Imaging and imagination: understanding the endo-lysosomal system

Lysosomes are specialized compartments for the degradation of endocytosed and intracellular material and essential regulators of cellular homeostasis. The importance of lysosomes is illustrated by the rapidly growing number of human disorders related to a defect in lysosomal functioning. Here, we review current insights in the mechanisms of lysosome biogenesis and protein sorting within the endo-lysosomal system. We present increasing evidence for the existence of parallel pathways for the delivery of newly synthesized lysosomal proteins directly from the trans-Golgi network (TGN) to the endo-lysosomal system. These pathways are either dependent or independent of mannose 6-phosphate receptors and likely involve multiple exits for lysosomal proteins from the TGN. In addition, we discuss the different endosomal intermediates and subdomains that are involved in sorting of endocytosed cargo. Throughout our review, we highlight some examples in the literature showing how imaging, especially electron microscopy, has made major contributions to our understanding of the endo-lysosomal system today

Nanoscale study of cartilage surfaces using atomic force microscopy

Articulating cartilage wear plays an important role in cartilage degeneration and osteoarthritis (OA) progression. This study investigated the changes of mechanical properties and surface roughness of sheep cartilages with wear progression at a nanometre scale. Young sheep's rear legs were subjected to a series of wear tests to generate worn cartilage samples to simulate the OA progression. Atomic force microscopy (AFM) was used to determine the effective indentation modulus and to measure the surface morphology of moist cartilage surfaces. The study has found that the mean effective indentation modulus values of worn cartilages were lower than that of healthy cartilage as the control sample. A medium-to-strong correlation between the effective indentation modulus values and the OA grades has been found. The relation between surface topography and effective indentation modulus values of the cartilage surfaces with OA progression was weakly correlated. The method established in this study can be implemented to investigate the effective indentation modulus values of clinical osteoarthritic cartilages and to assist in the understanding and assessment of OA

Measuring performance in the presence of stochastic demand for hospital services: an analysis of Belgian general care hospitals

Since demand for hospital services is subject to substantial variability, the relationship between uncertain demand, excess capacity, hospital costs and performance should be investigated thoroughly. In this paper a waiting time indicator to proxy hospital standby capacity is incorporated into a multi-product translog cost function for Belgian general care hospitals. The indicator is derived from queuing theory and improves on the conventionally used (inverse of the) occupancy rate. The multi-product stochastic frontier specification allows calculation of cost elasticities and marginal cost of seven hospital departments, as well as the degree of economies of scale and scope and enables identification of differences in efficiency. Copyright Springer Science+Business Media, LLC 2007Hospital costs, Stochastic demand, Efficiency, Productivity, Stochastic frontier analysis, Econometrics, Queuing theory, Multi-product cost function, C01, C13, C21, D24, H51, l11, l12,