Complex interactions between genes controlling trafficking in primary cilia

Cilia-associated human genetic disorders are striking in the diversity of their abnormalities and their complex inheritance. Inactivation of the retrograde ciliary motor by mutations in DYNC2H1 causes skeletal dysplasias that have strongly variable expressivity. Here we define previously unknown genetic relationships between Dync2h1 and other genes required for ciliary trafficking. Mutations in mouse Dync2h1 disrupt cilia structure, block Sonic hedgehog signaling and cause midgestation lethality. Heterozygosity for Ift172, a gene required for anterograde ciliary trafficking, suppresses cilia phenotypes, Sonic hedgehog signaling defects and early lethality of Dync2h1 homozygotes. Ift122, like Dync2h1, is required for retrograde ciliary trafficking, but reduction of Ift122 gene dosage also suppresses the Dync2h1 phenotype. These genetic interactions illustrate the cell biology underlying ciliopathies and argue that mutations in intraflagellar transport genes cause their phenotypes because of their roles in cilia architecture rather than direct roles in signaling.     

Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia

The evolutionarily conserved SLX4 protein, a key regulator of nucleases, is critical for DNA damage response. SLX4 nuclease complexes mediate repair during replication and can also resolve Holliday junctions formed during homologous recombination. Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness Fanconi anemia. Btbd12-deficient animals are born at sub-Mendelian ratios, have greatly reduced fertility, are developmentally compromised and are prone to blood cytopenias. Btbd12(-/-) cells prematurely senesce, spontaneously accumulate damaged chromosomes and are particularly sensitive to DNA crosslinking agents. Genetic complementation reveals a crucial requirement for Btbd12 (also known as Slx4) to interact with the structure-specific endonuclease Xpf-Ercc1 to promote crosslink repair. The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway.     

Improved method of large scale purification of acetylcholinesterase from the electric eel (Electrophorus electricus) by affinity chromatography

Résumé Une méthode basée sur d'affinité chromatographique nous a permis de purifier complètement l'acétylcholinestérase des organes électriques du gymnote (Electrophorus electricus). L'activité spécifique de l'acétylcholinestérase ainsi établie en milligrammes dépasse 950 mM de substrat hydrolysé (acétylcholine)/mg protéine/h et sa pureté a été vérifiée par électrophorèse sur gel de polyacrylamide.

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This work was supported by grants: USPHS No. GM-01839 and U.C. San Francisco Academic Senate Research Committee, Grant No. 46.     

先秦云梯形制辨

该文主要从先秦文献中所载之楼车及云梯形制，说明二者实有相同之功能，即用以窥伺敌军。从汉儒服《左传》时引用《兵法》一书，即提供了一项较少为右来学界注意的材料。后人由于二者名称各不相同，乃以二者并不相涉；文中则典籍所载，提出所谓“飞楼”者，当为设于云梯上用来观察敌情之塔楼，以证二者理应极有关系。     

The adequacy of thiamine in liquid diets used in animal models of alcoholism

Summary The effects of chronic administration of 2 types of liquid diets on brain thiamine pyrophosphate (TPP) levels have been investigated. With the Lieber-DeCarli diet, rats in the control group had significantly lower TPP levels compared with those of the ethanol group. The Nutrament diet used in mice was apparently adequate in the thiamine supply.Acknowledgment. The authors are thankful to Dr Hebe Greizerstein for her review and comments on this mansucript.     

我国移动通信量差异的人口学分析

引人了地理迁移关系模型和社会网络人类动力学模型,将前一个模型中的“1个原型网络系统和2个变形网络系统”转换为演变过程的原始状态、迁移及适应3个阶段,将后一个模型中的“社会网络的典型特征——较高的集聚和较短的平均路径”分解为2个类型(非群体类型和群体类型),作为我国移动通信量人口学分析的研究方法.构建了我国各省的包括3个人口迁移指标、4个人口技术构成指标在内的人口学数据系统,针对3个重要的移动通信指标,分别解释人口学要素与移动通信量的内在联系.研究发现:1)应用地理迁移关系模型可以较好地描述不同演变阶段人口迁移对移动通信使用的影响,这种影响是通过保持原有链接、构建产生新链接而完成的;2)应用社会网络人类动力学模型可以较好地描述人口技术构成因素对移动通信使用的影响.     

The utility F-box for protein destruction

A signature feature of all living organisms is their utilization of proteins to construct molecular machineries that undertake the complex network of cellular activities. The abundance of a protein element is temporally and spatially regulated in two opposing aspects: de novo synthesis to manufacture the required amount of the protein, and destruction of the protein when it is in excess or no longer needed. One major route of protein destruction is coordinated by a set of conserved molecules, the F-box proteins, which promote ubiquitination in the ubiquitin-proteasome pathway. Here we discuss the functions of F-box proteins in several cellular scenarios including cell cycle progression, synapse formation, plant hormone responses, and the circadian clock. We particularly emphasize the mechanisms whereby F-box proteins recruit specific substrates and regulate their abundance in the context of SCF E3 ligases. For some exceptions, we also review how F-box proteins function through non-SCF mechanisms.