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  • 1
    Publication Date: 2014-09-23
    Description: Viral infectivity factor (Vif) is required for lentivirus fitness and pathogenicity, except in equine infectious anemia virus (EIAV). Vif enhances viral infectivity by a Cullin5-Elongin B/C E3 complex to inactivate the host restriction factor APOBEC3. Core-binding factor subunit beta (CBF-β) is a cell factor that was recently shown to be important for the primate lentiviral Vif function. Non-primate lentiviral Vif also degrades APOBEC3 through the proteasome pathway. However, it is unclear whether CBF-β is required for the non-primate lentiviral Vif function. In this study, we demonstrated that the Vifs of non-primate lentiviruses, including feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), caprine arthritis encephalitis virus (CAEV), and maedi-visna virus (MVV), do not interact with CBF-β. In addition, CBF-β did not promote the stability of FIV, BIV, CAEV, and MVV Vifs. Furthermore, CBF-β silencing or overexpression did not affect non-primate lentiviral Vif-mediated APOBEC3 degradation. Our results suggest that non-primate lentiviral Vif induces APOBEC3 degradation through a different mechanism than primate lentiviral Vif. IMPORTANCE The APOBEC3 protein family members are host restriction factors that block retrovirus replication. Vif, an accessory protein of lentivirus, degrades APOBEC3 to rescue viral infectivity by forming Cullin5-Elongin B/C-based E3 complex. CBF-β was proved to be a novel regulator of primate lentiviral Vif function. In this study, we found that CBF-β knockdown or overexpression did not affect FIV Vif's function, which induced polyubiquitination and degradation of APOBEC3 by recruiting the E3 complex in a manner similar to that of HIV-1 Vif. We also showed that other non-primate lentiviral Vifs did not require CBF-β to degrade APOBEC3. CBF-β did not interact with non-primate lentiviral Vifs or promote their stability. These results suggest that a different mechanism exists for the Vif-APOBEC interaction and that non-primates are not suitable animal models for exploring pharmacological interventions that disrupt Vif–CBF-β interaction.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 2
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 19 (1996), S. 111-116 
    ISSN: 0935-6304
    Keywords: Polynuclear aromatic hydrocarbons ; Liquid chromatography ; Alcohols ; Micelles ; Enviromental samples ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A method for the separation of polycyclic aromatic hydrocarbons (PAHs) by high-performance liquid chromatography using a hybrid micellar mobile phase is described. The detection of PAHs was carried out using the fluorescence method with programmable excitation and emission wavelength. The method is applied to the analysis of several environmental samples (sea water, sediments, limpets, sea worms) and several of these compounds are quantitated at concentration below 70 ng L-1(kg-1) in the original samples.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Stamford, Conn. [u.a.] : Wiley-Blackwell
    Polymer Engineering and Science 30 (1990), S. 30-43 
    ISSN: 0032-3888
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: New block copolymers of polystyrene with polyesters have been synthesized and investigated as compatibilizing agents. The addition of block copolymers in immiscible blends of polybutylene terephthalate and (i) polystyrene, (ii) polystyrene/poly(2,6-dimethyl 1,4-phenylene oxide) as well as (iii) high impact polystyrene drastically reduced the dimensions of the dispersed phase and stabilized the phase growth with annealing time. Stress-strain curves for the binary blends indicate brittle behavior. The addition of more than 10 wt% of block copolymers transforms their brittle characteristics to ductile behavior.
