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排序方式: 共有203条查询结果,搜索用时 15 毫秒
1.
Johnathan L Meaders Erica F Geers Belen Fernandez‐Garcia Marvin E Tanenbaum 《The EMBO journal》2012,31(21):4179-4190
The microtubule motor protein kinesin‐5 (Eg5) provides an outward force on centrosomes, which drives bipolar spindle assembly. Acute inhibition of Eg5 blocks centrosome separation and causes mitotic arrest in human cells, making Eg5 an attractive target for anti‐cancer therapy. Using in vitro directed evolution, we show that human cells treated with Eg5 inhibitors can rapidly acquire the ability to divide in the complete absence of Eg5 activity. We have used these Eg5‐independent cells to study alternative mechanisms of centrosome separation. We uncovered a pathway involving nuclear envelope (NE)‐associated dynein that drives centrosome separation in prophase. This NE‐dynein pathway is essential for bipolar spindle assembly in the absence of Eg5, but also functions in the presence of full Eg5 activity, where it pulls individual centrosomes along the NE and acts in concert with Eg5‐dependent outward pushing forces to coordinate prophase centrosome separation. Together, these results reveal how the forces are produced to drive prophase centrosome separation and identify a novel mechanism of resistance to kinesin‐5 inhibitors. 相似文献
2.
System Development for Linked-Fermentation Production of Solvents from Algal Biomass 总被引:5,自引:3,他引:2 下载免费PDF全文
J. P. Nakas M. Schaedle C. M. Parkinson C. E. Coonley S. W. Tanenbaum 《Applied microbiology》1983,46(5):1017-1023
Five species of the genus Dunaliella (D. tertiolecta, D. primolecta, D. parva, D. bardawil, and D. salina) were examined for glycerol accumulation, growth rate, cell density, and protein and chlorophyll content. The suitability of each algal species for use as a fermentation substrate was judged according to glycerol accumulation and quantities of neutral solvents produced after sequential bacterial fermentations. When grown in 2 M NaCl, with 24 mM NaHCO3 or 3% CO2 at 28°C and with 10,000 to 15,000 lx of incident light on two sides of a glass aquarium, four of the five species tested produced ca. 10 to 20 mg of glycerol per liter of culture. Clostridium pasteurianum was found to convert an algal biomass mixture supplemented with 4% glycerol to ca. 16 g of mixed solvents (n-butanol, 1,3-propanediol, and ethanol) per liter. Acetone was not detected. Additionally, it has been demonstrated that Dunaliella concentrates of up to 300-fold can be directly fermented to an identical pattern of mixed solvents. Overall solvent yields were reduced by >50% when fermentations were performed in the presence of 2% NaCl. These results are discussed in terms of practical application in tropical coastal zones. 相似文献
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A study of the mechanism of action of cytochalasin A (CA) in relation to its structural features and to its selective inhibition of certain contractile processes has been initiated. Quantitative structure-function analyses with several CA-related cytochalasins — including synthetic 21, 22-dihydro-CA (DHCA), the 22-β-mercaptoethanol CA-adduct, (CA-2ME), and the 22-dithiothreitol CA-adduct (CA-DTT) — have been carried out in a temperature sensitive gel-sol extract from Ehrlich ascites tumor cells. Each drug congener was purified to homogeneity by HPLC prior to biological testing. The undiminished inhibitory indices of DHCA and CA-2ME overrules the prior circumstantial evidence accumulated for the obligatory electrophilic interaction of this drug, at its α-β-unsaturated ketone region, with presumptive receptor nucleophiles. 相似文献
6.
Convenient procedures for the biosynthesis, isolation, and isotope labeling of cytochalasins. 下载免费PDF全文
Efforts to improve small-scale yields of useful cytochalasins by fermentation resulted in selection of an enriched aflatoxin medium which increased yields by fivefold over those reported in the literature. With Helminthosporium dematoideum and Zygosporium masonii in stationary culture for 3 weeks, cytochalasins B and D were obtained in quantities approaching 700 and 500 mg/liter, respectively. It appears that the critical component in this growth medium is factors associated with whole wheat. By using these procedures, coupled with improvements in isolation, supplementation with two radioactive phenylalanine species readily produced [14C]- or [3H]cytochalasin B. Oxidation of carrier-free radioactive cytochalasin B to cytochasasin A readily provided this labeled congener as well. The isotopic ocnversion of precursor to crystalline products that met analytical criteria ranged from 2 to 4% of the administered radioactivity. 相似文献
7.
The changes in germination, peroxidase activity and isoperoxidase spectrum have been studied in apple embryos at 5°C (stratification) and at 20°C in the presence or absence of seed coats. The embryo dormancy is progressively released at 5°C, but not at 20°C. The peroxidase activity in embryos covered with seed coats is very low at 5°C as well as at 20°C which corresponds to a restricted number of isoenzymes. In isolated embryos the peroxidase activity increases significantly. This is due to an increase in both the number and the activity of the isoperoxidases and it is more pronounced at 20°C than at 5°C. The obtained results suggest that the soluble peroxidases are not involved in the process of the release of embryo dormancy. The variations observed are attributed to the growth process following germination, which can occur even at low temperature. 相似文献
8.
