CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.     

甜菜夜蛾核多角体病毒基因组13.7～21.6 m.u.区域的分析

甜菜夜蛾核多角体病毒(Spodoptera exigua multicapsid nucleopolyhedrovirus,SeMNPV)基因组13．7～21．6m．u．区域是SeMNPV的重组热点区。以SeMNPV美国分离株SeUS1为模板,长片段PCR对SeUS1的13．7～21．6m．u．区域扩增,得到11．3kb,2．0kb和0．7kb3个片段。对照已发表的SeMNPV基因组序列,11．3kb片段是具完整SeMNPV序列基因型的产物,2.0kb和0．7kb片段表明SeUS1中还存在两种缺失突变株。对2．0kb和0．7kb片段的序列分析揭示了这两株突变株在缺失部位的DNA一级结构。对三株重组SeMNPV病毒(SeXDl、SeXD2和SeXD3)的分析发现,它们和野生型病毒SeUS1中的一个基因型一样,均缺失了SeMNPV nt 18513～29105之间长10593bp的片段,暗示SeUS1中一株自发形成的缺失突变体在离体细胞中具有复制优势。将该片段基因排列与其它10种基因组序列已测定的杆状病毒比较,发现两个在GroupⅡ NPVs中保守的基因簇。最大简约性法对部分基因的系统发育分析表明,缺失片段中某些基因可能存在于杆状病毒分化之前的病毒基因组中。     

烯-二炔”模型化合物前体：6-硫杂-13-氧杂双环［9．3．0］-3，8-十四二炔的合成

以顺 1,2 ,3,6 四氢邻苯二甲酸酐为原料 ,经还原 ,羟基保护 ,双键臭氧化开环 ,Wittig反应 ,双炔化 ,酯化 ,二醇化 ,二磺酸酯化 ,硫化 ,醇缩合共十步 ,合成了“烯 二炔”前体物 :6 硫杂 13 氧杂双环 [9.3.0 ] 3,8 十四二炔 .该合成法收率较高 ,反应条件温和 ,新化合物 ( 8) ,( 10 ) ,( 11)经元素分析 ,核磁 ,红外 ,质谱确证结构 .