Hexapeptides from mammalian inhibitory hormone hunt activate and inactivate nematode reproduction

© 2022 Hart et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. https://creativecommons.org/licenses/by/4.0/Background: Biopurification has been used to disclose an evolutionarily conserved inhibitory reproductive hormone involved in tissue mass determination. A (rat) bioassay-guided physicochemical fractionation using ovine materials yielded via Edman degradation a 14-residue amino acid (aa) sequence. As a 14mer synthetic peptide (EPL001) this displayed antiproliferative and reproduction-modulating activity, while representing only a part of the native polypeptide. Even more unexpectedly, a scrambled-sequence control peptide (EPL030) did likewise. Methods: Reproduction has been investigated in the nematode Steinernema siamkayai, using a fermentation system supplemented with different concentrations of exogenous hexapeptides. Peptide structure-activity relationships have also been studied using prostate cancer and other mammalian cells in vitro, with peptides in solution or immobilized, and via the use of mammalian assays in vivo and through molecular modelling. Results: Reproduction increased (x3) in the entomopathogenic nematode Steinernema siamkayai after exposure to one synthetic peptide (IEPVFT), while fecundity was reduced (x0.5) after exposure to another (KLKMNG), both effects being dose-dependent. These hexamers are opposite ends of the synthetic peptide KLKMNGKNIEPVFT (EPL030). Bioactivity is unexpected as EPL030 is a control compound, based on a scrambled sequence of the test peptide MKPLTGKVKEFNNI (EPL001). EPL030 and EPL001 are both bioinformatically obscure, having no convincing matches to aa sequences in the protein databases. EPL001 has antiproliferative effects on human prostate cancer cells and rat bone marrow cells in vitro. Intracerebroventricular infusion of EPL001 in sheep was associated with elevated growth hormone in peripheral blood and reduced prolactin. The highly dissimilar EPL001 and EPL030 nonetheless have the foregoing biological effects in common in mammalian systems, while being divergently pro- and anti-fecundity respectively in the nematode Caenorhabditis elegans. Peptides up to a 20mer have also been shown to inhibit the proliferation of human cancer and other mammalian cells in vitro, with reproductive upregulation demonstrated previously in fish and frogs, as well as nematodes. EPL001 encodes the sheep neuroendocrine prohormone secretogranin II (sSgII), as deduced on the basis of immunoprecipitation using an anti-EPL001 antibody, with bespoke bioinformatics. Six sSgII residues are key to EPL001’s bioactivity: MKPLTGKVKEFNNI. A stereospecific bimodular tri-residue signature is described involving simultaneous accessibility for binding of the side chains of two specific trios of amino acids, MKP & VFN. An evolutionarily conserved receptor is conceptualised having dimeric binding sites, each with ligand-matching bimodular stereocentres. The bioactivity of the 14mer control peptide EPL030 and its hexapeptide progeny is due to the fortuitous assembly of subsets of the novel hormonal motif, MKPVFN, a default reproductive and tissue-building OFF signal.Peer reviewe

Emotional cues enhance the attentional effects on spatial and temporal resolution

In the present study, we demonstrated that the emotional significance of a spatial cue enhances the effect of covert attention on spatial and temporal resolution (i.e., our ability to discriminate small spatial details and fast temporal flicker). Our results indicated that fearful face cues, as compared with neutral face cues, enhanced the attentional benefits in spatial resolution but also enhanced the attentional deficits in temporal resolution. Furthermore, we observed that the overall magnitudes of individuals’ attentional effects correlated strongly with the magnitude of the emotion × attention interaction effect. Combined, these findings provide strong support for the idea that emotion enhances the strength of a cue’s attentional response

Reward-based learning for virtual neurorobotics through emotional speech processing

Reward-based learning can easily be applied to reallife with a prevalence in teaching methods for children. It alsoallows machines and software agents to automatically determinethe ideal behavior from a simple reward feedback (e.g. encouragement) to maximize their performance. Advancements inaffective computing, especially emotional speech processing (ESP)have allowed for more natural interaction between humans androbots. Our research focuses on integrating a novel ESP systemin a relevant virtual neurorobotic application. We created anemotional speech classifier that successfully distinguished happyand sad utterances. The accuracy of the system was 95.3%and 98.7% during the offline mode (using an emotional speechdatabase) and the live mode (using live recordings), respectively.It was then integrated in a neurorobotic scenario, where a virtualneurorobot had to learn a simple exercise through reward-based learning. If the correct decision was made the robotreceived a spoken reward, which in turn stimulated synapses (inour simulated model) undergoing spike-timing dependent plas-ticity (STDP) and reinforced the corresponding neural pathways.Both our emotional speech processing and neurorobotic systemsallowed our neurorobot to successfully and consistently learnthe exercise. The integration of ESP in real-time computationalneuroscience architecture is a first step toward the combinationof human emotions and virtual neurorobotics