ドラッグデリバリーシステムの光学的生体内追跡と時空間制御

学位の種別:課程博士University of Tokyo(東京大学

Ferromagnetic state with large magnetic moments realized in epitaxially strained Sr3Ru2O7 films

Technical advancement of oxide molecular beam epitaxy (MBE) has opened new avenues for studying various quantum transport phenomena in correlated transition-metal oxides, as exemplified by the exotic superconductivity of Sr$_2$RuO$_4$ and quantum oscillations of SrRuO$_3$. On the other hand, film research of another Ruddlesden-Popper strontium ruthenate Sr$_3$Ru$_2$O$_7$ which exhibits a unique quantum phase related to metamagnetism in bulk systems did not progress well. Here we report the fabrication of high-quality Sr$_3$Ru$_2$O$_7$ thin films by oxide MBE and the observation of a strain-induced ferromagnetic ground state. The change in magnetic exchange coupling evaluated by first-principles calculations indicates a systematic relation between the compression of the $c$-axis length and induced ferromagnetism. Giant epitaxial strain in high-quality films will be a key to a comprehensive understanding of the magnetism in Ruddlesden-Popper strontium ruthenates Sr$_{n+1}$Ru$_n$O$_{3n+1}$, which sensitively depends on the ratio of in-plane to out-of-plane Ru-Ru distances.Comment: 15 pages, 4 figure

High resolution carbon isotope stratigraphy across the Cenomaian/Turonian boundary in the Tappu area, Hokkaido, Japan : correlation with world reference sections

Received March 2, 2010 and accepted in revised from March 11, 201

TbGT8 is a bifunctional glycosyltransferase that elaborates<em> N</em>-linked glycans on a protein phosphatase AcP115 and a GPI-anchor modifying glycan in <em>Trypanosoma brucei</em>

AbstractThe procyclic form of Trypanosoma brucei expresses procyclin surface glycoproteins with unusual glycosylphosphatidylinositol-anchor side chain structures that contain branched N-acetyllactosamine and lacto-N-biose units. The glycosyltransferase TbGT8 is involved in the synthesis of the branched side chain through its UDP-GlcNAc: βGal β1-3N-acetylglucosaminyltransferase activity. Here, we explored the role of TbGT8 in the mammalian bloodstream form of the parasite with a tetracycline-inducible conditional null T. brucei mutant for TbGT8. Under non-permissive conditions, the mutant showed significantly reduced binding to tomato lectin, which recognizes poly-N-acetyllactosamine-containing glycans. Lectin pull-down assays revealed differences between the wild type and TbGT8 null-mutant T. brucei, notably the absence of a broad protein band with an approximate molecular weight of 110kDa in the mutant lysate. Proteomic analysis revealed that the band contained several glycoproteins, including the acidic ecto-protein phosphatase AcP115, a stage-specific glycoprotein in the bloodstream form of T. brucei. Western blotting with an anti-AcP115 antibody revealed that AcP115 was approximately 10kDa smaller in the mutant. Enzymatic de-N-glycosylation demonstrated that the underlying protein cores were the same, suggesting that the 10-kDa difference was due to differences in N-linked glycans. Immunofluorescence microscopy revealed the colocalization of hemagglutinin epitope-tagged TbGT8 and the Golgi-associated protein GRASP. These data suggest that TbGT8 is involved in the construction of complex poly-N-acetyllactosamine-containing type N-linked and GPI-linked glycans in the Golgi of the bloodstream and procyclic parasite forms, respectively

EDITORIAL

Ligand-mediated drug delivery systems have enormous potential for improving the efficacy of cancer treatment. In particular, Arg-Gly-Asp peptides are promising ligand molecules for targeting α_vβ₃/α_vβ₅ integrins, which are overexpressed in angiogenic sites and tumors, such as intractable human glioblastoma (U87MG). We here achieved highly efficient drug delivery to U87MG tumors by using a platinum anticancer drug-incorporating polymeric micelle (PM) with cyclic Arg-Gly-Asp (cRGD) ligand molecules. Intravital confocal laser scanning microscopy revealed that the cRGD-linked polymeric micelles (cRGD/m) accumulated rapidly and had high permeability from vessels into the tumor parenchyma compared with the PM having nontargeted ligand, “cyclic-Arg-Ala-Asp” (cRAD). As both cRGD/m- and cRAD-linked polymeric micelles have similar characteristics, including their size, surface charge, and the amount of incorporated drugs, it is likely that the selective and accelerated accumulation of cRGD/m into tumors occurred <i>via</i> an active internalization pathway, possibly transcytosis, thereby producing significant antitumor effects in an orthotopic mouse model of U87MG human glioblastoma