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81.
Lethal effects of apidaecin on Escherichia coli involve sequential molecular interactions with diverse targets. 总被引:3,自引:0,他引:3
Apidaecins, short proline-arginine-rich peptides from insects, are highly bactericidal through a mechanism that includes stereoselective elements but is completely devoid of any pore-forming activity. The spectrum of antibacterial activity, always limited to Gram-negatives, is further dependent on a small number of variable residues and can be manipulated. We show here that mutations in the evolutionary conserved regions result in a more general loss of function, and we have used such analogs to probe molecular interactions in Escherichia coli. First, an assay was developed to measure selectively chiral association with cellular targets. By using this method, we find that apidaecin uptake is energy-driven and irreversible and yet can be partially competed by proline in a stereospecific fashion, results upholding a model of a permease/transporter-mediated mechanism. This putative transporter is not the end point of apidaecin action, for failure of certain peptide analogs to kill cells after entering indicates the existence of another downstream target. Tetracycline-induced loss of bactericidal activity and dose-dependent in vivo inhibition of translation by apidaecin point at components of the protein synthesis machinery as likely candidates. These findings provide new insights into the antibacterial mechanism of a unique group of peptides and perhaps, by extension, for distant mammalian relatives such as PR-39. 相似文献
82.
83.
Phosphoprotein phosphatase (EC 3.1.3.-) activity was found in human platelet homogenates and this activity was stimulated up to 20-fold by preincubation with trypsin. Both Mg2+ and Mn2+ greatly decreased the activity of trypsin-activated phosphatase but the activity of the untreated phosphatase was not affected by increasing the concentration of these divalent cations. It was also shown that the activity of the phosphatase underwent a transient inhibition upon addition of ATP and a permanent one with ATP-gamma-S. 相似文献
84.
Balasubramanian N Scott DW Castle JD Casanova JE Schwartz MA 《Nature cell biology》2007,9(12):1381-1391
Integrin-mediated adhesion regulates membrane binding sites for Rac1 within lipid rafts. Detachment of cells from the substratum triggers the clearance of rafts from the plasma membrane through caveolin-dependent internalization. The small GTPase Arf6 and microtubules also regulate Rac-dependent cell spreading and migration, but the mechanisms are poorly understood. Here we show that endocytosis of rafts after detachment requires F-actin, followed by microtubule-dependent trafficking to recycling endosomes. When cells are replated on fibronectin, rafts exit from recycling endosomes in an Arf6-dependent manner and return to the plasma membrane along microtubules. Both of these steps are required for the plasma membrane targeting of Rac1 and for its activation. These data therefore define a new membrane raft trafficking pathway that is crucial for anchorage-dependent signalling. 相似文献
85.
Susceptibility of immatures of the glassy-winged sharpshooter, Homalodisca coagulata (Say) (Hemiptera: Cicadellidae), to 10 insecticides that included chlorpyrifos, dimethoate, endosulfan, bifenthrin, cyfluthrin, esfenvalerate, fenpropathrin, acetamiprid, imidacloprid, and thiamethoxam was evaluated in the laboratory. All five instars were exposed to different doses of each foliar insecticide by the petri dish technique, whereas a systemic uptake method was used to assess the toxicity to imidacloprid and thiamethoxam. All test insecticides exhibited high toxicity to all immature stages of H. coagulata at concentrations below the field recommended rates of each insecticide. Although all five instars were susceptible to test insecticides, mortality was significantly higher in first instars than in the older immatures based on low LC50 values (ranging from 0.017 to 5.75 ng(AI)/ml) with susceptibility decreasing with each successive stage. Fifth instars were generally the least sensitive (LC50 values ranging from 0.325 to 216.63 ng (AI)/ml). These results show that mortality was directly related to age of the insect and suggest that chemical treatment at early stages is more effective than at late stages. Acetamiprid (neonicotinoid) and bifenthrin (pyrethroid) were the most toxic to all five instars, inducing most mortality within 24 h and showing lower LC50 values ranging from 0.017 to 0.686 ng/ml compared with other insecticides (LC50 values ranging from 0.191 to 216.63 ng(AI)/ml). Our data suggest that a diverse group of very effective insecticides are available to growers for controlling all stages of H. coagulata. Knowledge on toxicity of select insecticides to H. coagulata immatures may contribute to our understanding of resistance management in future for this pest by targeting specific life stages instead of the adult stage alone. 相似文献
86.
