Understanding the Sequence-Dependence of DNA Groove Dimensions: Implications for DNA Interactions

BACKGROUND: The B-DNA major and minor groove dimensions are crucial for DNA-protein interactions. It has long been thought that the groove dimensions depend on the DNA sequence, however this relationship has remained elusive. Here, our aim is to elucidate how the DNA sequence intrinsically shapes the grooves. METHODOLOGY/PRINCIPAL FINDINGS: The present study is based on the analysis of datasets of free and protein-bound DNA crystal structures, and from a compilation of NMR (31)P chemical shifts measured on free DNA in solution on a broad range of representative sequences. The (31)P chemical shifts can be interpreted in terms of the BI↔BII backbone conformations and dynamics. The grooves width and depth of free and protein-bound DNA are found to be clearly related to the BI/BII backbone conformational states. The DNA propensity to undergo BI↔BII backbone transitions is highly sequence-dependent and can be quantified at the dinucleotide level. This dual relationship, between DNA sequence and backbone behavior on one hand, and backbone behavior and groove dimensions on the other hand, allows to decipher the link between DNA sequence and groove dimensions. It also firmly establishes that proteins take advantage of the intrinsic DNA groove properties. CONCLUSIONS/SIGNIFICANCE: The study provides a general framework explaining how the DNA sequence shapes the groove dimensions in free and protein-bound DNA, with far-reaching implications for DNA-protein indirect readout in both specific and non specific interactions

Moving Forward in Fostering Humour: Towards Training Lighter Forms of Humour in Multicultural Contexts

The following theoretical position paper has the aim to outline two important future directions of humour intervention research. Firstly, existing humour trainings have not differentiated explicitly between different uses of humour or humour that may be virtuous or not. Within the realm of Positive Psychology, all virtuous forms of humour need to be identified and interventions developed that aim at fostering these benevolent/lighter forms. Secondly, most humour trainings have been adapted and conducted in one cultural context. Future trainings should consider cross-cultural perspectives to allow for comparative research and practice. Thus, the current paper first gives an overview on the extant literature on the distinction between lighter and darker forms of humour, as well as showing how humour can serve the virtues proposed by Peterson and Seligman (2004). Then, we elaborate on the findings on humour and well-being, as well as findings on existing humour interventions. The second section starts with open questions and hypotheses on how a new generation of trainings targeting lighter forms of humour could look like. Then, we discuss (potential) cultural differences in humour and how this may affect the design of interventions. When aiming for cross-cultural adaptations of the same humour program, several challenges have to be overcome, such as the term “humour” not having the same meaning in every culture, and cultural rules on what can be laughed at

The thermodesorption mechanism of ammonia from Ru(0001)

Thermodesorption rates for the desorption of ammonia from Ru(0 0 0 1) are calculated by Transition State Theory including small curvature tunneling corrections. The potential energy surface is derived on a model cluster employing hybrid density functional theory (B3LYP). Two desorption pathways can be identified, just distinguished by the orientation of the leaving ammonia entity. It is found that the rate dominating mechanism comprises an umbrella-like flipping movement of the hydrogen atoms during the desorption. Nevertheless tunneling does not play any significant role in the reaction as the hydrogen movements are shown to occur at the low energy regions of the barrier. © 2006 Elsevier B.V. All rights reserved

Rates of the reaction C2H3+H-2 -> C2H4+H

The reaction C2H3 + H2 → C 2H4 + H has been studied by different direct ab initio approaches. Accurate rate constants in the temperature range 200-1200 K have been derived by time-independent scattering theory, employing R-matrix propagation on a 2D reduced dimensional G3B3 potential energy surface. Reported experimental reaction rates at room temperature vary over 3 orders of magnitude as they have to be determined indirectly. The computed room temperature rate of 2.1 × 10-18 cm3 molecule-1 s-1 in this study should remove this ambiguity. At higher temperatures the calculated rates meet experimental rates from direct measurements very well. The use of a reduced dimensionality model is justified by comparing full-dimensional semiclassical tunnelling contributions to those derived on a 2D potential with the same method. The employed semiclassical approach (small curvature tunnelling) yields very similar rates to the scattering approach, thus showing that small curvature tunnelling is a very reliable method to describe reactions like these

Rates of the reaction C2H3+H-2 -> C2H4+H

The reaction C2H3 + H2 → C 2H4 + H has been studied by different direct ab initio approaches. Accurate rate constants in the temperature range 200-1200 K have been derived by time-independent scattering theory, employing R-matrix propagation on a 2D reduced dimensional G3B3 potential energy surface. Reported experimental reaction rates at room temperature vary over 3 orders of magnitude as they have to be determined indirectly. The computed room temperature rate of 2.1 × 10-18 cm3 molecule-1 s-1 in this study should remove this ambiguity. At higher temperatures the calculated rates meet experimental rates from direct measurements very well. The use of a reduced dimensionality model is justified by comparing full-dimensional semiclassical tunnelling contributions to those derived on a 2D potential with the same method. The employed semiclassical approach (small curvature tunnelling) yields very similar rates to the scattering approach, thus showing that small curvature tunnelling is a very reliable method to describe reactions like these

Significance of ligand tails for interaction with the minor groove of B-DNA.

Minor groove binding ligands are of great interest due to their extraordinary importance as transcription controlling drugs. We performed three molecular dynamics simulations of the unbound d(CGCGAATTCGCG)(2) dodecamer and its complexes with Hoechst33258 and Netropsin. The structural behavior of the piperazine tail of Hoechst33258, which has already been shown to be a contributor in sequence-specific recognition, was analyzed. The simulations also reveal that the tails of the ligands are able to influence the width of the minor groove. The groove width is even sensitive for conformational transitions of these tails, indicating a high adaptability of the minor groove. Furthermore, the ligands also exert an influence on the B(I)/B(II) backbone conformational substate behavior. All together these results are important for the understanding of the binding process of sequence-specific ligands

Estimation of the Electron Density From Spacecraft Potential During High‐Frequency Electric Field Fluctuations

Spacecraft potential has often been used to infer electron density with much higher time resolution than is typically possible with plasma instruments. However, recently two studies by Torkar et al. 2017 and Graham et al. 2018 have shown that external electric fields can also have an effect on the spacecraft potential by enhancing photoelectron escape from the surface. Consequently, should the electron density derived from the spacecraft potential be used during an event with a large electric field, the estimation would be contaminated and the user would see the effects of the electric field rather than density perturbations. The goal of this paper is to propose a method to remove the electric field effects to allow the density derived from spacecraft potential to be used even during large amplitude wave events such as Langmuir waves or upper hybrid waves.Comment: Published in JGR Space Physic