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  • 1
    Publication Date: 2018-05-30
    Description: As a virus-encoded actin nucleation promoting factor (NPF), P78/83 induces actin polymerization to assist in Autographa californica multiple nucleopolyhedrovirus (AcMNPV) propagation. According to our previous study, although P78/83 actively undergoes ubiquitin-independent proteasomal degradation, AcMNPV encodes budded virus/occlusion derived virus (BV/ODV)-C42 (C42), which allows P78/83 to function as a stable NPF by inhibiting its degradation during viral infection. However, whether there are other viral proteins involved in regulating P78/83-induced actin polymerization has yet to be determined. In this study, we found that Ac102, an essential viral gene product previously reported to play a key role in mediating the nuclear accumulation of actin during AcMNPV infection, is a novel regulator of P78/83-induced actin polymerization. By characterizing an ac102 knockout bacmid, we demonstrated that Ac102 participates in regulating nuclear actin polymerization as well as the morphogenesis and distribution of capsid structures in the nucleus. These regulatory effects are heavily dependent on an interaction between Ac102 and C42. Further investigation revealed that Ac102 binds to C42 to suppress K48-linked ubiquitination of C42, which decreases C42 proteasomal degradation and consequently allows P78/83 to function as a stable NPF to induce actin polymerization. Thus, Ac102 and C42 form a regulatory cascade to control viral NPF activity, representing a sophisticated mechanism for AcMNPV to orchestrate actin polymerization in both a ubiquitin-dependent and ubiquitin-independent manner. IMPORTANCE Actin is one of the most functionally important proteins in eukaryotic cells. Morphologically, actin can be found in two forms: a monomeric form called globular actin (G-actin) and a polymeric form called filamentous actin (F-actin). G-actin can polymerize to form F-actin, and nucleation promoting factor (NPF) is the initiator of this process. Many viral pathogens harness the host actin polymerization machinery to assist in virus propagation. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) induces actin polymerization in host cells. P78/83, a viral NPF, is responsible for this process. Previously, we identified that BV/ODV-C42 (C42) binds to P78/83 and protects it from degradation. In this report, we determined that another viral protein, Ac102, is involved in modulating C42 ubiquitination and, consequently, ensures P78/83 activity as an NPF to initiate actin polymerization. This regulatory cascade represents a novel mechanism by which a virus can harness the cellular actin cytoskeleton to assist in viral propagation.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 2
    Publication Date: 2018-09-21
    Description: Perovskite solar cells (PSCs) have witnessed rapidly rising power conversion efficiencies, together with advances in stability and upscaling. Despite these advances, their limited stability and need to prove upscaling remain crucial hurdles on the path to commercialization. We summarize recent advances toward commercially viable PSCs and discuss challenges that remain. We expound the development of standardized protocols to distinguish intrinsic and extrinsic degradation factors in perovskites. We review accelerated aging tests in both cells and modules and discuss the prediction of lifetimes on the basis of degradation kinetics. Mature photovoltaic solutions, which have demonstrated excellent long-term stability in field applications, offer the perovskite community valuable insights into clearing the hurdles to commercialization.
    Keywords: Physics, Applied, Chemistry, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2018-07-05
    Description: Metastatic cancer is considered a fatal progression of cancer worldwide. It has been shown that a key player in this scenario is the CXC chemokine receptor 2 (CXCR2). To identify novel CXCR2 antagonists, a pharmacophore model was built with the H ip H op program by screening a database containing compounds which were designed based on the known structure–activity relationship (SAR) of the diarylurea series CXCR2 antagonists. Compound 1a bearing the novel skeleton was selected from database screening and subjected to the in vitro biological test which showed a moderate CXCR2 antagonist potential. With further modification and exploration of SAR, compound 1e demonstrated improved CXCR2 antagonist activity with an IC 50 value of 14.8 µM. Furthermore, wound healing assay using the NCI-H1299 cell line indicated that 1e showed an excellent anti-cancer metastatic effect (72% inhibition in cell migration at 50 µg ml –1 ).
