Lizofoszfolipid mediátorok receptorai. Szfingo- és glicerolipid növekedési faktorokat kötő fehérjék azonosítása és jellemzése. = Identification and characterization of specific proteins for sphingo- and glycerolipid growth factors

A legegyszerűbb foszfolipidek, a lizofoszfatidsav (LPA) és a szfingozin-1-foszfát (S1P) jelátvivő molekulák, amelyek részt vesznek a sejtek túlélésének, osztódásának és mozgásainak szabályozásában az egyszerű organizmusoktól az emberig. Kutatásaink célja ezen foszfolipidek hatásmechanizmusának megismerése, a kölcsönható fehérjék azonosítása. Az LPA és az S1P hatását elsősorban sejtfelszíni receptorokon keresztül fejti ki. Az LPA-receptortípusokra szelektív aktiváló és gátló molekulák két új csoportját azonosítottuk és jellemeztük: a zsíralkohol-foszfátokat és az oligoprenil-foszfátokat. Sikeresen azonosítottuk az S1P1-es típusú receptor ligandkötésében résztvevő apoláros aminosavakat, teljessé téve ezzel korábbi munkánkat a kötőhely feltérképezésére. Eredményeink a lizofoszfolipid receptorok farmakológiai vizsgálatának új lehetőségeit teremtik meg. Az S1P különlegessége, hogy másodlagos hírvivő is. Egyértelmű bizonyítékot szolgáltattunk arra, hogy az S1P valóban intracellulárisan is képes a kalcium-ionok felszabadítására. Legújabban kimutattuk, hogy az S1P-rokon szfingozilfoszforilkolin köti és gátolja a kalcium hatását univerzálisan közvetítő kalmodulint. Az S1P a sejtben keletkezik, tehát sejtfelszíni receptorai aktiválásához ki kell jutnia onnan. Vizsgáltuk egyes ABC-transzporterek szerepét ebben a folyamatban. Kimutattuk, hogy az MRP1-fehérje az S1P egyik lehetséges kipumpálója. E fehérje működése során fellépő kooperatív kölcsönhatásokat is azonosítottunk. | The simplest phospholipids, lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lipid mediators regulating survival, proliferation, and migration of cells. Our aim is to characterize the mechanisms of action of these phospholipids and to identify their interacting proteins. LPA and S1P exert their actions mainly through cell surface G protein-coupled receptors. We identified two new sets of LPA receptor subtype selective ligands: fatty alcohol phosphates and oligoprenyl phosphates. We also successfully completed the mapping of the ligand binding pocket of the S1P1 receptor, by determining the amino acids lining the hydrophobic part of the binding site. Our results make new pharmacologic interventions possible at lysophospholipid receptors. S1P is unique because it also acts as a second messenger. We provided strict evidence for the action of S1P on the intracellular calcium mobilization from endoplasmic reticulum, independent of cell surface receptors. Very recently we have shown that the related lipid sphingosylphosphorylcholine binds to and inhibits the actions of calmodulin, the ubiquitous calcium sensor of cells. S1P is formed inside cells by the action of sphingosine kinases. It should leave the cell to act as an autocrine/paracrine mediator. We investigated the role of ABC transporters in this process and identified MRP1 as a potential efflux pump for S1P. We also identified cooperative interactions between the ATP and drug binding sites of MRP1

Goldinduzierte Nanostrukturierung vicinaler Si(001)-Oberflächen

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Step and kink correlations on vicinal Ge(100) surfaces investigated by electron diffraction

Using spot profile analysis in low-energy electron diffraction, we have investigated vicinal Ge(100) surfaces, which were miscut by 2.7° and 5.4°, respectively, in [011] direction with respect to the surface normal. Within the kinematic approximation the morphology was evaluated quantitatively both perpendicular and parallel to the step edge direction. In contrast to vicinal Si(100) surfaces with similar miscut angles, the Ge(100) surfaces still show an alternating configuration of (2×1) and (1×2) reconstructed (100) terraces, which are separated by steps of single atomic height. From the spot profiles and their energy dependence we extracted the morphological parameters such as the average terrace width, the variance of the terrace size distribution, and the average kink separation. Furthermore, step energies on the vicinal Ge(100) surfaces were estimated. These turn out to be significantly lower than for Si(100) and lead to the formation of the observed double domain structure. © 2002 The American Physical SocietyDFGK+S Grupp

Morphological diagram of diffusion driven aggregate growth in plane: competition of anisotropy and adhesion

Two-dimensional structures grown with Witten and Sander algorithm are investigated. We analyze clusters grown off-lattice and clusters grown with antenna method with $N_{fp}=3,4,5,6,7$ and 8 allowed growth directions. With the help of variable probe particles technique we measure fractal dimension of such clusters $D(N)$ as a function of their size $N$. We propose that in the thermodynamic limit of infinite cluster size the aggregates grown with high degree of anisotropy ($N_{fp}=3,4,5$) tend to have fractal dimension $D$ equal to 3/2, while off-lattice aggregates and aggregates with lower anisotropy ($N_{fp}>6$) have $D \approx 1.710$. Noise-reduction procedure results in the change of universality class for DLA. For high enough noise-reduction value clusters with $N_{fp} \ge 6$ have fractal dimension going to $3/2$ when $N\rightarrow\infty$.Comment: 6 pages, 8 figures, conference CCP201

Selecting a single orientation for millimeter sized graphene sheets

We have used Low Energy Electron Microscopy (LEEM) and Photo Emission Electron Microscopy (PEEM) to study and improve the quality of graphene films grown on Ir(111) using chemical vapor deposition (CVD). CVD at elevated temperature already yields graphene sheets that are uniform and of monatomic thickness. Besides domains that are aligned with respect to the substrate, other rotational variants grow. Cyclic growth exploiting the faster growth and etch rates of the rotational variants, yields films that are 99 % composed of aligned domains. Precovering the substrate with a high density of graphene nuclei prior to CVD yields pure films of aligned domains extending over millimeters. Such films can be used to prepare cluster-graphene hybrid materials for catalysis or nanomagnetism and can potentially be combined with lift-off techniques to yield high-quality, graphene based electronic devices

Momentum space separation of quantum path interferences between photons and surface plasmon polaritons in nonlinear photoemission microscopy

Quantum path interferences occur whenever multiple equivalent and coherent transitions result in a common final state. Such interferences strongly modify the probability of a particle to be found in that final state, a key concept of quantum coherent control. When multiple nonlinear and energy-degenerate transitions occur in a system, the multitude of possible quantum path interferences is hard to disentangle experimentally. Here, we analyze quantum path interferences during the nonlinear emission of electrons from hybrid plasmonic and photonic fields using time-resolved photoemission electron microscopy. We experimentally distinguish quantum path interferences by exploiting the momentum difference between photons and plasmons and through balancing the relative contributions of their respective fields. Our work provides a fundamental understanding of the nonlinear photon-plasmon-electron interaction. Distinguishing emission processes in momentum space, as introduced here, will ultimately allow nano-optical quantum-correlations to be studied without destroying the quantum path interferences