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.     

Rheological behavior and structural interpretation of waxy crude oil gels

A waxy crude oil which gels below a threshold temperature has been investigated under static and dynamic conditions, using a combination of rheological methods, optical microscopy, and DSC. Particular attention is given in this work to the influence of the mechanical history on gel strength and to describing the time-dependent rheological behavior. The gels display a strong dependence of the yield stress and moduli on the shear history, cooling rate, and stress loading rate. Of particular interest is the partial recovery of the gel structure after application of small stress or strain (much smaller than the critical values needed for flow onset) during cooling, which can be used to reduce the ultimate strength of the crude oil gel formed below the pour point. A second focus of this study is to further develop the physical interpretation of the mechanism by which wax crystallization produces gelation. Gelation of the waxy crude oil studied is suggested to be the result of the association between wax crystals, which produces an extended network structure, and it is shown that the system displays features common to attractive colloidal gels, for one of which, fumed silica (Aerosil 200) in paraffin oil, rheological data are reported. The colloidal gel model provides a simple and economical basis for explaining the response of the gelled oil to various mechanical perturbations and constitutes a fruitful basis from which to develop technologies for controlling the gelation phenomenon, as suggested by the rheological results reported.     

Metal-directed synthesis and photophysical studies of trinuclear v-shaped and pentanuclear x-shaped ruthenium and osmium metallorods and metallostars based upon 4'-(3,5-dihydroxyphenyl)-2,2':6',2''-terpyridine divergent units

A new series of V-shaped trinuclear metallorods and X-shaped pentanuclear metallostars has been prepared by the reaction of metal complexes bearing pendant phenolic functionalities with complexes containing electrophilic ligands. Specifically, {M(tpy)2} motifs (M=Ru or Os; tpy=2,2':6',2'-terpyridine) bearing one or two pendant 3,5-dihydroxyphenyl substituents at the 4-position of the central ring of the tpy have been reacted with the complexes [Ru(tpy)(Xtpy)]2+ (X=Cl or Br) to form new ether-linked species. The energy transfer from ruthenium to osmium in these complexes has been investigated in detail and the efficiency of transfer shown to be highly temperature dependent; the energy transfer is highly efficient at low temperature, whereas at room temperature nonradiative and nontransfer deactivation of the excited {Ru(tpy)2}* domains is most significant.     

Solvent effects in the reaction of 2-thiophenesulfonyl chloride with aniline

The second order rate constants k₂ and the activation parameters for the reaction of 2-thiophenesulfonyl chloride with aniline together with solution enthalpies of the reactants have been measured in methanol, ethanol, 2-propanol, acetonitrile and acetone. The reaction rates are slower in dipolar aprotic solvents than in protic ones due to a remarkable activation negative entropy. The rate constants k₂ are correlated with empirical solvent polarity parameters. The data seem in accord with a S_AN reaction mechanism.     

Dimer asymmetry in superoxide dismutase studied by molecular dynamics simulation

Summary Molecular dynamics (MD) simulations of 100 ps have been carried out to study the active-site behaviour of the Cu,Zn superoxide dismutase dimer (SOD) in water. The active site of each subunit was monitored during the whole simulation by calculating the distances between functional residues and the catalytic copper. The results indicate that charge orientation is maintained at each active site but the solvent accessibility varies. Analysis of the MD simulation, carried out by using the atomic displacement covariance matrix, has shown a different intra-subunit correlation pattern for the two monomers and the presence of inter-subunit correlations. The MD simulation presented here indicates an asymmetry in the two active sites and different dynamic behaviour of the two SOD subunits.     

C 1 surface interpolation with constraints

Givenn pairwise distinct and arbitrarily spaced pointsP _i in a domainD of thex–y plane andn real numbersf _i, consider the problem of computing a bivariate functionf(x, y) of classC ¹ inD whose values inP _i are exactlyf _i,i=1,,n, and whose first or second order partial derivatives satisfy appropriate equality and inequality constraints on a given set ofp pointsQ _l inD.In this paper we present a method for solving the above problem, which is designed for extremely large data sets. A step of this method requires the solution of a large scale quadratic programming (QP) problem.The main purpose of this work is to analyse an iterative method for determining the solution of this QP problem: such a method is very efficient and well suited for parallel implementation on a multiprocessor system.Work supported by MURST Project of Computational Mathematics, Italy.     

Preserving the chromatographic integrity of high-speed supercritical fluid chromatography separations using time-of-flight mass spectrometry

The advantage of high-speed time-of-flight-mass spectrometry (TOF-MS) detection for ultrafast qualitative supercritical fluid chromatography/mass spectrometry (SFC/MS) applications allows the superior resolving power of SFC to be exploited in high-throughput analysis. A chromatographic comparison of quadrupole MS and TOF-MS shows high-speed TOF total ion current data point sampling to be more indicative of fast SFC separations and corresponding short (1-2 s) baseline peak widths. Results shown for analysis of a six-compound mixture with two peaks eluting at 0.86 and 0.89 min exhibit >50% resolution by high-speed TOF data sampling, whereas the same peaks appear to coelute using quadrupole MS data sampling. Additionally, a marked improvement in the peak baseline widths is afforded by fast TOF data acquisition of 0.1 s/spectrum, resulting in a reduction in the baseline width, 1.6 s, of sulfanilamide in a four-compound mixture that is more than 2-fold greater than that achieved at the slower data acquisition of 0.5 s/spectrum. The resulting increase in resolution and improved peak shapes allow automatic integration routines to perform more effectively. For most classes of compounds amenable to high performance liquid chromatography, including druglike species, steroids, and polymers, the union of SFC with TOF-MS provides the maximum density of chemical information per unit time available with any high-speed chromatographic/mass spectrometric method.