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.     

Three New Polyoxygenated Steroids from Two Species of the South China Sea Gorgonian Muricella flexuosa and Menella verrucosa Brundin

Three new polyoxygenated steroids, muricesteroid ( 1 ), and menellsteroids A ( 2 ) and B ( 3 ), were isolated from two species of the South China Sea gorgonian Muricella flexuosa and Menella verrucosa Brundin , respectively. The structures of these new compounds were elucidated on the basis of extensive spectroscopic analysis, chemical methods and comparison with known related compounds.     

Anomale änderungen physikalischer Eigenschaften beim heterogenen Zerfall übersättigter Fe-Ni-Cu-Legierungen

Zusammenfassung Einige charakteristische ?nderungen physikalischer Werkstoffeigenschaften beim heterogenen Zerfall übers?ttigter Mischkristalle werden am Beispiel der fl?chenzentrierten Eisen-Nickel-Kupfer-Legierungen beschrieben. Bei der Behandlung des Einflusses der Ausscheidungsvorg?nge auf die Rekristallisationserscheinungen tritt die Bedeutung des übers?ttigungsgrades der zerfallenden festen L?sung für den Ablauf dieser Zustands?nderungen besonders klar zutage. Kritische Stadien der Ausscheidung und der Koagulation der heterogenen Phasen sind bei diesen Legierungen für die Erzeugung besonders hochwertiger magnetischer Eigenschaften verantwortlich. Der vorliegende Bericht wurde von Herrn Prof., Dr. Wo. Ostwald angeregt. Für das diesem Arbeitsgebiet entgegengebrachte Interesse m?chte ich Herrn Prof. Ostwald meinen besten Dank aussprechen.     

Radiochemical proton activation analysis for the determination of cadmium and lead in sediment reference materials

Proton activation analysis was used for the determination of cadmium and lead in three sediment reference materials. The method is based on the^111,112Cd(p, xn)¹¹¹ In and the^206,207,208Pb(p, xn)²⁰⁶Bi reactions.¹¹¹In and²⁰⁶Bi were chemically separated by anion exchange. The results obtained were taken into account for the certification of the materials and are in the excellent agreement with the certified values.     

Modulation of the distance dependence of paramagnetic relaxation enhancements by CSA × DSA cross-correlation

Paramagnetic metal ions with fast-relaxing electronic spin and anisotropic susceptibility tensor provide a rich source of structural information that can be derived from pseudo-contact shifts, residual dipolar couplings, dipole-dipole Curie spin cross-correlation, and paramagnetic relaxation enhancements. The present study draws attention to a cross-correlation effect between nuclear relaxation due to anisotropic chemical shielding (CSA) and due to the anisotropic dipolar shielding (DSA) caused by the electronic Curie spin. This CSA x DSA cross-correlation contribution seems to have been overlooked in previous interpretations of paramagnetic relaxation enhancements. It is shown to be sufficiently large to compromise the 1/r6 distance dependence usually assumed. The effect cannot experimentally be separated from auto-correlated DSA relaxation. It can increase or decrease the observed paramagnetic relaxation enhancement. Under certain conditions, the effect can dominate the entire paramagnetic relaxation, resulting in nuclear resonances narrower than in the absence of the paramagnetic center. CSAxDSA cross-correlation becomes important when paramagnetic relaxation is predominantly due to the Curie rather than the Solomon mechanism. Therefore the effect is most pronounced for relaxation by metal ions with large magnetic susceptibility and fast-relaxing electron spin. It most strongly affects paramagnetic enhancements of transverse relaxation in macromolecules and of longitudinal relaxation in small molecules.     

Strong approximation ofGSBV functions by piecewise smooth functions

Let Ω be an open and bounded subset ofR ⁿ with locally Lipschitz boundary. We prove that the functionsv∈SBV(Ω,R ^m ) whose jump setS _vis essentially closed and polyhedral and which are of classW ^{k, ∞} (S _v,R ^m) for every integerk are strongly dense inGSBV ^p(Ω,R ^m ), in the sense that every functionu inGSBV ^p(Ω,R ^m ) is approximated inL ^p(Ω,R ^m ) by a sequence of functions {v _k{_j∈N with the described regularity such that the approximate gradients ∇v _jconverge inL ^p(Ω,R ^nm ) to the approximate gradient ∇u and the (n−1)-dimensional measure of the jump setsS _{v j} converges to the (n−1)-dimensional measure ofS _u. The structure ofS _v can be further improved in casep≤2.

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Sunto Sia Ω un aperto limitato diR ⁿ con frontiera localmente Lipschitziana. In questo lavoro si dimostra che le funzioniv∈SBV(Ω,R ^m ) con insieme di saltoS _v essenzialmente chiuso e poliedrale che sono di classeW ^{k, ∞} (S _v,R ^m ) per ogni interok sono fortemente dense inGSBV ^p(Ω,R ^m ), nel senso che ogni funzioneu∈GSBV ^p(Ω,R ^m ) è approssimata inL ^p(Ω,R ^m ) da una successione di funzioni {v _j}_j∈N con la regolaritá descritta tali che i gradienti approssimati ∇v _jconvergono inL ^p(Ω,R ^nm ) al gradiente approssimato ∇u e la misura (n−1)-dimensionale degli insiemi di saltoS _{v j}converge alla misura (n−1)-dimensionale diS _u. La struttura diS _vpuó essere migliorata nel caso in cuip≤2.