Effects of modulators of myosin light-chain kinase activity in single smooth muscle cells

Phosphorylation of myosin light chains by a calmodulin-myosin light-chain kinase (MLCK) pathway is considered to be responsible for coupling increased calcium concentration with contraction in smooth muscle. This simple view has, however, recently been questioned. To test this hypothesis directly, we microinjected individual smooth muscle cells with modulators of the MLCK pathway while measuring contraction and calcium-ion concentration. Injection of a constitutively active proteolyzed form of MLCK causes contraction but no change in calcium concentration. By contrast, injection of peptide inhibitors of MLCK blocks contraction in response to K+ depolarization, despite the fact that the change in calcium concentration in response to stimulation was enhanced over controls. These results provide a direct demonstration at the level of a single cell that activation of the calmodulin-MLCK pathway is both necessary and sufficient to trigger contraction of smooth muscle.     

供应链中的部分信息共享模型

研究了部分信息共享情况下的双层供应链问题。在对双层供应链模型中的完全信息共享模型进行简单描述的基础上,利用动态规划方法构建了该问题的部分信息共享模型,探讨了市场波动情况、补货等待时间等因素对于部分信息共享对象选择的影响。最后给出了一个计算实例,并利用MATLB进行了模拟计算。     

Control of tension development in scallop muscle fibres with foreign regulatory light chains

We have shown previously that chemically skinned fibre bundles from scallop muscle can be desensitized to the action of calcium by the removal of the regulatory light chains of myosin and that sensitivity can be restored by the re-addition of scallop light chains. We have now confirmed these results and extended our observations to fibre bundles from which one or both of the regulatory light chains per myosin have been removed (by treatment with EDTA at 7 and 25 degrees C, respectively) and replaced by the corresponding light chains from other species. In the case of a double substitution--where both light chains were replaced--sensitivity was restored completely by light chains from other molluscs and from gizzard muscle; for a single substitution there was restoration of sensitivity by all the light chains tested.     

Structure of the backbone in myosin filaments of muscle

New X-ray data suggest how myosin rods, themselves alpha-helical coiled coils, form the thick filament backbone of crustacean muscles by additional supercoiling. Natural transformations of this structure may describe the myosin backbone in many other animals also.     

枳实、青皮对平滑肌运动的影响

概述了枳实、青皮对平滑肌运动的影响及其作用机理的有关研究，枳实煎剂对胃肠、子宫平滑肌的作用及作用机理及平滑肌所处的机能状态有关；在体时呈兴奋作用，离体时呈抑制作用；枳实对胃肠平滑肌的兴奋作用是通过兴奋胆碱能途径及抑制神经纤维一氧化氮合成酶的活性实现的，其抑制作用是通过一氧化氮及肾上腺素能系统实现的，青皮煎剂影响胃肠、子宫、膀胱平滑肌的收缩活动，但因作用部位不同其作用及作用机理也不同，对胃平滑肌呈抑制作用，主要是由胆碱能M受体介导；对肠平滑肌（除回肠）呈抑制作用，主要是药物直接作用于平滑肌的结果；对子宫平滑肌、回肠纵行肌呈抑制作用，而对膀胱平滑肌却呈兴奋作用，上述效应均是通过肾上腺素能途径实现的。     

Location of the ATPase site of myosin determined by three-dimensional electron microscopy

Both ATP hydrolysis by myosin and the accompanying cyclic association-dissociation of actin and myosin are essential for muscle contraction. It is important for understanding the molecular mechanism of contraction to know the three-dimensional locations of the two major functional sites of myosin: the ATPase site and the actin-binding site. We have determined the position of the ATPase site of myosin using three-dimensional image reconstruction from electron micrographs and site-specific labelling with the avidin-biotin system. The ATPase site is about 5 nm from the tip of the myosin head and is about 4 nm away from the actin-binding site of myosin. This is the first report of the three-dimensional location of an enzyme active site by electron microscopy.     

Somatic variants of murine immunoglobulin lambda light chains

Studies of the murine lambda light chains produced by myeloma cells provided the first evidence for somatic point mutation of germ-line variable (V) region genes. An examination of the variable regions of 19 lambda 1 chains revealed seven which differed from a common sequence by one to three amino acid substitutions. Subsequently, one of these presumed somatic variants of the single lambda 1 V gene was characterized by DNA sequence analysis of the rearranged functional gene. The predicted DNA sequence alteration was observed and no silent mutation was evident. These studies of lambda chain variants suggested that the hypervariable, complementarity-determining regions (CDRs) ht be a preferred site of somatic mutation because all seven characterized variants contained substitutions only in these regions. By contrast, comparisons of closely related kappa chain variable region amino acid sequences, and more recently VK and VH genes, have suggested that somatic mutation probably occurs in codons for both framework and CDR residues. To examine this apparent discrepancy between the sites of somatic mutations in lambda and kappa genes, we have determined the nucleotide sequence of two lambda 1 gene from hybridomas and a lambda 2 gene from a myeloma. These sequences demonstrate that somatic mutation in lambda genes can occur in both the framework and CDR residues.