Adult skeletal muscle stem cell migration is mediated by a blebbing/amoeboid mechanism

Adult skeletal muscle possesses a resident stem cell population called satellite cells which are responsible for tissue repair following damage. Satellite cell migration is crucial in promoting rapid tissue regeneration but is a poorly understood process. Furthermore, the mechanisms facilitating satellite cell movement have yet to be elucidated. Here the process of satellite cell migration has been investigated revealing that they undergo two distinct phases of movement; firstly under the basal lamina and then rapidly increasing their velocity when on the myofibre surface. Most significantly we show that satellite cells move using a highly dynamic blebbing based mechanism and not via lamellopodia mediated propulsion. We show that nitric oxide and non-canonical Wnt signalling pathways are necessary for regulating the formation of blebs and the migration of satellite cells. In summary, we propose that the formation of blebs and their necessity for satellite cell migration has significant implications in the future development of therapeutic regimes aimed at promoting skeletal muscle regeneration

Anisotropic behaviour of human gallbladder walls

Inverse estimation of biomechanical parameters of soft tissues from non-invasive measurements has clinical significance in patient-specific modelling and disease diagnosis. In this paper, we propose a fully nonlinear approach to estimate the mechanical properties of the human gallbladder wall muscles from in vivo ultrasound images. The iteration method consists of a forward approach, in which the constitutive equation is based on a modified Hozapfel–Gasser–Ogden law initially developed for arteries. Five constitutive parameters describing the two orthogonal families of fibres and the matrix material are determined by comparing the computed displacements with medical images. The optimisation process is carried out using the MATLAB toolbox, a Python code, and the ABAQUS solver. The proposed method is validated with published artery data and subsequently applied to ten human gallbladder samples. Results show that the human gallbladder wall is anisotropic during the passive refilling phase, and that the peak stress is 1.6 times greater than that calculated using linear mechanics. This discrepancy arises because the wall thickness reduces by 1.6 times during the deformation, which is not predicted by conventional linear elasticity. If the change of wall thickness is accounted for, then the linear model can used to predict the gallbladder stress and its correlation with pain. This work provides further understanding of the nonlinear characteristics of human gallbladder

A finite strain nonlinear human mitral valve model with fluid structure interaction

A simulated human mitral valve under a physiological pressure loading is developed using a hybrid finite element immersed boundary method, which incorporates experimentally based constitutive laws in a three-dimensional fluid-structure interaction framework. A transversely isotropic material constitutive model is used for characterizing the mechanical behaviour of the mitral valve tissue based on recent mechanical tests of healthy human mitral leaflets. Our results show good agreement, in terms of the flow rate and the closing and opening configurations, with the measurements from the magnetic resonance images. The stresses in the anterior leaflet are found to be higher than those in the posterior leaflet, and concentrated around the annulus trigons and free edges of the valve leaflets. Those areas are located where the leaflet has the highest curvature. Effects of the chordae tendineae in the material model are studied and the results show that these chordae play an important role in providing a secondary orifice for the flow when valve opens. Although there are some discrepancies to be overcome in future works, our simulations show that the developed computational model is promising in mimicking the in vivo mitral valve dynamics and providing important information that are not obtainable by in vivo measurements. This article is protected by copyright. All rights reserved

A coupled mitral valve -- left ventricle model with fluid-structure interaction

Understanding the interaction between the valves and walls of the heart is important in assessing and subsequently treating heart dysfunction. With advancements in cardiac imaging, nonlinear mechanics and computational techniques, it is now possible to explore the mechanics of valve-heart interactions using anatomically and physiologically realistic models. This study presents an integrated model of the mitral valve (MV) coupled to the left ventricle (LV), with the geometry derived from in vivo clinical magnetic resonance images. Numerical simulations using this coupled MV-LV model are developed using an immersed boundary/finite element method. The model incorporates detailed valvular features, left ventricular contraction, nonlinear soft tissue mechanics, and fluid-mediated interactions between the MV and LV wall. We use the model to simulate the cardiac function from diastole to systole, and investigate how myocardial active relaxation function affects the LV pump function. The results of the new model agree with in vivo measurements, and demonstrate that the diastolic filling pressure increases significantly with impaired myocardial active relaxation to maintain the normal cardiac output. The coupled model has the potential to advance fundamental knowledge of mechanisms underlying MV-LV interaction, and help in risk stratification and optimization of therapies for heart diseases.Comment: 25 pages, 6 figure

Nonaxisymmetric mathematical model of the cardiac left ventricle anatomy

We describe a mathematical model of the shape and fibre direction field of the cardiac left ventricle. The ventricle is composed of surfaces which model myocardial sheets. On each surface, we construct a set of curves corresponding to myocardial fibres. Tangents to these curves form the myofibres direction field. The fibres are made as images of semicircle chords parallel to its diameter. To specify the left ventricle shape, we use a special coordinate system where the left ventricle boundaries are coordinate surfaces. We propose an analytic mapping from the semicircle to the special coordinate system. The model is correlated with Torrent-Guasp’s concept of the unique muscular band and with Pettigrew’s idea of nested surfaces. Subsequently, two models of concrete normal canine and human left ventricles are constructed based on experimental Diffusion Tensor Magnetic Resonance Imaging data. The input data for the models is only the left ventricle shape. In a local coordinate system connected with the left ventricle meridional section, we calculate two fibre inclination angles, i.e. true fibre angle and helix angle. We obtained the angles found from the Diffusion Tensor Magnetic Resonance Imaging data and compared them with the model angles. We give the angle plots and show that the model adequately reproduces the fibre architecture in the majority of the left ventricle wall. Based on the mathematical model proposed, one can construct a numerical mesh that makes it possible to solve electrophysiological and mechanical left ventricle activity problems in norm and pathology. In the special coordinate system mentioned, the numerical scheme is written in a rectangular area and the boundary conditions can simply be written. By changing the model parameters, one can set a general or regional ventricular wall thickening or the left ventricle shape change, which is typical for certain cardiac pathologies

