Regulating chromatin: On code and dynamic models

In this short comment on the contributions by Arndt Benecke, Francois Fuks and Helmut Schiessel I refer to some recent experimental work which sheds light on the histone code hypothesis. Further, I make some remarks on the role theoretical approaches can play in decoding chromatin regulation.     

Chromatin code, local non-equilibrium dynamics, and the emergence of transcription regulatory programs

Chromatin is a, if not the, hallmark of eukaryotic life. Any molecular process entailing genomic DNA or the nucleus by default provokes or depends on chromatin structural dynamics on various space and time scales. Chromatin dynamics are result of changes in the physico-chemical properties of the chromatin constituents themselves or the nuclear environment. Chromatin has been found in the former case to undergo many different covalent enzyme-mediated chemical modifications. Their identification sheds light on the molecular mechanisms and the physico-chemical properties underlying chromatin dynamics, and allows the development of quantitative models for the chromatin fiber. The abundance of the different modifications, their dynamics, and short- as well as long-range correlation phenomena between different modifications also point to a second layer of genomic coding implemented at the level of chromatin. Especially, gene regulatory coding seems to depend on such a second-level code. The information-theoretical properties of chromatin in the context of gene regulatory coding are discussed. A model for the emergence of cellular differentiation from the intricate interplay between genomic and chromatin code is presented and discussed in light of recent experimental insights.     

Chromatin physics: Replacing multiple, representation-centered descriptions at discrete scales by a continuous, function-dependent self-scaled model

This commentary on the inspiring works and ideas by Langowski, Mangeol et al., Lee et al., Bundschuh and Gerland, Schiessel, Vaillant et al., Lesne and Victor, Claudet and Bednar, Fuks, Allemand et al., and Blossey, all appearing in this issue (Eur. Phys. J. E 19 (2006)), expresses our felt need of novel approaches to chromatin modeling.     

Comment on “Chromatin fiber functional organization: Some plausible models” by A. Lesne and J.-M. Victor

In this comment on the contribution of A. Lesne and J.-M. Victor I provide some additional ideas on the hypothesis that higher-order chromatin structures stamp their marks on their small subunits.     

On the equilibria of the MAPK cascade: Cooperativity, modularity and bistability

In this paper we present a discussion of a phenomenological model of the MAPK cascade which was originally proposed by Angeli et al. [D. Angeli, J.E. Ferrell, Jr., E.D. Sontag, PNAS 101 (2004), 1822]. The model and its solution are extended in several respects: (a) an analytical solution is given for the cascade equilibria, exploiting a parameter-based symmetry of the rate equations; (b) we discuss the cooperativity (Hill coefficients) of the cascade and show that a feedforward loop within the cascade increases its cooperativity. The relevance of this result for the notion of modularity is discussed; (c) the feedback model for cascade bistability by Angeli et al. is reconsidered. We argue that care must be taken in modeling the interactions and a biologically realistic phenomenological model cannot be too reductionist. The inclusion of a time-dependent degradation rate is needed to account for a switching of the cascade.     

Vesicle self-reproduction: The involvement of membrane hydraulic and solute permeabilities

Conditions for self-reproduction are sought for a growing vesicle with its growth defined by an exponential increase of vesicle membrane area and by adequate flow of the solution across the membrane. In the first step of the presumed vesicle self-reproduction process, the initially spherical vesicle must double its volume in the doubling time of the membrane area and, through the appropriate shape transformations, attain the shape of two equal spheres connected by an infinitesimally thin neck. The second step involves separation of the two spheres and relies on conditions that cause the neck to be broken. In this paper we consider the first step of this self-reproduction process for a vesicle suspended in a solution whose solute can permeate the vesicle membrane. It is shown that vesicle self-reproduction occurs only for certain combinations of the values of membrane hydraulic and solute permeabilities and the external solute concentration, these quantities being related to the mechanical properties of the membrane and the membrane area doubling time. The analysis includes also the relaxation of a perturbed system towards stationary self-reproduction behavior and the case where the final shape consists of two connected spheres of different radii.     

Evolving genetic code

In 1985, we reported that a bacterium, Mycoplasma capricolum, used a deviant genetic code, namely UGA, a "universal" stop codon, was read as tryptophan. This finding, together with the deviant nuclear genetic codes in not a few organisms and a number of mitochondria, shows that the genetic code is not universal, and is in a state of evolution. To account for the changes in codon meanings, we proposed the codon capture theory stating that all the code changes are non-disruptive without accompanied changes of amino acid sequences of proteins. Supporting evidence for the theory is presented in this review. A possible evolutionary process from the ancient to the present-day genetic code is also discussed.     

