Longitudinal Experience-Wide Association Studies-A Framework for Studying Personality Change

The importance of personality for predicting life outcomes in the domains of love, work, and health is well established, as is evidence that personality traits, while relatively stable, can change. However, little is known about the sources and processes that drive changes in personality traits and how such changes might impact important life outcomes. In this paper, we make the case that the research paradigms and methodological approaches commonly used in personality psychology need to be revised to advance our understanding of the sources and processes of personality change. We proposeLongitudinal Experience-Wide Association Studiesas a framework for studying personality change that can address the limitations of current methods, and we discuss strategies for overcoming some of the challenges associated withLongitudinal Experience-Wide Association Studies.Peer reviewe

Why stop at two opinions? Reply to McCrae (2020)

McCrae (2020) argues that it is premature to explore interventions focused on personality change. In his commentary, he suggests that interventions should be promoted only if their effects in self-report data are confirmed by the additional opinion of informants. We agree with the essence of his position and would go further by envisioning a new framework for rigorous collaborative research on personality change (Bleidorn et al., 2020). We nevertheless maintain that policymakers would benefit from considering the additional opinion of personality scientists. (PsycInfo Database Record (c) 2020 APA, all rights reserved)

PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism

Pseudomonas aeruginosa produces a number of alkylquinolone-type secondary metabolites best known for their antimicrobial effects and involvement in cell-cell communication. In the alkylquinolone biosynthetic pathway, the β-ketoacyl-(acyl carrier protein) synthase III (FabH)-like enzyme PqsBC catalyzes the condensation of octanoyl-coenzyme A and 2-aminobenzoylacetate (2-ABA) to form the signal molecule 2-heptyl-4(1H)-quinolone. PqsBC, a potential drug target, is unique for its heterodimeric arrangement and an active site different from that of canonical FabH-like enzymes. Considering the sequence dissimilarity between the subunits, a key question was how the two subunits are organized with respect to the active site. In this study, the PqsBC structure was determined to a 2 Å resolution, revealing that PqsB and PqsC have a pseudo-2-fold symmetry that unexpectedly mimics the FabH homodimer. PqsC has an active site composed of Cys-129 and His-269, and the surrounding active site cleft is hydrophobic in character and approximately twice the volume of related FabH enzymes that may be a requirement to accommodate the aromatic substrate 2-ABA. From physiological and kinetic studies, we identified 2-aminoacetophenone as a pathway-inherent competitive inhibitor of PqsBC, whose fluorescence properties could be used for in vitro binding studies. In a time-resolved setup, we demonstrated that the catalytic histidine is not involved in acyl-enzyme formation, but contributes to an acylation-dependent increase in affinity for the second substrate 2-ABA. Introduction of Asn into the PqsC active site led to significant activity toward the desamino substrate analog benzoylacetate, suggesting that the substrate 2-ABA itself supplies the asparagine-equivalent amino function that assists in catalysis

Homohalocyclization: Electrophilic Bromine-Induced Cyclizations of Cyclopropanes

An efficient method for the halocyclization of cyclopropanes has been developed. The cyclopropanes undergo a 1,3-addition reaction to form homohalocyclization products compared to conventional alkene halocyclizations. The reaction can be induced by various electrophilic halogenating agents including 1,3-dibromo-5,5-dimethylhydantoin and <i>N</i>-iodosuccinimide. In cyclopropane derivatives with a preexisting stereocenter, excellent induced diastereoselectivities can be observed

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

Selectively methylated analogues of naturally occurring 2-heptyl-4(1H)-quinolones, which are alkaloids common within the Rutaceae family and moreover are associated with quorum sensing and virulence of the human pathogen Pseudomonas aeruginosa, have been prepared. While the synthesis by direct methylation was successful for 3-unsubstituted 2-heptyl-4(1H)-quinolones, methylated derivatives of the Pseudomonas quinolone signal (PQS) were synthesized from 3-iodinated quinolones by methylation and iodine–metal exchange/oxidation. The two N- and O-methylated derivatives of the PQS showed strong quorum sensing activity comparable to that of PQS itself. Staphylococcus aureus, another pathogenic bacterium often co-occurring with P. aeruginosa especially in the lung of cystic fibrosis patients, was inhibited in planktonic growth and cellular respiration by the 4-O-methylated derivatives of HQNO and HHQ, respectively