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microRNAs (miRNAs) function as genetic rheostats to control gene output. Based on their role as modulators, it has been postulated that miRNAs canalize development and provide genetic robustness. Here, we uncover a previously unidentified regulatory layer of chemokine signaling by miRNAs that confers genetic robustness on primordial germ cell (PGC) migration. In zebrafish, PGCs are guided to the gonad by the ligand Sdf1a, which is regulated by the sequestration receptor Cxcr7b. We find that miR-430 regulates sdf1a and cxcr7 mRNAs. Using target protectors, we demonstrate that miR-430-mediated regulation of endogenous sdf1a (also known as cxcl12a) and cxcr7b (i) facilitates dynamic expression of sdf1a by clearing its mRNA from previous expression domains, (ii) modulates the levels of the decoy receptor Cxcr7b to avoid excessive depletion of Sdf1a and (iii) buffers against variation in gene dosage of chemokine signaling components to ensure accurate PGC migration. Our results indicate that losing miRNA-mediated regulation can expose otherwise buffered genetic lesions leading to developmental defects.  相似文献   
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Cher.  AA 《世界科学》1989,11(11):11-14
40年前A.爱因斯坦给M.玻恩的一封信中写道,“上帝不玩骰子。”爱因斯坦是始终反对量子论的概率解释的,他不倦地探索着与经典力学更为直接的类比,即考虑没有概率不定性的确定过程。如今,40年过去了,没有人会惊讶:甚至在一个经典哈密顿动力系统中也存在着(chas)在物理客体规则运动的领域内,在没有人预期会有的地方冒出  相似文献   
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二甲基甲酰胺中Sm(Ⅲ)电化学性质及其合金膜研究   总被引:1,自引:0,他引:1  
通过循环伏安法研究二甲基甲酰胺中Sm(Ⅲ)在Pt上的电化学性质,表明Sm(Ⅲ)在Pt上的还原为不可逆反应,同时测得传递系数α=0.0289,扩散系数D0=1.288×10^-5cm^2·S^-1;通过塔菲尔曲线求得交换电流密度i0=1.596×10^-7A/cm^2;对Sm(Ⅲ)在Pt上离子成核机理研究表明,Sm(Ⅲ)在Pt电极上是按三维模式扩散控制下连续成核的;用恒电位法可以制得有金属光泽、附着力好、表面均匀致密的Sm-Ni-Co合金膜,与Ni-Co合金膜相比较结构性能有所提高.  相似文献   
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Generation of a diverse and self-tolerant T-cell repertoire requires appropriate interpretation of T-cell antigen receptor (TCR) signals by CD4(+?) CD8(+) double-positive thymocytes. Thymocyte cell fate is dictated by the nature of TCR-major-histocompatibility-complex (MHC)-peptide interactions, with signals of higher strength leading to death (negative selection) and signals of intermediate strength leading to differentiation (positive selection). Molecules that regulate T-cell development by modulating TCR signal strength have been described but components that specifically define the boundaries between positive and negative selection remain unknown. Here we show in mice that repression of TCR-induced death pathways is critical for proper interpretation of positive selecting signals in vivo, and identify schnurri-2 (Shn2; also known as Hivep2) as a crucial death dampener. Our results indicate that Shn2(-/-) double-positive thymocytes inappropriately undergo negative selection in response to positive selecting signals, thus leading to disrupted T-cell development. Shn2(-/-) double-positive thymocytes are more sensitive to TCR-induced death in vitro and die in response to positive selection interactions in vivo. However, Shn2-deficient thymocytes can be positively selected when TCR-induced death is genetically ablated. Shn2 levels increase after TCR stimulation, indicating that integration of multiple TCR-MHC-peptide interactions may fine-tune the death threshold. Mechanistically, Shn2 functions downstream of TCR proximal signalling compenents to dampen Bax activation and the mitochondrial death pathway. Our findings uncover a critical regulator of T-cell development that controls the balance between death and differentiation.  相似文献   
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Cold purification filter cakes generated in the hydrometallurgical processing of Angouran mine zinc concentrate commonly contain significant amounts of Zn, Cd, and Ni ions and thus are valuable resources for metal recovery. In this research, a nickel containing solution that was obtained from sulfuric acid leaching of the filter cake following cadmium and zinc removal was subjected to solvent extraction experiments using 10vol% LIX984N diluted in kerosene. Under optimum experimental conditions (pH 5.3, volume ratio of organic/aqueous (O:A) = 2:1, and contact time = 5 min), more than 97.1% of nickel was extracted. Nickel was stripped from the loaded organic by contacting with a 200 g/L sulfuric acid solution, from which 77.7% of nickel was recovered in a single contact at the optimum conditions (pH 1–1.5, O:A = 5:1, and contact time = 15 min).  相似文献   
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