Hemmungswirkung verschiedener Chinone auf die Eiweißspaltung durch Papain

Summary With the intention to clarify the mechanism of action of the antibiotic effect of some quinones the inhibition of the activity of papain by various quinones was measured. The results let it appear improbable that there is any relation between the antibacterial effect of the quinones and their inhibition power on papain. On the other hand a close parallelism was found in the strength of inhibition of the same quinones on papain, urease and catalase. The mechanism of action of the quinone inhibition of these three enzymes must be regarded as a very similar one.

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Ausführliche Veröffentlichung mit weiteren Belegen folgt in den Monatsheften für Chemie (Wien).     

Antibiotika als pflanzliche Plasmagifte

Summary The toxic action oflycomarasmine (a wilting agent produced byFusarium lycopersici Sacc., the causal organism of tomato-wilting) and ofpatulin (clavacin, an antibiotic produced byPenicillium patulum and by some other fungi) on some test-objects is studied (anthocyanin-test with red turnips, plasma-streaming test withSpirogyra etc.). Both substances are able to destroy for instance the semipermeability of the plasma boundary layer; but patulin proves to be more toxic for these objects than lycomarasmine, the specific poison of the tomato wilting disease.     

Hemmungswirkungen verschiedener Indophenole auf die Wasserstoff-peroxydzersetzung durch Blutkatalase

Summary Some indophenol derivatives inhibit strongly the activity of blood catalase. These effects were investigated quantitatively and compared with similar effects due to other oxidizing and reducing agents.     

Interference among deleterious mutations favours sex and recombination in finite populations

Sex and recombination are widespread, but explaining these phenomena has been one of the most difficult problems in evolutionary biology. Recombination is advantageous when different individuals in a population carry different advantageous alleles. By bringing together advantageous alleles onto the same chromosome, recombination speeds up the process of adaptation and opposes the fixation of harmful mutations by means of Muller's ratchet. Nevertheless, adaptive substitutions favour sex and recombination only if the rate of adaptive mutation is high, and Muller's ratchet operates only in small or asexual populations. Here, by tracking the fate of modifier alleles that alter the frequency of sex and recombination, we show that background selection against deleterious mutant alleles provides a stochastic advantage to sex and recombination that increases with population size. The advantage arises because, with low levels of recombination, selection at other loci severely reduces the effective population size and genetic variance in fitness at a focal locus (the Hill-Robertson effect), making a population less able to respond to selection and to rid itself of deleterious mutations. Sex and recombination reveal the hidden genetic variance in fitness by combining chromosomes of intermediate fitness to create chromosomes that are relatively free of (or are loaded with) deleterious mutations. This increase in genetic variance within finite populations improves the response to selection and generates a substantial advantage to sex and recombination that is fairly insensitive to the form of epistatic interactions between deleterious alleles. The mechanism supported by our results offers a robust and broadly applicable explanation for the evolutionary advantage of recombination and can explain the spread of costly sex.     

The content of noradrenaline and adrenaline in the rat heart after administration of rauwolfia alkaloids

Zusammenfassung Die chemisch verwandten Rauwolfia-Alkaloide Raunescin, Isoraunescin, Deserpidin, Rescinnamin und Reserpin verursachen einen starken Abfall des Noradrenalingehaltes des Rattenherzens, wenn sie intraperitoneal in einer Dosis von 5 mg/kg gegeben werden. Der Adrenalingehalt wird nicht deutlich oder einheitlich ver?ndert. α-Yohimbin, das chemisch zu einer andern Gruppe geh?rt, hat keine Wirkung auf den Noradrenalingehalt des Herzens.

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This work was supported by a grant from the U. S. Public Health Service (H-2205) and by funds from the Eugene Higgins Trust.     

Abnormal TNF activity in Timp3-/- mice leads to chronic hepatic inflammation and failure of liver regeneration

Tumor-necrosis factor (TNF), a pleiotropic cytokine, triggers physiological and pathological responses in several organs. Here we show that deletion of the mouse gene Timp3 resulted in an increase in TNF-alpha converting enzyme activity, constitutive release of TNF and activation of TNF signaling in the liver. The increase in TNF in Timp3(-/-) mice culminated in hepatic lymphocyte infiltration and necrosis, features that are also seen in chronic active hepatitis in humans. This pathology was prevented when deletion of Timp3 was combined with Tnfrsf1a deficiency. In a liver regeneration model that requires TNF signaling, Timp3(-/-) mice succumbed to liver failure. Hepatocytes from Timp3(-/-) mice completed the cell cycle but then underwent cell death owing to sustained activation of TNF. This hepatocyte cell death was completely rescued by a neutralizing antibody to TNF. Dysregulation of TNF occurred specifically in Timp3(-/-), and not Timp1(-/-) mice. These data indicate that TIMP3 is a crucial innate negative regulator of TNF in both tissue homeostasis and tissue response to injury.     

Mutations in a novel gene,NPHP3, cause adolescent nephronophthisis,tapeto-retinal degeneration and hepatic fibrosis

Nephronophthisis (NPHP), a group of autosomal recessive cystic kidney disorders, is the most common genetic cause of progressive renal failure in children and young adults. NPHP may be associated with Leber congenital amaurosis, tapeto-retinal degeneration, cerebellar ataxia, cone-shaped epiphyses, congenital oculomotor apraxia and hepatic fibrosis. Loci associated with an infantile type of NPHP on 9q22-q31 (NPHP2), juvenile types of NPHP on chromosomes 2q12-q13 (NPHP1) and 1p36 (NPHP4) and an adolescent type of NPHP on 3q21-q22 (NPHP3) have been mapped. NPHP1 and NPHP4 have been identified, and interaction of the respective encoded proteins nephrocystin and nephrocystin-4 has been shown. Here we report the identification of NPHP3, encoding a novel 1,330-amino acid protein that interacts with nephrocystin. We describe mutations in NPHP3 in families with isolated NPHP and in families with NPHP with associated hepatic fibrosis or tapeto-retinal degeneration. We show that the mouse ortholog Nphp3 is expressed in the node, kidney tubules, retina, respiratory epithelium, liver, biliary tract and neural tissues. In addition, we show that a homozygous missense mutation in Nphp3 is probably responsible for the polycystic kidney disease (pcy) mouse phenotype. Interventional studies in the pcy mouse have shown beneficial effects by modification of protein intake and administration of methylprednisolone, suggesting therapeutic strategies for treating individuals with NPHP3.     

Evolution of the polarization of the optical afterglow of the gamma-ray burst GRB030329

The association of a supernova with GRB030329 strongly supports the 'collapsar' model of gamma-ray bursts, where a relativistic jet forms after the progenitor star collapses. Such jets cannot be spatially resolved because gamma-ray bursts lie at cosmological distances; their existence is instead inferred from 'breaks' in the light curves of the afterglows, and from the theoretical desire to reduce the estimated total energy of the burst by proposing that most of it comes out in narrow beams. Temporal evolution of the polarization of the afterglows may provide independent evidence for the jet structure of the relativistic outflow. Small-level polarization ( approximately 1-3 per cent) has been reported for a few bursts, but its temporal evolution has yet to be established. Here we report polarimetric observations of the afterglow of GRB030329. We establish the polarization light curve, detect sustained polarization at the per cent level, and find significant variability. The data imply that the afterglow magnetic field has a small coherence length and is mostly random, probably generated by turbulence, in contrast with the picture arising from the high polarization detected in the prompt gamma-rays from GRB021206 (ref. 18).