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21.
Identification of a new membrane-permeable inhibitor against inositol-1,4,5-trisphosphate-3-kinase A
Dominik Schröder Christoph Rehbach Carola Seyffarth Martin Neuenschwander Jens V. Kries Sabine Windhorst 《Biochemical and biophysical research communications》2013
Ectopic expression of the neuron-specific inositol-1,4,5-trisphosphate-3-kinase A (ITPKA) in lung cancer cells increases their metastatic potential because the protein exhibits two actin regulating activities; it bundles actin filaments and regulates inositol-1,4,5-trisphosphate (InsP3)-mediated calcium signals by phosphorylating InsP3. Thus, in order to inhibit the metastasis-promoting activity of ITPKA, both its actin bundling and its InsP3kinase activity has to be blocked. In this study, we performed a high throughput screen in order to identify specific and membrane-permeable substances against the InsP3kinase activity. Among 341,44 small molecules, 237 compounds (0.7%) were identified as potential InsP3kinase inhibitors. After determination of IC50-values, the three compounds with highest specificity and highest hydrophobicity (EPPC-3, BAMB-4, MEPTT-3) were further characterized. Only BAMB-4 was nearly completely taken up by H1299 cells and remained stable after cellular uptake, thus exhibiting a robust stability and a high membrane permeability. Determination of the inhibitor type revealed that BAMB-4 belongs to the group of mixed type inhibitors. Taken together, for the first time we identified a highly membrane-permeable inhibitor against the InsP3kinase activity of ITPKA providing the possibility to partly inhibit the metastasis-promoting effect of ITPKA in lung tumor cells. 相似文献
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植物体和植物根际均是复杂的微生态系统,其内栖息着关系复杂的共生微生物,共同影响植物的生长发育.为探讨混合接种真菌与细菌对兰科植物生长的影响,筛选出真菌与细菌的优势促生组合,本研究选取经分离、筛选获得的4株促生内生真菌(铁皮石斛内生真菌C22、C35,美花石斛内生真菌L12、L28)和3株促生内生细菌(铁皮石斛菌内生细菌TX-7、TX-16、TX-19),以"真菌+细菌"的方式混合接种于铁皮石斛无菌组培苗中,共培养120 d.结果获得了3组优势组合:C22+TX-19、L28+TX-16和L28+TX-19,它们对铁皮石斛组培苗的生长均表现出正效应,其中C22+TX-19和L28+TX-19对促进组培苗生物量的增长具有协同效应,L28+TX-19对提高组培苗的根分枝率具有协同效应,3个组合对增加组培苗的分蘖数和根尖数均表现为累加效应.研究结果表明,内生真菌与内生细菌的共同作用可显著促进铁皮石斛的生长,混合接种有可能更大地发挥微生物的效能. 相似文献
25.
Othman Wan-Norafikah Wasi Ahmad Nazni Han Lim Lee Pawanchee Zainol-Ariffin Mohd Sofian-Azirun 《Saudi Journal of Biological Sciences》2013,20(3):241-250
The resistance status towards permethrin among the laboratory strain, the permethrin-selected strain and four field strains of Culex quinquefasciatus collected in Kuala Lumpur, Malaysia was determined using three standard laboratory methods: WHO larval bioassay, WHO adult bioassay and biochemical microplate assay. Cx. quinquefasciatus permethrin-selected strain larvae were the least susceptible to permethrin with a resistance ratio of 47.28-folds, whereas all field strain larvae of the same species were tolerant to permethrin with resistance ratios of more than 3-folds. In contrast, in adult stage, the permethrin exposed permethrin-selected strain (resistance ratio = 1.27) was found to be more susceptible to permethrin than all permethrin-exposed field strains (resistance ratios = 2.23–2.48). Complete mortalities for all strains of Cx. quinquefasciatus adults proved the effectiveness of the synergist; piperonyl butoxide (PBO). For the biochemical microplate assay, the reduction of the mean optical density of elevated oxidase activity of three field strains upon exposure to PBO confirmed the association between oxidase activity and permethrin tolerance. On the other hand, irregular patterns of the mean optical density of elevated oxidase activity in the laboratory strain, permethrin-selected strain and Jalan Fletcher strain illustrated the gene variation within these mosquito colonies as well as the involvement of other enzyme activities in the permethrin resistance occurred. 相似文献
26.
In the present study, the interaction between the HSA and MnCORM in vitro under physiological conditions, was investigated through ultraviolet-visible (UV-vis) absorption, fluorescence, time-resolved fluorescence, circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopic techniques and in silico molecular docking methods. Binding parameters such as the binding constant, number of binding sites and binding force were obtained from the fluorescence data. Thermodynamic interaction revealed that the reaction was spontaneous (ΔG < 0) and hydrogen bond and van der Waals interaction were primarily involved in the binding. The changes induced in the secondary structure conformation due to the MnCORM interaction were monitored using CD and FT-IR spectroscopic techniques. The results showed reduction in α-helix conformation and corresponding increase in β-sheet and unordered structures due to slight unfolding. The time-resolved fluorescence decay confirmed the static quenching mechanism of the MnCORM. The molecular docking studies revealed that the MnCORM interacted at Sudlow’s site II of domain IIIA through hydrogen bond and van der Waals interactions. In order to understand the drug distribution and elimination, studies on the drug molecule interaction with HSA are vital. Therefore, it is evident that MnCORM interacts with HSA through ground state complex formation and thus suitable for in vivo delivery. 相似文献
27.
