Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes

The ezrin-radixin-moesin (ERM) family of proteins crosslink actin filaments and integral membrane proteins. Radixin (encoded by Rdx) is the dominant ERM protein in the liver of wildtype mice and is concentrated at bile canalicular membranes (BCMs). Here we show that Rdx(-/-) mice are normal at birth, but their serum concentrations of conjugated bilirubin begin to increase gradually around 4 weeks, and they show mild liver injury after 8 weeks. This phenotype is similar to human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury. In wildtype mice, Mrp2 concentrates at BCMs to secrete conjugated bilirubin into bile. In the BCMs of Rdx(-/-) mice, Mrp2 is decreased compared with other BCM proteins such as dipeptidyl peptidase IV (CD26) and P-glycoproteins. In vitro binding studies show that radixin associates directly with the carboxy-terminal cytoplasmic domain of human MRP2. These findings indicate that radixin is required for secretion of conjugated bilirubin through its support of Mrp2 localization at BCMs.     

太阳耀斑和相关电离层吸收事件

利用23周太阳峰期期间南极中山站(不变磁纬74.5°S)成像式宇宙噪声接收机的观测结果, 对由太阳质子和X射线耀斑引起的日侧电离层吸收事件进行了分析, 定量地给出电离层吸收和X射线耀斑强度的对应关系, 同时还利用北极Ny-Alesund(不变磁纬76.08癗)站的观测数据对此关系进行对比研究, 得出了在理论和观测上都较为一致的结论. 同时, 认为M级以上的X射线耀斑才能引起日侧电离层较为明显的吸收.     

Aragusterol C: A novel halogenated marine steroid from an Okinawan sponge,Xestospongia sp., possessing potent antitumor activity

A novel chlorinated steroid, aragusterol C, was isolated from an Okinawan marine sponge of the genusXestospongia. The compound strongly inhibited the proliferation of KB cells in vitro, and also showed potent in vivo antitumor activity against L1210 cells in mice. The complete structure of aragusterol C was determined by spectroscopic analysis and X-ray crystallographic analysis.     

Materials chemistry: a synthetic enamel for rapid tooth repair

The conventional treatment of dental caries involves mechanical removal of the affected part and filling of the hole with a resin or metal alloy. But this method is not ideal for tiny early lesions because a disproportionate amount of healthy tooth must be removed to make the alloy or resin stick. Here we describe a dental paste of synthetic enamel that rapidly and seamlessly repairs early caries lesions by nanocrystalline growth, with minimal wastage of the natural enamel.     

Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage

Diabetic hyperglycaemia causes a variety of pathological changes in small vessels, arteries and peripheral nerves. Vascular endothelial cells are an important target of hyperglycaemic damage, but the mechanisms underlying this damage are not fully understood. Three seemingly independent biochemical pathways are involved in the pathogenesis: glucose-induced activation of protein kinase C isoforms; increased formation of glucose-derived advanced glycation end-products; and increased glucose flux through the aldose reductase pathway. The relevance of each of these pathways is supported by animal studies in which pathway-specific inhibitors prevent various hyperglycaemia-induced abnormalities. Hyperglycaemia increases the production of reactive oxygen species inside cultured bovine aortic endothelial cells. Here we show that this increase in reactive oxygen species is prevented by an inhibitor of electron transport chain complex II, by an uncoupler of oxidative phosphorylation, by uncoupling protein-1 and by manganese superoxide dismutase. Normalizing levels of mitochondrial reactive oxygen species with each of these agents prevents glucose-induced activation of protein kinase C, formation of advanced glycation end-products, sorbitol accumulation and NFkappaB activation.