AB Kane RP Stanton EG Raymond ME Dobson ME Knafelc JL Farber 《The Journal of cell biology》1980,87(3):643-651
The relationship between intracellular lysosomal rupture and cell death caused by silica was studied in P388d(1) macrophages. After 3 h of exposure to 150 μg silica in medium containing 1.8 mM Ca(2+), 60 percent of the cells were unable to exclude trypan blue. In the absence of extracellular Ca(2+), however, all of the cells remained viable. Phagocytosis of silica particles occurred to the same extent in the presence or absence of Ca(2+). The percentage of P388D(1) cells killed by silica depended on the dose and the concentration of Ca(2+) in the medium. Intracellular lyosomal rupture after exposure to silica was measured by acridine orange fluorescence or histochemical assay of horseradish peroxidase. With either assay, 60 percent of the cells exposed to 150 μg silica for 3 h in the presence of Ca(2+) showed intracellular lysosomal rupture, was not associated with measureable degradation of total DNA, RNA, protein, or phospholipids or accelerated turnover of exogenous horseradish peroxidase. Pretreatment with promethazine (20 μg/ml) protected 80 percent of P388D(1) macrophages against silica toxicity although lysosomal rupture occurred in 60-70 percent of the cells. Intracellular lysosomal rupture was prevented in 80 percent of the cells by pretreatment with indomethacin (5 x 10(-5)M), yet 40-50 percent of the cells died after 3 h of exposure to 150 μg silica in 1.8 mM extracellular Ca(2+). The calcium ionophore A23187 also caused intracellular lysosomal rupture in 90-98 percent of the cells treated for 1 h in either the presence or absence of extracellular Ca(2+). With the addition of 1.8 mM Ca(2+), 80 percent of the cells was killed after 3 h, whereas all of the cells remained viable in the absence of Ca(2+). These experiments suggest that intracellular lysosomal rupture is not causally related to the cell death cause by silica or . Cell death is dependent on extracellular Ca(2+) and may be mediated by an influx of these ions across the plasma membrane permeability barrier damaged directly by exposure to these toxins. A23187相似文献
9.
A covalently bound photoisomerizable agonist. Comparison with reversibly bound agonists at electrophorus electroplaques 总被引:2,自引:2,他引:0 下载免费PDF全文
HA Lester ME Krouse MM Nass NH Wassermann BF Erlanger 《The Journal of general physiology》1980,75(2):207-232
After disulphide bonds are reduced with dithiothreitol, trans-3- (α-bromomethyl)-3’-[α- (trimethylammonium)methyl]azobenzene (trans-QBr) alkylates a sulfhydryl group on receptors. The membrane conductance induced by this “tethered agonist” shares many properties with that induced by reversible agonists. Equilibrium conductance increases as the membrane potential is made more negative; the voltage sensitivity resembles that seen with 50 [mu]M carbachol. Voltage- jump relaxations follow an exponential time-course; the rate constants are about twice as large as those seen with 50 μM carbachol and have the same voltage and temperature sensitivity. With reversible agonists, the rate of channel opening increases with the frequency of agonist-receptor collisions: with tethered trans-Qbr, this rate depends only on intramolecular events. In comparison to the conductance induced by reversible agonists, the QBr-induced conductance is at least 10-fold less sensitive to competitive blockade by tubocurarine and roughly as sensitive to “open-channel blockade” bu QX-222. Light-flash experiments with tethered QBr resemble those with the reversible photoisomerizable agonist, 3,3’,bis-[α-(trimethylammonium)methyl]azobenzene (Bis-Q): the conductance is increased by cis {arrow} trans photoisomerizations and decreased by trans {arrow} cis photoisomerizations. As with Bis-Q, ligh-flash relaxations have the same rate constant as voltage-jump relaxations. Receptors with tethered trans isomer. By comparing the agonist-induced conductance with the cis/tans ratio, we conclude that each channel’s activation is determined by the configuration of a single tethered QBr molecule. The QBr-induced conductance shows slow decreases (time constant, several hundred milliseconds), which can be partially reversed by flashes. The similarities suggest that the same rate-limiting step governs the opening and closing of channels for both reversible and tethered agonists. Therefore, this step is probably not the initial encounter between agonist and receptor molecules. 相似文献
10.
Owing to its lipophilic property, carbon tetrachloride (CCl4) is rapidly absorbed by both the liver and brain. We investigated the protective effects of crocin against brain damage caused by CCl4. Fifty rats were divided into five groups of ten: control, corn oil, crocin, CCl4 and CCl4 + crocin. CCl4 administration decreased glutathione (GSH) and total antioxidant status (TAS) levels, and catalase (CAT) activity, while significant increases were observed in malondialdehyde (MDA) and total oxidant status (TOS) levels and superoxide dismutase (SOD) activity. The cerebral cortex nuclear lamina developed a spongy appearance, neuronal degeneration was observed in the hippocampus, and heterochromatic and pyknotic neurons with increased cytoplasmic eosinophilia were observed in the hippocampus after CCl4 treatment. Because crocin exhibits strong antioxidant properties, crocin treatment increased GSH and TAS levels and CAT activities, and decreased MDA and TOS levels and SOD activity; significant improvements also were observed in histologic architecture. We found that crocin administration nearly eliminated CCl4 induced brain damage by preventing oxidative stress. 相似文献