Pro-domain removal in ASP-2 and the cleavage of the amyloid precursor are influenced by pH

Background

One of the signatures of Alzheimer's disease is the accumulation of aggregated amyloid protein, Aβ, in the brain. Aβ arises from cleavage of the Amyloid Precursor protein by β and γ secretases, which present attractive candidates for therapeutic targeting. Two β-secretase candidates, ASP-1 and ASP-2, were identified as aspartic proteases, both of which cleave the amyloid precursor at the β-site. These are produced as immature transmembrane proteins containing a pro-segment.

Results

ASP-2 expressed in HEK293-cells cleaved the Swedish mutant amyloid precursor at different β-sites at different pHs in vitro. Recent reports show that furin cleaves the pro-peptide of ASP-2, whereas ASP-1 undergoes auto-catalysis. We show that purified recombinant ASP-2 cleaves its own pro-peptide at ph 5 but not pH 8.5 as seen by mass spectrometry, electrophoresis and N-terminal sequencing.

Conclusion

We suggest that ASP-2 processing as well as activity are influenced by pH, and hence the cellular localisation of the protein may have profound effects on the production of Aβ. These factors should be taken into consideration in the design of potential inhibitors for these enzymes.     

Spektrochemische Bestimmung von Spurenelementen in Eisen und Stahl

Zusammenfassung Ein zweites spektrochemisches Verfahren zur Bestimmung von Silber, Blei, Zinn, Wismut, Tellur, Arsen und Antimon in Eisen und Stahl wurde entwickelt. Auch hier wird die spektrographische Analyse nach Auflösen der Probe in Salpetersäure und Eindampfen der Lösung zur Trockne durchgeführt. Die leichtflüchtigen Elemente werden ohne Puffer durch Anwendung eines inhomogenen Magnetfeldes und einer zweckmäßigen Elektrodenform störungsfrei und mit guter Reproduzierbarkeit bestimmt. Dabei sind die unteren Bestünmungsgrenzen gleich oder niedriger als die anderer spektrochemischer Methoden, die bisher beschrieben wurden. Das Verfahren zeichnet sich durch Schnelligkeit und Einfachheit aus.

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Spectrochemical determination of trace elements in iron and steelPart II. determination of Ag, Pb, Sn, Bi, Te, As and Sb by using an inhomogeneous magnetic field

A second spectrochemical method for the determination of silver, lead, tin, bismuth, tellurium, arsenic and antimony in iron and steel has been developed. Here also the spectrographic analysis is to be carried out after dissolution of the sample in nitric acid and evaporation of the solution to dryness. Without buffer, the easily volatile elements are determined free of interferences and with good reproducibility by using an inhomogeneous magnetic field and electrodes of an appropriate form. The lower limits of determination are the same or lower than those obtained by any other spectrochemical method described. The method is characterised by rapidity and simplicity of procedure.

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Teil I: diese Z. 254, 16 (1971).     

Spectroscopic and photophysical properties of hexanuclear rhenium(III) chalcogenide clusters

The electronic, vibrational, and excited-state properties of hexanuclear rhenium(III) chalcogenide clusters based on the [Re(6)(mu(3)-Q)(8)](2+) (Q = S, Se) core have been investigated by spectroscopic and theoretical methods. Ultraviolet or visible excitation of [Re(6)Q(8)](2+) clusters produces luminescence with ranges in maxima of 12 500-15 100 cm(-)(1), emission quantum yields of 1-24%, and emission lifetimes of 2.6-22.4 microseconds. Nonradiative decay rate constants and the luminescence maxima follow the trend predicted by the energy gap law (EGL). Examination of 24 clusters in solution and 14 in the solid phase establish that exocluster ligands engender the observed EGL behavior; clusters with oxygen- or nitrogen-based apical ligands achieve maximal quantum yields and the longest lifetimes. The excited-state decay mechanism was investigated by applying nonradiative decay models to temperature-dependent emission experiments. Solid-state Raman spectra were recorded to identify vibrational contributions to excited-state deactivation; spectral assignments were enabled by normal coordinate analysis afforded from Hartree-Fock and DFT calculations. Excited-state decay is interpreted with a model where normal modes largely centered on the [Re(6)Q(8)](2+) core induce nonradiative relaxation. Hartree-Fock and DFT calculations of the electronic structure of the hexarhenium family of compounds support such a model. These experimental and theoretical studies of [Re(6)Q(8)](2+) luminescence provide a framework for elaborating a variety of luminescence-based applications of the largest series of isoelectronic clusters yet discovered.     

Stress-Strain Behavior of Shape Memory Polymers by 1WE Method: Application to Tecoflex®

Thermomechanical cycles including programming, cooling, unloading and heating to trigger the 1WE were examined for a shape memory polymer (SMP), Tecoflex® (TFX EG-72D). Cycles were performed at 60°C with 50% and 225% strains and the recovery time of 10 min. Strains evolving with time were estimated during the thermomechanical treatments for the total 44 cycles using 50% strains and the total 50 cycles using 225% strains. Recovery ratios for 50% strains and 225% were also estimated. It turns out that programming, cooling, unloading and heating to trigger the 1WE causes an increase of irreversible strain and is associated with a corresponding decrease of the intensity of the 1WE in particular during the first thermomechanical cycles. In parallel scanning electron microscopic study using secondary electron imaging shows a very slight wavy surface structure evolved during cycling.     

Acid-Catalyzed RNA-Oligomerization from 3’,5’-cGMP

The assembly of ancient informational polymers from nucleotide precursors is the central challenge of life's origin on our planet. Among the possible solutions, dry polymerization of 3’,5’-cyclic guanosine monophosphate (3’,5’-cGMP) has been proposed as a candidate to create oligonucleotides of 15–20 units in length. However, the reported sensitivity of the reaction to the presence of cations raised questions of whether this chemistry could be relevant in a geological context. The experiments in this study show that the presence of cations is not restrictive as long as the reaction is conducted in an acidic environment, in contrast to previous reports that suggested optimal conditions at pH 9.