A Novel Signal Processing Measure to Identify Exact and Inexact Tandem Repeat Patterns in DNA Sequences

The identification and analysis of repetitive patterns are active areas of biological and computational research. Tandem repeats in telomeres play a role in cancer and hypervariable trinucleotide tandem repeats are linked to over a dozen major neurodegenerative genetic disorders. In this paper, we present an algorithm to identify the exact and inexact repeat patterns in DNA sequences based on orthogonal exactly periodic subspace decomposition technique. Using the new measure our algorithm resolves the problems like whether the repeat pattern is of period Open image in new window or its multiple (i.e., 2 Open image in new window , 3 Open image in new window , etc.), and several other problems that were present in previous signal-processing-based algorithms. We present an efficient algorithm of Open image in new window , where Open image in new window is the length of DNA sequence and Open image in new window is the window length, for identifying repeats. The algorithm operates in two stages. In the first stage, each nucleotide is analyzed separately for periodicity, and in the second stage, the periodic information of each nucleotide is combined together to identify the tandem repeats. Datasets having exact and inexact repeats were taken up for the experimental purpose. The experimental result shows the effectiveness of the approach.     

Gene Systems Network Inferred from Expression Profiles in Hepatocellular Carcinogenesis by Graphical Gaussian Model

Hepatocellular carcinoma (HCC) in a liver with advanced-stage chronic hepatitis C (CHC) is induced by hepatitis C virus, which chronically infects about 170 million people worldwide. To elucidate the associations between gene groups in hepatocellular carcinogenesis, we analyzed the profiles of the genes characteristically expressed in the CHC and HCC cell stages by a statistical method for inferring the network between gene systems based on the graphical Gaussian model. A systematic evaluation of the inferred network in terms of the biological knowledge revealed that the inferred network was strongly involved in the known gene-gene interactions with high significance Open image in new window , and that the clusters characterized by different cancer-related responses were associated with those of the gene groups related to metabolic pathways and morphological events. Although some relationships in the network remain to be interpreted, the analyses revealed a snapshot of the orchestrated expression of cancer-related groups and some pathways related with metabolisms and morphological events in hepatocellular carcinogenesis, and thus provide possible clues on the disease mechanism and insights that address the gap between molecular and clinical assessments.     

Oxygen cost of dynamic or isometric exercise relative to recruited muscle mass

Background

Oxygen cost of different muscle actions may be influenced by different recruitment and rate coding strategies. The purpose of this study was to account for these strategies by comparing the oxygen cost of dynamic and isometric muscle actions relative to the muscle mass recruited via surface electrical stimulation of the knee extensors.

Methods

Comparisons of whole body pulmonary Δ $\dot{V}$O₂ were made in seven young healthy adults (1 female) during 3 minutes of dynamic or isometric knee extensions, both induced by surface electrical stimulation. Recruited mass was quantified in T₂ weighted spin echo magnetic resonance images.

Results

The Δ $\dot{V}$O₂ for dynamic muscle actions, 242 ± 128 ml ? min^-1 (mean ± SD) was greater (p = 0.003) than that for isometric actions, 143 ± 99 ml ? min^-1. Recruited muscle mass was also greater (p = 0.004) for dynamic exercise, 0.716 ± 282 versus 0.483 ± 0.139 kg. The rate of oxygen consumption per unit of recruited muscle (${\dot{V}\text{O}}_{2^{\text{RM}}}$) was similar in dynamic and isometric exercise (346 ± 162 versus 307 ± 198 ml ? kg^-1 ? min^-1; p = 0.352), but the ${\dot{V}\text{O}}_{2^{\text{RM}}}$ calculated relative to initial knee extensor torque was significantly greater during dynamic exercise 5.1 ± 1.5 versus 3.6 ± 1.6 ml ? kg^-1 ? Nm^-1 ? min^-1 (p = 0.019).

Conclusion

These results are consistent with the view that oxygen cost of dynamic and isometric actions is determined by different circumstances of mechanical interaction between actin and myosin in the sarcomere, and that muscle recruitment has only a minor role.

     

On optimal control policy for probabilistic Boolean network: a state reduction approach

Background

Probabilistic Boolean Network (PBN) is a popular model for studying genetic regulatory networks. An important and practical problem is to find the optimal control policy for a PBN so as to avoid the network from entering into undesirable states. A number of research works have been done by using dynamic programming-based (DP) method. However, due to the high computational complexity of PBNs, DP method is computationally inefficient for a large size network. Therefore it is natural to seek for approximation methods.

