CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation and establishing laterality. Cilia motility defects cause primary ciliary dyskinesia (PCD, MIM244400), a disorder affecting 1:15,000-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive ciliary bending. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD-linked loci. Here we show that the zebrafish cilia paralysis mutant schmalhans (smh(tn222)) encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a-regulated gene product. Screening 146 unrelated PCD families identified individuals in six families with reduced outer dynein arms who carried mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103/Pr46b functions as a tightly bound, axoneme-associated protein. These results identify Ccdc103 as a dynein arm attachment factor that causes primary ciliary dyskinesia when mutated.     

Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.     

Navigating the signalling network in mouse cardiac myocytes

Cardiac myocytes have a complex network of signals that regulates their essential role in the rhythmic pumping of the heart. This network is an appealing model system in which to study the basic principles underlying cellular signalling mechanisms. Progress in this effort has come through the establishment of standardized myocyte isolation and culture procedures and characterization of important signalling responses.     

Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease

Darier disease (DD) is an autosomal-dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently we constructed a 2.4-Mb, P1-derived artificial chromosome contig spanning the DD candidate region on chromosome 12q23-24.1. After screening several genes that mapped to this region, we identified mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca2(+)-ATPase type 2 isoform (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were identified, including frameshift deletions, in-frame deletions or insertions, splice-site mutations and non-conservative missense mutations in functional domains. Our results demonstrate that mutations in ATP2A2 cause DD and disclose a role for this pump in a Ca(2+)-signalling pathway regulating cell-to-cell adhesion and differentiation of the epidermis.     

声学多孔材料的孔结构优化

介绍了一种基于微结构的声学模型,可用来对多孔材料的微组织结构进行优化,从而使多孔材料具备最佳的声学性能.该模型是一种适用于低雷诺数的非稳态线性声学模型,主要微结构考虑平行排列的柱形杆件或圆球列阵,包括3个子模型:①声波传播方向平行于圆柱形杆件的子模型;②声波传播方向垂直于圆柱形杆件的子模型;③声波在圆球列阵中传播和吸收的子模型.前2个子模型通过考虑多边形周期边界条件的影响,计及了相邻圆柱形杆件间的交互作用.由于模型是线性的,因此可以结合起来描述任意角度入射声波的传播特性.第3个子模型可用于描述胞状多孔材料中节点处的情形.文中利用这3个子模型来扩大吸声材料的设计空间,根据不同用途所要求的声学特性计算最优的胞元结构,并对这种模型的应用领域进行了分析讨论.     

Aquatic invertebrate fauna of a northern prairie stream: range extensions and water quality characteristics

The benthic macroinvertebrate fauna of southern Saskatchewan, Canada, has received little attention relative to other regions of western North America. Therefore, little is known of the related aquatic ecosystem health and biogeography of regional aquatic insects. Here we present the results of an aquatic macroinvertebrate survey for the Pipestone Creek watershed in southeastern Saskatchewan. We qualitatively sampled aquatic macroinvertebrates in 5 sites on 4 dates through spring, summer, and fall 2006. Sampling produced 294 taxa of macroinvertebrates including 25 provincial range extensions to the southeast corner of the province. Presence/absence data of taxa grouped the sites into lentic and lotic sites. However, the relative proportions of the taxa varied greatly among sites, with no 2 sites having a community similarity greater than 50%. Functional feeding group analyses separated the sites into collector-dominated and scraper/grazer-dominated sites. However, the taxonomic make-up of the feeding groups varied among sites and also among dates. A modified Hilsenhoff Biotic Index of the site communities indicated that all were influenced by organic pollution. Results of this study suggest that although the watershed is enormously diverse, its biological communities are likely influenced by organic pollution. Further, range expansions of species found here, such as the stonefly Perlesta placida , have implications for invasion pathways and post-glaciation species islands in a prairie landscape.