Geometry of the nucleosomal DNA superhelix

Nucleosome stability is largely an indirect measure of DNA sequence based on the material properties of DNA and the ability of a sequence to assume the required left-handed superhelical conformation. Here we focus attention only on the geometry of the superhelix and present two distinct mathematical expressions that rely on the DNA helical parameters (Shift, Slide, Rise, Tilt, Roll, Twist). One representation requires torsion for superhelix formation; the other requires shear. To compare these mathematical expressions to experimental data we develop a strategy for Fourier-filtering the helical parameters that identifies necessary and sufficient conditions to achieve a high-resolution model of the nucleosome superhelix. We apply this filtering strategy to 24 high-resolution structures of the nucleosome and demonstrate that all structures have a highly conserved distribution of Roll, Slide and Twist that involves two length scales. One length scale spans the entire length of nucleosomal DNA. The other is associated with the helix repeat. Our strategy also enables us to identify ground state or simple nucleosomes and altered nucleosome structures. These results form a basis for characterizing structural variations in the emerging family of nucleosome structures and a method for further developing structure-based models of nucleosome stability.     

Fractal properties of DNA walks

We describe two dimensional DNA walks, and analyze their fractal properties. We show results for the complete genome of S. cerevisiae. We find that the mean square deviation of the walks is superdifussive, corresponding to a fractal structure of dimension lower than two. Furthermore, the coding part of the genome seems to have smaller fractal dimension, and longer correlations, than noncoding parts.     

Geometry and mechanics of DNA superhelicity

This paper analyzes the elastic equilibrium conformations of duplex DNA constrained by the constancy of its molecular linking number, Lk. The DNA is regarded as having the mechanical properties of a homogeneous, linearly elastic substance with symmetric cross section. Integral representations of the writhing number Wr and of Lk are developed, in terms of which the equilibria are given as solutions to an isoperimetric problem. It is shown that the Euler angles defining equilibrium conformations must obey equations identical to those governing unconstrained equilibria. A scaling law is developed stating that molecules supercoiled the same amount ΔLk will have geometrically similar elastic equilibria regardless of their length. Thus, comparisons among molecules of properties related to their large-scale tertiary structure should be referred to differences in ΔLk rather than to their superhelix densities. Specific conditions on the elastic equilibrium conformations are developed that are necessary for ring closure. The equilibrium superhelical conformations accessible to closed-ring molecules are shown to approximate toroidal helices. Questions relating to the stability and nonuniqueness of equilibria are treated briefly. A comparison is made between these toroidal conformations and interwound configurations, which are shown to be stable, although they are not equilibria in the present sense. It is suggested that entropic factors are responsible for favouring the toroidal conformation in solution.     

Structure of Three-Way DNA Junctions 1. Non-Planar DNA Geometry

Abstract

Three-way junctions were obtained by annealing two synthetic DNA-oligomers. One of the strands contains a short palindrome sequence, leading to the formation of a hairpin with four base pairs in the stem and four bases in the loop. Another strand is complementary to the linear arms of the first hairpin-containing strand. Both strands were annealed to form a three-way branched structure with sticky ends on the linear arms. The branched molecules were ligated, and the ligation mixture was analysed on a two-dimensional gel in conditions which separated linear and circular molecules. Analysis of 2D-electrophoresis data shows that circular molecules with high mobility are formed. Formation of circular molecules is indicative of bends between linear arms. We estimate the magnitude of the angle between linear arms from the predominant size of the circular molecules formed. When the junction-to-junction distance is 20–21 bp, trimers and tetramers are formed predominately, giving an angle between linear arms as small as 60–90°. Rotation of the hairpin position in the three- way junction allowed us to measure angles between other arms, yielding similar values. These results led us to conclude that the three-way DNA junction possesses a non-planar pyramidal geometry with 60–90° between the arms. Computer modeling of the three-way junction with 60° pyramidal geometry showed a predominantly B-form structure with local distortions at the junction points that diminish towards the ends of the helices. The size distributions of circular molecules are rather broad indicating a dynamic flexibility of three-way DNA junctions.     

