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The chromium-binding oligopeptide chromodulin (also known as low-molecular-weight chromium-binding substance) has been shown to activate the tyrosine kinase activity of the insulin receptor in response to insulin and has been proposed to be part of a novel autoamplification mechanism for insulin signaling. The model requires that Cr3+ be moved from the blood to insulin-sensitive tissues in response to insulin and subsequently be lost in the urine as chromodulin; however, the model has not been tested by in vivo studies. In vivo studies with rats have shown that the iron transport protein transferrin serves as the major chromic ion transport agent and that this transport is stimulated by insulin. The ion is transported to a variety of tissues, while liver and kidneys are the major target. In hepatocytes, chromodulin occurs in appreciable levels in the cytosol and in the nucleus. Apochromodulin levels appear to be maintained under homeostatic control, although the only detectable form of urinary chromium is probably chromodulin. Increases in urinary chromium loss in response to insulin are reflected by increases in chromodulin, establishing a direct link between carbohydrate metabolism and the oligopeptide.  相似文献   
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Adverse effects of glucocorticoids could be limited by developing new compounds that selectively modulate anti-inflammatory activity of the glucocorticoid receptor (GR). We have synthesized a novel series of steroidal GR ligands, including potent agonists, partial agonists and antagonists with a wide range of effects on inhibiting secretion of interleukin-6. Some of these new ligands were designed to directly impact conformational stability of helix-12, in the GR ligand-binding domain (LBD). These compounds modulated GR activity and glucocorticoid-induced gene expression in a manner that was inversely correlated to the degree of inflammatory response. In contrast, compounds designed to directly modulate LBD epitopes outside helix-12, led to dissociated levels of GR-mediated gene expression and inflammatory response. Therefore, these new series of compounds and their derivatives will be useful to dissect the ligand-dependent features of GR signaling specificity.  相似文献   
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The flexibility and self-healing properties of animal cell surface membranes are well known. These properties have been best exploited in various micrurgical studies on living cells (2, 3), especially in amoebae (7, 20). During nuclear transplantation in amoebae, the hole in the membrane through which a nucleus passes can have a diameter of 20-30 μm, and yet such holes are quickly sealed, although some cytoplasm usually escapes during the transfer. While enucleating amoebae in previous studies, we found that if a very small portion of a nucleus was pushed through the membrane and exposed to the external medium, the amoeba expelled such a nucleus on its own accord. When this happened, a new membrane appeared to form around the embedded portion of the nucleus and no visible loss of cytoplasm occurred during nuclear extrusion. In the present study, we examined amoebae that were at different stages of expelling partially exposed nuclei, to follow the sequence of events during the apparent new membrane formation. Unexpectedly, we found that a new membrane is not formed around the nucleus from inside but a hole is sealed primarily by a constriction of the existing membrane, and that cytoplasmic filaments are responsible for the prevention of the loss of cytoplasm.  相似文献   
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The occurrence of third-stage larvae of the arterial worm (Elaeophora schneideri) in populations of the horse fly, Tabanus lineola hinellus, was studied on South Island, Georgetown County, South Carolina. Over the period from mid-April to mid-October 1982, horse flies had a bimodal pattern of abundance with peak populations in June and September. During individual bimonthly horse fly collections, the prevalence of infection of T. l. hinellus ranged from 0 to 1.23%. Prevalence of infected horse flies was biphasic with peaks in mid-May (1.23%) and mid-August (1.22%), 2 to 4 wk prior to peaks in horse fly populations. The intensity of infection of T. l. hinellus increased as time progressed and was highest in late summer. This increase resulted in greater recovery of infective larvae during August-September (mean intensity = 25) than in May-June (mean intensity = 4). Both prevalence and intensity of infection of T. l. hinellus were low compared to primary intermediate hosts of E. schneideri in the western U.S.  相似文献   
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