Soluble IL-18 receptor complex: a new star in the firmament of rheumatoid arthritis diagnosis?

It has long been recognized that laboratory tests are useful in the diagnosis of disease and to monitor treatment outcome. Their performance has become even more demanding with the development of personalized medicine. In patients with rheumatoid arthritis (RA) the standard biochemical tests measure serological markers of disease, such as C-reactive protein, and RA-associated auto-antibodies, such as rheumatoid factor and anti-citrullinated protein antibodies. The information obtained from these markers does not, however, provide a complete picture of the disease and treatment efficacy. New biomarkers based on cytokine receptor complexes are promising for RA theragnostics.     

Interdependent MHC-DRB exon-plus-intron evolution in artiodactyls

Exon 2 sequences of an expressed MHC-DRB locus from sheep were examined for polymorphisms in both the antigen-binding regions and the adjacent intronic mixed simple tandem repeat. Twenty-one novel exon 2 Ovar-DRB alleles were identified. Short nucleotide motifs are extensively shared between certain exon 2 regions of Ovar-DRB alleles. The simple repeat variations, the number of different amino acids at usually polymorphic sites, and the number of silent substitutions were reduced in the intraspecies analyses of sheep DRB sequences, compared with those of cattle and goats. It was paradoxical that the abundance of different sheep alleles was similar to that of cattle and goats. This paradox may be explained by postulating a relatively small number of "ancient" alleles, with the present-day Ovar-DRB alleles being generated by reciprocal exchange of nucleotide motifs. At the antigen-binding sites, new combinations of amino acids were maintained in Ovar-DRB alleles by strong positive selection. In sheep--and less pronounced in goats and cattle--the DRB alleles can be divided into two groups. In one group, silent substitutions are increased when compared with the other. This suggests separate evolutionary pathways for certain groups of DRB alleles within a species. The simple repetitive sequences are also discussed with respect to the evolution of DRB alleles.      

Deciphering membrane protein structures from protein sequences

ABSTRACT: Co-evolving positions within protein sequences have been used as spatial constraints to develop a computational approach for modeling membrane protein structures.     

Bilayer balance and regulation of red cell shape changes

Discocytic human red cells undergo discocyte-echinocyte and discocytestomatocyte transformations under the action of a wide variety of lipid-soluble anionic and cationic agents respectively. These shape transformations are explained by the bilayer couple hypothesis of Sheetz and Singer to be the result of preferential distribution of the anionic agents in the outer half of the bilayer and the cationic agents in the inner half of the bilayer. We demonstrate that echinocytogenic effects indeed occur when the naturally occurring phospholipid lysophosphatidylcholine (LPC) is localized in the outer half of the bilayer, and stomatocytogenic effects occur when LPC is in the inner half. However, in contrast to the bilayer couple hypothesis, our results show that simple equivalent membrane surface area expansion on each layer is insufficient to maintain the discocytic shape and there exists a differential concentration effect of LPC on the two halves of the bilayer.     

尊重斯德哥尔摩的历史中心—骑士岛的激活改造

瑞典国家财产委员会拥有骑士岛的所有权与管理权,并计划对该岛上所有的公共空间进行更新和开发,以提高其可达性与吸引力。该项目的核心是找到一种更新和修复岛屿的方法,从而在尊重历史价值的同时满足现代功能需求。对骑士岛南部的改造是岛上公共空间更新的第一部分。设计的关键条件是沿滨水区域创造可以供人步行与停坐的大面积空间,并在保持开放海港氛围的同时,对旧的道路铺装进行管理。设计者设计了一套灵活使用公共空间的综合解决方案,将开放空间与之前的码头一样,沿着水滨的形态进行布局。