Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.     

Effect of catalysts on the reaction between a cycloaliphatic diisocyanate (H-MDI) and n-butanol

Kinetics of the reaction between bis(4-isocyanatocyclohexyl)methane, H-MDI, and n-butanol was studied in toluene at 100°C. Effects of various catalysts, such as Hg(CH₃COO)₂, Zn(CH₃COO)₂ · 2H₂O, SnCl₄ · 5H₂O, and dibutyltindilaurate on the reaction rate and kinetics were also investigated. Reactions were followed by determining the unreacted isocyanate as a function of reaction time, using the standard dibutylamine back titration method. All catalysts seem to be very effective in increasing of the rate of the reaction compared to the uncatalyzed system. Depending on the initial stoichiometric ratio of (NCO) and (OH) and the concentration of the catalyst used, it seems possible to have preferential catalysis of the primary reaction between (NCO) and (OH) over the side reactions.     

Converting harmonic oscillations into chaos

A new simple model of a system with chaotic dynamics, based on the equations of bistable systems, is considered. The possibility of converting harmonic signals into chaotic oscillations, which represent intermittent irregular and switching quasi-regular motions, is demonstrated by numerical methods. The mechanism of chaotization is analyzed using the results of numerical calculations.     

Fast internal dynamics in polyelectrolyte gels measured by dynamic light scattering

Summary Dynamic light scattering was used to investigate the dynamics of sodium poly(styrene sulfonate) and fully neutralized poly(acrylic acid) gels as a function of the degree of swelling and weight ratio of cross-linking agent. It was shown that the collective diffusion coefficient increases with increasing degree of swelling and that the diffusion coefficient shows stronger concentration dependence than predicted by scaling arguments. For gel samples measured at the swelling equilibrium, the diffusion coefficient increases with increasing gel concentration for both gel systems.