    Additional Material: 14 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 52 (1994), S. 651-655 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This theoretical study was to determine the relative stability of the different species proposed experimentally and to establish which of the two pathways suggested is the most probable. A conformational study of the geometries of the stable compounds has been carried out using the semiempirical quantum mechanic method AM1. © 1994 John Wiley & Sons, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Publication Date: 2011-10-14
    Description: In 2009 and 2010, the Cassini spacecraft made seven targeted Enceladus flybys along trajectories parallel to the equatorial plane. The magnetometer on board Cassini made a complete set of vector field distribution measurements on these tracks and observed significant perturbations that further constrained the location of the momentum-exchange region. These observations were made not only above and below the moon Enceladus, but also above and below the momentum-loading center. The observed field perturbations are consistent with previous interpretations of the interaction. Southernly-biased Io-type, Alfvén-wing signatures are penetrated by Cassini. In addition to the draping due to the slowing down, the magnetic field drapes away from Saturn, indicating that the dust in the plume is predominantly negatively charged. No Saturnward or anti-Saturnward tilt of the plume is identified.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
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  • 6
    Publication Date: 2018-06-01
    Description: Staphylococcus aureus is the main pathogen that causes skin and skin structure infections and is able to survive and persist in keratinocytes of the epidermis. Since the evolution of multidrug-resistant bacteria, the use of phages and their lysins has presented a promising alternative approach to treatment. In this study, a cell wall hydrolase (also called lysin) derived from Staphylococcus phage JD007 (JDlys) was identified. JDlys showed strong lytic activity against methicillin-resistant Staphylococcus aureus (MRSA) strains from different sources and of different multilocus sequence typing (MLST) types. Furthermore, a fusion protein consisting of a cell-penetrating peptide derived from the trans -activating transcription (Tat) factor fused to JDlys (CPP Tat -JDlys) was used to kill MRSA bacteria causing intracellular infections. CPP Tat -JDlys, in which the fusion of CPP Tat to JDlys had almost no effect on the bacteriolytic activity of JDlys, was able to effectively eliminate intracellular MRSA bacteria and alleviate the inflammatory response and cell damage caused by MRSA. Specifically, CPP Tat -JDlys was able to combat MRSA-induced murine skin infections and, consequently, expedite the healing of cutaneous abscesses. These data suggest that the novel antimicrobial CPP-JDlys may be a worthwhile candidate as a treatment for skin and skin structure infections caused by MRSA. IMPORTANCE S. aureus is the main cause of skin and skin structure infections due to its ability to invade and survive in the epithelial barrier. Due to the overuse of antibiotics in humans and animals, S. aureus has shown a high capacity for acquiring and accumulating mechanisms of resistance to antibiotics. Moreover, most antibiotics are usually limited in their ability to overcome the intracellular persistence of bacteria causing skin and skin structure infections. So, it is critical to seek a novel antimicrobial agent to eradicate intracellular S. aureus . In this study, a cell-penetrating peptide fused to lysin (CPP-JDlys) was engineered. Our results show that CPP-JDlys can enter keratinocytes and effectively eliminate intracellular MRSA. Meanwhile, experiments with mice revealed that CPP-JDlys efficiently inhibits the proliferation of MRSA in murine skin and thus shortens the course of wound healing. Our results indicate that the CPP-fused lysin has potential for use for the treatment of skin infections caused by MRSA.
    Print ISSN: 0099-2240
    Electronic ISSN: 1098-5336
    Topics: Biology
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  • 7
    Publication Date: 2018-06-22
    Description: Streptococcus suis has received increasing attention for its involvement in severe human infections worldwide as well as in multidrug resistance. Two-component signaling systems (TCSSs) play important roles in bacterial adaptation to various environmental stimuli. In this study, we identified a novel TCSS located in S. suis serotype 2 (SS2), designated VraSR SS , which is involved in bacterial pathogenicity and susceptibility to antimicrobials. Our data demonstrated that the yvqF SS gene, located upstream of vraSR SS , shared the same promoter with the TCSS genes, which was directly regulated by VraSR SS , as shown in electrophoretic mobility shift assays. Notably, YvqF SS and VraSR SS constitute a novel multidrug resistance module of SS2 that participates in resistance to certain groups of antimicrobials. Further analyses showed that VraSR SS inactivation significantly attenuated bacterial virulence in animal models, which, coupled with the significant activation of VraSR SS expression observed in host blood, strongly suggested that VraSR SS is an important regulator of SS2 pathogenicity. Indeed, RNA-sequencing analyses identified 106 genes that were differentially expressed between the wild-type and vraSR SS strains, including genes involved in capsular polysaccharide (CPS) biosynthesis. Subsequent studies confirmed that VraSR SS indirectly regulated the transcription of CPS gene clusters and, thus, controlled the CPS thickness shown by transmission electron microscopy. Decreased CPS biosynthesis caused by vraSR SS deletion subsequently increased bacterial adhesion to epithelial cells and attenuated antiphagocytosis against macrophages, which partially clarified the pathogenic mechanism mediated by VraSR SS . Taken together, our data suggest that the novel TCSS, VraSR SS , plays critical roles for multidrug resistance and full virulence in SS2.
