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201.
Shi J Zhou L Zhang H McBrayer TR Detorio MA Johns M Bassit L Powdrill MH Whitaker T Coats SJ Götte M Schinazi RF 《Bioorganic & medicinal chemistry letters》2011,21(23):7094-7098
Thirty novel α- and β-d-2'-deoxy-2'-fluoro-2'-C-methyl-7-deazapurine nucleoside analogs were synthesized and evaluated for in vitro antiviral activity. Several α- and β-7-deazapurine nucleoside analogs exhibited modest anti-HCV activity and cytotoxicity. Four synthesized 7-deazapurine nucleoside phosphoramidate prodrugs (18-21) showed no anti-HCV activity, whereas the nucleoside triphosphates (22-24) demonstrated potent inhibitory effects against both wild-type and S282T mutant HCV polymerases. Cellular pharmacology studies in Huh-7 cells revealed that the 5'-triphosphates were not formed at significant levels from either the nucleoside or the phosphoramidate prodrugs, indicating that insufficient phosphorylation was responsible for the lack of anti-HCV activity. Evaluation of anti-HIV-1 activity revealed that an unusual α-form of 7-carbomethoxyvinyl substituted nucleoside (10) had good anti-HIV-1 activity (EC(50)=0.71±0.25 μM; EC(90)=9.5±3.3 μM) with no observed cytotoxicity up to 100 μM in four different cell lines. 相似文献
202.
Pedrosa FO Monteiro RA Wassem R Cruz LM Ayub RA Colauto NB Fernandez MA Fungaro MH Grisard EC Hungria M Madeira HM Nodari RO Osaku CA Petzl-Erler ML Terenzi H Vieira LG Steffens MB Weiss VA Pereira LF Almeida MI Alves LR Marin A Araujo LM Balsanelli E Baura VA Chubatsu LS Faoro H Favetti A Friedermann G Glienke C Karp S Kava-Cordeiro V Raittz RT Ramos HJ Ribeiro EM Rigo LU Rocha SN Schwab S Silva AG Souza EM Tadra-Sfeir MZ Torres RA Dabul AN Soares MA Gasques LS Gimenes CC Valle JS Ciferri RR 《PLoS genetics》2011,7(5):e1002064
The molecular mechanisms of plant recognition, colonization, and nutrient exchange between diazotrophic endophytes and plants are scarcely known. Herbaspirillum seropedicae is an endophytic bacterium capable of colonizing intercellular spaces of grasses such as rice and sugar cane. The genome of H. seropedicae strain SmR1 was sequenced and annotated by The Paraná State Genome Programme--GENOPAR. The genome is composed of a circular chromosome of 5,513,887 bp and contains a total of 4,804 genes. The genome sequence revealed that H. seropedicae is a highly versatile microorganism with capacity to metabolize a wide range of carbon and nitrogen sources and with possession of four distinct terminal oxidases. The genome contains a multitude of protein secretion systems, including type I, type II, type III, type V, and type VI secretion systems, and type IV pili, suggesting a high potential to interact with host plants. H. seropedicae is able to synthesize indole acetic acid as reflected by the four IAA biosynthetic pathways present. A gene coding for ACC deaminase, which may be involved in modulating the associated plant ethylene-signaling pathway, is also present. Genes for hemagglutinins/hemolysins/adhesins were found and may play a role in plant cell surface adhesion. These features may endow H. seropedicae with the ability to establish an endophytic life-style in a large number of plant species. 相似文献
203.
Silvina Fernanda Ruspini Johanna Romina Zuccoli Jimena Verónica Lavandera Marìa Del Carmen Martínez Leda María Oliveri Esther Noemí Gerez Alcira María Del Carmen Batlle Ana María Buzaleh 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(6):1296-1305
Background
Acute Intermittent Porphyria (AIP) is an inherited disease produced by a deficiency of Porphobilinogen deaminase (PBG-D). The aim of this work was to evaluate the effects of Isoflurane and Sevoflurane on heme metabolism in a mouse genetic model of AIP to further support our previous proposal for avoiding their use in porphyric patients. A comparative study was performed administering the porphyrinogenic drugs allylisopropylacetamide (AIA), barbital and ethanol, and also between sex and mutation using AIP (PBG-D activity 70% reduced) and T1 (PBG-D activity 50% diminished) mice.Methods
The activities of 5-Aminolevulinic synthetase (ALA-S), PBG-D, Heme oxygenase (HO) and CYP2E1; the expression of ALA-S and the levels of 5-aminolevulinic acid (ALA) were measured in different tissues of mice treated with the drugs mentioned.Results
Isoflurane increased liver, kidney and brain ALA-S activity of AIP females but only affected kidney AIP males. Sevoflurane induced ALA-S activity in kidney and brain of female AIP group. PBG-D activity was further reduced by Isoflurane in liver male T1; in AIP male mice activity remained in its low basal levels. Ethanol and barbital also caused biochemical alterations. Only AIA triggered neurological signs similar to those observed during human acute attacks in male AIP being the symptoms less pronounced in females although ALA-S induction was greater. Heme degradation was affected.Discussion
Biochemical alterations caused by the porphyrinogenic drugs assayed were different in male and female mice and also between T1 and AIP being more affected the females of AIP group.General significance
This is the first study using volatile anaesthetics in an AIP genetic model confirming Isoflurane and Sevoflurane porphyrinogenicity. 相似文献204.
