Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis

The effect of high-density lipoprotein (HDL) in protecting against atherosclerosis is usually attributed to its role in 'reverse cholesterol transport'. In this process, HDL particles mediate the efflux and the transport of cholesterol from peripheral cells to the liver for further metabolism and bile excretion. Thus, cell-surface receptors for HDL on hepatocytes are chief partners in the regulation of cholesterol homeostasis. A high-affinity HDL receptor for apolipoprotein A-I (apoA-I) was previously identified on the surface of hepatocytes. Here we show that this receptor is identical to the beta-chain of ATP synthase, a principal protein complex of the mitochondrial inner membrane. Different experimental approaches confirm this ectopic localization of components of the ATP synthase complex and the presence of ATP hydrolase activity at the hepatocyte cell surface. Receptor stimulation by apoA-I triggers the endocytosis of holo-HDL particles (protein plus lipid) by a mechanism that depends strictly on the generation of ADP. We confirm this effect on endocytosis in perfused rat liver ex vivo by using a specific inhibitor of ATP synthase. Thus, membrane-bound ATP synthase has a previously unsuspected role in modulating the concentrations of extracellular ADP and is regulated by a principal plasma apolipoprotein.     

Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6

Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous disease involving abnormalities of melanosomes, platelet dense granules and lysosomes. Here we have used positional candidate and transgenic rescue approaches to identify the genes mutated in ruby-eye 2 and ruby-eye mice (ru2 and ru, respectively), two 'mimic' mouse models of HPS. We also show that these genes are orthologs of the genes mutated in individuals with HPS types 5 and 6, respectively, and that their protein products directly interact. Both genes are previously unknown and are found only in higher eukaryotes, and together represent a new class of genes that have evolved in higher organisms to govern the synthesis of highly specialized lysosome-related organelles.     

Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells

Several proteins implicated in the pathogenesis of polycystic kidney disease (PKD) localize to cilia. Furthermore, cilia are malformed in mice with PKD with mutations in TgN737Rpw (encoding polaris). It is not known, however, whether ciliary dysfunction occurs or is relevant to cyst formation in PKD. Here, we show that polycystin-1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by Pkd1 and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD, co-distribute in the primary cilia of kidney epithelium. Cells isolated from transgenic mice that lack functional PC1 formed cilia but did not increase Ca(2+) influx in response to physiological fluid flow. Blocking antibodies directed against PC2 similarly abolished the flow response in wild-type cells as did inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins, phospholipase C and InsP(3) receptors had no effect. These data suggest that PC1 and PC2 contribute to fluid-flow sensation by the primary cilium in renal epithelium and that they both function in the same mechanotransduction pathway. Loss or dysfunction of PC1 or PC2 may therefore lead to PKD owing to the inability of cells to sense mechanical cues that normally regulate tissue morphogenesis.     

A multiple intelligent agent system for credit risk prediction via an optimization of localized generalization error with diversity

Company bankruptcies cost billions of dollars in losses to banks each year. Thus credit risk prediction is a critical part of a bank＇s loan approval decision process. Traditional financial models for credit risk prediction are no longer adequate for describing today＇s complex relationship between the financial health and potential bankruptcy of a company. In this work, a multiple classifier system （embedded in a multiple intelligent agent system） is proposed to predict the financial health of a company. In our model, each individual agent （classifier） makes a prediction on the likelihood of credit risk based on only partial information of the company. Each of the agents is an expert, but has limited knowledge （represented by features） about the company. The decisions of all agents are combined together to form a final credit risk prediction. Experiments show that our model out-performs other existing methods using the benchmarking Compustat American Corporations dataset.     

Spatial differences in rock uplift rates inferred from channel steepness indices along the northern flank of the Qilian Mountain, northeast Tibetan Plateau

The rate and distribution of deformation along the Qilian Mountain, on the northeastern Tibetan Plateau, is needed to understand the evolution of high topography associated with the plateau. Recently, a number of empirical studies have provided support for the contention, common to most models of fluvial incision, that rock uplift rate exerts a first-order control on the gradient of longitudinal river profiles. Along the northern Qilian Mountain, this method is used to extract information about the spatial patterns of differential rock uplift. Analysis of the longitudinal profiles of bedrock channels reveals systematic differences in the channel steepness index along the trend of the frontal ranges. Local comparisons of channel steepness reveal that lithology and precipitation have limited influence on channel steepness. Similarly, there is little evidence suggesting that channel steepness is influenced by differences in the sediment loads. We argue that the distribution of channel steepness in the Qilian Mountain is mostly the result of differential rates of rock uplift. Thus, channel steepness indices reveal a lower rock uplift rate in the eastern portion of the Qilian Mountain and a higher rate in the middle and west. The highest rates appear to occur in the middle-west portions of the range, just to the west of the Yumu Shan.     

Soft sediment benthic macroinvertebrate communities of the Green River at the Ouray National Wildlife Refuge, Uintah County, Utah

Benthic macroinvertebrates from four habitat types (river channel, ephemeral side channel, river backwater, and seasonally inundated wetland) were examined from the Green River at the Ouray National Wildlife Refuge, Uintah County, UT, June-August 1991. For major taxa (Nematoda, Oligochaeta, Diptera: Ceratopogonidea, and Chironomidae) were quantified. Chuster analysis of densities showed that habitat types with comparable flow conditions were the most similar. Highest to lowest overall benthic invertebrate densities of the four habitats were as follows: ephemeral side channel, river backwater, seasonally inundated wetland, and river channel. Nematodes were the most abundant taxon in all habitat types and sample dates except the August sample of the river channel and river backwater and the July sample of the seasonally inundated wetland.     

Electrophoretic study of cutthroat trout populations in Utah

Thirty - nine Utah streams were sampled for cutthroat trout. Of these, 31 contain cutthroat or cutthroat / rainbow hybrid populations. By using starch gel electrophoresis, these populations were segregated into three groups. One group consisted predominately of fish from the Sevier River (of the Bonneville Basin) and Colorado drainages. A second was primarily populations from the Bear River Drainage (Bonneville Basin) as well as some scattered populations along the Wasatch Front (Bonneville Basin). The third consisted of Wasatch Front populations and populations that have hybridized with rainbow trout. Since different subspecies of cutthroat trout are native to the Colorado and Bonneville drainages, one would expect the populations from within the Bonneville Basin to be more similar to one another and less similar to the Colorado River populations. That this did not occur raises questions concerning the evolutionary relationships of the subspecies and the populations. It is clear that at least a northern (Bear River) and southern (Sevier River) form of the Bonneville cutthroat exists. The Wasatch Front may represent an intermediate zone where these two forms intergrade.