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991.
Alzheimer's disease is associated with the formation of paired helical filaments composed of hyperphospharylated tau protein. Phosphatase 2B, calcineurin can dephosphorylate the tau protein and, therefore, might prevent the assembly of paired helical filaments and even Alzheimer's disease. Calcipressin 1, the DSCR1(Adapt78) gene product, can bind and inactivate calcineurin. Here we hypothesize that while short-term induction of calcipressin1 can provide stress protection, its long-term or chronic induction may cause gradual accumulation of hyperphosphorylated tau protein, eventually leading to Alzheimer's disease. 相似文献
992.
Linder CC 《Comparative medicine》2003,53(2):119-125
Modern genetic engineering technologies enable us to manipulate the mouse genome in increasingly complex ways to model human biology and disease. As a result, the number of mouse strains carrying transgenes or induced mutations has increased markedly. Thorough understanding of strain and gene nomenclature is essential to ensure that investigators know what kind of mouse they have, and what to expect in terms of phenotype. Genetically engineered mice alter gene function by over-expressing, eliminating, or modifying a gene product. The resulting phenotype is often unexpected and not completely understood, necessitating special care and potentially complex breeding and husbandry strategies. Animal care technicians responsible for routine maintenance of the colony, facility managers, veterinarians, and research personnel working with mice should be well informed about the nature of the mutation, distinguishing characteristics, and necessary precautions in handling the mice. Personnel working with mice also must be aware of the multitude of factors intrinsic to the mouse and present in the environment that can influence reproductive performance. Finally, diligent adherence to the maintenance of genetic quality in conjunction with cryopreservation of germplasm is the best insurance against loss of a colony. 相似文献
993.
Determinants in mammalian telomerase RNA that mediate enzyme processivity and cross-species incompatibility
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Telomerase contains two essential components: an RNA molecule that templates telomeric repeat synthesis and a catalytic protein component. Human telomerase is processive, while the mouse enzyme has much lower processivity. We have identified nucleotide determinants in the telomerase RNA that are responsible for this difference in processivity. Mutations adjacent to the template region of human and mouse telomerase RNA significantly altered telomerase processivity both in vitro and in vivo. We also identified functionally important nucleotides in the pseudoknot domain of telomerase RNA that potentially mediate the incompatibility between human TERT and mouse telomerase RNA. These experiments identify essential residues of the telomerase RNA that regulate telomerase activity and processivity. 相似文献
994.
Eyespot placement and assembly in the green alga Chlamydomonas 总被引:2,自引:0,他引:2
Dieckmann CL 《BioEssays : news and reviews in molecular, cellular and developmental biology》2003,25(4):410-416
The eyespot organelle of the green alga Chlamydomonas allows the cell to phototax toward (or away) from light to maximize the light intensity for photosynthesis and minimize photo-damage. At cytokinesis, the eyespot is resorbed at the cleavage furrow and two new eyespots form in the daughter cells 180 degrees from each other. The eyespots are positioned asymmetrically with respect to the microtubule cytoskeleton. Eyespots are assembled from all three chloroplast membranes and carotenoid-filled granules, which form a sandwich structure overlaid by the tightly apposed plasma membrane. This review describes (1) my interest in cellular asymmetry and organelle biology, (2) isolation of mutations that describe four genes governing eyespot placement and assembly, (3) the characterization of the EYE2 gene, which encodes a thioredoxin superfamily member, and (4) the characterization of the MIN1 gene, which is required for the layered organization of granules and membranes in the eyespot. BioEssays 25:410-416, 2003. 相似文献
995.
Feinberg H Uitdehaag JC Davies JM Wallis R Drickamer K Weis WI 《The EMBO journal》2003,22(10):2348-2359
Serum mannose-binding proteins (MBPs) are C-type lectins that recognize cell surface carbohydrate structures on pathogens, and trigger killing of these targets by activating the complement pathway. MBPs circulate as a complex with MBP-associated serine proteases (MASPs), which become activated upon engagement of a target cell surface. The minimal functional unit for complement activation is a MASP homodimer bound to two MBP trimeric subunits. MASPs have a modular structure consisting of an N-terminal CUB domain, a Ca(2+)-binding EGF-like domain, a second CUB domain, two complement control protein modules and a C-terminal serine protease domain. The CUB1-EGF-CUB2 region mediates homodimerization and binding to MBP. The crystal structure of the MASP-2 CUB1-EGF-CUB2 dimer reveals an elongated structure with a prominent concave surface that is proposed to be the MBP-binding site. A model of the full six-domain structure and its interaction with MBPs suggests mechanisms by which binding to a target cell transmits conformational changes from MBP to MASP that allow activation of its protease activity. 相似文献
996.
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998.
Down Syndrome (DS), one of the major genetic causes of mental retardation, is characterized by disrupted corticogenesis produced, in part, by an abnormal layering of neurons in cortical laminas II and III. Because defects in the normal migration of neurons during corticogenesis can result in delayed cortical radial expansion and abnormalities in cortical layering, we have examined neuronal migration in murine trisomy 16 (Ts16), a mouse model for DS. Using an in vitro assay for chemotaxis, our data demonstrate that the number of acutely dissociated Ts16 cortical neurons migrating in response to glutamate or N-methyl-D-aspartate (NMDA), known chemotactic factors, was decreased compared to normal littermates, suggesting a defect in NMDA receptor- (NMDAR-) mediated events. Ts16 neurons did not lack NMDAR since expression of mRNA and protein for NMDAR subunits was observed in Ts16 cells. However, the number of cells that generated an observable current in response to NMDA was decreased compared to normal littermates. Similar to DS, Ts16 CNS demonstrated an inherent oxidative stress likely caused by the triplication of genes such as SOD1. To determine if the abnormal redox state was a factor in the failure of NMDAR-mediated migration in Ts16, we treated Ts16 neurons with either n-acetyl cysteine (NAC) or dithiothrietol (DTT), known antioxidants. The reduction in NMDAR-mediated migration observed in Ts16 neurons was returned to normal littermate values by NAC or DTT. Our data indicate that oxidative stress may play a key role in the abnormal glutamate-mediated responses during cortical development in the Ts16 mouse and may have an impact on neuronal migration at critical stages. 相似文献
999.
1000.
Bidirectional regulation of hippocampal mossy fiber filopodial motility by kainate receptors: a two-step model of synaptogenesis 总被引:7,自引:0,他引:7
The rapid motility of axonal filopodia and dendritic spines is prevalent throughout the developing CNS, although the function of this motility remains controversial. Using two-photon microscopy, we imaged hippocampal mossy fiber axons in slice cultures and discovered that filopodial extensions are highly motile. Axonal filopodial motility is actin based and is downregulated with development, although it remains in mature cultures. This motility is correlated with free extracellular space yet is inversely correlated with contact with postsynaptic targets, indicating a potential role in synaptogenesis. Filopodial motility is differentially regulated by kainate receptors: synaptic stimulation of kainate receptors enhances motility in younger slices, but it inhibits it in mature slices. We propose that neuronal activity controls filopodial motility in a developmentally regulated manner, in order to establish synaptic contacts in a two-step process. A two-step model of synaptogenesis can also explain the opposite effects of neuronal activity on the motility of dendritic protrusions. 相似文献