Results

Inspired by the state reduction strategies, we consider using dynamic programming in conjunction with state reduction approach to reduce the computational cost of the DP method. Numerical examples are given to demonstrate both the effectiveness and the efficiency of our proposed method.

Conclusions

Finding the optimal control policy for PBNs is meaningful. The proposed problem has been shown to be ${\sum }_2^p\mathsf{\text{ - hard}}$. By taking state reduction approach into consideration, the proposed method can speed up the computational time in applying dynamic programming-based algorithm. In particular, the proposed method is effective for larger size networks.

     

Polynomial algorithms for the Maximal Pairing Problem: efficient phylogenetic targeting on arbitrary trees

Background

The Maximal Pairing Problem (MPP) is the prototype of a class of combinatorial optimization problems that are of considerable interest in bioinformatics: Given an arbitrary phylogenetic tree T and weights ω _xy for the paths between any two pairs of leaves (x, y), what is the collection of edge-disjoint paths between pairs of leaves that maximizes the total weight? Special cases of the MPP for binary trees and equal weights have been described previously; algorithms to solve the general MPP are still missing, however.

Results

We describe a relatively simple dynamic programming algorithm for the special case of binary trees. We then show that the general case of multifurcating trees can be treated by interleaving solutions to certain auxiliary Maximum Weighted Matching problems with an extension of this dynamic programming approach, resulting in an overall polynomial-time solution of complexity Open image in new window (n⁴ log n) w.r.t. the number n of leaves. The source code of a C implementation can be obtained under the GNU Public License from http://www.bioinf.uni-leipzig.de/Software/Targeting. For binary trees, we furthermore discuss several constrained variants of the MPP as well as a partition function approach to the probabilistic version of the MPP.

Conclusions

The algorithms introduced here make it possible to solve the MPP also for large trees with high-degree vertices. This has practical relevance in the field of comparative phylogenetics and, for example, in the context of phylogenetic targeting, i.e., data collection with resource limitations.

     

Ship-borne Nonindigenous Species Diminish Great Lakes Ecosystem Services

We used structured expert judgment and economic analysis to quantify annual impacts on ecosystem services in the Great Lakes, North America of nonindigenous aquatic species introduced by ocean-going ships. For the US waters, median damages aggregated across multiple ecosystem services were Open image in new window 138 million per year, and there is a 5% chance that for sportfishing alone losses exceeded Open image in new window 800 million annually. Plausible scenarios of future damages in the US waters alone were similar in magnitude to the binational benefits of ocean-going shipping in the Great Lakes, suggesting more serious consideration is warranted for policy options to reduce the risk of future invasions via the St. Lawrence Seaway.     

Multiple feature affixation in Seenku plural formation

Nominal plural formation in Seenku involves two surface changes: fronting of the final vowel and raising of the final tone. Diachronically, the plural patterns likely derive from a suffix *- Open image in new window , which has been obscured through the loss of falling sonority diphthongs. By comparing plural formation to other morphophonological processes in Seenku, this paper argues that the plural suffix has been restructured as a featural suffix consisting of two features: the vocalic feature [+front], resulting in vowel fronting, and the tonal feature [+raised], resulting in tone raising. Given the atomic nature of the morphosyntactic feature plural, Seenku plural formation represents a strong case of multiple feature affixation, albeit a case that can be accounted for through Max constraints on feature values (Lombardi 2001, etc.) and Realize-Morpheme (van Oostendorp 2005; Trommer 2012) rather than the constraint Max-Flt argued for by Wolf (2007). A level-ordered approach retaining the vocalic suffix is also considered but is shown to suffer from a number of shortcomings, particularly with respect to tone and a challenging class of nasal stems. In short, this paper explores how the synchronic grammar copes with the vestiges of affixal morphology in a language that has undergone heavy reduction.     

Contribution on the diagnosis ofStaphylococcus aureus rosenbach

Возможность трансформации прогестерона, стероида ?S? (11-дезокси-17-гидроксикортикостерон), дегидроэпиандростерона и

     

Generalized spring tensor models for protein fluctuation dynamics and conformation changes

Background

In the last decade, various coarse-grained elastic network models have been developed to study the large-scale motions of proteins and protein complexes where computer simulations using detailed all-atom models are not feasible. Among these models, the Gaussian Network Model (GNM) and Anisotropic Network Model (ANM) have been widely used. Both models have strengths and limitations. GNM can predict the relative magnitudes of protein fluctuations well, but due to its isotropy assumption, it can not be applied to predict the directions of the fluctuations. In contrast, ANM adds the ability to do the latter, but loses a significant amount of precision in the prediction of the magnitudes.

