Systematic profiling of Caenorhabditis elegans locomotive behaviors reveals additional components in G-protein Gαq signaling

Genetic screens have been widely applied to uncover genetic mechanisms of movement disorders. However, most screens rely on human observations of qualitative differences. Here we demonstrate the application of an automatic imaging system to conduct a quantitative screen for genes regulating the locomotive behavior in Caenorhabditis elegans. Two hundred twenty-seven neuronal signaling genes with viable homozygous mutants were selected for this study. We tracked and recorded each animal for 4 min and analyzed over 4,400 animals of 239 genotypes to obtain a quantitative, 10-parameter behavioral profile for each genotype. We discovered 87 genes whose inactivation causes movement defects, including 50 genes that had never been associated with locomotive defects. Computational analysis of the high-content behavioral profiles predicted 370 genetic interactions among these genes. Network partition revealed several functional modules regulating locomotive behaviors, including sensory genes that detect environmental conditions, genes that function in multiple types of excitable cells, and genes in the signaling pathway of the G protein Gαq, a protein that is essential for animal life and behavior. We developed quantitative epistasis analysis methods to analyze the locomotive profiles and validated the prediction of the γ isoform of phospholipase C as a component in the Gαq pathway. These results provided a system-level understanding of how neuronal signaling genes coordinate locomotive behaviors. This study also demonstrated the power of quantitative approaches in genetic studies.     

European participation in major intensive care journals

To evaluate the recent evolution of the European contribution to the international literature in intensive care medicine, we reviewed the source of all original articles and case reports published from 1989 to 1993 in 5 major journals:Critical Care Medicine, Intensive Care Medicine, Chest, The American Review of Respiratory Disease andCirculatory Shock. There was an overall decline in the US contributions and a corresponding increase in the European participations toChest andthe American Review of Respiratory Disease, but not toCritical Care Medicine orCirculatory Shock. The European participation toIntensive Care Medicine remained largely predominant. The evaluation of the contributions of major European countries to these 5 journals revealed a progressive increase in the French, Italian and Spanish contributions, whilst the German contribution remained stable and the UK contributions decreased. The UK contribution, which was the first in 1989, became second in 1993, after France.     

Serum myoglobin in muscular dystrophy

Elevated levels of serum myoglobin (MGB) were found in patients with several types of myopathic disorders, namely, Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), facioscapulohumeral dystrophy, and limb-girdle dystrophy. The frequency of hypermyoglobinemia was greatest in patients with DMD and BMD (91.7% and 100%, respectively). There was no precise direct relationship between serum creatine kinase (CK) and MGB levels, although the disorders with the highest CK levels tended to be the ones with the highest MGB levels. Among the patients with DMD, hypermyoglobinemia was slightly less marked in older children with restricted ability to walk than in the younger ones. Hypermyoglobinemia was noted among 43.8% of the mothers and 41.7% of the sisters of patients with DMD, slightly greater frequencies than for abnormal CK determinations in this group. Multiple serum samples were analyzed from 10 of these women, and the overall frequency of abnormal MGB levels was the same as that of abnormal CK levels; however, levels of CK and MGB were discrepant in some individual serum samples. For this reason, serum MGB determination may be a useful adjunct in the study of possible DMD carriers.