scholarly journals A Stochastic Spatiotemporal Model of Rat Ventricular Myocyte Calcium Dynamics Demonstrated Necessary Features for Calcium Wave Propagation

Membranes ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 989
Author(s):  
Tuan Minh Hoang-Trong ◽  
Aman Ullah ◽  
William Jonathan Lederer ◽  
Mohsin Saleet Jafri
Keyword(s):  
Computational Model ◽  
Cell Biology ◽  
Computational Models ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Three Dimensional ◽  
Ionic Currents ◽  
Cardiac Contraction ◽  
Calcium Dynamics ◽  
Deterministic Models

Calcium (Ca2+) plays a central role in the excitation and contraction of cardiac myocytes. Experiments have indicated that calcium release is stochastic and regulated locally suggesting the possibility of spatially heterogeneous calcium levels in the cells. This spatial heterogeneity might be important in mediating different signaling pathways. During more than 50 years of computational cell biology, the computational models have been advanced to incorporate more ionic currents, going from deterministic models to stochastic models. While periodic increases in cytoplasmic Ca2+ concentration drive cardiac contraction, aberrant Ca2+ release can underly cardiac arrhythmia. However, the study of the spatial role of calcium ions has been limited due to the computational expense of using a three-dimensional stochastic computational model. In this paper, we introduce a three-dimensional stochastic computational model for rat ventricular myocytes at the whole-cell level that incorporate detailed calcium dynamics, with (1) non-uniform release site placement, (2) non-uniform membrane ionic currents and membrane buffers, (3) stochastic calcium-leak dynamics and (4) non-junctional or rogue ryanodine receptors. The model simulates spark-induced spark activation and spark-induced Ca2+ wave initiation and propagation that occur under conditions of calcium overload at the closed-cell condition, but not when Ca2+ levels are normal. This is considered important since the presence of Ca2+ waves contribute to the activation of arrhythmogenic currents.

The Ryanodine Receptor/Calcium Release Channel and its Interaction Partners

1998 ◽  
Vol 4 (S2) ◽  
pp. 968-969
Author(s):  
Terry Wagenknecht ◽  
Montserrat Samso
Keyword(s):  
Calcium Release ◽  
Striated Muscle ◽  
Ryanodine Receptors ◽  
Three Dimensional ◽  
Structural Complexity ◽  
Body Representation ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Fk506 Binding Protein ◽  
Dimensional Reconstruction

Ryanodine receptors (RyRs) function as the major intracellular calcium release channels in striated muscle, where they also play a central role in excitation-contraction (e-c) coupling, the signal transduction process by which neuron-induced depolarization of the muscle plasma membrane leads to release of Ca from the sarcoplasmic reticulum. Structurally, RyRs are the largest ion channels known, being composed of 4 identical large subunits (565 kDa). In situ, RyRs interact with numerous proteins that are essential for e-c coupling or regulation thereof. Some of these ligands include calmodulin, a 12-kDa FK506-binding protein (FKBP, an immunophi1 in), calsequestrin, triadin, and the dihydropyridine receptor (DHPR).Detergent-solubilized, purified RyRs appear to retain their native structure as assessed by electron cryo-microscopy, and are amenable to three-dimensional reconstruction by single-particle image processing techniques. In Fig. 1, a solid-body representation of the reconstructed skeletal muscle RyR shows the structural complexity that is revealed at moderate resolutions (3-4 nm).

Noninvasive In Vivo Characterization of Pediatric Human Spine: 3-D Finite Element Study

2011 ◽  
Author(s):  
Elizabeth S. Doughty ◽  
Nesrin Sarigul-Klijn
Keyword(s):  
Finite Element ◽  
Computational Model ◽  
Muscle Activation ◽  
Computational Models ◽  
Three Dimensional ◽  
Pediatric Spine ◽  
Element Analysis ◽  
Spine Stabilization ◽  
Surgical Tool

