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排序方式: 共有470条查询结果,搜索用时 22 毫秒
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Ajit G. Thomas Rita Sattler Karen Tendyke Kara A. Loiacono Hans Hansen Vishal Sahni Yutaka Hashizume Camilo Rojas Barbara S. Slusher 《PloS one》2015,10(8)
The cystine-glutamate antiporter (system xc
-) is a Na+-independent amino acid transporter that exchanges extracellular cystine for intracellular glutamate. It is thought to play a critical role in cellular redox processes through regulation of intracellular glutathione synthesis via cystine uptake. In gliomas, system xc
- expression is universally up-regulated while that of glutamate transporters down-regulated, leading to a progressive accumulation of extracellular glutamate and excitotoxic cell death of the surrounding non-tumorous tissue. Additionally, up-regulation of system xc
- in activated microglia has been implicated in the pathogenesis of several neurodegenerative disorders mediated by excess glutamate. Consequently, system xc
- is a new drug target for brain cancer and neuroinflammatory diseases associated with excess extracellular glutamate. Unfortunately no potent and selective small molecule system xc
- inhibitors exist and to our knowledge, no high throughput screening (HTS) assay has been developed to identify new scaffolds for inhibitor design. To develop such an assay, various neuronal and non-neuronal human cells were evaluated as sources of system xc
-. Human glioma cells were chosen based on their high system xc
- activity. Using these cells, [14C]-cystine uptake and cystine-induced glutamate release assays were characterized and optimized with respect to cystine and protein concentrations and time of incubation. A pilot screen of the LOPAC/NINDS libraries using glutamate release demonstrated that the logistics of the assay were in place but unfortunately, did not yield meaningful pharmacophores. A larger, HTS campaign using the 384-well cystine-induced glutamate release as primary assay and the 96-well 14C-cystine uptake as confirmatory assay is currently underway. Unexpectedly, we observed that the rate of cystine uptake was significantly faster than the rate of glutamate release in human glioma cells. This was in contrast to the same rates of cystine uptake and glutamate release previously reported in normal human fibroblast cells. 相似文献
3.
N. Helge Meyer Hubert Mayerhofer Konstantinos Tripsianes Silke Blindow Daniela Barths Astrid Mewes Thomas Weimar Thies K?hli Steffen Bade Tobias Madl Andreas Frey Helmut Haas Jochen Mueller-Dieckmann Michael Sattler Gabriele Schramm 《The Journal of biological chemistry》2015,290(36):22111-22126
The IL-4-inducing principle from Schistosoma mansoni eggs (IPSE/α-1), the major secretory product of eggs from the parasitic worm S. mansoni, efficiently triggers basophils to release the immunomodulatory key cytokine interleukin-4. Activation by IPSE/α-1 requires the presence of IgE on the basophils, but the detailed molecular mechanism underlying activation is unknown. NMR and crystallographic analysis of IPSEΔNLS, a monomeric IPSE/α-1 mutant, revealed that IPSE/α-1 is a new member of the βγ-crystallin superfamily. We demonstrate that this molecule is a general immunoglobulin-binding factor with highest affinity for IgE. NMR binding studies of IPSEΔNLS with the 180-kDa molecule IgE identified a large positively charged binding surface that includes a flexible loop, which is unique to the IPSE/α-1 crystallin fold. Mutational analysis of amino acids in the binding interface showed that residues contributing to IgE binding are important for IgE-dependent activation of basophils. As IPSE/α-1 is unable to cross-link IgE, we propose that this molecule, by taking advantage of its unique IgE-binding crystallin fold, activates basophils by a novel, cross-linking-independent mechanism. 相似文献
4.
Martin F. J. Taylor Paul S. Sattler Megan Evans Richard A. Fuller James E. M. Watson Hugh P. Possingham 《Biodiversity and Conservation》2011,20(4):767-777
Despite the growing numbers of threatened species and high levels of spending on their recovery worldwide, there is surprisingly
little evidence about which conservation approaches are effective in arresting or reversing threatened species declines. Using
two government data sets, we examined associations between population trends for 841 nationally-threatened terrestrial species
in Australia, and four measures of conservation effort: (a) how much their distribution overlaps with strictly protected areas
(IUCN I–IV), (b) and other protected areas (IUCN V–VI), (c) the number of recovery activities directed at the species, and
(d) numbers of natural resource conservation activities applied in areas where populations of the threatened species occur.
