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Two legal problems highlighted by the DeFunis litigation are: (1) the proper role of race in undergraduate admissions; and (2) the procedure of underground graduate admissions. (Author/KE)

Recent genetic studies have shown that PCSK9, one of the key genes in cholesterol metabolism, plays a critical role by controlling the level of low-density lipoprotein receptor. However, how PCSK9 mediates LDLR degradation is still unknown. By combining a shotgun proteomic method and differential analysis of natural occurring mutations of the PCSK9 gene, we found that an E3 ubiquitin ligase c-IAP1 binds and processes PCSK9 protein. One of the ‘gain-of-function’ mutations, S127R, is defective with respect to binding to c-IAP1, and thus has defective autocatalytic activity. Knockdown of c-IAP1 impairs PCSK9 processing and autocatalytic cleavage. In c-IAP1 null mouse embryonic fibroblasts (MEFs), there is a dramatic decrease in secreted mature PCSK9 protein accompanied by a significant increase in LDLR protein levels compared with matched wild-type MEF cells. c-IAP1 also acts as an E3 ligase for ubiquitination of PCSK9. Ubiquitin containing only lysine-27 mediated PCSK9 ubiquitination by c-IAP1. Given K27-linked polyubiquitination promotes lysosomal localization, the finding indicates the c-IAP1 acts on both secretion of PCSK9 and its lysosomal localization. The novel pathway described here will open new avenues for exploring novel disease treatments.

This is the River Eden RHS and geomorphology evaluation: Final report October 2001 produced by the Environment Agency North West in 2001. This report analysed the River Habitat Survey (RHS) and geomorphology data to evaluate the level of habitat quality and the geomorphological characteristics of the River Eden and sub-catchments. RHS data and geomorphological assessment data was collected within the study areas by CEH and Fluvial Environmental Services Ltd. The River Eden and its sub-catchments are being considered as a Special Area for Conservation (SAC) due to the presence of habitat types and species, which are rare or threatened within Europe. The purpose of the project is to provide an overview of the state of the catchment in terms of river habitats and geomorphological processes in order to aid the derivation of sound management for this proposed SAC.The aim of this report was to determine the state of the environment within the Eden and sub-catchments and identify the main pressures on the system in order to derive sound management options. Environment Agency Archives North West

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