Inhibition of cholesterol recycling impairs cellular PrPSc propagation

The infectious agent in prion diseases consists of an aberrantly folded isoform of the cellular prion protein (PrP^c), termed PrP^Sc, which accumulates in brains of affected individuals. Studies on prion-infected cultured cells indicate that cellular cholesterol homeostasis influences PrP^Sc propagation. Here, we demonstrate that the cellular PrP^Sc content decreases upon accumulation of cholesterol in late endosomes, as induced by NPC-1 knock-down or treatment with U18666A. PrP^c trafficking, lipid raft association, and membrane turnover are not significantly altered by such treatments. Cellular PrP^Sc formation is not impaired, suggesting that PrP^Sc degradation is increased by intracellular cholesterol accumulation. Interestingly, PrP^Sc propagation in U18666A-treated cells was partially restored by overexpression of rab 9, which causes redistribution of cholesterol and possibly of PrP^Sc to the trans-Golgi network. Surprisingly, rab 9 overexpression itself reduced cellular PrP^Sc content, indicating that PrP^Sc production is highly sensitive to alterations in dynamics of vesicle trafficking.     

A low level of extragalactic background light as revealed by gamma-rays from blazars

The diffuse extragalactic background light consists of the sum of the starlight emitted by galaxies through the history of the Universe, and it could also have an important contribution from the 'first stars', which may have formed before galaxy formation began. Direct measurements are difficult and not yet conclusive, owing to the large uncertainties caused by the bright foreground emission associated with zodiacal light. An alternative approach is to study the absorption features imprinted on the gamma-ray spectra of distant extragalactic objects by interactions of those photons with the background light photons. Here we report the discovery of gamma-ray emission from the blazars H 2356 - 309 and 1ES 1101 - 232, at redshifts z = 0.165 and z = 0.186, respectively. Their unexpectedly hard spectra provide an upper limit on the background light at optical/near-infrared wavelengths that appears to be very close to the lower limit given by the integrated light of resolved galaxies. The background flux at these wavelengths accordingly seems to be strongly dominated by the direct starlight from galaxies, thus excluding a large contribution from other sources-in particular from the first stars formed. This result also indicates that intergalactic space is more transparent to gamma-rays than previously thought.     

Die Reizbewegungen der Mimosoideen und ihre Hormone

Summary The irritation substances of various plants of the family of Mimosoideae are highly sensitive to oxygen, and their chemical behaviour is that of reductones. Just the same substances were also found in non-sensitive plants. Meso-inositol is perhaps one of the original compounds leading to the active substances. It became possible to explain some characteristics of the irritation-process ofMimosa pudica by regarding known properties of reductones, i.e. the irritation reaction, the restitution, the influence of sun-light and their sleeping in darkness.

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Herrn Prof.Arthur Stoll zum 70. Geburtstag gewidmet.

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Aus dem chemischen Institut der Universität Freiburg i. Br. und dem Institut für organische Chemie an der Universität Erlangen.

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Mein lieber Freund Dr.B. Banerjee hat die Fortsetzung dieser Untersuchung nicht mehr erlebt. Noch während seines Aufenthalts in Deutschland überfiel ihn die tückische Krankheit, der er kurz nach seiner Heimkehr erlag.     

Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humans

Fibrogenesis or scarring of the liver is a common consequence of all chronic liver diseases. Here we refine a quantitative trait locus that confers susceptibility to hepatic fibrosis by in silico mapping and show, using congenic mice and transgenesis with recombined artificial chromosomes, that the gene Hc (encoding complement factor C5) underlies this locus. Small molecule inhibitors of the C5a receptor had antifibrotic effects in vivo, and common haplotype-tagging polymorphisms of the human gene C5 were associated with advanced fibrosis in chronic hepatitis C virus infection. Thus, the mouse quantitative trait gene led to the identification of an unknown gene underlying human susceptibility to liver fibrosis, supporting the idea that C5 has a causal role in fibrogenesis across species.     

The t complex-encoded GTPase-activating protein Tagap1 acts as a transmission ratio distorter in mice

Transmission ratio distortion in the mouse is caused by several t-complex distorters (Tcds) acting in trans on the t-complex responder (Tcr). Tcds additively affect the flagellar movement of all spermatozoa derived from t/+ males; sperm carrying Tcr are rescued, resulting in an advantage for t sperm in fertilization. Here we show that Tagap1, a GTPase-activating protein, can act as a distorter. Tagap1 maps to the Tcd1 interval and has four t loci, which encode altered proteins including a C-terminally truncated form. Overexpression of wild-type Tagap1 in sperm cells phenocopied Tcd function, whereas a loss-of-function Tagap1 allele reduced the transmission rate of the t6 haplotype. The combined data strongly suggest that the t loci of Tagap1 produce Tcd1a. Our results unravel the molecular nature of a Tcd and demonstrate the importance of small G proteins in transmission ratio distortion in the mouse.     

Quantitative paper chromatography of lipids

Zusammenfassung Ein qualitatives Verfahren zur papierchromatographischen Trennung von Fettsäuren und Derivaten liess sich zur quantitativen Bestimmung ausbauen. Die Methode hat eine Fehlergrenze von etwa ± 5% und ist unabhängig von den funktionellen Gruppen der Moleküle. Sie ist für gesättigte Di- und Triglyceride nicht direkt anwendbar.

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This work has been supported by a research grant from the National Institutes of Health (P. H. S. 4226) and by the Hormel Foundation. Hormel Institute publication No. 143.