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Berlin Brandenburg

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  • 1
    Language: English
    In: Science (New York, N.Y.), 11 June 2010, Vol.328(5984), pp.1394-8
    Description: Gamma-interferon-inducible lysosomal thiolreductase (GILT) promotes major histocompatibility complex (MHC) class II-restricted presentation of exogenous antigens containing disulfide bonds. Here, we show that GILT also facilitates MHC class I-restricted recognition of such antigens by CD8+ T cells, or cross-presentation. GILT is essential for cross-presentation of a CD8+ T cell epitope of glycoprotein B (gB) from herpes simplex virus 1 (HSV-1) but not for its presentation by infected cells. Initiation of the gB-specific CD8+ T cell response during HSV-1 infection, or cross-priming, is highly GILT-dependent, as is initiation of the response to the envelope glycoproteins of influenza A virus. Efficient cross-presentation of disulfide-rich antigens requires a complex pathway involving GILT-mediated reduction, unfolding, and partial proteolysis, followed by translocation into the cytosol for proteasomal processing.
    Keywords: Cross-Priming ; Antigens, Viral -- Immunology ; Herpes Simplex -- Immunology ; Herpesvirus 1, Human -- Immunology ; Oxidoreductases -- Metabolism ; Viral Envelope Proteins -- Immunology
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 2
    Language: English
    In: Science, 11 June 2010, Vol.328(5984), pp.1394-1398
    Description: Gamma-interferon-inducible lysosomal thiolreductase (GILT) promotes major histocompatibility complex (MHC) class II—restricted presentation of exogenous antigens containing disulfide bonds. Here, we show that GILT also facilitates MHC class I—restricted recognition of such antigens by CDe⁺ T cells, or cross-presentation. GILT is essential for cross-presentation of a CD8⁺ T cell epitope of glycoprotein B (gB) from herpes simplex virus 1 (HSV-1) but not for its presentation by infected cells. Initiation of the gB-specific CD8⁺ T cell response during HSV-1 infection, or cross-priming, is highly GILT-dependent, as is initiation of the response to the envelope glycoproteins of influenza A virus. Efficient crosspresentation of disulfide-rich antigens requires a complex pathway involving GILT-mediated reduction, unfolding, and partial proteolysis, followed by translocation into the cytosol for proteasomal processing.
    ISSN: 00368075
    E-ISSN: 10959203
    Source: Archival Journals (JSTOR)
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  • 3
    Language: English
    In: Science, 11 June 2010, Vol.328(5984), pp.1394-1398
    Description: Gamma-interferon-inducible lysosomal thiolreductase (GILT) promotes major histocompatibility complex (MHC) class II—restricted presentation of exogenous antigens containing disulfide bonds. Here, we show that GILT also facilitates MHC class I—restricted recognition of such antigens by CDe⁺ T cells, or cross-presentation. GILT is essential for cross-presentation of a CD8⁺ T cell epitope of glycoprotein B (gB) from herpes simplex virus 1 (HSV-1) but not for its presentation by infected cells. Initiation of the gB-specific CD8⁺ T cell response during HSV-1 infection, or cross-priming, is highly GILT-dependent, as is initiation of the response to the envelope glycoproteins of influenza A virus. Efficient crosspresentation of disulfide-rich antigens requires a complex pathway involving GILT-mediated reduction, unfolding, and partial proteolysis, followed by translocation into the cytosol for proteasomal processing.
