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491.
Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) is an indispensable component of the HCV replication and assembly machineries. Although its precise mechanism of action is not yet clear, current evidence indicates that its structure and function are regulated by the cellular peptidylprolyl isomerase cyclophilin A (CyPA). CyPA binds to proline residues in the C-terminal half of NS5A, in a distributed fashion, and modulates the structure of the disordered domains II and III. Cyclophilin inhibitors (CPIs), including cyclosporine (CsA) and its nonimmunosuppressive derivatives, inhibit HCV infection of diverse genotypes, both in vitro and in vivo. Here we report a mechanism by which CPIs inhibit HCV infection and demonstrate that CPIs can suppress HCV assembly in addition to their well-documented inhibitory effect on RNA replication. Although the interaction between NS5A and other viral proteins is not affected by CPIs, RNA binding by NS5A in cell culture-based HCV (HCVcc)-infected cells is significantly inhibited by CPI treatment, and sensitivity of RNA binding is correlated with previously characterized CyPA dependence or CsA sensitivity of HCV mutants. Furthermore, the difference in CyPA dependence between a subgenomic and a full-length replicon of JFH-1 was due, at least in part, to an additional role that CyPA plays in HCV assembly, a conclusion that is supported by experiments with the clinical CPI alisporivir. The host-directed nature and the ability to interfere with more than one step in the HCV life cycle may result in a higher genetic barrier to resistance for this class of HCV inhibitors. 相似文献
492.
N. Wada Y. Kanda M. Tokuriki K. Kanda 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2000,186(7-8):771-779
We studied neuronal pathways from low-threshold muscle (group I, II) and cutaneous afferents (group A(alpha)beta) innervating the tail to motoneurons innervating trunk muscles (m. iliocostalis lumborum and m. obliquus externus abdominus) in 18 spinalized cats. Stimulation of group I muscle afferents produced excitatory postsynaptic potentials or excitatory postsynaptic potentials followed by inhibitory postsynaptic potentials in all motoneurons innervating the m. iliocostalis lumborum which showed effects (32%), and predominantly inhibitory postsynaptic potentials in motoneurons innervating the m. obliquus externus abdominus (47%). Stimulation of group I+II afferents produced significant increases of the incidence of motoneurons showing postsynaptic potentials (the notoneurons innervating the m. iliocostalis lumborum, 87%; the motoneurons innervating the m. obliquus externus abdominus, 82%). The effects of low threshold cutaneous afferents were bilateral, predominantly producing inhibitory postsynaptic potentials in motoneurons innervating both muscles. These results suggest that neuronal pathways from muscle afferents to back muscle motoneurons mainly increase the stiffness of the trunk to maintain its stability, while those to abdominal muscles help to extend the dorsal column by decreasing their activities. The results also indicate that neuronal pathways from cutaneous afferents to trunk motoneurons functionallY disconnect the tail from the trunk. 相似文献
493.
494.
The fully enclosed Taiaro lagoon is hypersaline (42.5 psu) and non-tidal; constant salinity and water level result from strong
evaporation balanced by low percolation through the lagoon floor. Seawater can flow over the atoll rim during exceptionally
high seas and may then replenish lagoonal communities with propagules of oceanic origin. The distinctive water chemistry of
the lagoon suggests a possible way of identifying these immigrants. We established this potential by analysing stable isotopes
of carbon and oxygen in the recent growth layers of otoliths of two adult reef fishes, Chaetodon ulietensis and Acanthurus triostegus, collected from both sides of the atoll rim. Fish from the two locations were discriminated by their isotopic signatures,
suggesting that analysis of the microchemical signatures deposited during the larval development could be used in future work
to determine which individuals and species complete their life-cycles in this unusual lagoon.
Accepted: 28 August 1997 相似文献
495.
The liver and kidney of rat underwent severe histopathological lesions when treated with a single bolus dose of carbendazim, a fungicide, particularly affecting the hepatocytes and the renal corpuscles, respectively. The effects appear to be manifestations of the microtubule-disrupting activity of carbendazim. Treatment of carbendazim-treated rats with the powder of tuberous root of Withania somnifera (Ashwagandha) for 48 days resulted in complete cure of these organs. The results indicate that Withania somnifera would be an effective curative for carbendazim-induced histopathological changes in the liver and kidney. 相似文献
496.
