Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations

Evidence for the etiology of autism spectrum disorders (ASDs) has consistently pointed to a strong genetic component complicated by substantial locus heterogeneity. We sequenced the exomes of 20 individuals with sporadic ASD (cases) and their parents, reasoning that these families would be enriched for de novo mutations of major effect. We identified 21 de novo mutations, 11 of which were protein altering. Protein-altering mutations were significantly enriched for changes at highly conserved residues. We identified potentially causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3. In the FOXP1 mutation carrier, we also observed a rare inherited CNTNAP2 missense variant, and we provide functional support for a multi-hit model for disease risk. Our results show that trio-based exome sequencing is a powerful approach for identifying new candidate genes for ASDs and suggest that de novo mutations may contribute substantially to the genetic etiology of ASDs.     

Etude du métabolisme d'une substance affectant la coagulation sanguine par la méthode des indicateurs radioactifs

Summary Radioactive 2-bromo-3-hydroxy-1:4-naphtoquinone has been used for the exploration of the metabolism of substances which influence the course of blood-clotting. It has been found that this substance diffuses very rapidly into the blood, and that the liver is not characterized by any elective fixation-power.     

Biosynthesis of deuteriated amino acids byCandida lipolytica

Summary Biosynthesis of a whole series of deuteriated amino acids has been carried out, by cultivation of the yeastCandida lipolytica in an artificial medium composed of a deuterio-alkane, heavy water, water and some mineral salts.Acknowledgments. This work has been carried out with the aid of grants from The Swedish Medical Research Council. Thanks are due to Mr Nils Engström for his skilful technical assistance during the yeast growth, and to Mrs Monica Olsson for the Moore-Stein analysis.     

Effect of Splice Marking on Fabric Roll Planning

Minimising the fabric loss during spreading can reduce the total production costs of garment manufacturing. Although marker planning is a major determinant of material utilisation, considerable savings on materials also will be made from the area of spreading loss. In the spreading process, it is general to have variance on the fabric yardage between each fabric roll, and the number of splice markings on each cutting lay is also varied. This paper aim to study how the fabric roll planning and the number of splice marks of a cutting lay will affect the material usage in the spreading process. By using a genetic algorithm approach, the amount of fabric to be saved by optimising the fabric roll sequence was derived by comparing the best arrangement and the worst arrangement of the fabric roll sequences of a cutting lay. The result of the study showed that both fabric roll planning and the number of splice marking have effect on the fabric loss. The findings could help the apparel manufacturer to reduce the     

我国物流企业生产效率与规模效率

首先利用DEACCR/BCC模型对我国在沪深港证券市场上市的55家物流企业的生产效率和规模效率进行实证比较分析,然后通过相关性分析及多项回归分析研究了规模效率及固定资产规模与生产效率的关系.结果表明：1)大型物流企业相对中小型物流企业而言并不具备显著的效率优势.2)我国物流企业不存在显著的规模效率差异,不应盲目追求资产规模的扩张和重组.3)我国物流企业的纯技术效率大于规模效率对生产效率的影响,物流企业的技术改进比规模扩张更具重要性.4)物流企业生产成本是影响企业生产效率的主要因素,而资产规模和职工工资对生产效率没有显著影响.     

Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein.

N-linked glycosylation of proteins in eukaryotic cells follows a highly conserved pathway. The tetradecasaccharide substrate (Glc3Man9GlcNAc2) is first assembled at the membrane of the endoplasmic reticulum (ER) as a dolichylpyrophosphate (Dol-PP)-linked intermediate, and then transferred to nascent polypeptide chains in the lumen of the ER. The assembly of the oligosaccharide starts on the cytoplasmic side of the ER membrane with the synthesis of a Man5GlcNAc2-PP-Dol intermediate. This lipid-linked intermediate is then translocated across the membrane so that the oligosaccharides face the lumen of the ER, where the biosynthesis of Glc3Man9GlcNAc2-PP-Dol continues to completion. The fully assembled oligosaccharide is transferred to selected asparagine residues of target proteins. The transmembrane movement of lipid-linked Man5GlcNAc2 oligosaccharide is of fundamental importance in this biosynthetic pathway, and similar processes involving phospholipids and glycolipids are essential in all types of cells. The process is predicted to be catalysed by proteins, termed flippases, which to date have remained elusive. Here we provide evidence that yeast RFT1 encodes an evolutionarily conserved protein required for the translocation of Man5GlcNAc2-PP-Dol from the cytoplasmic to the lumenal leaflet of the ER membrane.     

Variants conferring risk of atrial fibrillation on chromosome 4q25

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans and is characterized by chaotic electrical activity of the atria. It affects one in ten individuals over the age of 80 years, causes significant morbidity and is an independent predictor of mortality. Recent studies have provided evidence of a genetic contribution to AF. Mutations in potassium-channel genes have been associated with familial AF but account for only a small fraction of all cases of AF. We have performed a genome-wide association scan, followed by replication studies in three populations of European descent and a Chinese population from Hong Kong and find a strong association between two sequence variants on chromosome 4q25 and AF. Here we show that about 35% of individuals of European descent have at least one of the variants and that the risk of AF increases by 1.72 and 1.39 per copy. The association with the stronger variant is replicated in the Chinese population, where it is carried by 75% of individuals and the risk of AF is increased by 1.42 per copy. A stronger association was observed in individuals with typical atrial flutter. Both variants are adjacent to PITX2, which is known to have a critical function in left-right asymmetry of the heart.