Persistence of Environmental DNA in Freshwater Ecosystems

The precise knowledge of species distribution is a key step in conservation biology. However, species detection can be extremely difficult in many environments, specific life stages and in populations at very low density. The aim of this study was to improve the knowledge on DNA persistence in water in order to confirm the presence of the focus species in freshwater ecosystems. Aquatic vertebrates (fish: Siberian sturgeon and amphibian: Bullfrog tadpoles) were used as target species. In control conditions (tanks) and in the field (ponds), the DNA detectability decreases with time after the removal of the species source of DNA. DNA was detectable for less than one month in both conditions. The density of individuals also influences the dynamics of DNA detectability in water samples. The dynamics of detectability reflects the persistence of DNA fragments in freshwater ecosystems. The short time persistence of detectable amounts of DNA opens perspectives in conservation biology, by allowing access to the presence or absence of species e.g. rare, secretive, potentially invasive, or at low density. This knowledge of DNA persistence will greatly influence planning of biodiversity inventories and biosecurity surveys

Characterisation of tissue-type metabolic content in secondary progressive multiple sclerosis: a magnetic resonance spectroscopic imaging study

Proton magnetic resonance spectroscopy yields metabolic information and has proved to be a useful addition to structural imaging in neurological diseases. We applied short-echo time Spectroscopic Imaging in a cohort of 42 patients with secondary progressive multiple sclerosis (SPMS). Linear modelling with respect to brain tissue type yielded metabolite levels that were significantly different in white matter lesions compared with normal-appearing white matter, suggestive of higher myelin turnover (higher choline), higher metabolic rate (higher creatine) and increased glial activity (higher myo-inositol) within the lesions. These findings suggest that the lesions have ongoing cellular activity that is not consistent with the usual assumption of ‘chronic’ lesions in SPMS, and may represent a target for repair therapies

Efficient discovery of bioactive scaffolds by activity-directed synthesis

The structures and biological activities of natural products have often provided inspiration in drug discovery. The functional benefits of natural products to the host organism steers the evolution of their biosynthetic pathways. Here, we describe a discovery approach-which we term activity-directed synthesis-in which reactions with alternative outcomes are steered towards functional products. Arrays of catalysed reactions of α-diazo amides, whose outcome was critically dependent on the specific conditions used, were performed. The products were assayed at increasingly low concentration, with the results informing the design of a subsequent reaction array. Finally, promising reactions were scaled up and, after purification, submicromolar ligands based on two scaffolds with no previous annotated activity against the androgen receptor were discovered. The approach enables the discovery, in tandem, of both bioactive small molecules and associated synthetic routes, analogous to the evolution of biosynthetic pathways to yield natural products

Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates

Using asymmetric catalysis to simultaneously form carbon-carbon bonds and generate single isomer products is strategically important. Suzuki-Miyaura cross-coupling is widely used in the academic and industrial sectors to synthesize drugs, agrochemicals and biologically active and advanced materials. However, widely applicable enantioselective Suzuki-Miyaura variations to provide 3D molecules remain elusive. Here we report a rhodium-catalyzed asymmetric Suzuki-Miyaura reaction with important partners including aryls, vinyls, heteroaromatics and heterocycles. The method can be used to couple two heterocyclic species so the highly enantioenriched products have a wide array of cores. We show that pyridine boronic acids are unsuitable, but they can be halogen-modified at the 2-position to undergo reaction, and this halogen can then be removed or used to facilitate further reactions. The method is used to synthesize isoanabasine, preclamol, and niraparib – an anticancer agent in several clinical trials. We anticipate this method will be a useful tool in drug synthesis and discovery. A correction to this article is available at: https://doi.org/10.1038/ncomms1621