There are no full three-dimensional computational models of the pediatric spine to study the many diseases and disorders that afflict the immature spine using finite element analysis. To fully characterize the pediatric spine, we created a pediatric specific computational model of C1-L5 using noninvasive in vivo techniques to incorporate the differences between the adult and pediatric spines: un-fused vertebrae, lax ligaments, and higher water content in the intervertebral discs. Muscle follower loads were included in the model to simulate muscle activation for five muscles involved in spine stabilization. This paper is the first pediatric three-dimensional model developed to date. Due to a lack of experimental pediatric spinal studies, this 3-D computational model has the potential to become a surgical tool to ensure that the most appropriate technique is chosen for treating pediatric spinal dysfunctions such as congenital abnormalities, idiopathic scoliosis, and vertebral fractures.

scholarly journals The Roles of Space and Stochasticity in Computational Simulations of Cellular Biochemistry: Quantitative Analysis and Qualitative Insights

2020 ◽  
Author(s):  
M. E. Johnson ◽  
A. Chen ◽  
J. R. Faeder ◽  
P. Henning ◽  
I. I. Moraru ◽  
...  
Keyword(s):  
Cell Biology ◽  
Computational Models ◽  
Computational Simulation ◽  
Three Dimensional ◽  
Building Blocks ◽  
Molecular Structures ◽  
Stochastic Methods ◽  
Specific Cell ◽  
Test Cases ◽  
Computational Approaches

ABSTRACTMost of the fascinating phenomena studied in cell biology emerge from interactions among highly organized multi-molecular structures and rapidly propagating molecular signals embedded into complex and frequently dynamic cellular morphologies. For the exploration of such systems, computational simulation has proved to be an invaluable tool, and many researchers in this field have developed sophisticated computational models for application to specific cell biological questions. However it is often difficult to reconcile conflicting computational results that use different simulation approaches (for example partial differential equations versus particle-based stochastic methods) to describe the same phenomenon. Moreover, the details of the computational implementation of any particular algorithm may give rise to quantitatively or even qualitatively different results for the same set of starting assumptions and parameters. In an effort to address this issue systematically, we have defined a series of computational test cases ranging from very simple (bimolecular binding in solution) to moderately complex (spatial and temporal oscillations generated by proteins binding to membranes) that represent building blocks for comprehensive three-dimensional models of cellular function. Having used two or more distinct computational approaches to solve each of these test cases with consistent parameter sets, we generally find modest but measurable differences in the solutions of the same problem, and a few cases where significant deviations arise. We discuss the strengths and limitations of commonly used computational approaches for exploring cell biological questions and provide a framework for decision-making by researchers wishing to develop new models for cell biology. As computational power and speed continue to increase at a remarkable rate, the dream of a fully comprehensive computational model of a living cell may be drawing closer to reality, but our analysis demonstrates that it will be crucial to evaluate the accuracy of such models critically and systematically.

A REALISTIC 3D COMPUTATIONAL MODEL OF THE CLOSURE OF SKIN WOUND WITH INTERRUPTED SUTURES

2017 ◽  
Vol 17 (01) ◽  
pp. 1750025 ◽  
Author(s):  
ARNAB CHANDA ◽  
VINU UNNIKRISHNAN
Keyword(s):  
Computational Model ◽  
Material Properties ◽  
Computational Models ◽  
Wound Closure ◽  
Three Dimensional ◽  
Skin Wound ◽  
Cross Sectional ◽  
Maximum Value ◽  
Robotic Surgeries ◽  
First Time

