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181.
Dukhande VV Malthankar-Phatak GH Hugus JJ Daniels CK Lai JC 《Neurochemical research》2006,31(11):1349-1357
Manganese (Mn) is neurotoxic: the underlying mechanisms have not been fully elucidated. l-Buthionine-(S,R)-sulfoximine (BSO) is an irreversible inhibitor of γ-glutamylcysteine synthetase, an important enzyme in glutathione (GSH) synthesis. To test the hypothesis that BSO modulates Mn toxicity, we investigated the effects of treatment of U-87 or SK-N-SH cells with MnCl2, BSO, or MnCl2 plus BSO. We monitored cell viability using MTT assay, staining with HO-33342 to assess live and/or apoptotic cells, and staining with propidium iodide (PI) to assess necrotic cells; we also measured cellular glutathione. Our results indicate decreased viability in both cell types when treated with MnCl2 or BSO: Mn was more toxic to SK-N-SH cells, whereas BSO was more toxic to U-87 cells. Because BSO treatment accentuated Mn toxicity in both cell lines, GSH may act to combat Mn toxicity. Thus, further investigation in oxidative stress mediated by glutathione depletion will unravel new Mn toxicity mechanism(s). 相似文献
182.
The activation of an immune response to invading microorganisms generally requires recognition by pattern recognition receptors. Beta 1, 3-glucan recognition proteins (GRPs) have specific affinity for beta 1, 3-glucan, a component on the surface of fungi and bacteria. In this study, we show that GRP from Armigeres subalbatus mosquitoes (AsGRP) is able to bind different bacterial species, and that this binding varies from species to species and is independent of Gram type. AsGRP knockdown with double-stranded RNA increases the mortality of mosquitoes to those bacteria that strongly bind AsGRP, but not to bacteria that do not detectably bind AsGRP. This increase in susceptibility is partially evidenced by decreased melanization in Salmonella typhimurium. Furthermore, AsGRP expression is differentially affected by the presence of different species of bacteria. These results demonstrate that AsGRP is selective in its affinity to different bacteria and; therefore, plays a role in the antibacterial immune response of mosquitoes. 相似文献
183.
We present full-genome genotype imputations for 100 classical laboratory mouse strains, using a novel method. Using genotypes at 549,683 SNP loci obtained with the Mouse Diversity Array, we partitioned the genome of 100 mouse strains into 40,647 intervals that exhibit no evidence of historical recombination. For each of these intervals we inferred a local phylogenetic tree. We combined these data with 12 million loci with sequence variations recently discovered by whole-genome sequencing in a common subset of 12 classical laboratory strains. For each phylogenetic tree we identified strains sharing a leaf node with one or more of the sequenced strains. We then imputed high- and medium-confidence genotypes for each of 88 nonsequenced genomes. Among inbred strains, we imputed 92% of SNPs genome-wide, with 71% in high-confidence regions. Our method produced 977 million new genotypes with an estimated per-SNP error rate of 0.083% in high-confidence regions and 0.37% genome-wide. Our analysis identified which of the 88 nonsequenced strains would be the most informative for improving full-genome imputation, as well as which additional strain sequences will reveal more new genetic variants. Imputed sequences and quality scores can be downloaded and visualized online. 相似文献
184.
