Receptor-associated protein facilitates proper folding and maturation of the low-density lipoprotein receptor and its class 2 mutants

Familial hypercholesterolemia is the consequence of various mutations in the low-density lipoprotein receptor (LDLR). In the current study, we show that a specialized molecular chaperone, the receptor-associated protein (RAP), promotes proper folding and subsequent exocytic trafficking of the wild-type LDLR and several of its class 2 mutants. Co-immunoprecipitation with anti-RAP antibody demonstrates that RAP interacts with the LDLR. Kinetic analyses of LDLR posttranslational folding and maturation in the absence or presence of RAP coexpression show that RAP prevents aggregation and promotes the maturation of the LDLR. Additionally, depletion of Ca(2+) in intact cells impairs LDLR folding, and coexpression of RAP partially corrects this misfolding. Finally, we show that the increased mature cell surface LDLR in the presence of RAP coexpression is functional in its ability to endocytose and degrade (125)I-LDL. Taken together, our results show that the folding, trafficking, and maturation of the LDLR and its class 2 mutants are promoted by RAP.     

Assessment of Sensitivities to Anilinopyrimidine- and Strobilurin-fungicides in Populations of the Apple Scab Fungus Venturia inaequalis

The sensitivity of Venturia inaequalis populations to the anilinopyrimidine fungicides pyrimethanil and cyprodinil was analysed by microscopic in vivo analysis of conidiophore formation. The sensitivity to the strobilurin kresoxim-methyl was analysed using an in vitro germination assay and by determination of the diseased leaf area and conidia produced in vivo. Baseline sensitivities were determined with V. inaequalis populations from control orchards that had never been treated with fungicides. Comparison of the baseline sensitivities with sensitivities of populations obtained from orchards that had received 43 anilinopyrimidine treatments over 4 years, or from an orchard with 54 kresoxim-methyl treatments over 6 years indicated that no resistance to these fungicides has developed at the sites sampled.     

Regional vascular influences on tail-cuff measurements of drug-induced changes in systolic pressure.

When drug effects are quantified using the tail-cuff method, changes in systemic arterial pressure are extrapolated from those occurring in the caudal artery. The validity of this extrapolation was tested in anesthetized rats by recording drug-induced changes in phasic arterial pressure simultaneously from catheters inserted into the lower abdominal aorta, carotid, and caudal arteries. Pressor responses to norepinephrine or angiotensin were of equal magnitude at all three sites, but phentolamine reduced systolic pressure in the aorta or caudal artery more than that in the carotid artery. Unlike previous discrepancies between carotid and tail-cuff systolic pressures, aortic hypotension caused by injections of phentolamine or pentolinium in awake normotensive or spontaneously hypertensive rats was accurately predicted by the tail-cuff method. Because drug-induced changes in diastolic pressure always varied much less than those in systolic pressure, should indirect measurement of diastolic pressure become technically feasible, it might be preferable for assessing drug effects on blood pressure.     

SIMPLE: a simplifying-ensembling framework for parallel community detection from large networks

Community detection is a classic and very difficult task in complex network analysis. As the increasingly explosion of social media, scaling community detection methods to large networks has attracted considerable recent interests. In this paper, we propose a novel SIMPLifying and Ensembling (SIMPLE) framework for parallel community detection. It employs the random link sampling to simplify the network and obtain basic partitionings on every sampled graphs. Then, the K-means-based Consensus Clustering is used to ensemble a number of basic partitionings to get high-quality community structures. All of phases in SIMPLE, including random sampling, sampled graph partitioning, and consensus clustering, are encapsulated into MapReduce for parallel execution. Experiments on six real-world social networks analyze key parameters and factors inside SIMPLE, and demonstrate both effectiveness and efficiency of the SIMPLE.