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  • Oxford University Press  (72)
  • Molecular Diversity Preservation International  (34)
  • 1
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    Selenite targets eIF4E-binding protein-1 to inhibit translation initiation and induce the assembly of non-canonical stress granules (2012)
    Oxford University Press
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    Publikationsdatum: 2012-09-13
    Beschreibung: Stress granules (SGs) are large cytoplasmic ribonucleoprotein complexes that are assembled when cells are exposed to stress. SGs promote the survival of stressed cells by contributing to the reprogramming of protein expression as well as by blocking pro-apoptotic signaling cascades. These cytoprotective effects implicated SGs in the resistance of cancer cells to radiation and chemotherapy. We have found that sodium selenite, a selenium compound with chemotherapeutic potential, is a potent inducer of SG assembly. Selenite-induced SGs differ from canonical mammalian SGs in their morphology, composition and mechanism of assembly. Their assembly is induced primarily by eIF4E-binding protein1 (4EBP1)-mediated inhibition of translation initiation, which is reinforced by concurrent phosphorylation of eIF2α. Selenite-induced SGs lack several classical SG components, including proteins that contribute to pro-survival functions of canonical SGs. Our results reveal a new mechanism of mammalian SG assembly and provide insights into how selenite cytotoxicity may be exploited as an anti-neoplastic therapy.
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
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    New susceptibility variants to narcolepsy identified in HLA class II region (2015)
    Oxford University Press
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    Publikationsdatum: 2015-01-13
    Beschreibung: Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10–30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 ( P = 1.4 x 10 –10 , odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found ( P = 2.5 x 10 –9 , OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01 . In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1 . This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 x 10 –5 , OR = 2.45; DPB1*05:01 , P = 8.1 x 10 –3 , OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.
    Print ISSN: 0964-6906
    Digitale ISSN: 1460-2083
    Thema: Biologie , Medizin
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
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    Identification of a splicing variant that regulates type 2 diabetes risk factor CDKAL1 level by a coding-independent mechanism in human (2014)
    Oxford University Press
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    Publikationsdatum: 2014-08-03
    Beschreibung: Single-nucleotide polymorphisms (SNPs) in CDKAL1 have been associated with the development of type 2 diabetes (T2D). CDKAL1 catalyzes 2-methylthio modification of adenosine at position 37 of tRNA Lys (UUU). A deficit of this modification causes aberrant protein synthesis, and is associated with impairment of insulin secretion in both mouse model and human. However, it is unknown whether the T2D-associated SNPs in CDKAL1 are associated with downregulation of CDKAL1 by regulating the gene expression. Here, we report a specific splicing variant of CDKAL1 termed CDKAL1-v1 that is markedly lower in individuals carrying risk SNPs of CDKAL1 . Interestingly, CDKAL1-v1 is a non-coding transcript, which regulates the CDKAL1 level by competitive binding to a CDKAL1 -targeting miRNA. By direct editing of the genome, we further show that the nucleotides around the SNP regions are critical for the alternative splicing of CDKAL1-v1 . These findings reveal that the T2D-associated SNPs in CDKAL1 reduce CDKAL1-v1 levels by impairing splicing, which in turn increases miRNA-mediated suppression of CDKAL1. Our results suggest that CDKAL1-v1 -mediated suppression of CDKAL1 might underlie the pathogenesis of T2D in individuals carrying the risk SNPs.
    Print ISSN: 0964-6906
    Digitale ISSN: 1460-2083
    Thema: Biologie , Medizin
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
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    Interaction of the phospholipid flippase Drs2p with the F-box protein Rcy1p plays an important role in early endosome to trans-Golgi network vesicle transport in yeast (2014)
    Oxford University Press
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    Publikationsdatum: 2014-01-07
    Beschreibung: Phospholipid composition of biological membranes differs between the cytoplasmic and exoplasmic leaflets. The type 4 P-type ATPases are phospholipid flippases that generate such membrane phospholipid asymmetry. Drs2p, a flippase in budding yeast, is involved in the endocytic recycling pathway. Drs2p is implicated in clathrin-coated vesicle formation, but the underlying mechanisms are not clearly understood. Here we show that the carboxyl-terminal cytoplasmic region of Drs2p directly binds to Rcy1p, an F-box protein that is also required for endocytic recycling. The Drs2p-binding region was mapped to the amino acids 574–778 region of Rcy1p and a mutant Rcy1p lacking this region was defective in endocytic recycling of a v-SNARE Snc1p. We isolated Drs2p point mutants that reduced the interaction with Rcy1p. The mutation sites were clustered within a small region (a.a. 1260–1268) of Drs2p. Although these point mutants did not exhibit clear phenotypes, combination of them resulted in cold-sensitive growth, defects in endocytic recycling of Snc1p and defective localization of Rcy1p to endosomal membranes like the drs2 null mutant. These results suggest that the interaction of Drs2p with Rcy1p plays an important role for Drs2p function in the endocytic recycling pathway.