    Keywords: medicinal chemistry, computer-aided design
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  83. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20120516-20120520; Mainz; DOC12hnod332 /20120404/
    Publication Date: 2012-04-05
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Meteorology and atmospheric physics 51 (1993), S. 227-235 
    ISSN: 1436-5065
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Summary A model of the polluted arctic troposphere is constructed to estimate the magnitude and seasonal variation of the climate forcing function of arctic haze. Using a pill-box “bathtub model” for the Arctic and envisioning it to be filled with pollution from industrial sources in Eurasia, we estimate that maximum climate perturbation from arctic contamination occurs in the spring months. The major perturbation to the radiation budget is a lowering of the albedo (heating) of the earth-atmosphere system around the vernal equinox and is due to a trace amount (about 5% by mass) of black carbon associated with the removal-resistant submicron mode of aerosols. The black carbon over the reflecting polar ice/snow introduces a heating of about 1.5 degree per day into the haze layer.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Infection 19 (1991), S. 174-177 
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Resistenzmechanismen gegen Trimethoprim wurden bei 11 britischen Isolaten vonHaemophilus influenzae untersucht. Die Dihydrofolat-Reduktase-Aktivitäten in ungereinigten Extrakten aus vier resistenten Wildtyp-Stämmen waren mit denen empfindlicher Kontrollen vergleichbar. Dagegen waren die Enzymaktivitäten in den Extrakten aus den anderen sieben Wildtyp-Isolaten und aus Transformanten zwei dieser Stämme mindestens dreimal so hoch wie bei empfindlichen Stämmen. Gegen Trimethoprim resistente Stämme wurdenin vitro bei längerer Exposition gegenüber der Substanz selektiert. Die Resistenz der Mutanten war mit erhöhter Dihydrofolat-Reduktase-Aktivität assoziiert. Dennoch waren die Dihydrofolat-Reduktasen jeweils sehr gut durch Trimethoprim hemmbar. Nach Inkubation mit 10−8M Trimethoprim wurden die Enzymaktivitäten in den vier Extrakten einschließlich dem Extrakt aus dem Transformanten einer resistenten Mutante um mindestens 45% reduziert. Nach diesen Ergebnissen ist möglicherweise die Überproduktion des chromosomal kodierten Enzyms Dihydrofolat-Reduktase bei einigen Stämmen für die Resistenz verantwortlich. Die sehr viel niedrigeren Dihydrofolat-Reduktase-Aktivitäten in Extrakten anderer resistenter Isolate könnten darauf beruhen, daß in diesen Stämmen chromosomal kodierte Enzyme mit verminderter Empfindlichkeit gegenüber Trimethoprim gebildet werden.
    Notes: Summary The mechanisms of resistance to trimethoprim in eleven U.K. clinical isolates ofHaemophilus influenzae were studied. The levels of dihydrofolate reductase (DHFR) activities in crude extracts from four resistant wild-types were similar to those in susceptible controls. However, activities in extracts from the other seven resistant wild-type isolates, and transformants of two of these, were at least triple those in the sensititive strains. Resistance to trimethoprim was also selected forin vitro during prolonged exposure to the drug and was associated with increased levels of DHFR specific activity in the mutants. DHFR enzymes were, however, still very susceptible to inhibition by trimethoprim. Activities in four extracts, including one from a transformant of a resistant mutant, were reduced by at least 45% following incubation with 10−8 M trimethoprim. The results suggested that overproduction of the chromosomal DHFR enzyme may be the resistance mechanism in some organisms. The much lower DHFR activities measured in extracts from other resistant isolates may reflect synthesis of chromosomal enzymes that have reduced susceptibility to trimethoprim.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1279-8517
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1420-9071
    Keywords: Key words. Rheumatoid arthritis; interleukin 1; tumor necrosis factor; cytokine; rat; adjuvant arthritis; IL-1ra; soluble receptor.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) play dominant roles in mediating the progression of many inflammatory joint diseases, including rheumatoid arthritis in humans, collagen-induced arthritis in mice and rats, and adjuvant arthritis in rats. Blockade of either cytokine partially controls these diseases. The present study investigated the value of combination anti-cytokine therapy in arthritis: the efficacy of IL-1 receptor antagonist (IL-1ra) and 30 kDa polyethylene glycol (PEG)-conjugated soluble TNF receptor type I (PEG sTNF-RI) given together was assessed in Lewis rats with adjuvant arthritis. Administration of either IL-1ra or PEG sTNF-RI partially alleviated joint inflammation, loss of bone mineral density, and loss of body weight. In contrast, combination of these anti-cytokine treatments exhibited a synergistic capacity to inhibit these changes, even when combining doses of IL-1ra and PEG sTNF-RI that did not affect lesion severity when used alone. Statistical analysis of these adjuvant arthritis data using the isobologram method proved that IL-1ra and PEG sTNF-RI were clearly synergistic in inhibiting inflammation, loss of bone mineral density, loss of body weight, and histopathologic parameters of inflammation and joint destruction. These results suggest that treating autoimmune arthritic diseases with combinations of anti-IL-1 and anti-TNF molecules will achieve superior efficacy compared to the use of a single class of anti-cytokine agent and may allow for dose reductions that could prove useful in minimizing potential side effects.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1279-8517
    Keywords: Iliac crest flap ; Iliolumbar artery ; Anatomy ; Clinical application
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This paper presents the anatomy and clinical applications of an iliac crest flap pedicled on the iliolumbar artery. 54 iliolumbar arteries were filled with pink plastic in 27 adult cadavers. Their origin, course and branches, and the surroundings were investigated, and the external diameter, length of segments and terminal distribution were measured. The iliolumbar artery was constant, but with a few variations. Its length was 7.0 ± 3.9 cm, and the outer diameter 2.0 ± 0.4 mm at the lateral edge of the psoas major muscle. Based on the anatomic findings, the surgical technique for a bone flap based on the iliolumbar artery was designed. Its clinical applications included both free bone grafting (in 2 patients) and pedicled bone transfer (in another 2 patients). The clinical results were satisfactory. The iliac crest flap pedicled on the iliolumbar artery is a reliable bone flap for clinical usage.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1279-8517
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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