Comparative in silico analysis identifies bona fide MyoD binding sites within the Myocyte Stress 1 gene promoter

<p>Abstract</p> <p>Background</p> <p>Myocyte stress 1 (MS1) is a striated muscle actin binding protein required for the muscle specific activity of the evolutionary ancient myocardin related transcription factor (MRTF)/serum response factor (SRF) transcriptional pathway. To date, little is known about the molecular mechanisms that govern skeletal muscle specific expression of MS1. Such mechanisms are likely to play a major role in modulating SRF activity and therefore muscle determination, differentiation and regeneration. In this study we employed a comparative <it>in silico </it>analysis coupled with an experimental promoter characterisation to delineate these mechanisms.</p> <p>Results</p> <p>Analysis of MS1 expression in differentiating C2C12 muscle cells demonstrated a temporal differentiation dependent up-regulation in <it>ms1 </it>mRNA. An <it>in silico </it>comparative sequence analysis identified two conserved putative myogenic regulatory domains within the proximal 1.5 kbp of 5' upstream sequence. Co-transfecting C2C12 myoblasts with <it>ms1 </it>promoter/luciferase reporters and myogenic regulatory factor (MRF) over-expression plasmids revealed specific sensitivity of the <it>ms1 </it>promoter to MyoD. Subsequent mutagenesis and EMSA analysis demonstrated specific targeting of MyoD at two distinct E-Boxes (E1 and E2) within identified evolutionary conserved regions (ECRs, α and β). Chromatin immunoprecipitation (ChIP) analysis indicates that co-ordinated binding of MyoD at E-Boxes located within ECRs α and β correlates with the temporal induction in <it>ms1 </it>mRNA.</p> <p>Conclusion</p> <p>These findings suggest that the tissue specific and differentiation dependent up-regulation in <it>ms1 </it>mRNA is mediated by temporal binding of MyoD at distinct evolutionary conserved E-Boxes within the <it>ms1 </it>5' upstream sequence. We believe, through its activation of <it>ms1</it>, this is the first study to demonstrate a direct link between MyoD activity and SRF transcriptional signalling, with clear implications for the understanding of muscle determination, differentiation and regeneration.</p

Classifying States of a Finite Markov Chain with Membrane Computing

In this paper we present a method to classify the states of a finite Markov chain through membrane computing. A specific P system with external output is designed for each boolean matrix associated with a finite Markov chain. The computation of the system allows us to decide the convergence of the process because it determines in the environment the classification of the states (recurrent, absorbent, and transient) as well as the periods of states. The amount of resources required in the construction is polynomial in the number of states of the Markov chain.Ministerio de Ciencia y Educación TIN2005-09345-C04-01Junta de Andalucía TIC-58

Dynamical robustness of biological networks with hierarchical distribution of time scales

We propose the concepts of distributed robustness and r-robustness, well adapted to functional genetics. Then we discuss the robustness of the relaxation time using a chemical reaction description of genetic and signalling networks. First, we obtain the following result for linear networks: for large multiscale systems with hierarchical distribution of time scales the variance of the inverse relaxation time (as well as the variance of the stationary rate) is much lower than the variance of the separate constants. Moreover, it can tend to 0 faster than 1/n, where n is the number of reactions. We argue that similar phenomena are valid in the nonlinear case as well. As a numerical illustration we use a model of signalling network that can be applied to important transcription factors such as NFkB

Future Contingents and the Logic of Temporal Omniscience

At least since Aristotle’s famous 'sea-battle' passages in On Interpretation 9, some substantial minority of philosophers has been attracted to the doctrine of the open future--the doctrine that future contingent statements are not true. But, prima facie, such views seem inconsistent with the following intuition: if something has happened, then (looking back) it was the case that it would happen. How can it be that, looking forwards, it isn’t true that there will be a sea battle, while also being true that, looking backwards, it was the case that there would be a sea battle? This tension forms, in large part, what might be called the problem of future contingents. A dominant trend in temporal logic and semantic theorizing about future contingents seeks to validate both intuitions. Theorists in this tradition--including some interpretations of Aristotle, but paradigmatically, Thomason (1970), as well as more recent developments in Belnap, et. al (2001) and MacFarlane (2003, 2014)--have argued that the apparent tension between the intuitions is in fact merely apparent. In short, such theorists seek to maintain both of the following two theses: (i) the open future: Future contingents are not true, and (ii) retro-closure: From the fact that something is true, it follows that it was the case that it would be true. It is well-known that reflection on the problem of future contingents has in many ways been inspired by importantly parallel issues regarding divine foreknowledge and indeterminism. In this paper, we take up this perspective, and ask what accepting both the open future and retro-closure predicts about omniscience. When we theorize about a perfect knower, we are theorizing about what an ideal agent ought to believe. Our contention is that there isn’t an acceptable view of ideally rational belief given the assumptions of the open future and retro-closure, and thus this casts doubt on the conjunction of those assumptions

