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Wilna J. Moree Bin-Feng Li Said Zamani-Kord Jinghua Yu Timothy Coon Charles Huang Dragan Marinkovic Fabio C. Tucci Siobhan Malany Margaret J. Bradbury Lisa M. Hernandez Jianyun Wen Hua Wang Samuel R.J. Hoare Robert E. Petroski Kayvon Jalali Chun Yang Aida Sacaan Ajay Madan Paul D. Crowe Graham Beaton 《Bioorganic & medicinal chemistry letters》2010,20(19):5874-5878
Analogs of the known H1-antihistamine R-dimethindene with suitable selectivity for key GPCRs, P450 enzymes and hERG channel were assessed for metabolism profile and in vivo properties. Several analogs were determined to exhibit diverse metabolism. One of these compounds, 10a, showed equivalent efficacy in a rat EEG/EMG model to a previously identified clinical candidate and a potentially superior pharmacokinetic profile as determined from a human microdose study. 相似文献
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The aim of the study was to determine the impact of demographic and anthropometric parameters on the gastric myoelectrical activity characteristics in a healthy Croatian population. The influence of age, sex, body mass index (BMI) and menstrual cycle phase on the gastric myoelectrical activity characteristics was assessed. The study included 120 healthy subjects of both sexes (60 male and 60 female), divided into four age groups (18-35, 36-50, 51-65 and > 65 years) and three BMI groups (BMI < 25, 25-30 and > 30). Female subjects of reproductive age were divided into three groups according to menstrual cycle phase (day 1-3, day 4-8 and day 9-20 of menstruation). All study subjects underwent percutaneous electrogastrography (EGG) for 60 min before and 60 min after a test meal. The following parameters of the gastric myoelectrical activity were observed: dominant frequency (DF); dominant frequency within normal range (DFNR, %); coefficient of variation for dominant frequency (CVDF); dominant strength (DS. mV); postprandial increase intensity in dominant strength (PPIIDS, %); bradygastria (BG, c/min, %); tachygastria (TG, c/min, %); and arrhythmia (AR). Age was found to influence preprandial but not postprandial DFNR, CVDF and AR. Sex influenced preprandial DF, CVDF, DS and BG, and postprandial DF, CVDF, PPIIDS and TG. BMI exerted an impact on preprandial TG and AR, and postprandial DF, CVDF and AR. The phase of menstrual cycle influenced DF in preprandial period and none of EGG parameters in postprandial period. 相似文献
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de Morrée A Hensbergen PJ van Haagen HH Dragan I Deelder AM 't Hoen PA Frants RR van der Maarel SM 《PloS one》2010,5(11):e13854
Dysferlin is critical for repair of muscle membranes after damage. Mutations in dysferlin lead to a progressive muscular dystrophy. Recent studies suggest additional roles for dysferlin. We set out to study dysferlin's protein-protein interactions to obtain comprehensive knowledge of dysferlin functionalities in a myogenic context. We developed a robust and reproducible method to isolate dysferlin protein complexes from cells and tissue. We analyzed the composition of these complexes in cultured myoblasts, myotubes and skeletal muscle tissue by mass spectrometry and subsequently inferred potential protein functions through bioinformatics analyses. Our data confirm previously reported interactions and support a function for dysferlin as a vesicle trafficking protein. In addition novel potential functionalities were uncovered, including phagocytosis and focal adhesion. Our data reveal that the dysferlin protein complex has a dynamic composition as a function of myogenic differentiation. We provide additional experimental evidence and show dysferlin localization to, and interaction with the focal adhesion protein vinculin at the sarcolemma. Finally, our studies reveal evidence for cross-talk between dysferlin and its protein family member myoferlin. Together our analyses show that dysferlin is not only a membrane repair protein but also important for muscle membrane maintenance and integrity. 相似文献
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Nemanja Barać Sandra Škrivanj Zoran Bukumirić Milan Barać Dragan Manojlović Rada Petrović 《Soil & Sediment Contamination》2015,24(6):656-674
This article reports the results of a study focused on the presence and bioavailability of arsenic in agricultural soil in the mining and industrial regions of northern Kosovo and southern Serbia, as well as uptake and bioaccumulation of arsenic in two commonly cultivated plant species (Zea mays L. and Solanum tuberosum L.). This area was one of the most important mining districts in Europe. The collected soil samples were subjected to a modified BCR three-step sequential extraction procedure in order to investigate the chemical partitioning of arsenic in the soils. The general distribution of arsenic in various fractions was: exchangeable < reducible < oxidizable fractions. Highest concentrations of total arsenic in soil were found close to industrial facilities and tailing ponds. In addition, fluvisols were significantly more enriched with arsenic than soils at a distance from the river flows. The edible parts of the plant specimen showed different As contents, suggesting that these plant species have different propensities for the uptake and bioaccumulation of arsenic from soil. 相似文献
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Dijana Krstić-Milošević Teodora Janković Branka Uzelac Dragan Vinterhalter Branka Vinterhalter 《Plant Cell, Tissue and Organ Culture》2017,128(3):631-640
Abandoned metalliferous wastes can be spontaneously colonized by specialized species or ecotypes, and therefore representatives from such populations might be exploited in phytoremediation. Thus, this study was focused on determining the conditions for culture initiation and elaborating the propagation protocol of wild calamine ecotype of Dianthus carthusianorum. The proper propagation medium proved modified MS enriched with 1.0 mg/L 2iP and 0.2 mg/L IAA. The massive majority (93%) of microplantlets were successfully transferred to ex vitro conditions. Micropropagated calamine ecotype of D. carthusianorum has proved to be useful for phytoremediation application. The obtained plants experimentally cultivated on post-flotation wastes generated during the process of zinc-lead ore enrichment were monitored, and compared with specimens of the population obtained as a result of seed sowing. Plants propagated through tissue culture grew better, developed faster and more abundantly bloomed in comparison with the generatively propagated control material. This is one of the few reports concerning the possibility of using in vitro technique for effective production of plant material ready to be used in chemically degraded area. 相似文献