A microsatellite baseline for genetic stock identification of European Atlantic salmon (Salmo salar L.)

Atlantic salmon (Salmo salar L.) populations from different river origins mix in the North Atlantic during the marine life stage. To facilitate marine stock identification, we developed a genetic baseline covering the European component of the species’ range excluding the Baltic Sea, from the Russian River Megra in the north-east, the Icelandic Ellidaar in the west, and the Spanish Ulla in the south, spanning 3737 km North to South and 2717 km East to West. The baseline encompasses data for 14 microsatellites for 26 822 individual fish from 13 countries, 282 rivers, and 467 sampling sites. A hierarchy of regional genetic assignment units was defined using a combination of distance-based and Bayesian clustering. At the top level, three assignment units were identified comprising northern, southern, and Icelandic regions. A second assignment level was also defined, comprising eighteen and twenty-nine regional units for accurate individual assignment and mixed stock estimates respectively. The baseline provides the most comprehensive geographical coverage for an Atlantic salmon genetic data-set, and a unique resource for the conservation and management of the species in Europe. It is freely available to researchers to facilitate identification of the natal origin of European salmon

Discovery of Novel Highly Potent Hepatitis C Virus NS5A Inhibitor (AV4025)

A series of next in class small-molecule hepatitis C virus (HCV) NS5A inhibitors with picomolar potency containing 2-pyrrolidin-2-yl-5-{4-[4-(2-pyrrolidin-2-yl-1<i>H</i>-imidazol-5-yl)­buta-1,3-diynyl]­phenyl}-1<i>H</i>-imidazole cores was designed based on the SAR studies available for the reported NS5A inhibitors. Compound <b>13a</b> (AV4025), with (<i>S</i>,<i>S</i>,<i>S</i>,<i>S</i>)-stereochemistry (EC₅₀ = 3.4 ± 0.2 pM, HCV replicon genotype 1b), was dramatically more active than were the compounds with two (<i>S</i>)- and two (<i>R</i>)-chiral centers. Human serum did not significantly reduce the antiviral activity (<4-fold). Relatively favorable pharmacokinetic features and good oral bioavailability were observed during animal studies. Compound <b>13a</b> was well tolerated in rodents (in mice, LD₅₀ = 2326 mg/kg or higher), providing a relatively high therapeutic index. During safety, pharmacology and subchronic toxicity studies in rats and dogs, it was not associated with any significant pathological or clinical findings. This compound is currently being evaluated in phase I/II clinical trials for the treatment of HCV infection