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51.
Malgorzata E. Sztolsztener Slawomir Pikula Joanna Bandorowicz-Pikula 《Archives of biochemistry and biophysics》2010,493(2):221-4123
Lysosome-like storage organelles (LSOs) play a crucial role in excessive accumulation of cholesterol in the Niemann-Pick type C (NPC) disease characterized by altered vesicular traffic of lipids. Annexin A6 (AnxA6) is mainly present in cytosol but upon elevation of [Ca2+]in binds to membranes. In addition, a pH or cholesterol-dependent mechanism of AnxA6 interaction with membranes was described. We found a several fold enrichment of AnxA6 in LSO compartment in fibroblasts isolated from NPC patients in comparison with fibroblasts from healthy individuals. We observed that AnxA6 relocates from cytosol to LSOs in a cholesterol-dependent manner. Cholesterol depletion caused reduction in the binding of AnxA6. Moreover, we found that in NPC cells AnxA6 translocates to the perinuclear region containing late endosomes (LE) loaded with cholesterol. We conclude that AnxA6 may participate in formation of cholesterol-rich platforms on LE and therefore may contribute to the pathology of the NPC disease. 相似文献
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LISA WINGATE ULLI SEIBT† KADMIEL MASEYK‡ JÉRÔME OGÉE§ PEDRO ALMEIDA¶ DAN YAKIR‡ JOAO S. PEREIRA¶ MAURIZIO MENCUCCINI 《Global Change Biology》2008,14(9):2178-2193
The oxygen stable isotope composition (δ18O) of CO2 is a valuable tool for studying the gas exchange between terrestrial ecosystems and the atmosphere. In the soil, it records the isotopic signal of water pools subjected to precipitation and evaporation events. The δ18O of the surface soil net CO2 flux is dominated by the physical processes of diffusion of CO2 into and out of the soil and the chemical reactions during CO2–H2O equilibration. Catalytic reactions by the enzyme carbonic anhydrase, reducing CO2 hydration times, have been proposed recently to explain field observations of the δ18O signatures of net soil CO2 fluxes. How important these catalytic reactions are for accurately predicting large‐scale biosphere fluxes and partitioning net ecosystem fluxes is currently uncertain because of the lack of field data. In this study, we determined the δ18O signatures of net soil CO2 fluxes from soil chamber measurements in a Mediterranean forest. Over the 3 days of measurements, the observed δ18O signatures of net soil CO2 fluxes became progressively enriched with a well‐characterized diurnal cycle. Model simulations indicated that the δ18O signatures recorded the interplay of two effects: (1) progressive enrichment of water in the upper soil by evaporation, and (2) catalytic acceleration of the isotopic exchange between CO2 and soil water, amplifying the contributions of ‘atmospheric invasion’ to net signatures. We conclude that there is a need for better understanding of the role of enzymatic reactions, and hence soil biology, in determining the contributions of soil fluxes to oxygen isotope signals in atmospheric CO2. 相似文献
54.
将刺梨提取物用于卷烟加料,用二氯甲烷同时蒸馏萃取刺梨提取物,分别用极性柱和非极性柱进行GC/MS分析.结果表明,刺梨提取物与烟香谐调,具有增加香气质和香气量、掩盖杂气、改善余味的作用,是安全有效的天然烟用香料;采用双柱分析的方法共检出62种化合物,比用单一极性柱分析更能相对客观、全面的反映刺梨提取物中的致香成分的状况;... 相似文献
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We describe here a new method for specific staining of mast cells using ferroin. Different hamster tissues were fixed in 4% formalin and processed for paraffin embedding. Sections were stained with hematoxylin followed by ferroin acidified with 2.5 N sulfuric acid to pH 4.0. Mast cells stained an intense orange color that contrasted markedly with bluish violet nuclei. High contrast was also observed when ferroin colored sections were counterstained with light green instead of hematoxylin. To evaluate the specificity of the stain, hamster cheek pouch sections were stained with toluidine blue, alcian blue-safranin O, and ferroin. Quantitative evaluation of mast cells stained with the three techniques showed no statistical difference. The simplicity and selectivity of this method is sufficient for image analysis of mast cells. 相似文献
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Malgorzata E. Sztolsztener Anita Brewinska Bernard Guiard Agnieszka Chacinska 《Traffic (Copenhagen, Denmark)》2013,14(3):309-320
The conserved MIA pathway is responsible for the import and oxidative folding of proteins destined for the intermembrane space of mitochondria. In contrast to a wealth of information obtained from studies with yeast, the function of the MIA pathway in higher eukaryotes has remained enigmatic. Here, we took advantage of the molecular understanding of the MIA pathway in yeast and designed a model of the human MIA pathway. The yeast model for MIA consists of two critical components, the disulfide bond carrier Mia40 and sulfhydryl oxidase Erv1/ALR. Human MIA40 and ALR substituted for their yeast counterparts in the essential function for the oxidative biogenesis of mitochondrial intermembrane space proteins. In addition, the sulfhydryl oxidases ALR/Erv1 were found to be involved in the mitochondrial localization of human MIA40. Furthermore, the defective accumulation of human MIA40 in mitochondria underlies a recently identified disease that is caused by amino acid exchange in ALR. Thus, human ALR is an important factor that controls not only the ability of MIA40 to bind and oxidize protein clients but also the localization of human MIA40 in mitochondria. 相似文献
57.
