Über den Einfluß von Inhomogenitäten im Grundmagnetfeld auf die Tripelquantengefilterte Natrium-MR-Spektroskopie und -Bildgebung

Mit einer tripelquantengefilterten (TQF) Natrium-MR-Messung kann das Signal von Natrium-Ionen isoliert werden, die in ihrer Beweglichkeit durch Wechselwirkung mit makromolekularen Strukturen etwa im intrazellulären Kompartiment eingeschränkt sind. Das TQF-Signal ist jedoch vergleichsweise schwach, und bei Inhomogenitäten im Grundmagnetfeld B0 kann es aufgrund von destruktiver Interferenz der Signalkomponenten zu Auslöschungen kommen, wenn wie in der üblicherweise verwendeten Dreipuls-Sequenz kein zusätzlicher Refokussierungspuls geschaltet wird. In der vorliegenden Arbeit wird die Abhängigkeit der TQF-Signalintensität von den Startphasen des zur Tripelquantenfilterung eingesetzten Phasenzyklus hergeleitet. Eine neue Methode zur Korrektur von Artefakten aufgrund von B0-Inhomogenität wird vorgestellt, die durch eine adäquate Wahl der Startphasen nur zwei TQF-Aufnahmen benötigt, solange die B0-Inhomogenität O nicht zu stark und die Pulsbreiten tp nicht zu lang sind (3 O tp << 1). Verglichen mit einer früheren Methode zur B0-Inhomogenitätskorrektur kann damit entweder die Meßzeit halbiert oder in den korrigierten TQF-Aufnahmen ein bis zu 30% höheres Signalrausch-Verhältnis gemessen werden. Nach dem ersten Puls läßt sich bei einem Spin-3/2-Kern eine Mehrquantenfilterung zwischen geraden und ungeraden Kohärenzordnungen durch die Wahl der Startphasen realisieren, wenn die Bedingung 3 O tp << 1 erfüllt ist. In diesem Fall kann auf einen sonst zusätzlich benötigten Phasenzyklus verzichtet und die Meßzeit halbiert werden. Eine Filterung von Kohärenzordnungen nach dem zweiten Puls ist allerdings allein über die Einstellung der Startphasen nicht möglich

The Surface Topography of a Magnetic Fluid -- a Quantitative Comparison between Experiment and Numerical Simulation

The normal field instability in magnetic liquids is investigated experimentally by means of a radioscopic technique which allows a precise measurement of the surface topography. The dependence of the topography on the magnetic field is compared to results obtained by numerical simulations via the finite element method. Quantitative agreement has been found for the critical field of the instability, the scaling of the pattern amplitude and the detailed shape of the magnetic spikes. The fundamental Fourier mode approximates the shape to within 10% accuracy for a range of up to 40% of the bifurcation parameter of this subcritical bifurcation. The measured control parameter dependence of the wavenumber differs qualitatively from analytical predictions obtained by minimization of the free energy.Comment: 21 pages, 16 figures; corrected typos, added reference to Kuznetsov and Spector(1976), S.J. Fortune(1995) and Harkins&Jordan (1930). Figures revise

Quantum dynamics of two bosons in an anharmonic trap: Collective vs internal excitations

This work deals with the effects of an anharmonic trap on an interacting two-boson system in one dimension. Our primary focus is on the role of the induced coupling between the center of mass and the relative motion as both anharmonicity and the (repulsive) interaction strength are varied. The ground state reveals a strong localization in the relative coordinate, counteracting the tendency to fragment for stronger repulsion. To explore the quantum dynamics, we study the system's response upon (i) exciting the harmonic ground state by continuously switching on an additional anharmonicity, and (ii) displacing the center of mass, this way triggering collective oscillations. The interplay between collective and internal dynamics materializes in the collapse of oscillations, which are explained in terms of few-mode models.Comment: 8 pages, 7 figure

Cryo-EM demonstrates the in vitro proliferation of an ex vivo amyloid fibril morphology by seeding

Several studies showed that seeding of solutions of monomeric fibril proteins with ex vivo amyloid fibrils accelerated the kinetics of fibril formation in vitro but did not necessarily replicate the seed structure. In this research we use cryo-electron microscopy and other methods to analyze the ability of serum amyloid A (SAA)1.1-derived amyloid fibrils, purified from systemic AA amyloidosis tissue, to seed solutions of recombinant SAA1.1 protein. We show that 98% of the seeded fibrils remodel the full fibril structure of the main ex vivo fibril morphology, which we used for seeding, while they are notably different from unseeded in vitro fibrils. The seeded fibrils show a similar proteinase K resistance as ex vivo fibrils and are substantially more stable to proteolytic digestion than unseeded in vitro fibrils. Our data support the view that the fibril morphology contributes to determining proteolytic stability and that pathogenic amyloid fibrils arise from proteolytic selection

cGMP-dependent protein kinase Iα associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake

<p>Abstract</p> <p>Background</p> <p>The Na⁺/Cl^--dependent serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) is a critical element in neuronal 5-HT signaling, being responsible for the efficient elimination of 5-HT after release. SERTs are not only targets for exogenous addictive and therapeutic agents but also can be modulated by endogenous, receptor-linked signaling pathways. We have shown that neuronal A3 adenosine receptor activation leads to enhanced presynaptic 5-HT transport <it>in vitro </it>and an increased rate of SERT-mediated 5-HT clearance <it>in vivo</it>. SERT stimulation by A3 adenosine receptors derives from an elevation of cGMP and subsequent activation of both cGMP-dependent protein kinase (PKG) and p38 mitogen-activated protein kinase. PKG activators such as 8-Br-cGMP are known to lead to transporter phosphorylation, though how this modification supports SERT regulation is unclear.</p> <p>Results</p> <p>In this report, we explore the kinase isoform specificity underlying the rapid stimulation of SERT activity by PKG activators. Using immortalized, rat serotonergic raphe neurons (RN46A) previously shown to support 8-Br-cGMP stimulation of SERT surface trafficking, we document expression of PKGI, and to a lower extent, PKGII. Quantitative analysis of staining profiles using permeabilized or nonpermeabilized conditions reveals that SERT colocalizes with PKGI in both intracellular and cell surface domains of RN46A cell bodies, and exhibits a more restricted, intracellular pattern of colocalization in neuritic processes. In the same cells, SERT demonstrates a lack of colocalization with PKGII in either intracellular or surface membranes. In keeping with the ability of the membrane permeant kinase inhibitor DT-2 to block 8-Br-cGMP stimulation of SERT, we found that DT-2 treatment eliminated cGMP-dependent kinase activity in PKGI-immunoreactive extracts resolved by liquid chromatography. Similarly, treatment of SERT-transfected HeLa cells with small interfering RNAs targeting endogenous PKGI eliminated 8-Br-cGMP-induced regulation of SERT activity. Co-immunoprecipitation studies show that, in transporter/kinase co-transfected cells, PKGIα specifically associates with hSERT.</p> <p>Conclusion</p> <p>Our findings provide evidence of a physical and compartmentalized association between SERT and PKGIα that supports rapid, 8-Br-cGMP-induced regulation of SERT. We discuss a model wherein SERT-associated PKGIα supports sequentially the mobilization of intracellular transporter-containing vesicles, leading to enhanced surface expression, and the production of catalytic-modulatory SERT phosphorylation, leading to a maximal enhancement of 5-HT clearance capacity.</p