Analysis and Optimization of Bulk DNA Sampling with Binary Scoring for Germplasm Characterization

The strategy of bulk DNA sampling has been a valuable method for studying large numbers of individuals through genetic markers. The application of this strategy for discrimination among germplasm sources was analyzed through information theory, considering the case of polymorphic alleles scored binarily for their presence or absence in DNA pools. We defined the informativeness of a set of marker loci in bulks as the mutual information between genotype and population identity, composed by two terms: diversity and noise. The first term is the entropy of bulk genotypes, whereas the noise term is measured through the conditional entropy of bulk genotypes given germplasm sources. Thus, optimizing marker information implies increasing diversity and reducing noise. Simple formulas were devised to estimate marker information per allele from a set of estimated allele frequencies across populations. As an example, they allowed optimization of bulk size for SSR genotyping in maize, from allele frequencies estimated in a sample of 56 maize populations. It was found that a sample of 30 plants from a random mating population is adequate for maize germplasm SSR characterization. We analyzed the use of divided bulks to overcome the allele dilution problem in DNA pools, and concluded that samples of 30 plants divided into three bulks of 10 plants are efficient to characterize maize germplasm sources through SSR with a good control of the dilution problem. We estimated the informativeness of 30 SSR loci from the estimated allele frequencies in maize populations, and found a wide variation of marker informativeness, which positively correlated with the number of alleles per locus.     

阿达玛变换显微图象法测定乳腺癌DNA含量

以吖啶橙为细胞DNA荧光探针,用阿达玛(Hadamard)变换显微图象分析仪和显微荧光光度计分别测定了4例乳腺肿瘤的细胞DNA含量(倍性),并对分析结果进行了比较,二者的分析结果均与病理学诊断结论相吻合.阿达玛变换显微图象分析仪作为一种新的细胞定量分析仪器,其分析结果的准确度可与显微荧光光度计相媲美,而且阿达玛变换显微图象分析仪还具有其独特的优点,如信噪比高、具有同时分析多个细胞和同步扣除背景信号的能力等.     

The Duplexing of the Genetic Code and Sequence-Dependent DNA Geometry

It is well known that sequences of bases in DNA are translated into sequences of amino acids in cells via the genetic code. More recently, it has been discovered that the sequence of DNA bases also influences the geometry and deformability of the DNA. These two correspondences represent a naturally arising example of duplexed codes, providing two different ways of interpreting the same DNA sequence. This paper will set up the notation and basic results necessary to mathematically investigate the relationship between these two natural DNA codes. It then undertakes two very different such investigations: one graphical approach based only on expected values and another analytic approach incorporating the deformability of the DNA molecule and approximating the mutual information of the two codes. Special emphasis is paid to whether there is evidence that pressure to maximize the duplexing efficiency influenced the evolution of the genetic code. Disappointingly, the results fail to support the hypothesis that the genetic code was influenced in this way. In fact, applying both methods to samples of realistic alternative genetic codes shows that the duplexing of the genetic code found in nature is just slightly less efficient than average. The implications of this negative result are considered in the final section of the paper.     

Geometry of mediating protein affects the probability of loop formation in DNA

Recent single molecule experiments have determined the probability of loop formation in DNA as a function of the DNA contour length for different types of looping proteins. The optimal contour length for loop formation as well as the probability density functions have been found to be strongly dependent on the type of looping protein used. We show, using Monte Carlo simulations and analytical calculations, that these observations can be replicated using the wormlike-chain model for double-stranded DNA if we account for the nonzero size of the looping protein. The simulations have been performed in two dimensions so that bending is the only mode of deformation available to the DNA while the geometry of the looping protein enters through a single variable which is representative of its size. We observe two important effects that seem to directly depend on the size of the enzyme: 1), the overall propensity of loop formation at any given value of the DNA contour length increases with the size of the enzyme; and 2), the contour length corresponding to the first peak as well as the first well in the probability density functions increases with the size of the enzyme. Additionally, the eigenmodes of the fluctuating shape of the looped DNA calculated from simulations and theory are in excellent agreement, and reveal that most of the fluctuations in the DNA occur in regions of low curvature.     