Universality and scaling study of the critical behavior of the two-dimensional Blume-Capel model in short-time dynamics

In this paper we study the short-time behavior of the Blume-Capel model at the tricritical point as well as along the second order critical line. Dynamic and static exponents are estimated by exploring scaling relations for the magnetization and its moments at early stage of the dynamic evolution. Our estimates for the dynamic exponents, at the tricritical point, are $z= 2.215(2)$ and $\theta= -0.53(2)$.Comment: 12 pages, 9 figure

Bessel Process and Conformal Quantum Mechanics

Different aspects of the connection between the Bessel process and the conformal quantum mechanics (CQM) are discussed. The meaning of the possible generalizations of both models is investigated with respect to the other model, including self adjoint extension of the CQM. Some other generalizations such as the Bessel process in the wide sense and radial Ornstein- Uhlenbeck process are discussed with respect to the underlying conformal group structure.Comment: 28 Page

Is It Rational to Assume that Infants Imitate Rationally? A Theoretical Analysis and Critique

It has been suggested that preverbal infants evaluate the efficiency of others' actions (by applying a principle of rational action) and that they imitate others' actions rationally. The present contribution presents a conceptual analysis of the claim that preverbal infants imitate rationally. It shows that this ability rests on at least three assumptions: that infants are able to perceive others' action capabilities, that infants reason about and conceptually represent their own bodies, and that infants are able to think counterfactually. It is argued that none of these three abilities is in place during infancy. Furthermore, it is shown that the idea of a principle of rational action suffers from two fallacies. As a consequence, is it suggested that it is not rational to assume that infants imitate rationally. Copyright (C) 2012 S. Karger AG, Base

Commensurate and Incommensurate Vortex Lattice Melting in Periodic Pinning Arrays

We examine the melting of commensurate and incommensurate vortex lattices interacting with square pinning arrays through the use of numerical simulations. For weak pinning strength in the commensurate case we observe an order-order transition from a commensurate square vortex lattice to a triangular floating solid phase as a function of temperature. This floating solid phase melts into a liquid at still higher temperature. For strong pinning there is only a single transition from the square pinned lattice to the liquid state. For strong pinning in the incommensurate case, we observe a multi-stage melting in which the interstitial vortices become mobile first, followed by the melting of the entire lattice, consistent with recent imaging experiments. The initial motion of vortices in the incommensurate phase occurs by an exchange process of interstitial vortices with vortices located at the pinning sites. We have also examined the vortex melting behavior for higher matching fields and find that a coexistence of a commensurate pinned vortex lattice with an interstitial vortex liquid occurs while at higher temperatures the entire vortex lattice melts. For triangular arrays at incommensurate fields higher than the first matching field we observe that the initial vortex motion can occur through a novel correlated ring excitation where a number of vortices can rotate around a pinned vortex. We also discuss the relevance of our results to recent experiments of colloidal particles interacting with periodic trap arrays.Comment: 8 figure

Heat release by controlled continuous-time Markov jump processes

We derive the equations governing the protocols minimizing the heat released by a continuous-time Markov jump process on a one-dimensional countable state space during a transition between assigned initial and final probability distributions in a finite time horizon. In particular, we identify the hypotheses on the transition rates under which the optimal control strategy and the probability distribution of the Markov jump problem obey a system of differential equations of Hamilton-Bellman-Jacobi-type. As the state-space mesh tends to zero, these equations converge to those satisfied by the diffusion process minimizing the heat released in the Langevin formulation of the same problem. We also show that in full analogy with the continuum case, heat minimization is equivalent to entropy production minimization. Thus, our results may be interpreted as a refined version of the second law of thermodynamics.Comment: final version, section 2.1 revised, 26 pages, 3 figure