Solution-Phase, parallel synthesis and pharmacological evaluation of acylguanidine derivatives as potential sodium channel blockers

Solution-phase synthesis of various acylguanidine derivatives and the evaluation of a small library of compounds as potential sodium channel blockers are described.     

The distribution of the orange‐striped green anemone,Diadumene lineata,in relation to environmental factors along coastal British Columbia,Canada

The cosmopolitan nonindigenous sea anemone, Diadumene lineata, has been recorded from the Pacific coast of Canada since 1859. Despite its long historical presence in the region, the factors influencing the distribution of this species in British Columbia, Canada, are poorly understood, as are the factors that may restrict its local abundance. We conducted large‐scale surveys of D. lineata during the winter and summer of 2016, coupled with higher frequency surveys at one focal site. Furthermore, we used laboratory and field experiments to determine the potential importance of a large‐scale driver, salinity, and a small‐scale driver, microhabitat within boulders, in setting distributional limits at various spatial scales. Our results confirm that D. lineata is widely distributed within the Salish Sea. This broad distribution may be facilitated by post‐introduction dispersal; we observed anemones attached to floating substrata, and a few mature specimens contained eggs, suggesting that reproduction is perhaps not limited to asexual fission. We found that D. lineata was abundant throughout the year, although absent from the lowest salinity sites. This corresponded with our laboratory experiments, in which survival of individuals of D. lineata declined at salinities below 10 psu, and no survivors were observed at or below 2 psu. Manipulative experiments in the field demonstrated that survival was high under rocks where D. lineata is commonly found, but was reduced on the tops of rocks, highlighting the importance of microhabitat refugia in buffering temperature and reducing desiccation. A better understanding of the factors that limit the broad‐scale and local distribution of this anemone are an important step in determining potential ecological impacts of this organism and how distributions may shift into the future.     

Glypican Is a Modulator of Netrin-Mediated Axon Guidance

Netrin is a key axon guidance cue that orients axon growth during neural circuit formation. However, the mechanisms regulating netrin and its receptors in the extracellular milieu are largely unknown. Here we demonstrate that in Caenorhabditis elegans, LON-2/glypican, a heparan sulfate proteoglycan, modulates UNC-6/netrin signaling and may do this through interactions with the UNC-40/DCC receptor. We show that developing axons misorient in the absence of LON-2/glypican when the SLT-1/slit guidance pathway is compromised and that LON-2/glypican functions in both the attractive and repulsive UNC-6/netrin pathways. We find that the core LON-2/glypican protein, lacking its heparan sulfate chains, and secreted forms of LON-2/glypican are functional in axon guidance. We also find that LON-2/glypican functions from the epidermal substrate cells to guide axons, and we provide evidence that LON-2/glypican associates with UNC-40/DCC receptor–expressing cells. We propose that LON-2/glypican acts as a modulator of UNC-40/DCC-mediated guidance to fine-tune axonal responses to UNC-6/netrin signals during migration.