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S P Wolff 《Nature》1992,356(6368):375-376
The introduction of human insulin to treat diabetics seemed straightforward. What can account for the problems that have followed?  相似文献   
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Vitamin B12 (methylcobalamin) was administered orally (3 mg/day) to 9 healthy subjects for 4 weeks. Nocturnal melatonin levels after exposure to bright light (ca. 2500 lx) were determined, as well as the levels of plasma melatonin over 24 h. The timing of sleep was also recorded. Vitamin B12 was given blind to the subjects and crossed over with placebo. We found that the 24-h melatonin rhythm was significantly phase-advanced (1.1 h) in the vitamin B12 trial as compared with that in the placebo trial. In addition, the 24-h mean of plasma melatonin level was much lower in the vitamin B12 trial than with the placebo. Furthermore, the nocturnal melatonin levels during bright light exposure were significantly lower in the vitamin B12 trial than with the placebo. On the other hand, vitamin B12 did not affect the timing of sleep. These findings raise the possibility that vitamin B12 phase-advances the human circadian rhythm by increasing the light sensitivity of the circadian clock.  相似文献   
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Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum.   总被引:39,自引:0,他引:39  
K Sandvig  O Garred  K Prydz  J V Kozlov  S H Hansen  B van Deurs 《Nature》1992,358(6386):510-512
Shiga toxin and some other protein toxins that act on targets in the cytosol have previously been shown to enter the trans-Golgi network. Transport by this route may be necessary for translocation of the toxin to the cytosol and for intoxication, but it is not known whether the enzymatically active part of the toxins actually enters the cytosol from the trans-Golgi network. It has been suggested that such toxins are transported in a retrograde manner to the endoplasmic reticulum and that translocation occurs in this organelle, but retrograde transport of endocytosed material beyond the trans-Golgi network has never been demonstrated. Here we show that in butyric acid-treated A431 cells endocytosed Shiga toxin is not only transported to the trans-Golgi network, but also to all Golgi stacks, to the endoplasmic reticulum and to the nuclear envelope. Furthermore, butyric acid sensitizes the cells to Shiga toxin, which is consistent with the possibility that retrograde transport is required for translocation of the toxin to the cytosol.  相似文献   
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S J Weintraub  C A Prater  D C Dean 《Nature》1992,358(6383):259-261
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1 Results This paper presents the development of platinum nanocomposites structures based on organically modified c.a.2 nm core platinum nanoparticles.The chemical modification of the 4-mercaptoaniline functionalized particles by various in coming molecules is evidenced and precisely quantified.The particles can be dissolved like molecules in various solvents depending on the features of the new crown and X-rays shows that the interparticle distance is affected by the crown modification.These platinum n...  相似文献   
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1 Results The development of the concepts of nanotechnology has given an important impact on the design of new polymer based materials which are in most cases characterized by a multiphase morphology. When at least one phase has nanometric dimension(s) the system can be considered as a nanocomposite where the interface is not only determining for the adhesion but also may play a role in some bulk properties. Indeed in nanostructured multiphase solids the interface is significant as a bulk component. The...  相似文献   
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