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91.
Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination 总被引:20,自引:0,他引:20
Otto EA Schermer B Obara T O'Toole JF Hiller KS Mueller AM Ruf RG Hoefele J Beekmann F Landau D Foreman JW Goodship JA Strachan T Kispert A Wolf MT Gagnadoux MF Nivet H Antignac C Walz G Drummond IA Benzing T Hildebrandt F 《Nature genetics》2003,34(4):413-420
Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination. 相似文献
92.
Compartments revealed in food-web structure 总被引:1,自引:0,他引:1
Compartments in food webs are subgroups of taxa in which many strong interactions occur within the subgroups and few weak interactions occur between the subgroups. Theoretically, compartments increase the stability in networks, such as food webs. Compartments have been difficult to detect in empirical food webs because of incompatible approaches or insufficient methodological rigour. Here we show that a method for detecting compartments from the social networking science identified significant compartments in three of five complex, empirical food webs. Detection of compartments was influenced by food web resolution, such as interactions with weights. Because the method identifies compartmental boundaries in which interactions are concentrated, it is compatible with the definition of compartments. The method is rigorous because it maximizes an explicit function, identifies the number of non-overlapping compartments, assigns membership to compartments, and tests the statistical significance of the results. A graphical presentation reveals systemic relationships and taxa-specific positions as structured by compartments. From this graphic, we explore two scenarios of disturbance to develop a hypothesis for testing how compartmentalized interactions increase stability in food webs. 相似文献
93.
The brownian motion of mesoscopic particles is ubiquitous and usually random. But in systems with periodic asymmetric barriers to movement, directed or 'rectified' motion can arise and may even modulate some biological processes. In man-made devices, brownian ratchets and variants based on optical or quantum effects have been exploited to induce directed motion, and the dependence of the amplitude of motion on particle size has led to the size-dependent separation of biomolecules. Here we demonstrate that the one-dimensional pores of a macroporous silicon membrane, etched to exhibit a periodic asymmetric variation in pore diameter, can act as massively parallel and multiply stacked brownian ratchets that are potentially suitable for large-scale particle separations. We show that applying a periodic pressure profile with a mean value of zero to a basin separated by such a membrane induces a periodic flow of water and suspended particles through the pores, resulting in a net motion of the particles from one side of the membrane to the other without moving the liquid itself. We find that the experimentally observed pressure dependence of the particle transport, including an inversion of the transport direction, agrees with calculations of the transport properties in the type of ratchet devices used here. 相似文献
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鉴于目前没有一种方法能独立解决溢油鉴别的所有问题[1],本文提出近红外光谱技术结合主成分聚类分析鉴别溢油种类的方法.通过有机溶剂萃取出自行配制的汽油、柴油和润滑油模拟样品中的溢油后记录其近红外光谱,对5 800~6 200 cm-1区段范围内的近红外谱图经过多元散射校正(MSC),Norris一阶导数平滑预处理处理后求其主成分,并在主成分的基础上引入Ward聚类分析法(离差平方和法)对样品分类. 相似文献
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Business organisations have always existed in a constantly changing environment. To survive it is necessary for them to adapt and adjust to the changes. When analysing complex entities, such as organisations, researchers have frequently adopted the methods of action research. But with the advent of greater use of information and communication technology businesses are changing in their composition and one practical manifestation of this is the rise of virtual teams. Virtual teams reflect the trend for an organisation to comprise ‘satellites’ or clusters of expertise in different parts of the globe. Such a transformation of what we can now take as an organisation creates new challenges for managers and for those inquiring into organisational problems. In this paper we attempt to address the question whether action research is any longer a valid way of organisational intervention for the researcher and consultant alike. In this paper we describe field research in which a soft method of Action Research was used during the analysis phase of IS development as a means of understanding the problem domain, identifying information requirements, evaluating technologies and reducing conflicts. The research was conducted between two institutions that were separated by several thousand miles and all participants connected from individual locations using virtual synchronous ICT. The study provided insight into the use of AR in virtual settings and as a means of conflict resolution in virtual teams. The findings have implications for IS development (which is increasingly conducted in virtual teams), education and management among others. 相似文献
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Identification of ten loci associated with height highlights new biological pathways in human growth 总被引:1,自引:0,他引:1
Lettre G Jackson AU Gieger C Schumacher FR Berndt SI Sanna S Eyheramendy S Voight BF Butler JL Guiducci C Illig T Hackett R Heid IM Jacobs KB Lyssenko V Uda M;Diabetes Genetics Initiative;FUSION;KORA;Prostate Lung Colorectal Ovarian Cancer Screening Trial;Nurses' Health Study;SardiNIA Boehnke M Chanock SJ Groop LC Hu FB Isomaa B Kraft P Peltonen L Salomaa V Schlessinger D Hunter DJ Hayes RB Abecasis GR Wichmann HE Mohlke KL Hirschhorn JN 《Nature genetics》2008,40(5):584-591
Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait. 相似文献