Cross-linking of histone H5 in hen erythrocyte nuclei

Following treatment of hen erythrocyte nuclei with dimethyl 3,3'-dithiobispropionimidate, dimers between histones H1a, H1b, and H5 were extracted with 5% perchloric acid. They resolved electrophoretically into four sub-bands and these were identified by non-reducing/reducing gel electrophoresis. The H5-H5 homodimer species was purified by gel electrophoresis and was treated sequentially with BrCN and dithiothreitol. The pattern of resulting fragments indicates that cross-links were mainly formed between the COOH-terminal portions and at a significantly lower frequency between the COOH-terminal and the NH2-terminal portions.     

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Analyses

     

Reduction of N(ω)-hydroxy-L-arginine by the mitochondrial amidoxime reducing component (mARC)

NOSs (nitric oxide synthases) catalyse the oxidation of L-arginine to L-citrulline and nitric oxide via the intermediate NOHA (N(ω)-hydroxy-L-arginine). This intermediate is rapidly converted further, but to a small extent can also be liberated from the active site of NOSs and act as a transportable precursor of nitric oxide or potent physiological inhibitor of arginases. Thus its formation is of enormous importance for the nitric-oxide-generating system. It has also been shown that NOHA is reduced by microsomes and mitochondria to L-arginine. In the present study, we show for the first time that both human isoforms of the newly identified mARC (mitochondrial amidoxime reducing component) enhance the rate of reduction of NOHA, in the presence of NADH cytochrome b? reductase and cytochrome b?, by more than 500-fold. Consequently, these results provide the first hints that mARC might be involved in mitochondrial NOHA reduction and could be of physiological significance in affecting endogenous nitric oxide levels. Possibly, this reduction represents another regulative mechanism in the complex regulation of nitric oxide biosynthesis, considering a mitochondrial NOS has been identified. Moreover, this reduction is not restricted to NOHA since the analogous arginase inhibitor NHAM (N(ω)-hydroxy-N(δ)-methyl-L-arginine) is also reduced by this system.     

Zuchtversuche mit Heringslarven (Clupea harengus L.)

Ohne ZusammenfassungMit 4 Abbildungen im Text.Anm. Die Arbeit wurde durch eine Beihilfe der deutschen Forschungsgemeinschaft ermöglicht.     

Ein seltener bathypelagischer Fisch (Familie Melanostomiatidae) aus dem östlichen Atlantik

A fish, 218 mm standard length, member of the melanostomiatid genusPachystomias and tentatively identified asPachystomias (?)microdon (Günther 1878) is figured and thoroughly described. The relation to other members of the genus (only 5 specimens of 2 species are known up to now) is discussed. The fish was caught on “Meteor” station no. 4/66 (position 43° 10′ N. lat. and 13° 51′ W. long.) by the Isaac-Kidd-Midwater-Trawl on March 1, 1966. The towing speed was 5 n.m./h. at 3.500 m. wire out; from this the maximum fishing depth is estimated to have been 900 to 1000 meters.     

Incorporation of neutral C-terminal residues in 3-amidinophenylalanine-derived matriptase inhibitors

A novel series of matriptase inhibitors based on previously identified tribasic 3-amidinophenylalanine derivatives was prepared. The C-terminal basic group was replaced by neutral residues to reduce the hydrophilicity of the inhibitors. The most potent compound 22 inhibits matriptase with a K_i value of 0.43 nM, but lacks selectivity towards factor Xa. By combination with neutral N-terminal sulfonyl residues several potent thrombin inhibitors were identified, which had reduced matriptase affinity.     

Cloning of human and rat ABCA5/Abca5 and detection of a human splice variant

We presently report the cloning of cDNA sequences encoding the novel rat ATP-binding cassette (ABC) transporter Abca5 and the orthologous human transporter, recently designated as ABCA5. Furthermore, the existence of a novel non-translated exon of the ABCA5 gene, previously assigned to an ABCA gene cluster in the chromosomal region 17q24.2-3, is demonstrated. Abca5 and ABCA5 cDNAs are predicted to give rise to proteins of 1642 amino acids which exhibit the typical domain arrangement of ABC full transporters and share 90% identity within the amino acid sequences. A cDNA representing an ABCA5 mRNA splice variant was cloned which would result in a truncated protein equivalent to an ABC half transporter. Northern blot analyses revealed expression of ABCA5 or Abca5 mRNA in several tissues, but particularly high Abca5 mRNA expression was observed in rat testis. Up-regulation of Abca5 mRNA expression during culture of primary rat hepatocytes suggests that hepatocyte cultures should provide a basis for investigation of Abca5 gene regulation and elucidation of Abca5 function.     

Hoplostethus islandicus,nov. spec. (Acanthopterygia,Abt. Beryciformes,Familie Trachichthyidae) aus den südisländischen Gewässern

Ohne ZusammenfassungMit 2 Tabellen und 26 Abbildungen im Text     

Erstnachweis vonPolycheles typhlops (Decapoda reptantia) für isländische Gewässer

Zusammenfassung 1. Das Vorkommen vonPolycheles typhlops in den borealen isländischen Gewässern wird erstmals nachgewiesen.2. Eine typische, bei anderen Dekapoden nicht beobachtete Scherenhaltung konnte bei den im Aquarium gehaltenen Tieren festgestellt werden; sie kann mit der Lebensweise der Tiere in Verbindung gebracht werden.

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First record ofPolycheles typhlops (Decapoda reptantia) in Icelandic waters

During the ICNAF NORWESTLANT SURVEY 2, June 1963, two femalePolycheles typhlops Heller 1862, 10 and 12 cm long respectively, were caught with an otter trawl off the southwest coast of Iceland at a depht of 450 m. Up to now this species has only been known to inhabit the abyssal regions in the moderate and warm areas of the Atlantic Ocean (including the Mediterranean) and the Indian Ocean. Our specimens are the first of this species to be found in boreal waters; its distribution seems therefore to be wider than hitherto assumed. Since juvenile stages, previously described as a distinct crustacean species,Eryoneicus puritani, are occasionally found in plankton catches of the central North Atlantic, there is no doubt that this species is native to these waters and does not occure by chance in this area. A list of previous records of its occurrence, probably not complete, is given in Table 1.

     

Synthesis and biological evaluation of L-valine-amidoximeesters as double prodrugs of amidines

In general, drugs containing amidines suffer from poor oral bioavailability and are often converted into amidoxime prodrugs to overcome low uptake from the gastrointestinal tract. The esterification of amidoximes with amino acids represents a newly developed double prodrug principle creating derivatives of amidines with both improved oral availability and water solubility. N-valoxybenzamidine (1) is a model compound for this principle, which has been transferred to the antiprotozoic drug pentamidine (8). Prodrug activation depends on esterases and mARC and is thus independent from activation by P450 enzymes. Therefore, drug-drug interactions or side effects will be minimized. The synthesis of these two compounds was established, and their biotransformation was studied in vitro and in vivo. Bioactivation of N-valoxybenzamidine (1) and N,N'-bis(valoxy)pentamidine (7) via hydrolysis and reduction has been demonstrated in vitro with porcine and human subcellular enzyme preparations and the mitochondrial Amidoxime Reducing Component (mARC). Moreover, activation of N-valoxybenzamidine (1) by porcine hepatocytes was studied. In vivo, the bioavailability in rats after oral application of N-valoxybenzamidine (1) was about 88%. Similarly, N,N'-bis(valoxy)pentamidine (7) showed oral bioavailability. Analysis of tissue samples revealed high concentrations of pentamidine (8) in liver and kidney.