Nutritional sources of meio- and macrofauna at hydrothermal vents and adjacent areas: Natural-abundance radiocarbon and stable isotope analyses

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nomaki, H., Uejima, Y., Ogawa, N. O., Yamane, M., Watanabe, H. K., Senokuchi, R., Bernhard, J. M., Kitahashi, T., Miyairi, Y., Yokoyama, Y., Ohkouchi, N., & Shimanaga, M. Nutritional sources of meio- and macrofauna at hydrothermal vents and adjacent areas: Natural-abundance radiocarbon and stable isotope analyses. Marine Ecology Progress Series, 622, (2019): 49-65, doi:10.3354/meps13053.Deep-sea hydrothermal vents host unique marine ecosystems that rely on organic matter produced by chemoautotrophic microbes together with phytodetritus. Although meiofauna can be abundant at such vents, the small size of meiofauna limits studies on nutritional sources. Here we investigated dietary sources of meio- and macrofauna at hydrothermal vent fields in the western North Pacific using stable carbon and nitrogen isotope ratios (δ13C, δ15N) and natural-abundance radiocarbon (Δ14C). Bacterial mats and Paralvinella spp. (polychaetes) collected from hydrothermal vent chimneys were enriched in 13C (up to -10‰) and depleted in 14C (-700 to -580‰). The δ13C and Δ14C values of dirivultid copepods, endemic to hydrothermal vent chimneys, were -11‰ and -661‰, respectively, and were similar to the values in the bacterial mats and Paralvinella spp. but distinct from those of nearby non-vent sediments (δ13C: ~-24‰) and water-column plankton (Δ14C: ~40‰). In contrast, δ13C values of nematodes from vent chimneys were similar to those of non-vent sites (ca. -25‰). Results suggest that dirivultids relied on vent chimney bacterial mats as their nutritional source, whereas vent nematodes did not obtain significant nutrient amounts from the chemolithoautotrophic microbes. The Δ14C values of Neoverruca intermedia (vent barnacle) suggest they gain nutrition from chemoautotrophic microbes, but the source of inorganic carbon was diluted with bottom water much more than those of the Paralvinella habitat, reflecting Neoverruca’s more distant distribution from active venting. The combination of stable and radioisotope analyses on hydrothermal vent organisms provides valuable information on their nutritional sources and, hence, their adaptive ecology to chemosynthesis-based ecosystems.We are grateful to the crews and scientists of the R/V ‘Natsushima’ and the ROV ‘Hyper-Dolphin’ of the Japan Agency for Marine-Earth Science and Technology (JAMSTEC) during the NT12-10, NT13-09 and NT14-06 cruises, and the R/V ‘Kaimei’ and the KM-ROV of JAMSTEC during the KM-ROV training cruise. We thank Yuki Iwadate for her help on sample preparations and 2 anonymous reviewers and the editor, who provided helpful comments on an earlier version of this manuscript. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (Scientific Research C 26440246 to M.S.), the Japan Society for the Promotion of Science (Invitational fellowships for research in Japan, S14032 to J.M.B.), the WHOI Robert W. Morse Chair for Excellence in Oceanography, and The Investment in Science Fund at WHOI

DOGS: Reaction-Driven de novo Design of Bioactive Compounds

We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design of Genuine Structures) features a ligand-based strategy for automated ‘in silico’ assembly of potentially novel bioactive compounds. The quality of the designed compounds is assessed by a graph kernel method measuring their similarity to known bioactive reference ligands in terms of structural and pharmacophoric features. We implemented a deterministic compound construction procedure that explicitly considers compound synthesizability, based on a compilation of 25'144 readily available synthetic building blocks and 58 established reaction principles. This enables the software to suggest a synthesis route for each designed compound. Two prospective case studies are presented together with details on the algorithm and its implementation. De novo designed ligand candidates for the human histamine H4 receptor and γ-secretase were synthesized as suggested by the software. The computational approach proved to be suitable for scaffold-hopping from known ligands to novel chemotypes, and for generating bioactive molecules with drug-like properties

Sirt7 Deficiency Attenuates Neointimal Formation Following Vascular Injury by Modulating Vascular Smooth Muscle Cell Proliferation

Background: Sirt7 is a recently identified sirtuin and has important roles in various pathological conditions, including cancer progression and metabolic disorders. It has previously been reported that Sirt7 is a key molecule in acute myocardial wound healing and pressure overload-induced cardiac hypertrophy. In this study, the role of Sirt7 in neointimal formation after vascular injury is investigated. Methods and Results: Systemic (Sirt7(-/-)) and smooth muscle cell-specific Sirt7-deficient mice were subjected to femoral artery wire injury. Primary vascular smooth muscle cells (VSMCs) were isolated from the aorta of wild type (WT) and Sirt7(-/-) mice and their capacity for cell proliferation and migration was compared. Sirt7 expression was increased in vascular tissue at the sites of injury. Sirt7(-/-) mice demonstrated significant reduction in neointimal formation compared to WT mice. In vitro, Sirt7 deficiency attenuated the proliferation of serum-induced VSMCs. Serum stimulation-induced upregulation of cyclins and cyclin-dependent-kinase 2 (CDK2) was significantly attenuated in VSMCs of Sirt7(-/-) compared with WT mice. These changes were accompanied by enhanced expression of the microRNA 290-295 cluster, the translational negative regulator of CDK2, in VSMCs of Sirt7(-/-) mice. It was confirmed that smooth muscle cell-specific Sirt7-deficient mice showed significant reduction in neointima compared with control mice. Conclusions: Sirt7 deficiency attenuates neointimal formation after vascular injury. Given the predominant role in vascular neointimal formation, Sirt7 is a potentially suitable target for treatment of vascular diseases

Noncatalytic reaction of isonitriles and carboxylic acids en route to amide-type linkages.

This protocol describes the preparation of an N-methyl-asparagine-linked glycosyl amino acid, on the basis of a reaction between carboxylic acids and isonitriles. Under microwave/thermolysis, carboxylic acids can couple with isonitriles without an external catalyst to form N-formyl-amides, which may be further advanced to the corresponding amides, N-methyl amide and N-methyloyl amide. The example reaction of beta-galactopyranosyl isonitrile (7) with a protected aspartic acid under microwave condition in 30 min stereoselectively leads to a beta-galactopyranosyl-N-formyl-asparagine (9). Further chemical transformations readily convert 9 into beta-galactopyranosyl-N-methyl-asparagine (11).link_to_subscribed_fulltex