A terahertz metamaterial with unnaturally high refractive index

Controlling the electromagnetic properties of materials, going beyond the limit that is attainable with naturally existing substances, has become a reality with the advent of metamaterials. The range of various structured artificial 'atoms' has promised a vast variety of otherwise unexpected physical phenomena, among which the experimental realization of a negative refractive index has been one of the main foci thus far. Expanding the refractive index into a high positive regime will complete the spectrum of achievable refractive index and provide more design flexibility for transformation optics. Naturally existing transparent materials possess small positive indices of refraction, except for a few semiconductors and insulators, such as lead sulphide or strontium titanate, that exhibit a rather high peak refractive index at mid- and far-infrared frequencies. Previous approaches using metamaterials were not successful in realizing broadband high refractive indices. A broadband high-refractive-index metamaterial structure was theoretically investigated only recently, but the proposed structure does not lend itself to easy implementation. Here we demonstrate that a broadband, extremely high index of refraction can be realized from large-area, free-standing, flexible terahertz metamaterials composed of strongly coupled unit cells. By drastically increasing the effective permittivity through strong capacitive coupling and decreasing the diamagnetic response with a thin metallic structure in the unit cell, a peak refractive index of 38.6 along with a low-frequency quasi-static value of over 20 were experimentally realized for a single-layer terahertz metamaterial, while maintaining low losses. As a natural extension of these single-layer metamaterials, we fabricated quasi-three-dimensional high-refractive-index metamaterials, and obtained a maximum bulk refractive index of 33.2 along with a value of around 8 at the quasi-static limit.     

Redefinition of Nipponbathynella based on the four new species from East Asia (Crustacea: Bathynellacea: Parabathynellidae)

Four new species of the parabathynellid genus Nipponbathynella Schminke, 1973 are described from South Korea (Nipponbathynella leesookyungae sp. nov., Nipponbathynella donggangensis sp. nov. and Nipponbathynella wanjuensis sp. nov.) and Japan (Nipponbathynella shigaensis sp. nov.), raising the number of known species to seven. Nipponbathynella leesookyungae is characterized by the convex ventral surface of the labrum and the rich ornamentation (with three spinules and two teeth) of the exopod of male thoracopod VIII; N. donggangensis by the distal spine on the distal maxillular segment with many dentils; N. wanjuensis by the endopod of the male thoracopod VIII with one seta (instead of two) and the serrated endopodal spur of the uropod; and N. shigaensis by the basipod of thoracopods II–VII carrying strong hairs on their outer margin. The three new and one known (Nipponbathynella pectina) South Korean species share a bur-like inner lobe of the male thoracopod VIII, suggesting their close relationship. Based on the one-segmented exopod on thoracopod I and two-segmented exopod on the thoracopods II–VII, the bell-shaped male thoracopod VIII and the uropod with sympod carrying a large distal spine in addition to several proximal spines of smaller size, with endopod drawn into a spur and with exopod carrying a seta, a close phylogenetic relationship between Nipponbathynella and Arisubathynella Park and Eun, 2012 is proposed.

http://zoobank.org/urn:lsid:zoobank.org:pub:9650379F-C249-473C-AAA4-B3D638B96322     

BRD7 regulates the insulin-signaling pathway by increasing phosphorylation of GSK3β

Reduced hepatic expression levels of bromodomain-containing protein 7 (BRD7) have been suggested to play a role in the development of glucose intolerance in obesity. However, the molecular mechanism by which BRD7 regulates glucose metabolism has remained unclear. Here, we show that BRD7 increases phosphorylation of glycogen synthase kinase 3β (GSK3β) in response to activation of the insulin receptor-signaling pathway shortly after insulin stimulation and the nutrient-sensing pathway after feeding. BRD7 mediates phosphorylation of GSK3β at the Serine 9 residue and this effect on GSK3β occurs even in the absence of AKT activity. Using both in vitro and in vivo models, we further demonstrate that BRD7 mediates phosphorylation of ribosomal protein S6 kinase (S6K) and leads to increased phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and, therefore, relieves its inhibition of the eukaryotic translation initiation factor 4E (eIF4E). However, the increase in phosphorylation of 4E-BP1 with BRD7 overexpression is blunted in the absence of AKT activity. In addition, using liver-specific BRD7 knockout (LBKO) mice, we show that BRD7 is required for mTORC1 activity on its downstream molecules. These findings show a novel basis for understanding the molecular dynamics of glucose metabolism and suggest the unique function of BRD7 in the regulation of glucose homeostasis.     