Neuromuscular organization and aminergic modulation of contractions in the Drosophila ovary

Background: The processes by which eggs develop in the insect ovary are well characterized. Despite a large number of Drosophila mutants that cannot lay eggs, the way that the egg is moved along the reproductive tract from ovary to uterus is less well understood. We remedy this with an integrative study on the reproductive tract muscles (anatomy, innervation, contractions, aminergic modulation) in female flies. Results: Each ovary, consisting of 15-20 ovarioles, is surrounded by a contractile meshwork, the peritoneal sheath. Individual ovarioles are contained within a contractile epithelial sheath. Both sheaths contain striated muscle fibres. The oviduct and uterine walls contain a circular striated muscle layer. No longitudinal muscle fibres are seen. Neurons that innervate the peritoneal sheath and lateral oviduct have many varicosities and terminate in swellings just outside the muscles of the peritoneal sheath. They all express tyrosine decarboxylase (required for tyramine and octopamine synthesis) and Drosophila vesicular monoamine transporter (DVMAT). No fibres innervate the ovarioles. The common oviduct and uterus are innervated by two classes of neurons, one with similar morphology to those of the peritoneal sheath and another with repeated branches and axon endings similar to type I neuromuscular junctions. In isolated genital tracts from 3- and 7-day old flies, each ovariole contracts irregularly (12.5 +/- 6.4 contractions/minute; mean +/- 95% confidence interval). Peritoneal sheath contractions (5.7 +/- 1.6 contractions/minute) move over the ovary, from tip to base or vice versa, propagating down the oviduct. Rhythmical spermathecal rotations (1.5 +/- 0.29 contractions/minute) also occur. Each genital tract organ exhibits its own endogenous myogenic rhythm. The amplitude of contractions of the peritoneal sheath increase in octopamine (100 nM, 81% P < 0.02) but 1 mu M tyramine has no effect. Neither affects the frequency of peritoneal sheath contractions. Conclusion: The muscle fibres of the reproductive tract are circular and have complex bursting myogenic rhythms under octopaminergic neuromodulation. We propose a new model of tissue-specific actions of octopamine, in which strengthening of peritoneal sheath contractions, coupled with relaxation of the oviduct, eases ovulation. This model accounts for reduced ovulation in flies with mutations in the octopaminergic system

Ergonomics of the Operative Field in Paediatric Minimal Access Surgery

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Structure, ontogeny and evolution of the patellar tendon in emus (Dromaius novaehollandiae) and other palaeognath birds

The patella (kneecap) exhibits multiple evolutionary origins in birds, mammals, and lizards, and is thought to increase the mechanical advantage of the knee extensor muscles. Despite appreciable interest in the specialized anatomy and locomotion of palaeognathous birds (ratites and relatives), the structure, ontogeny and evolution of the patella in these species remains poorly characterized. Within Palaeognathae, the patella has been reported to be either present, absent, or fused with other bones, but it is unclear how much of this variation is real, erroneous or ontogenetic. Clarification of the patella’s form in palaeognaths would provide insight into the early evolution of the patella in birds, in addition to the specialized locomotion of these species. Findings would also provide new character data of use in resolving the controversial evolutionary relationships of palaeognaths. In this study, we examined the gross and histological anatomy of the emu patellar tendon across several age groups from five weeks to 18 months. We combined these results with our observations and those of others regarding the patella in palaeognaths and their outgroups (both extant and extinct), to reconstruct the evolution of the patella in birds. We found no evidence of an ossified patella in emus, but noted its tendon to have a highly unusual morphology comprising large volumes of adipose tissue contained within a collagenous meshwork. The emu patellar tendon also included increasing amounts of a cartilage-like tissue throughout ontogeny. We speculate that the unusual morphology of the patellar tendon in emus results from assimilation of a peri-articular fat pad, and metaplastic formation of cartilage, both potentially as adaptations to increasing tendon load. We corroborate previous observations of a ‘double patella’ in ostriches, but in contrast to some assertions, we find independent (i.e., unfused) ossified patellae in kiwis and tinamous. Our reconstructions suggest a single evolutionary origin of the patella in birds and that the ancestral patella is likely to have been a composite structure comprising a small ossified portion, lost by some species (e.g., emus, moa) but expanded in others (e.g., ostriches)

Modelling mitral valvular dynamics–current trend and future directions

Dysfunction of mitral valve causes morbidity and premature mortality and remains a leading medical problem worldwide. Computational modelling aims to understand the biomechanics of human mitral valve and could lead to the development of new treatment, prevention and diagnosis of mitral valve diseases. Compared with the aortic valve, the mitral valve has been much less studied owing to its highly complex structure and strong interaction with the blood flow and the ventricles. However, the interest in mitral valve modelling is growing, and the sophistication level is increasing with the advanced development of computational technology and imaging tools. This review summarises the state-of-the-art modelling of the mitral valve, including static and dynamics models, models with fluid-structure interaction, and models with the left ventricle interaction. Challenges and future directions are also discussed