Insect taxonomy can be difficult: a noctuid moth (Agaristinae: Aletopus imperialis) and a geometrid moth (Sterrhinae: Cartaletis dargei) combined into a cryptic species complex in eastern Africa (Lepidoptera).

The systematic position of a large and strikingly coloured reddish-black moth, Cartaletis dargei Herbulot, 2003 (Geometridae: Sterrhinae) from Tanzania, has remained questionable since its description. Here we present molecular and morphological evidence showing that Cartaletis dargei only superficially resembles true Cartaletis Warren, 1894 (the relative name currently considered a junior synonym of Aletis Hübner, 1820), which are unpalatable diurnal moths superficially resembling butterflies, and that it is misplaced in the family Geometridae. We transfer it to Noctuidae: Agaristinae, and combine it with the genus Aletopus Jordan, 1926, from Tanzania, as Aletopus dargei (Herbulot, 2003) (new combination). We revise the genus Aletopus to contain three species, but find that it is a cryptic species complex that needs to be revised with more extensive taxon sampling. Our results demonstrate the difficulties in interpreting and classifying biological diversity. We discuss the problems in species delimitation and the potential drivers of evolution in eastern Africa that led to phenotypic similarity in unrelated lepidopteran lineages.

Long-term large-scale decline in relative abundances of butterfly and burnet moth species across south-western Germany.

Current studies have shown a severe general decline in insect species diversity, their abundance, and a biomass reduction of flying insects. Most of previous studies have been performed at single sites, or were spatially restricted at the landscape level. In this study, we analyse trends of species richness and shifts in species composition of butterflies and burnet moth species across the federal state of Baden-Württemberg in south-western Germany, covering an area of 35,750 km2. The data set consists of 233,474 records and covers a period from 1750 until today. We grouped species according to their species´ specific functional traits and analyse how species with different habitat requirements and behaviour respond to land-use changes over time. Our data document a significant loss of relative abundance for most species, especially since the 1950s until today. Species demanding specific habitat requirements are more seriously suffering under this trend than generalists. This in particular affects taxa adapted to extensively used xerothermic grasslands, bogs or other habitats maintained by traditional low-productivity agricultural practices of the past. Our data indicate large-scale decline in relative abundance of many butterfly and burnet moth species, which happened in particular during the past few decades.

Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors.

Herein we report the discovery of a novel series of phosphodiesterase 10A inhibitors. Optimization of a HTS hit (17) resulted in potent, selective, and brain penetrant 23 and 26; both exhibited much lower clearance in vivo and decreased volume of distribution (rat PK) and have thus the potential to inhibit the PDE10A target in vivo at a lower efficacious dose than the reference compound WEB-3.

Discovery of Novel Aminotetralines and Aminochromanes as Selective and Competitive Glycine Transporter 1 (GlyT1) Inhibitors.

The glycine transporter 1 (GlyT1) has emerged as a key novel target for the treatment of schizophrenia. Herein, we report the synthesis and biological evaluation of aminotetralines and aminochromanes as novel classes of competitive GlyT1 inhibitors. Starting from a high-throughput screening hit, structure-activity relationship studies led first to the discovery of aminotetralines displaying high GlyT1 potency and selectivity, with favorable pharmacokinetic properties. Systematic investigations of various parameters (e.g., topological polar surface area, number of hydrogen bond donors) guided by ex vivo target occupancy evaluation resulted in lead compounds possessing favorable brain penetration properties as for (7 S,8 R)-27a. Further optimization revealed compounds with reduced efflux liabilities as for aminochromane 51b. In an in vivo efficacy model (7 S,8 R)-27a, dose-dependently reversed L-687,414 induced hyperlocomotion in mice with an ED50 of 0.8 mg/kg. All these results suggest (7 S,8 R)-27a and 51b as new GlyT1 inhibitors worthy of further profiling.

Inhibitors of GlyT1 affect glycine transport via discrete binding sites.

In the forebrain, synaptic glycine concentrations are regulated through the glycine transporter GlyT1. Because glycine is a coagonist of the N-methyl-D-aspartate (NMDA) receptor (NMDAR), which has been implicated in schizophrenia, inhibition of GlyT1 is thought to provide an option for the treatment of schizophrenia. In support of this hypothesis, GlyT1 inhibitors facilitate in vivo NMDAR function and demonstrate antipsychotic-like effects in animal models. Among the specific GlyT1 inhibitors, substituted N-methyl-glycine (sarcosine) derivatives (e.g., (R)-N[3-(4'fluorophenyl)-3-(4'phenyl-phenoxy)propyl]-sarcosine [NFPS], (R)-N[3-phenyl-3-(4'-(4-toluoyl)phenoxy)-propyl]sarcosine [(R)-NPTS], and (R,S)-(+/-)N-methyl-N-[(4-trifluoromethyl)phenoxy]-3-phenyl-propylglycine [Org24589]), and non-sarcosine-containing inhibitors, such as 2-chloro-N-[(S)-phenyl[(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide, monohydrochloride (SSR504734), have been described. In the present study, we analyzed the mode of interaction of these compounds with GlyT1 by using electrophysiological measurements in Xenopus laevis oocytes, and with two binding assays, using [(3)H](R)-NPTS or 2-chloro-N-[(S)-phenyl[(2S)-N-methylpiperidin-2-yl]-methyl]-3-trifluoromethyl benzamide monohydrochloride ([(3)H]N-methyl-SSR504734) as radioligands. Inhibition of electrogenic glycine transport by sarcosine-based compounds was apparently irreversible and independent of glycine concentration. The latter indicates a noncompetitive mode of action. In contrast, both SSR504734 and N-methyl-SSR504734 exhibited reversible and competitive inhibition of glycine transport. In GlyT1-expressing membranes, the binding of the novel radioligand [(3)H]N-methyl-SSR504734 to a single site on GlyT1 was competitively displaced by glycine and SSR504734 but noncompetitively by sarcosine-based compounds. Inversely, [(3)H](R)-NPTS binding was competitively inhibited by sarcosine-based compounds, whereas glycine, SSR504734, and N-methyl-SSR504734 noncompetitively decreased maximal binding. Our data indicate that besides exerting an apparently irreversible or reversible inhibition, GlyT1 inhibitors differ by exhibiting either a noncompetitive or competitive mode of inhibition. The divergent modes of inhibition may significantly affect the efficacy and tolerability of these drugs.

A brain-like neural network for periodicity analysis.

This paper introduces a brain-like neural model for sound processing. The periodicity analyzing network (PAN) is a bio-inspired neural network of spiking neurons. The PAN consists of complex models of neurons, which can be used for understanding the dynamics of individual neurons and neuronal networks. On a technical level, the PAN is able to compute the ratio of modulation and carrier frequency of harmonic sound signals. The PAN model may, therefore, be used in audio signal processing applications, such as sound source separation, periodicity analysis, and the cocktail party problem.