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961.
Xin Z Zhao H Serby MD Liu B Liu M Szczepankiewicz BG Nelson LT Smith HT Suhar TS Janis RS Cao N Camp HS Collins CA Sham HL Surowy TK Liu G 《Bioorganic & medicinal chemistry letters》2008,18(15):4298-4302
A series of structurally novel stearoyl-CoA desaturase1 (SCD1) inhibitors has been identified via molecular scaffold manipulation. Preliminary structure–activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(methyl carbamoyl)phenyl]piperidine-1-carboxamide 4c exhibited robust in vivo activity with dose-dependent desaturation index lowering effects. 相似文献
962.
The purpose of the present study was to evaluate the effects of serum-starvation, contact-inhibition and roscovitine treatments on cell-cycle synchronization at the G0/G1 stage of ear skin fibroblasts isolated from transgenic cloned cattle. The developmental competence of re-cloned embryos was also examined. Our results showed that the proportion of G0/G1 cells from the serum-starved group at 3, 4 or 5 days was significantly higher compared with 1 or 2 days only (91.5, 91.7 and 93.5% versus 90.1 and 88.8%, respectively, p < 0.05); whilst there was no statistical difference among cells at 3, 4 or 5 days. For roscovitine-treated cells, the proportion of G0/G1 cells at 2, 3, 4 or 5 days was significantly higher than those treated for 1 day only (91.1, 90.1, 89.4 and 91.3% versus 86.51%, respectively, p < 0.05). The proportion of contact-inhibited G0/G1 cells rose significantly with treatment time, but was similar at 3, 4 and 5 days (89.4, 90.4, 91.4, 91.6 and 92.1%, respectively, p < 0.05). The efficiency of obtaining G0/G1 phase cells was lower when roscovitine treatment was employed to synchronize the cell cycle compared with the serum-starvation and contact-inhibition methods (89.7 versus 91.1% and 91.0%, p < 0.05). Moreover, obvious differences were observed in the rate of fused couplets and blastocysts (89.88 +/- 2.70 versus 87.40 +/- 5.13; 44.10 +/- 8.62 versus 58.38 +/- 13.28, respectively, p < 0.05), when nuclear transfer embryos were reconstructed using donors cells that had been serum starved or contact inhibited for 3 days. Our data indicate that 3 day treatment is feasible for harvesting sufficient G0/G1 cells to produce re-cloned transgenic bovine embryos, regardless of whether serum-starvation, contact-inhibition or roscovitine treatments are used as the synchronization methods. 相似文献
963.
The COP9 signalosome: more than a protease 总被引:1,自引:0,他引:1
The COP9 signalosome (CSN) is a conserved protein complex that functions in the ubiquitin-proteasome pathway. After two decades of research, we now know that the CSN is a multi-subunit protease that regulates the activity of cullin-RING ligase (CRL) families of ubiquitin E3 complexes. The CSN is rapidly emerging as a key player in the DNA-damage response, cell-cycle control and gene expression. The independent functions of CSN5 (also known as JAB1) add to the complexity of the CSN machinery. Here, we provide an updated view of the structure, functions and regulation of this protein complex. 相似文献
964.
Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases 总被引:1,自引:0,他引:1
965.
Protein kinase Cζ PKCζ mediates cancer cell chemotaxis by regulating cytoskeleton rearrangement and cell adhesion. In the research for its upstream regulator, we investigated the role of Akt2 in chemotaxis and metastasis of human breast cancer cells. Reduction of Akt2 expression by siRNA inhibited chemotaxis of MDA-MB-231, T47D, and MCF7 cells, three representative human breast cancer cells. Expression of a wild type Akt2 in siRNA transfected cells rescued the phenotype. EGF-induced integrin β1 phosphorylation was dampened, consistent with defects in adhesion. Phosphorylation of LIMK and cofilin, a critical step of cofilin recycle and actin polymerization, was also impaired. Thus, Akt2 regulates both cell adhesion and cytoskeleton rearrangement during chemotaxis. Depletion of Akt2 by siRNA impaired the activation of PKCζ while inhibition of PKCζ did not interfere with EGF induced phosphorylation of Akt. Furthermore, EGF induced co-immunoprecipitation between PKCζ and Akt2, but not Akt1, suggesting that a direct interaction between PKCζ and Akt2 in chemotaxis. Protein levels of integrin β1, LIMK, cofilin, and PKCζ didn't alter, suggesting that Akt2 does not regulate the expression of these signaling molecules. In a Severe Combine Immunodeficiency mouse model, Akt2 depleted MDA-MB-231 cells showed a marked reduction in metastasis to mouse lungs, demonstrating the biological relevancy of Akt2 in cancer metastasis in vivo. Taken together, our results suggest that Akt2 directly mediates EGF-induced chemotactic signaling pathways through PKCζ and its expression is critical during the extravasation of circulating cancer cells. 相似文献
966.
