Transport and diffusion of Tau protein in neurons

In highly polarized and elongated cells such as neurons, Tau protein must enter and move down the axon to fulfill its biological task of stabilizing axonal microtubules. Therefore, cellular systems for distributing Tau molecules are needed. This review discusses different mechanisms that have been proposed to contribute to the dispersion of Tau molecules in neurons. They include (1) directed transport along microtubules as cargo of tubulin complexes and/or motor proteins, (2) diffusion, either through the cytosolic space or along microtubules, and (3) mRNA-based mechanisms such as transport of Tau mRNA into axons and local translation. Diffusion along the microtubule lattice or through the cytosol appear to be the major mechanisms for axonal distribution of Tau protein in the short-to-intermediate range over distances of up to a millimetre. The high diffusion coefficients ensure that Tau can distribute evenly throughout the axonal volume as well as along microtubules. Motor protein-dependent transport of Tau dominates over longer distances and time scales. At low near-physiological levels, Tau is co-transported along with short microtubules from cell bodies into axons by cytoplasmic dynein and kinesin family members at rates of slow axonal transport.     

d-Ribosylated Tau forms globular aggregates with high cytotoxicity

Although the glycation of Tau that is involved in paired helical filament formation in Alzheimer’s disease has been widely studied, little attention has been paid to the role of d-ribose in the glycation of Tau. Here, we show that Tau is rapidly glycated in the presence of d-ribose, resulting in oligomerization and polymerization. Glycated derivatives appeared after 24 h incubation. Western blotting indicated the formation of advanced glycation end-products (AGEs) during initial stages of glycation. Thioflavin T-positive (ThT-positive) aggregations that appeared from day 4 indicated the globular-like features. Atomic force microscopy revealed that the surface morphology of ribosylated Tau40 was globular-like. Kinetic studies suggested that d-ribosylated Tau is slowly oligomerized and rapidly polymerized with ThT-positive features. Moreover, d-ribosylated Tau aggregates were highly toxic to SHSY5Y cells and resulted in both apoptosis and necrosis. This work has demonstrated that d-ribose reacted with Tau protein rapidly, producing ThT-positive aggregations which had high cytotoxicity. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Area and degree of occupation of the surface of precipitates of barium sulphate

Zusammenfassung Die spezifische Oberfläche von BaSO₄-Niederschlägen wurde bestimmt durch Messung des Austausches von Oberflächen-Ba-Ionen mit-radioaktiven Ba¹³¹-Ionen (spezifische Aktivität etwa 1 mc/g) einer gesättigten BaSO₄-Lösung. Die spezifische Oberfläche war 5150 cm²/g.Dann wurden die Adsorptionsisothermen von Farbstoffen (Kristallviolett, Methylenblau und Pikrinsäure) an der Oberfläche von BaSO₄-Teilchen bestimmt. Unter der Annahme, dass jedes Farbstoffmolekül im adsorbierten Zustand eine Oberfläche von 100 A² einnimmt, ergab sich ein maximaler Besetzungsgrad von 22–30%.     

Mechanism of action of boseimycin

Zusammenfassung Unmittelbar nach Zugabe von Boseimycin zuB. subtilis werden Wachstum und Proteinsynthese verhindert. DNA und RNA werden erst später beeinflusst. Die hemmende Wirkung von Boseimycin auf die behandelten Zellen ist nach Waschung mit Phosphatpuffer reversibel.     

Blocking by picrotoxin of nigra-evoked inhibition of neurons of ventromedial nucleus of the thalamus

Summary The transmitter substance released by nigro-thalamic fibres is proposed to be -aminobutyric acid, since picrotoxin blocked nigra-evoked monosynaptic inhibition of thalamic neurons.Supported by grants Nos 212009 and 311410 from Ministry of Education of Japan.The authors wish to thank Dr Marjorie Anderson, University of Washington, Seattle, for improving the English.