The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E + V -SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online (http://bioinf.spbau.ru/spades). It is distributed as open source software.
1 Certain heterocyclic N-oxides are vasodilators and inhibitors of platelet aggregation. The pharmacological activity of the furoxan derivative condensed with pyridazine di-N-oxide 4,7-dimethyl-1,2,5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide (FPTO) and the corresponding furazan (FPDO) was studied. 2 FPTO reacted with thiols generating nitrite (NO), S-nitrosoglutathione and hydroxylamine (nitroxyl) and converted oxyHb to metHb. FPDO did not generate detectable amounts of NO-like species but reacted with thiols and oxyHb. 3 FPTO and FPDO haem-dependently stimulated the activity of soluble guanylate cyclase (sGC) and this stimulation was inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and by 0.1 mM dithiothreitol. 4 FPTO relaxed noradrenaline-precontracted aortic rings and its concentration-response curve was biphasic (pIC 50 =9.03+0.13 and 5.85+0.06). FPDO was signi®cantly less potent vasodilator (pIC 50 =5.19+0.14). The vasorelaxant activity of FPTO and FPDO was inhibited by ODQ. oxyHb signi®cantly inhibited only FPTO-dependent relaxation. 5 FPTO and FPDO were equipotent inhibitors of ADP-induced platelet aggregation (IC 50 =0.63+0.15 and 0.49+0.05 mM, respectively). The antiplatelet activity of FPTO (but not FPDO) was partially suppressed by oxyHb. The antiaggregatory eects of FPTO and FPDO were only partially blocked by sGC inhibitors. 6 FPTO and FPDO (10 ± 20 mM) signi®cantly increased cyclic GMP levels in aortic rings and platelets and this increase was blocked by ODQ. 7 Thus, FPTO can generate NO and, like FPDO, reacts with thiols and haem. The vasorelaxant activity of FPTO and FPDO is sGC-dependent and a predominant role is played by NO at FPTO concentrations below 1 mM. On the contrary, inhibition of platelet aggregation is only partially related to sGC activation.
The title methods involve the [4+2] cycloaddition of enamine or norbornadiene to the triazine ring of triazinfuroxans followed by one‐pot transformation of the formed intermediates affording a series of polyheterocyclic compounds combining furoxan and pyridine rings in one molecule through a C—C bond.
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