Summary
The neural circuit mechanisms underlying emotion states remain poorly understood. Drosophila offers powerful genetic approaches for dissecting neural circuit function, but whether flies exhibit emotion-like behaviors has not been clear. We recently proposed that model organisms may express internal states displaying “emotion primitives,” which are general characteristics common to different emotions, rather than specific anthropomorphic emotions such as “fear” or “anxiety”. These emotion primitives include scalability, persistence, valence and generalization to multiple contexts. Here we have applied this approach to determine whether flies' defensive responses to shadows are purely reflexive, or may express underlying emotion states. We describe a new behavioral assay in which flies confined in an enclosed arena are repeatedly exposed to an overhead translational shadow. Repetitive shadows promoted graded (scalable) and persistent increases in locomotor velocity and hopping, and occasional freezing. The shadow also dispersed feeding flies from a food resource, suggesting both negative valence and context generalization. Strikingly, there was a significant delay before the flies returned to the food following shadow-induced dispersal, suggestive of a slowly decaying internal defensive state. The length of this delay was increased when more shadows were delivered for initial dispersal. These responses can be mathematically modeled by assuming an internal state that behaves as a leaky integrator of shadow exposure. Our results suggest that flies' responses to repetitive shadow stimuli express an internal state exhibiting canonical emotion primitives, possibly analogous to “fear” in mammals. The mechanistic basis of this state can now be investigated in a genetically tractable insect species.
Host-defense peptides, also called antimicrobial peptides (AMPs), whose protective action has been used by animals for millions of years, fulfill many requirements of the pharmaceutical industry, such as: (1) broad spectrum of activity; (2) unlike classic antibiotics, they induce very little resistance; (3) they act synergically with conventional antibiotics; (4) they neutralize endotoxins and are active in animal models. However, it is considered that many natural peptides are not suitable for drug development due to stability and biodisponibility problems, or high production costs. This review describes the efforts to overcome these problems and develop new antimicrobial drugs from these peptides or inspired by them. The discovery process of natural AMPs is discussed, as well as the development of synthetic analogs with improved pharmacological properties. The production of these compounds at acceptable costs, using different chemical and biotechnological methods, is also commented. Once these challenges are overcome, a new generation of versatile, potent and long-lasting antimicrobial drugs is expected.
In this paper, the impact of residential distributed energy resources (DER) on the power quality is investigated in four feeder types of the electrical LV distribution network in Flanders, Belgium. The investigated power quality issues are over-voltage, under-voltage and unbalance. The results of the simulations are discussed in detail. The paper leads to an estimation of the compliance to the power quality standard EN 50160, and a summary of issues in the distribution grids when increasing the amount of DER.
The electron-acceptor properties of series of related sulfides and disulfides were investigated in N,N-dimethylformamide with homogeneous (redox catalysis) and/or heterogeneous (cyclic voltammetry and convolution analysis) electrochemical techniques. The electron-transfer rate constants were determined as a function of the reaction free energy and the corresponding intrinsic barriers were determined. The dependence of relevant thermodynamic and kinetic parameters on substituents was assessed. The kinetic data were also analyzed in relation to corresponding data pertaining to reduction of diaryl disulfides. All investigated reductions take place by stepwise dissociative electron transfer (DET) which causes cleavage of the C(alkyl)--S or S--S bond. A generalized picture of how the intrinsic electron-transfer barrier depends on molecular features, ring substituents, and the presence of spacers between the frangible bond and aromatic groups was established. The reduction mechanism was found to undergo a progressive (and now predictable) transition between common stepwise DET and DET proceeding through formation of loose radical anions. The intrinsic barriers were compared with available results for ET to several classes of dissociative- and nondissociative-type acceptors, and this led to verification that the heterogeneous and the homogeneous data correlate as predicted by the Hush theory.
Mechanistic evidence observed in Hofmann-Löffler-Freytag-type reactions has been crucial to achieve the chemoselective functionalization of methyl groups under mild conditions. Radical-mediated methyl iodination and subsequent oxidative deiodination are the key steps in this functionalization, where iodine chemistry has a pivotal role on the formation of the C-N bond. The concepts of single hydrogen atom transfer (SHAT) and multiple hydrogen atom transfer (MHAT) are introduced to describe the observed chemoselectivity.
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