Displacement of hepatic ornithine carbamoyltransferase from mitochondria to cytosol in Reye's syndrome.

In two patients with fatal Reye's Syndrome, total ornithine carbamoyltransferase (OCTase) activity in the liver was 50 and 75% of that found in three control livers. The levels of enzymatic activity would not be expected to have resulted in the 7- and 17-fold elevations in plasma ammonia levels found in the patients. Levels of 47 and 60% of the OCTase activity, however, were found in the cytosolic fraction compared to an average of 7% for control livers. Thus, the amount of enzymatic activity in the mitochondrial fractions was only 20 and 30% of that found in control mitochondrial fractions. This study suggests that, if only mitochondrial OCTase is active in the urea cycle, the decreases in functional enzyme found in Reye's Syndrome may be considerably greater than that reflected in total enzyme assays.     

Psychological correlates of self-reported functional limitation in patients with ankylosing spondylitis

Introduction  

Functional status is an integral component of health-related quality of life in patients with ankylosing spondylitis (AS). The purpose of this study was to investigate the role of psychological variables in self-reported functional limitation in patients with AS, while controlling for demographic and medical variables.     

The cytoplasmic tail of CD4 targets chimeric molecules to a degradative pathway.

Many different cell surface receptors undergo endocytosis via coated pits. Once having entered the cell, the receptors are sorted into diverse pathways. Which path a given receptor will follow is determined by signals inherent in the receptor's structure. The nature of these structural features is not yet known. In this study, we have taken the approach of constructing chimeric molecules to localize the domain of the T-cell surface molecule CD4 which is responsible for targeting it for degradation. Chimeric molecules bearing the cytoplasmic domain of CD4 and the extracellular domain of either the low-density lipoprotein receptor or a major histocompatibility complex (MHC) class I molecule were both internalized in response to phorbol 12-myristate 13-acetate and were subsequently degraded, indicating that the cytoplasmic tail of CD4 contains all the information required for both processes. The ability to modulate the level of MHC class I molecules on the cell surface offers an approach to investigating quantitative aspects of antigen presentation, the initial possibilities of which are explored herein.     

Optimal chemostat cascades for periplasmic protein production.

This theoretical work predicts the optimal system design for the steady-state production of secreted protein in a chemostat cascade, using bakers' yeast (Saccharomyces cerevisiae) as the host organism. The protein of interest, mutant invertase, is secreted to the periplasmic space instead of the culture medium on account of its large size. This work uses the secretion model developed and tested by Park and Ramirez (1988). It is shown that the highest productivity is achieved when the chemostat cascade contains two stages, although the improvement over the single-stage productivity is small. When no recycle is used, the advantage of two stages results from the tradeoff between maximizing the cell concentration and maximizing the rate of protein production per cell. When recycle is used, the cell concentration and protein productivity are increased, and the advantage of two stages results from the tradeoff between maximizing the specific protein production rate and maximizing the specific protein secretion rate. Cascades with three stages were also investigated, but these were found to have no improvement over the corresponding two-stage cascades.     

Mlc1p Is a Light Chain for the Unconventional Myosin Myo2p in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, the unconventional myosin Myo2p is of fundamental importance in polarized growth. We explore the role of the neck region and its associated light chains in regulating Myo2p function. Surprisingly, we find that precise deletion of the six IQ sites in the neck region results in a myosin, Myo2-Δ6IQp, that can support the growth of a yeast strain at 90% the rate of a wild-type isogenic strain. We exploit this mutant in a characterization of the light chains of Myo2p. First, we demonstrate that the localization of calmodulin to sites of polarized growth largely depends on the IQ sites in the neck of Myo2p. Second, we demonstrate that a previously uncharacterized protein, Mlc1p, is a myosin light chain of Myo2p. MLC1 (YGL106w) is an essential gene that exhibits haploinsufficiency. Reduced levels of MYO2 overcome the haploinsufficiency of MLC1. The mutant MYO2-Δ6IQ is able to suppress haploinsufficiency but not deletion of MLC1. We used a modified gel overlay assay to demonstrate a direct interaction between Mlc1p and the neck of Myo2p. Overexpression of MYO2 is toxic, causing a severe decrease in growth rate. When MYO2 is overexpressed, Myo2p is fourfold less stable than in a wild-type strain. High copies of MLC1 completely overcome the growth defects and increase the stability of Myo2p. Our results suggest that Mlc1p is responsible for stabilizing this myosin by binding to the neck region.     

Anti-actin immunoreactivity is retained in rhabdoms of Drosophila ninaC photoreceptors

Summary The Drosophila ninaC mutation produces small rhabdomeres with the axial filament of the microvillar cytoskeleton reduced or missing. Using post-embedding immunogold labelling of LR White-embedded eyes, we show that several alleles of this mutation retain positive anti-actin immunoreactivity in the rhabdomeres, comparable to that of wild-type flies.