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991.
992.
Huntington disease (HD), an autosomal dominant, progressive neurodegenerative disorder, is caused by an expanded CAG repeat sequence leading to an increase in the number of glutamine residues in the encoded protein. The normal CAG repeat range is 5-36, whereas 38 or more repeats are found in the diseased state; the severity of disease is roughly proportional to the number of CAG repeats. HD shows anticipation, in which subsequent generations display earlier disease onsets due to intergenerational repeat expansion. For longer repeat lengths, somatic instability of the repeat size has been observed both in human cases at autopsy and in transgenic mouse models containing either a genomic fragment of human HD exon 1 (ref. 9) or an expanded repeat inserted into the endogenous mouse gene Hdh (ref. 10). With increasing repeat number, the protein changes conformation and becomes increasingly prone to aggregation, suggesting important functional correlations between repeat length and pathology. Because dinucleotide repeat instability is known to increase when the mismatch repair enzyme MSH2 is missing, we examined instability of the HD CAG repeat by crossing transgenic mice carrying exon 1 of human HD (ref. 16) with Msh2-/- mice. Our results show that Msh2 is required for somatic instability of the CAG repeat. 相似文献
993.
At the end of mitosis, daughter cells are separated from each other by cytokinesis. This process involves equal partitioning
and segregation of cytoplasm between the two cells. Despite years of study, the mechanism driving cytokinesis in animal cells
is not fully understood. Actin and myosin are major components of the contractile ring, the structure at the equator between
the dividing cells that provides the force necessary to constrict the cytoplasm. Despite this, there are also tantalizing
results suggesting that cytokinesis can occur in the absence of myosin. It is unclear what the roles are of the few other
contractile ring components identified to date. While it has been difficult to identify important proteins involved in cytokinesis,
it has been even more challenging to pinpoint the regulatory mechanisms that govern this vital process. Cytokinesis must be
precisely controlled both spatially and temporally; potential regulators of these parameters are just beginning to be identified.
This review discusses the recent progress in our understanding of cytokinesis in animal cells and the mechanisms that may
regulate it.
Received 24 August 1998; received after revision 9 October 1998; accepted 9 October 1998 相似文献
994.
Images, calculated from electron micrographs, show the three-dimensional structures of microtubules and tubulin sheets decorated stoichiometrically with motor protein molecules. Dimeric motor domains (heads) of kinesin and ncd, the kinesin-related protein that moves in the reverse direction, each appeared to bind to tubulin in the same way, by one of their two heads. The second heads show an interesting difference in position that seems to be related to the directions of movement of the two motors. X-ray crystallographic results showing the structures of kinesin and ncd to be very similar at atomic resolution, and homologous also to myosin, suggest that the two motor families may use mechanisms that have much in common. Nevertheless, myosins and kinesins differ kinetically. Also, whereas conformational changes in the myosin catalytic domain are amplified by a long lever arm that connects it to the stalk domain, kinesin and ncd do not appear to possess a structure with a similar function but may rely on biased diffusion in order to move along microtubules. 相似文献
995.
Amin AR Attur MG Pillinger M Abramson SB 《Cellular and molecular life sciences : CMLS》1999,56(3-4):305-312
Recent studies have suggested that aspirin and aspirin-like compounds have a variety of actions in addition to their well-studied
ability to inhibit cyclooxygenases. These actions include inhibition of the uncoupling of oxidative phosphorylation, decreases
in adenosine triphosphate stores, increases in extracellular adenosine, downregulation of the expression and activity of inducible
nitric oxide synthetase, inhibition and/or stimulation of various mitogen-activated protein kinase activities and inhibition
of nuclear factor binding κB site (NF-κB) activation. Moreover, aspirin-like compounds have recently been shown to have previously
unappreciated clinical and biological effects, some apparently independent of cyclooxygenase. In this review we discuss the
various mechanisms of action of aspirin-like compounds and their relevance to clinical disease and therapy.
Received 1 February 1999; received after revision 1 April 1999; accepted 7 May 1999 相似文献
996.
A population of ventral neural tube cells has recently been shown to migrate out of the hind brain neural tube via the vagus
nerve and contribute to the developing gastrointestinal tract. Since liver is also innervated by the vagus nerve, we sought
to determine if these cells also migrate into the liver. Ventral neural tube cells in the caudal hindbrain of chick embryos
were tagged with a replication-deficient retroviral vector containing the LacZ gene on embryonic day 2. Embryos were processed
for detection of labeled cells on embryonic day 5 and 11. Labeled cells were seen in the liver on both days and identified
as hepatocytes. Previously, it was believed that all hepatocytes develop from the gut endoderm. Results of the present study
show an additional source for the formation of liver cells.
Received 25 August 1998; received after revision 5 November 1998; accepted 5 November 1998 相似文献
997.
998.
Epithelial antimicrobial peptides: innate local host response elements 总被引:23,自引:0,他引:23
Schröder JM 《Cellular and molecular life sciences : CMLS》1999,56(1-2):32-46
Multicellular organisms have to survive in an environment laden with numerous microorganisms, which represent a potential hazard to life. Different strategies have been developed to ward off infections by preventing microorganisms from entering surfaces and by preventing the attack of microorganisms that have already entered the epithelia. Therefore, it is not surprising that epithelia are equipped with various antimicrobial substances that act rapidly to kill a broad range of microorganisms. This review summarizes our present knowledge about epithelial peptide antibiotics produced in plants, invertebrates, and vertebrates including humans. There is now strong evidence that in addition to constitutively secreted peptide antibiotics, others are induced upon contact with microorganisms or by proinflammatory cytokines. beta-Defensins represent one family of vertebrate antimicrobial peptides, members of which are inducible and have recently been identified in humans. The defensin-characteristic local expression pattern may indicate that specialized surfaces express a characteristic surface antimicrobial peptide pattern that might define the characteristic microflora as well as the density of microorganisms present on the surface. 相似文献
999.