Results

In this article, we develop a single model, called generalized spring tensor model (STeM), that is able to predict well both the magnitudes and the directions of the fluctuations. Specifically, STeM performs equally well in B-factor predictions as GNM and has the ability to predict the directions of fluctuations as ANM. This is achieved by employing a physically more realistic potential, the Gō-like potential. The potential, which is more sophisticated than that of either GNM or ANM, though adds complexity to the derivation process of the Hessian matrix (which fortunately has been done once for all and the MATLAB code is freely available electronically at http://www.cs.iastate.edu/~gsong/STeM), causes virtually no performance slowdown.

Conclusions

Derived from a physically more realistic potential, STeM proves to be a natural solution in which advantages that used to exist in two separate models, namely GNM and ANM, are achieved in one single model. It thus lightens the burden to work with two separate models and to relate the modes of GNM with those of ANM at times. By examining the contributions of different interaction terms in the Gō potential to the fluctuation dynamics, STeM reveals, (i) a physical explanation for why the distance-dependent, inverse distance square (i.e., Open image in new window ) spring constants perform better than the uniform ones, and (ii), the importance of three-body and four-body interactions to properly modeling protein dynamics.

     

Genome-wide analysis of codon usage bias patterns in an enterotoxigenic <Emphasis Type="Italic">Escherichia coli</Emphasis> F18 strain

Enterogenic Escherichia coli (ETEC) F18 strains are the main pathogenic bacteria causing severe diarrhea in humans and domestic animals. However, the information about synonymous codon usage pattern of ETEC F18 genome remains unclear. We conducted a genome-wide analysis of synonymous codon usage patterns in the ETEC F18 strain SRA: SAMN02471895. After filtering of the complete genome sequence, 4327 coding sequences were analyzed using multivariate statistical methods to calculate synonymous codon usage patterns and to evaluate the influence of various factors in shaping the codon usage. The mean GC content was 51.38%, with a slight preference for G/C-ending codons. Twenty-two codons were determined as ‘‘optimal codons”. ENC plots showed some of the genes were on or close to the expected curve, while only points with low-ENC values were below the curve. PR2 analysis showed that GC and AT were not used proportionally, suggesting major roles for mutational pressure and natural selection in shaping usage. Neutrality plots showed a significant correlation between GC12 and GC3, suggesting that mutational pressure is responsible for nucleotide composition in shaping the strength of codon usage. Translational selection was the main factor shaping the codon usage pattern of ETEC F18 genome, while other factors such as protein length, GRAVY and ARO values also influenced codon usage to some extent. We analyzed the codon usage pattern systematically and identified the factors shaping codon usage bias in the ETEC F18 genome. Such information further elucidates the mechanisms of synonymous codon usage bias and provides the basis of molecular genetic engineering and evolutionary studies.     

Conformational analysis of cyclic dipeptides: I. , , , and

Conformational analysis of two pairs of synthetic cyclodipeptides formed by interaction of both side chain functional groups ( , and ) and of the main and side chains ( , and ) was achieved by the method of molecular mechanics. The energetically optimal conformational states of the molecules under study were determined. It was shown that the conformational motility of cyclic system of the compounds under study depends on the relative arrangement of the amide groups and the number of atoms in the cycle.     

The margination propensity of spherical particles for vascular targeting in the microcirculation

The propensity of circulating particles to drift laterally towards the vessel walls (margination) in the microcirculation has been experimentally studied using a parallel plate flow chamber. Fluorescent polystyrene particles, with a relative density to water of just 50 g/cm ³comparable with that of liposomal or polymeric nanoparticles used in drug delivery and bio-imaging, have been used with a diameter spanning over three order of magnitudes from 50 nm up to 10 μm. The number of particles marginating per unit surface have been measured through confocal fluorescent microscopy for a horizontal chamber, and the corresponding total volume of particles has been calculated. Scaling laws have been derived as a function of the particle diameter d. In horizontal capillaries, margination is mainly due to the gravitational force for particles with d > 200 nm and increases with d ⁴; whereas for smaller particles increases with d ³. In vertical capillaries, since the particles are heavier than the fluid they would tend to marginate towards the walls in downward flows and towards the center in upward flows, with increasing with d ^9/2. However, the margination in vertical capillaries is predicted to be much smaller than in horizontal capillaries. These results suggest that, for particles circulating in an external field of volume forces (gravitation or magnetic), the strategy of using larger particles designed to marginate and adhere firmly to the vascular walls under flow could be more effective than that of using particles sufficiently small (d < 200 nm) to hopefully cross a discontinuous endothelium.     

