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991.
Chemotherapy and cancer stem cells 总被引:1,自引:0,他引:1
Cancer stem cells are subsets of tumor cells defined through the capacity to initiate tumors and have been linked to therapeutic resistance. In this issue of Cell Stem Cell, Todaro et al. (2007) demonstrate that targeting tumor IL-4 sensitizes colon cancer stem cells to chemotherapy. 相似文献
992.
BDCA2/Fc epsilon RI gamma complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells
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Dendritic cells are equipped with lectin receptors to sense the extracellular environment and modulate cellular responses. Human plasmacytoid dendritic cells (pDCs) uniquely express blood dendritic cell antigen 2 (BDCA2) protein, a C-type lectin lacking an identifiable signaling motif. We demonstrate here that BDCA2 forms a complex with the transmembrane adapter Fc epsilon RI gamma. Through pathway analysis, we identified a comprehensive signaling machinery in human pDCs, similar to that which operates downstream of the B cell receptor (BCR), which is distinct from the system involved in T cell receptor (TCR) signaling. BDCA2 crosslinking resulted in the activation of the BCR-like cascade, which potently suppressed the ability of pDCs to produce type I interferon and other cytokines in response to Toll-like receptor ligands. Therefore, by associating with Fc epsilon RI gamma, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs. 相似文献
993.
Nguyen CT Nguyen NB Sung WK Zhang L 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2007,4(3):394-402
The small parsimony problem is studied for reconstructing recombination networks from sequence data. The small parsimony problem is polynomial-time solvable for phylogenetic trees. However, the problem is proved NP-hard even for galled recombination networks. A dynamic programming algorithm is also developed to solve the small parsimony problem. It takes O(dn2(3h)) time on an input recombination network over length-d sequences in which there are h recombination and n - h tree nodes. 相似文献
994.
Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40 总被引:1,自引:0,他引:1
Chen Y Xu Y Bao Q Xing Y Li Z Lin Z Stock JB Jeffrey PD Shi Y 《Nature structural & molecular biology》2007,14(6):527-534
The small t antigen (ST) of DNA tumor virus SV40 facilitates cellular transformation by disrupting the functions of protein phosphatase 2A (PP2A) through a poorly defined mechanism. The crystal structure of the core domain of SV40 ST bound to the scaffolding subunit of human PP2A reveals that the ST core domain has a novel zinc-binding fold and interacts with the conserved ridge of HEAT repeats 3-6, which overlaps with the binding site for the B' (also called PR61 or B56) regulatory subunit. ST has a lower binding affinity than B' for the PP2A core enzyme. Consequently, ST does not efficiently displace B' from PP2A holoenzymes in vitro. Notably, ST inhibits PP2A phosphatase activity through its N-terminal J domain. These findings suggest that ST may function mainly by inhibiting the phosphatase activity of the PP2A core enzyme, and to a lesser extent by modulating assembly of the PP2A holoenzymes. 相似文献
995.
The immunosuppressant FK506 binds Plasmodium falciparum FK-506 binding protein 35 (PfFKBP35) and shows anti-malarial activity. To understand molecular mechanism of the drug on the
parasite, we have done NMR studies. Here, we report the assignment of FK506-binding domain of PfFKBP35. 相似文献
996.
The nature of somaclonal variation at the nucleotide sequence level was studied in rice cv. Nipponbare. First, we investigated genomic variations by using 2 molecular marker systems: RAPD (random amplified polymorphic DNA) and ISSR (inter-simple sequence repeat). This was followed by sequencing of selected bands that represented genomic variations, and pairwise sequence analysis taking advantage of the whole genome sequence of rice. In addition, transpositional activity of the active MITE, mPing, was analysed by locus-specific PCR amplifications. The 2-year-old calli and their regenerated plants, analysed with 24 RAPD and 20 ISSR primers, showed moderate levels of genomic variation (20.83% and 17.04%, respectively). To test whether DNA methylation plays a role in somaclonal variation, the calli were treated with 5-azacytidine, a chemical agent that reduces cytosine methylation by blocking the activity of DNA methyltransferase. Though dwarfism occurred in regenerants from treated calli (a hallmark of the drug treatment), there was only a slight increase in the frequency of somaclonal variation detected in the treated calli and their regenerated plants relative to untreated controls. The transposon mPing also remained immobile in both treated and untreated calli. Nevertheless, dendrograms constructed according to the Jaccard coefficient calculated by UPGMA of the ISSR bands revealed that the 5-azacytidine-treated and untreated somaclones were grouped into 2 distinct clusters, suggesting a possible indirect effect of the treatment on the genomic changes, depending on the marker used. Sequence analysis indicated a low level of variation (0.31%), with single-base-pair substitutions predominating. 相似文献
997.
Zhang L Bao Z Cheng J Li H Huang X Wang S Zhang C Hu J 《Marine biotechnology (New York, N.Y.)》2007,9(5):606-612
Zhikong scallop (Chlamys farreri Jones et Preston, 1904) is one of the most commercially important bivalves in China, but research on its genome is underdeveloped.