Geometry and Physics of Catenanes Applied to the Study of DNA Replication

The concept of ideal geometric configurations was recently applied to the classification and characterization of various knots. Different knots in their ideal form (i.e., the one requiring the shortest length of a constant-diameter tube to form a given knot) were shown to have an overall compactness proportional to the time-averaged compactness of thermally agitated knotted polymers forming corresponding knots. This was useful for predicting the relative speed of electrophoretic migration of different DNA knots. Here we characterize the ideal geometric configurations of catenanes (called links by mathematicians), i.e., closed curves in space that are topologically linked to each other. We demonstrate that the ideal configurations of different catenanes show interrelations very similar to those observed in the ideal configurations of knots. By analyzing literature data on electrophoretic separations of the torus-type of DNA catenanes with increasing complexity, we observed that their electrophoretic migration is roughly proportional to the overall compactness of ideal representations of the corresponding catenanes. This correlation does not apply, however, to electrophoretic migration of certain replication intermediates, believed up to now to represent the simplest torus-type catenanes. We propose, therefore, that freshly replicated circular DNA molecules, in addition to forming regular catenanes, may also form hemicatenanes.     

High-Speed Laser Image Analysis of Plume Angles for Pressurised Metered Dose Inhalers: The Effect of Nozzle Geometry

The aim of this study is to investigate aerosol plume geometries of pressurised metered dose inhalers (pMDIs) using a high-speed laser image system with different actuator nozzle materials and designs. Actuators made from aluminium, PET and PTFE were manufactured with four different nozzle designs: cone, flat, curved cone and curved flat. Plume angles and spans generated using the designed actuator nozzles with four solution-based pMDI formulations were imaged using Oxford Lasers EnVision system and analysed using EnVision Patternate software. Reduced plume angles for all actuator materials and nozzle designs were observed with pMDI formulations containing drug with high co-solvent concentration (ethanol) due to the reduced vapour pressure. Significantly higher plume angles were observed with the PTFE flat nozzle across all formulations, which could be a result of the nozzle geometry and material’s hydrophobicity. The plume geometry of pMDI aerosols can be influenced by the vapour pressure of the formulation, nozzle geometries and actuator material physiochemical properties.     

Simple Elastic Network Models for Exhaustive Analysis of Long Double-Stranded DNA Dynamics with Sequence Geometry Dependence

Simple elastic network models of DNA were developed to reveal the structure-dynamics relationships for several nucleotide sequences. First, we propose a simple all-atom elastic network model of DNA that can explain the profiles of temperature factors for several crystal structures of DNA. Second, we propose a coarse-grained elastic network model of DNA, where each nucleotide is described only by one node. This model could effectively reproduce the detailed dynamics obtained with the all-atom elastic network model according to the sequence-dependent geometry. Through normal-mode analysis for the coarse-grained elastic network model, we exhaustively analyzed the dynamic features of a large number of long DNA sequences, approximately ∼150 bp in length. These analyses revealed positive correlations between the nucleosome-forming abilities and the inter-strand fluctuation strength of double-stranded DNA for several DNA sequences.     

Automated Digitization of the Cardiotocography Signals from Real Scene Image of Binary Clinic Report

ObjectiveCardiotocography (CTG) is a popular clinical tool to assess foetal health status. Automatic CTG analysis can remove the judgement differences of inter- and intra- doctors. However, absence of CTG database has hindered the development of automatic CTG analysis based on deep learning. Therefore, digitization of CTG signal from clinic report is an important way to enrich CTG database, and in turn promote the automatic CTG analysis.MethodThe proposed digitization method extracts digital signal from the commonly used binary CTG paper reports. An adaptive region positioning algorithm based on statistical calculation is used to locate signal regions. Then, by deducing the dynamic minimal weight sum in theory, methods based on statistical calculation and on the weight sum are designed to remove grid lines. Next, according to different breakpoint types and signal line trends, different signal reconstruction methods are formulated. This realize extracting the signal line from binary background grid lines. Finally, a calibration method based on segmented sampling is designed to reduce calibration error due to smartphone lens distortion.ResultsThe experimental results show that the correlation coefficients of FHR and UC of proposed method both reached 0.98. After three expert gynaecologists's evaluations, there are no clinically relevant differences were identified between the extracted signals and the reference ones.     

Fractal Analysis of Cervical Intraepithelial Neoplasia

Introduction

Cervical intraepithelial neoplasias (CIN) represent precursor lesions of cervical cancer. These neoplastic lesions are traditionally subdivided into three categories CIN 1, CIN 2, and CIN 3, using microscopical criteria. The relation between grades of cervical intraepithelial neoplasia (CIN) and its fractal dimension was investigated to establish a basis for an objective diagnosis using the method proposed.

