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Berlin Brandenburg

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  • 1
    Language: English
    In: PLoS ONE, 2011, Vol.6(4), p.e18577
    Description: H5N1 influenza vaccines, including live intranasal, appear to be relatively less immunogenic compared to seasonal analogs. The main influenza virus surface glycoprotein hemagglutinin (HA) of highly pathogenic avian influenza viruses (HPAIV) was shown to be more susceptible to acidic pH treatment than that of human or low pathogenic avian influenza viruses. The acidification machinery of the human nasal passageway in response to different irritation factors starts to release protons acidifying the mucosal surface (down to pH of 5.2). We hypothesized that the sensitivity of H5 HA to the acidic environment might be the reason for the low infectivity and immunogenicity of intranasal H5N1 vaccines for mammals. ; We demonstrate that original human influenza viruses infect primary human nasal epithelial cells at acidic pH (down to 5.4), whereas H5N1 HPAIVs lose infectivity at pH≤5.6. The HA of A/Vietnam/1203/04 was modified by introducing the single substitution HA2 58K→I, decreasing the pH of the HA conformational change. The H5N1 reassortants containing the indicated mutation displayed an increased resistance to acidic pH and high temperature treatment compared to those lacking modification. The mutation ensured a higher viral uptake as shown by immunohistochemistry in the respiratory tract of mice and 25 times lower mouse infectious dose. Moreover, the reassortants keeping 58K→I mutation designed as a live attenuated vaccine candidate lacking an NS1 gene induced superior systemic and local antibody response after the intranasal immunization of mice. ; Our finding suggests that an efficient intranasal vaccination with a live attenuated H5N1 virus may require a certain level of pH and temperature stability of HA in order to achieve an optimal virus uptake by the nasal epithelial cells and induce a sufficient immune response. The pH of the activation of the H5 HA protein may play a substantial role in the infectivity of HPAIVs for mammals.
    Keywords: Research Article ; Biology ; Medicine ; Virology ; Immunology ; Infectious Diseases
    E-ISSN: 1932-6203
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  • 2
    In: Pigment Cell & Melanoma Research, August 2011, Vol.24(4), pp.656-665
    Description: Human endogenous retroviruses (HERVs) represent a cellular reservoir of potentially pathogenic retroviral genes. A growing body of evidence indicates that the activation of endogenous retroviral sequences might be involved in the transformation of melanocytes. In this study, we investigated the effects of ultraviolet radiation (UVR) on the expression of human endogenous retrovirus type K (HERV‐K) in melanoma cells and non‐melanoma cells in vitro. Solely in melanoma cell lines, irradiation with UVB (200 mJ/cm) resulted in a significant transcriptional activation of the retroviral gene as well as in an enhanced expression of the retroviral envelope protein (env). In addition, UVB treatment induced the production of retroviral particles in the supernatants of melanoma cell lines. These data indicate that HERV‐K expression can be activated by UVB irradiation and suggest an involvement of HERV‐K in UVR‐related melanoma pathogenesis.
    Keywords: Melanoma ; Human Endogenous Retrovirus Type K ; Ultraviolet Radiation
    ISSN: 1755-1471
    E-ISSN: 1755-148X
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  • 3
    Language: English
    In: Waste Management, 2011, Vol.31(5), pp.871-883
    Description: Methane emissions from active or closed landfills can be reduced by means of microbial methane oxidation enhanced by properly designed landfill covers and engineered biocovers. Composts produced using different waste materials have already been proven to support methane oxidation, and may represent a low-cost alternative to other suitable substrates such as sandy or humic-rich soils, which are frequently not available in sufficient amounts or are too costly. In the present study a data set of 30 different compost materials (different age and input materials) and mixtures, as well as seven soils and mineral substrates were tested to assess methane oxidation rate under similar conditions in a laboratory column set-up. Multivariate data analysis (discriminant analysis) was applied to predict the influence of 21 different parameters (chemical, maturation and physical) on methane oxidation rate in a PLS-DA model. The results show that bulk density, total nutrient content (nitrogen and phosphorus), as well as the quantity and quality (with respect to maturity) of organic matter determined methane oxidation rate in this data set. The model explained 50% of the data variation, indicating how characterisation of oxidation rate by single, even diverse conventional parameters was limited. Thus for the first time, Fourier Transform Infrared (FTIR) spectroscopy was applied to a series of samples to better determine the characteristics of methane-oxidising materials. The initial data obtained in this study appear to be most promising. The prediction of specific methane oxidation rate of a potential biocover material from FTIR spectra and multivariate data analyses is a target to be focused on in the future.