    Keywords: Biological sciences -- Biology -- Physiology -- Lymphocytes ; Health sciences -- Medical sciences -- Immunology -- Epitopes ; Health sciences -- Medical sciences -- Immunology -- Epitopes ; Biological sciences -- Biology -- Cytology -- Epitopes ; Biological sciences -- Biology -- Microbiology -- Epitopes ; Health sciences -- Medical sciences -- Immunology -- Epitopes ; Physical sciences -- Physics -- Microphysics -- Epitopes ; Biological sciences -- Biology -- Cytology -- Epitopes ; Biological sciences -- Biochemistry -- Biomolecules -- Epitopes ; Biological sciences -- Biology -- Microbiology -- Epitopes
    ISSN: 00368075
    E-ISSN: 10959203
    Source: Archival Journals (JSTOR)
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  • 4
    Language: English
    In: Cancer Research, 04/15/2012, Vol.72(8 Supplement), pp.5243-5243
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 5
    Language: English
    In: Cancer Research, 04/15/2012, Vol.72(8 Supplement), pp.5241-5241
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 6
    Language: English
    Keywords: Environmental Energy Technologies
    Source: eScholarship
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  • 7
    Language: English
    In: Bioorganic & Medicinal Chemistry Letters, 2010, Vol.20(7), pp.2306-2310
    Description: Heterocyclic benzimidazole derivatives and have been synthesized by via microwave irradiation in good yields and their evaluation for anti-inflammatory and anticancer activity is reported. Heterocyclic benzimidazole derivatives – , – and – have been synthesized by condensation of succinic acid ( ) homophthalic acid ( ) and 2,3-pyrazinedicarboxlic acid ( ) with various substituted diamines under microwave irradiation in good yields. Structures assigned to – , – and – are fully supported by spectral data. All these compounds were screened for anti-inflammatory and anticancer activities. At a dose of 50 mg/kg po compounds (39.4%) and (39.2%) exhibited anti-inflammatory activity, comparable to standard ibuprofen which showed 39% activity at 50 mg/kg po and compound exhibit good anticancer activity against ovary (IGR-OV-1), breast (MCF-7) and CNS(SF-295) human cancer cell lines.
    Keywords: Benzimidazole ; Heterocyclic ; Anti-Inflammatory ; Anticancer ; Microwave ; Medicine ; Chemistry ; Anatomy & Physiology
    ISSN: 0960-894X
    E-ISSN: 1464-3405
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  • 8
    In: Nature, 2008, Vol.455(7217), p.1244
    Description: Listeria monocytogenes is a Gram-positive, intracellular, food-borne pathogen that can cause severe illness in humans and animals. On infection, it is actively phagocytosed by macrophages; it then escapes from the phagosome, replicates in the cytosol, and subsequently spreads from cell to cell by a non-lytic mechanism driven by actin polymerization. Penetration of the phagosomal membrane is initiated by the secreted haemolysin listeriolysin O (LLO), which is essential for vacuolar escape in vitro and for virulence in animal models of infection. Reduction is required to activate the lytic activity of LLO in vitro, and we show here that reduction by the enzyme -interferon-inducible lysosomal thiol reductase (GILT, also called Ifi30) is responsible for the activation of LLO in vivo. GILT is a soluble thiol reductase expressed constitutively within the lysosomes of antigen-presenting cells, and it accumulates in macrophage phagosomes as they mature into phagolysosomes. The enzyme is delivered by a mannose-6-phosphate receptor-dependent mechanism to the endocytic pathway, where amino- and carboxy-terminal pro-peptides are cleaved to generate a 30-kDa mature enzyme. The active site of GILT contains two cysteine residues in a CXXC motif that catalyses the reduction of disulphide bonds. Mice lacking GILT are deficient in generating major histocompatibility complex class-II-restricted CD4sup + T-cell responses to protein antigens that contain disulphide bonds. Here we show that these mice are resistant to L. monocytogenes infection. Replication of the organism in GILT-negative macrophages, or macrophages expressing an enzymatically inactive GILT mutant, is impaired because of delayed escape from the phagosome. GILT activates LLO within the phagosome by the thiol reductase mechanism shared by members of the thioredoxin family. In addition, purified GILT activates recombinant LLO, facilitating membrane permeabilization and red blood cell lysis. The data show that GILT is a critical host factor that facilitates L. monocytogenes infection. [PUBLICATION ]
    Keywords: Macrophages ; Reduction ; Enzymes ; Thiols ; Reductases ; Mice ; Mathematical Models ; Animals ; Membranes ; Disulfides ; Listeria Monocytogenes ; In Vitro Testing ; Documents ; Spreads ; Biocompatibility ; Proteins ; Virulence ; Penetration ; Activation ; General and Nonclassified (MD) ; General and Nonclassified (EC) ; General and Nonclassified (Ed) ; General and Nonclassified (Ep) ; Surveying, Theory, and Analysis (CE) ; Design Principles, Theory, and Analysis (Mt) ; Computing Milieux (General) (Ci) ; Electronics and Communications Milieux (General) (Ea) ; Solid State Milieux (General) (So) ; Article;
    ISSN: 0028-0836
    E-ISSN: 14764687
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  • 9
    Language: English
    In: Filomat, 2017, Vol.31(8), pp.2459-2466
    Description: The Bessel wavelet transform on Xu and Qu type spaces of exponential growth are investigated and their properties discussed by using the theory of the Hankel transform. Using this said theory, the integral equation of Fredholm type is defined and some examples associated with this integral equation are given.
