Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions.

Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated PrP27 - 30 detectable by the 3F4 antibody against human PrP109 - 112. We recently identified a new PK-resistant PrP species, designated PrP*20, in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97 - 108 but not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP*20 molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic mutant PrP accumulate not only PrP*20 but also a small amount of 3F4-detected PK-resistant PrP27 - 30. Remarkably, during the course of human prion disease, a transition from an increase in 1E4-detected PrP*20 to the occurrence of the 3F4-detected PrP27 - 30 was observed. Our study suggests that an increase in the level of PrP*20 characterizes the early stages of prion diseases.

Prion: the chameleon protein.

From Creutzfeldt-Jakob disease (CJD) to variant CJD through Gerstmann-Sträussler-Scheinker syndrome, kuru and fatal familial insomnia, the journey leading to current understanding of the basic aspects of human prion diseases has been full of unexpected, but often dramatic and always fascinating twists. Recent progress in modeling prion diseases and characterization of the various prion protein forms reveal that such a wide spectrum of the diseases is associated with the chameleon-like conformational features of prions.

Large low-field magnetoresistance in nanocrystalline magnetite prepared by sol-gel method.

Nanocrystalline magnetite Fe3O4 samples with a grain size of about 40 nm have been synthesized by an optimized sol-gel method. The single phase of spinel magnetite was confirmed by both X-ray diffraction and transmission electron microscopy. It has been found that the magnetoresistance of the samples at low field (LFMR) is relatively large, and with the decrease of temperature its value at a field of 0.5 T changes dramatically from -2.5% at 300 K to -17.0% at 55 K. With the further decrease of temperature a sharp drop occurs for the magnitude of the magnetoresistance (MR), regarded as a spin (cluster) glass transition in the surface region of the grains that can be confirmed by the zero-field-cooled and field-cooled magnetization and ac susceptibility measurement. The mechanism of the magnetic and transport properties was discussed.

All or none fibrillogenesis of a prion peptide.

Amyloid proteins and peptides comprise a diverse group of molecules that vary both in size and amino-acid sequence, yet assemble into amyloid fibrils that have a common core structure. Kinetic studies of amyloid fibrillogenesis have revealed that certain amyloid proteins form oligomeric intermediates prior to fibril formation. We have investigated fibril formation with a peptide corresponding to residues 195-213 of the human prion protein. Through a combination of kinetic and equilibrium studies, we have found that the fibrillogenesis of this peptide proceeds as an all-or-none reaction where oligomeric intermediates are not stably populated. This variation in whether oligomeric intermediates are stably populated during fibril formation indicates that amyloid proteins assemble into a common fibrillar structure; however, they do so through different pathways.

[Stress and dietary salt intake in the pathogenesis of hypertension: role of the renal and sympathetic nervous system].

Using the methods of electrophysiology, biochemistry, radioimmunoassay, and electron microscopy, changes of sympathetic nervous system and renal function in hypertensive SD rats induced by stress and high-salt intake were investigated. The results are as follows: (1) Renal plasma flow (RPF) and urinary sodium excretion obviously increased in salt-loading rats. Stress could result in marked reduction of RPF. (2) Electron micrography showed a dramatic increase in cell and mitochondrial volume in the proximal and distal convoluted tubules of high-salt diet rats. After stress of two weeks, the cells of the tubule became atrophic and mitochondrial volume decreased. (3) The same recovery from the declining renal cortical Na-K-ATPase activity in high-salt diet rats could be observed by maintained stress. (4) Low frequency (0.2-0.9 Hz) of BP variability was higher in stress rats as compared to control. (5) Both plasma renin activity (PRA) and angiotensin II (ANG II) levels increased in stress rats, but the decrease in high-salt diet rats gradually reached the high level of the former in two weeks. (6) Increase of BP, fall in RPF, or augment in PRA and ANG II were not observed in stress rats subjected to bilateral renal denervation. The above results indicate that the renal mechanism mediated by increased renal sympathetic nervous system plays an important role in stress- and salt-induced hypertension pathogenesis.