To study the role of caspase‐6 during nuclear disassembly, we generated a chicken DT40 cell line in which both alleles of the caspase‐6 gene were disrupted. No obvious morphological differences were observed in the apoptotic process in caspase‐6‐ deficient cells compared with the wild type. However, examination of apoptosis in a cell‐free system revealed a block in chromatin condensation and apoptotic body formation when nuclei from HeLa cells expressing lamin A or lamin A‐transfected Jurkat cells were incubated in caspase‐6‐deficient apoptotic extracts. Transfection of exogenous caspase‐6 into the clone reversed this phenotype. Lamins A and C, which are caspase‐6‐only substrates, were cleaved by the wild‐type and heterozygous apoptotic extracts but not by the extracts lacking caspase‐6. Furthermore, the caspase‐6 inhibitor z‐VEID‐fmk mimicked the effects of caspase‐6 deficiency and prevented the cleavage of lamin A. Taken together, these observations indicate that caspase‐6 activity is essential for lamin A cleavage and that when lamin A is present it must be cleaved in order for the chromosomal DNA to undergo complete condensation during apoptotic execution.

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer¹. Cell entry of HCV² and other pathogens^3,4,5 is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver–chimeric mouse model⁶, we show that a monoclonal antibody specific for the TJ protein claudin-1 (ref. 7) eliminates chronic HCV infection without detectable toxicity. This antibody inhibits HCV entry, cell-cell transmission and virus-induced signaling events. Antibody treatment reduces the number of HCV-infected hepatocytes in vivo, highlighting the need for de novo infection by means of host entry factors to maintain chronic infection. In summary, we demonstrate that an antibody targeting a virus receptor can cure chronic viral infection and uncover TJ proteins as targets for antiviral therapy.

Biomolecular screening is now a crucial component of the drug discovery process, and this glossary will be of use to practitioners in the field of screening and to those who interact with the screening community. The glossary contains definitions related to various aspects of the screening process such as assay types, data handling, and relevant technologies. Many of the terms used in this discipline are not covered by existing glossaries, and where they are, the definitions are often not appropriate for this field. Where appropriate, this document provides new or modified definitions to better reflect the new context. The field of biomolecular screening is multidisciplinary in nature, and this glossary, containing authoritative definitions, will be useful not only for regular practitioners, but also for those who make use of data generated during the screening process.