A general model of codon bias due to GC mutational bias

Background

In spite of extensive research on the effect of mutation and selection on codon usage, a general model of codon usage bias due to mutational bias has been lacking. Because most amino acids allow synonymous GC content changing substitutions in the third codon position, the overall GC bias of a genome or genomic region is highly correlated with GC3, a measure of third position GC content. For individual amino acids as well, G/C ending codons usage generally increases with increasing GC bias and decreases with increasing AT bias. Arginine and leucine, amino acids that allow GC-changing synonymous substitutions in the first and third codon positions, have codons which may be expected to show different usage patterns.

Principal Findings

In analyzing codon usage bias in hundreds of prokaryotic and plant genomes and in human genes, we find that two G-ending codons, AGG (arginine) and TTG (leucine), unlike all other G/C-ending codons, show overall usage that decreases with increasing GC bias, contrary to the usual expectation that G/C-ending codon usage should increase with increasing genomic GC bias. Moreover, the usage of some codons appears nonlinear, even nonmonotone, as a function of GC bias. To explain these observations, we propose a continuous-time Markov chain model of GC-biased synonymous substitution. This model correctly predicts the qualitative usage patterns of all codons, including nonlinear codon usage in isoleucine, arginine and leucine. The model accounts for 72%, 64% and 52% of the observed variability of codon usage in prokaryotes, plants and human respectively. When codons are grouped based on common GC content, 87%, 80% and 68% of the variation in usage is explained for prokaryotes, plants and human respectively.

Conclusions

The model clarifies the sometimes-counterintuitive effects that GC mutational bias can have on codon usage, quantifies the influence of GC mutational bias and provides a natural null model relative to which other influences on codon bias may be measured.     

An ant colony optimization algorithm for phylogenetic estimation under the minimum evolution principle

Background  

Distance matrix methods constitute a major family of phylogenetic estimation methods, and the minimum evolution (ME) principle (aiming at recovering the phylogeny with shortest length) is one of the most commonly used optimality criteria for estimating phylogenetic trees. The major difficulty for its application is that the number of possible phylogenies grows exponentially with the number of taxa analyzed and the minimum evolution principle is known to belong to the -hard class of problems.     

Isolation and phylogenetic study of Rift Valley fever virus from the first imported case to China

<正>Dear Editor,Rift Valley fever(RVF)is an anthropozoonosis caused by Rift Valley fever virus(RVFV).RVFV belongs to the Phlebovirus genus in the family Bunyaviridae,which is circulating among ruminants.Human infection with RVFV is generally asymptomatic,however,minority of patients develop severe RVF diseases like encephalitis or     

Characterization of a recombinant Akabane mutant virus with knockout of a nonstructural protein NSs in a pregnant goat model

正Dear Editor,Akabane virus(AKAV),an orthobunyavirus,is transmitted primarily by biting midges and is widely distributed throughout the world except the Europe.AKAV was first isolated from mosquitoes in Japan(Oya et al.,1961).Although pregnant cows,ewes,and goats infected with AKAV exhibit no clinical signs of disease,in utero infections result in abortion,premature birth,stillbirth,and     

CD95-CD95L interaction mediates the growth control of MHV68 immortalized B cells by cytotoxic T cells

<正>Dear Editor,The main limitation of the viral pathogenesis study of human gammaherpesviruses Epstein-Barr virus(EBV)and Kaposi sarcoma-associated herpesvirus(KSHV)is the absence of animal model owing to the narrow host tropism of both EBV and KSHV.Murine gammaherpesvirus 68(MHV68)encodes several genes involved in     

Construction of an infectious cDNA clone of Tembusu virus isolated from breeder Peking ducks

正Dear Editor,Since April 2010,an outbreak of a new disease has elicited symptoms of high fever,loss of appetite,and reduction in egg production in layer ducks in eastern China;this phenomenon has now spread throughout China(Cao et al.,2011;Su et al.,2011).The causative agent of the disease was identified as Tembusu virus(TMUV),which was classified into the genus Flavivirus,