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Tau is a microtubule-associated protein that loses microtubule binding activity and aggregates into paired helical filaments (PHFs) in Alzheimer's disease. Nonenzymic glycation is one of the posttranslational modifications detected in PHF-tau, but not in normal tau. PHF-tau has reduced ability to bind to microtubules. To determine whether glycation of tau occurs in its microtubule binding domains, we have characterized in vitro glycation sites of the longest isoform of tau, which has four microtubule binding domains (Tau-4). The identified glycation sites are Lys-87, 132, 150, 163, 174, 225, 234, 259, 280, 281, 347, 353, and 369. We have also studied glycation of another isoform of tau, which has only three microtubule binding domains (Tau-3). This isoform is modified by glucose 15-20% more slowly than Tau-4. However, the glycation sites appear to be the same in both isoforms, except for Lys-280 and 281; these are located in the second microtubule binding domain, which is missing in Tau-3. Lys-150, 163, and 174 are located within or proximal to the sequence of tau that is involved in the microtubule nucleation activity, and Lys-259, 280, 281, 347, 353, and 369 are located in the microtubule binding domains. Glycation at these sites can affect the functional properties of tau, and advanced glycation at these sites might lead to the formation of insoluble aggregates similar to the ones seen in Alzheimer's disease.  相似文献   

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HLA-G is a non-classical class Ib gene with many unusual features. Because of its unique expression pattern, which is primarily limited to fetal cells at the maternal fetal interface, this gene has gained the attention of many investigators. In this paper we review some of the novel features of HLA-G, with particular reference to polymorphic variants in the gene, and discuss the implications of these features for the potential function and evolutionary history of HLA-G.  相似文献   

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Membranous vestibular labyrinths from the oyster toadfish, Opsanus tau, were fixed, dissected from the animal, stained, and embedded in rectangular blocks of clear histological resin. Photomicrographs of complete embedded labyrinths were taken from six orthogonal directions and used to construct three-dimensional (3D) geometrical models of the semicircular canals, ampullae, utricular vestibule and common crus. Membraneous ducts and ampullae were modeled using a set of cross-sectional elliptical curves laced together to generate curved tubular models of each structure. The ensemble of these curved tubes was used to generate a complete 3D reconstruction of the outside surface of the membranous labyrinth. When viewed from six orthogonal directions, reconstructions closely matched the embedded tissue. Dimensions of the reconstruction and histological sections were compared to measurements of fresh tissue taken from the same animals prior to fixation and used to correct the reconstructions for tissue shrinkage. Results provide estimates of the endolymphatic volumes, local cross-sectional areas and elliptical eccentricities as well as 3D orientations of the geometric canal planes relative to the skull. Ten micrometer histological sections of the material were also prepared to measure wall thickness in various regions of the labyrinth.  相似文献   

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