    Keywords: Mathematics;
    ISSN: 0354-5180
    E-ISSN: 2406-0933
    Source: CrossRef
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  • 10
    In: Rapid Communications in Mass Spectrometry, 15 April 2017, Vol.31(7), pp.631-638
    Description: Byline: Reshma Singh, Louis W. Bezuidenhout, Abebaw Jemere, Zhen Wang, Michael Brett, D. Jed Harrison Rationale Thin, nanoporous films fabricated using Glancing Angle Deposition (GLAD) technology are demonstrated for solid matrix laser desorption/ionization mass spectrometry (SMALDI-MS). GLAD allows facile engineering of nanoporosity, film thickness, post alignment, and material composition, as demonstrated here by the fabrication of Co-GLAD and Si-GLAD films for SMALDI, and by exploration of the SMALDI performance as a function of thickness, post density, and angle of the post relative to surface normal. Methods GLAD films were prepared by electron beam evaporation onto silicon substrates, using steep angles of incidence for the vacuum deposition, with computer controlled substrate rotation. LDI from the GLAD films was evaluated using an MDS-Sciex time-of-flight (TOF) MALDI mass spectrometer. Results Co-GLAD films give a limit of quantitation of 6 fmol for complex carbohydrate derivatives, and slanted-post Si-GLAD films show up to three times higher sensitivity than vertical post structures. Reproducibility of both Si and Co films is much higher than conventional MALDI methods for m/z below at least 2100 Da. Both reproducibility and detection limits are comparable to or better than other nano-structured materials. Co-GLAD films are significantly better in performance than Co powders or Co thin films on silicon substrates previously evaluated. Conclusions The flexibility of GLAD for thin film fabrication of LDI materials is demonstrated by the range of nanoporous materials that can be grown, and the fine control over structural conformation, thickness and porosity. Copyright [c] 2017 John Wiley & Sons, Ltd. CAPTION(S): Supplemental Fig. 1. Absorption of Co films at 337 nm wavelength as a function of film thickness, deposited at 88[degrees]. Supplemental Fig. 2. Signal to noise ratio (S/N) for 1 pmol verapamil obtained from Co GLAD films as a function of film thickness, using the same laser intensity for each film. Supplemental Fig. 3. Determination of the optimum arbitrary laser fluence for 250 nm thick Co films deposited at 88[degrees], using 10 pmol verapamil samples. Supplemental Fig. 4. Relative peak intensity (maximum intensity =100%) from 15 different sample spots on 250 nm Co GLAD films. Results are shown for 100 shots averaged on each spot, and for a single shot on each spot. Supplemental Fig. 5. A) SMALDI Mass spectrum of [beta] cyclodextrin, and B) SMALDI Mass spectrum of triacetyl [beta] cyclodextrin. Both taken using a 250 nm thick Co GLAD film deposited at 88[degrees], with added Na+. See supplemental information Fig. 6 for structures. Supplemental Fig. 6. Chemical structures of [beta] cyclodextrin and triacetyl-[beta] cyclodextrin
    Keywords: Mass Spectrometry ; Silicon ; Thin Films;
    ISSN: 0951-4198
    E-ISSN: 1097-0231
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