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A Kaushansky P G Metzger A N Douglass S A Mikolajczak V Lakshmanan H S Kain S HI Kappe 《Cell death & disease》2013,4(8):e762
Intracellular eukaryotic parasites and their host cells constitute complex, coevolved cellular interaction systems that frequently cause disease. Among them, Plasmodium parasites cause a significant health burden in humans, killing up to one million people annually. To succeed in the mammalian host after transmission by mosquitoes, Plasmodium parasites must complete intracellular replication within hepatocytes and then release new infectious forms into the blood. Using Plasmodium yoelii rodent malaria parasites, we show that some liver stage (LS)-infected hepatocytes undergo apoptosis without external triggers, but the majority of infected cells do not, and can also resist Fas-mediated apoptosis. In contrast, apoptosis is dramatically increased in hepatocytes infected with attenuated parasites. Furthermore, we find that blocking total or mitochondria-initiated host cell apoptosis increases LS parasite burden in mice, suggesting that an anti-apoptotic host environment fosters parasite survival. Strikingly, although LS infection confers strong resistance to extrinsic host hepatocyte apoptosis, infected hepatocytes lose their ability to resist apoptosis when anti-apoptotic mitochondrial proteins are inhibited. This is demonstrated by our finding that B-cell lymphoma 2 family inhibitors preferentially induce apoptosis in LS-infected hepatocytes and significantly reduce LS parasite burden in mice. Thus, targeting critical points of susceptibility in the LS-infected host cell might provide new avenues for malaria prophylaxis. 相似文献
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The genes involved in DNA repair system play a crucial role in the protection against mutations. It has been hypothesized
that functional deficiencies in highly conserved DNA repair processes resulting from polymorphic variation may increase genetic
susceptibility to breast cancer (BC). The aim of the present study was to evaluate the association of genetic polymorphisms
in 2 DNA repair genes, XPD (Asp312Asn) and XRCC1 (A399G), with BC susceptibility. We further investigated the potential combined
effect of these DNA repair variants on BC risk. Both XPD (xeroderma pigmentosum group D) and XRCC1 (X-ray repair cross-complementing
group 1) polymorphisms were characterized in 100 BC Egyptian females and 100 healthy women who had no history of any malignancy
by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method and PCR with confronting two-pair
primers (PCR-CTPP), using DNA from peripheral blood in a case control study. Our results revealed that the frequencies of
AA genotype of XPD codon 312 polymorphism were significantly higher in the BC patients than in the normal individuals (P ≤ 0.003), and did not observe any association between the XRCC1 Arg399Gln polymorphism and risk of developing BC. Also, no
association between both XPD Asp312Asn and XRCC1 A399G polymorphisms and the clinical characteristics of disease. Finally,
the combination of AA(XPD) + AG(XRCC1) were significantly associated with BC risk. Our results suggested that, XPD gene is
an important candidate gene for susceptibility to BC. Also, gene–gene interaction between XPD(AA) + XRCC1(AG) polymorphism
may be associated with increased risk of BC in Egyptian women. 相似文献
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Valiyaveettil M Bentley AA Gursahaney P Hussien R Chakravarti R Kureishy N Prag S Adams JC 《The Journal of cell biology》2008,182(4):727-739
The evolutionarily conserved kelch-repeat protein muskelin was identified as an intracellular mediator of cell spreading. We discovered that its morphological activity is controlled by association with RanBP9/RanBPM, a protein involved in transmembrane signaling and a conserved intracellular protein complex. By subcellular fractionation, endogenous muskelin is present in both the nucleus and the cytosol. Muskelin subcellular localization is coregulated by its C terminus, which provides a cytoplasmic restraint and also controls the interaction of muskelin with RanBP9, and its atypical lissencephaly-1 homology motif, which has a nuclear localization activity which is regulated by the status of the C terminus. Transient or stable short interfering RNA–based knockdown of muskelin resulted in protrusive cell morphologies with enlarged cell perimeters. Morphology was specifically restored by complementary DNAs encoding forms of muskelin with full activity of the C terminus for cytoplasmic localization and RanBP9 binding. Knockdown of RanBP9 resulted in equivalent morphological alterations. These novel findings identify a role for muskelin–RanBP9 complex in pathways that integrate cell morphology regulation and nucleocytoplasmic communication. 相似文献
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【目的】为研究土壤细菌对蔬菜灰霉病的生防价值, 从辽宁、山东等地区的蔬菜种植基地采集土壤样本56份, 分离、筛选出对灰霉病具有稳定拮抗作用的细菌9株。【方法】采用平板对峙培养法进行初筛、复筛, 用抑菌圈法测定其抑菌效果, 并进行离体果实试验验证其对蔬菜灰霉病的防治效果, 通过形态学特征、生理生化特征及16S rRNA基因序列分析研究其分类地位。【结果】细菌CNY-04对蔬菜灰霉病的拮抗能力最强且遗传稳定, 抑菌圈直径达到34 mm; 初步鉴定该菌株为格氏沙雷菌(Serratia grimesii), 尚未见该菌在生防上的报道; CNY-04液体菌剂对离体番茄果实灰霉病的防效为69.23%, 50%多菌灵防效为75.39%, 24 h时接种CNY-04处理的番茄发病率为40.0%, 而48 h时接种处理的发病率为51.1%。【结论】CNY-04是一株较为理想的拮抗菌, 丰富了生防资源。 相似文献
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Protoplasma - Many studies have been carried out to investigate the histological structure of the trachea in many species of birds. However, the cellular organization of the trachea in the mallard... 相似文献
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Muhammad Asim Helmi Hussien Luis Poveda John Thor Arnason Tony Durst 《Phytochemistry》2010,71(11-12):1418-1422
Five spirocaracolitone triterpenoids were isolated from the dichloromethane-soluble fraction of the bark of Ruptiliocarpon caracolito, and their structures were determined mainly by application of 1D and 2D NMR spectroscopy. Two known CD-spirotriterpenoids were also isolated from the same source. This brings the total number of known CD-spirotriterpenoids from this source to 17. The discovery of such a large number of closely-related compounds in a single species represents an excellent example of phytochemical redundancy as a defense mechanism. 相似文献
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