A fitter code for Deep Virtual Compton Scattering and Generalized Parton Distributions

We have developed a fitting code based on the leading-twist handbag Deep Virtual Compton Scattering (DVCS) amplitude in order to extract Generalized Parton Distribution (GPD) information from DVCS observables in the valence region. In a first stage, with simulations and pseudo-data, we show that the full GPD information can be recovered from experimental data if enough observables are measured. If only some of these observables are measured, valuable information can still be extracted, with certain observables being particularly sensitive to certain GPDs. In a second stage, we make a practical application of this code to the recent DVCS Jefferson Lab Hall-A data from which we can extract numerical constraints for the two H GPD Compton form factors. An erratum to this article can be found at     

Chromatin supraorganization, mitotic abnormalities and proliferation in cells with increased or down-regulated lox expression: Indirect evidence of a LOX-histone H1 interaction in vivo

Lysyl oxidases (LOXs) are enzymes that permit the covalent crosslinking of the component chains of collagen and elastin. These enzymes are present inside the nuclei of certain mammalian cells. Previous studies have proposed LOX binding to histone H1 in vitro, and histone H1 is known to control global chromatin compaction and mitotic chromosome architecture. Therefore, in the present study, we analyzed chromatin supraorganizational changes, mitotic abnormalities, mitotic indices and cell death ratios in COS-7 and NRK-49F cells with high and low lox expression levels, respectively. The objective was to support biochemical data of LOX-H1 interaction, by providing evidence of chromatin remodeling in vivo, under different lox expressions. Chromatin decondensation assessed by image analysis was observed in COS-7 cells with increased lox expression. This decondensation is suggested to be promoted by LOX actions on histone H1, which loosens the DNA-H1 complex. In NRK-49F cells transfected with antisense lox or subjected to treatment with beta-aminopropionitrile (BAPN), chromatin condensation and nuclear phenotypic variability were found, which may be due to reduced LOX-H1 interaction. When lox expression was increased in COS-7 cells, the frequency of irregular chromosome plates was not affected, but cell proliferation decreased and "cell death preceded by multinucleation" increased. In NRK-49F cells there was accelerated proliferation induced by transfection with the antisense lox, and confirmed when cells were treated with BAPN. Apoptosis increased in NRK-49F cells only with BAPN treatment whereas cell death preceded by multinucleation increased only after antisense lox transfection. The data presented herein regarding chromatin remodeling indirectly support the hypothesis that LOX binds to histone H1 in vivo. Cell proliferation in COS-7 and NRK-49F cells and cell death at least in COS-7 cells agree with predicted effects of LOX interference in these processes.     

JMCT与子通道程序耦合方法研究及验证

蒙特卡罗与热工水力的耦合计算是目前反应堆数值模拟的重要研究方向,在蒙特卡罗方法连续能量点截面的基础上结合热工程序的温度反馈,反应堆中子计算的准确性得到大幅提高。为了提高计算精度,堆芯模型分辨率也需进一步提高,相比于组件均匀化模型,pin-by-pin的建模方式能够获得更好的结果。利用蒙特卡罗程序JMCT与子通道程序COBRA-EN实现了蒙特卡罗-热工的内耦合,内耦合方式通过内存进行数据传递,其计算效率及安全性均优于外耦合方法。随后利用NURISP项目迷你堆的pin-by-pin模型对耦合程序进行验证。计算结果与同类耦合程序相似,验证了程序的准确性。同时,对耦合过程的收敛性问题进行了初步分析。     

Modelling the attenuation in the ATHENA finite elements code for the ultrasonic testing of austenitic stainless steel welds

Multipass welds made in austenitic stainless steel, in the primary circuit of nuclear power plants with pressurized water reactors, are characterized by an anisotropic and heterogeneous structure that disturbs the ultrasonic propagation and makes ultrasonic non-destructive testing difficult. The ATHENA 2D finite element simulation code was developed to help understand the various physical phenomena at play. In this paper, we shall describe the attenuation model implemented in this code to give an account of wave scattering phenomenon through polycrystalline materials. This model is in particular based on the optimization of two tensors that characterize this material on the basis of experimental values of ultrasonic velocities attenuation coefficients. Three experimental configurations, two of which are representative of the industrial welds assessment case, are studied in view of validating the model through comparison with the simulation results. We shall thus provide a quantitative proof that taking into account the attenuation in the ATHENA code dramatically improves the results in terms of the amplitude of the echoes. The association of the code and detailed characterization of a weld’s structure constitutes a remarkable breakthrough in the interpretation of the ultrasonic testing on this type of component.     