Goodin JL Nellis DF Powell BS Vyas VV Enama JT Wang LC Clark PK Giardina SL Adamovicz JJ Michiel DF 《Protein expression and purification》2007,53(1):63-79
The F1-V vaccine antigen, protective against Yersinia pestis, exhibits a strong tendency to multimerize that affects larger-scale manufacture and characterization. In this work, the sole F1-V cysteine was replaced with serine by site-directed mutagenesis for characterization of F1-V non-covalent multimer interactions and protective potency without participation by disulfide-linkages. F1-V and F1-V(C424S) proteins were overexpressed in Escherichia coli, recovered using mechanical lysis/pH-modulation and purified from urea-solubilized soft inclusion bodies, using successive ion-exchange, ceramic hydroxyapatite, and size-exclusion chromatography. This purification method resulted in up to 2mg/g of cell paste of 95% pure, mono-disperse protein having < or =0.5 endotoxin units per mg by a kinetic chromogenic limulus amoebocyte lysate reactivity assay. Both F1-V and F1-V(C424S) were monomeric at pH 10.0 and progressively self-associated as pH conditions decreased to pH 6.0. Solution additives were screened for their ability to inhibit F1-V self-association at pH 6.5. An L-arginine buffer provided the greatest stabilizing effect. Conversion to >500-kDa multimers occurred between pH 6.0 and 5.0. Conditions for efficient F1-V adsorption to the cGMP-compatible alhydrogel adjuvant were optimized. Side-by-side evaluation for protective potency against subcutaneous plague infection in mice was conducted for F1-V(C424S) monomer; cysteine-capped F1-V monomer; cysteine-capped F1-V multimer; and a F1-V standard reported previously. After a two-dose vaccination with 2 x 20 microg of F1-V, respectively, 100%, 80%, 80%, and 70% of injected mice survived a subcutaneous lethal plague challenge with 10(8) LD(50)Y. pestis CO92. Thus, vaccination with F1-V monomer and multimeric forms resulted in significant, and essentially equivalent, protection. 相似文献
185.
CD200 expression on tumor cells suppresses antitumor immunity: new approaches to cancer immunotherapy 总被引:1,自引:0,他引:1
Kretz-Rommel A Qin F Dakappagari N Ravey EP McWhirter J Oltean D Frederickson S Maruyama T Wild MA Nolan MJ Wu D Springhorn J Bowdish KS 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(9):5595-5605
Although the immune system is capable of mounting a response against many cancers, that response is insufficient for tumor eradication in most patients due to factors in the tumor microenvironment that defeat tumor immunity. We previously identified the immune-suppressive molecule CD200 as up-regulated on primary B cell chronic lymphocytic leukemia (B-CLL) cells and demonstrated negative immune regulation by B-CLL and other tumor cells overexpressing CD200 in vitro. In this study we developed a novel animal model that incorporates human immune cells and human tumor cells to address the effects of CD200 overexpression on tumor cells in vivo and to assess the effect of targeting Abs in the presence of human immune cells. Although human mononuclear cells prevented tumor growth when tumor cells did not express CD200, tumor-expressed CD200 inhibited the ability of lymphocytes to eradicate tumor cells. Anti-CD200 Ab administration to mice bearing CD200-expressing tumors resulted in nearly complete tumor growth inhibition even in the context of established receptor-ligand interactions. Evaluation of an anti-CD200 Ab with abrogated effector function provided evidence that blocking of the receptor-ligand interaction was sufficient for control of CD200-mediated immune modulation and tumor growth inhibition in this model. Our data indicate that CD200 expression by tumor cells suppresses antitumor responses and suggest that anti-CD200 treatment might be therapeutically beneficial for treating CD200-expressing cancers. 相似文献
186.
The dynamics of top-down and bottom-up effects in food webs of varying prey diversity, composition, and productivity 总被引:1,自引:0,他引:1
Jeremy W. Fox 《Oikos》2007,116(2):189-200
Prey diversity is thought to mediate the strength of top-down and bottom-up effects, but few experiments directly test this hypothesis. I assembled food webs of bacteria and bacterivorous protist prey in laboratory microcosms with all combinations of five productivity levels, two top predator treatments (present or absent), and three prey compositions. Depauperate food chains contained one of two edible prey species, while more diverse food webs contained both edible prey species plus two additional less-edible/inedible prey. Equilibrium theory predicts that prey diversity should weaken the top-down and bottom-up effects on trophic level biomasses, due to density compensation among prey species. Top-down effects should increase with productivity in food chains, but decrease with productivity in food webs. Results revealed highly dynamic top-down effects, the strength of which varied more over time than among treatments. Further, top-down effects did not merely vary in absolute strength over time, but also in relative strength across different prey compositions and productivity levels. It might be expected that equilibrium models would qualitatively reproduce time-averaged results. However, time-averaged data largely failed to support equilibrium predictions. This failure may reflect strong temporal variability in treatment effects combined with nonlinear density dependence of species' per-capita growth rates. Strong temporal variability in the strength of top-down effects has not previously been demonstrated, but likely is common in nature as well. 相似文献
187.
