Activated protein C binds directly to Tie2: possible beneficial effects on endothelial barrier function

Activated protein C (APC) is a natural anticoagulant with strong anti-inflammatory, anti-apoptotic, and barrier stabilizing properties. These cytoprotective properties of APC are thought to be exerted through its pathway involving the binding of APC to endothelial protein C receptor and cleavage of protease-activated receptors. In this study, we found that APC enhanced endothelial barrier integrity via a novel pathway, by binding directly to and activating Tie2, a transmembrane endothelial tyrosine kinase receptor. Binding assays demonstrated that APC competed with the only known ligands of Tie2, the angiopoietins (Angs). APC bound directly to Tie2 (Kd ~3 nM), with markedly stronger binding affinity than Ang2. After binding, APC rapidly activated Tie2 to enhance endothelial barrier function as shown by Evan’s blue dye transfer across confluent cell monolayers and in vivo studies. Blocking Tie2 restricted endothelial barrier integrity. This study highlights a novel mechanism by which APC binds directly to Tie2 to enhance endothelial barrier integrity, which helps to explain APC’s protective effects in vascular leakage-related pathologies.     

Late Pleistocene-early Holocene history of coniferous woodlands in the Lucerne Valley region, Mohave Desert, California

The composition of four radiocarbon-dated, late Pleistocene woodrat middens is reported and analyzed. A date of 11,850 ±550 BP records the first reported macrofossil occurrence in this region of late Pleistocene Pinus monophylla-Juniperus osteosperma woodlands. A 7,800 ±350 BP date documents the most recent J. osteosperma woodlands in this presently coniferless desert area, while a date of 12,100 ±400 BP is the oldest record of juniper woodlands among the four middens. Other juniper and creosote bush desert flora radiocarbon dates along with six pollen profiles were obtained. The research suggests that as recently as 7,800 BP this part of the Mohave Desert was subject to a cooler, moister climate than at present, and that the aboriginal food resources of pinyon seeds and juniper berries were probably available to early prehistoric man in this area.     

低温氧化作用对中国黄土记录剩磁的影响

系统地研究了黄土/古土壤样品在加热中磁性矿物及其粒径的变化. 实验结果表明, 在100~200℃之间, 因样品中有机质燃烧而产生的还原环境可以提高样品所含磁铁矿的纯度, 并影响样品的岩石磁学性质, 主要表现在: (1) 样品的矫顽力(Hc)和剩磁矫顽力(Hcr)显著减小; (2) 多畴(MD)磁性矿物的含量增多, 而超顺磁(SP)磁性矿物的含量降低; (3) 天然剩磁热退磁有异常显示; (4) 上述变化随成土作用增强而减弱. 进一步的研究表明, 这一还原过程可有效地消除黄土中MD磁铁矿由天然低温氧化作用(LTO)而携带的次生化学剩磁.     

The finished DNA sequence of human chromosome 12

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.     

Global distribution and conservation of rare and threatened vertebrates

Global conservation strategies commonly assume that different taxonomic groups show congruent geographical patterns of diversity, and that the distribution of extinction-prone species in one group can therefore act as a surrogate for vulnerable species in other groups when conservation decisions are being made. The validity of these assumptions remains unclear, however, because previous tests have been limited in both geographical and taxonomic extent. Here we use a database on the global distribution of 19,349 living bird, mammal and amphibian species to show that, although the distribution of overall species richness is very similar among these groups, congruence in the distribution of rare and threatened species is markedly lower. Congruence is especially low among the very rarest species. Cross-taxon congruence is also highly scale dependent, being particularly low at the finer spatial resolutions relevant to real protected areas. 'Hotspots' of rarity and threat are therefore largely non-overlapping across groups, as are areas chosen to maximize species complementarity. Overall, our results indicate that 'silver-bullet' conservation strategies alone will not deliver efficient conservation solutions. Instead, priority areas for biodiversity conservation must be based on high-resolution data from multiple taxa.     

The effect of endotoxin on membrane fatty acid composition in BCG-sensitized mice

The effects of endotoxin on mouse liver phospholipid fatty acid composition have been investigated. Administration of endotoxin from Salmonella abortus equi led to a decrease in the polyunsaturated fatty acid content of livers from mice sensitized with Bacille Calmette Guérin (BCG). The content of arachidonic acid fell significantly in both the phosphatidylcholine and phosphatidylinositol fractions whereas in the phosphatidylethanolamine fraction the linoleic acid content was significantly reduced. The polyunsaturated fatty acids were replaced by increased amounts of oleic acid and palmitic acid, leading to a reduction in the polyunsaturated to saturated fatty acid ratio.