We found that all populations of 606 (72%) species were in decline. Species with greater distributional overlap with strictly
protected areas had proportionately more populations that were increasing or stable. This effect was robust to geographic
range size, data quality differences and extent of protection. Measures other than strictly protected areas showed no positive
associations with stable or increasing trends. Indeed, species from regions with more natural resource conservation activities
were found to be more likely to be declining, consistent with differential targeting of such generalised conservation activities
to highly disturbed landscapes. Major differences in trends were also found among the different jurisdictions in which species
predominantly occurred, which may be related to different legislative protections against habitat destruction. Although we
were not able to test causation, this research corroborates other evidence that protected areas contribute to the stabilization
or recovery of threatened species, and provides little empirical support for other conservation approaches. 相似文献
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6.
Donato Santovito Virginia Egea Kiril Bidzhekov Lucia Natarelli Andr Mouro Xavier Blanchet Kanin Wichapong Maria Aslani Coy Brunßen Michael Horckmans Michael Hristov Arie Geerlof Esther Lutgens Mat J. A. P. Daemen Tilman Hackeng Christian Ries Triantafyllos Chavakis Henning Morawietz Ronald Naumann Philipp Von Hundelshausen Sabine Steffens Johan Duchêne Remco T. A. Megens Michael Sattler Christian Weber 《Autophagy》2020,16(12):2294
7.
Improved Sugar Conversion and Ethanol Yield for Forage Sorghum (Sorghum bicolor L. Moench) Lines with Reduced Lignin Contents 总被引:1,自引:0,他引:1
Bruce S. Dien Gautam Sarath Jeffrey F. Pedersen Scott E. Sattler Han Chen Deanna L. Funnell-Harris Nancy N. Nichols Michael A. Cotta 《Bioenergy Research》2009,2(3):153-164
Lignin is known to impede conversion of lignocellulose into ethanol. In this study, forage sorghum plants carrying brown midrib (bmr) mutations, which reduce lignin contents, were evaluated as bioenergy feedstocks. The near-isogenic lines evaluated were: wild type, bmr-6, bmr-12, and bmr-6 bmr-12 double mutant. The bmr-6 and bmr-12 mutations were equally efficient at reducing lignin contents (by 13% and 15%, respectively), and the effects were additive (27%) for the double mutant. Reducing lignin content was highly beneficial for improving biomass conversion yields. Sorghum biomass samples were pretreated with dilute acid and recovered solids washed and hydrolyzed with cellulase to liberate glucose. Glucose yields for the sorghum biomass were improved by 27%, 23%, and 34% for bmr-6, bmr-12, and the double mutant, respectively, compared to wild type. Sorghum biomass was also pretreated with dilute acid followed by co-treatment with cellulases and Saccharomyces cerevisiae for simultaneous saccharification and fermentation (SSF) into ethanol. Conversion of cellulose to ethanol for dilute-acid pretreated sorghum biomass was improved by 22%, 21%, and 43% for bmr-6, bmr-12, and the double mutant compared to wild type, respectively. Electron microscopy of dilute-acid treated samples showed an increased number of lignin globules in double-mutant tissues as compared to the wild-type, suggesting the lignin had become more pliable. The mutations were also effective for improving ethanol yields when the (degrained) sorghum was pretreated with dilute alkali instead of dilute acid. Following pretreatment with dilute ammonium hydroxide and SSF, ethanol conversion yields were 116 and 130 mg ethanol/g dry biomass for the double-mutant samples and 98 and 113 mg/g for the wild-type samples. 相似文献
8.
B. Le S. Tchize Ndejouong I. Sattler H.-M. Dahse E. Kothe C. Hertweck 《Bioorganic & medicinal chemistry letters》2009,19(22):6473-6476
Six novel isoflavone derivatives along with four known isoflavones were isolated from a culture of a highly nickel-resistant strain of Streptomyces mirabilis from a former uranium mining area. The structures of 7-hydroxy-3′,5′-dihydroxyisoflavone (5), 5,7-dihydroxy-3′,5′-dihydroxyisoflavone (6), 2′-hydroxy-3′-methoxygenistein (7), as well as hydroisoflavones A–C (8–10) were elucidated by MS and NMR analyses. Compounds 8–10 feature yet unprecedented types of non-aromatic, hydroxylated B rings, which result from plant isoflavone biotransformation. All new compounds display weak cytotoxic but potent antiproliferative activities. The anti-oestrogenic properties of 8 against MCF-7 human breast cancer cell line (GI50: 6 μM) is even higher than the reference compound genistein. 相似文献
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