BackgroundChronic increases in the levels of the inflammatory cytokine interleukin-6 (IL-6) in serum and skeletal muscle are thought to contribute to the progression of muscular dystrophy. Dystrophin/utrophin double-knockout (dKO) mice develop a more severe and progressive muscular dystrophy than the mdx mice, the most common murine model of Duchenne muscular dystrophy (DMD). In particular, dKO mice have smaller body sizes and muscle diameters, and develop progressive kyphosis and fibrosis in skeletal and cardiac muscles. As mdx mice and DMD patients, we found that IL-6 levels in the skeletal muscle were significantly increased in dKO mice. Thus, in this study, we aimed to analyze the effects of IL-6 receptor (IL-6R) blockade on the muscle pathology of dKO mice.MethodsMale dKO mice were administered an initial injection (200 mg/kg intraperitoneally (i.p.)) of either the anti-IL-6R antibody MR16-1 or an isotype-matched control rat IgG at the age of 14 days, and were then given weekly injections (25 mg/kg i.p.) until 90 days of age.ResultsTreatment of dKO mice with the MR16-1 antibody successfully inhibited the IL-6 pathway in the skeletal muscle and resulted in a significant reduction in the expression levels of phosphorylated signal transducer and activator of transcription 3 in the skeletal muscle. Pathologically, a significant increase in the area of embryonic myosin heavy chain-positive myofibers and muscle diameter, and reduced fibrosis in the quadriceps muscle were observed. These results demonstrated the therapeutic effects of IL-6R blockade on promoting muscle regeneration. Consistently, serum creatine kinase levels were decreased. Despite these improvements observed in the limb muscles, degeneration of the diaphragm and cardiac muscles was not ameliorated by the treatment of mice with the MR16-1 antibody.ConclusionAs no adverse effects of treatment with the MR16-1 antibody were observed, our results indicate that the anti-IL-6R antibody is a potential therapy for muscular dystrophy particularly for promoting skeletal muscle regeneration.Electronic supplementary materialThe online version of this article (10.1186/s13395-017-0140-z) contains supplementary material, which is available to authorized users.

Ferredoxin (Fd), which plays a pivotal role in photosynthesis as an electron carrier, forms a transient complex with various Fd-dependent enzymes, such as nitrite reductase (NiR), to achieve efficient intermolecular electron transfer. We studied the protein-protein interaction of Fd and NiR by NMR spectroscopy and determined three acidic regions of Fd to be major sites for the interaction with NiR, indicating that the complex is stabilized through electrostatic interaction. During this study, we found Fds from higher plant and cyanobacterium, in spite of their high structural similarities including the above acidic regions, differ remarkably in the interaction with cyanobacterial NiR. In activity assay of NiR, K(m) value for maize Fd (74.6 µM) was 9.6 times larger than that for Leptolyngbya boryana Fd (7.8 µM). The two Fds also showed a similar difference in binding assay to NiR-immobilized resin. Comparative site-specific mutagenesis of two Fds revealed that their discriminative ability for the interaction with NiR is attributed mainly to non-charged residues in the peripheral region of [2Fe-2S] cluster. These non-charged residues are conserved separately between Fds of plant and cyanobacterial origins. Our data highlight that intermolecular force(s) other than electrostatic attraction is(are) also crucial for the molecular interaction between Fd and partner enzyme.

BackgroundTransforming growth factor-β1 (TGF-β1) reportedly acts as a tumor suppressor in tumorigenesis. However, little is known as to how TGF-β1 concentrations change prior to the development of hepatocellular carcinoma (HCC) in humans. We examined the association between the serum TGF-β1 concentrations and death from HCC to determine whether the serum TGF-β1 can be a predictor of incident HCC.MethodsWe conducted a nested case-controlled study of participants in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. We used a conditional logistic regression analysis to estimate the adjusted relative risks (aRRs) of death from HCC according to the serum TGF-β1 concentrations among 1940 participants including 83 patients with HCC and 1857 controls matched for age, sex, and hepatitis C virus (HCV)-antibody seropositivity.FindingsWhen serum TGF-β1 was modelled as a continuous variable, the aRR of death from HCC associated with a decrement of 7.9 ng/mL (one standard deviation) in the serum TGF-β1 concentrations was 2.3 (95% CI 1.7–3.0, P < 0.001) for all the subjects. The area under the receiver operating characteristic curve for the serum TGF-β1 concentrations was 0.78 (P < 0.05).InterpretationOur finding suggests that TGF-β1 serves as a predictor for HCC.

This article examines innovation in the securities industry with the central objective of identifying factors that separate innovators from non‐innovators. Akira Iwamura and Vijay Jog report results based on their survey of corporate finance vice presidents or CEO's of 43 investment houses from around the world. They conclude that innovative companies seem to be larger and have a well‐defined strategy, with management defining the focus of the business. In addition, the firms have developed better communication channels, both internally and with their customers. Yet, the most significant difference that separates innovators from non‐innovators is their management of the idea generation process, including concept generation and management's support. Innovators tend to approach idea generation in the following ways: they employ a variety of idea sources, both internal and external; they assign a specific person or group to be in charge of developing new ideas; they encourage employees at all levels to generate new ideas; they use a variety of innovative techniques to stimulate creativity; they reward their employees by non‐monetary means; and they encourage group‐level participation in evaluation decisions.

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