The Impact of Halogenated Phenylalanine Derivatives on NFGAIL Amyloid Formation

The hexapeptide hIAPP_22–27 (NFGAIL) is known as a crucial amyloid core sequence of the human islet amyloid polypeptide (hIAPP) whose aggregates can be used to better understand the wild-type hIAPP′s toxicity to β-cell death. In amyloid research, the role of hydrophobic and aromatic-aromatic interactions as potential driving forces during the aggregation process is controversially discussed not only in case of NFGAIL, but also for amyloidogenic peptides in general. We have used halogenation of the aromatic residue as a strategy to modulate hydrophobic and aromatic-aromatic interactions and prepared a library of NFGAIL variants containing fluorinated and iodinated phenylalanine analogues. We used thioflavin T staining, transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) to study the impact of side-chain halogenation on NFGAIL amyloid formation kinetics. Our data revealed a synergy between aggregation behavior and hydrophobicity of the phenylalanine residue. This study introduces systematic fluorination as a toolbox to further investigate the nature of the amyloid self-assembly process.     

Comparison of direct and alternating current vacuum ultraviolet lamps in atmospheric pressure photoionization

A direct current induced vacuum ultraviolet (dc-VUV) krypton discharge lamp and an alternating current, radio frequency (rf) induced VUV lamp that are essentially similar to lamps in commercial atmospheric pressure photoionization (APPI) ion sources were compared. The emission distributions along the diameter of the lamp exit window were measured, and they showed that the beam of the rf lamp is much wider than that of the dc lamp. Thus, the rf lamp has larger efficient ionization area, and it also emits more photons than the dc lamp. The ionization efficiencies of the lamps were compared using identical spray geometries with both lamps in microchip APPI mass spectrometry (μAPPI-MS) and desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS). A comprehensive view on the ionization was gained by studying six different μAPPI solvent compositions, five DAPPI spray solvents, and completely solvent-free DAPPI. The observed reactant ions for each solvent composition were very similar with both lamps except for toluene, which showed a higher amount of solvent originating oxidation products with the rf lamp than with the dc lamp in μAPPI. Moreover, the same analyte ions were detected with both lamps, and thus, the ionization mechanisms with both lamps are similar. The rf lamp showed a higher ionization efficiency than the dc lamp in all experiments. The difference between the lamp ionization efficiencies was greatest when high ionization energy (IE) solvent compositions (IEs above 10 eV), i.e., hexane, methanol, and methanol/water, (1:1 v:v) were used. The higher ionization efficiency of the rf lamp is likely due to the larger area of high intensity light emission, and the resulting larger efficient ionization area and higher amount of photons emitted. These result in higher solvent reactant ion production, which in turn enables more efficient analyte ion production.     

Electroless synthesis of 3 nm wide alloy nanowires inside Tobacco mosaic virus

We show that 3 nm wide cobalt-iron alloy nanowires can be synthesized by simple wet chemical electroless deposition inside tubular Tobacco mosaic virus particles. The method is based on adsorption of Pd(II) ions, formation of a Pd catalyst, and autocatalytic deposition of the alloy from dissolved metal salts, reduced by a borane compound. Extensive energy-filtering TEM investigations at the nanoscale revealed that the synthesized wires are alloys of Co, Fe, and Ni. We confirmed by high-resolution TEM that our alloy nanowires are at least partially crystalline, which is compatible with typical Co-rich alloys. Ni traces bestow higher stability, presumably against corrosion, as also known from bulk CoFe. Alloy nanowires, as small as the ones presented here, might be used for a variety of applications including high density data storage, imaging, sensing, and even drug delivery.     

Aqueous solubility diagrams for cementitious waste stabilization systems. 3. Mechanism of zinc immobilizaton by calcium silicate hydrate

