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Abstract: We describe a nanoscale gating effect by an atypical tether-containing polythiophene, [poly(thiophene-3-carboxylic acid 2-(2-(2-(2-ethoxy-ethoxymethyl sulfonate)-ethoxy)-ethoxy)-amide], referred to as poly(TP-OEG-SO4). Cyclic voltammetry data permitted us to calculate liquid-phase ion diffusivities in the polymer as a function of its oxidation state. Diffusivities are more than 350 times higher in the oxidized state versus the reduced state. As a control, poly 3′,4′-dimethyl-[2,2′;5′,2″] terthiophene (DMPT) was synthesized and characterized. On comparing both polymers in the reduced state, we find diffusivities in poly(TP-OEG-SO4) to be more than 4500 times lower than in poly(DMPT). To explain this behavior, we propose a model that features a charge-balancing mechanism by the sulfonate tethers in poly(TP-OEG-SO4), which causes nanoporous regions around the polymer main chains to be opened and closed, leading to the large observed differences in diffusivities. These data suggest that the polymer poly(TP-OEG-SO4) is evidently able to act as a reversible “nanogate” with an open pore structure when oxidized, and a closed one when reduced. [Copyright &y& Elsevier]

The human placenta and its specialized cytotrophoblasts rapidly develop, have a compressed lifespan, govern pregnancy outcomes, and program the offspring's health. Understanding the molecular underpinnings of these behaviors informs development and disease. Profiling the extraembryonic epigenome and transcriptome during the 2nd and 3rd trimesters revealed H3K9 trimethylation overlapping deeply DNA hypomethylated domains with reduced gene expression and compartment-specific patterns that illuminated their functions. Cytotrophoblast DNA methylation increased, and several key histone modifications decreased across the genome as pregnancy advanced. Cytotrophoblasts from severe preeclampsia had substantially increased H3K27 acetylation globally and at genes that are normally downregulated at term but upregulated in this syndrome. In addition, some cases had an immature pattern of H3K27ac peaks, and others showed evidence of accelerated aging, suggesting subtype-specific alterations in severe preeclampsia. Thus, the cytotrophoblast epigenome dramatically reprograms during pregnancy, placental disease is associated with failures in this process, and H3K27 hyperacetylation is a feature of severe preeclampsia. • The epigenome of human placental cytotrophoblasts rapidly evolves over gestation • At genome scale, DNA methylation increases, and modified histones are lost • H3K9me3 occupancy of deeply hypomethylated DNA silences cytotrophoblast genes • Global increases in H3K27ac occupancy typify placental disease, for example, severe preeclampsia Zhang, Kim et al. show significant alterations in the cytotrophoblast epigenome over pregnancy, including increased DNA methylation and loss of modified histones. Throughout gestation, H3K9 trimethylation overlapping DNA hypomethylated domains reduces gene expression. In placental disease, for example, severe preeclampsia, cytotrophoblasts have global increases in H3K27 acetylation and at misexpressed genes. [ABSTRACT FROM AUTHOR]