    Keywords: Engineering ; Chemistry
    ISSN: 0956-053X
    E-ISSN: 1879-2456
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  • 4
    Language: English
    In: Cancer research, 01 February 2006, Vol.66(3), pp.1658-63
    Description: We previously described the expression of melanoma-associated endogenous retrovirus (MERV) proteins and viral particles in human melanomas and metastases. The objective of the present study was to determine whether a humoral immune response to MERV proteins occurs in melanoma. Candidate B-cell epitopes on MERV proteins were predicted using bioinformatic screening. The reactivity of MERV peptides corresponding to the predicted epitopes with antibodies prevalent in sera of melanoma patients was analyzed. An immunodominant peptide located in the env protein of MERV was identified. Subsequent analyzes using 81 samples from stage I to stage IV melanoma patients and 95 sera from healthy subjects revealed statistically significant differences in seroprevalence of antibodies in melanoma sera samples when compared with reference samples from healthy subjects. The prevalence of anti-MERV antibodies in melanoma patient sera was confirmed by immunofluorescence on env-transfected cells. These data indicate the potential of this candidate peptide as target for diagnosis and immunotherapy.
    Keywords: Biomarkers, Tumor -- Immunology ; Endogenous Retroviruses -- Immunology ; Melanoma -- Virology ; Viral Envelope Proteins -- Immunology
    ISSN: 0008-5472
    E-ISSN: 15387445
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  • 5
    In: Melanoma Research, 2008, Vol.18(5), pp.314-321
    Description: Azidothymidine (AZT), currently used for HIV treatment, was also shown to induce cell growth inhibition and apoptosis in different human tumors. The objective of this study was to investigate the ability of AZT to inhibit the growth of human melanoma cells in vitro and in vivo. In cytotoxicity assays, treatment of cells with varying concentrations of AZT-induced inhibition of cell growth and apoptosis in three human melanoma cell lines without affecting the growth of nontumorigenic cells. AZT-dependent inhibition of proliferation was accompanied by a significant S-phase arrest of the cell cycle. Coexposure of cells to AZT during cisplatin treatment showed a synergistic effect on cytotoxicity. Moreover, AZT monotreatment of melanoma in a severe combined immunodeficiency-mouse xenotransplantation model resulted in significant tumor reduction. These results demonstrate for the first time the antimelanoma activity of AZT, suggesting its clinical utilization either as a sole agent or in combination with other chemotherapeutic agents.
    Keywords: Antineoplastic Agents -- Pharmacology ; Apoptosis -- Drug Effects ; Cell Proliferation -- Drug Effects ; Melanoma -- Drug Therapy ; Zidovudine -- Pharmacology;
    ISSN: 0960-8931
    E-ISSN: 14735636
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  • 6
    Language: English
    In: Virus Research, 2007, Vol.123(2), pp.211-215
    Description: We have shown that melanoma cells produce viral particles that contain sequences which are homologous to human endogenous retroviruses. In this study particles derived from different melanoma cell lines and from melanoma cells of a lymph node metastasis were characterized. We determined the density and the reverse transcriptase (RT) activity of viral particles. Furthermore, we analyzed the sequence variability of multiple clones of each particle preparation. The particles were found to package sequences, which vary for each of the analyzed cell lines. Moreover, even particles derived from the same cell line contain heterologous sequences.