Maria Francesca Cardone Pietro D'Addabbo Can Alkan Carlo Bergamini Claudia Rita Catacchio Fabio Anaclerio Giorgia Chiatante Annamaria Marra Giuliana Giannuzzi Rocco Perniola Mario Ventura Donato Antonacci 《The Plant journal : for cell and molecular biology》2016,88(4):648-661
Grapevine (Vitis vinifera L.) is one of the world's most important crop plants, which is of large economic value for fruit and wine production. There is much interest in identifying genomic variations and their functional effects on inter‐varietal, phenotypic differences. Using an approach developed for the analysis of human and mammalian genomes, which combines high‐throughput sequencing, array comparative genomic hybridization, fluorescent in situ hybridization and quantitative PCR, we created an inter‐varietal atlas of structural variations and single nucleotide variants (SNVs) for the grapevine genome analyzing four economically and genetically relevant table grapevine varieties. We found 4.8 million SNVs and detected 8% of the grapevine genome to be affected by genomic variations. We identified more than 700 copy number variation (CNV) regions and more than 2000 genes subjected to CNV as potential candidates for phenotypic differences between varieties. 相似文献
205.
Eugenia Migliavacca Christelle Golzio Katrin M?nnik Ian Blumenthal Edwin?C. Oh Louise Harewood Jack A. Kosmicki Maria?Nicla Loviglio Giuliana Giannuzzi Loyse Hippolyte Anne?M. Maillard Ali?Abdullah Alfaiz p. European Consortium Mieke M. van Haelst Joris Andrieux James F. Gusella Mark J. Daly Jacques S. Beckmann Sébastien Jacquemont Michael E. Talkowski Nicholas Katsanis Alexandre Reymond 《American journal of human genetics》2015,96(5):784-796
206.
Hernández Sanabria MX Afonso LC Golgher D Tafuri WL Vieira LQ 《Microbes and infection / Institut Pasteur》2007,9(9):1124-1134
Vaccine-induced protection against leishmaniasis is largely dependent on cell-mediated type 1 response and IL-12-driven IFN-gamma production. Surprisingly, our previous data showed that IL-12/23p40(-/-) mice could be vaccinated against L. amazonensis and were able to produce limited amounts of IFN-gamma. Since the role of CD8+ T in immunization against L. amazonensis is obscure, the aim of this study was to evaluate the effects of CD8+ cells in protection against L. amazonensis in IL-12/23p40(-/-) mice. In order to deplete CD8+ cells, one group of vaccinated animals was treated with anti-CD8 mAb. Infection was followed for 8 weeks. The vaccinated CD8+ -depleted group developed smaller lesions than the non-depleted group. CD8 depletion did not affect tissue parasitism or antibody response against the parasite, and treated animals displayed milder inflammation and better tissue integrity. IFN-gamma production in spleen and draining lymph node was impaired in the depleted group, suggesting that CD8+ cells produced this cytokine in IL-12-independent vaccination. Such results suggest that this T cell subset contributes to augmented pathology in IL12/23p40(-/-) mice vaccinated and challenged with L. amazonensis. Although these cells could produce some IFN-gamma the in the absence of IL-12, they do not affect the parasite tissue load. 相似文献
207.
Pedelini L Marquina M Ariño J Casamayor A Sanz L Bollen M Sanz P Garcia-Gimeno MA 《The Journal of biological chemistry》2007,282(5):3282-3292
We have recently characterized Ypi1 as an inhibitory subunit of yeast Glc7 PP1 protein phosphatase. In this work we demonstrate that Ypi1 forms a complex with Glc7 and Sds22, another Glc7 regulatory subunit that targets the phosphatase to substrates involved in cell cycle control. Interestingly, the combination of equimolar amounts of Ypi1 and Sds22 leads to an almost full inhibition of Glc7 activity. Because YPI1 is an essential gene, we have constructed conditional mutants that demonstrate that depletion of Ypi1 leads to alteration of nuclear localization of Glc7 and cell growth arrest in mid-mitosis with aberrant mitotic spindle. These phenotypes mimic those produced upon inactivation of Sds22. The fact that progressive depletion of either Ypi1 or Sds22 resulted in similar physiological phenotypes and that both proteins inhibit the phosphatase activity of Glc7 strongly suggest a common role of these two proteins in regulating Glc7 nuclear localization and function. 相似文献
208.
209.
Vanessa J. De-Paula Evelin L. Schaeffer Leda L. Talib Wagner F. Gattaz Orestes V. Forlenza 《Prostaglandins, leukotrienes, and essential fatty acids》2010,82(1):57-60
BackgroundArachidonic acid is released from cellular membranes by the action of phospholipase A2 (PLA2) and is implicated in microtubule-associated protein Tau phosphorylation. Tau hyperphosphorylation affects its ability to stabilize microtubules.ObjectiveTo determine the effect of PLA2 inhibition on the phosphorylation state of Tau phosphoepitopes in primary cultures of hippocampal neurons.Methods4 DIC neurons were incubated at different concentrations of methyl-arachidonylfluorophosphonate (MAFP), an irreversible inhibitor of cPLA2 and iPLA2. Changes on Tau phosphorylation were determined by Western blotting with a panel of anti-Tau antibodies (C-terminal, Ser199/202, Ser202/205, Ser396 and Ser214).ResultsThe Ser214 site was hyperphosphorylated upon MAFP treatment. Significant differences were observed with 10 μM (p=0.01), 50 μM (p=0.01) and 100 μM (p=0.05) of MAFP. Less-intense changes were found in other phosphoepitopes.ConclusionThe present findings indicate that the phosphorylation of Ser214 is regulated by c- and/or iPLA2, whereas other phosphoepitopes primarily regulated by GKS3b were not affected. 相似文献
210.