may be beneficial in accurate and discrete cortical control of the muscle. Larger cortical representations are related to skill demanding coactivation of proximal and distal lower limb muscles.

Highly efficient in vivo delivery of PMO into regenerating myotubes and rescue in laminin-α2 chain-null congenital muscular dystrophy mice

Phosphorodiamidate morpholino oligomer (PMO)-mediated exon skipping is among the more promising approaches to the treatment of several neuromuscular disorders including Duchenne muscular dystrophy. The main weakness of this approach arises from the low efficiency and sporadic nature of the delivery of charge-neutral PMO into muscle fibers, the mechanism of which is unknown. In this study, to test our hypothesis that muscle fibers take up PMO more efficiently during myotube formation, we induced synchronous muscle regeneration by injection of cardiotoxin into the tibialis anterior muscle of Dmd exon 52-deficient mdx52 and wild-type mice. Interestingly, by in situ hybridization, we detected PMO mainly in embryonic myosin heavy chain-positive regenerating fibers. In addition, we showed that PMO or 2′-O-methyl phosphorothioate is taken up efficiently into C2C12 myotubes when transfected 24–72 h after the induction of differentiation but is poorly taken up into undifferentiated C2C12 myoblasts suggesting efficient uptake of PMO in the early stages of C2C12 myotube formation. Next, we tested the therapeutic potential of PMO for laminin-α2 chain-null dy3K/dy3K mice: a model of merosin-deficient congenital muscular dystrophy (MDC1A) with active muscle regeneration. We confirmed the recovery of laminin-α2 chain and slightly prolonged life span following skipping of the mutated exon 4 in dy3K/dy3K mice. These findings support the idea that PMO entry into fibers is dependent on a developmental stage in myogenesis rather than on dystrophinless muscle membranes and provide a platform for developing PMO-mediated therapies for a variety of muscular disorders, such as MDC1A, that involve active muscle regeneration.

Microstimulation Activates a Handful of Muscle Synergies

Muscle synergies have been proposed as a mechanism to simplify movement control. Whether these coactivation patterns have any physiological reality within the nervous system remains unknown. Here we applied electrical microstimulation to motor cortical areas of rhesus macaques to evoke hand movements. Movements tended to converge toward particular postures, driven by synchronous bursts of muscle activity. Across stimulation sites, the muscle activations were reducible to linear sums of a few basic patterns-each corresponding to a muscle synergy evident in voluntary reach, grasp, and transport movements made by the animal. These synergies were represented nonuniformly over the cortical surface. We argue that the brain exploits these properties of synergies-postural equivalence, low dimensionality, and topographical representation-to simplify motor planning, even for complex hand movements.

Low-grade Smooth Muscle Tumors of the Primary and the Secondary Mullerian System

Some patients with bland smooth muscle tumors in the uterus have synchronous or asynchronous smooth muscle tumors in the peritoneum and/or the retroperitoneum. It is usually assumed that the uterine tumor is the primary lesion, and the extrauterine neoplasm represents its metastasis. Thus, they are designated as low-grade leiomyosarcomas because they lack the diagnostic features of a conventional spindle cell leiomyosarcoma. Nineteen such cases were retrieved from the files of the Department of Pathology at The University of Texas M.D. Anderson Cancer Center, covering a period of 18 yr. Institutional Review Board approval was obtained before the initiation of this study. In addition, 31 cases of conventional uterine leiomyosarcomas of a high grade were reviewed for comparison. Clinicopathologic features such as patients' age, tumor location, histologic features, stage, treatment, and follow-up were recorded. Immunohistochemical stains for estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and WT-1 were performed in the initially detected tumor and the subsequent neoplasm of all cases with available material in the low-grade group and selected cases in the high-grade group. Compared with high-grade leiomyosarcomas, the low-grade group cases were found at an early age (45 vs. 52.8 yr), had a longer median time of "recurrence" (42 mo for the low-grade group vs. 12 mo for high-grade leiomyosarcomas), longer median survival (165 mo for the low-grade group vs. 41 mo for the high-grade group), and a much better overall survival (84% vs. 13%). Three (16%) patients died of disease in the low-grade group versus 27 (87%) patients in the high-grade leiomyosarcoma group. We also found a difference in the location of the extrauterine tumors. Most cases of low-grade tumors were found in the pelvis, abdomen, or retroperitoneum, whereas most high-grade leiomyosarcomas involved the lung. In the low-grade tumors, there were some differences in the immunophenotype between the uterine and the extrauterine neoplasms, but in the high-grade tumors, there were no differences in the immunohistochemistry between the primary tumor and the metastasis. In addition to these differences between the 2 groups in the age of the patients, sites of recurrences, and the immunophenotype of the uterine and extrauterine tumor, neither the uterine nor the extrauterine low-grade lesions had histologic features of malignancy. On the basis of these differences, the possibility that the extrauterine lesions in the low-grade group represent independent primaries involving the secondary mullerian system is proposed.