Multispecies-compatible antitumor effects of a cross-species small-interfering RNA against mammalian target of rapamycin

Successful development of sequence-specific siRNA (small interfering RNA)-based drugs requires an siRNA design that functions consistently in different organisms. Utilizing the CAPSID program previously developed by our group, we here designed siRNAs against mammalian target of rapamycin (mTOR) that are entirely complementary among various species and investigated their multispecies-compatible gene-silencing properties. The mTOR siRNAs markedly reduced mTOR expression at both the mRNA and protein levels in human, mouse, and monkey cell lines. The reduction in mTOR expression resulted in inactivation of both mTOR complex I and II signaling pathways, as confirmed by reduced phosphorylation of p70S6K (70-kDa ribosomal protein S6 kinase), 4EBP1 (eIF4E-binding protein 1), and AKT, and nuclear accumulation of FOXO1 (forkhead box O1), with consequent cell-cycle arrest, proliferation inhibition, and autophagy activation. Moreover, interfering with mTOR activity in vivo using mTOR small-hairpin RNA-expressing recombinant adeno-associated virus led to significant antitumor effects in xenograft and allograft models. Thus, the present study demonstrates that cross-species siRNA successfully silences its target and readily produces multispecies-compatible phenotypic alterations-antitumor effects in the case of mTOR siRNA. Application of cross-species siRNA should greatly facilitate the development of siRNA-based therapeutic agents.     

Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer

Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer.     

Galectin-3 stabilizes heterogeneous nuclear ribonucleoprotein Q to maintain proliferation of human colon cancer cells

Comparative analysis of proteomes using 5-fluorouracil (5-FU)-resistant human colon cancer cell line revealed that decreased galectin-3 expression was significantly associated with retarded proliferation. However, in the presence of 5-FU proliferation rate of cells with suppressed galectin-3 expression did not differ from that of cells with normal galectin-3 expression, even galectin-3 suppression augmented apoptosis. Mechanism by which galectin-3 regulates cancer cell proliferation has been identified in immunoprecipitates of the anti-galectin-3 antibody. Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) was identified as a protein interacting with galectin-3. Interestingly, while galectin-3 protein was not affected by the hnRNP Q level, its suppression was accompanied by a decrease in hnRNP Q expression. The present study demonstrates that galectin-3 stabilizes hnRNP Q via complex formation, and reduction in the hnRNP Q level leads to slow proliferation and less susceptibility to 5-FU. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. B.C.Yoo; S-H.Hong; These two authors contributed equally to this work. Received 10 September 2008; received after revision 19 October 2008; accepted 07 November 2008     

Enhancement of T-cell activation by the CD43 molecule whose expression is defective in Wiskott-Aldrich syndrome

CD43 (sialophorin, leukosialin, leukocyte large sialoglycoprotein), a heavily sialylated molecule found on most leukocytes and platelets, was initially identified as a major glycoprotein of mouse, rat and human T cells. CD43 expression is defective on the T cells of males with the Wiskott-Aldrich syndrome, an X chromosome-linked recessive immunodeficiency disorder. Affected males are susceptible to opportunistic infections and do not respond to polysaccharide antigens, reflecting defects in cytotoxic and helper T-cell functions. Anti-CD43 monoclonal antibodies have a modest costimulatory effect on T cells, natural killer cells, B cells and monocytes, and one such antibody has been shown to activate T cells directly. To investigate a possible physiological role for CD43, a complementary DNA encoding the human protein was introduced into an antigen-responsive murine T-cell hybridoma. We observed that CD43 enhances the antigen-specific activation of T cells and that the intracellular domain of CD43, which is hyperphosphorylated during T-cell activation, is required for this function. We also found that antigen-presenting cells can bind specifically to immobilized purified CD43 and that the binding can be inhibited by liposomes containing CD43 as well as by anti-CD43 monoclonal antibodies.     

应用扩展的Monod模型关联醋酸菌比生长速率

应用扩展的Ｍｏｎｏｄ模型关联了醋酸菌ＩＡＭ１８０２和Ｍ２３的比生长速率，ＩＡＭ１８０２的比生长速率关联式为μ＝０．４８７（１－ＣＰ／２３．８）＾０．２４８ＣＡ／ＣＭ＋ＣＡ；Ｍ２３的关联式为μ＝０．５６８（１－ＣＰ／６１．０）＾０．３０６ＣＡ／ＣＭ＋ＣＡ除临界生长抑制剂浓度附近外，模型良好地表达了两种醋力的比生长速率。