Emma Roig-Molina Mirian Domenech María de Gracia Retamosa Montserrat Nácher-Vázquez Luis Rivas Beatriz Maestro Pedro García Ernesto García Jesús M. Sanz 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(1):96-104
Antibiotic resistance is a global current threat of increasing importance. Moreover, biofilms represent a medical challenge since the inherent antibiotic resistance of their producers demands the use of high doses of antibiotics over prolonged periods. Frequently, these therapeutic measures fail, contributing to bacterial persistence, therefore demanding the development of novel antimicrobials. Esters of bicyclic amines (EBAs), which are strong inhibitors of Streptococcus pneumoniae growth, were initially designed as inhibitors of pneumococcal choline-binding proteins on the basis of their structural analogy to the choline residues in the cell wall. However, instead of mimicking the characteristic cell chaining phenotype caused by exogenously added choline on planktonic cultures of pneumococcal cells, EBAs showed an unexpected lytic activity. In this work we demonstrate that EBAs display a second, and even more important, function as cell membrane destabilizers. We then assayed the inhibitory and disintegrating activity of these molecules on pneumococcal biofilms. The selected compound (EBA 31) produced the highest effect on S. pneumoniae (encapsulated and non-encapsulated) biofilms at very low concentrations. EBA 31 was also effective on mixed biofilms of non-encapsulated S. pneumoniae plus non-typeable Haemophilus influenzae, two pathogens frequently forming a self-produced biofilm in the human nasopharynx. These results support the role of EBAs as a promising alternative for the development of novel, broad-range antimicrobial drugs encompassing both Gram-positive and Gram-negative pathogens. 相似文献
28.
The population dynamics of Aphanizomenon flos-aquae var. klebahnii Elenk. (Cyanophyceae) was studied in an artificial pond for 32 months from May 2002 to December 2004. Our previous in vitro
study showed that the lower limits of water temperature and pH for its growth are within the ranges of 11°–14°C and 7.1–7.4,
respectively, and it appeared that these findings are applicable to the emergence and disappearance of Ap. flos-aquae in the pond. Based on the change in the water temperature, the emergence of Ap. flos-aquae in 2004 was expected to be in late April, whereas emergence occurred after a 1-month lag period. During this period, Ankistrodesmus falcatus (Corda) Ralfs (Chlorophyceae) dominated the phytoplankton assemblage, which raised the possibility that the growth of Ap. flos-aquae was restricted by the existence of An. falcatus. We conducted mixed cultures of Ap. flos-aquae and An. falcatus at four temperatures (14°, 19°, 24°, and 29°C). After 18 days of incubation, An. falcatus dominated at 14° and 29°C whereas Ap. flos-aquae dominated at 19°C. This result indicates that a slightly higher water temperature than the growth threshold value is needed
for Ap. flosaquae to outcompete An. falcatus, which agrees with the field observation. Contrary to the results of the mixed culture, the summer phytoplankton assemblage
was dominated by Ap. flos-aquae, and the population of An. falcatus was less or almost absent. This variation seemed to be partly caused by the difference in nutrient conditions; concentrations
of dissolved inorganic nitrogen and phosphorus in the pond were far lower than those in the culture medium. The lack of nitrogen
fixation of An. falcatus seemed to be a growth disadvantage during the summer when the concentration of dissolved inorganic nitrogen was low. 相似文献
29.
目的:探讨混合甲醛固定液固定大肠癌淋巴结标本的最佳免疫组化效果。方法:采用不同pH值(6.0、7.0、8.0)的混合甲醛固定液对39枚大肠癌淋巴结标本进行不同时间(6 h、6 h-12 h、1 d-7 d)的固定处理。以细胞角蛋白20(CK20)为目标抗原,运用OIympusdp 70图像采集分析仪抽选出混合甲醛固定液最佳免疫组化染色的pH值及固定时间。结果:经pH值为7.0混合甲醛固定液处理后,阳性率为92.31%,高于经pH值为6.0、8.0的混合甲醛固定液处理后的76.92%、74.36%,且经pH值为7.0、8.0处理后的阳性率比较有统计差异(P0.05)。混合甲醛固定液的固定时间在6 h-12 h时的阳性率为94.87%,高于固定时间为6 h、1 d-7 d处理的30.77%、76.92%(P0.05)。结论:对于大肠癌淋巴结标本,以CK20为目标抗原,选择pH值为7.0的混合甲醛固定液固定6 h-12 h能够得到质量较佳的免疫组化染色效果。 相似文献
30.
《Journal of Asia》2022,25(2):101882
Honey bees and stingless bees are generalist visitors of several wild and cultivated plants. They forage with a high degree of floral fidelity and thereby help in the pollination services of those plants. We hypothesized that pollination efficiency might be influenced by flowering phenology, floral characteristics, and resource collection modes of the worker bees. In this paper, we surveyed the foraging strategies of honey bees (Apis cerana, Apis dorsata, and Apis florea) and stingless bees (Tetragonula iridipennis) concerning their pollination efficiencies. Bees showed different resource gathering strategies, including legitimate (helping in pollination as mixed foragers and specialized foragers) and illegitimate (serving as nectar robbers and pollen thieves) types of flower visitation patterns. Foraging strategies are influenced by the shape of flowers, the timing of the visitation, floral richness, and bee species. Honey bees and stingless bees mainly acted as legitimate visitors in most plants studied. Sometimes honey bees served as nectar robbers in tubular flowers and stingless bees as pollen thieves in large-sized flowers. Among the legitimate categories, mixed foragers have a comparatively lower flower visitation rate than the specialized nectar and pollen foragers. However, mixed foragers have greater abundance and higher values of the single-visit pollination efficiency index (PEi) than nectar and pollen foragers. The value of the combined parameter ‘importance in pollination (PI)’ was thus higher in mixed foragers than in nectar and pollen foragers. 相似文献