Morgann C. Reilly Steven B. Levery Sherry A. Castle J. Stacey Klutts Tamara L. Doering 《The Journal of biological chemistry》2009,284(52):36118-36127
Cryptococcus neoformans is a fungal pathogen that causes serious disease in immunocompromised individuals. The organism produces a distinctive polysaccharide capsule that is necessary for its virulence, a predominantly polysaccharide cell wall, and a variety of protein- and lipid-linked glycans. The glycan synthetic pathways of this pathogen are of great interest. Here we report the detection of a novel glycosylphosphotransferase activity in C. neoformans, identification of the corresponding gene, and characterization of the encoded protein. The observed activity is specific for UDP-xylose as a donor and for mannose acceptors and forms a xylose-α-1-phosphate-6-mannose linkage. This is the first report of a xylosylphosphotransferase activity in any system. 相似文献
87.
Md. Touhidul Islam Steven J. Castle & Shunxiang Ren 《Entomologia Experimentalis et Applicata》2010,134(1):28-34
A study on the compatibility of the entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin (Ascomycota: Hypocreales) with neem was conducted against sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), on eggplant. Initially, three concentrations of B. bassiana (106 , 107 , and 108 conidia ml−1 ) and three concentrations of neem (0.25, 0.5, and 1.0%) were used as individual treatments against B. tabaci . The highest concentration of B. bassiana yielded the highest B. tabaci egg (25.2%) and nymph mortalities (73.0%), but this was not significantly different from the mortalities caused by the 107 conidia ml−1 suspension. Similarly, the highest concentration of neem yielded the highest egg (27.3%) and nymph mortalities (75.5%), which was also not significantly different from the 0.5% suspension. Therefore, 0.5% neem was used along with 107 B. bassiana conidia ml−1 suspension as an integrated pest management program against B. tabaci . The combination of B. bassiana and neem yielded the highest B. tabaci egg (29.5%) and nymph mortalities (97.2%), and the lowest LT50 (2.08 day) value. Moreover, an integrated combination of B. bassiana with neem caused 27.6 and 20.5% more nymphal mortality than individual treatments of B. bassiana and neem, respectively, 7 days post-application. Thus, a combined application of an entomopathogenic fungus and a botanical insecticide may benefit from both, and it has proven effective for the control of B. tabaci on eggplant. 相似文献
88.
High-throughput approaches are beginning to have an impact on many areas of yeast biology. Two recent studies, using different experimental platforms, provide insight into new pathways involved in the response of yeast to DNA damage. 相似文献
89.
E. S. Castle 《The Journal of general physiology》1932,15(5):487-489
Alleged reversal of the phototropism of the sporangiophores of Phycomyces by high intensities of light does not occur if infra-red radiation is properly excluded. Phototropic "indifference" alone occurs at high intensities due to equal photic action on both sides of the sporangiophore. If heat radiation is not screened out, a gradual, negative thermotropic bending takes place. 相似文献
90.
Structure-activity relationship of a novel class of naphthyl amide KATP channel openers 总被引:1,自引:0,他引:1
Turner SC Carroll WA White TK Brune ME Buckner SA Gopalakrishnan M Fabiyi A Coghlan MJ Scott VE Castle NA Daza AV Milicic I Sullivan JP 《Bioorganic & medicinal chemistry letters》2003,13(10):1741-1744
We have discovered a novel series of N-[2-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-naphthalen-1-yl] amides that are potent openers of K(ATP) channels and investigated structure-activity relationships (SAR) around the 1,2-disubstituted naphthyl core. A-151892, a prototype compound of this series, was found to be a potent and efficacious potassium channel opener in vitro in transfected Kir6.2/SUR2B cells and pig bladder strips. Additionally, A-151892 was found to selectively inhibit unstable bladder contractions in vivo in an obstructed rat model of myogenic bladder function 相似文献