Sorting permutations by cut-circularize-linearize-and-paste operations

<p>Abstract</p> <p>Background</p> <p>Genome rearrangements are studied on the basis of genome-wide analysis of gene orders and important in the evolution of species. In the last two decades, a variety of rearrangement operations, such as reversals, transpositions, block-interchanges, translocations, fusions and fissions, have been proposed to evaluate the differences between gene orders in two or more genomes. Usually, the computational studies of genome rearrangements are formulated as problems of sorting permutations by rearrangement operations.</p> <p>Result</p> <p>In this article, we study a sorting problem by cut-circularize-linearize-and-paste (CCLP) operations, which aims to find a minimum number of CCLP operations to sort a signed permutation representing a chromosome. The CCLP is a genome rearrangement operation that cuts a segment out of a chromosome, circularizes the segment into a temporary circle, linearizes the temporary circle as a linear segment, and possibly inverts the linearized segment and pastes it into the remaining chromosome. The CCLP operation can model many well-known rearrangements, such as reversals, transpositions and block-interchanges, and others not reported in the biological literature. In addition, it really occurs in the immune response of higher animals. To distinguish those CCLP operations from the reversal, we call them as non-reversal CCLP operations. In this study, we use permutation groups in algebra to design an <it>O</it>(<it>δn</it>) time algorithm for solving the weighted sorting problem by CCLP operations when the weight ratio between reversals and non-reversal CCLP operations is 1:2, where <it>n</it> is the number of genes in the given chromosome and <it>δ</it> is the number of needed CCLP operations.</p> <p>Conclusion</p> <p>The algorithm we propose in this study is very simple so that it can be easily implemented with 1-dimensional arrays and useful in the studies of phylogenetic tree reconstruction and human immune response to tumors.</p

Pronounced activation of protein kinase C, ornithine decarboxylase and c-jun proto-oncogene by paraquat-generated active oxygen species in WI-38 human lung cells

AbstractParaquat (methyl viologen, PQ) is a widely used herbicide that produces oxygen-derived free radicals and severely injures human lungs. In this study we examined the effects of PQ on the protein kinase C (PKC), ornithine decarboxylase (ODC) and c-jun oncogene expression in WI-38 human lung cells. Exposure of cells to 25–200 μM PQ resulted in an increase of [3H]phorbol dibutyrate (PDBu) binding and PKC redistribution in a dose-dependent manner. Interestingly, a superoxide dismutase mimic, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 2.5 mM) and catalase (400 μg/ml) could significantly reduce the PQ-stimulated increase of phorbol ester binding and particular PKC phosphorylatiog activity, but dimethylsulfoxide (DMSO, 1.5%), an effective ·OH trapping agent, failed to prevent this stimulation. In addition, an endogenous substrate of PKC, 80 kDa protein, was found to be highly phosphorylated in intact WI-38 cells treated with 50 AM PQ. The increase of phosphorylated proteins could be completely or partly abolished by Tempol or catalase, but only the phosphorylation of 80 kDa protein was diminished by protein kinase C inhibitor, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7). A maximal peak of ODC activity was observed at 6 h of treatment with 50 μM PQ. PQ induced activity was reduced at the following rates, Tempol 85%, DMSO 80% and catalase 45%, but H-7 failed to do so. Furthermore, we found that the level of c-jun mRNA was transiently increased by PQ and the peak appeared at 1 h of treatment. When correlated with the PKC result, Tempol, catalase and H-7 all effectively blocked PQ-elicited c-jun transcript expression, but DMSO only exhibited a weakly inhibitory effect. We therefore propose that superoxide anion (O2− and H2O2 generated by PQ could activate PKC and lead to induction of c-jun gene expression; on the other hand, O2− and ·OH might trigger other kinase pathways to elevate ODC activity. Finally, the sequential expression of c-jun oncogene, and ODC may cooperate to relieve the oxidative damages elicited by PQ

iPARTS: an improved tool of pairwise alignment of RNA tertiary structures

iPARTS is an improved web server for aligning two RNA 3D structures based on a structural alphabet (SA)-based approach. In particular, we first derive a Ramachandran-like diagram of RNAs by plotting nucleotides on a 2D axis using their two pseudo-torsion angles η and θ. Next, we apply the affinity propagation clustering algorithm to this η-θ plot to obtain an SA of 23-nt conformations. We finally use this SA to transform RNA 3D structures into 1D sequences of SA letters and continue to utilize classical sequence alignment methods to compare these 1D SA-encoded sequences and determine their structural similarities. iPARTS takes as input two RNA 3D structures in the PDB format and outputs their global alignment (for determining overall structural similarity), semiglobal alignments (for detecting structural motifs or substructures), local alignments (for finding locally similar substructures) and normalized local structural alignments (for identifying more similar local substructures without non-similar internal fragments), with graphical display that allows the user to visually view, rotate and enlarge the superposition of aligned RNA 3D structures. iPARTS is now available online at http://bioalgorithm.life.nctu.edu.tw/iPARTS/

Analysis of PCR Kinetics inside a Microfluidic DNA Amplification System

In order to analyze the DNA amplification numerically with integration of the DNA kinetics, three-dimensional simulations, including flow and thermal fields, and one-dimensional polymerase chain reaction (PCR) kinetics are presented. The simulated results are compared with experimental data that have been applied to the operation of a continuous-flow PCR device. Microchannels fabricated by Micro Electro-Mechanical Systems (MEMS) technologies are shown. Comprehensive simulations of the flow and thermal fields and experiments measuring temperatures during thermal cycling are presented first. The resultant velocity and temperature profiles from the simulations are introduced to the mathematical models of PCR kinetics. Then kinetic equations are utilized to determine the evolution of the species concentrations inside the DNA mixture along the microchannel. The exponential growth of the double-stranded DNA concentration is investigated numerically with the various operational parameters during PCR. Next a 190-bp segment of Bartonella DNA is amplified to evaluate the PCR performance. The trends of the experimental results and numerical data regarding the DNA amplification are similar. The unique architecture built in this study can be applied to a low-cost portable PCR system in the future

Analysis of Thermal Performance in a Bidirectional Thermocycler by Including Thermal Contact Characteristics

This paper illustrates an application of a technique for predicting the thermal characteristics of a bidirectional thermocycling device for polymerase chain reaction (PCR). The micromilling chamber is oscillated by a servo motor and contacted with different isothermal heating blocks to successfully amplify the DNA templates. Because a comprehensive database of contact resistance factors does not exist, it causes researchers to not take thermal contact resistance into consideration at all. We are motivated to accurately determine the thermal characteristics of the reaction chamber with thermal contact effects existing between the heater surface and the chamber surface. Numerical results show that the thermal contact effects between the heating blocks and the reaction chamber dominate the temperature variations and the ramping rates inside the PCR chamber. However, the influences of various temperatures of the ambient conditions on the sample temperature during three PCR steps can be negligible. The experimental temperature profiles are compared well with the numerical simulations by considering the thermal contact conductance coefficient which is empirical by the experimental fitting. To take thermal contact conductance coefficients into consideration in the thermal simulation is recommended to predict a reasonable temperature profile of the reaction chamber during various thermal cycling processes. Finally, the PCR experiments present that Hygromycin B DNA templates are amplified successfully. Furthermore, our group is the first group to introduce the thermal contact effect into theoretical study that has been applied to the design of a PCR device, and to perform the PCR process in a bidirectional thermocycler