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181.
The nematode Caenorhabditis elegans is commonly used as a genetic model organism for dissecting integration of the sensory and motor systems. Despite extensive genetic and behavioural analyses that have led to the identification of many genes and neural circuits involved in regulating C. elegans locomotion behaviour, it remains unclear whether and how somatosensory feedback modulates motor output during locomotion. In particular, no stretch receptors have been identified in C. elegans, raising the issue of whether stretch-receptor-mediated proprioception is used by C. elegans to regulate its locomotion behaviour. Here we have characterized TRP-4, the C. elegans homologue of the mechanosensitive TRPN channel. We show that trp-4 mutant worms bend their body abnormally, exhibiting a body posture distinct from that of wild-type worms during locomotion, suggesting that TRP-4 is involved in stretch-receptor-mediated proprioception. We show that TRP-4 acts in a single neuron, DVA, to mediate its function in proprioception, and that the activity of DVA can be stimulated by body stretch. DVA both positively and negatively modulates locomotion, providing a unique mechanism whereby a single neuron can fine-tune motor activity. Thus, DVA represents a stretch receptor neuron that regulates sensory-motor integration during C. elegans locomotion. 相似文献
182.
Deregulated expression of c-Myc depletes epidermal stem cells 总被引:30,自引:0,他引:30
The beta-catenin/TCF signaling pathway is essential for the maintenance of epithelial stem cells in the small intestine. c-Myc a downstream target of beta-catenin/TCF (ref. 2), can induce differentiation of epidermal stem cells in vitro. To determine the role of c-Myc in epidermal stem cells in vivo, we have targeted expression of human MYC2 to the hair follicles and the basal layer of mouse epidermis using a keratin 14 vector (K14.MYC2). Adult K14.MYC2 mice gradually lose their hair and develop spontaneous ulcerated lesions due to a severe impairment in wound healing; their keratinocytes show impaired migration in response to wounding. The expression of beta1 integrin, which is preferentially expressed in epidermal stem cells is unusually low in the epidermis of K14.MYC2 mice. Label-retaining analysis to identify epidermal stem cells reveals a 75% reduction in the number of stem cells in 3-month-old K14.MYC2 mice, compared with wildtype mice. We conclude that deregulated expression of c-Myc in stem cells reduces beta1 integrin expression, which is essential to both keratinocyte migration and stem cell maintenance. 相似文献
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The effects of dehydroepiandrosterone sulfate (DHEAS) on thymocyte apoptosis induced by dexamethasone (DEX) were investigated.
Apoptosis was measured by using agarose gel electrophoresis of DNA, the terminal deoxynucleotidyltransferase (TdT)- mediated
dUTP nick end labeling (TUNEL) assay and flow cytometry. Our results showed that preincubation with 1×10−4 M DHEAS protected thymocytes from DEX-induced apoptosis in vitro. Moreover, we found no blocking effect on the DEX-induced
activation of caspase-3 and caspase-6 by the preincubation of thymocytes with DHEAS. This may be interpreted to mean that
the antagonism of DHEAS to DEX-induced apoptosis is not related to the activation of these downstream caspases which play
a critical role in the execution of apoptosis.
Received 25 June 1999; received after revision 1 September 1999; accepted 13 September 1999 相似文献
186.
Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. 总被引:21,自引:0,他引:21
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188.
DNA methylation represses transcription in vivo. 总被引:9,自引:0,他引:9
189.
The SARS-CoV S glycoprotein 总被引:7,自引:0,他引:7
The severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein alone can mediate the membrane fusion required for virus entry and cell fusion. It is also a major immunogen and a target for entry inhibitors. Recent rapid advances in our knowledge of the structure and function of this protein have lead to the development of a number of candidate vaccine immunogens and SARS-CoV entry inhibitors. 相似文献
190.
Han X 《Cellular and molecular life sciences : CMLS》2004,61(15):1896-1906
The critical roles of apolipoprotein E (apoE) in regulating plasma lipid and lipoprotein levels have been
extensively studied for over 2 decades. However, an understanding of the roles of apoE in the central nervous
system (CNS) is less certain. This review will summarize the available experimental results on the role of apoE
in CNS lipid homeostasis with respect to its modulation of sulfatide trafficking, alteration of CNS cholesterol
homeostasis and apoE-induced changes in phospholipid molecular species in specialized subcellular membrane
fractions. The results indicate that apoE mediates sulfatide trafficking and metabolism in the CNS. Moreover,
although apoE does not affect the cholesterol mass content or the phospholipid mass levels and composition in the
CNS as a whole, apoE modulates cholesterol and phospholipid homeostasis in selective subcellular membrane
compartments. Through elucidating the roles of apoE in CNS lipid metabolism, new insights into overall functions
of apoE in neurobiology can be accrued ultimately, leading to an increased understanding of CNS lipid metabolism
and the identification of novel therapeutic targets for CNS diseases.Received 9 January 2004; received after revision 28 February 2004; accepted 10 March 2004 相似文献