Model simulation of the SPOC wave in a bundle of striated myofibrils.
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ABSTRACT:
SUBMITTER: Nakagome K
PROVIDER: S-EPMC5060095 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Muscles perform a wide range of motile functions in animals. Among various types are skeletal and cardiac muscles, which exhibit a steady auto-oscillation of force and length when they are activated at an intermediate level of contraction. This phenomenon, termed spontaneous oscillatory contraction or SPOC, occurs devoid of cell membranes and at fixed concentrations of chemical substances, and is thus the property of the contractile system per se. We have previously developed a theoretical model of SPOC and proposed that the oscillation emerges from a dynamic force balance along both the longitudinal and lateral axes of sarcomeres, the contractile units of the striated muscle. Here, we experimentally tested this hypothesis by developing an imaging-based analysis that facilitates detection of the structural changes of single sarcomeres at unprecedented spatial resolution. We found that the sarcomere width oscillates anti-phase with the sarcomere length in SPOC. We also found that the oscillatory dynamics can be altered by osmotic compression of the myofilament lattice structure of sarcomeres, but they are unchanged by a proteolytic digestion of titin/connectin-the spring-like protein that provides passive elasticity to sarcomeres. Our data thus reveal the three-dimensional mechanical dynamics of oscillating sarcomeres and suggest a structural requirement of steady auto-oscillation.
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Project description:Studying seismic wave propagation through complex media is crucial to numerous aspects of geophysics and engineering including seismic hazard assessment. In particular, small-scale structure such as sedimentary basins and their edges can have significant effects on high-frequency earthquake ground motion, which is the main cause for the damage to buildings and infrastructure. However, such structural effects are poorly understood due to limitations in numerical and analytical methods. To overcome this challenge, for the first time, we utilize the 3D printing technique to build a scaled-down physical representation of geological structure and perform lab-scale seismic experiments on it. Specifically, a physical model based on the Los Angeles Basin is printed and used as synthetic medium to propagate ultrasonic waves, to mimic seismic wave propagation from local earthquakes. Our results show clear body and surface waves recorded at expected time and locations, as well as waves that are scattered from the basin edges. We find that high-frequency energies are significantly reduced at the basin, which is at odds with the conventional view of basins as ground motion amplifiers. This novel waveform modeling approach with 3D printed Earth models is largely automated and provides an effective means to tackle geophysical problems of significance.
| S-EPMC8931089 | biostudies-literature
Project description:Since it was first described >20 yr ago, the SPOC domain (Spen paralog and ortholog C-terminal domain) has been identified in many proteins all across eukaryotic species. SPOC-containing proteins regulate gene expression on various levels ranging from transcription to RNA processing, modification, export, and stability, as well as X-chromosome inactivation. Their manifold roles in controlling transcriptional output implicate them in a plethora of developmental processes, and their misregulation is often associated with cancer. Here, we provide an overview of the biophysical properties of the SPOC domain and its interaction with phosphorylated binding partners, the phylogenetic origin of SPOC domain proteins, the diverse functions of mammalian SPOC proteins and their homologs, the mechanisms by which they regulate differentiation and development, and their roles in cancer.
| S-EPMC10111866 | biostudies-literature
Project description:BackgroundSkeletal muscle differentiation requires assembly of contractile proteins into organized myofibrils. The Drosophila ladybird homeobox gene (lad) functions in founder cells of the segmental border muscle to promote myoblast fusion and muscle shaping. Tetrapods have two homologous genes (Lbx). Lbx1 functions in migration and/or proliferation of hypaxial myoblasts, whereas the function of Lbx2 is poorly understood.ResultsTo elucidate the role of Lbx in vertebrate myogenesis, we examined Lbx function in zebrafish. Zebrafish lbx2 transcripts appear in newly formed paraxial mesoderm and become restricted to adaxial cells, precursors of slow muscle. Slow muscles lose lbx2 expression as they differentiate, while a subset of differentiating fast muscle cells transiently expresses lbx2. Fin and hyoid muscle express lbx2 later. In contrast, lbx1b expression first appears lateral to the somites at late segmentation stages and is later restricted to fin muscle. Morpholino knockdown of Lbx1b and Lbx2 suppresses hypaxial muscle development. Moreover, knockdown of Lbx2 results in malformation of muscle fibers and reduced fusion of fast precursors, although no obvious effects on induction or specification are observed. Expression of myofilament genes, including actin and myosin, requires the engrailed repressor domain of Lbx2.ConclusionOur results elucidate a new function of Lbx2 as a regulator of myofibril formation.
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Project description:The hair bundle, an apical specialization of the hair cell composed of several rows of regularly organized stereocilia and a kinocilium, is essential for mechanotransduction in the ear. Its precise organization allows the hair bundle to convert mechanical stimuli to electrical signals; mutations that alter the bundle's morphology often cause deafness. However, little is known about the proteins involved in the process of morphogenesis and how the structure of the bundle arises through interactions between these molecules. We present a mathematical model based on simple reaction-diffusion mechanisms that can reproduce the shape and organization of the hair bundle. This model suggests that the boundary of the cell and the kinocilium act as signaling centers that establish the bundle's shape. The interaction of two proteins forms a hexagonal Turing pattern--a periodic modulation of the concentrations of the morphogens, sustained by local activation and long-range inhibition of the reactants--that sets a blueprint for the location of the stereocilia. Finally we use this model to predict how different alterations to the system might impact the shape and organization of the hair bundle.
