The Orphan G Protein-coupled Receptor GPR17 Negatively Regulates Oligodendrocyte Differentiation via Gαi/o and Its Downstream Effector Molecules

Recent studies have recognized G protein-coupled receptors as important regulators of oligodendrocyte development. GPR17, in particular, is an orphan G protein-coupled receptor that has been identified as oligodendroglial maturation inhibitor because its stimulation arrests primary mouse oligodendrocytes at a less differentiated stage. However, the intracellular signaling effectors transducing its activation remain poorly understood. Here, we use Oli-neu cells, an immortalized cell line derived from primary murine oligodendrocytes, and primary rat oligodendrocyte cultures as model systems to identify molecular targets that link cell surface GPR17 to oligodendrocyte maturation blockade. We demonstrate that stimulation of GPR17 by the small molecule agonist MDL29,951 (2-carboxy-4,6-dichloro-1H-indole-3-propionic acid) decreases myelin basic protein expression levels mainly by triggering the Gα_i/o signaling pathway, which in turn leads to reduced activity of the downstream cascade adenylyl cyclase-cAMP-PKA-cAMP response element-binding protein (CREB). In addition, we show that GPR17 activation also diminishes myelin basic protein abundance by lessening stimulation of the exchange protein directly activated by cAMP (EPAC), thus uncovering a previously unrecognized role for EPAC to regulate oligodendrocyte differentiation. Together, our data establish PKA and EPAC as key downstream effectors of GPR17 that inhibit oligodendrocyte maturation. We envisage that treatments augmenting PKA and/or EPAC activity represent a beneficial approach for therapeutic enhancement of remyelination in those demyelinating diseases where GPR17 is highly expressed, such as multiple sclerosis.     

The Anopheles gambiae Odorant Binding Protein 1 (AgamOBP1) Mediates Indole Recognition in the Antennae of Female Mosquitoes

Haematophagous insects are frequently carriers of parasitic diseases, including malaria. The mosquito Anopheles gambiae is the major vector of malaria in sub-Saharan Africa and is thus responsible for thousands of deaths daily. Although the role of olfaction in A. gambiae host detection has been demonstrated, little is known about the combinations of ligands and odorant binding proteins (OBPs) that can produce specific odor-related responses in vivo. We identified a ligand, indole, for an A. gambiae odorant binding protein, AgamOBP1, modeled the interaction in silico and confirmed the interaction using biochemical assays. RNAi-mediated gene silencing coupled with electrophysiological analyses confirmed that AgamOBP1 binds indole in A. gambiae and that the antennal receptor cells do not respond to indole in the absence of AgamOBP1. This case represents the first documented instance of a specific A. gambiae OBP–ligand pairing combination, demonstrates the significance of OBPs in odor recognition, and can be expanded to the identification of other ligands for OBPs of Anopheles and other medically important insects.     

Crop processing of <Emphasis Type="Italic">Olea europaea</Emphasis> L.: an experimental approach for the interpretation of archaeobotanical olive remains

Archaeobotanical research, ethnographic observations and laboratory experiments are put together to create model sequences of olive processing, which are developed, presented and explored as an aid for the interpretation of rich archaeobotanical assemblages of Olea. We conclude that the remains of different processing stages are reasonably distinctive in the archaeobotanical record and assist in the identification of different types of olive remains, such as fragmented olive stones, the inner kernels, and fruit flesh     

Habitat properties and plant traits interact as drivers of non‐native plant species’ seed production at the local scale

To answer the long‐standing question if we can predict plant invader success based on characteristics of the environment (invasibility) or the invasive species (invasiveness), or the combination of both, there is a need for detailed observational studies in which habitat properties, non‐native plant traits, and the resulting invader success are locally measured. In this study, we assess the interaction of gradients in the environmental and trait space on non‐native species fitness, expressed as seed production, for a set of 10 invasive and noninvasive non‐native species along a wide range of invaded sites in Flanders. In our multidimensional approach, most of the single environmental gradients (temperature, light availability, native plant species diversity, and soil fertility) and sets of non‐native plant traits (plant size, photosynthesis, and foliar chemical attributes) related positively with invader seed production. Yet correlation with seed production was much stronger when several environmental gradients were assessed in interaction, and even more so when we combined plant traits and habitat properties. The latter increased explanatory power of the models on average by 25% for invasive and by 7% for noninvasive species. Additionally, we report a 70‐fold higher seed production in invasive than in noninvasive species and fundamentally different correlations of seed production with plant traits and habitat properties in noninvasive versus invasive species. We conclude that locally measured traits and properties deserve much more attention than they currently get in invasion literature and thus encourage further studies combining this level of detail with the generality of a multiregion and multispecies approach across different stages of invasion.     

Identification and activation of novel biosynthetic gene clusters by genome mining in the kirromycin producer <Emphasis Type="Italic">Streptomyces collinus</Emphasis> Tü 365

Streptomycetes are prolific sources of novel biologically active secondary metabolites with pharmaceutical potential. S. collinus Tü 365 is a Streptomyces strain, isolated 1972 from Kouroussa (Guinea). It is best known as producer of the antibiotic kirromycin, an inhibitor of the protein biosynthesis interacting with elongation factor EF-Tu. Genome Mining revealed 32 gene clusters encoding the biosynthesis of diverse secondary metabolites in the genome of Streptomyces collinus Tü 365, indicating an enormous biosynthetic potential of this strain. The structural diversity of secondary metabolisms predicted for S. collinus Tü 365 includes PKS, NRPS, PKS-NRPS hybrids, a lanthipeptide, terpenes and siderophores. While some of these gene clusters were found to contain genes related to known secondary metabolites, which also could be detected in HPLC–MS analyses, most of the uncharacterized gene clusters are not expressed under standard laboratory conditions. With this study we aimed to characterize the genome information of S. collinus Tü 365 to make use of gene clusters, which previously have not been described for this strain. We were able to connect the gene clusters of a lanthipeptide, a carotenoid, five terpenoid compounds, an ectoine, a siderophore and a spore pigment-associated gene cluster to their respective biosynthesis products.