Modeling Synchronous Muscle Function in Insect Flight: a Bio-Inspired Approach to Force Control in Flapping-Wing MAVs

Micro-aerial vehicles (MAV) and their promising applications--such as undetected surveillance or exploration of environments with little space for land-based maneuvers--are a well-known topic in the field of aerial robotics. Inspired by high maneuverability and agile flight of insects, over the past two decades a significant amount of effort has been dedicated to research on flapping-wing MAVs, most of which aim to address unique challenges in morphological construction, force production, and control strategy. Although remarkable solutions have been found for sufficient lift generation, effective methods for motion control still remain an open problem. The focus of this paper is to investigate general flight control mechanisms that are potentially used by real insects, thereby providing inspirations for flapping-wing MAV control. Through modeling the insect flight muscles, we show that stiffness and set point of the wing's joint can be respectively tuned to regulate the wing's lift and thrust forces. Therefore, employing a suitable controller with variable impedance actuators at each wing joint is a prospective approach to agile flight control of insect-inspired MAVs. The results of simulated flight experiments with one such controller are provided and support our claim.

Length Dependent Activation in Synchronous Flight Muscle from Manduca Sexta

In most striated muscles, the amount of force generated at a given concentration of activating calcium is greater at long sarcomere length (SL) than at shorter SL, referred to as “length dependent activation” (LDA). LDA is prominent in mammalian cardiac muscle and underlies the so-called Frank-Starling Law of the Heart” allowing cardiac output to be adjusted on a beat-to-beat basis. The molecular basis for LDA is not yet understood. The dorsal longitudinal flight muscle (DLM) of the Hawkmoth Manduca sexta is an emerging model system for structural and functional studies of muscle. It is a synchronous muscle, requiring a neural impulse for every muscle twitch, as in mammalian skeletal and cardiac striated muscle, but it is structurally similar to the more widely studied asynchronous insect flight muscles of Drosophila and Lethocerus. Its force-length curve has been shown to be remarkably similar to mammalian cardiac muscle (Tu & Daniel, J Exp Biol 207: 2455. 2004) indicating that Manduca flight muscle might be a useful model system to elucidate various aspects of cardiac function in comparative studies. The present studies were undertaken to characterize LDA in Manduca flight muscle. Conditions were found that allowed chemical skinning of the muscles while maintaining good structural order as assessed by by light and X-ray diffraction. Force-pCa curves were collected as a function of SL. Dorsally located DLMs (cooler in vivo) were compared to ventrally located DLM's (warmer in vivo). We found that both dorsal and ventral DLMs show length-dependent activation. Our study also showed that ventrally located DLM's are less cooperative (Hill coefficient nH ∼1-1.2) than the dorsally located DLM's (nH ∼1.8–1.9) which may be related to their different functions in vivo. Supported by NSF IOS 1022058 and NIH RR08630.

The development of rhythm regularity, neuromuscular strategies, and movement smoothness during repetitive reaching in typically developing children

IntroductionThis study examined the development of paced coordinated reaching characterized by the successful entrainment of the movement to an external pacer, synchronous muscle activations and movement smoothness. MethodsThirty children, 5–10years of age, and ten adults were instructed to repeatedly reach for and move an object from a lower shelf to an upper shelf in time to a metronome. Surface electromyography data were recorded. Amplitude and cross-correlations were calculated on three muscle pairs crossing the shoulder and elbow. A motion capture system captured the space curve accelerations of hand, forearm and upper arm segments to quantify movement smoothness. ResultsThe 5–6year old children showed the greatest amount of temporal variability, followed by 7–10year olds and then the adults. Correlations between muscle pairs stabilizing the shoulder girdle were higher in each group as compared to the other two muscle pairs but the correlations for all pairs were consistently higher for adults. Movement smoothness for children 9–10years of age was closer to an adult-like pattern with respect to control of the upper arm, but the hand segment had the greatest variability across groups. ConclusionsThe increased temporal variability and decreased movement smoothness of the hand and forearm segments suggest that control of more distal musculature may be more difficult in children. The neuromuscular strategies adopted by adults were more optimal than those adopted by children as reflected by smoother and more consistent reaching.