| S-EPMC4217459 | biostudies-literature
Project description:We conceptually designed a robust nano-scale waveguide structure suitable for potential use as a spin-wave duplexer that allows signal propagation only of selected narrow-band frequencies and duplex transmission in a three-port device comprising a receiver, a transmitter, and their common antenna. The waveguide structure combines three different arms and a circular ring, both made of nanostrip waveguides and a single magnetic material for reliably controllable propagations of spin waves. We attribute the observed duplex transmission of spin waves of narrow pass bands to scattering of spin waves by edge solitons placed at contact areas between the arms and the circular ring. This work proposes the first concept of nano-scale magnonic duplexers operating beyond GHz-frequency ranges.
| S-EPMC6220281 | biostudies-literature
Project description:AbstractIntermediate care units (ImCUs) have been shown as appropriate units for the management of selected septic patients. Developing specific protocols for residents in training may be useful for their medical performance. The objective of this study was to analyze whether a simulation-based learning bundle is useful for residents while acquiring competencies in the management of sepsis during their internship in an ImCU.A prospective study, set in a tertiary-care academic medical center was performed enrolling residents who performed their internship in an ImCU from 2014 to 2017. The pillars of the simulation-based learning bundle were sepsis scenario in the simulation center, instructional material, and sepsis lecture, and management of septic patients admitted in the ImCU. Each resident was evaluated in the beginning and at the end of their internship displaying a sepsis-case scenario in the simulation center. The authors developed a sepsis-checklist that residents must fulfill during their performance which included 5 areas: hemodynamics (0-10), oxygenation (0-5), antibiotic therapy (0-9), organic injury (0-5), and miscellaneous (0-4).Thirty-four residents from different years of residency and specialties were evaluated. The total median score (interquartile range) increased significantly after training: 12 (25) vs 23 (16), P = .001. First-year residents scored significantly lower than older residents at baseline: 10 (14) vs 14.5 (19), P = .024. However, the performance at the end of the training period was similar in both groups: 21.5 (11) vs 23 (16), P = 1.000. Internal Medicine residents scored significantly higher than residents from other specialties: 18 (17) vs 10.5 (21), P = .007. Nonetheless, the performance at the end of the training period was similar in both groups: 24.5 (9) vs 22 (13), P = 1.000.Combining medical simulation with didactic lectures and a rotation in an ImCU staffed by hospitalists seems to be useful in acquiring competencies to manage critically ill patients with sepsis. We designed a checklist to assure an objective evaluation of the performance of the residents and to identify those aspects that could be potentially improved.
| S-EPMC7870168 | biostudies-literature
Project description:BackgroundPostoperative junctional ectopic tachycardia (JET) occurs frequently after pediatric cardiac surgery. R-wave synchronized atrial (AVT) pacing is used to re-establish atrioventricular synchrony. AVT pacing is complex, with technical pitfalls. We sought to establish and to test a low-cost simulation model suitable for training and analysis in AVT pacing.MethodsA simulation model was developed based on a JET simulator, a simulation doll, a cardiac monitor, and a pacemaker. A computer program simulated electrocardiograms. Ten experienced pediatric cardiologists tested the model. Their performance was analyzed using a testing protocol with 10 working steps.ResultsFour testers found the simulation model realistic; 6 found it very realistic. Nine claimed that the trial had improved their skills. All testers considered the model useful in teaching AVT pacing. The simulation test identified 5 working steps in which major mistakes in performance test may impede safe and effective AVT pacing and thus permitted specific training. The components of the model (exclusive monitor and pacemaker) cost less than $50. Assembly and training-session expenses were trivial.ConclusionsA realistic, low-cost simulation model of AVT pacing is described. The model is suitable for teaching and analyzing AVT pacing technique.
| S-EPMC4778927 | biostudies-literature
Project description:Mammalian hearing relies on a cochlear hydrodynamic sensor embodied in the inner hair cell stereocilia bundle. It is presumed that acoustical stimuli induce a fluid shear-driven motion between the tectorial membrane and the reticular lamina to deflect the bundle. It is hypothesized that ion channels are opened by molecular gates that sense tension in tip-links, which connect adjacent stepped rows of stereocilia. Yet almost nothing is known about how the fluid and bundle interact. Here we show using our microfluidics model how each row of stereocilia and their associated tip links and gates move in response to an acoustical input that induces an orbital motion of the reticular lamina. The model confirms the crucial role of the positioning of the tectorial membrane in hearing, and explains how this membrane amplifies and synchronizes the timing of peak tension in the tip links. Both stereocilia rotation and length change are needed for synchronization of peak tip link tension. Stereocilia length change occurs in response to accelerations perpendicular to the oscillatory fluid shear flow. Simulations indicate that nanovortices form between rows to facilitate diffusion of ions into channels, showing how nature has devised a way to solve the diffusive mixing problem that persists in engineered microfluidic devices.
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Project description:The calculated folding thermodynamics of a simple off-lattice three-helix-bundle protein model under equilibrium conditions shows the experimentally observed protein transitions: a collapse transition, a disordered-to-ordered globule transition, a globule to native-state transition, and the transition from the active native state to a frozen inactive state. The cooperativity and physical origin of the various transitions are explored with a single "optimization" parameter and characterized with the Lindemann criterion for liquid versus solid-state dynamics. Below the folding temperature, the model has a simple free energy surface with a single basin near the native state; the surface is similar to that calculated from a simulation of the same three-helix-bundle protein with an all-atom representation [Boczko, E. M. & Brooks III, C. L. (1995) Science 269, 393-396].
| S-EPMC25010 | biostudies-literature