We use graph theory to analyze chromatin interaction (Hi-C) data in the human genome. We show that a key functional feature of the genome--"master" replication origins--corresponds to DNA loci of ...maximal network centrality. These loci form a set of interconnected hubs both within chromosomes and between different chromosomes. Our results open the way to a fruitful use of graph theory concepts to decipher DNA structural organization in relation to genome functions such as replication and transcription. This quantitative information should prove useful to discriminate between possible polymer models of nuclear organization.
Alteration of Formula: see text channel functions (channelopathies) has been encountered in various hereditary muscle diseases. Formula: see text channel mutations lead to aberrant excitability in ...skeletal muscle myotonia and paralysis. In general, these mutations disable inactivation of the Formula: see text channel, producing either repetitive action potential firing (myotonia) or electrical dormancy (flaccid paralysis) in skeletal muscles. These "sick-excitable" cell conditions were shown to correlate with a mechanical stretch-driven left shift of the conductance factors of the two gating mechanisms of a fraction of Formula: see text channels, which make them firing at inappropriate hyperpolarised (left-shifted) voltages. Here we elaborate on a variant of the Hodgkin-Huxley model that includes a stretch elasticity energy component in the activation and inactivation gate kinetic rates. We show that this model reproduces fairly well sick-excitable cell behaviour and can be used to predict the parameter domains where aberrant excitability or paralysis may occur. By allowing us to separate the incidences of activation and inactivation gate impairments in Formula: see text channel excitability, this model could be a strong asset for diagnosing the origin of excitable cell disorders.
From the statistical analysis of nucleosome positioning data for chromosome III of S. cerevisiae, we demonstrate that long-range correlations (LRC) in the genomic sequence strongly influence the ...organization of nucleosomes. We present a physical explanation of how LRC may significantly condition the overall formation and positioning of nucleosomes including the nucleosome-free regions observed at gene promoters. From grand canonical Monte Carlo simulations based upon a simple sequence-dependent nucleosome model, we show that LRC induce a patchy nucleosome occupancy landscape with alternation of "crystal-like" phases of confined regularly spaced nucleosomes and "fluidlike" phases of rather diluted nonpositioned nucleosomes.
The nucleosome ordering observed in vivo along yeast genes is described by a thermodynamical model of nonuniform fluid of 1D hard rods confined by two excluding energy barriers at gene extremities. ...For interbarrier distances L less than or approximately equal to 1.5 kbp, nucleosomes equilibrate into a crystal-like configuration with a nucleosome repeat length (NRL) L/n approximately 165 bp, where n is the number of regularly positioned nucleosomes. We also observe "bistable" genes with a fuzzy chromatin resulting from a statistical mixing of two crystal states, one with an expanded chromatin (NRL approximately L/n) and the other with a compact one (NRL approximately L/(n+1)). By means of single nucleosome switching, bistable genes may drastically alter their expression level as suggested by their higher transcriptional plasticity. These results enlighten the role of the intragenic chromatin on gene expression regulation.
Alteration of Na v channel functions (channelopathies) has been encountered in various hereditary muscle diseases. Na v channel mutations lead to aberrant excitability in skeletal muscle myotonia and ...paralysis. In general, these mutations disable inactivation of the Na v channel, producing either repetitive action potential firing (myotonia) or electrical dormancy (flaccid paralysis) in skeletal muscles. These "sick-excitable" cell conditions were shown to correlate with a mechanical stretch-driven left shift of the conductance factors of the two gating mechanisms of a fraction of Na v channels, which make them firing at inappropriate hyperpolarised (left-shifted) voltages. Here we elaborate on a variant of the Hodgkin-Huxley model that includes a stretch elasticity energy component in the activation and inactivation gate kinetic rates. We show that this model reproduces fairly well sick-excitable cell behaviour and can be used to predict the parameter domains where aberrant excitability or paralysis may occur. By allowing us to separate the incidences of activation and inactivation gate impairments in Na v channel excitability, this model could be a strong asset for diagnosing the origin of excitable cell disorders.
•Standard terms of EEG/ECoG morphology are ill-suited to analyzing seizure variants.•Categorical descriptions are used because morphology eludes numerical definition.•Morphological variation in SWDs ...can be quantified using spectral phase and power.•Proof-of-concept testing shows our algorithm is able to quantify SWD morphology.•A tool to discriminate morphological subtypes can accelerate biomedical discovery.
Spike-wave discharges (SWD) found in neuroelectrical recordings are pathognomonic to absence epilepsy. The characteristic spike-wave morphology of the spike-wave complex (SWC) constituents of SWDs can be mathematically described by a subset of possible spectral power and phase values. Morlet wavelet transform (MWT) generates time-frequency representations well-suited to identifying this SWC-associated subset.
MWT decompositions of SWDs reveal spectral power concentrated at harmonic frequencies. The phase relationships underlying SWC morphology were identified by calculating the differences between phase values at SWD fundamental frequency from the 2nd, 3rd, and 4th harmonics, then using the three phase differences as coordinates to generate a density distribution in a {360°×360°×360°} phase difference space. Strain-specific density distributions were generated from SWDs of mice carrying the Gria4, Gabrg2, or Scn8a mutations to determine whether SWC morphological variants reliably mapped to the same regions of the distribution, and if distribution values could be used to detect SWD.
To the best of our knowledge, this algorithm is the first to employ spectral phase to quantify SWC morphology, making it possible to computationally distinguish SWC morphological subtypes and detect SWDs.
Proof-of-concept testing of the SWDfinder algorithm shows: (1) a major pattern of variation in SWC morphology maps to one axis of the phase difference distribution, (2) variability between the strain-specific distributions reflects differences in the proportions of SWC subtypes generated during SWD, and (3) regularities in the spectral power and phase profiles of SWCs can be used to detect waveforms possessing SWC-like morphology.
The 2D wavelet transform modulus maxima method is used to obtain quantitative information on the fractal/multifractal nature and anisotropic structure of Galactic atomic hydrogen (H I) from the ...Canadian Galactic Plane Survey. Five mosaics were analyzed in the second quadrant of the Milky Way, corresponding to the Local, Perseus, and Outer spiral arms, as well as two "interarm" regions located between these three spiral arms. A monofractal signature is found for all five mosaics. An anisotropic signature is detected: the rms roughness fluctuations of the mosaics in the latitude direction differ from those in the longitude direction. This anisotropy is scale-independent for the interarm regions while it is scale-dependent for the spiral arms. The longitudinal matter distribution of H I structure is similar for all five mosaics while the latitudinal distribution is smoother in the spiral arms. These results hold for all physical length scales studied, from 62 pc in the Local arm to 644 pc in the Outer arm. Several hypotheses are investigated to provide a physical explanation: the scale-height gradient, the density wave, star formation activity, photolevitation of dusty clouds, random motion of H I clouds, corrugation, and turbulence. The slopes of the power spectra for an increasing number of velocity channels were compared for 11 sections of the Local arm column density mosaic. All slopes are identical within the uncertainties (-3.0) and we do not detect for the Galactic plane the change in the power law index predicted by Lazarian and Pogosyan.
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