Analyses of constraints on high speed optical code division multiplexing access (OCDMA) link parameters due to fiber optic chromatic dispersion

In direct sequence-optical code division multiplexing access (DS-OCDMA) system networks, data rate and data spreading technique involved in such systems require a high chip rate. Transmission link in these systems is significantly affected by the fiber chromatic dispersion. In this study, we have developed and employed a simple model to estimate the G652 fiber dispersion effects. OCDMA technique has been employed to investigate fiber chromatic dispersion effects on multiple access interference (MAI). We have found that, at a short optical fiber length, the optical fiber dispersion has a significant impact on the high data rate transmission systems (higher than 750 Mbit/s). The performance and optimization of optical orthogonal code (OOC) in the OCDMA system is reported. We have demonstrated that, for a high data rate, even if dispersion compensated devices are not deployed, the BER can be significantly improved when the OOC desired length is selected. We have shown that when compensation dispersion devices are not deployed in the system, there is a trade off between the limited dispersion effects and the MAI.     

Performance of run-length limited (4, 18) code for optical storage systems

In this paper, the authors investigate the performance of recently presented run-length limited (4, 18) code for high density optical storage systems. The construction of the code is described simply. The code has code rate R = 1/3 and density ratio (DR) = 1.67. The bit error rate (BER) performance for decision feedback equalizer (DFE) and partial response maximum likelihood (PRML) detector are simulated, considering signal-to-noise ratio (SNR) and optical channel jitter. The result shows that the performance of the code is acceptable. The encoder and decoder of the code are implemented by complex programmable logic device (CPLD) chip and the hardware resources required for encoder and decoder arelow.     

A general two-cycle network model of molecular motors

Molecular motors are single macromolecules that generate forces at the piconewton range and nanometer scale. They convert chemical energy into mechanical work by moving along filamentous structures. In this paper, we study the velocity of two-head molecular motors in the framework of a mechanochemical network theory. The network model, a generalization of the recently work of Liepelt and Lipowsky [Steffen Liepelt, Reinhard Lipowsky, Kinesins network of chemomechanical motor cycles, Physical Review Letters 98 (25) (2007) 258102], is based on the discrete mechanochemical states of a molecular motor with multiple cycles. By generalizing the mathematical method developed by Fisher and Kolomeisky for a single cycle motor [Michael E. Fisher, Anatoly B. Kolomeisky, Simple mechanochemistry describes the dynamics of kinesin molecules, Proceedings of the National Academy of Sciences 98 (14) (2001) 7748-7753], we are able to obtain an explicit formula for the velocity of a molecular motor.     

Information value and information content in the evolutionary strategy of the genetic code

Summary In previous papers we defined the information value of a genetic code as a measure of its efficiency in the utilization of the information stored in the DNA molecule. Here the genetic codes which have been proposed to be intermediate steps in evolution are analysed in terms of information theory. The results show that evolution follows an optimization strategy between increasing the information content and decreasing the information value,i.e. in each evolutionary step the average information value per unitary information content decreases and at the same time the probability of nonsense mutations goes down as the code evolves. To speed up publication, the authors of this paper have agreed to not recive the proofs for correction.     

中子时空动力学计算程序CORCA-K的进展

主要介绍了自主化中子时空动力学程序CORCA-K的相关研发进展。CORCA-K程序是中核集团自主研发的NESTOR软件包中的三维瞬态中子学计算软件。其核心功能是采用数值计算方法,求解三维瞬态中子扩散方程。其空间离散采用第二类边界条件节块格林函数方法,与三维稳态扩散计算程序CORCA-3D保持自洽性;时间离散采用对角线隐式龙格库塔格式,可在向后欧拉格式的基础上叠加实现,且具备时步自适应功能。以三维LMW基准问题、三维LRA基准问题和秦山核电厂3号机组第5循环为计算对象,开展了瞬态计算验证。结果表明,CORCA-K计算结果与参考程序符合较好,且在保证计算精度的条件下,具有更高的计算效率。