In this study, we constructed the first Zhikong scallop fosmid library, and analyzed the fosmid end sequences to provide a
preliminary assessment of the genome. The library consists of 133,851 clones with an average insert size of about 40 kb, amounting
to 4.3 genome equivalents. Fosmid stability assays indicate that Zhikong scallop DNA was stable during propagation in the
fosmid system. Library screening with two genes and seven microsatellite markers yielded between two and eight positive clones,
and none of those tested was absent from the library. End-sequencing of 480 individual clones generated 828 sequences after
trimming, with an average sequence length of 624 bp. BLASTN searches of the nr and EST databases of GenBank and BLASTX searches
of the nr database resulted in 213 (25.72%) and 44 (5.31%) significant hits (E < e−5), respectively. Repetitive sequences analysis resulted in 375 repeats, accounting for 15.84% of total length, which were
composed of interspersed repetitive sequences, tandem repeats, and low-complexity sequences. The fosmid library, in conjunction
with the fosmid end sequences, will serve as a useful resource for physical mapping and positional cloning, and provide a
better understanding of the Zhikong scallop genome. 相似文献
998.
Binding properties of palmatine to DNA: spectroscopic and molecular modeling investigations
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Palmatine, an isoquinoline alkaloid, is an important medicinal herbal extract with diverse pharmacological and biological properties. In this work, spectroscopic and molecular modeling approaches were employed to reveal the interaction between palmatine and DNA isolated from herring sperm. The absorption spectra and iodide quenching results indicated that groove binding was the main binding mode of palmatine to DNA. Fluorescence studies indicated that the binding constant (K) of palmatine and DNA was ~ 104 L·mol?1. The associated thermodynamic parameters, ΔG, ΔH, and ΔS, indicated that hydrogen bonds and van der Waals forces played major roles in the interaction. The effects of chemical denaturant, thermal denaturation and pH on the interaction were investigated and provided further support for the groove binding mode. In addition to experimental approaches, molecular modeling was conducted to verify binding pattern of palmatine–DNA. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
999.
Jinlong Zhang Guijuan Feng Guofeng Bao Guanhua Xu Yuyu Sun Weidong Li Lingling Wang Jiajia Chen Huricha Jin Zhiming Cui 《Cell cycle (Georgetown, Tex.)》2015,14(16):2609-2618
Aberrant functionality of the cell cycle has been implicated in the pathology of traumatic SCI. Although it has been reported that the expressions of various cell cycle related proteins were altered significantly following SCI, detailed information on the subject remains largely unclear. The embryonic pyruvate kinase M2 (PKM2) is an important metabolic kinase in aerobic glycolysis or the warburg effect, however, its functions in central nervous system (CNS) injury remains elusive. Here we demonstrate that PKM2 was not only significantly upregulated by western blot and immunohistochemistry but certain traumatic stimuli also induced translocation of PKM2 into the nucleus in astrocytes following spinal cord injury (SCI). Furthermore, the expression levels and localization of p-β-catenin, p27, cyclin D1 and PCNA were correlated with PKM2 after SCI. In vitro, we also found that PKM2 co-immunoprecipitation with p-β-catenin and p27 respectively. Knockdown of PKM2 apparently decreased the level of PCNA, cyclinD1, p27 in primary astrocyte cells. Taken together, our findings indicate that nuclear translocation of PKM2 promotes astrocytes proliferation after SCI through modulating cell cycle signaling. These discoveries firstly uncovered the role of PKM2 in spinal cord injury and provided a potential therapeutic target for CNS injury and repair. 相似文献
1000.
Cheng Tan Li Zhang Xian Cheng Xiu-Feng Lin Rong-Rong Lu Jian-Dong Bao Hui-Xin Yu 《Experimental biology and medicine (Maywood, N.J.)》2015,240(7):925-935
Curcumin, traditionally used as food and medicinal purposes, has recently been reported to have protective efficacy against hypoxia. Hypoxia is one of the important reactive factors in tumor metastasis, which is a key problem in clinical thyroid cancer therapy. In present study, we investigate the anti-metastatic effect of curcumin on the K1 papillary thyroid cancer cells as well as its potential mechanisms. The results show that curcumin effectively inhibits hypoxia-induced reactive oxygen species (ROS) upregulation and significantly decreases the mRNA and protein expression levels of hypoxia-inducible factor-1α (HIF-1α) in K1 cells. Curcumin also decreases the DNA binding ability of HIF-1α to hypoxia response element (HRE). Furthermore, curcumin enhances E-cadherin expression, inhibits metalloproteinase-9 (MMP-9) enzyme activity, and weakens K1 cells migration under hypoxic conditions. In summary, these results indicate that curcumin possesses a potent anti-metastatic effect and might be an effective tumoristatic agent for the treatment of aggressive papillary thyroid cancers. 相似文献