Differentiation of activated satellite cells in denervated muscle following single fusions in situ and in cell culture

Satellite cells represent a cellular source of regeneration in adult skeletal muscle. It remains unclear why a large pool of stem myoblasts in denervated muscle does not compensate for the loss of muscle mass during post-denervation atrophy. In this study, we present evidence that satellite cells in long-term denervated rat muscle are able to activate synthesis of contractile proteins after single fusions in situ. This process of early differentiation leads to formation of abnormally diminutive myotubes. The localization of such dwarf myotubes beneath the intact basal lamina on the surface of differentiated muscle fibers shows that they form by fusion of neighboring satellites or by the progeny of a single satellite cell following one or two mitotic divisions. We demonstrated single fusions of myoblasts using electron microscopy, immunocytochemical labeling and high resolution confocal digital imaging. Sequestration of nascent myotubes by the rapidly forming basal laminae creates a barrier that limits further fusions. The recruitment of satellite cells in the formation of new muscle fibers results in a progressive decrease in their local densities, spatial separation and ultimate exhaustion of the myogenic cell pool. To determine whether the accumulation of aberrant dwarf myotubes is explained by the intrinsic decline of myogenic properties of satellite cells, or depends on their spatial separation and the environment in the tissue, we studied the fusion of myoblasts isolated from normal and denervated muscle in cell culture. The experiments with a culture system demonstrated that the capacity of myoblasts to synthesize contractile proteins without serial fusions depended on cell density and the availability of partners for fusion. Satellite cells isolated from denervated muscle and plated at fusion-permissive densities progressed through the myogenic program and actively formed myotubes, which shows that their myogenic potential is not considerably impaired. The results of this study suggest that under conditions of denervation, progressive spatial separation and confinement of many satellite cells within the endomysial tubes of atrophic muscle fibers and progressive interstitial fibrosis are the important factors that prevent their normal differentiation. Our findings also provide an explanation of why denervated muscle partially and temporarily is able to restore its functional capacity following injury and regeneration: the release of satellite cells from their sublaminal location provides the necessary space for a more active regenerative process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47397/1/418_2005_Article_12.pd

Type-II B\"acklund Transformations via Gauge Transformations

The construction of type II Backlund transformation for the sine-Gordon and the Tzitzeica-Bullough-Dodd models are obtained from gauge transformation. An infinite number of conserved quantities are constructed from the defect matrices. This guarantees that the introduction of type II defects for these models does not spoil their integrability. In particular, modified energy and momentum are derived and compared with those presented in recent literature.Comment: Latex 19 pages, 2 tables. v2: Comments and two references adde

Large Isoforms of UNC-89 (Obscurin) Are Required for Muscle Cell Architecture and Optimal Calcium Release in Caenorhabditis elegans

Calcium, a ubiquitous intracellular signaling molecule, controls a diverse array of cellular processes. Consequently, cells have developed strategies to modulate the shape of calcium signals in space and time. The force generating machinery in muscle is regulated by the influx and efflux of calcium ions into the muscle cytoplasm. In order for efficient and effective muscle contraction to occur, calcium needs to be rapidly, accurately and reliably regulated. The mechanisms underlying this highly regulated process are not fully understood. Here, we show that the Caenorhabditis elegans homolog of the giant muscle protein obscurin, UNC-89, is required for normal muscle cell architecture. The large immunoglobulin domain-rich isoforms of UNC-89 are critical for sarcomere and sarcoplasmic reticulum organization. Furthermore, we have found evidence that this structural organization is crucial for excitation-contraction coupling in the body wall muscle, through the coordination of calcium signaling. Thus, our data implicates UNC-89 in maintaining muscle cell architecture and that this precise organization is essential for optimal calcium mobilization and efficient and effective muscle contraction

Parent formulation at the Lagrangian level

The recently proposed first-order parent formalism at the level of equations of motion is specialized to the case of Lagrangian systems. It is shown that for diffeomorphism-invariant theories the parent formulation takes the form of an AKSZ-type sigma model. The proposed formulation can be also seen as a Lagrangian version of the BV-BRST extension of the Vasiliev unfolded approach. We also discuss its possible interpretation as a multidimensional generalization of the Hamiltonian BFV--BRST formalism. The general construction is illustrated by examples of (parametrized) mechanics, relativistic particle, Yang--Mills theory, and gravity.Comment: 26 pages, discussion of the truncation extended, typos corrected, references adde

Effective Theory Approach to the Spontaneous Breakdown of Lorentz Invariance

We generalize the coset construction of Callan, Coleman, Wess and Zumino to theories in which the Lorentz group is spontaneously broken down to one of its subgroups. This allows us to write down the most general low-energy effective Lagrangian in which Lorentz invariance is non-linearly realized, and to explore the consequences of broken Lorentz symmetry without having to make any assumptions about the mechanism that triggers the breaking. We carry out the construction both in flat space, in which the Lorentz group is a global spacetime symmetry, and in a generally covariant theory, in which the Lorentz group can be treated as a local internal symmetry. As an illustration of this formalism, we construct the most general effective field theory in which the rotation group remains unbroken, and show that the latter is just the Einstein-aether theory.Comment: 45 pages, no figures