    Keywords: Melanoma ; Herv ; Variability ; Biology
    ISSN: 0168-1702
    E-ISSN: 1872-7492
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  • 7
    Language: English
    In: Vaccine, 11 May 2009, Vol.27(21), pp.2851-7
    Description: We discovered a unique, single amino acid mutation in the influenza B M1 protein promoting viral growth of NS1 truncation mutants in Vero cells. Due to this mutation, we were able to generate an influenza B virus lacking the complete NS1 open reading frame (DeltaNS1-B virus) by reverse genetics, which was growing to titers of 8log(10)TCID(50)/ml in a Vero cell culture-based micro-carrier fermenter. The DeltaNS1-B vaccine candidate was attenuated in IFN-competent hosts such as human alveolar epithelial cells (A549) similar to influenza A DeltaNS1 viruses. In ferrets, the DeltaNS1-B virus was replication-deficient and did not provoke any clinical symptoms. Importantly, a single intranasal immunization of ferrets at a dose as low as 6 log(10)TCID(50)/animal induced a significant HAI response and provided protection against challenge with wild-type influenza B virus. So far, the lack of a DeltaNS1-B virus component growing to high titers in cell culture has been limiting the possibility to formulate a trivalent vaccine based on deletion of the NS1 gene. Our study closes this gap and paves the way for the clinical evaluation of a seasonal, trivalent, live replication-deficient DeltaNS1 intranasal influenza vaccine.
    Keywords: Influenza B Virus -- Immunology ; Influenza Vaccines -- Administration & Dosage ; Viral Nonstructural Proteins -- Immunology
    ISSN: 0264-410X
    E-ISSN: 18732518
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  • 8
    Language: English
    In: Vaccine, 2009, Vol.27(21), pp.2851-2857
    Description: We discovered a unique, single amino acid mutation in the influenza B M1 protein promoting viral growth of NS1 truncation mutants in Vero cells. Due to this mutation, we were able to generate an influenza B virus lacking the complete NS1 open reading frame (ΔNS1-B virus) by reverse genetics, which was growing to titers of 8 log TCID /ml in a Vero cell culture-based micro-carrier fermenter. The ΔNS1-B vaccine candidate was attenuated in IFN-competent hosts such as human alveolar epithelial cells (A549) similar to influenza A ΔNS1 viruses. In ferrets, the ΔNS1-B virus was replication-deficient and did not provoke any clinical symptoms. Importantly, a single intranasal immunization of ferrets at a dose as low as 6 log TCID /animal induced a significant HAI response and provided protection against challenge with wild-type influenza B virus. So far, the lack of a ΔNS1-B virus component growing to high titers in cell culture has been limiting the possibility to formulate a trivalent vaccine based on deletion of the NS1 gene. Our study closes this gap and paves the way for the clinical evaluation of a seasonal, trivalent, live replication-deficient ΔNS1 intranasal influenza vaccine.
    Keywords: Influenza Ns1 Vaccine ; Live-Attenuated Vaccine ; Mucosal Immunization ; Medicine ; Biology ; Veterinary Medicine ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0264-410X
    E-ISSN: 1873-2518
    Source: ScienceDirect Journals (Elsevier)
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  • 9
  • 10
    Language: English
    In: IFAC PapersOnLine, 2015, Vol.48(1), pp.352-353
    Description: Modeling the interaction of fluids with moving, flexible structures is a major and still very challenging subject in the field of multi-physics problems. In this work, an efficient computational approach based on the coupling of modally reduced flexible multibody systems with fluids modeled by means of smoothed particle hydrodynamics is outlined.
    Keywords: Flexible Multibody Dynamics ; Fluid-Structure Interaction ; Generalized Component Mode Synthesis ; Smoothed Particle Hydrodynamics ; Simulator Coupling
    ISSN: 2405-8963
    Source: ScienceDirect Journals (Elsevier)
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