A site of action of light on14C-acetate incorporation into human skin sterols

Zusammenfassung Die Synthese von Sterolen in menschlicher Haut, welche im langwelligen Spektralbereich bestrahlt worden war, wurde mit radioaktiv markiertem Acetyl-Co A, Acetat and Pyruvat geprüft. Von Acetyl-Co A konnte nur geringe Hemmung nachgewiesen werden, während Licht eine merkbare Hemmung von Acetat und Pyruvatinkorporation verursachte. Die Resultate lassen vermuten dass die Acetataktivierung die von Licht beeinflussbare Stufe in der Biosynthese von Sterolen ist.     

Orchestrating size and shape during morphogenesis

Living organisms exhibit tremendous diversity, evident in the large repertoire of forms and considerable size range. Scientists have discovered that conserved mechanisms control the development of all organisms. Drosophila has proved to be a particularly powerful model system with which to identify the signalling pathways that organize tissue patterns. More recently, much has been learned about the control of tissue growth, tissue shape and their coordination at the cellular and tissue levels. New models integrate how specific signals and mechanical forces shape tissues and may also control their size.     

Structural insight into filament formation by mammalian septins

Septins are GTP-binding proteins that assemble into homo- and hetero-oligomers and filaments. Although they have key roles in various cellular processes, little is known concerning the structure of septin subunits or the organization and polarity of septin complexes. Here we present the structures of the human SEPT2 G domain and the heterotrimeric human SEPT2-SEPT6-SEPT7 complex. The structures reveal a universal bipolar polymer building block, composed of an extended G domain, which forms oligomers and filaments by conserved interactions between adjacent nucleotide-binding sites and/or the amino- and carboxy-terminal extensions. Unexpectedly, X-ray crystallography and electron microscopy showed that the predicted coiled coils are not involved in or required for complex and/or filament formation. The asymmetrical heterotrimers associate head-to-head to form a hexameric unit that is nonpolarized along the filament axis but is rotationally asymmetrical. The architecture of septin filaments differs fundamentally from that of other cytoskeletal structures.     

Bending Hysteresis of Twill Woven Fabrics in Various Directions

This paper investigates the bending hysteresis of twill woven fabrics in various directions. In this research, existing models for the prediction of bending rigidity of woven fabrics are applied to bending hysteresis. Wide range of cotton twill woven fabrics is examined by comparing the theoretical data and experimental results. The results of this paper indicated that Peirce's, Shinohara et al's and Cooper's models can be applied to the prediction of bending hysteresis of twill woven fabrics. Besides, the results also show that ratio V, introduced by Cooper, of a cotton twill fabric is found to have the range between 0.8 and 1.4. The general shape of the polar diagram of bending hysteresis along the weft direction is spreading outwards with the increase in ratio V from the range 0.8 to 1. However, the general shape of bending hysteresis will collapse around the weft direction when ratio V is increased from 1 and 1.4.     

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.     

Many sequence variants affecting diversity of adult human height

Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene.     

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)

Activated RAS promotes dimerization of members of the RAF kinase family. ATP-competitive RAF inhibitors activate ERK signalling by transactivating RAF dimers. In melanomas with mutant BRAF(V600E), levels of RAS activation are low and these drugs bind to BRAF(V600E) monomers and inhibit their activity. This tumour-specific inhibition of ERK signalling results in a broad therapeutic index and RAF inhibitors have remarkable clinical activity in patients with melanomas that harbour mutant BRAF(V600E). However, resistance invariably develops. Here, we identify a new resistance mechanism. We find that a subset of cells resistant to vemurafenib (PLX4032, RG7204) express a 61-kDa variant form of BRAF(V600E), p61BRAF(V600E), which lacks exons 4-8, a region that encompasses the RAS-binding domain. p61BRAF(V600E) shows enhanced dimerization in cells with low levels of RAS activation, as compared to full-length BRAF(V600E). In cells in which p61BRAF(V600E) is expressed endogenously or ectopically, ERK signalling is resistant to the RAF inhibitor. Moreover, a mutation that abolishes the dimerization of p61BRAF(V600E) restores its sensitivity to vemurafenib. Finally, we identified BRAF(V600E) splicing variants lacking the RAS-binding domain in the tumours of six of nineteen patients with acquired resistance to vemurafenib. These data support the model that inhibition of ERK signalling by RAF inhibitors is dependent on levels of RAS-GTP too low to support RAF dimerization and identify a novel mechanism of acquired resistance in patients: expression of splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner.     

少油断路器机械特性智能测试仪研究

对少油断路器机械特性智能测试仪的硬件组成原理、智能化方法进行了深入探讨.并在软件设计中论述了模糊故障诊断原理及此技术在智能化装置中的应用.