Stochastic model for nucleosome sliding in the presence of DNA ligands

Heat-induced mobility of nucleosomes along DNA is an experimentally well-studied phenomenon. A recent experiment shows that the repositioning is modified in the presence of minor-groove binding DNA ligands. We present here a stochastic three-state model for the diffusion of a nucleosome along DNA in the presence of such ligands. It allows us to describe the dynamics and the steady state of such a motion analytically. The analytical results are in excellent agreement with numerical simulations of this stochastic process.With this model, we study the response of a nucleosome to an external force and how it is affected by the presence of ligands.Comment: 10 pages, 8 figures, submitted to Eur. Phys. J.

Predicting nucleosome positions on the DNA: combining intrinsic sequence preferences and remodeler activities

Nucleosome positions on the DNA are determined by the intrinsic affinities of histone proteins to a given DNA sequence and by the ATP-dependent activities of chromatin remodeling complexes that can translocate nucleosomes with respect to the DNA. Here, we report a theoretical approach that takes into account both contributions. In the theoretical analysis two types of experiments have been considered: in vitro experiments with a single reconstituted nucleosome and in vivo genome-scale mapping of nucleosome positions. The effect of chromatin remodelers was described by iteratively redistributing the nucleosomes according to certain rules until a new steady state was reached. Three major classes of remodeler activities were identified: (i) the establishment of a regular nucleosome spacing in the vicinity of a strong positioning signal acting as a boundary, (ii) the enrichment/depletion of nucleosomes through amplification of intrinsic DNA-sequence-encoded signals and (iii) the removal of nucleosomes from high-affinity binding sites. From an analysis of data for nucleosome positions in resting and activated human CD4+ T cells [Schones et al., Cell 132, p. 887] it was concluded that the redistribution of a nucleosome map to a new state is greatly facilitated if the remodeler complex translocates the nucleosome with a preferred directionality

Characterizations of dissimilar S32205/316L welds using austenitic, super-austenitic and super-duplex filler metals

UNS S32205 duplex stainless steel plates were welded to AISI 316L stainless steel using the pulsed gas tungsten arc welding process with three different filler metals: ER2594, ER312, and ER385. The microstructures of the welds were characterized using optical and scanning electron microscopy, and all of the specimens were evaluated by ferrite measurements. The mechanical properties were studied through hardness, tensile, and impact tests. In addition, the pitting resistance equivalent number was calculated and cyclic polarization tests were performed to evaluate the corrosion resistance of the weld metal. The results showed that chromium nitride was formed in the heat-affected zone of the duplex side, whereas no sigma phase was detected in any of the specimens. The ferrite number increased from the root pass to the final pass. The absorbed energies of the impact test decreased with increasing ferrite number, whereas the tensile strength was enhanced. The fully austenitic microstructure of the specimen welded with ER385 exhibited the highest resistance to pitting corrosion at 25°C, and the super-duplex weld metal presented superior corrosion resistance at 50°C

Effect of Delta Ferrite on the Mechanical Properties of Dissimilar Ferritic-Austenitic Stainless Steel Welds

The dissimilar welds of AISI 304 to AISI 430 stainless steel was investigated by using gas tungsten arc welding. Three filler metals including ER309L, ER316L and ER2594 were applied. The weakest region of the welds was the heat affected zone of 430 stainless steel due to the formation of martensite. Also, the wide grain growth zone was observed in this side. The ferrite number for type 309L, 316L and 2594 weld metals was about 15, 32 and 57, respectively. The hardness and tensile strength values of the weld metals were higher than that of the heat affected zones and the base metals. The ferrite presented higher hardness values than the austenite in type 316L and 309L joints; while the hardness of austenite and ferrite was comparable in type 2594 weld metal

The rs4846049 polymorphism in the 3’UTR region of the MTHFR gene increases the migraine susceptibility in an Iranian population

Mohaddeseh Salehi,1,* Mona Amin-Beidokhti,2,* Behnam Safarpour Lima,3 Milad Gholami,2 Gholam-Reza Javadi,1 Reza Mirfakhraie2,4 1Department of Biology, Islamic Azad University, Science and Research Branch, 2Department of Medical Genetics, 3Department of Neurology, School of Medicine, 4Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Introduction: Migraine is a painful complex neurovascular disease characterized by recurrent moderate-to-severe headaches. Increased level of homocysteine is related to dilation of cerebral vessels and endothelial injury that could trigger migraine attacks. Functional polymorphisms in the MTHFR gene affect homocysteine metabolism and, therefore, play an important role in the etiology of the disease. Objectives: We aimed to investigate the possible association between MTHFR gene rs4846049, C677T, and A1298C polymorphisms and the risk of migraine in Iranian population. Methods: In this genetic association study, 498 individuals were enrolled, including 223 migraine patients and 275 healthy controls. Genotyping was performed using tetra-primer ARMS-PCR for rs4846049 and PCR-restriction fragment length polymorphism for C677T and A1298C polymorphisms. Results: The association between rs4846049 and C677T polymorphisms and migraine was observed. For the rs4846049 polymorphism, the association was detected under a dominant model (P=0.007; odds ratio [OR] =0.60; 95% confidence interval [CI], 0.41–0.87), and for the C677T polymorphism, the TT genotype frequency was significantly different in the studied groups (P=0.009; OR =2.48; 95% CI, 1.25–4.92). No significant differences in the genotype or allele frequencies were found for the A1298C polymorphism between the migraineurs and controls. Conclusion: Present data provide evidence for the association of rs4846049 and C677T polymorphisms in the MTHFR gene and migraine. Further studies are required to validate the significance of the studied genetic variations in diverse ethnic populations. Keywords: migraine, genetic association study, MTHFR, single nucleotide polymorphis