BARBARA RANDLKOFER ELISABETH OBERMAIER JÉRÔME CASAS TORSTEN MEINERS 《Ecological Entomology》2010,35(4):446-455
1. A heterogeneous habitat structure can have a profound impact on foraging carnivorous arthropods. In the present study, we examined which elements of complex vegetation structure influence the searching movement of a parasitoid model organism. 2. Previous field work showed that tall and dense vegetation reduces the parasitism success of the eulophid egg parasitoid Oomyzus galerucivorus while the probability of host egg deposition increased close to plant tips. 3. In laboratory bioassays, dried grass stems were arranged according to the natural situation in different setups. The wasps' walking time on stems increased with increasing stem height and density. High stem density decreased the walking time of the parasitoids on the ground and an increased stem height reduced the propensity to fly to the ground. Connectivity had a minor positive effect on the number of stem contacts, but considerably reduced the number of wasps reaching the upper part of grass stems by two‐thirds. 4. Thus, although enhanced vegetation complexity enhances walking activity of the parasitoids in the vegetation, laying eggs at the tip of long grass stems in dense vegetation can be an adaptive strategy for the host, as it maximises the number of connections between plant parts to cross by parasitoids before reaching the host. The connection points disorient the wasps, which lose time, reverse their direction or fly away. 相似文献
58.
Karen Silence Torsten Dreier Mahan Moshir Peter Ulrichts Sofie ME Gabriels Michael Saunders Harald Wajant Peter Brouckaert Leander Huyghe Tim Van Hauwermeiren Alain Thibault Hans J De Haard 《MABS-AUSTIN》2014,6(2):523-532
Overexpression of CD70 has been documented in a variety of solid and hematological tumors, where it is thought to play a role in tumor proliferation and evasion of immune surveillance. Here, we describe ARGX-110, a defucosylated IgG1 monoclonal antibody (mAb) that selectively targets and neutralizes CD70, the ligand of CD27.
ARGX-110 was generated by immunization of outbred llamas. The antibody was germlined to 95% human identity, and its anti-tumor efficacy was tested in several in vitro assays. ARGX-110 binds CD70 with picomolar affinity. In depletion studies, ARGX-110 lyses tumor cells with greater efficacy than its fucosylated version. In addition, ARGX-110 demonstrates strong complement-dependent cytotoxicity and antibody-dependent cellular phagocytosis activity. ARGX-110 inhibits signaling of CD27, which results in blocking of the activation and proliferation of Tregs. In a Raji xenograft model, administration of the fucosylated version of ARGX-110 resulted in a prolonged survival at doses of 0.1 mg/kg and above. The pharmacokinetics of ARGX-110 was tested in cynomolgus monkeys; the calculated half-life is 12 days.
In conclusion, ARGX-110 is a potent blocking mAb with a dual mode of action against both CD70-bearing tumor cells and CD70-dependent Tregs. This antibody is now in a Phase 1 study in patients with advanced malignancies expressing CD70 (). NCT01813539相似文献
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Margot ME Gosman Dirkje S Postma Judith M Vonk Bea Rutgers Monique Lodewijk Mieke Smith Marjan A Luinge Nick HT ten Hacken Wim Timens 《Respiratory research》2008,9(1):1-9