Inverting Small Molecule-Protein Recognition by the Fluorine Gauche Effect: Selectivity Regulated by Multiple H→F Bioisosterism

Fluorinated motifs have a venerable history in drug discovery, but as C(sp3 )@F-rich 3D scaffolds appear with increasing frequency, the effect of multiple bioisosteric changes on molecular recognition requires elucidation. Herein we demonstrate that installation of a 1,3,5-stereotriad, in the substrate for a commonly used lipase from Pseudomonas fluorescens does not inhibit recognition, but inverts stereoselectivity. This provides facile access to optically active, stereochemically well-defined organofluorine compounds (up to 98% ee). Whilst orthogonal recognition is observed with fluorine, the trend does not hold for the corresponding chlorinated substrates or mixed halogens. This phenomenon can be placed on a structural basis by considering the stereoelectronic gauche effect inherent to F@C@C@X systems (s!s*). Docking reveals that this change in selectivity (H versus F) with a common lipase results from inversion in the orientation of the bound substrate being processed as a consequence of conformation. This contrasts with the stereochemical interpretation of the biogenetic isoprene rule, whereby product divergence from a common starting material is also a consequence of conformation, albeit enforced by two discrete enzymes

Developing fencing policies in dryland ecosystems

The daily energy requirements of animals are determined by a combination of physical and physiological factors, but food availability may challenge the capacity to meet nutritional needs. Western gorillas (Gorilla gorilla) are an interesting model for investigating this topic because they are folivore-frugivores that adjust their diet and activities to seasonal variation in fruit availability. Observations of one habituated group of western gorillas in Bai-Hokou, Central African Republic (December 2004-December 2005) were used to examine seasonal variation in diet quality and nutritional intake. We tested if during the high fruit season the food consumed by western gorillas was higher in quality (higher in energy, sugar, fat but lower in fibre and antifeedants) than during the low fruit season. Food consumed during the high fruit season was higher in digestible energy, but not any other macronutrients. Second, we investigated whether the gorillas increased their daily intake of carbohydrates, metabolizable energy (KCal/g OM), or other nutrients during the high fruit season. Intake of dry matter, fibers, fat, protein and the majority of minerals and phenols decreased with increased frugivory and there was some indication of seasonal variation in intake of energy (KCal/g OM), tannins, protein/fiber ratio, and iron. Intake of non-structural carbohydrates and sugars was not influenced by fruit availability. Gorillas are probably able to extract large quantities of energy via fermentation since they rely on proteinaceous leaves during the low fruit season. Macronutrients and micronutrients, but not digestible energy, may be limited for them during times of low fruit availability because they are hind-gut fermenters. We discuss the advantages of seasonal frugivores having large dietary breath and flexibility, significant characteristics to consider in the conservation strategies of endangered species

Decisional and emotional forgiveness scales: Psychometric validity and correlates with personality and vengeance.

Forgiveness is an internal process to overcome negative aspects (e.g., anger, bitterness, resentment) towards an offender, being associated to a range of variables (e.g., well-being, quality of loving relationships, resilience). Forgiveness can happen through two different types: (1) decisional, which is a behavioural modification to reduce direct hostility; and (2) emotional, which is a transformation of negative emotions into positive. The current research aimed to gather psychometric evidences for the Decisional Forgiveness Scale (DFS) and the Emotional Forgiveness Scale (EFS), using a Brazilian sample. Two studies were conducted. In Study 1 (n = 181), the bifactorial structures were replicated, also providing satisfactory reliability levels. Through Item Response Theory, results indicated good discrimination, difficulty levels, and considerable information to all the items from both measures. In Study 2 (n = 220), confirmatory factor analyses confirmed their structure, presenting good model fit. The measures were also invariant regarding participants’ gender. Finally, the measures presented significant results when correlated to personality and vengeance. In sum, the instruments demonstrated satisfactory psychometric properties, evidencing the possibility of their use in the respective context.The authors acknowledge financial support from the CAPES Foundation (Brazil, http://www.capes.gov.br/) for the Ph.D. scholarship to the second author. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The influence of red on impression formation in a job application context

Recent research has shown that the color red can influence psychological functioning. In the present research we tested the hypothesis that red influences impression formation related to another person’s abilities. We conducted three experiments examining the influence of red on the evaluation of male target persons. In Experiment 1, participants viewing red, relative to green, on the shirt of a person presented on a photograph perceived him to be less intelligent. This effect was strongest in a job application context compared to other contexts. In Experiment 2, focusing solely on the job application context, participants viewing red, relative to blue, on an applicants’ tie perceived him to have less earning and leadership potential. In Experiment 3, participants viewing red, relative to green, on a job applicants’ tie rated him as less likely to be hired, and perceptions of ability and leadership potential mediated this effect. Both the conceptual and applied implications of these findings are discussed

Tying knots: an activity theory analysis of student learning goals in clinical education

© 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education Context: Learning goal programmes are often created to help students develop self-regulated learning skills; however, these programmes do not necessarily consider the social contexts surrounding learning goals or how they fit into daily educational practice. Objectives: We investigated a high-frequency learning goal programme in which students generated and shared weekly learning goals with their clinical teams in core Year 3 clerkships. Our study explores: (i) how learning goals were incorporated into the clinical work, and (ii) the factors that influenced the use of students’ learning goals in work-based learning. Methods: We conducted semi-structured interviews with 14 students and 14 supervisors (attending physicians and residents) sampled from all participating core clerkships. Interviews were coded for emerging themes. Using cultural historical activity theory and knotworking as theoretical lenses, we developed a model of the factors that influenced students’ learning goal usage in a work-based learning context. Results: Students and supervisors often faced the challenge of reconciling contradictions that arose when the desired outcomes of student skill development, grading and patient care were not aligned. Learning goals could function as tools for developing new ways of acting that overcame those contradictions by facilitating collaborative effort between students and their supervisors. However, for new collaborations to take place, both students and supervisors had to engage with the goals, and the necessary patients needed to be present. When any one part of the system did not converge around the learning goals, the impact of the learning goals programme was limited. Conclusions: Learning goals are potentially powerful tools to mediate interactions between students, supervisors and patients, and to reconcile contradictions in work-based learning environments. Learning goals provide a means to develop not only learners, but also learning systems

Ultra-high cycling stability of poly(vinylphenothiazine) as a battery cathode material resulting from π–π interactions

Organic cathode materials are promising candidates for a new generation of “green batteries”, since they have low toxicity and can be produced from renewable resources or from oil. Especially suitable are organic redox polymers that can be reversibly oxidized and reduced. Because of their often-insulating nature, however, many redox polymers have limited rate capabilities. Their cycling stabilities, which are of high importance for the long cycle-life of a battery cell, rarely exceed 1000 cycles. Here, we present a new concept for redox polymers as cathode materials, in which the oxidized states are stabilized through π–π interactions between redox-active groups. We found that due to these interactions poly(3-vinyl-N-methylphenothiazine) showed excellent cycling stability (after 10[thin space (1/6-em)]000 cycles at a 10C rate, 93% of the initial capacity was retained) in addition to a high rate capability because of supramolecular hole transport. We propose this concept to be used in the future design of redox polymers for batteries