The genome sequence of the filamentous fungus Neurospora crassa

Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes--more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism, and important differences in Ca2+ signalling as compared with plants and animals. Neurospora possesses the widest array of genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes.     

Nitric oxide mediates histamine induced down-regulation of H<Subscript>2</Subscript> receptor mRNA and internalization of the receptor protein (R1)

During agonist-dependent long-term stimulation of cells, histamine receptor subtypes are frequently down-regulated. However, the mechanisms underlying the modulation of receptor expression during long-term histamine stimulation have yet to be resolved. Based on our recently reported results showing an H₁-mediated down-regulation of histamine H₂ receptor mRNA in endothelial cells, our aim was to characterize the mechanism controlling rapid and long-term histamine-mediated modulation of H₂ receptor expression in more detail. We were able to show that the histamine-induced down-regulation of H₂ receptor mRNA and cell surface expression lasting for 24 h was accompanied by augmentation of the receptor protein level in the cytoplasmatic fraction of endothelial cells for this time period. Furthermore, changes in receptor protein levels in whole-cell lysate were negligible, indicating that the rapid and prolonged modulation of cell surface H₂ receptor levels by histamine was regulated solely via internalization. The role of nitric oxide (NO) as a key mediator in histamine-stimulated cell responses was underlined by subsequent studies showing the attenuation of histamine-induced H₂ receptor mRNA down-regulation and protein trafficking following NO synthase isozyme inhibition.Received 11 March 2003; received after revision 11 June 2003; accepted 17 June 2003     

Recent advances in cerebellar granule cell migration

In the developing brain, postmitotic neurons exhibit dynamic changes in mode, direction, tempo and rate of migration as they traverse different cortical layers. Such changes in cell migration require orchestrated activities of multiple guidance cues and transmembrane signals. In this article, we first describe when, where and how cerebellar granule cells alter their migratory behavior during the entire course of their migration. We then present how internal (inherent) programs regulate the sequential changes in the migratory behavior of granule cells in vitro. Finally, we discuss the roles of external guidance cues and transmembrane signals in controlling granule cell migration.     

Sex-peptides: seminal peptides of the <Emphasis Type="Italic">Drosophila</Emphasis> male

Mating affects the reproductive behaviour of insect females: the egg-laying rate increases and courting males are rejected. These post-mating responses are induced mainly by seminal fluid. In Drosophila melanogaster, males transfer two peptides (sex-peptides, = Sps) that reduce receptivity and elicit increased egg laying in their mating partners. Similarities in the open reading frames of the genes suggest that they have arisen by gene duplication. In females, Sps bind to specific sites in the central and peripheral nervous system, and to the genital tract. The binding proteins of the nervous system and genital tract are membrane proteins, but they differ molecularly. The former protein is proposed to be a receptor located at the top of a signalling cascade leading to the two post-mating responses, whereas the latter is a carrier protein moving Sps from the genital tract into the haemolymph. Sps bind to sperm. Together with sperm they are responsible for the persistence of the two post-mating responses. But Sps are the molecular basis of the sperm effect; sperm is merely the carrier.Received 10 February 2003; received after revision 25 April 2003; accepted 1 May 2003This article is dedicated to the 85th birthday of the discover of the sex-peptide, Prof. Dr. Pei Shen Chen, Zoological Institute, University of Zürich, Switzerland. P. S. Chen has served on the Editorial Board of Experientia (now CMLS) from 1974 to 1988.     

Increase in neuronal nitric oxide synthase content of the gastroduodenal tract of diabetic rats

This study examined the changes occurring in the pattern of distribution and expression of neuronal nitric oxide synthase (nNOS)-positive nerves in the gastroduodenal tract of streptozotocin-induced diabetic rats. The ganglion cells of the myenteric plexus of the gastric antrum of normal rats contain nNOS. We also observed nNOS-positive neurons and fibres in the myenteric plexus of the duodenum of normal rats. After the onset of diabetes, the number and intensity of staining of nNOS-positive nerve profiles in the gastric antrum and duodenum did not change significantly. However, Western blotting showed a significant increase in the expression of nNOS after the onset of diabetes. In conclusion, diabetes of 4 and 32 weeks duration induced an increase in the tissue content of nNOS in the gastroduodenum of rat. The increase in the level of nNOS in the gastroduodenum of diabetic rats may explain why impaired gastric emptying is common in patients with diabetes.     

Polyamine-dependent gene expression

The polyamines spermidine and spermine along with the diamine putrescine are involved in many cellular processes, including chromatin condensation, maintenance of DNA structure, RNA processing, translation and protein activation. The polyamines influence the formation of compacted chromatin and have a well-established role in DNA aggregation. Polyamines are used in the posttranslational modification of eukaryotic initiation factor 5A, which regulates the transport and processing of specific RNA. The polyamines also participate in a novel RNA-decoding mechanism, a translational frameshift, of at least two known genes, the TY1 transposon and mammalian antizyme. Polyamines are crucial for their own regulation and are involved in feedback mechanisms affecting both polyamine synthesis and catabolism. Recently, it has become apparent that the polyamines are able to influence the action of the protein kinase casein kinase 2. Here we address several roles of polyamines in gene expression.Received 27 November 2002; received after revision 9 January 2003; accepted 31 January 2003