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.     

Genome partitioning of genetic variation for complex traits using common SNPs

We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ～45%, ～17%, ～25% and ～21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ～0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein.     

De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly

De novo somatic mutations in focal areas are well documented in diseases such as neoplasia but are rarely reported in malformation of the developing brain. Hemimegalencephaly (HME) is characterized by overgrowth of either one of the two cerebral hemispheres. The molecular etiology of HME remains a mystery. The intractable epilepsy that is associated with HME can be relieved by the surgical treatment hemispherectomy, allowing sampling of diseased tissue. Exome sequencing and mass spectrometry analysis in paired brain-blood samples from individuals with HME (n = 20 cases) identified de novo somatic mutations in 30% of affected individuals in the PIK3CA, AKT3 and MTOR genes. A recurrent PIK3CA c.1633G>A mutation was found in four separate cases. Identified mutations were present in 8-40% of sequenced alleles in various brain regions and were associated with increased neuronal S6 protein phosphorylation in the brains of affected individuals, indicating aberrant activation of mammalian target of rapamycin (mTOR) signaling. Thus HME is probably a genetically mosaic disease caused by gain of function in phosphatidylinositol 3-kinase (PI3K)-AKT3-mTOR signaling.     

IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy

Jeune asphyxiating thoracic dystrophy, an autosomal recessive chondrodysplasia, often leads to death in infancy because of a severely constricted thoracic cage and respiratory insufficiency; retinal degeneration, cystic renal disease and polydactyly may be complicating features. We show that IFT80 mutations underlie a subset of Jeune asphyxiating thoracic dystrophy cases, establishing the first association of a defective intraflagellar transport (IFT) protein with human disease. Knockdown of ift80 in zebrafish resulted in cystic kidneys, and knockdown in Tetrahymena thermophila produced shortened or absent cilia.     

Biology and conservation of the Coral Pink Sand Dunes tiger beetle, Cicindela limbata albissima Rumpp

This study investigated the distribution, abundance, and biology of Cicindela limbata albissima Rumpp, an endemic tiger beetle known only from the Coral Pink Sand Dunes (CPSD) in southwestern Utah. A recently implemented conservation agreement between BLM, USFWS, Utah State Parks, and Kane County protects most of the known habitat of this beetle from off-highway vehicle (OHV) use. A search of collection records and field surveys of 19 Great Basin sand dune sites indicated that this species occurs only at CPSD. Yearly index counts of adults (1992-1998) during peak season in May ranged from 331 in 1997 to 895 in 1993, but the actual population size is probably 2-3 times higher than the index counts. Nearly all of the population is found in the primary habitat, a 300-m-wide × 2.7-km-long area in the southern part of the dune field. Small numbers of adults and larvae have been found at the far north end of the dune field. Mark-recapture studies indicated that most adults moved only short distances ( Surveys of dominant plant species, arthropod (potential tiger beetle prey) abundance, and OHV activity indicated that these vary throughout the dune field and may explain, in part, the distribution of C. l. albissima . The primary habitat is a transition area between the highly dynamic south end of the dune field and the more stabilized north end. Psoralidium lanceolatum Rybd., Sophora stenophylla Gray, and Stipa hymenoides R.&S. are the dominant plants in the interdunal swales of the primary habitat, but other species are dominant in other parts of the dune field. Numbers of arthropod individuals and taxa are greatest in the primary habitat. Off-highway vehicle activity was greatest at the south end of the dune field and lowest at the far north end. Run-over trials and observational data revealed that adult beetles are killed by OHVs, but more important impacts may be damage to vegetation, reduction of arthropod prey of C. l. albissima , and disturbance and increased desiccation of the larval microhabitat. We anticipate that the conservation agreement will provide long-term protection for this species at CPSD.     

一种丙烯酸聚合物锅炉水处理药剂性能研究

对一种锅炉水处理药剂的除垢、防垢性能、毒性能等进行了实验。实验得到了该药剂用于防垢时的锅炉原水硬度和用量关系式:y=0.095 1x+0.002 31以及除垢时的用量曲线。实验结果表明:该药剂使用温度广(100~223℃),可钝化锅炉金属,对锅炉蒸汽无污染,可用于食品、药品等对蒸汽品质有特殊要求的工业领域。     

道路交通驾驶员差异性分类定量研究

驾驶员个体差异是影响城市道路交通运营、效率及安全的一个重要因素之一。为了实现对驾驶员差异性的影响分析,采用驾驶模拟舱研究平台对驾驶员样本进行和归类。本研究分别选取了反映驾驶员特征的静态驾驶适性和动态驾驶两类共计15个指标。采用因子分析的方法将相关指标归纳为驾驶员的5个类因子,并通过主成份分析的方法找出每类因子中的主导指标,并以此指标作为聚类分析的输入变量。结果表明聚类分析得到的三类驾驶员具有明显的各自特征。