High-dose clevudine impairs mitochondrial function and glucose-stimulated insulin secretion in INS-1E cells

<p>Abstract</p> <p>Background</p> <p>Clevudine is a nucleoside analog reverse transcriptase inhibitor that exhibits potent antiviral activity against hepatitis B virus (HBV) without serious side effects. However, mitochondrial myopathy has been observed in patients with chronic HBV infection taking clevudine. Moreover, the development of diabetes was recently reported in patients receiving long-term treatment with clevudine. In this study, we investigated the effects of clevudine on mitochondrial function and insulin release in a rat clonal β-cell line, INS-1E.</p> <p>Methods</p> <p>The mitochondrial DNA (mtDNA) copy number and the mRNA levels were measured by using quantitative PCR. MTT analysis, ATP/lactate measurements, and insulin assay were performed.</p> <p>Results</p> <p>Both INS-1E cells and HepG2 cells, which originated from human hepatoma, showed dose-dependent decreases in mtDNA copy number and cytochrome c oxidase-1 (Cox-1) mRNA level following culture with clevudine (10 μM-1 mM) for 4 weeks. INS-1E cells treated with clevudine had reduced total mitochondrial activities, lower cytosolic ATP contents, enhanced lactate production, and more lipid accumulation. Insulin release in response to glucose application was markedly decreased in clevudine-treated INS-1E cells, which might be a consequence of mitochondrial dysfunction.</p> <p>Conclusions</p> <p>Our data suggest that high-dose treatment with clevudine induces mitochondrial defects associated with mtDNA depletion and impairs glucose-stimulated insulin secretion in insulin-releasing cells. These findings partly explain the development of diabetes in patients receiving clevudine who might have a high susceptibility to mitochondrial toxicity.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Liquid crystal clad near-infrared metamaterials with tunable negative-zero-positive refractive indices

Near-infrared metamaterials that possess a reconfigurable index of refraction from negative through zero to positive values are presented. Reconfigurability is achieved by cladding thin layers of liquid crystal both as a superstrate and a substrate on an established negative-index metamaterial, and adjusting the permittivity of the liquid crystal. Numerical results show that the index of refraction for the proposed structure can be changed over the range from -1 to +1.8 by tuning the liquid crystal permittivity from 2 to 6 at a wavelength of 1.4 mu m

Tunable optical negative-index metamaterials employing anisotropic liquid crystals

A full-wave analysis technique based on the finite element-boundary integral method is developed and used to rigorously treat the scattering from periodically structured metamaterials incorporating anisotropic liquid crystals (LCs) and dispersive materials. Reconfiguration of the negative-index metamaterials is achieved by controlling the magnetic resonance via tuning permittivity of the embedded anisotropic LCs. Numerical results show that the refractive index of the metamaterials can be reconfigured by tuning the director orientation of anisotropic LCs or by using temperature-dependent LCs. The design configurations and their characteristics in the near- and the mid-infrared ranges are presented

East Asian capitalism: Towards a normative framework

This essay attempts to identify the features of East Asian capitalism that seem, prima facie, to serve desirable social and political purposes while also being compatible with, if not beneficial for, the requirements of economic productivity in an age of intense international competition. It argues that East Asian countries should build on areas of competitive advantage instead of heeding calls to shed all the old ways of doing things in favor of American-style shareholder capitalism.