Rational Design of 2D Supramolecular Networks Switchable by External Electric Fields.

The reversible formation of hydrogen bonds is a ubiquitous mechanism for controlling molecular assembly in biological systems. However, achieving predictable reversibility in artificial two-dimensional (2D) materials remains a significant challenge. Here, we use an external electric field (EEF) at the solid/liquid interface to trigger the switching of H-bond-linked 2D networks using a scanning tunneling microscope. Assisted by density functional theory and molecular dynamics simulations, we systematically vary the molecule-to-molecule interactions, i.e., the hydrogen-bonding strength, as well as the molecule-to-substrate interactions to analyze the EEF switching effect. By tuning the building block's hydrogen-bonding ability (carboxylic acids vs aldehydes) and substrate nature and charge (graphite, graphene/Cu, graphene/SiO2), we induce or freeze the switching properties and control the final polymorphic output in the 2D network. Our results indicate that the switching ability is not inherent to any particular building block but instead relies on a synergistic combination of the relative adsorbate/adsorbate and absorbate/substrate energetic contributions under surface polarization. Furthermore, we describe the dynamics of the switching mechanism based on the rotation of carboxylic groups and proton exchange, which generate the polarizable species that are influenced by the EEF. This work provides insights into the design and control of reversible molecular assembly in 2D materials, with potential applications in a wide range of fields, including sensors and electronics.

The DUX4 protein is a co-repressor of the progesterone and glucocorticoid nuclear receptors.

DUX4 is a transcription factor required during early embryonic development in placental mammals. In this work, we provide evidence that DUX4 is a co-repressor of nuclear receptors (NRs) of progesterone (PR) and glucocorticoids (GR). The DUX4 C-ter and N-ter regions, including the nuclear localization signals and homeodomain motifs, contribute to the co-repressor activity of DUX4 on PR and GR. Immunoprecipitation studies, using total protein extracts of cells expressing tagged versions of DUX4 and GR, support that these proteins are physically associated. Our studies suggest that DUX4 could modulate gene expression by co-regulating the activity of hormone NRs. This is the first report highlighting a potential endocrine role for DUX4.

A pH-Sensitive Supramolecular Switch Based on Mixed Carboxylic Acid Terminated Self-Assembled Monolayers on Au(111).

We show that homogeneously mixed self-assembled monolayers (SAMs) of mercaptoalkanoic acids of different chain lengths can be used to build up a pH-sensitive supramolecular switch. The acids with short and long alkyl chains interact via the strong hydrogen bond between carboxylic acid groups. The pH acts as a trigger by breaking or restoring the hydrogen bond interaction in basic or acidic solutions, respectively. The corresponding changes in the monolayer structure were determined by ellipsometry, surface-enhanced Raman spectroscopy, and contact angle measurements. Density functional theory (DFT) calculations were performed to elucidate the structures of interacting molecules compatible with the surface coverage obtained from electrochemical reductive desorption experiments. The simplicity of the preparation procedure assures a high reproducibility whereas the stability of the homogeneous mixed SAM guarantees the reversibility of the switching process.

Plasmid expression of mutS, -L and/or -H gene in Escherichia coli dam cells results in strains that display reduced mutation frequency.

Escherichia colidam cells have an active but non-directed mismatch repair system; therefore, assembly of MutSLH complex at a mismatched base pair can result in MutH-mediated cleavage of GATC sites in both DNA strands. Unpaired double-strand breaks on a fraction of the replication errors occurring in dam cells presumably cause cell death, selectively eliminating these putative mutants from the population. We show that E. colidam cells transformed with plasmids containing either the mutS, mutL or mutH gene display a mutation frequency three to eight times lower than that of the parental dam strain, due to increased mismatch-stimulated cell killing. Transformed strains are also more susceptible to killing by the base analogue 2-aminopurine. However, dam and dam transformed cells have similar duplication time, proportion of live/dead cells and morphology.

Pseudomonas aeruginosa MutL protein functions in Escherichia coli.

Escherichia coli MutS, MutL and MutH proteins act sequentially in the MMRS (mismatch repair system). MutH directs the repair system to the newly synthesized strand due to its transient lack of Dam (DNA-adenine methylase) methylation. Although Pseudomonas aeruginosa does not have the corresponding E. coli MutH and Dam homologues, and consequently the MMRS seems to work differently, we show that the mutL gene from P. aeruginosa is capable of complementing a MutL-deficient strain of E. coli. MutL from P. aeruginosa has conserved 21 out of the 22 amino acids known to affect functioning of E. coli MutL. We showed, using protein affinity chromatography, that the C-terminal regions of P. aeruginosa and E. coli MutL are capable of specifically interacting with E. coli MutH and retaining the E. coli MutH. Although, the amino acid sequences of the C-terminal regions of these two proteins are only 18% identical, they are 88% identical in the predicted secondary structure. Finally, by analysing (E. coli-P. aeruginosa) chimaeric MutL proteins, we show that the N-terminal regions of E. coli and P. aeruginosa MutL proteins function similarly, in vivo and in vitro. These new findings support the hypothesis that a large surface, rather than a single amino acid, constitutes the MutL surface for interaction with MutH, and that the N- and C-terminal regions of MutL are involved in such interactions.