The Cytotoxic Effect of α-Synuclein Aggregates

Parkinson's disease is a neurodegenerative disorder involving a functional protein, α-synuclein, whose primary function is related to vesicle trafficking. However, α-synuclein is prone to form aggregates, and these inclusions, known as Lewy bodies, are the hallmark of Parkinson's disease. α-synuclein can alter its conformation and acquire aggregating capacity, forming aggregates containing β-sheets. This protein's pathogenic importance is based on its ability to form oligomers that impair synaptic transmission and neuronal function by increasing membrane permeability and altering homeostasis, generating a deleterious effect over cells. First, we establish that oligomers interfere with the mechanical properties of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane, as demonstrated by nanoindentation curves. In contrast, nanoindentation revealed that the α-synuclein monomer's presence leads to a much more resistant lipid bilayer. Moreover, the oligomers’ interaction with cell membranes can promote lactate dehydrogenase (LDH) release, suggesting the activation of cytotoxic events.     

Functionalized Silver-Ion-Mediated α-dC/β-dC Hybrid Base Pairs with Exceptional Stability: α-d-5-Iodo-2′-Deoxycytidine and Its Octadiynyl Derivative in Metal DNA

Silver-mediated α-dC–Ag⁺–β-dC hybrid base pairs decorated with 5-iodo- or 5-octadiynyl residues are well accommodated in duplex DNA. A strong T_m increase and favorable thermodynamic data for duplex DNA were observed after addition of silver ions. The phenomenon is particularly obvious when both nucleobases of the base pairs are functionalized. Neither the position of the base pair, nor the type of 5-substituent had a negative influence. On the contrary, functionalization of conventional silver-mediated β-dC–Ag⁺–β-dC homo base pairs showed a negative impact induced by the bulky substituents. To this end, cytosine modified 12-mer oligodeoxynucleotides were prepared by solid-phase synthesis employing new α-anomeric 2′-deoxycytidine phosphoramidites. A multigram scale synthesis was developed for 5-iodo-α-d -2′-deoxycytidine ( 1 ) employing the direct glycosylation of cytosine with Hoffer's α-d -halogenose followed by separation of anomeric DMT nucleosides. Regarding base-pair stability and functionalization silver-mediated α/β-dC hybrid base pairs were found to be superior to β/β-dC homo pairs. According to their extraordinary properties, they might find applications in DNA diagnostics, material science, or nanotechnology.     

Zur indirecten Bestimmung des Chlors und Broms

Ohne Zusammenfassung     

Eine neue volumetrische Methode zur Bestimmung der salpetrigen S?ure

Ohne Zusammenfassung     

An effect of application of chiral aluminium alkoxides and amides as adducts to zirconium catalyzed carbo- and cycloalumination of olefins

This paper is dedicated to a study of properties of the following novel optically active organoaluminium compounds (OACs): (1S,2S)-l,7,7-trimethyl-2-[(dialkylalumina)oxy]-bicyclo[2.2.1]heptanes and (1S)-N-(dialkylalumina)-6,7-dimethoxy-1-methyl-1,2,3,4- tetrahydroisoquinolines. The synthesis of the chiral OACs was carried out in the reaction of either natural camphor or salsolidine with both AlEt₃ and i-Bu₂AlH. The main goal of the research was to investigate the stereodifferentiating activity of the chiral OACs in the olefin carbo- and cycloalumination reactions, catalyzed by Cp₂ZrCl₂.     

Fairness in Scheduling

On-line machine scheduling has been studied extensively, but the fundamental issue of fairness in scheduling is still mostly open. In this paper we explore the issue in settings where there are long-lived processes which should be repeatedly scheduled for various tasks throughout the lifetime of a system. For any such instance we develop a notion ofdesiredload of a process, which is a function of the tasks it participates in. Theunfairnessof a system is the maximum, taken over all processes, of the difference between the desired load and the actual load.An example of such a setting is thecarpool problemsuggested by Fagin and Williams [IBM Journal of Research and Development27(2) (1983), 133–139]. In this problem, a set ofnpeople form a carpool. On each day a subset of the people arrive and one of them is designated as the driver. A scheduling rule is required so that the driver will be determined in a “fair” way.We investigate this problem under various assumptions on the input distribution. We also show that the carpool problems can capture several other problems of fairness in scheduling.     

Effective synthesis of ortho-substituted triphenol amines via reductive amination

An efficient synthesis of ortho-substituted triphenolamines via reductive amination is reported. This approach allows access to this increasingly important class of ligands in a structurally systematic way using either commercially or easily synthesizable building blocks.     

Disorder arising from the location of enantiomers in a twist-boat structure: 2,6-trans-2,4,6-tris(trichloromethyl)-1-oxa-3,5-dithian

Crystals of the title compound are orthorhombic, Pca2₁;a=27.586(4),b=10.509(3),c=11.080(2) Å,V=3212(1) ų,Z=8. The structure was solved by direct methods, from data collected at room temperature on an Enraf-Nonius CAD4 diffractometer, and refined by full-matrix least squares to a finalR value of 0.055 using 2043 reflections. One of the two independent molecules in the asymmetric unit is disordered. The disorder is manifested mainly between the oxygen atom and one sulfur atom and is caused by opposite enantiomers occupying corresponding positions in different unit cells. The endocyclic torsion angles in both independent molecules are very similar but the disposition of the heteroatoms on the twist-boat framework is different in the two molecules. Site occupancy of the two models on this framework in the disordered molecule is in the ratio 2179 with the smaller proportion being very similar to the ordered molecule and the remainder similar to that found in the normal molecule oftrans-4-chloro-2,4,6-tris(trichloromethyl)-1-oxa-3,5-dithian (Irving and Irving, 1988).