PubMed · 9540658
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W G Dickerson. 1994. Pressed ceramic restorations.. https://pubmed.ncbi.nlm.nih.gov/9540658/
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In expanded CAG repeat diseases such as Huntington's disease, proteins containing polyglutamine (poly(Gln)) sequences with repeat lengths of about 37 residues or more are associated with development of both disease symptoms and neuronal intranuclear inclusions (NIIs). Disease physiology in animal and cellular models does not always correlate with NII formation, however, and the mechanism by which aggregate formation might lead to cytotoxicity is unknown. To help evaluate various possible mechanisms, we determined the biophysical properties of a series of simple poly(Gln) peptides. The circular dichroism spectra of poly(Gln) peptides with repeat lengths of five, 15, 28 and 44 residues are all nearly identical and are consistent with a high degree of random coil structure, suggesting that the length-dependence of disease is not related to a conformational change in the monomeric states of expanded poly(Gln) sequences. In contrast, there is a dramatic increase in both the kinetics and the thermodynamic favorability of the spontaneous formation of ordered, amyloid-like aggregates for poly(Gln) peptides with repeat lengths of greater than 37 residues. At the same time, poly(Gln) peptides with repeat lengths in the 15-20 residue range, despite their poor abilities to support spontaneous, self-nucleated aggregation, are capable of efficiently adding to an already-formed aggregate. We also find that morphologically small, finely divided aggregates are much more efficient at recruiting poly(Gln) peptides than are large aggregates, suggesting a possible explanation for why disease pathology does not always correlate with the observable NII burden. Together, these data are consistent with a model for disease pathology in which critical cellular proteins possessing poly(Gln) sequences of modest length become inactivated when they are recruited into aggregates of an expanded poly(Gln) protein.
Halorhodopsin (HR) was investigated with atomic force microscopic techniques (AFM) in aqueous solution. Two-dimensional (2D) crystals of HR were obtained by purifying an HR membrane fraction with the same buoyant density as the purple membrane (HR-PM) from the overexpressing strain Halobacterium salinarum D2. The membrane patches of HR were immobilized on mica. Images with a resolution up to 14 A were recorded. Crystals showed an orthogonal structure and the orientation of the molecules showed p42(1)2 symmetry; thus, alternate tetramers are inverted in the membrane. The crystal surface was found to display different structures depending on the imaging force used, indicating that some parts of the HR molecule are more rigid but others more compressible. From samples with single tetramers missing in the crystalline patches dimensions of the unit cell could be determined. Helix-connecting loops in single molecules of halorhodopsin were assigned. The images indicate that the large extracellular BC loop covers the whole molecule and is very flexible.
Chromium is found in soil from natural sources and anthropogenic activities. The ingestion of soil contaminated with chromium especially by children can have toxic consequences. Therefore, it is important to quantify the oral bioaccessibility of chromium in chromium in contaminated soil. In this study, chromium-51 as chromic (III) chloride and sodium chromate (VI), was mixed with an Atsion sandy soil and a Keyport clay soil and stored for 4 mo at either 21-25 degrees C or 2-4 degrees C. Utilizing simulated gastric conditions, the oral bioaccessibility of chromium in soil was determined. When the effects of soil on the bioaccessibility of chromium were compared, the data revealed the the bioaccessibility of chromium (III) from the clay soil was significantly lower than from the sandy at 21-25 degrees C. However, at 2-4 degrees C, more chromium (III) was extracted by synthetic gastric fluid from the clay soil than from the sandy soil. Temperature was also a factor as evidenced by the higher bioaccessibility of chromium (IV) in the sandy soil at 2-4 degrees C and of both chromium species in the clay soil at the same temperature. Reduction of the soluble chromium (VI) chemical to the nonsoluble chromium (III) compound in the acidic soils by naturally occurring organic matter in soil would explain the lower bioaccessibilty of chromium (VI) at 21-25 degrees C. At 2-4 degrees C, the data indicate that the rate of chromium (VI) reduction to chromium (III) was slowed. Although the results of this study are limited to one low concentration of chromium (III) and chromium (VI) and indicate that the bioaccessibility of chromium in soil can range between 18% and 72%, the data also suggest that there may be a potential health hazard from oral exposure to chromium in heavily contaminated sites. Therefore, more extensive research should be conducted to determine if thes findings can be extended to environmentally relevant concentrations.