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81.
The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein-coupled sphingosine 1-phosphate receptors. Here, we present the crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme (S1P(1)-T4L) in complex with an antagonist sphingolipid mimic. Extracellular access to the binding pocket is occluded by the amino terminus and extracellular loops of the receptor. Access is gained by ligands entering laterally between helices I and VII within the transmembrane region of the receptor. This structure, along with mutagenesis, agonist structure-activity relationship data, and modeling, provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P(1), resulting in the modulation of immune and stromal cell responses.  相似文献   
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We describe the case of a 14-year-old Domestic Short Hair male cat that presented with a single mammary tumour one centimetre in diameter, classified as invasive micropapillary carcinoma. Histology and immunohistochemistry revealed a high mitotic index, a KI-67 index of 10%, a lack of reactivity to myoepithelial markers, and a dense infiltration with T and B lymphocytes at the periphery of the tumour. Micrometastases were detected in the regional lymph node at the time of surgery. Overall survival time was 10 months with a disease-free interval of 7.5 months. Distant metastases in the sublumbar lymph nodes confirmed the aggressiveness of this tumour, which has recently been subtyped in female cats. This is the first case reported in male cats with a complete follow-up, highlighting the importance of prompt and aggressive treatment in the presence of mammary tumours in male cats.  相似文献   
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Total methanolic extracts of Saponaria vaccaria seed derived from several varieties, as well as various purified components obtained through successive chromatographic separations of total extracts were evaluated for their growth inhibitory activity in WiDr (colon), MDA-MB-231 (breast), NCI-417 (lung) and PC-3 (prostate) human cancer cells as well as the non-tumorigenic fibroblast BJ (CRL-2522) cell line using MTT colorimetric assay. Purified bisdesmosidic saponins segetoside H and I were further examined using microscopy and apoptosis assays. Bisdesmosidic saponins exhibited dose-dependent growth inhibitory and selective apoptosis-inducing activity. Growth inhibitory effects were particularly strong in a breast (MDA-MB-231) and a prostate (PC-3) cancer cell line. Total extracts exhibited a different preference being most active against a colon cancer cell line (WiDr). In a comparison of varieties, all of the total seed extracts exhibited similar dose-dependent activities, but with some variation in potency. Monodesmosidic saponins vaccarosides A and B, phenolic vaccarin, and cyclopeptide segetalin A, co-occurring seed substituents, did not exhibit activity. The non-tumorigenic fibroblast cell line BJ (CRL 2522) was growth inhibited but did not undergo apoptosis when treated with bisdesmosidic saponins at low micromolar concentrations. Saponin-rich extracts from Kochia scoparia seed and Chenopodium quinoa were also evaluated alongside Saponaria saponins but did not exhibit activity. Closely related Quillaja saponins exhibited activity but were less potent.  相似文献   
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Our study objective was to determine the ability of milk urea-nitrogen concentrations ([MUN]) to predict fecal nitrogen concentrations ([Fecal N]) in commercial dairy herds. A total of 83 dairy herds were each visited 3 times within 48 h after a monthly herd milk test. For each farm visit, forages were sampled for nutrient analyses, which were entered into a computerized ration evaluator, and fecal samples were taken per rectum from each of 6 cows (2 early-, 2 mid-, and 2 late-lactation). Fecal samples were pooled, mixed, and analyzed for nitrogen content. Fecal nitrogen concentrations were compared with the routinely measured nutritional parameters from the ration evaluation, and the herd average [MUN] for the previous milk test date using mixed linear regression analyses. Total protein supplied in the ration was significantly positively associated with [Fecal N], but herd average [MUN] was not associated (P > 0.10) with [Fecal N].  相似文献   
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