First order parent formulation for generic gauge field theories

We show how a generic gauge field theory described by a BRST differential can systematically be reformulated as a first order parent system whose spacetime part is determined by the de Rham differential. In the spirit of Vasiliev's unfolded approach, this is done by extending the original space of fields so as to include their derivatives as new independent fields together with associated form fields. Through the inclusion of the antifield dependent part of the BRST differential, the parent formulation can be used both for on and off-shell formulations. For diffeomorphism invariant models, the parent formulation can be reformulated as an AKSZ-type sigma model. Several examples, such as the relativistic particle, parametrized theories, Yang-Mills theory, general relativity and the two dimensional sigma model are worked out in details.Comment: 36 pages, additional sections and minor correction

Personalized online information search and visualization

BACKGROUND: The rapid growth of online publications such as the Medline and other sources raises the questions how to get the relevant information efficiently. It is important, for a bench scientist, e.g., to monitor related publications constantly. It is also important, for a clinician, e.g., to access the patient records anywhere and anytime. Although time-consuming, this kind of searching procedure is usually similar and simple. Likely, it involves a search engine and a visualization interface. Different words or combination reflects different research topics. The objective of this study is to automate this tedious procedure by recording those words/terms in a database and online sources, and use the information for an automated search and retrieval. The retrieved information will be available anytime and anywhere through a secure web server. RESULTS: We developed such a database that stored searching terms, journals and et al., and implement a piece of software for searching the medical subject heading-indexed sources such as the Medline and other online sources automatically. The returned information were stored locally, as is, on a server and visible through a Web-based interface. The search was performed daily or otherwise scheduled and the users logon to the website anytime without typing any words. The system has potentials to retrieve similarly from non-medical subject heading-indexed literature or a privileged information source such as a clinical information system. The issues such as security, presentation and visualization of the retrieved information were thus addressed. One of the presentation issues such as wireless access was also experimented. A user survey showed that the personalized online searches saved time and increased and relevancy. Handheld devices could also be used to access the stored information but less satisfactory. CONCLUSION: The Web-searching software or similar system has potential to be an efficient tool for both bench scientists and clinicians for their daily information needs

Grafted block complex coacervate core micelles and their effect on protein adsorption on silica and polystyrene

We have studied the formation and the stability of grafted block complex coacervate core micelles (C3Ms) in solution and the influence of grafted block C3M coatings on the adsorption of the proteins β-lactoglobulin, bovine serum albumin, and lysozyme. The C3Ms consist of a grafted block copolymer PAA21-b-PAPEO14 (poly(acrylic acid)-b-poly(acrylate methoxy poly(ethylene oxide)), with a negatively charged PAA block and a neutral PAPEO block and a positively charged homopolymer P2MVPI (poly(N-methyl 2-vinyl pyridinium iodide). In solution, these C3Ms partly disintegrate at salt concentrations between 50 and 100 mM NaCl. Adsorption of C3Ms and proteins has been studied with fixed-angle optical reflectometry, at salt concentrations ranging from 1 to 100 mM NaCl. In comparison with the adsorption of PAA21-b-PAPEO14 alone adsorption of C3Ms significantly increases the amount of PAA21-b-PAPEO14 on the surface. This results in a higher surface density of PEO chains. The stability of the C3M coatings and their influence on protein adsorption are determined by the composition and the stability of the C3Ms in solution. A C3M-PAPEO14/P2MVPI43 coating strongly suppresses the adsorption of all proteins on silica and polystyrene. The reduction of protein adsorption is the highest at 100 mM NaCl (>90%). The adsorbed C3M-PAPEO14/P2MVPI43 layer is partly removed from the surface upon exposure to an excess of β-lactoglobulin solution, due to formation of soluble aggregates consisting of β-lactoglobulin and P2MVPI43. In contrast, C3M-PAPEO14/P2MVPI228 which has a fivefold longer cationic block enhances adsorption of the negatively charged proteins on both surfaces at salt concentrations above 1 mM NaCl. A single PAA21-b-PAPEO14 layer causes only a moderate reduction of protein adsorption

Exact Hybrid Particle/Population Simulation of Rule-Based Models of Biochemical Systems

Detailed modeling and simulation of biochemical systems is complicated by the problem of combinatorial complexity, an explosion in the number of species and reactions due to myriad protein-protein interactions and post-translational modifications. Rule-based modeling overcomes this problem by representing molecules as structured objects and encoding their interactions as pattern-based rules. This greatly simplifies the process of model specification, avoiding the tedious and error prone task of manually enumerating all species and reactions that can potentially exist in a system. From a simulation perspective, rule-based models can be expanded algorithmically into fully-enumerated reaction networks and simulated using a variety of network-based simulation methods, such as ordinary differential equations or Gillespie's algorithm, provided that the network is not exceedingly large. Alternatively, rule-based models can be simulated directly using particle-based kinetic Monte Carlo methods. This "network-free" approach produces exact stochastic trajectories with a computational cost that is independent of network size. However, memory and run time costs increase with the number of particles, limiting the size of system that can be feasibly simulated. Here, we present a hybrid particle/population simulation method that combines the best attributes of both the network-based and network-free approaches. The method takes as input a rule-based model and a user-specified subset of species to treat as population variables rather than as particles. The model is then transformed by a process of "partial network expansion" into a dynamically equivalent form that can be simulated using a population-adapted network-free simulator. The transformation method has been implemented within the open-source rule-based modeling platform BioNetGen, and resulting hybrid models can be simulated using the particle-based simulator NFsim. Performance tests show that significant memory savings can be achieved using the new approach and a monetary cost analysis provides a practical measure of its utility. © 2014 Hogg et al