    Print ISSN: 0021-924X
    Digitale ISSN: 1756-2651
    Thema: Biologie , Chemie und Pharmazie
    Publiziert von Oxford University Press im Namen von The Japanese Biochemical Society (JBS).
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
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    MSIdV: a versatile tool to visualize biological indices from mass spectrometry imaging data (2016)
    Oxford University Press
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    Publikationsdatum: 2016-12-20
    Beschreibung: : Mass spectrometry imaging (MSI) visualizes the simultaneous lateral distribution of multiple compounds on sample surface. However, it is still difficult to visualize biological indices such as energy charge index from multiple compounds because of the lack of publicly available tools. Here we present MSIdV, a visualization tool for biological indices calculated from mass spectrometry imaging data, which can effectively scan a series of mass spectra and process, calculate and visualize user-defined index measures accurately with a number of signal processing features. Availability and Implementation: MSIdV is implemented in Python 2.7 and is freely available on the web at https://sourceforge.net/projects/msidv/ . Contact: eisuke.hayakawa@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Digitale ISSN: 1460-2059
    Thema: Biologie , Informatik , Medizin
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
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    Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion (2017)
    Oxford University Press
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    Publikationsdatum: 2017-01-10
    Beschreibung: The 2-methylthio (ms 2 ) modification at A37 of tRNAs is critical for accurate decoding, and contributes to metabolic homeostasis in mammals. However, the regulatory mechanism of ms 2 modification remains largely unknown. Here, we report that cysteine hydropersulfide (CysSSH), a newly identified reactive sulfur species, is involved in ms 2 modification in cells. The suppression of intracellular CysSSH production rapidly reduced ms 2 modification, which was rescued by the application of an exogenous CysSSH donor. Using a unique and stable isotope-labeled CysSSH donor, we show that CysSSH was capable of specifically transferring its reactive sulfur atom to the cysteine residues of ms 2 -modifying enzymes as well as ms 2 modification. Furthermore, the suppression of CysSSH production impaired insulin secretion and caused glucose intolerance in both a pancreatic β-cell line and mouse model. These results demonstrate that intracellular CysSSH is a novel sulfur source for ms 2 modification, and that it contributes to insulin secretion.
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
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    Prominent IgE-binding and cytokine-inducing capacities of a newly cloned N-terminal region of Der f 14, an apolipophorin-like house dust mite allergen (2018)
    Oxford University Press
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    Publikationsdatum: 2018-03-06
    Beschreibung: We previously characterized a 177-kDa allergen, M-177, from Dermatophagoides farinae . Thereafter, a counterpart to M-177 for Euroglyphus maynei was cloned as Eur m 14, and its sequence revealed that two environmental allergens, Mag 1 and Mag 3, are digested fragments of M-177. The aims of this study were to clone the cDNA of Der f 14 corresponding to M-177 and to elucidate the allergenic capacities of the N-terminal fragment of Der f 14 (Der f 14-N). Recombinant allergens were produced as trigger-factor-fused proteins in Escherichia coli . Der f 14-N showed the highest IgE-binding frequency among Der f 14-derived fragments in patients allergic to house dust mite by enzyme-linked immunosorbent assay. Der f 14-N showed the highest capacity to induce cell proliferation in murine lymphocyte and human peripheral mononuclear cells among Der f 14-derived fragments. Der f 14-N induced IL-13, IFN-γ and IL-17 production more than Der f 1 and Der f 2 in mouse, and induced IL-5 and IFN-γ production at levels comparable to those of Der f 1 and Der f 2 in some patients. The high prevalence of IgE binding to the Der f 14-N indicates that it could be an important mite allergen.
    Print ISSN: 0021-924X
    Digitale ISSN: 1756-2651
    Thema: Biologie , Chemie und Pharmazie
    Publiziert von Oxford University Press im Namen von The Japanese Biochemical Society (JBS).