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
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  • 8
    Publication Date: 2018-03-29
    Description: The group of highly related avian leukosis viruses (ALVs) in chickens are thought to have evolved from a common retroviral ancestor into six subgroups, A to E and J. These ALV subgroups use diverse cellular proteins encoded by four genetic loci in chickens as receptors to gain entry into host cells. Hosts exposed to ALVs might be under selective pressure to develop resistance to ALV infection. Indeed, resistance alleles have previously been identified in all four receptor loci in chickens. The tvb gene encodes a receptor, which determines the susceptibility of host cells to ALV subgroup B (ALV-B), ALV-D, and ALV-E. Here we describe the identification of two novel alleles of the tvb receptor gene, which possess independent insertions each within exon 4. The insertions resulted in frameshift mutations that reveal a premature stop codon that causes nonsense-mediated decay of the mutant mRNA and the production of truncated Tvb protein. As a result, we observed that the frameshift mutations in the tvb gene significantly lower the binding affinity of the truncated Tvb receptors for the ALV-B, ALV-D, and ALV-E envelope glycoproteins and significantly reduce susceptibility to infection by ALV-B, ALV-D and ALV-E in vitro and in vivo . Taken together, these findings suggest that frameshift mutation can be a molecular mechanism of reducing susceptibility to ALV and enhance our understanding of virus-host coevolution. IMPORTANCE Avian leukosis virus (ALV) once caused devastating economic loss to the U.S. poultry industry prior the current eradication schemes in place, and it continues to cause severe calamity to the poultry industry in China and Southeast Asia, where deployment of a complete eradication scheme remains a challenge. The tvb gene encodes the cellular receptor necessary for subgroup B, D, and E ALV infection. Two tvb allelic variants that resulted from frameshift mutations have been identified in this study, which have been shown to have significantly reduced functionality in mediating subgroup B, D, and E ALV infection. Unlike the control of herpesvirus-induced diseases by vaccination, the control of avian leukosis in chickens has relied totally on virus eradication measures and host genetic resistance. This finding enriches the allelic pool of the tvb gene and expands the potential for genetic improvement of ALV resistance in varied chicken populations by selection.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 9
    Publication Date: 2013-11-20
    Description: The development of a safe and efficient dengue vaccine represents a global challenge in public health. Chimeric dengue viruses (DENV) based on an attenuated flavivirus have been well developed as vaccine candidates by using reverse genetics. In this study, based on the full-length infectious cDNA clone of the well-known Japanese encephalitis virus live vaccine strain SA14-14-2 as a backbone, a novel chimeric dengue virus (named ChinDENV) was rationally designed and constructed by replacement with the premembrane and envelope genes of dengue 2 virus. The recovered chimeric virus showed growth and plaque properties similar to those of the parental DENV in mammalian and mosquito cells. ChinDENV was highly attenuated in mice, and no viremia was induced in rhesus monkeys upon subcutaneous inoculation. ChinDENV retained its genetic stability and attenuation phenotype after serial 15 passages in cultured cells. A single immunization with various doses of ChinDENV elicited strong neutralizing antibodies in a dose-dependent manner. When vaccinated monkeys were challenged with wild-type DENV, all animals except one that received the lower dose were protected against the development of viremia. Furthermore, immunization with ChinDENV conferred efficient cross protection against lethal JEV challenge in mice in association with robust cellular immunity induced by the replicating nonstructural proteins. Taken together, the results of this preclinical study well demonstrate the great potential of ChinDENV for further development as a dengue vaccine candidate, and this kind of chimeric flavivirus based on JE vaccine virus represents a powerful tool to deliver foreign antigens.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 10
    Publication Date: 2012-10-07
    Description: Subgroup J avian leukosis virus (ALV-J) isolate GDKP1202 was isolated from a 50-day-old local yellow commercial broiler in the Guangdong province of China in 2012. Here we report the complete genomic sequence of the GDKP1202 isolate, which caused high mortality, serious growth suppression, thymic atrophy, and liver enlargement in commercial broilers. A novel potential binding site (5'-GGCACCTCC-3') for c- myb was identified in the GDKP1202 genome. These findings will provide additional insights into the molecular characteristics in the genomes and pathogenicity of ALV-J.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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