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31.
Sean V. Murphy Rebecca Lim Philip Heraud Marian Cholewa Mark Le Gros Martin D. de Jonge Daryl L. Howard David Paterson Courtney McDonald Anthony Atala Graham Jenkin Euan M. Wallace 《PloS one》2012,7(9)
Cystic fibrosis, an autosomal recessive disorder caused by a mutation in a gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), remains a leading cause of childhood respiratory morbidity and mortality. The respiratory consequences of cystic fibrosis include the generation of thick, tenacious mucus that impairs lung clearance, predisposing the individual to repeated and persistent infections, progressive lung damage and shortened lifespan. Currently there is no cure for cystic fibrosis. With this in mind, we investigated the ability of human amnion epithelial cells (hAECs) to express functional CFTR. We found that hAECs formed 3-dimensional structures and expressed the CFTR gene and protein after culture in Small Airway Growth Medium (SAGM). We also observed a polarized CFTR distribution on the membrane of hAECs cultured in SAGM, similar to that observed in polarized airway cells in vivo. Further, hAECs induced to express CFTR possessed functional iodide/chloride (I−/Cl−) ion channels that were inhibited by the CFTR-inhibitor CFTR-172, indicating the presence of functional CFTR ion channels. These data suggest that hAECs may be a promising source for the development of a cellular therapy for cystic fibrosis. 相似文献
32.
Los FC Kao CY Smitham J McDonald KL Ha C Peixoto CA Aroian RV 《Cell host & microbe》2011,10(2):147-157
Sequence variation of antigenic proteins allows pathogens to evade antibody attack. The variable protein commonly includes a hypervariable region (HVR), which represents a key target for antibodies and is therefore predicted to be immunodominant. To understand the mechanism(s) of antibody evasion, we analyzed the clinically important HVR-containing M proteins of the human pathogen Streptococcus pyogenes. Antibodies elicited by M proteins were directed almost exclusively against the C-terminal part and not against the N-terminal HVR. Similar results were obtained for mice and humans with invasive S.?pyogenes infection. Nevertheless, only anti-HVR antibodies protected efficiently against infection, as shown by passive immunizations. The HVR fused to an unrelated protein elicited no antibodies, implying that it is inherently weakly immunogenic. These data indicate that the M protein HVR evades antibody attack not only through antigenic variation but also by weak immunogenicity, a paradoxical observation that may apply to other HVR-containing proteins. 相似文献
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34.
Over nearly three decades, Suzanne Prober has played a pivotal role in shifting research in Australian agricultural landscapes to include a focus on native woodlands, and to examine ways woodland conservation can co‐exist with production, contributing to new models for conservation within multi‐use landscapes. 相似文献
35.
Bacterial kidney disease (BKD), caused by Renibacterium salmoninarum, is a widespread problem with major implications for salmonid fish species. The mechanisms by which the bacterium has reached high levels of infection previously unrecorded in the Laurentian Great Lakes are presently unknown. Research involving reservoirs and mechanisms of R. salmoninarum transmission in fish is lacking because of the ecologic complexity of heterogeneous habitats and the lack of adequate funding. Herein, we report on the isolation of R. salmoninarum from the kidneys of the sea lamprey (Petromyzon marinus). The bacterium was cultured from kidneys of 16% and 4% of lampreys collected from two locations within the Lake Ontario watershed in 2003 and 2004, respectively. The identity of bacterial colonies was verified with the nested polymerase chain reaction and quantitative enzyme-linked immunosorbent assay. 相似文献
36.
