生物学概念的变化

面对目前迅猛发展的生物科学研究手段和研究方法，阐述了传统生物学概念的变化，现代生物学存在的不足和适应这种变化要做的工作．     

Simplification of the ecdysteroid radioimmunoassay by the use of protein A fromStaphylococcus aureus

Summary Three methods of separating antibody-bound ligand from free ligand were compared for an ecdysteroid radioimmunoassay. Ecdysteroid antibody concentration and ligand specific radioactivity were adjusted to measure 2 ranges of ecdysone concentrations (0.01–2.0 ng and 0.25–32.0 ng). In comparison with the tradiotional separating agent, ammonium sulfate, neither protein A nor polyethylene glycol altered sensitivity or specificity of the radioimmunoassays. The protein A immunoglobulin precipitation method is quick and simple, making it a preferred alternative protocol for terminating ecdysteroid radioimmunoassays.Supported by grants AM-30118 from the National Institutes of Health and PCM-8116931 from the National Science Foundation.     

Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex

Mutations in LMAN1 (also called ERGIC-53) result in combined deficiency of factor V and factor VIII (F5F8D), an autosomal recessive bleeding disorder characterized by coordinate reduction of both clotting proteins. LMAN1 is a mannose-binding type 1 transmembrane protein localized to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC; refs. 2,3), suggesting that F5F8D could result from a defect in secretion of factor V and factor VIII (ref. 4). Correctly folded proteins destined for secretion are packaged in the ER into COPII-coated vesicles, which subsequently fuse to form the ERGIC. Secretion of certain abundant proteins suggests a default pathway requiring no export signals (bulk flow; refs. 6,7). An alternative mechanism involves selective packaging of secreted proteins with the help of specific cargo receptors. The latter model would be consistent with mutations in LMAN1 causing a selective block to export of factor V and factor VIII. But approximately 30% of individuals with F5F8D have normal levels of LMAN1, suggesting that mutations in another gene may also be associated with F5F8D. Here we show that inactivating mutations in MCFD2 cause F5F8D with a phenotype indistinguishable from that caused by mutations in LMAN1. MCFD2 is localized to the ERGIC through a direct, calcium-dependent interaction with LMAN1. These findings suggest that the MCFD2-LMAN1 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins.