Penicillopepsin from Penicillium janthinellum crystal structure at 2.8 A and sequence homology with porcine pepsin.

The polypeptide chain of the acid protease penicillo pepsin folds via an 18-stranded mixed beta-sheet into two distinct lobes separated by a 30-A long groove which is the extended substrate binding site. The catalytic residues Asp-32 and Asp-215 are located in this groove and their carboxyl groups are in intimate contact. Alignment of the amino acid sequence with that of pepsin shows regions of high homology.     

The phorbol ester TPA induces metamorphosis in Red Sea coral planulae (Cnidaria: Anthozoa)

Controlled experiments on the metamorphosis of marine invertebrate larvae require artificial inducers. These inducers can be used for studying the involvement of known signal transduction pathways in settlement and metamorphosis. The ability of the tumor-promoting phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) to induce metamorphosis in planulae of the Red Sea soft coral speciesHeteroxenia fuscescens, Xenia umbellata, Dendronephthya hemprichii, Litophyton arboreum andParerythropodium fulvum fulvum, and the stony coralStylophora pistillata, was examined by using various concentrations of TPA. The chemical induced metamorphosis in all six species. The effect was unspecific and concentration-related. For all the corals except forX. umbellata the highest mean percentages of metamorphosis were obtained with 8.1×10^–7–10^–9 M TPA. ForX. umbellata, the percentage of metamorphosis was lower, and was obtained within a wider TPA concentration range. The present results, along with previous studies on Hydrozoa and Scyphozoa, demonstrate that TPA is the first common artificial inducer for these classes of Cnidaria. TPA is known to activate the enzyme protein kinase C (PKC) and therefore plays an important role in studying the phosphatidylinositol signal transduction system. Evidence for the involvement of this pathway in triggering metamorphosis has already been reported for Hydrozoa and Scyphozoa. Our results suggest that PKC is also involved in initiating metamorphosis in Anthozoa.     

Purified dihydropyridine-binding site from skeletal muscle t-tubules is a functional calcium channel

Many excitable cells contain at least two different voltage-dependent Ca channels (L- and T-type). The cardiac, slow, L-type Ca channel is further modulated by cyclic AMP-dependent phosphorylation, which increases the probability of it being open, and is readily blocked by Ca channel blockers including dihydropyridines and phenylalkylamines. The tritiated congeners of these blockers bind in vitro to sites which have the same pharmacological characteristics as those observed in vivo, that is, stereospecific and allosteric interaction between distinct sites. The dihydropyridine-binding site purified from skeletal muscle t-tubules contains three peptides of relative molecular mass (Mr) 142,000 (142K), 56K and 31K. The cAMP kinase incorporates one mol phosphate per mol of the 142K peptide and binding of (+)PN-200/110, a potent Ca antagonist, is allosterically affected by D-cis-diltiazem and verapamil. The purified dihydropyridine-receptor complex has also been incorporated into phospholipid bilayer membranes. Here, we show for the first time that the complex can be reconstituted to form a functional 20-pS Ca channel that retains the principal regulatory, biochemical and pharmacological properties of membrane-bound L-type Ca channels.     

Spektraler farbintegrator

Summary Development of a spectral colour integrator enabling to reproduce on a screen any colour up to the theoretical limits and to determine quantitatively important notions of colour metric.      

Orbital forcing of Cretaceous river discharge in tropical Africa and ocean response

The tropics have been suggested as the drivers of global ocean and atmosphere circulation and biogeochemical cycling during the extreme warmth of the Cretaceous period; but the links between orbital forcing, freshwater runoff and the biogeochemistry of continental margins in extreme greenhouse conditions are not fully understood. Here we present Cretaceous records of geochemical tracers for freshwater runoff obtained from a sediment core off the Ivory Coast that indicate that alternating periods of arid and humid African climate were driven by orbital precession. Our simulations of the precession-driven patterns of river discharge with a global climate model suggest that ocean anoxia and black shale sedimentation were directly caused by high river discharge, and occurred specifically when the northern equinox coincided with perihelion (the minimum distance between the Sun and the Earth). We conclude that, in a warm climate, the oceans off tropical continental margins respond rapidly and sensitively to even modest changes in river discharge.     

Influence of (-)3-hydroxy-N-propargyl-morphinan on the respiratory depressant action of codeine

Zusammenfassung Es wird festgestellt, dass Ro 1-7780 die atemdepressive Wirkung von Codein aufhebt. Die Dosis muss zweimal so gross wie die von Levallorphan sein. Das Dosisverhältnis zwischen Ro 1-7780 und Codein ist 1:50 bis 1:75.     

Wirkung vonδ-tubocurarinchlorid auf den O2-verbrauch der eier vonPsammechinus microtuberculatus

Summary -Tubocurarinchloride is shown to inhibit the respiration of sea-urchin eggsin vitro in concentrations up to 1.2 mg%. This effect is not inhibited by Prostigmin or Mestinon.     

Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling

B-cell antigen receptor (BCR) expression is an important feature of chronic lymphocytic leukaemia (CLL), one of the most prevalent B-cell neoplasias in Western countries. The presence of stereotyped and quasi-identical BCRs in different CLL patients suggests that recognition of specific antigens might drive CLL pathogenesis. Here we show that, in contrast to other B-cell neoplasias, CLL-derived BCRs induce antigen-independent cell-autonomous signalling, which is dependent on the heavy-chain complementarity-determining region (HCDR3) and an internal epitope of the BCR. Indeed, transferring the HCDR3 of a CLL-derived BCR provides autonomous signalling capacity to a non-autonomously active BCR, whereas mutations in the internal epitope abolish this capacity. Because BCR expression was required for the binding of secreted CLL-derived BCRs to target cells, and mutations in the internal epitope reduced this binding, our results indicate a new model for CLL pathogenesis, with cell-autonomous antigen-independent signalling as a crucial pathogenic mechanism.