Orotic acid prevents changes in cardiac sarcolemmal glycoproteins and contractility associated with muscular dystrophy in hamsters

Summary Orotic acid included in the diet of cardiomyopathic hamsters during the myolytic phase of the disease (30–60 days of age) prevented the reduction in cardiac sarcolemmal sialic acid, calcium binding, sialyltransferase activity and contractile activity associated with the cardiomyopathy.This work was supported by research grants from the MRC of Canada, the Muscular Dystrophy Association of Canada and the Nova Scotia Heart Foundation. I thank Dr Peter E. Dresel for his encouragement and Ms Jane Benjamin and Mr Steven Couban for their technical assistance.     

A new anaesthetic technique for slugs

Résumé On a étudié l'effet anesthésique de l'anhydride carbonique sur les limaces. La technique décrite permet une anesthésie totale pendant une heure avec une guérison de 100%.     

DNA sequence and analysis of human chromosome 9

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.     

Mutations in EFHC1 cause juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.     

The hormone resistin links obesity to diabetes

Diabetes mellitus is a chronic disease that leads to complications including heart disease, stroke, kidney failure, blindness and nerve damage. Type 2 diabetes, characterized by target-tissue resistance to insulin, is epidemic in industrialized societies and is strongly associated with obesity; however, the mechanism by which increased adiposity causes insulin resistance is unclear. Here we show that adipocytes secrete a unique signalling molecule, which we have named resistin (for resistance to insulin). Circulating resistin levels are decreased by the anti-diabetic drug rosiglitazone, and increased in diet-induced and genetic forms of obesity. Administration of anti-resistin antibody improves blood sugar and insulin action in mice with diet-induced obesity. Moreover, treatment of normal mice with recombinant resistin impairs glucose tolerance and insulin action. Insulin-stimulated glucose uptake by adipocytes is enhanced by neutralization of resistin and is reduced by resistin treatment. Resistin is thus a hormone that potentially links obesity to diabetes.     

Trace co-attractants in synthetic sex lures for 22 noctuid moths

Summary Trace components contributed significantly to the potency of synthetic sex attractant lures for males of many species of Noctuidae. Improved synthetic blends for 12 moths includingEuxoa ochrogaster andTrichoplusia ni, and new lure blends for 10 moths are described. In every case the trace constituents were structural analogs of the main lure components.     

The sedimentary structure of linear sand dunes

Linear sand dunes--dunes that extend parallel to each other rather than in star-like or crescentic forms--are the most abundant type of desert sand dune. But because their development and their internal structure are poorly understood, they are rarely recognized in the rock record. Models of linear dune development have not been able to take into account the sub-surface structure of existing dunes, but have relied instead either on the extrapolation of short-term measurements of winds and sediment transport or on observations of near-surface internal sedimentary structures. From such studies, it has not been clear if linear dunes can migrate laterally. Here we present images produced by ground penetrating radar showing the three-dimensional sedimentary structure of a linear dune in the Namib sand sea, where some of the world's largest linear dunes are situated. These profiles show clear evidence for lateral migration in a linear dune. Moreover, the migration of a sinuous crest-line along the dune produces divergent sets of cross-stratification, which can become stacked as the dune height increases, and large linear dunes can support superimposed dunes that produce stacked sets of trough cross-stratification. These clear structural signatures of linear dunes should facilitate their recognition in geological records.     

Heterologous expression of a bacterial haemoglobin improves the growth properties of recombinant Escherichia coli

Rational design of novel as well as improved cellular biocatalysts by genetic manipulation of cellular metabolism has recently attracted considerable interest. A wide range of bacteria have been genetically modified by integrating new enzymatic functions into their metabolic network. A central problem in the aerobic growth of any cell culture is the maintenance of dissolved oxygen (DO) concentrations above growth-limiting levels especially in high cell-density fermentations which are usually of a fed-batch type. The optimal rate of nutrient addition (and consequently the productivity) is ultimately limited by the rate at which cells can aerobically catabolize the carbon source without generating growth-inhibitory metabolites such as lactate and acetate. All approaches thus far have concentrated on improving the oxygen mass transfer rates by manipulating various environmental parameters. We have isolated the gene for a haemoglobin-like molecule, expressed by the aerobic bacterium Vitreoscilla in poorly-oxygenated environments, and expressed it in Escherichia coli. The recombinant cells contain enhanced haem as well as active haemoglobin, and they grow faster and to considerably greater cell densities than comparable plasmid-containing cells which do not express haemoglobin. This haemoglobin increases the rate of oxygen use, especially when dissolved oxygen is less than 5% of air saturation.