Lighting Up the Plasma Membrane: Development and Applications of Fluorescent Ligands for Transmembrane Proteins

Despite the fact that transmembrane proteins represent the main therapeutic targets for decades, complete and in-depth knowledge about their biochemical and pharmacological profiling is not fully available. In this regard, target-tailored small-molecule fluorescent ligands are a viable approach to fill in the missing pieces of the puzzle. Such tools, coupled with the ability of high-precision optical techniques to image with an unprecedented resolution at a single-molecule level, helped unraveling many of the conundrums related to plasma proteins’ life-cycle and druggability. Herein, we review the recent progress made during the last two decades in fluorescent ligand design and potential applications in fluorescence microscopy of voltage-gated ion channels, ligand-gated ion channels and G-coupled protein receptors.     

Neutral-pion photoproduction off protons in the energy range 0.3 GeV<E(gamma)<3 GeV

Single pi(0) photoproduction has been studied with the CB-ELSA experiment at Bonn using tagged photon energies between 0.3 and 3.0 GeV. The experimental setup covers a very large solid angle of approximately 98% of 4pi. Differential cross sections dsigma/dOmega have been measured. Complicated structures in the angular distributions indicate a variety of different resonances being produced in the s channel intermediate state gammap-->N(*)(Delta(*))-->ppi(0). A combined analysis including the data presented in this letter along with other data sets reveals contributions from known resonances and evidence for a new resonance N(2070)D15.     

The use of acoustoelectrochemistry to investigate rectified diffusion

This paper describes the approach to bubble related phenomena using a novel 'acoustoelectrochemical' technique designed to investigate the physical and chemical effects of the acoustically induced motion of the bubble wall. In particular it describes the behaviour of a suspended gas bubble irradiated with sound of an appropriate frequency and pressure to induce bubble wall oscillation. The first electrochemical measurement of the growth of a bubble through rectified diffusion is demonstrated. The technique employed relies on the sensitivity of a scanning electrochemical microscope (SECM) deployed close to the gas/liquid interface of a bubble. The growth rate of the bubble (<0.1 microms(-1)) is reported. It will be also demonstrated that gas exchange across the phase boundary at the bubble wall, can be successfully probed when the bubble is stationary.     

Substrate electric dipole moment exerts a pH-dependent effect on electron transfer in Escherichia coli photolyase

Transient absorption spectroscopy is used to demonstrate that the electric dipole moment of the substrate cyclobutane thymine dimer affects the charge recombination reaction between fully reduced flavin adenine dinucleotide (FADH-) and the neutral radical tryptophan 306 (Trp306*) in Escherichia coli DNA photolyase. At pH 7.4, the charge recombination is slowed by a factor of 1.75 in the presence of substrate, but not at pH 5.4. Photolyase does bind substrate at pH 5.4, and it seems that this pH effect originates from the conversion of FADH- to FADH2 at lower pH. The free-energy changes calculated from the electric field parameters and from the change in electron transfer rate are in good agreement and support the idea that the substrate electric dipole is responsible for the observed change in electron transfer rate. It is expected that the substrate electric field will also modify the physiologically important from excited 1FADH- to the substrate in the DNA repair reaction.     

Neuronal expression of muskelin in the rodent central nervous system

Background  

The kelch repeat protein muskelin mediates cytoskeletal responses to the extracellular matrix protein thrombospondin 1, (TSP1), that is known to promote synaptogenesis in the central nervous system (CNS). Muskelin displays intracellular localization and affects cytoskeletal organization in adherent cells. Muskelin is expressed in adult brain and has been reported to bind the Cdk5 activator p39, which also facilitates the formation of functional synapses. Since little is known about muskelin in neuronal tissues, we here analysed the tissue distribution of muskelin in rodent brain and analysed its subcellular localization using cultured neurons from multiple life stages.     

Multivariable structural characterization of semicrystalline polymer blends by small‐angle light scattering

A new multi‐variable‐measurement approach for characterizing and correlating the nanoscale and microscale morphology of crystal‐amorphous polymer blends with melt‐phase behavior is described. A vertical small‐angle light scattering (SALS) instrument optimized for examining the scattering and light transmitted from structures ranging from 0.5 to 50 μm, thereby spanning the size range characteristic of the initial‐to‐late stages of thermal‐phase transitions (e.g., melt‐phase separation and crystallization) in crystal‐amorphous polymer blends, was constructed. The SALS instrument was interfaced with differential scanning calorimetry (DSC), and simultaneous SALS/DSC/transmission measurements were performed. We show that the measurement of transmitted light and SALS under H_V (cross‐polarized) optical alignments during melting can be used to reliably measure the thermodynamic (e.g., crystal melting and melt‐phase separation temperatures) and structural variables (e.g., crystalline fraction within the superstructures and volume fraction of superstructures) necessary for describing the multiphase behavior of crystal‐amorphous blends in one combined measurement. We also evaluate the orientation correlations of crystalline volume elements within the superstructures. Our results indicate that simultaneous measurement of transmitted light can provide a reliable estimate of the total scattering from density and orientation fluctuations and the melt‐phase separation temperature of polymer blends. For solution‐cast poly(?‐caprolactone)/poly(D,L‐lactic acid) blends, our multivariable measurements during melting provide the parameters necessary to generate a crystal–liquid and liquid–liquid phase diagram and characterize the solid‐state morphology. This opens up the challenge to explore use of our vertical SALS instrument as a rapid and convenient method for developing structure–property relationships for crystal‐amorphous polymer blends. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 2714–2727, 2002     

A new material for hydrogen storage; ScAl0.8Mg0.2

A novel aluminium rich alloy for hydrogen storage has been discovered, ScAl_0.8Mg_0.2, which has very promising properties regarding hydrogen storage capacity, kinetics and stability towards air oxidation in comparison to hydrogen absorption in state-of-the-art intermetallic compounds. The absorption of hydrogen was found to be very fast, even without adding any catalyst, and reversible. The discovered alloy crystallizes in a CsCl-type structure, but decomposes to ScH₂ and Al(Mg) during hydrogen absorption. Detailed analysis of the hydrogen absorption in ScAl_0.8Mg_0.2 has been performed using in situ synchrotron radiation powder X-ray diffraction, neutron powder diffraction and quantum mechanical calculations. The results from theory and experiments are in good agreement with each other.     

Untersuchung von Honig und Honigkuchen

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