110 research outputs found

    Pinning Down Viral Proteins: A New Prototype for Virus–Host Cell Interaction

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    Pin 1 is an enzyme that specifically catalyzes the cis–trans isomerization of phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif in its substrate proteins. Recent studies demonstrate that stability of several viral proteins is regulated by phosphorylation-dependent prolyl-isomerization by a host factor Pin1. Pin1 is now positioned as an important modulator of the molecular crosstalk between virus and host cells and could be a unique target for anti-virus therapy. This new type of post-translational modification by Pin1 might be involved in the regulation of other viral proteins

    Vaccination with Human Induced Pluripotent Stem Cells Creates an Antigen-Specific Immune Response Against HIV-1 gp160

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    Induced pluripotent stem cells (iPSCs) are artificially derived from somatic cells that have been transduced with defined reprogramming factors. A previous report has indicated the possibility of using iPSCs as an immune stimulator to generate antigen-specific immunity. In our current study, we have investigated whether human iPSCs (hiPSCs) have the ability to enhance specific immune response against a human immunodeficiency virus type 1 (HIV-1) antigen in a xenogenic mouse model. Our results show that BALB/c mice immunized with hiPSCs transduced with an adenoviral vector encoding HIV-1 gp160 exhibited prominent antigen-specific cellular immune responses. We further found that pre-treatment of hiPSCs with ionizing radiation promotes the secretion of pro-inflammatory cytokines such as interleukin-1 alpha (IL-1α), IL-12, and IL-18. These cytokines might promote the activation of antigen-presenting cells and the effective induction of cellular immunity. Our present findings thus demonstrate that a hiPSCs-based vaccine has the potential to generate cellular immunity against viral antigens such as HIV-1 gp160 in a xenogenic condition

    コウシュウハ イオンプレーティング ホウ ニ ヨル ハクマク ケイセイ ニ カンスル ケンキュウ

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    The nanostructural hydrogenated graphite (CnanoHx) was synthesized from graphite by ball milling under hydrogen (H2) atmosphere. In this product, characteristic hydrogenated states in the form of polarized hydrocarbon groups (―CH, ―CH2, and ―CH3) are realized in the nanoscale. By synthesizing the composite of CnanoHx and lithium hydride (LiH), known as the Li―C―H system, hydrogen was desorbed at 350 °C, which is a lower temperature compared to the decomposition temperature of each component. It is considered that this hydrogen desorption would be induced by destabilization of each hydrogen absorbed state due to an interaction between the polarized C―H groups in CnanoHx and LiH. Therefore, in order to understand the hydrogen absorption/desorption mechanism of the Li―C―H system, it is an important issue to investigate the change in the C―H groups during hydrogen absorption/desorption reactions in the composite. The correlations among atoms contained in this composite are examined by neutron diffraction measurements, where the protium/deuterium (H/D) isotopic substitution was used to clarify the location of hydrogen atoms in this composite. Some C―D and Li―D correlations are found from the radial distribution function [RDF(r)] obtained by the neutron diffraction for the CnanoDx and LiD composite. After dehydrogenation, C―C triple bond and Li―C bond, ascribed to lithium carbide (Li2C2), are observed. Furthermore, the RDF(r) corresponding to rehydrogenated composite indicates the presence of not only the Li―D correlation but also the C―D one

    The anharmonic vibration of Li in lithium amide

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    A large amplitude rattling-type anharmonic vibration of Li is possible without guest-host type structure, as we report here for tetragonal LiNH2 crystal. The low temperature (0.4–300 K) specific heat capacity and Raman spectroscopy support the phonon model of site-specific Li activities governed by the symmetry of the potential energy distribution around the Li atoms in LiNH2, which yields the anharmonic Li3 vibration (optical) in one direction (either X or Y axis of the crystal), while the Li1 and Li2 atoms remain silent. Our finding may help to correlate ionic conductivity, thermal, and hydrogenation properties of LiNH2

    Detection of Progeny Immune Responses after Intravenous Administration of DNA Vaccine to Pregnant Mice

