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961.
962.
963.
The cellular events that govern patterning during animal development must be precisely regulated. This is achieved by extrinsic factors and through the action of both positive and negative feedback loops. Wnt/Wg signals are crucial across species in many developmental patterning events. We report that Drosophila nemo (nmo) acts as an intracellular feedback inhibitor of Wingless (Wg) and that it is a novel Wg target gene. Nemo antagonizes the activity of the Wg signal, as evidenced by the finding that reduction of nmo rescues the phenotypic defects induced by misexpression of various Wg pathway components. In addition, the activation of Wg-dependent gene expression is suppressed in wing discs ectopically expressing nmo and enhanced cell autonomously in nmo mutant clones. We find that nmo itself is a target of Wg signaling in the imaginal wing disc. nmo expression is induced upon high levels of Wg signaling and can be inhibited by interfering with Wg signaling. Finally, we observe alterations in Arm stabilization upon modulation of Nemo. These observations suggest that the patterning mechanism governed by Wg involves a negative feedback circuit in which Wg induces expression of its own antagonist Nemo. 相似文献
964.
965.
Lucas R Villamón E Payá M Alves M del Olmo E Gozalbo D Gil ML 《FEMS immunology and medical microbiology》2004,40(3):239-242
LAAE-14, a lipidic acid-amido ether derivative, has been recently described as a new anti-inflammatory drug. We have studied the effect of treatment with this compound on the susceptibility of mice to in vivo experimental Candida albicans infection. ICR mice orally treated with LAAE-14 (25 mg kg(-1)) and experimentally intravenously infected showed a significantly increased survival as compared to control mice. In vitro, the compound did not inhibit the growth of C. albicans yeast cells or the yeast-to-hyphal transition. The in vitro production of prostaglandin E2 by peritoneal macrophages in response to the yeasts and hyphae of C. albicans was significantly decreased upon treatment with LAAE-14, in a dose-dependent manner. Thus, reduced prostaglandin production during fungal infection could be an important factor in controlling fungal colonisation and infection. 相似文献
966.
Somjen D Knoll E Vaya J Stern N Tamir S 《The Journal of steroid biochemistry and molecular biology》2004,91(3):147-155
Post-menopausal women have higher incidence of heart diseases compared to pre-menopausal women, suggesting a protective role for estrogen. The recently Women's Health Initiative (WHI) randomized controlled trial concluded that the overall heart risk exceeded benefits from use of combined estrogen and progestin as hormone replacement therapy for an average of five years among healthy postmenopausal US women. Therefore, there is an urgent need for new agents with tissue-selective activity with no deleterious effects. In the present study, we tested the effects on vascular tissues in vitro and in vivo of two natural compounds derived from licorice root: glabridin, the major isoflavan, and glabrene, an isoflavene, both demonstrated estrogen-like activities. Similar to estradiol-17beta (E2), glabridin (gla) stimulated DNA synthesis in human endothelial cells (ECV-304; E304) and had a bi-phasic effect on proliferation of human vascular smooth muscle cells (VSMC). Raloxifene inhibited gla as well as E2 activities. In animal studies, both intact females or after ovariectomy, gla similar to E2 stimulated the specific activity of creatine kinase (CK) in aorta (Ao) and in left ventricle of the heart (Lv). Glabrene (glb), on the other hand, had only the stimulatory effect on DNA synthesis in vascular cells, with no inhibition by raloxifene, suggesting a different mechanism of action. To further elucidate the mechanism of action of glb, cells were pre-incubated with glb and then exposed to either E2 or to gla; the DNA stimulation at low doses was unchanged but there was abolishment of the inhibition of VSMC cell proliferation at high doses as well as inhibition of CK stimulation by both E2 and by gla. We conclude that glb behaved differently than E2 or gla, but similarly to raloxifene, being a partial agonist/antagonist of E2. Glabridin, on the other hand, demonstrated only estrogenic activity. Therefore, we suggest the use of glb with or without E2 as a new agent for modulation of vascular injury and atherogenesis for the prevention of cardiovascular diseases in post-menopausal women. 相似文献
967.