Wounds or cuts are the most common form of skin injuries. While a shallow wound may heal over time, deep wounds often require clinical interventions such as suturing to ensure the wound closure and timely healing. To date, suturing practices are based on a surgeon's experience and there is no benchmark to what is right or wrong. In the literature, there have been few attempts to characterize wound closure and suture mechanics using simple 2D computational models. In our current work, for the first time, a realistic three-dimensional (3D) computational model of the skin with the two layers, namely the epidermis and dermis, have been developed. A 3D diamond shaped wound with a varying cross-section has been modeled, and interrupted sutures have been placed numerically in multiple steps to close the wound. Nonlinear hyperelastic material properties have been adopted for the skin and a skin pre-stress was applied bi-axially. The force requirements for each suture were estimated numerically using a novel suture pulling technique. The suture forces were found to lie in the range of 0–5 N with a maximum value at the center. Also, the center suture was observed to require an approximately four times pull force compared to the first end suture. All these findings provide important guidelines for suturing. Additionally, the suture force can be approximated as a polynomial function of the displacement. Given a wound geometry, wound depth, skin material properties, skin pre-stress, suture wire material and cross-sectional area, using our computational model, such a relationship can be used to estimate and characterize the suture force requirements accurately. To our knowledge, such a 3D computational model of skin wound closure with interrupted sutures have not been developed till date, and would be indispensable for planning robotic surgeries and improving clinical suturing practices in the future.

Exploration of cell wall architecture with the rapid-freeze deep-etch technique

1993 ◽  
Vol 51 ◽  
pp. 128-129
Author(s):  
Béatrice Satiat-Jeunemaitre ◽  
Chris Hawes
Keyword(s):  
Plant Cell ◽  
Cell Walls ◽  
Cell Biology ◽  
Molecular Model ◽  
Three Dimensional ◽  
Secretory Activity ◽  
Wall Structure ◽  
Specimen Preparation ◽  
Molecular Architecture ◽  
Plant Cell Walls

The comprehension of the molecular architecture of plant cell walls is one of the best examples in cell biology which illustrates how developments in microscopy have extended the frontiers of a topic. Indeed from the first electron microscope observation of cell walls it has become apparent that our understanding of wall structure has advanced hand in hand with improvements in the technology of specimen preparation for electron microscopy. Cell walls are sub-cellular compartments outside the peripheral plasma membrane, the construction of which depends on a complex cellular biosynthetic and secretory activity (1). They are composed of interwoven polymers, synthesised independently, which together perform a number of varied functions. Biochemical studies have provided us with much data on the varied molecular composition of plant cell walls. However, the detailed intermolecular relationships and the three dimensional arrangement of the polymers in situ remains a mystery. The difficulty in establishing a general molecular model for plant cell walls is also complicated by the vast diversity in wall composition among plant species.

CSBPI_Site：Multi-Information Sources of Features to RNA Binding Sites Prediction

2021 ◽  
Vol 15 ◽  
Author(s):  
Lichao Zhang ◽  
Zihong Huang ◽  
Liang Kong
Keyword(s):  
Computational Model ◽  
Binding Sites ◽  
Noncoding Rna ◽  
Computational Models ◽  
Information Sources ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Gradient Boosting ◽  
Position Information ◽  
Rna Binding Sites

Background: RNA-binding proteins establish posttranscriptional gene regulation by coordinating the maturation, editing, transport, stability, and translation of cellular RNAs. The immunoprecipitation experiments could identify interaction between RNA and proteins, but they are limited due to the experimental environment and material. Therefore, it is essential to construct computational models to identify the function sites. Objective: Although some computational methods have been proposed to predict RNA binding sites, the accuracy could be further improved. Moreover, it is necessary to construct a dataset with more samples to design a reliable model. Here we present a computational model based on multi-information sources to identify RNA binding sites. Method: We construct an accurate computational model named CSBPI_Site, based on xtreme gradient boosting. The specifically designed 15-dimensional feature vector captures four types of information (chemical shift, chemical bond, chemical properties and position information). Results: The satisfied accuracy of 0.86 and AUC of 0.89 were obtained by leave-one-out cross validation. Meanwhile, the accuracies were slightly different (range from 0.83 to 0.85) among three classifiers algorithm, which showed the novel features are stable and fit to multiple classifiers. These results showed that the proposed method is effective and robust for noncoding RNA binding sites identification. Conclusion: Our method based on multi-information sources is effective to represent the binding sites information among ncRNAs. The satisfied prediction results of Diels-Alder riboz-yme based on CSBPI_Site indicates that our model is valuable to identify the function site.

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