Search

The hardening distortions with respect to base body, clutch teeth and helical gears are investigated for a serial-produced main shaft gear of a 20NiCrMoS6-4 steel. The influences of casting geometr ...

The hardening distortions of serial produced crown wheels are studied with respect to gear runout, inner diameter and back-face tilt. The data analysed originates from a production data base from o ...

Low pH has a strong stabilising effect on the fibrillar assembly of amyloid β, which is associated with Alzheimer's disease. The stabilising effect is already pronounced at pH 6.0, suggesting that protonation of histidines might mediate this effect. Through the systematic substitution of the three native histidines in Aβ for alanines, we have evaluated their role in fibril stability. Using surface plasmon resonance, we show that at neutral pH the fibrillar forms of all His-Ala variants are destabilised by a factor of 4-12 compared to wild-type Aβ. However, none of the His-Ala Aβ variants impair the stabilising effect of the fibril at low pH. Alternative title: The role of histidines in amyloid beta fibril assembly

Archaeological flint artefacts from the late Mesolithic/early Neolithic site of Vuollerim, northern Sweden, have been geochemically investigated with ICP-SFMS and MC-ICP-MS in search for the geolog ...

We show that operator-valued Bergman inner functions have the so-called expansive multiplier property generalizing a well-known result of Hedenmalm in the scalar case. This analysis leads to norm bounds for input output maps for a related class of discrete time linear systems. The proof uses properties of the biharmonic Green function. (C) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Alzheimer's disease, a neurodegenerative disorder causing synaptic impairment and neuronal cell death, is strongly correlated with aggregation of the amyloid-beta peptide (Abeta). Divalent metal ions such as Cu(2+) and Zn(2+) are known to significantly affect the rate of aggregation and morphology of Abeta assemblies in vitro and are also found at elevated levels within cerebral plaques in vivo. The present investigation characterized the architecture of the aggregated forms of Abeta(1-40) and Abeta(1-42) in the presence or absence of either Cu(2+) or Zn(2+) using quenched hydrogen/deuterium exchange combined with solution NMR spectroscopy. The NMR analyses provide a quantitative and residue-specific structural characterization of metal-induced Abeta aggregates, showing that both the peptide sequence and the type of metal ion exert an impact on the final architecture. Common features among the metal-complexed peptide aggregates are two solvent-protected regions with an intervening minimum centered at Asn27, and a solvent-accessible N-terminal region, Asp1-Lys16. Our results suggest that Abeta in complex with either Cu(2+) or Zn(2+) can attain an aggregation-prone beta-strand-turn-beta-strand motif, similar to the motif found in fibrils, but where the metal binding to the N-terminal region guides the peptide into an assembly distinctly different from the fibril form.

Human transthyretin (hTTR) is one of several proteins known to cause amyloid disease. Conformational changes in its native structure result in aggregation of the protein, leading to insoluble amylo ...

Background For all forms of amyloidosis, the amyloid-generating mechanism is unknown. Familial amyloidotic polyneuropathy type I is caused by a variant transthyretin (TTR Met-30). As electrospray ionization mass spectrometry (ESI-MS) discloses both thiol-conjugated and -unconjugated forms of wild-type and variant TTR, we wanted to investigate the relationship between TTR conjugation and clinically overt amyloid disease. Methods Plasma from 35 individuals (12 symptomatic TTR Met-30 carriers, nine asymptomatic and 14 healthy control subjects) were analysed using ESI-MS. Results The total TTR concentration was significantly lower in symptomatic TTR Met-30 carriers than in control subjects. An increased percentage of conjugated TTR Met-30 was found in symptomatic carriers compared with asymptomatic, whereas the percentage conjugated wild-type TTR was similar for control subjects, asymptomatic and symptomatic TTR Met-30 carriers. Conclusion The finding of a decreased ratio of unconjugated to conjugated TTR Met-30 in plasma samples from symptomatic TTR Met-30 carriers indicates that thiol conjugation of TTR could be involved in amyloid formation.

Electron crystallography constitutes a powerful new method for determining the structure of biological macromolecules. This method is best adapted to the study of ordered assemblies of macromolecules, and principally to two-dimensional (2-D) crystals of proteins. Obtaining protein 2-D crystals ordered at high resolution constitutes the major limiting step in the application of this approach. Considerable interest has been raised by the development of a rational method of 2-D crystallization based on the specific binding of proteins to planar lipid films. The applicability of this method is quasi-general in the case of soluble proteins. Its basic principles, together with examples taken from work in our group, are presented here.