Megan C. McDonald Mohammad Razavi Timothy L. Friesen Patrick C. Brunner Bruce A. McDonald 《Fungal genetics and biology : FG & B》2012,49(11):882-895
The origin of the fungal wheat pathogen Phaeosphaeria nodorum remains unclear despite earlier intensive global population genetic and phylogeographical studies. We sequenced 1683 bp distributed across three loci in 355 globally distributed Phaeosphaeria isolates, including 74 collected in Iran near the center of origin of wheat. We identified nine phylogenetically distinct clades, including two previously unknown species tentatively named P1 and P2 collected in Iran. Coalescent analysis indicates that P1 and P2 are sister species of P. nodorum and the other Phaeosphaeria species identified in our analysis. Two species, P. nodorum and P. avenaria f. sp. tritici 1 (Pat1), comprised ~85% of the sampled isolates, making them the dominant wheat-infecting pathogens within the species complex. We designed a PCR-RFLP assay to distinguish P. nodorum from Pat1. Approximately 4% of P. nodorum and Pat1 isolates showed evidence of hybridization. Measures of private allelic richness at SSR and sequence loci suggest that the center of origin of P. nodorum coincides with its host in the Fertile Crescent. We hypothesize that the origin of this species complex is also in the Fertile Crescent, with four species out of nine found exclusively in the Iranian collections. 相似文献
37.
Force generation in striated muscle is coupled with inorganic phosphate (Pi) release from myosin, because force falls with increasing Pi concentration ([Pi]). However, it is unclear which steps in the cross-bridge cycle limit loaded shortening and power output. We examined the role of Pi in determining force, unloaded and loaded shortening, power output, and rate of force development in rat skinned cardiac myocytes to discern which step in the cross-bridge cycle limits loaded shortening. Myocytes (n = 6) were attached between a force transducer and position motor, and contractile properties were measured over a range of loads during maximal Ca2+ activation. Addition of 5 mM Pi had no effect on maximal unloaded shortening velocity (Vo) (control 1.83 ± 0.75, 5 mM added Pi 1.75 ± 0.58 muscle lengths/s; n = 6). Conversely, addition of 2.5, 5, and 10 mM Pi progressively decreased force but resulted in faster loaded shortening and greater power output (when normalized for the decrease in force) at all loads greater than 10% isometric force. Peak normalized power output increased 16% with 2.5 mM added Pi and further increased to a plateau of 35% with 5 and 10 mM added Pi. Interestingly, the rate constant of force redevelopment (ktr) progressively increased from 0 to 10 mM added Pi, with ktr 360% greater at 10 mM than at 0 mM added Pi. Overall, these results suggest that the Pi release step in the cross-bridge cycle is rate limiting for determining shortening velocity and power output at intermediate and high relative loads in cardiac myocytes. muscle mechanics; force-velocity relationship; cross-bridge cycle 相似文献
38.
Pebernard S Wohlschlegel J McDonald WH Yates JR Boddy MN 《Molecular and cellular biology》2006,26(5):1617-1630
Stabilization and processing of stalled replication forks is critical for cell survival and genomic integrity. We characterize a novel DNA repair heterodimer of Nse5 and Nse6, which are nonessential nuclear proteins critical for chromosome segregation in fission yeast. The Nse5/6 dimer facilitates DNA repair as part of the Smc5-Smc6 holocomplex (Smc5/6), the basic architecture of which we define. Nse5-Nse6 [corrected] (Nse5 and Nse6) [corrected] mutants display a high level of spontaneous DNA damage and mitotic catastrophe in the absence of the master checkpoint regulator Rad3 (hATR). Nse5/6 mutants are required for the response to genotoxic agents that block the progression of replication forks, acting in a pathway that allows the tolerance of irreparable UV lesions. Interestingly, the UV sensitivity of Nse5/6 [corrected] is suppressed by concomitant deletion of the homologous recombination repair factor, Rhp51 (Rad51). Further, the viability of Nse5/6 mutants depends on Mus81 and Rqh1, factors that resolve or prevent the formation of Holliday junctions. Consistently, the UV sensitivity of cells lacking Nse5/6 can be partially suppressed by overexpressing the bacterial resolvase RusA. We propose a role for Nse5/6 mutants in suppressing recombination that results in Holliday junction formation or in Holliday junction resolution. 相似文献
39.
Background
Many studies of biochemical networks have analyzed network topology. Such work has suggested that specific types of network wiring may increase network robustness and therefore confer a selective advantage. However, knowledge of network topology does not allow one to predict network dynamical behavior – for example, whether deleting a protein from a signaling network would maintain the network's dynamical behavior, or induce oscillations or chaos. 相似文献40.
Cathepsin C: a chloride-requiring enzyme 总被引:2,自引:0,他引:2