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
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    Analysis of a Serial/Parallel Type of Electromagnetic Actuator (2020)
    Molecular Diversity Preservation International
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    Publikationsdatum: 2020-05-12
    Beschreibung: This paper describes the design and analysis of a small-sized and high thrust electromagnetic actuator. The proposed actuator is supposed to be used for application control of the hotmelt adhesive. The hotmelt has different characteristics for each material and the electromagnetic actuator is required variable characteristics. However, the problem seems to lie in the fact that it is necessary to remake another mold again to change the characteristics of the conventional electromagnetic actuator. Therefore, this paper presents small-sized electromagnetic actuator called a basic model that can stack it in the axial direction or in the radial direction. As the analysis comparison at the same size, the characteristics of conventional two serial model which stack two basic models in the axial direction and proposed three serial models have been compared by three-dimensional finite element method. In the proposed model, characteristics have been improved by reducing the core volume and increasing the number of stacks in the basic model from the viewpoint of magnetic flux density. In addition, various electromagnetic actuators that stack basic models in the axial direction or in the radial direction have been analyzed. The analysis results have been clearly shown as characteristics mapping and it has indicated that the proposed electromagnetic actuator can be constructed easily by stacking the basic model.
    Digitale ISSN: 1424-8220
    Thema: Chemie und Pharmazie , Elektrotechnik, Elektronik, Nachrichtentechnik
    Publiziert von Molecular Diversity Preservation International
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
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    In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy (2020)
    Molecular Diversity Preservation International
    Details
    Publikationsdatum: 2020-09-23
    Beschreibung: Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer appears to be a suitable target for BPA-BNCT, because the expression levels of L-type amino acid transporter 1 (LAT1), one of the amino acid transporters responsible for BPA uptake, are elevated in most cases of H&N cancer. However, in other types of cancer including malignant brain tumors, LAT1 is not always highly expressed. To expand the possibility of BNCT for these cases, we previously developed poly-arginine peptide (polyR)-conjugated mercaptoundecahydrododecaborate (BSH). PolyR confers the cell membrane permeability and tumor selectivity of BSH. However, the molecular determinants for the properties are not fully understood. In this present study, we have identified the cluster of differentiation 44 (CD44) protein and translational machinery proteins as a major cell surface target and intracellular targets of BSH-polyR, respectively. CD44, also known as a stem cell-associated maker in various types of cancer, is required for the cellular uptake of polyR-conjugated molecules. We showed that BSH-polyR was predominantly delivered to a CD44High cell population of cancer cells. Once delivered, BSH-polyR interacted with the translational machinery components, including the initiation factors, termination factors, and poly(A)-biding protein (PABP). As a proof of principle, we performed BSH-polyR-based BNCT against glioma stem-like cells and revealed that BSH-polyR successfully induced BNCT-dependent cell death specifically in CD44High cells. Bioinformatics analysis indicated that BSH-polyR would be suitable for certain types of malignant tumors. Our results shed light on the biochemical properties of BSH-polyR, which may further contribute to the therapeutic optimization of BSH-BNCT in the future.
    Digitale ISSN: 2073-4409
    Thema: Biologie
    Publiziert von Molecular Diversity Preservation International
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
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    Multicolor Emission and Photophysical Properties of Proton-Responsive Cyclometallated Iridium(III) Complex in Transparent Cation-Exchange Membrane (2020)
    Molecular Diversity Preservation International
    Details
    Publikationsdatum: 2020-07-30
    Beschreibung: A transparent film allowing tunable multicolor emission based on a composite of an organometallic compound and a cation-exchange membrane has been developed, in which the cyclometallated iridium(III) complex [IrIII(4Py-ppy)3] (=tris[2-(2-pyridinyl-κN)-4-(4-pyridinyl)phenyl-κC]iridium) (1) with pH-dependent emission wavelengths has been incorporated into Nafion by cation exchange. Soaking Nafion in the solution of 1 for 24 h and exposed to buffers at pH 2, 4, and 10 resulted in maximum emission wavelengths of 587, 560, and 503 nm, respectively. The photophysical properties of 1@Nafion were also enhanced, as its maximum emission wavelength was more blue-shifted than those of 602, 564, and 503 nm in the solutions. The emission quantum yields (Φ) and lifetimes (τ) of 1@Nafion prepared under an acidic condition were up to Φ = 1.8% and τ = 0.11, 0.92 μs, which are considerably higher than the corresponding solutions of Φ = 0.5% and τ = 0.02, 0.18 μs. This is attributed to the fact that 1 is surrounded by the polymer chains of Nafion and immobilized in a relatively rigid medium, which hinders non-radiative deactivation such as thermal relaxation.
    Digitale ISSN: 2073-4352
    Thema: Physik
    Publiziert von Molecular Diversity Preservation International
    Standort Signatur Erwartet Verfügbarkeit
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