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    A number of factors influence the development of tolerance, including the nature, concentration and mode of antigen presentation to the immune system, as well as the age of the host. The studies were conducted to determine whether immunizing pregnant mice with liposome-encapsulated DNA vaccines had an effect on the immune status of their offspring. Two different plasmids (encoding antigens from HIV-1 and influenza virus) were administered intravenously to pregnant mice. At 9.5 days post conception with cationic liposomes, injected plasmid was present in the tissues of the fetus, consistent with trans-placental transfer. When the offspring of vaccinated dams were immunized with DNA vaccine, they mounted stronger antigen-specific immune responses than controls and were protected against challenge by homologous influenza virus after vaccination. Moreover, such immune responses were strong in the offspring of mothers injected with DNA plasmid 9.5 days after coitus. These results suggest that DNA vaccinated mothers confer the antigen-specific immunity to their progeny. Here we describe the methods in detail as they relate to our previously published work

    Thymic Alterations in GM2 Gangliosidoses Model Mice

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    BACKGROUND: Sandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of GM2 ganglioside and related glycolipids. We have previously found that the progressive neurologic disease induced in Hexb(-/-) mice, an animal model for Sandhoff disease, is associated with the production of pathogenic anti-glycolipid autoantibodies. METHODOLOGY/PRINCIPAL FINDINGS: In our current study, we report on the alterations in the thymus during the development of mild to severe progressive neurologic disease. The thymus from Hexb(-/-) mice of greater than 15 weeks of age showed a marked decrease in the percentage of immature CD4(+)/CD8(+) T cells and a significantly increased number of CD4(+)/CD8(-) T cells. During involution, the levels of both apoptotic thymic cells and IgG deposits to T cells were found to have increased, whilst swollen macrophages were prominently observed, particularly in the cortex. We employed cDNA microarray analysis to monitor gene expression during the involution process and found that genes associated with the immune responses were upregulated, particularly those expressed in macrophages. CXCL13 was one of these upregulated genes and is expressed specifically in the thymus. B1 cells were also found to have increased in the thy mus. It is significant that these alterations in the thymus were reduced in FcRγ additionally disrupted Hexb(-/-) mice. CONCLUSIONS/SIGNIFICANCE: These results suggest that the FcRγ chain may render the usually poorly immunogenic thymus into an organ prone to autoimmune responses, including the chemotaxis of B1 cells toward CXCL13

    モモのさし木繁殖に関する基礎的研究 V : 発根促進処理についての二, 三の知見(農学部門)

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    モモ・白桃の休眠枝ざしにおいて, さし穂基部組織中にはIAAと相乗作用を持つRooting cofactorが存在し, 発根過程に伴い量的に変化することが認められ, 不定根形成を制御する一要因と考えられた。発根能力の旺盛なチュウゴクオウトウの新鮮葉にもRooting cofactorが存在し, in vitroで野生モモ枝梢由来callus上に不定根形成を促し, またモモ・大久保の緑枝ざしにおける不定根形成に対し, 外生IBAと相乗的に促進作用を示した。このことからモモのさし木繁殖において, チュウゴクオウトウのRooting cofactor施用は発根促進処理の一つとして期待できる。さし穂基部の切り口に関しては斜め切りが, さし床用土に関しては鹿沼土が発根に対し良好な効果を示し, 繁殖条件の基本要因と考えられた。It was found on hardwood cuttings of peach cv. Hakuto that the rooting cofactor, which showed a strong synergistic effect with IAA on the root formation of mung bean cuttings, was present in the basal stem tissues and reached maximum level of content 4-7 days before the rooting followed by a decrease. Thus, the physiological meaning of the rooting cofactor is considered to be one of the factors regulating the rooting process. The extracts from fresh leaf tissues of chinese cherry (Prunus pauciflora Bunge), an easy-to-root species, had a high content of the rooting cofactor, which promoted the root formation on callus derived from wild peach shoot in vitro, and on the softwood cuttings of peach cv. Okubo with exogenous IBA. From these facts, the application of chinese cherry\u27s rooting cofactor to cuttings may be an available technique on propagation of peach. On the other hands, high percentage of rooting was obtained with an oblique basal end surface of cutting and on Kanumatsuchi as bed soil, therefore these conditions appears to be essential ones on propagation by stem cuttings
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