Anti-DDB1 monoclonal antibody Made to order

Hepatitis C virus (HCV) infection often causes long-term persistent hepatitis, which eventually leads to liver cirrhosis and hepatocellular carcinoma. HCV-encoded NS3/4A protease plays an important role in HCV immune evasion by cleaving key adapter proteins VISA and TRIF of the RIG-I-like receptors and Toll-like receptors mediated interferon (IFN) induction pathways. To further understand the roles of NS3/4A in HCV life cycle, we identified DDB1 as a cellular substrate of NS3/4A protease by biochemical purification and mass spectrometry analysis. NS3/4A interacted with DDB1 and cleaved DDB1 in HCV-infected cells. Mutagenesis indicated that NS3/4A cleaved DDB1 at the residue of C378. Overexpression of DDB1 potentiated HCV replication, whereas knockdown of DDB1 dramatically inhibited HCV replication. Furthermore, our data indicated that the cleavage of DDB1 by NS3/4A protease was required for HCV replication. Our findings suggest that DDB1 is a cellular substrate of NS3/4A required for HCV replication and provide new insight into the interaction between HCV and host cells. (C) 2012 Elsevier Inc. All rights reserved.

Genetic association studies in admixed populations are underrepresented in the genomics literature, with a key concern for researchers being the adequate control of spurious associations due to population structure. Linear mixed models (LMMs) are well suited for genome-wide association studies (GWAS) because they account for both population stratification and cryptic relatedness and achieve increased statistical power by jointly modeling all genotyped markers. Additionally, Bayesian LMMs allow for more flexible assumptions about the underlying distribution of genetic effects, and can concurrently estimate the proportion of phenotypic variance explained by genetic markers. Using three recently published Bayesian LMMs, Bayes R, BSLMM, and BOLT-LMM, we investigate an existing data set on eye (n = 625) and skin (n = 684) color from Cape Verde, an island nation off West Africa that is home to individuals with a broad range of phenotypic values for eye and skin color due to the mix of West African and European ancestry. We use simulations to demonstrate the utility of Bayesian LMMs for mapping loci and studying the genetic architecture of quantitative traits in admixed populations. The Bayesian LMMs provide evidence for two new pigmentation loci: one for eye color (AHRR) and one for skin color (DDB1).