Monoacylcadaverines as substrates for both monoamine oxidase and diamine oxidase; low rates of activity

Summary Monoacetylcadaverine and monopropionylcadaverine were found to be substrates for both rat liver monoamine oxidase and hog kidney diamine oxidase, but all the K_m-values for the oxidases were very high. The amines were common substrates for type A and type B monoamine oxidase.     

Enzyme replacement in grafted nerve of twitcher mouse

"Twitcher' is a recently recognized mouse mutant which, on the basis of morphological and enzymatic criteria, represents a murine model for globoid-cell leukodystrophy in man. In the twitcher mouse, myelin sheaths develop normally in peripheral nerves until about the fifteenth day when the rate of myelination declines, demyelination begins and Krabbe-type inclusions are seen in macrophages and Schwann cells. With age, demyelination becomes extensive, affecting fibres of all sizes. The axons are relatively spared, although they are smaller than normal. Twitcher peripheral nerves transplanted into normal hosts show, after 2 months, all the characteristics associated with globoid-cell leukodystrophy. After longer periods of time, however, pathological changes within the grafts appear considerably improved with only occasional evidence of myelin loss, little endoneurial oedema and few globoid cells. Migration of host Schwann cells into the graft can be excluded as a possible explanation. In the experiments reported here, we have attempted to determine whether the morphological improvement of grafted twitcher nerves is accompanied by an increase in activity of the enzyme galactosylceramidase. Our results show that galactosylceramidase activity in twitcher sciatic nerves grafted into normal hosts is variable after 1-2 months but indistinguishable from those in the host nerves and much higher than those in intact twitcher nerves after 4.5-9 months. In addition to migration of host Schwann cells, other tissues originating from the host can be excluded as cause of the high enzyme activity. This is the first evidence of long-term in vivo enzyme replacement, accompanied by improved pathology, in a genetic sphingolipidosis.     

Occurrence of mitochondrial monoamine oxidase in human semen

Summary Mitochondrial monoamine oxidase (MAO) was found in human semen, showing its K_m and V_max values of 91.7 M and 290 pmoles/mg of protein/60 min, respectively, with kynuramine as substrate. A major part of the activity was due to type A MAO.     

Influences of temperature change on the relaxation and amplitude inhibition by noradrenaline in the rabbit jejunum

Summary In the rabbit jejunum, the elevation of temperature within the range of 25–37°C diminished the sensitivity to noradrenaline (NA) for both the relaxation and amplitude inhibition. The relaxation by NA was mainly mediated via adrenergic -receptors at 25, 30 or 37°C. The amplitude inhibition was mediated via -receptors at 37°C, and both - and -receptors at 30 or 25°C.     

BAX activation is initiated at a novel interaction site

BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.     

Discovery of the short gamma-ray burst GRB 050709

Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, the energy scale and the progenitors of the short bursts have remained a mystery. Here we report the discovery of a short-hard burst whose accurate localization has led to follow-up observations that have identified the X-ray afterglow and (for the first time) the optical afterglow of a short-hard burst; this in turn led to the identification of the host galaxy of the burst as a late-type galaxy at z = 0.16 (ref. 10). These results show that at least some short-hard bursts occur at cosmological distances in the outskirts of galaxies, and are likely to be caused by the merging of compact binaries.     

Evolutionary origin of a calcium-dependent protease by fusion of genes for a thiol protease and a calcium-binding protein?

Calcium-dependent protease (calcium protease) is apparently involved in a variety of cellular processes. Here we have attempted to clarify the role and regulatory mechanism of calcium protease by analysing its structure. The complete primary structure of calcium protease (relative molecular mass (Mr) 80,000 (80K), 705 amino acids) was deduced from the nucleotide sequence of cloned complementary DNA. The protein contains four distinct domains, and we have observed a marked similarity between the second and fourth domains and the papain-like thiol proteases and calmodulin-like calcium-binding proteins, respectively. This finding suggests that calcium protease arose from the fusion of genes for proteins of completely different function and evolutionary origin. Further, it provides functional insight into cellular regulatory mechanisms mediated by Ca2+ through calcium-binding proteins.     

Continued in vitro and in vivo release of an antitumor drug from albumin microspheres

Heated albumin microspheres with an average diameter of 45 +/- 8 microns and containing mitomycin C, released, in vitro, about 20% of this antibiotic over a 3-day period. VX-2 tumors were implanted into the hind leg of rabbits and the drug-containing microspheres were injected into the femoral artery of these animals. High levels of the drug were maintained for several hours in the tumor and growth of the tumor was inhibited considerably, compared to findings in control rabbits given the conventional mitomycin C. Half the number of the rabbits treated with our new method are alive with no evidence of tumor.     

Up-grading of natural ilmenite ore by combining oxidation and acid leaching

Rutile (TiO₂) is heavily used in pigments and colorants, and the most abundant source of rutile is ilmenite. Upon oxidation of ilmenite, rutile can be formed with modest energy consumption; furthermore, after leaching, only a few byproducts are formed. Unfortunately, one drawback is the necessarily long oxidative process of typically used methods. In this study, we show that a fluidized bed reactor can be used to oxidize ilmenite ore to rapidly form rutile and pseudobrookite (Fe₂TiO₅) phases. Ilmenite was oxidized with 5vol% O₂ in Ar at temperatures of 1173 K or 1223 K and subsequently leached using a diluted H₂SO₄ solution to dissolve the pseudobrookite phase. The effects of acid concentration, temperature, and cooling rate after oxidation were investigated. We show that the ilmenite was rapidly oxidized to form rutile and pseudobrookite phases at 1173 and 1223 K in a 5vol% O₂/95vol% Ar environment within 40 min. The final maximum rutile yield was 84.2mol% after leaching in (1 + 1) H₂SO₄ solution at 393 K for 12 h.