Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog

Loss of the human mucolipin-1 gene underlies mucolipidosis type IV (MLIV), a lysosomal storage disease that results in severe developmental neuropathology. Unlike other lysosomal storage diseases, MLIV is not associated with a lack of lysosomal hydrolases; instead, MLIV cells display abnormal endocytosis of lipids and accumulate large vesicles, indicating that a defect in endocytosis may underlie the disease. Here we report the identification of a loss-of-function mutation in the Caenorhabditis elegans mucolipin-1 homolog, cup-5, and show that this mutation results in an enhanced rate of uptake of fluid-phase markers, decreased degradation of endocytosed protein and accumulation of large vacuoles. Overexpression of cup-5(+) causes the opposite phenotype, indicating that cup-5 activity controls aspects of endocytosis. Studies in model organisms such as C. elegans have helped illuminate fundamental mechanisms involved in normal cellular function and human disease; thus the C. elegans cup-5 mutant may be a useful model for studying conserved aspects of mucolipin-1 structure and function and for assessing the effects of potential therapeutic compounds.     

The Systemic Approach of SSM: The Case of a Brazilian Company

This paper aims to describe the application of Soft Systems Methodology (SSM) to the reality of a Brazilian enterprise. Systemic practices are ways of putting to use systemic thought in the real world, using the precepts of the systemic approach, which is very important for knowledge management and globalization. The systemic practice SSM is used in the resolution of ill-defined problems, which often involve behavioral variables and, thus, cannot be addressed by the so-called hard methodologies. In this paper, SSM is applied to the problematic of a middle-market business, an auto supply distributor, whose managers consulted the authors of this paper as regards proposing improvements of its performance. As a result of this work, the authors were able to propose core changes in attitudes, leading to changes in structure and process.