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91.
Marie Hamann Claire Pierra Jean-Pierre Sommadossi Chiara Musiu Luana Vargiu Michel Liuzzi Richard Storer Gilles Gosselin 《Bioorganic & medicinal chemistry》2009,17(6):2321-2326
Several thieno[3,4-d]pyrimidine derivatives, including four hitherto unknown 2′,3′-dideoxy- and 2′,3′-dideoxy-2′,3′-didehydro-C-nucleoside analogues of adenosine and inosine have been synthesized. When evaluated in cell culture experiments against human immunodeficiency virus, none of the tested compounds exhibited any significant antiviral effect, while two of them showed some cytotoxicity. 相似文献
92.
93.
Fran?ois Michaud Fran?ois Coulombe Eric Gaudreault Carine Paquet-Bouchard Marek Rola-Pleszczynski Jean Gosselin 《PloS one》2010,5(7)
Background
Epstein-Barr virus is recognized to cause lymphoproliferative disorders and is also associated with cancer. Evidence suggests that monocytes are likely to be involved in EBV pathogenesis, especially due to a number of cellular functions altered in EBV-infected monocytes, a process that may affect efficient host defense. Because type I interferons (IFNs) are crucial mediators of host defense against viruses, we investigated the effect of EBV infection on the IFNα pathway in primary human monocytes.Methodology/Principal Findings
Infection of monocytes with EBV induced IFNα secretion but inhibited the positive feedback loop for the amplification of IFNα. We showed that EBV infection induced the expression of suppressor of cytokine signaling 3 (SOCS3) and, to a lesser extent, SOCS1, two proteins known to interfere with the amplification of IFNα secretion mediated by the JAK/STAT signal transduction pathway. EBV infection correlated with a blockage in the activation of JAK/STAT pathway members and affected the level of phosphorylated IFN regulatory factor 7 (IRF7). Depletion of SOCS3, but not SOCS1, by small interfering RNA (siRNA) abrogated the inhibitory effect of EBV on JAK/STAT pathway activation and significantly restored IFNα secretion. Finally, transfection of monocytes with the viral protein Zta caused the upregulation of SOCS3, an event that could not be recapitulated with mutated Zta.Conclusions/Significance
We propose that EBV protein Zta activates SOCS3 protein as an immune escape mechanism that both suppresses optimal IFNα secretion by human monocytes and favors a state of type I IFN irresponsiveness in these cells. This immunomodulatory effect is important to better understand the aspects of the immune response to EBV. 相似文献94.
95.
Lemieux M Bouchard F Gosselin P Paquin J Mateescu MA 《Biochemical and biophysical research communications》2011,(3):429-434
The objective of this study was to evaluate the human NCI-N87 cell line as a model for gastric permeability drug studies under pH conditions of the stomach. The optimal conditions that led NCI-N87 cells to form a typical differentiated gastric epithelial barrier were a seeding density of 2.5 × 105 cells/cm2 on porous inserts and growth in serum-complemented RPMI-1640 medium until 18–27 days post-confluency. The resulting cell monolayers showed moderately high transepithelial electrical resistance (TEER) values of about 500 Ω cm2, cells of polygonal morphology expressing E-cadherin and ZO-1 proteins at their contact surfaces, and production of mucus clusters. The monolayers withstood apical pH of 7.4 down to 3.0 with the basal pH fixed at 7.4. The apparent permeability coefficients (Papp) of model compounds were evaluated in the apical-to-basolateral and basolateral-to-apical directions under different pH gradients. The monolayers were impermeable to the integrity marker Lucifer Yellow (low Papp of 0.3–1.1 × 10−6 cm/s). The furosemide Papp (0.4–1.5 × 10−5 cm/s) were slightly dependent on pH but remained moderate. The caffeine Papp (4.2–5.0 × 10−5 cm/s) were higher and insensitive to pH changes. The NCI-N87 cell line provides a useful in vitro tool to assess gastric drug permeability and absorption under physiologic conditions prevailing in the human stomach. 相似文献
96.
Haakon Hop Christopher J. Mundy Michel Gosselin Andrea L. Rossnagel David G. Barber 《Polar Biology》2011,34(12):1947-1958
Early summer in the Arctic with extensive ice melt and break-up represents a dramatic change for sympagic–pelagic fauna below
seasonal sea ice. As part of the International Polar Year-Circumpolar Flaw Lead system study (IPY-CFL), this investigation
quantified zooplankton in the meltwater layer below landfast ice and remaining ice fauna below melting ice during June (2008)
in Franklin Bay and Darnley Bay, Amundsen Gulf, Canada. The ice was in a state of advanced melt, with fully developed melt
ponds. Intense melting resulted in a 0.3- to 0.5-m-thick meltwater layer below the ice, with a strong halocline to the Arctic
water below. Zooplankton under the ice, in and below the meltwater layer, was sampled by SCUBA divers. Dense concentrations
(max. 1,400 ind. m−3) of Calanus glacialis were associated with the meltwater layer, with dominant copepodid stages CIV and CV and high abundance of nauplii. Less abundant
species included Pseudocalanus spp., Oithona similis and C. hyperboreus. The copepods were likely feeding on phytoplankton (0.5–2.3 mg Chl-a m−3) in the meltwater layer. Ice amphipods were present at low abundance (<10 ind. m−2) and wet biomass (<0.2 g m−2). Onisimus glacialis and Apherusa glacialis made up 64 and 51% of the total ice faunal abundance in Darnley Bay and Franklin Bay, respectively. During early summer,
the autochthonous ice fauna becomes gradually replaced by allochthonous zooplankton, with an abundance boom near the meltwater
layer. The ice amphipod bust occurs during late stages of melting and break-up, when their sympagic habitat is diminished
then lost. 相似文献
97.
Ram Krishna Thakur Vinod Kumar Yadav Akinchan Kumar Ankita Singh Krishnendu Pal Luke Hoeppner Dhurjhoti Saha Gunjan Purohit Richa Basundra Anirban Kar Rashi Halder Pankaj Kumar Aradhita Baral MJ Mahesh Kumar Alfonso Baldi Bruno Vincenzi Laura Lorenzon Rajkumar Banerjee Praveen Kumar Viji Shridhar Debabrata Mukhopadhyay Shantanu Chowdhury 《Nucleic acids research》2014,42(18):11589-11600
98.
Marieke?Pingen Ramin?Sarrami-Forooshani Annemarie?MJ?Wensing Petra?van Ham Agata?Drewniak Charles?AB?Boucher Teunis?BH?GeijtenbeekEmail author Monique?NijhuisEmail author 《Retrovirology》2014,11(1):113
Background
Different patterns of drug resistance are observed in treated and therapy naïve HIV-1 infected populations. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naïve population. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. However it is debated whether a diminished transmission efficacy of HIV variants with a reduced replication capacity can also contribute to the observed discrepancy in genotypic patterns.As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT). As control, we used HIV harboring the NNRTI mutation K103N (HIV-K103N) which has a minor effect on replication and is found at a similar prevalence in treated and untreated individuals.Results
In comparison to HIV-WT, the HIV-M184 variants were less efficiently transmitted to CCR5+ Jurkat T cells by both LCs and DCs. The transmission rate of HIV-K103N was slightly reduced to HIV-WT in LCs and even higher than HIV-WT in DCs. Replication experiments in CCR5+ Jurkat T cells revealed no apparent differences in replication capacity between the mutant viruses and HIV-WT. However, viral replication in LCs and DCs was in concordance with the transmission results; replication by the HIV-M184 variants was lower than replication by HIV-WT, and the level of replication of HIV-K103N was intermediate for LCs and higher than HIV-WT for DCs.Conclusions
Our data demonstrate that drug resistant M184-variants display a reduced replication capacity in LCs and DCs which directly impairs their transmission efficacy. As such, diminished transmission efficacy may contribute to the lower prevalence of drug resistant variants in therapy naive individuals.99.
INFLUENCE OF UV-B RADIATION ON NITROGEN UTILIZATION BY A NATURAL ASSEMBLAGE OF PHYTOPLANKTON 总被引:2,自引:0,他引:2
Juliette Fauchot† Michel Gosselin Maurice Levasseur Behzad Mostajir Claude Belzile Serge Demers Suzanne Roy Piedad Zulema Villegas 《Journal of phycology》2000,36(3):484-496
A 7‐day mesocosm experiment was conducted in July 1996 to investigate the effects of ambient UV‐B radiation (UVBR) exclusion and two UVBR enhancements above ambient levels on NO3?, NH4+ and urea utilization in a natural plankton community (<240 μm) from the Lower St. Lawrence Estuary. The phytoplankton community was dominated by diatoms during the first 3 days and, afterward, by flagellates and dinoflagellates. The results of 4‐h incubations just below the water surface show that, compared with ambient UVBR conditions, UVBR exclusion generally increased NO3?, NH4+, and urea uptakes. During the last 4 days of the experiment, the percent increase in the specific uptake rate of urea under excluded UVBR conditions varied between 17% and 130% and was a linear function of the ambient UVBR dose removed. During the first 3 days, the phytoplankton community dominated by diatoms was able to withstand UVBR enhancements without any perceptible effect on nitrogen uptake. However, during the post‐diatom bloom period, UVBR enhancements resulted in decreases in NO3?, NH4+, and urea uptake compared with ambient UVBR conditions. The reduction of urea uptake under UVBR enhancements during the last 3 days varied between 23% and 64% and was linearly related to the enhanced UVBR dose. However, the different UVBR treatments did not affect the internal organic nitrogen composition (internal urea, free amino acids, and proteins) of the phytoplankton community experiencing vertical mixing in the mesocosms. The discrepancy between short‐term uptake measurements at the surface and long‐term effects in the mesocosms emphasizes the importance of vertical mixing on UVBR effects in natural ecosystems. This suggests that an increase in ambient UVBR would have a minimal effect on nitrogen utilization by natural phytoplankton assemblages if these are vertically mixed. 相似文献
100.