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We simulate DNA suspension microchannel flows using the dissipative particle dynamics (DPD) method. Two developments make this simulation more realistic. One is to improve the dynamic characteristics of a DPD system by modifying the weighting function of the dissipative force and increasing its cutoff radius, so that the Schmidt number can be increased to a practical level. Another is to set up a wormlike chain model in the DPD framework, according to the measured extension properties of a DNA molecule in uniform flows. This chain model is then used to study flows of a DNA suspension through microchannels. Interesting results on the conformation evolution of DNA molecules passing through the microchannels, including periodic contraction-diffusion microchannels, are reported.

Recent genomewide association studies have found multiple genetic variants on chromosome 8q24 that are significantly associated with an increased susceptibility to prostate, colorectal, and breast cancer. These risk loci are located in a "gene desert," a few hundred kilobases telomeric to the Myc gene. To date, the biological mechanism(s) underlying these associations remain unclear. It has been speculated that these 8q24 genetic variant(s) might affect Myc expression by altering its regulation or amplification status. Here, we show that multiple enhancer elements are present within this region and that they can regulate transcription of Myc. We also demonstrate that one such enhancer element physically interacts with the Myc promoter via transcription factor Tcf-4 binding and acts in an allele specific manner to regulate Myc expression.

In the delivery of DNA molecules by microfluidic devices, the channel width is very often in the same order as the size of the DNA molecules and the applicability of continuum mechanics at this level may be questioned. In this paper we use finitely extendable nonlinear elastic (FENE) chains to model the DNA molecules and employ the dissipative particle dynamics (DPD) method to simulate their behavior in the flow. Simple DPD fluids are found to behave just like a Newtonian fluid in Poiseuille flow. However, the velocity profiles of FENE chain suspensions can be fitted with power-law curves, especially for dilute suspensions. Some results on the conformation and migration of FENE chains are also reported.

The chemical diversity of physiological DNA modifications has expanded with the identification of phosphorothioate (PT) modification in which the nonbridging oxygen in the sugar-phosphate backbone of DNA is replaced by sulfur. Together with DndFGH as cognate restriction enzymes, DNA PT modification, which is catalyzed by the DndABCDE proteins, functions as a bacterial restriction-modification (R-M) system that protects cells against invading foreign DNA. However, the occurrence of systems across a large number of bacterial genomes and their functions other than R-M are poorly understood. Here, a genomic survey revealed the prevalence of bacterial systems: 1,349 bacterial systems were observed to occur sporadically across diverse phylogenetic groups, and nearly half of these occur in the form of a solitary gene cluster that lacks the restriction counterparts. A phylogenetic analysis of 734 complete PT R-M pairs revealed the coevolution of M and R components, despite the observation that several PT R-M pairs appeared to be assembled from M and R parts acquired from distantly related organisms. Concurrent epigenomic analysis, transcriptome analysis, and metabolome characterization showed that a solitary PT modification contributed to the overall cellular redox state, the loss of which perturbed the cellular redox balance and induced to reconfigure its metabolism to fend off oxidative stress. An in vitro transcriptional assay revealed altered transcriptional efficiency in the presence of PT DNA modification, implicating its function in epigenetic regulation. These data suggest the versatility of PT in addition to its involvement in R-M protection.

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