Zinc oxide was added during hydration of alite (C3S) as an analogue for solidification/stabilization by cement of metal-bearing hazardous waste. Curing of samples was stopped at various intervals between 8 h and 100 d, and the reaction products were analyzed by both X-ray diffraction (XRD) and X-ray absorption spectroscopy (EXAFS at Zn, Ca, and Si K-edges). Calcium zincate hydrate (CaZn2(OH)6 x 2H2O) initially formed together with calcium silicate hydrate (CSH) vanishes from X-ray diffractograms after 14 d, and no other crystalline Zn-bearing phase could be detected thereafter. EXAFS Zn K-edge data analysis reveals that Zn(O,OH)4 tetrahedra continue to determine the first shell coordination. However, a new Zn-Si bond appears in the second coordination shell as indicated by both Zn K-edge and Si K-edge EXAFS. Together with the Ca-Zn and Ca-Ca shells derived from the Ca K-edge EXAFS spectra, a structural model for the site occupation of Zn in CSH is proposed, whereby the Zn(O,OH)4 tetrahedra are bound in layer rather than interlayer positions substituting for the silicate bridging tetrahedra and/or at terminal silicate chain sites. This structural model enables ultimately the formulation of a thermodyamic Lippmann model to predict the aqueous solubility of Zn in solid solution with a CSH phase of a Ca/Si ratio fixed to unity.     

Carboxy terminal variants of Epstein-Barr virus-encoded latent membrane protein 1 during long-term human immunodeficiency virus infection: reliable markers for individual strain identification

To assess the frequency and molecular polymorphism of malignancy-associated latent membrane protein 1 (LMP1) variants in human immunodeficiency virus type 1 (HIV-1) infection, 94 B-lymphoblastoid cell lines spontaneously derived from peripheral blood mononuclear cells (PBMC) and 30 PBMC samples at seroconversion and later (mean, 55 months) were analyzed by longitudinal comparative sequence analysis in 8 patients progressing to non-Hodgkin's lymphoma (AIDS-NHL), 7 patients to opportunistic infections, and 2 patients with long-term asymptomatic HIV-1 infection. The sequence polymorphism in the C-terminus of LMP1 was characteristic for strains harbored by individual patients, with high fidelity for strain identification. In 14 of the 17 patients, two different but characteristic LMP1 variants were identified. At HIV seroconversion in 8 of 15 patients, a 30-bp deletion (LMP1Delta) was present. Though serial analysis revealed a shift to LMP1Delta in some individuals, statistical analysis of the cohort does not support the hypothesis that accumulation of LMP1Delta variants in PBMC accounts for their observed high incidence in AIDS-NHL.     

Propofol, but not thiopentone or etomidate, enhances isoflurane-induced coronary vasodilatation in dogs

PURPOSE: To test the hypothesis that thiopentone, propofol, and etomidate alter the coronary vascular effects of abruptly administered isoflurane. METHODS: Dogs (n = 6) received inspired isoflurane 5% in the presence of thiopentone (20 mg.kg-1 induction dose and 20 mg.kg-1.hr-1 infusion), propofol (5 mg.kg-1 induction dose and 40 mg.kg-1.hr-1 infusion), etomidate (2 mg.kg-1 induction dose and 5 mg.kg-1.hr-1 infusion), or isoflurane (1.0 MAC) anaesthesia in a random fashion. Haemodynamics were assessed in the conscious state, during baseline anaesthesia, and at 30 sec intervals for five minutes after beginning isoflurane 5%. RESULTS: Rapidly administered isoflurane caused greater (P < 0.05) reductions in coronary vascular resistance in thiopentone- or propofol--than in isoflurane-anaesthetized dogs. Isoflurane produced greater (P < 0.05) increases in the ratio of coronary blood flow velocity to pressure-work index (an index of myocardial oxygen consumption; +109 +/- 19% during isoflurane alone vs +182 +/- 27% change from baseline during propofol and isoflurane) consistent with relatively greater direct coronary vasodilatation during baseline propofol than during baseline isoflurane anaesthesia. Isoflurane caused larger increases in coronary blood flow velocity in dogs anaesthetized with etomidate concomitant with higher coronary perfusion pressure and pressure-work index than in those anaesthetized with isoflurane alone. CONCLUSIONS: The results suggest that thiopentone, propofol, and etomidate each uniquely modify the coronary vascular responses to abrupt administration of high inspired concentrations of isoflurane in chronically instrumented dogs.     

Fallbeispiel Kluftgrundwasserleiter – Charakterisierung eines Grundwasserleiters im Rotliegendsandstein des Saar-Nahe-Beckens

Grundwasser - Das vorliegende Fallbeispiel führt unterschiedliche Feld- und Labormethoden zusammen und zeigt, wie für einen Standort in einem Kluftgrundwasserleiter die Kombination...