What’s new in the renin-angiotensin system?

The angiotensin AT(4) receptor was originally defined as the specific, high-affinity binding site for the hexapeptide angiotensin IV (Ang IV). Subsequently, the peptide LVV-hemorphin 7 was also demonstrated to be a bioactive ligand of the AT(4) receptor. Central administration of Ang IV, its analogues or LVV-hemorphin 7 markedly enhance learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia. The AT(4) receptor has a broad distribution and is found in a range of tissues, including the adrenal gland, kidney, lung and heart. In the kidney Ang IV increases renal cortical blood flow and decreases Na(+) transport in isolated renal proximal tubules. The AT(4) receptor has recently been identified as the transmembrane enzyme, insulin-regulated membrane aminopeptidase (IRAP). IRAP is a type II integral membrane spanning protein belonging to the M1 family of aminopeptidases and is predominantly found in GLUT4 vesicles in insulin-responsive cells. Three hypotheses for the memory-potentiating effects of the AT(4) receptor/IRAP ligands, Ang IV and LVV-hemorphin 7, are proposed: (i) acting as potent inhibitors of IRAP, they may prolong the action of endogenous promnestic peptides; (ii) they may modulate glucose uptake by modulating trafficking of GLUT4; (iii) IRAP may act as a receptor, transducing the signal initiated by ligand binding to its C-terminal domain to the intracellular domain that interacts with several cytoplasmic proteins.     

Oncogenic protein tyrosine kinases

Signals through Kit receptor tyrosine kinase are essential for development of erythrocytes, melanocytes, germ cells, mast cells and interstitial cells of Cajal (ICCs). Mice and rats with a double gene dose of loss-of-function mutations of Kit show depletion of these cells. Although human homozygotes with loss-of-function mutations of Kit have not been reported, gain-of-function mutations of Kit result in development of tumors from mast cells, germ cells and ICCs in humans. The ICC tumors are called gastrointestinal stromal tumors (GISTs), and GISTs are a good target for the Kit inhibitor imatinib mesylate. The interrelationship between the type of Kit gain-of-function mutations and the therapeutic effect of imatinib mesylate has been well characterized in GISTs. Kit is interesting from both a biological and clinical view-point.     

A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac

With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences.     

Vesicles carrying nuclear material in matureCyprinus carpio erythrocytes

Zusammenfassung Chromatinhaltige feulgenpositive Bläschen wurden im Cytoplasma der Erythrocyten vonCyprinus carpio gefunden. Sie haben ihren Ursprung in den unmittelbar an der Kernmembran anliegenden Mitochondrien, die während der Chromatinaufnahme allmählich ihre Struktur verlieren.

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The authors wish to thank Mrs.Vera Mondin Weisz and Mr.C. A. Gonçalves Silva for their technical assistance and Mrs.Sibylle Heller for her editorial aid and translation. This research has been supported by the Conselho Nacional de Pesquisas (Proc. No. 10112/71) and Fundo Especial de Despesas do Instituto Butantan.     

Deoxyribonuclease immobilized on the erythrocytes

Summary Bovine pancreatic deoxyribonuclease (DNase I) was immobilized on human erythrocytes with several procedures. DNase immobilized on the erythrocytes by chromic chloride showed DNase activity in vitro. Other binding procedures inhibit the immobilized DNase activity.     

Isolation of (−)-cryptosporiopsin,a chlorinated cyclopentenone fungitoxic metabolite fromPhialophora asteris f. sp.helianthi

Summary The (–)-enantiomer of cryptosporiopsin, a chlorinated cyclopentenone fungitoxic metabolite, was isolated fromPhialophora asteris f. sp.helianthi. Next to a comparable fungitoxic activity as shown by crypstosporiopsin, the product particularly inhibits growth ofSclerotinia sclerotiorum, an important pathogen on sunflower. Two further metabolites were tentatively identified as a stereoisomer of cryptosporiopsin and its dehydrated derivative.The authors are much indebted to Dr.G. M. Strunz (Canadian Forestry Service) for valuable suggestions and the generous gift of cryptosporiopsin and to the University of Utrecht for the part-time fellowship to one of us (Y.T.) given.