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11.
Nantermet PG Burgey CS Robinson KA Pellicore JM Newton CL Deng JZ Selnick HG Lewis SD Lucas BJ Krueger JA Miller-Stein C White RB Wong B McMasters DR Wallace AA Lynch JJ Yan Y Chen Z Kuo L Gardell SJ Shafer JA Vacca JP Lyle TA 《Bioorganic & medicinal chemistry letters》2005,15(11):2771-2775
In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxidative metabolism, it also overcomes the metabolic liability associated with the pyrazinones. An optimization study of the P(1) benzylamide delivered the potent thrombin inhibitor 21 (K(i) = 3.2 nM, 2xaPTT = 360 nM), which exhibited good plasma levels and half-life after oral dosing in the dog (C(max) = 2.6 microM, t(1/2) = 4.5 h). 相似文献
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Gracia-Marco L Valtueña J Ortega FB Pérez-López FR Vicente-Rodríguez G Breidenassel C Ferrari M Molnar D Widhalm K de Henauw S Kafatos A Diaz LE Gottrand F Maiani G Stehle P Castillo MJ Moreno LA González-Gross M;on behalf of the HELENA Study Group 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,113(4):566-573
There is a lack of studies that analyze the association between micronutrient-related biomarker status and physical fitness in adolescents. In the present study, biochemical parameters for iron and vitamin status were studied, along with objective measures of physical fitness in healthy male and female European adolescents. One thousand eighty-nine adolescents (580 girls, 12.5-17.5 yr) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were included. Hierarchical linear models were performed to determine the associations between micronutrient biomarkers and physical fitness. Age, seasonality, latitude, body mass index, menarche (in girls), and physical activity were used as covariates. For cardiorespiratory fitness, concentrations of hemoglobin, retinol, and vitamin C in male adolescents and β-carotene and 25(OH)D in female adolescents were associated with maximal oxygen consumption. For muscular fitness, concentrations of hemoglobin, β-carotene, retinol, and α-tocopherol in male adolescents and β-carotene and 25(OH)D in female adolescents were associated with better performance of the standing long jump test. In summary, concentrations of hemoglobin and most antioxidant vitamins in male adolescents and β-carotene and 25(OH)D in female adolescents were positively associated with cardiorespiratory and muscular fitness, after controlling for relevant confounders. The associations between physical fitness and iron or vitamin status observed in this cross-sectional study in adolescents should be followed up by a study specifically designed to evaluate causal relationships. 相似文献
13.
Christina Warinner Jade d��Alpoim Guedes David Goode 《Vegetation History and Archaeobotany》2011,20(3):241-244
Difficulty in accessing high quality reference materials has been a limiting factor in the advancement of archaeobotanical research. However, new developments in online open source content management technology and faster downloading capabilities make high quality and low cost dynamic online curation of archaeobotanical reference images increasingly feasible. We describe the establishment of Paleobot.org, an open access online reference collection database for macrobotanical, microbotanical and isotopic data to help standardize and improve the identification of archaeobotanical remains. 相似文献
14.
Jens Suffner Sebastian Kaserer Horst Hahn Christina Roth Frank Ettingshausen 《Liver Transplantation》2011,1(4):648-654
Sb‐doped SnO2 (ATO) is used as an alternative support material to replace carbon in the highly corrosive environment of a fuel cell cathode. Two ATO powders with different morphologies are decorated with Pt nanoparticles and afterwards used as the cathode catalyst. The commercial ATO powder exhibits crystallites in the nanometer range, while the home‐made ATO powder, which was synthesized by ultrasonic spray pyrolysis, consists of polycrystalline hollow spheres. The spheres have diameters in the micrometer range and are composed of individual nanocrystallites. The unusual morphology of the home‐made ATO offers nano‐ and microporosity at the same time and opens up new possibilities for the controlled design of electrode structures in low‐temperature polymer electrolyte fuel cells. Both materials are characterized by XRD, SEM, and TEM and tested in a single cell set‐up. While almost no current is gained from the membrane electrode assembly with the commercial ATO support, the cell with the home‐made ATO achieves a mediocre performance. This higher activity, however, is obtained with approximately half the Pt content compared to the catalyst with the commercial support. The different behaviours of both ATO powders can therefore mainly be attributed to differences in the specific support morphology. 相似文献
15.