Methods

Classical evaluation of the tissue samples was performed by an experienced gynecologic pathologist. Tissue samples were scanned and saved as digital images using Aperio scanner and software. After image segmentation the box counting method as well as multifractal methods were applied to determine the relation between fractal dimension and grades of CIN. A total of 46 images were used to compare the pathologist''s neoplasia grades with the predicted groups obtained by fractal methods.

Results

Significant or highly significant differences between all grades of CIN could be found. The confusion matrix, comparing between pathologist''s grading and predicted group by fractal methods showed a match of 87.1%. Multifractal spectra were able to differentiate between normal epithelium and low grade as well as high grade neoplasia.

Conclusion

Fractal dimension can be considered to be an objective parameter to grade cervical intraepithelial neoplasia.     

Geometry of the DNA strands within the RecA nucleofilament: role in homologous recombination

Homologous recombination consists of exchanging DNA strands of identical or almost identical sequence. This process is important for both DNA repair and DNA segregation. In prokaryotes, it involves the formation of long helical filaments of the RecA protein on DNA. These filaments incorporate double-stranded DNA from the cell's genetic material, recognize sequence homology and promote strand exchange between the two DNA segments. DNA processing by these nucleofilaments is characterized by large amplitude deformations of the double helix, which is stretched by 50% and unwound by 40% with respect to B-DNA. In this article, information concerning the structure and interactions of the RecA, DNA and ATP molecules involved in DNA strand exchange is gathered and analyzed to present a view of their possible arrangement within the filament, their behavior during strand exchange and during ATP hydrolysis, the mechanism of RecA-promoted DNA deformation and the role of DNA deformation in the process of homologous recombination. In particular, the unusual characteristics of DNA within the RecA filament are compared to the DNA deformations locally induced by architectural proteins which bind in the DNA minor groove. The possible role and location of two flexible loops of RecA are discussed.     

Fractal Analysis of Plant Root Systems

The morphology of root systems of crop plants was analysed byfractal geometry using an image processing system. Results indicatethat these root systems have a fractal structure (D; 1.48     

Fractal construction of constrained code words for DNA storage systems

The use of complex biological molecules to solve computational problems is an emerging field at the interface between biology and computer science. There are two main categories in which biological molecules, especially DNA, are investigated as alternatives to silicon-based computer technologies. One is to use DNA as a storage medium, and the other is to use DNA for computing. Both strategies come with certain constraints. In the current study, we present a novel approach derived from chaos game representation for DNA to generate DNA code words that fulfill user-defined constraints, namely GC content, homopolymers, and undesired motifs, and thus, can be used to build codes for reliable DNA storage systems.     

Detection of Glucose and Related Analytes by Biosensors: A Fractal Analysis

A fractal analysis is used to model the binding and dissociation kinetics of connective tissue interstitial glucose, adipose tissue interstitial glucose, insulin, and other related analytes on biosensor surfaces. The analysis provides insights into diffusion-limited analyte-receptor reactions occurring on heterogeneous biosensor surfaces. Numerical values obtained for the binding and the dissociation rate coefficients are linked to the degree of heterogeneity or roughness [fractal dimension (D_f)] present on the biosensor chip surface. The binding and dissociation rate coefficients are sensitive to the degree of heterogeneity on the surface. For example, for the binding of plasma insulin, as the fractal dimension value increases by a factor of 2.47 from D_f1 = 0.6827 to D_f2 = 1.6852, the binding rate coefficient increases by a factor of 4.92 from k₁ = 1.0232 to k₂ = 5.0388. An increase in the degree of heterogeneity on the probe surface leads to an increase in the binding rate coefficient. A dual-fractal analysis is required to fit the binding kinetics in most of the cases presented. A single fractal analysis is adequate to describe the dissociation kinetics. Affinity (ratio of the binding to the dissociation rate coefficient) values are also presented. Interferents for glucose, such as uric acid and ascorbic acid, were also detected by using glucose biosensors based on carbon nanotube (CNT) nanoelectrode ensembles (NEEs) (Lin Y, Lu F, Tu Y, Ren Z. Nano Lett 2004, 4, 191–195).