van Eijk MJ Broekhof JL van der Poel HJ Hogers RC Schneiders H Kamerbeek J Verstege E van Aart JW Geerlings H Buntjer JB van Oeveren AJ Vos P 《Nucleic acids research》2004,32(4):e47
Scalable multiplexed amplification technologies are needed for cost-effective large-scale genotyping of genetic markers such as single nucleotide polymorphisms (SNPs). We present SNPWave, a novel SNP genotyping technology to detect various subsets of sequences in a flexible fashion in a fixed detection format. SNPWave is based on highly multiplexed ligation, followed by amplification of up to 20 ligated probes in a single PCR. Depending on the multiplexing level of the ligation reaction, the latter employs selective amplification using the amplified fragment length polymorphism (AFLP) technology. Detection of SNPWave reaction products is based on size separation on a sequencing instrument with multiple fluorescence labels and short run times. The SNPWave technique is illustrated by a 100-plex genotyping assay for Arabidopsis, a 40-plex assay for tomato and a 10-plex assay for Caenorhabditis elegans, detected on the MegaBACE 1000 capillary sequencer. 相似文献
968.
Identification of C7orf11 (TTDN1) gene mutations and genetic heterogeneity in nonphotosensitive trichothiodystrophy
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969.
Caspase-12 and caspase-4 are not required for caspase-dependent endoplasmic reticulum stress-induced apoptosis 总被引:7,自引:0,他引:7
Alterations in cellular homeostasis that affect protein folding in the endoplasmic reticulum (ER) trigger a signaling pathway known as the unfolded protein response (UPR). The initially cytoprotective UPR will trigger an apoptotic cascade if the cellular insult is not corrected; however, the proteins required to initiate this cell death pathway are poorly understood. In this study, we show that UPR gene expression is induced in cells treated with ER stress agents in the presence or absence of murine caspase-12 or human caspase-4 expression and in cells that overexpress Bcl-x(L) or a dominant negative caspase-9. We further demonstrate that ER stress-induced apoptosis is a caspase-dependent process that does not require the expression of caspase-12 or caspase-4 but can be inhibited by overexpression of Bcl-x(L) or a dominant negative caspase-9. Additionally, treatment of human and murine cells with ER stress agents led to the cleavage of the caspase-4 fluorogenic substrate, LEVD-7-amino-4-trifluoromethylcoumarin, in the presence or absence of caspase-12 or caspase-4 expression, whereas Bcl-x(L) or a dominant negative caspase-9 overexpression inhibited LEVD-7-amino-4-trifluoromethylcoumarin cleavage. These data suggest that caspase-12 and caspase-4 are not required for the induction of ER stress-induced apoptosis and that caspase-4-like activity is not always associated with an initiating event. 相似文献
970.
Hurwitz E Klapper LN Wilchek M Yarden Y Sela M 《Cancer immunology, immunotherapy : CII》2000,49(4-5):226-234
Poly(ethylene glycol) (PEG) modification of substances with antitumor activity was shown to enhance penetration into growing
solid tumors and extend antitumor effects. Accordingly, PEG was introduced as a modifier to two types of monoclonal antibodies
(N12 and L26) specific to the ErbB2 (HER2) oncoprotein. These antibodies suppress the growth of tumors overexpressing ErbB2
(e.g. N87 human tumor) and the effect of PEG on their antitumor activity was evaluated. Methoxy-PEG-maleimide conjugated to
sulfhydryl groups at the hinge region of the antibodies impaired their antibody binding to N87 tumor cells and did not enhance
the antitumor inhibitory activity in tumor-bearing mice. A branched N-hydroxysuccinimide-activated PEG (PEG2), conjugated through amino groups of the protein, was used for binding to the whole
antibody (Ab) or to its monomeric Fab′ fragment. When tested against N87 cells in vitro, the binding activity and antitumor
cytotoxic effects of Ab-PEG2 were mostly preserved. PEG2 modification did not seem to alter the tumor-inhibitory activity
of the antibodies in vivo and the same pattern of tumor development was observed during the first few weeks following administration.
However, the stimulating effects of PEG were observed at later stages of tumor growth since tumor development was either slowed
down or completely arrested. Furthermore, a second tumor implanted into the same mice during this later stage was significantly
or completely inhibited, as compared to results in mice injected with the unmodified antibody. The Fab′-PEG2 monomeric derivative
was also shown to be effective in inhibiting the growth of a second tumor. The extended and prolonged enhancing effect of
PEG on the antitumor activity of antibodies or Fab′ fragments directed against ErbB2 may be of importance in the treatment
of ErbB2-overexpressing neoplasms.
Received: 2 September 1999 / Accepted: 19 February 2000 相似文献