Quantitative trait loci (QTL) analysis for rice grain width and fine mapping of an identified QTL allele gw-5 in a recombination hotspot region on chromosome 5 总被引:10,自引:0,他引:10
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Rice grain width and shape play a crucial role in determining grain quality and yield. The genetic basis of rice grain width was dissected into six additive quantitative trait loci (QTL) and 11 pairs of epistatic QTL using an F(7) recombinant inbred line (RIL) population derived from a single cross between Asominori (japonica) and IR24 (indica). QTL by environment interactions were evaluated in four environments. Chromosome segment substitution lines (CSSLs) harboring the six additive effect QTL were used to evaluate gene action across eight environments. A major, stable QTL, qGW-5, consistently decreased rice grain width in both the Asominori/IR24 RIL and CSSL populations with the genetic background Asominori. By investigating the distorted segregation of phenotypic values of rice grain width and genotypes of molecular markers in BC(4)F(2) and BC(4)F(3) populations, qGW-5 was dissected into a single recessive gene, gw-5, which controlled both grain width and length-width ratio. gw-5 was narrowed down to a 49.7-kb genomic region with high recombination frequencies on chromosome 5 using 6781 BC(4)F(2) individuals and 10 newly developed simple sequence repeat markers. Our results provide a basis for map-based cloning of the gw-5 gene and for marker-aided gene/QTL pyramiding in rice quality breeding. 相似文献
967.
Chen N Zinchenko AA Yoshikawa Y Araki S Adachi S Yamazoe M Hiraga S Yoshikawa K 《Journal of bacteriology》2008,190(10):3731-3737
Fluorescence microscopic observation of individual T4 DNA molecules revealed that the MukBEF complex (bacterial condensin) and its subunit, the MukB (a member of the SMC [structural maintenance of chromosomes] superfamily) homodimer, of Escherichia coli markedly shrunk large DNA molecules in the presence of hydrolyzable ATP. In contrast, in the presence of ADP or ATP-gammaS, the conformation of DNA was almost not changed. This suggests that the ATPase activity of subunit MukB is essential for shrinking large DNA molecules. Stretching experiments on the shrunken DNA molecules in the presence of ATP and MukBEF indicated a cross-bridging interaction between DNA molecules. 相似文献
968.
969.
Hong-sheng Wu Xiao-ming Yin Dong-yang Liu Ning Ling Wei Bao Rong-rong Ying Yi-yong Zhu Shi-wei Guo Qi-rong Shen 《Plant and Soil》2008,308(1-2):255-266
The impact of fusaric acid (FA) phytotoxin on the physiology of root leaf cells in watermelon seedlings was evaluated. Results revealed that the cell membrane potential treated with FA in 12 h was decreased by 61.9–81.8% compared with untreated controls. FA markedly accelerated the lipid peroxidase activity of watermelon leaves. Malondiadehyde in leaves treated with different concentrations of FA in 24 h was 5.2–11.0 fold as much as control. Phenylalanine ammonia-lyase activity (PAL) in leaves treated with FA was first increased and then decreased. The highest PAL activity was obtained after 6–12 h, which was 7.2–10.5 fold as much as control. Activities of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) were first increased and then decreased when the seedlings were treated with FA. The highest SOD and POD activities were observed after 12 h and then both declined. The β-1,3-glucanase and chitinase activities in leaves treated with FA were first quickly increased and then declined, the highest activities were found after 12 and 3 h. We concluded that FA strongly inhibited root and leaf cells functions physiologically responsible for fusarium wilt of watermelon. 相似文献
970.
A specific signaling role for H2O2 in Chlamydomonas reinhardtii was demonstrated by the definition of a promoter that specifically responded to this ROS. Expression of a nuclear-encoded
reporter gene driven by this promoter was shown to depend not only on the level of exogenously added H2O2 but also on light. In the dark, the induction of the reporter gene by H2O2 was much lower than in the light. This lower induction was correlated with an accelerated disappearance of H2O2 from the culture medium in the dark. Due to a light-induced reduction in catalase activity, H2O2 levels in the light remained higher. Photosynthetic electron transport mediated the light-controlled down-regulation of the
catalase activity since it was prevented by 3-(3′4′-dichlorophenyl)-1,1-dimethylurea (DCMU), an inhibitor of photosystem II.
In the presence of light and DCMU, expression of the reporter gene was low while the addition of aminotriazole, a catalase
inhibitor, led to a higher induction of the reporter gene by H2O2 in the dark. The role of photosynthetic electron transport and thioredoxin in this regulation was investigated by using mutants
deficient in photosynthetic electron flow and by studying the correlation between NADP-malate dehydrogenase and catalase activities.
It is proposed that, contrary to expectations, a controlled down-regulation of catalase activity occurs upon a shift of cells
from dark to light. This down-regulation apparently is necessary to maintain a certain level of H2O2 required to activate H2O2-dependent signaling pathways. 相似文献