Systematic pathway analysis using high-resolution fitness profiling of combinatorial gene deletions

Systematic genetic interaction studies have illuminated many cellular processes. Here we quantitatively examine genetic interactions among 26 Saccharomyces cerevisiae genes conferring resistance to the DNA-damaging agent methyl methanesulfonate (MMS), as determined by chemogenomic fitness profiling of pooled deletion strains. We constructed 650 double-deletion strains, corresponding to all pairings of these 26 deletions. The fitness of single- and double-deletion strains were measured in the presence and absence of MMS. Genetic interactions were defined by combining principles from both statistical and classical genetics. The resulting network predicts that the Mph1 helicase has a role in resolving homologous recombination-derived DNA intermediates that is similar to (but distinct from) that of the Sgs1 helicase. Our results emphasize the utility of small molecules and multifactorial deletion mutants in uncovering functional relationships and pathway order.     

Die Wirkung des Toluidinblaus und der Thrombokinase auf den Vorgang der Thrombininaktivierung

Summary The disappearance of thrombin—formed in the blood, or added to serum-follows a manomolecular reaction-type. Heparin increases the reaction-velocity of this thrombin-inactivating process.Our investigation established that toluidine blue or kinase, which, according to the literature, bind heparin, strongly reduce the speed of thrombin-inactivation too. Therefore the heparin-binding capacity of these substances is also manifested in the decrease of thrombin-inactivation.     

The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease

The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.     

Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia

Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia.     

浅谈新型墙体材料——煤矸石空心砖

煤矸石空心砖是一种新型环保墙体材料，符合国家及山西省出台的限制生产和使用实心黏土砖，鼓励发展新型建筑材料的政策。利用煤矸石制造的空心砖可以作为保温材料，既可节约建筑能耗，又可节约土地资源，减少环境污染。煤矸石空心砖同黏土实心砖相比，具有高强、轻质、隔音、隔热、保温、防震等优点，市场前景良好。     

A Framework to Support Agility Strategy Formulation

In the last decade, turbulent times and uncertainti es in the business environment have made ground for a new business era, and “chang e“ has become a major characteristic of the new era. This has resulted in tirele ss evolution of business systems and the creation of new manufacturing and manag ement philosophies. Agile Manufacturing (AM) is a step forward in generation of new means for better performance and success of business, and in practice is a s trategic approach to manufacturing by considering ...     

金属基复合材料界面层阻尼功能研究

采用CVD技术制备了具有不同界面层的C-f/Al金属基复合材料，获得了一种界面层阻尼功能设计的新方法. 研究发现具有特殊界面层的C-f/Al复合材料的抗拉强度、弹性模量和阻尼性能比无界面层时都有明显增加，并且不同界面层的效果不同. 碳层对复合材料阻尼性能的提高效果最大，硅层的提高效果不如碳层，碳硅混合层的效果居中. 涂层的厚度也影响了阻尼提高的效果，较厚的碳层效果更好，这是由于提高了复合材料的阻尼应变振幅效应而产生的. 研究认为发生在界面层的微滑移是其主要的阻尼机制.