Judith Murray-Rust Jeremy H Lakey Philip E Bourne 《Current opinion in structural biology》1999,9(6):659
A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Structural Biology. 相似文献
188.
189.
Klocko AD Schroeder JW Walsh BW Lenhart JS Evans ML Simmons LA 《Molecular microbiology》2011,82(3):648-663
Mismatch repair (MMR) corrects DNA polymerase errors occurring during genome replication. MMR is critical for genome maintenance, and its loss increases mutation rates several hundred fold. Recent work has shown that the interaction between the mismatch recognition protein MutS and the replication processivity clamp is important for MMR in Bacillus subtilis. To further understand how MMR is coupled to DNA replication, we examined the subcellular localization of MMR and DNA replication proteins fused to green fluorescent protein (GFP) in live cells, following an increase in DNA replication errors. We demonstrate that foci of the essential DNA polymerase DnaE-GFP decrease following mismatch incorporation and that loss of DnaE-GFP foci requires MutS. Furthermore, we show that MutS and MutL bind DnaE in vitro, suggesting that DnaE is coupled to repair. We also found that DnaE-GFP foci decrease in vivo following a DNA damage-independent arrest of DNA synthesis showing that loss of DnaE-GFP foci is caused by perturbations to DNA replication. We propose that MutS directly contacts the DNA replication machinery, causing a dynamic change in the organization of DnaE at the replication fork during MMR. Our results establish a striking and intimate connection between MMR and the replicating DNA polymerase complex in vivo. 相似文献
190.
Atomic Layer Deposition of Functional Layers for on Chip 3D Li‐Ion All Solid State Microbattery 下载免费PDF全文
Manon Létiche Etienne Eustache Jeremy Freixas Arnaud Demortière Vincent De Andrade Laurence Morgenroth Pascal Tilmant François Vaurette David Troadec Pascal Roussel Thierry Brousse Christophe Lethien 《Liver Transplantation》2017,7(2)
Nowadays, millimeter scale power sources are key devices for providing autonomy to smart, connected, and miniaturized sensors. However, until now, planar solid state microbatteries do not yet exhibit a sufficient surface energy density. In that context, architectured 3D microbatteries appear therefore to be a good solution to improve the material mass loading while keeping small the footprint area. Beside the design itself of the 3D microbaterry, one important technological barrier to address is the conformal deposition of thin films (lithiated or not) on 3D structures. For that purpose, atomic layer deposition (ALD) technology is a powerful technique that enables conformal coatings of thin film on complex substrate. An original, robust, and highly efficient 3D scaffold is proposed to significantly improve the geometrical surface of miniaturized 3D microbattery. Four functional layers composing the 3D lithium ion microbattery stacking has been successfully deposited on simple and double microtubes 3D templates. In depth synchrotron X‐ray nanotomography and high angle annular dark field transmission electron microscope analyses are used to study the interface between each layer. For the first time, using ALD, anatase TiO2 negative electrode is coated on 3D tubes with Li3PO4 lithium phosphate as electrolyte, opening the way to all solid‐state 3D microbatteries. The surface capacity is significantly increased by the proposed topology (high area enlargement factor – “thick” 3D layer), from 3.5 μA h cm?2 for a planar layer up to 0.37 mA h cm?2 for a 3D thin film (105 times higher). 相似文献