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  • Springer  (4)
  • BMJ Publishing Group  (1)
  • 2015-2019  (1)
  • 1975-1979  (3)
  • 1960-1964
  • 1950-1954  (1)
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  • 1
    Publication Date: 2018-02-09
    Description: Objective The stability of the covalently closed circular DNA (cccDNA) in nuclei of non-dividing hepatocytes represents a key determinant of HBV persistence. Contrarily, studies with animal hepadnaviruses indicated that hepatocyte turnover can reduce cccDNA loads but knowledge on the proliferative capacity of HBV-infected primary human hepatocytes (PHHs) in vivo and the fate of cccDNA in dividing PHHs is still lacking. This study aimed to determine the impact of human hepatocyte division on cccDNA stability in vivo. Methods PHH proliferation was triggered by serially transplanting hepatocytes from HBV-infected humanised mice into naïve recipients. Cell proliferation and virological changes were assessed by quantitative PCR, immunofluorescence and RNA in situ hybridisation. Viral integrations were analysed by gel separation and deep sequencing. Results PHH proliferation strongly reduced all infection markers, including cccDNA (median 2.4 log/PHH). Remarkably, cell division appeared to cause cccDNA dilution among daughter cells and intrahepatic cccDNA loss. Nevertheless, HBV survived in sporadic non-proliferating human hepatocytes, so that virological markers rebounded as hepatocyte expansion relented. This was due to reinfection of quiescent PHHs since treatment with the entry inhibitor myrcludex-B or nucleoside analogues blocked viral spread and intrahepatic cccDNA accumulation. Viral integrations were detected both in donors and recipient mice but did not appear to contribute to antigen production. Conclusions We demonstrate that human hepatocyte division even without involvement of cytolytic mechanisms triggers substantial cccDNA loss. This process may be fundamental to resolve self-limiting acute infection and should be considered in future therapeutic interventions along with entry inhibition strategies.
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 2
    ISSN: 1434-6036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Quench condensed binary alloy films are produced by evaporation from two separated furnaces. The films contain the whole composition range of the respective alloy system in well defined arrangement.T c is measured as a function of concentration. Eight predominantly amorphous alloy systems are studied: Bi—Ga, Pb—Ga, Pb—Bi, Be—Bi, Be—Pb, Be—Ga, Be—Al, Be—Li. In Bi—Ga and Pb—GaT c is a linear function of concentration in the amorphous composition range. In Pb—BiT c has a maximum. All Be-alloys show lower transition temperatures than pure quench condensed Be. Except for Be—Li all systems have aT c minimum. The experiments are compared to aT c calculation using tunelling spectroscopy data. Except for the Be-alloys the agreement is satisfying.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1572-9540
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Radioactive119In+ ions (T 1/2=2.1 min) obtained from the ISOLDE facility at CERN have been implanted into silicon single crystals at room temperature. Mössbauer emission spectra from the 24 keV γ-radiation of the daughter119Sn have been measured by fast resonance-counting technique. Five independent lines, characterized by their hyperfine parameters and Debye temperatures, have been found in the spectra. From the bonding configurations, deduced for the Sn impurity atoms, these are concluded to be located in four different defects in the silicon lattice. Simple models are proposed for the defects.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Lung 102 (1950), S. 512-518 
    ISSN: 1432-1750
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1435-1528
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Summary In this paper the proposal ofJackson andKaye is revised enabling one to determine both normal stress differences by measuring the axial thrust in a coneplate-distance rheometer. With two polymer melts it has been demonstrated that this technique yields reliable results. Within the operating range of the rheometer $$(\dot \gamma = 0,1...50sec^{ - 1} )$$ the first normal stress difference is positive. The second normal stress difference is shown to be zero up to $$\dot \gamma = 2sec^{ - 1} $$ and negative without doubt for values $$\dot \gamma 〉 2sec^{ - 1} $$ . According to our experiments one has to be very careful about misinterpreting deviations from viscometric flow at higher shear rates as second normal stress differences. For all experiments aWeissenberg Rheogoniometer has been employed with a new developed thrust measuring and temperature control device.
    Notes: Zusammenfassung Im Rahmen dieser Arbeit wird die vonJackson undKaye vorgeschlagene Kegel-Platte-Abstand-Methode überarbeitet, mit der es möglich ist, aneiner Meßprobe ohne Systemwechsel unter Anwendung nureiner Kraft-Meßmethodebeide Normalspannungsfunktionen zu ermitteln. An zwei Hochpolymeren wird gezeigt, daß die Kegel-Platte-Abstand-Anordnung in Verbindung mit einer hier entwickelten EDV-Auswertemethode ausreichend genau ist. Im gesamten Meßbereich $$(\dot \gamma = 0,1...50sek^{ - 1} )$$ werden für die erste Normalspannungsfunktion eindeutig positive Werte gefunden. Die zweite Normalspannungsfunktion ergibt sich im unteren Scherbereich $$(\dot \gamma〈 2sek^{ - 1} )$$ praktisch zu Null und oberhalb eindeutig als negative Meßgröße. Die Ergebnisse schließen aber nicht aus, daß allein die Abweichungen von der parallelen Schichtenströmung als Ursache für die rheometrisch ermittelten zweiten Normalspannungsdifferenzen verantwortlich sind. Für die Messungen wurde einWeißenberg-Rheogoniometer verwendet, für das die Kraftmeß- und Temperiereinrichtung neu entwickelt wurden.
    Type of Medium: Electronic Resource
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