BackgroundThe potential human health risks from graphene inhalation exposure have attracted substantial scientific interest as a result of the numerous exciting potential commercial applications of graphene. However, the long-term distribution of graphene in organisms after inhalation is unknown, largely as a result of challenges associated with accurate graphene quantification.MethodsCarbon-14 labeled FLG was used to quantify the in vivo distribution of FLG in mice after oral gavage or intratracheal instillation for up to 3 or 28 days after exposure, respectively.ResultsIntratracheally instilled FLG was mainly retained in the lung with 47 % remaining after 4 weeks. Exposure to non-labeled FLG resulted in dose-dependent acute lung injury and pulmonary edema, but these effects were alleviated with time despite the continued presence of FLG in the lungs. One percent and 0.18 % of the intratracheally instilled FLG was present in the liver and spleen, respectively, after 14 days by passing through the air-blood barrier, a finding supported by the results of oral gavage experiments which did not show detectable absorption through the gastrointestinal tract. In addition, 46.2 % of the intratracheally instilled FLG was excreted through the feces 28 d after exposure.ConclusionsQuantitative measurements revealed the elimination mechanism for FLG and its biodistribution for two exposure pathways. Graphene persistence in the lung only caused transient pulmonary effects. The in vivo distribution, elimination, and toxicity results provided here measured using a robust quantitative method support the human health risk assessment of graphene.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0120-1) contains supplementary material, which is available to authorized users.

Protein ubiquitination is a multifaceted post-translational modification that controls almost every process in eukaryotic cells. Recently, the Legionella effector SdeA was reported to mediate a unique phosphoribosyl-linked ubiquitination through successive modifications of the Arg42 of ubiquitin (Ub) by its mono-ADP-ribosyltransferase (mART) and phosphodiesterase (PDE) domains. However, the mechanisms of SdeA-mediated Ub modification and phosphoribosyl-linked ubiquitination remain unknown. Here we report the structures of SdeA in its ligand-free, Ub-bound and Ub-NADH-bound states. The structures reveal that the mART and PDE domains of SdeA form a catalytic domain over its C-terminal region. Upon Ub binding, the canonical ADP-ribosyltransferase toxin turn-turn (ARTT) and phosphate-nicotinamide (PN) loops in the mART domain of SdeA undergo marked conformational changes. The Ub Arg72 might act as a 'probe' that interacts with the mART domain first, and then movements may occur in the side chains of Arg72 and Arg42 during the ADP-ribosylation of Ub. Our study reveals the mechanism of SdeA-mediated Ub modification and provides a framework for further investigations into the phosphoribosyl-linked ubiquitination process.

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