Hermanrud CE Lucas CL Sykes M Huang CA Wang Z 《Protein expression and purification》2011,76(1):115-120
The anti-murine CD40L monoclonal antibody MR1 has been widely used in immunology research to block the CD40-CD40L interaction for induction of transplantation tolerance and to abrogate autoimmune diseases. The availability of recombinant CD40L with high binding capacity for MR1 would provide a valuable immunologic research tool. In this study, we constructed the single chain murine soluble CD40L monomer, dimer, trimer and successfully expressed them in yeast Pichia pastoris under the control of the alcohol oxidase promoter. The secreted single chain murine soluble CD40L monomers, dimers, and trimers were initially enriched through histidine tag capture by Ni-Sepharose 6 fast flow resin and further purified on a cation exchange resin. Purity reached more than 95% for the monomer and dimer forms and more than 90% for the trimer. Protein yield following purification was 16 mg/L for the monomer and dimer, and 8 mg/L for the trimer. ELISA analysis demonstrated that the CD40L dimers and trimers correctly folded in conformations exposing the MR1 antigenic determinant. 相似文献
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Christina McKee Mick Perez-Cruet Ferman Chavez G Rasul Chaudhry 《World journal of stem cells》2015,7(7):1064-1077
AIM: To devise a simplified and efficient method for long-term culture and maintenance of embryonic stem cells requiring less frequent passaging.METHODS: Mouse embryonic stem cells (ESCs) labeled with enhanced yellow fluorescent protein were cultured in three-dimensional (3-D) self-assembling scaffolds and compared with traditional two-dimentional (2-D) culture techniques requiring mouse embryonic fibroblast feeder layers or leukemia inhibitory factor. 3-D scaffolds encapsulating ESCs were prepared by mixing ESCs with polyethylene glycol tetra-acrylate (PEG-4-Acr) and thiol-functionalized dextran (Dex-SH). Distribution of ESCs in 3-D was monitored by confocal microscopy. Viability and proliferation of encapsulated cells during long-term culture were determined by propidium iodide as well as direct cell counts and PrestoBlue (PB) assays. Genetic expression of pluripotency markers (Oct4, Nanog, Klf4, and Sox2) in ESCs grown under 2-D and 3-D culture conditions was examined by quantitative real-time polymerase chain reaction. Protein expression of selected stemness markers was determined by two different methods, immunofluorescence staining (Oct4 and Nanog) and western blot analysis (Oct4, Nanog, and Klf4). Pluripotency of 3-D scaffold grown ESCs was analyzed by in vivo teratoma assay and in vitro differentiation via embryoid bodies into cells of all three germ layers.RESULTS: Self-assembling scaffolds encapsulating ESCs for 3-D culture without the loss of cell viability were prepared by mixing PEG-4-Acr and Dex-SH (1:1 v/v) to a final concentration of 5% (w/v). Scaffold integrity was dependent on the degree of thiol substitution of Dex-SH and cell concentration. Scaffolds prepared using Dex-SH with 7.5% and 33% thiol substitution and incubated in culture medium maintained their integrity for 11 and 13 d without cells and 22 ± 5 d and 37 ± 5 d with cells, respectively. ESCs formed compact colonies, which progressively increased in size over time due to cell proliferation as determined by confocal microscopy and PB staining. 3-D scaffold cultured ESCs expressed significantly higher levels (P < 0.01) of Oct4, Nanog, and Kl4, showing a 2.8, 3.0 and 1.8 fold increase, respectively, in comparison to 2-D grown cells. A similar increase in the protein expression levels of Oct4, Nanog, and Klf4 was observed in 3-D grown ESCs. However, when 3-D cultured ESCs were subsequently passaged in 2-D culture conditions, the level of these pluripotent markers was reduced to normal levels. 3-D grown ESCs produced teratomas and yielded cells of all three germ layers, expressing brachyury (mesoderm), NCAM (ectoderm), and GATA4 (endoderm) markers. Furthermore, these cells differentiated into osteogenic, chondrogenic, myogenic, and neural lineages expressing Col1, Col2, Myog, and Nestin, respectively.CONCLUSION: This novel 3-D culture system demonstrated long-term maintenance of mouse ESCs without the routine passaging and manipulation necessary for traditional 2-D cell propagation. 相似文献