Syntheses and characterizations of the in vivo replicative bypass and mutagenic properties of the minor-groove O2-alkylthymidine lesions.

Endogenous metabolism, environmental exposure, and treatment with some chemotherapeutic agents can all give rise to DNA alkylation, which can occur on the phosphate backbone as well as the ring nitrogen or exocyclic nitrogen and oxygen atoms of nucleobases. Previous studies showed that the minor-groove O(2)-alkylated thymidine (O(2)-alkyldT) lesions are poorly repaired and persist in mammalian tissues. In the present study, we synthesized oligodeoxyribonucleotides harboring seven O(2)-alkyldT lesions, with the alkyl group being a Me, Et, nPr, iPr, nBu, iBu or sBu, at a defined site and examined the impact of these lesions on DNA replication in Escherichia coli cells. Our results demonstrated that the replication bypass efficiencies of the O(2)-alkyldT lesions decreased with the chain length of the alkyl group, and these lesions directed promiscuous nucleotide misincorporation in E. coli cells. We also found that deficiency in Pol V, but not Pol II or Pol IV, led to a marked drop in bypass efficiencies for most O(2)-alkyldT lesions. We further showed that both Pol IV and Pol V were essential for the misincorporation of dCMP opposite these minor-groove DNA lesions, whereas only Pol V was indispensable for the T→A transversion introduced by these lesions. Depletion of Pol II, however, did not lead to any detectable alterations in mutation frequencies for any of the O(2)-alkyldT lesions. Thus, our study provided important new knowledge about the cytotoxic and mutagenic properties of the O(2)-alkyldT lesions and revealed the roles of the SOS-induced DNA polymerases in bypassing these lesions in E. coli cells

Effects of in-medium nucleon-nucleon cross section on collective flow and nuclear stopping in heavy-ion collisions in the Fermi-energy domain

With the newly updated version of the ultrarelativistic quantum molecular dynamics (UrQMD) model, a systematic investigation of the effects of in-medium nucleon-nucleon ($NN$) elastic cross section on the collective flow and the stopping observables in $^{197}\text{Au}+^{197}\text{Au}$ collisions at beam energies from 40 to 150 MeV/nucleon is performed. Simulations with the medium correction factor $\mathcal{F}=\sigma^{\text{in-medium}}_{NN}/\sigma^{\text{free}}_{NN}=0.2,~0.3,~0.5$, and the one obtained with the FU3FP1 parametrization which depends on both the density and the momentum are compared to the FOPI and INDRA experimental data. It is found that, to best fit the experimental data of the slope of the directed flow and the elliptic flow at mid-rapidity as well as the nuclear stopping, the correction factor $\mathcal{F}$=0.2 and 0.5 are required for reactions at beam energies of 40 and 150 MeV/nucleon, respectively. While calculations with the FU3FP1 parametrization can simultaneously reproduce these experimental data reasonably well. And, the observed increasing nuclear stopping with increasing beam energy in experimental data can also be reproduced by using the FU3FP1 parametrization, while the calculated stopping power in Au+Au collisions with beam energies from 40 to 150 MeV$/$nucleon almost keeps constant when take $\mathcal{F}$ equal to a fixed value.Comment: 7 pages, 6 figures, accepted by Phys. Rev.

EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs.

BackgroundPolycomb Repressive Complex 2 (PRC2) catalyzes histone methylation at H3 Lys27, and plays crucial roles during development and diseases in numerous systems. Its catalytic subunit EZH2 represents a key nuclear target for long non-coding RNAs (lncRNAs) that emerging to be a novel class of epigenetic regulator and participate in diverse cellular processes. LncRNAs are characterized by high tissue-specificity; however, little is known about the tissue profile of the EZH2- interacting lncRNAs.ObjectiveHere we performed a global screening for EZH2-binding lncRNAs in tissues including brain, lung, heart, liver, kidney, intestine, spleen, testis, muscle and blood by combining RNA immuno- precipitation and RNA sequencing. We identified 1328 EZH2-binding lncRNAs, among which 470 were shared in at least two tissues while 858 were only detected in single tissue. An RNA motif with specific secondary structure was identified in a number of lncRNAs, albeit not in all EZH2-binding lncRNAs. The EZH2-binding lncRNAs fell into four categories including intergenic lncRNA, antisense lncRNA, intron-related lncRNA and promoter-related lncRNA, suggesting diverse regulations of both cis and trans-mechanisms. A promoter-related lncRNA Hnf1aos1 bound to EZH2 specifically in the liver, a feature same as its paired coding gene Hnf1a, further confirming the validity of our study. In addition to the well known EZH2-binding lncRNAs like Kcnq1ot1, Gas5, Meg3, Hotair and Malat1, majority of the lncRNAs were firstly reported to be associated with EZH2.ConclusionOur findings provide a profiling view of the EZH2-interacting lncRNAs across different tissues, and suggest critical roles of lncRNAs during cell differentiation and maturation

Social contagions on interdependent lattice networks

Although an increasing amount of research is being done on the dynamical processes on interdependent spatial networks, knowledge of how interdependent spatial networks influence the dynamics of social contagion in them is sparse. Here we present a novel non-Markovian social contagion model on interdependent spatial networks composed of two identical two-dimensional lattices. We compare the dynamics of social contagion on networks with different fractions of dependency links and find that the density of final recovered nodes increases as the number of dependency links is increased. We use a finite-size analysis method to identify the type of phase transition in the giant connected components (GCC) of the final adopted nodes and find that as we increase the fraction of dependency links, the phase transition switches from second-order to first-order. In strong interdependent spatial networks with abundant dependency links, increasing the fraction of initial adopted nodes can induce the switch from a first-order to second-order phase transition associated with social contagion dynamics. In networks with a small number of dependency links, the phase transition remains second-order. In addition, both the second-order and first-order phase transition points can be decreased by increasing the fraction of dependency links or the number of initially-adopted nodes.This work was partially supported by National Natural Science Foundation of China (Grant Nos 61501358, 61673085), and the Fundamental Research Funds for the Central Universities. (61501358 - National Natural Science Foundation of China; 61673085 - National Natural Science Foundation of China; Fundamental Research Funds for the Central Universities)Published versio