C Verwaerde K Thiam A Delanoye R Fernandez-Gomez J D'Halluin C Auriault 《European cytokine network》1999,10(2):161-170
Within the context of microorganism/host interactions, those which last over weeks are expected to be sensitive to more or less sustained and targeted immuno-intervention, such as delivery of cytokines known to operate as down-regulators of acute inflammatory processes. IL-10 has received growing attention as a potential tool in immunotherapy, due to its anti-inflammatory and immunosuppressive properties. Therefore, using two experimental models of long-term interactions between parasites and laboratory mice, we monitored some effects of the systemic delivery of an adenovirus (Ad) expressing EBV-derived IL-10 (vIL-10) designated Ad-vIL-10. We first monitored the vIL-10 serum level following intranasal, intraperitoneal, intramuscular and intravenous administration. The i. p. and i.v. delivery of Ad-vIL-10 allowed a high serum level of vIL-10 (= 100 ng/ml), the i.v. route leading to a more sustained expression (up to 3 weeks). As a first model of parasite/mouse interaction, Schistosoma mansoni/C57Bl/6 mouse was selected. Ad-vIL-10 delivery was performed 4 weeks after S. mansoni infection i.e. at the time of egg-laying, and several parameters were monitored: (i) number of adult worms in the mesenteric vein, (ii) number of eggs trapped in the liver and intestine, (iii) liver fibrosis, (iv) serum levels of egg-reactive antibody subclasses, (v) serum content of cytokines, and (vi) cytokine production in the supernatant of antigen-stimulated mesenteric lymph node cells. No apparent effect was observed, either on the different parasitological parameters or on fibrosis development at day 70 of infection. Surprisingly, a marked increase in both Th1 and Th2 type cytokines was observed in the sera of the Ad-vIL-10 injected animals, as well as in the supernatants of their Ag-stimulated mesenteric lymph node cells. Nevertheless, polarization of the humoral response towards a Th2 profile was demonstrated by an increase in the IgE level in the Ad-vIL-10-injected animals. As far as the second model is concerned, namely the Leishmania amazonensis /C57Bl6 mouse interactions, Ad-vIL-10 was delivered intravenously one day before subcutaneous injection of stationary promastigotes and footpad swelling was monitored over 110 days. Under these conditions, vIL-10 exhibited a biphasic effect, decreasing the lesion size at the early stages of infection, but leading to a more pronounced lesion size during the chronic phase. This observation suggests a deactivation of the macrophage host cells under the influence of vIL-10. The results are discussed in the context of immunotherapy and the paradoxical effects observed in immunointervention with vIL-10. 相似文献
497.
Plants of four isolines of soyabean [Glycine max(L.) Merrill]Clark, vizL71-920 (maturity genecomplemente1e2e3 ), L80-5914 (E1e2e3), Clark(e1E2E3), and L65-3366 (E1E2E3), were grown inshort (12.25 h d - 1natural light) and long days (12.25 h d- 1natural light supplemented with 2.75 h d - 1low-irradianceartificial light) from first flowering to maturity in a polythenetunnel maintained at 30/24°C (day/night). Whereas therewere few differences among the isolines grown in short days,in long days the dominant alleles increased crop duration, biomassand seed yield substantially. Increases in biological and economicyield were not solely a consequence of longer crop duration:the dominant alleles also increased crop growth rate and radiationuse efficiency in long days (from 1.3 g MJ - 1total radiationine1e2e3 to 2.8 g MJ - 1inE1E2E3 ). Greater radiation use efficiencyresulted from a relatively longer leaf area duration, betterdistribution and orientation of a larger mass of leaves withinthe canopy, and smaller partitioning of assimilates to reproductivestructures. The work reveals the substantial effects of thethree lociE1 / e1, E2/ e2and E3/e3 on the response of plantgrowth, as well as development, to environment. Their relevanceto crop adaptation is discussed. Copyright 2000 Annals of BotanyCompany Glycine max(L.) Merrill, soyabean, maturity genes, flowering, phenology, growth, yield 相似文献
498.
S. L. GLOCKLING FLS G. W. BEAKES 《Botanical journal of the Linnean Society. Linnean Society of London》2001,136(3):329-338
Two new species of Haptoglossa , one zoosporic, H. northumbrica , and one aplanosporic, H. polymorphs, , were isolated from samples of manure and horse dung in north-east England. The zoosporic H. northumbrica is morphologically similar to H. dickii but differs in having slightly smaller infection gun cells with a unique internal arrangement of cones in the apical missile chamber. The thallus of the aplanosporic H. polymorpha is similar to H. heteromorpha but produces three different types of aplanospore. The smaller cysts either develop into broad, arcuate gun cells or form curved adhesive cells that have a rounded base. These curved adhesive cells have very different internal ultrastructural organization. The large cysts develop into infection cells that are morphologically similar to the curved adhesive cells, but their internal structure has not yet been observed. 相似文献
499.
L. A. Mikhailova 《Human physiology》2001,27(6):680-685
We studied 654 healthy ten- to twelve-year-old children living in the Russian Far North (Taimyr peninsula) and in Siberia (town of Krasnoyarsk). The state of the body oxygenation and the systems responsible for oxygen delivery were studied according to the length of time living in the Russian Far North and season of the year. An examination of newcomer children revealed the following changes during the first year of living in the Russian Far North: an increased respiration rate and changes in its circadian rhythm; an increase in the heart rate, cardiac output, and cardiac index; an increase in the mean corpuscular volume in the red blood system; the activation of lipid peroxidation, and the changes in electrolyte balance of cells. The control mechanisms of oxygen transport system gradually stabilized during the ages of two to five years. In children living more than five years in the Russian Far North, the increased oxygen demand was met by the activation of cardiovascular and red blood systems aimed at more effective and adequate oxygen delivery to tissues. 相似文献
500.
A. B. Savin 《Journal of Ichthyology》2012,52(7):449-462
Biomass of bottom and near-bottom fishes in the eastern Sea of Okhotsk has been calculated using results of a bottom trawl survey performed in the summer 2010 through depths of 200?C1000 m. Obtained data are compared with the results of investigations performed in compatible water areas during the same season of 1989 and 1997. Biomass variability patterns of major species have been revealed for the period of more than two recent decades. The bathymetric and spatial distribution of major fish species has been revealed using the modern information. Species are listed whose commercial catches could be enlarged. 相似文献