Transforming growth factor-beta 1 (TGF-beta 1) is synthesized as latent complexes with high molecular weights. The large latent complex of TGF-beta 1 in platelets is composed of three components, i.e. the mature TGF-beta 1, which is non-covalently associated with a disulphide-bonded complex of the N-terminal remnant of the TGF-beta 1 precursor (TGF-beta 1-latency associated peptide) and the latent TGF-beta 1 binding protein (LTBP). The TGF-beta 1-latency associated peptide is sufficient for the latency of TGF-beta 1, whereas the functions of LTBP remain to be elucidated. In a human erythroleukemia cell line, HEL, the production of the latent form of TGF-beta 1 was induced more than 100-fold by phorbol 12-myristate 13-acetate. Analysis by Northern blotting revealed that both the TGF-beta 1 precursor and LTBP were induced in a coordinated fashion. Analysis by immunoprecipitation using antibodies against LTBP and the TGF-beta 1 precursor dimer revealed that LTBP has a molecular size of 205 kd under reducing conditions in this cell type, i.e. similar to that from cells transfected with cDNA for LTBP, but larger than the platelet form (125-160 kd). Limited tryptic digestion of LTBP in HEL cells and analysis by SDS-PAGE showed protein bands of similar sizes to those of platelet LTBP, suggesting that the difference in molecular sizes of LTBP involves cell-specific processing. The biosynthesis of the latent TGF-beta 1 was studied by pulse-chase analysis. LTBP became covalently associated with the TGF-beta 1 precursor within 15 min after synthesis in this cell line. Secretion of the large latent TGF-beta 1 complex was observed as early as 30 min after the synthesis of LTBP; at the same time, a free form of LTBP not bound to the TGF-beta 1 precursor was seen. In contrast, the TGF-beta 1 precursor remained inside the cells in an unprocessed form for a longer time period and the TGF-beta 1 precursor dimer without LTBP was secreted only very slowly. Furthermore, the results of partial tryptic digestion of this molecule suggested that it contained improper disulphide bonding. These results suggest that LTBP plays a critical role in the assembly and secretion of the latent TGF-beta 1.

The cytolysin Perfringolysin O was applied to lipid layers and the obtained ring-shaped oligomers analyzed by electron microscopy and image processing. The final result shows the periodic repeat of 2.4 nm along the outer rim of the ring. The asymmetric protein unit, corresponding to one monomer, spans the ring from the convex to the concave surface. It shows a clear protein peak close to the outer radius and less density in the middle of the oligomer. The number of monomers in the average ring is 50, and the inner radius of the aggregate is approximately 15 nm.

Some aspects of digitization of electron micrographs have been investigated. The performances of a flat-bed, a rotating drum, and a diode array scanner have been evaluated. Estimates have been achieved for resolution, mechanical and optical stability, and optical density response. It is concluded that for routine transmission electron microscopy of, for example, negatively stained biologic specimens, a diode array scanner produces data good enough to obtain resolutions at a level normally expected. High speed is the major advantage with this type of equipment. However, for high-resolution work it is necessary to use a conventional scanner with a relatively slow scan speed.

The subjects were recruited from participants in a health examination of random samples of the adult population in Stockholm county. Those aged 18-64 years who admitted a high alcohol consumption (greater than 40 g 100% ethanol/day) among men and greater than 30 g among women) or had an elevated value of serum-gammaglutamyltransferase (GGT) (cut-off point 1.0 microkatal/l for men and 0.6 microkatal/l for women) or had certain other indications of a high alcohol consumption were included. More severe cases, and those with an elevated GGT due to reasons other than alcohol, were excluded. The remaining subjects, 70 men and 13 women, were allocated at random to either an intervention or a comparison group. An elevated GGT was the main inclusion criteria. The subjects in the comparison group were advised by the general practitioner to cut their alcohol consumption, while those in the intervention group made further visits to their general practitioner, who gave general support and used an elevated GGT as an indication of the recent level of alcohol consumption at consecutive visits. There were three visits on average, so we are comparing a group receiving advice with a group receiving further minimal intervention. At the one-year follow-up there were greater, however not significant, reduction in GGT-level, in self-reported alcohol consumption and in a 'problem index' in the minimal intervention group than in the comparison group.