Celia López

Molecular dynamics simulations have been performed to investigate the role of Mg2+ in the full-length hammerhead ribozyme cleavage reaction. In particular, the aim of this work is to characterize the binding mode and conformational events that give rise to catalytically active conformations and stabilization of the transition state. Toward this end, a series of eight 12 ns molecular dynamics simulations have been performed with different divalent metal binding occupations for the reactant, early and late transition state using recently developed force field parameters for metal ions and reactive intermediates in RNA catalysis. In addition, hybrid QM/MM calculations of the early and late transition state were performed to study the proton-transfer step in general acid catalysis that is facilitated by the catalytic Mg2+ ion. The simulations suggest that Mg2+ is profoundly involved in the hammerhead ribozyme mechanism both at structural and catalytic levels. Binding of Mg2+ in the active site plays a key structural role in the stabilization of stem I and II and to facilitate formation of near attack conformations and interactions between the nucleophile and G12, the implicated general base catalyst. In the transition state, Mg2+ binds in a bridging position where it stabilizes the accumulated charge of the leaving group while interacting with the 2′OH of G8, the implicated general acid catalyst. The QM/MM simulations provide support that, in the late transition state, the 2′OH of G8 can transfer a proton to the leaving group while directly coordinating the bridging Mg2+ ion. The present study provides evidence for the role of Mg2+ in hammerhead ribozyme catalysis. The proposed simulation model reconciles the interpretation of available experimental structural and biochemical data, and provides a starting point for more detailed investigation of the chemical reaction path with combined QM/MM methods. © 2008 American Chemical Society.

Results of a series of 12 ns molecular dynamics simulations of the reactant state and early and late transition state mimics are presented based on a recently reported crystal structure of a full-length hammerhead RNA. The simulation results support a catalytically active conformation with a Mg2+ ion bridging the A9 and scissile phosphates. In the reactant state, the Mg2+ spends significant time closely associated with the 2′OH of G8 but remains fairly distant from the leaving group Q5′ position. In the early TS mimic simulation, where the nucteophilic O2′ and leaving group O5′ are equidistant from the phosphorus, the Mg2+ ion remains tightly coordinated to the 2′OH of G8 but is positioned closer to the O5′ leaving group, stabilizing the accumulating charge. In the late TS mimic simulation, the coordination around the bridging Mg 2+ ion undergoes a transition whereby the coordination with the 2′OH of G8 is replaced by the leaving group O5′ that has developed significant charge. At the same time, the 2′OH of G8 forms a hydrogen bond with the leaving group O5′ and is positioned to act as a general acid catalyst. This work represents the first reported simulations of the full-length hammerhead structure and TS mimics and provides direct evidence for the possible role of a bridging Mg2+ ion in catalysis that is consistent with both crystallographic and biochemical data. © 2007 American Chemical Society.

Background: Biochemical characterization of voltage-dependent anion channel 2 is limited due to an inability to obtain functional protein. Results: The crystal structure ofVDAC2suggests a dimer interface that is confirmed by double electron-electron resonance and cross-linking. Conclusion: zfVDAC2 has a fractional dimeric population. Significance: VDAC isoforms are structurally similar, but this study has identified a number of hot spots that require further exploration. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Background Moral distress appears when a healthcare professional is not able to carry out actions in accordance with their professional ethical standards. The Moral Distress Scale-Revised is the most widely used to assess levels of moral distress, but it is not validated in Spanish. The aim of the study is to validate the Spanish version of the Moral Distress Scale – utilised within a sample of Spanish healthcare professionals treating COVID–19 patients. Methods The original (english) and the portuguese and french versions of the scale were translated into spanish by native or bilingual researchers and reviewed by an academic expert in ethics and moral philosophy as well as by a clinical expert. Research design: Descriptive cross-sectional study carried out using a self-reporting online survey. The data was collected between June- November 2020. A total of 661 professionals responded to the survey (N = 2873). Participants: healthcare professionals with more than two weeks of experience treating COVID–19 patients at the end of their life and working in the public sector of the Balearic Islands Health Service (Spain). Analyses included descriptive statistics, competitive confirmatory factor analysis, evidence on criterion-related validity and estimates of reliability. The study was approved by the Research Ethics Committee at the University of Balearic Islands. Results An unidimensional model in which a general factor of moral distress explained by 11 items of the Spanish version of the MDS–R scale was an adequate representation of the data: χ 2 (44) = 113.492 (p 0.001); Comparative Fit Index = 0.965; Root Mean Square Error of Approximation = 0.079[0.062,0.097]; and Standarized Root Mean-Square = 0.037. Evidence of reliability was excellent: Cronbach’s alpha = 0.886 and McDonald’s omega = 0.910. Moral distress was related to discipline, with nurses having statistically significant higher levels than physicians. Additionally, moral distress successfully predicted professional quality of life, with higher levels of moral distress being related to poorer quality of life. Conclusions The Spanish version of Moral Distress Scale–Revised can be used as a reliable and valid measurement tool for the evaluation of moral distress experienced by health professionals. This tool will be highly useful for managers and applicable to a variety of healthcare professionals and settings.

We focus on the literature about UBI and the experiments developed all around the world to test it in order to address how UBI implementation could affect entrepreneurship. Building on these findings and various strands of entrepreneurial theory, we develop a theoretical framework to explain how the implementation of UBI would dramatically change the environment of entrepreneurial activity, shaping entrepreneurial action at three levels: (i) the desirability of becoming an entrepreneur; (ii) the perceived feasibility of becoming an entrepreneur; (iii) the propensity to act. Consequently, UBI implementation would arguably facilitate the decision to become an entrepreneur. The contribution of the paper is threefold. It firstly provides a theoretical framework that opens new directions for further research on the relationship between UBI and entrepreneurship. Secondly, it offers new insights for policy makers by shedding light on potential effects of UBI implementation. Finally, it raises further questions that remains unsolved related to the role of non-pecuniary motivations and financial constraints.

Audiovisual communication is greatly contributing to the emerging research field of affective computing. The use of audiovisual stimuli within immersive virtual reality environments is providing very intense emotional reactions, which provoke spontaneous physical and physiological changes that can be assimilated into real responses. In order to ensure high-quality recognition, the artificial intelligence system must be trained with adequate data sets, including not only those gathered by smart sensors but also the tags related to the elicited emotion. Currently, there are very few techniques available for the labeling of emotions. Among them, the Self-Assessment Manikin devised by Lang is one of the most popular. This study shows experimentally that the graphic proposal for the original SAM labelling system, as devised by Lang, is not neutral to gender and contains gender biases in its design and representation. Therefore, a new graphic design has been proposed and tested according to the guidelines of expert judges. The results of the experiment show an overall improvement in the labeling of emotions in the pleasure–arousal–dominance affective space, particularly, for women. This research proves the relevance of applying the gender perspective in the validation of tools used throughout the years.