Mechanisms of Peptide Oxidation by Hydroxyl Radicals: Insight at the Molecular Scale

Molecular dynamics (MD) simulations were performed to provide atomic scale insight in the initial interaction between hydroxyl radicals (OH) and peptide systems in solution. These OH radicals are representative reactive oxygen species produced by cold atmospheric plasmas. The use of plasma for biomedical applications is gaining increasing interest, but the fundamental mechanisms behind the plasma modifications still remain largely elusive. This study helps to gain more insight in the underlying mechanisms of plasma medicine but is also more generally applicable to peptide oxidation, of interest for other applications. Combining both reactive and nonreactive MD simulations, we are able to elucidate the reactivity of the amino acids inside the peptide systems and their effect on their structure up to 1 μs. Additionally, experiments were performed, treating the simulated peptides with a plasma jet. The computational results presented here correlate well with the obtained experimental data and highlight the importance of the chemical environment for the reactivity of the individual amino acids, so that specific amino acids are attacked in higher numbers than expected. Furthermore, the long time scale simulations suggest that a single oxidation has an effect on the 3D conformation due to an increase in hydrophilicity and intra- and intermolecular interactions

Effects of Detergent on α-Synuclein Structure: A Native MS-Ion Mobility Study

The intrinsically disordered protein α-synuclein plays a major role in Parkinson’s disease. The protein can oligomerize resulting in the formation of various aggregated species in neuronal cells, leading to neurodegeneration. The interaction of α-synuclein with biological cell membranes plays an important role for specific functions of α-synuclein monomers, e.g., in neurotransmitter release. Using different types of detergents to mimic lipid molecules present in biological membranes, including the presence of Ca2+ ions as an important structural factor, we aimed to gain an understanding of how α-synuclein interacts with membrane models and how this affects the protein conformation and potential oligomerization. We investigated detergent binding stoichiometry, affinity and conformational changes of α-synuclein taking detergent concentration, different detergent structures and charges into account. With native nano-electrospray ionization ion mobility-mass spectrometry, we were able to detect unique conformational patterns resulting from binding of specific detergents to α-synuclein. Our data demonstrate that α-synuclein monomers can interact with detergent molecules irrespective of their charge, that protein-micelle interactions occur and that micelle properties are an important factor

Combining density functional theory (DFT) and collision cross-section (CCS) calculations to analyze the gas-phase behaviour of small molecules and their protonation site isomers

Electrospray ion mobility-mass spectrometry (IM-MS) data show that for some small molecules, two (or even more) ions with identical sum formula and mass, but distinct drift times are observed. In spite of showing their own unique and characteristic fragmentation spectra in MS/MS, no configurational or constitutional isomers are found to be present in solution. Instead the observation and separation of such ions appears to be inherent to their gas-phase behaviour during ion mobility experiments. The origin of multiple drift times is thought to be the result of protonation site isomers ('protomers'). Although some important properties of protomers have been highlighted by other studies, correlating the experimental collision cross-sections (CCSs) with calculated values has proven to be a major difficulty. As a model, this study uses the pharmaceutical compound melphalan and a number of related molecules with alternative (gas-phase) protonation sites. Our study combines density functional theory (DFT) calculations with modified MobCal methods (e.g. nitrogen-based Trajectory Method algorithm) for the calculation of theoretical CCS values. Calculated structures can be linked to experimentally observed signals, and a strong correlation is found between the difference of the calculated dipole moments of the protomer pairs and their experimental CCS separation

Measurement of double beta decay of ¹⁰⁰Mo to excited states in the NEMO 3 experiment

The double beta decay of ¹⁰⁰Mo to the 0_{1}^{+} and 2_{1}^{+} excited states of ¹⁰⁰Ru is studied using the NEMO 3 data. After the analysis of 8024 h of data the half-life for the two-neutrino double beta decay of ¹⁰⁰Mo to the excited 0_{1}^{+} state is measured to be T_{1/2}^{2v} = [5.7_{-0.9}^{+1.3} (stat.) ± 0.8 (syst.)] x 10²⁰ y. The signal-to-background ratio is equal to 3. Information about energy and angular distributions of emitted electrons is also obtained. No evidence for neutrinoless double beta decay to the excited 0_{1}^{+} state has been found. The corresponding half-life limit is T_{1/2}^{0v} (0⁺→0_{1}^{+}) > 8.9 x 10²² y (at 90% C.L.). The search for the double beta decay to the 2_{1}^{+} excited state has allowed the determination of limits on the half-life for the two neutrino mode T_{1/2}^{0v} (0⁺→2_{1}^{+}) > 1.1 x 10²¹ y (at 90% C.L.) and for the neutrinoless mode T_{1/2}^{0v} (0⁺→2_{1}^{+}) > 1.6 x 10²³ y (at 90% C.L.)

Measurement of double beta decay of 100Mo to excited states in the NEMO 3 experiment

The double beta decay of 100Mo to the 0^+_1 and 2^+_1 excited states of 100Ru is studied using the NEMO 3 data. After the analysis of 8024 h of data the half-life for the two-neutrino double beta decay of 100Mo to the excited 0^+_1 state is measured to be T^(2nu)_1/2 = [5.7^{+1.3}_{-0.9}(stat)+/-0.8(syst)]x 10^20 y. The signal-to-background ratio is equal to 3. Information about energy and angular distributions of emitted electrons is also obtained. No evidence for neutrinoless double beta decay to the excited 0^+_1 state has been found. The corresponding half-life limit is T^(0nu)_1/2(0^+ --> 0^+_1) > 8.9 x 10^22 y (at 90% C.L.). The search for the double beta decay to the 2^+_1 excited state has allowed the determination of limits on the half-life for the two neutrino mode T^(2nu)_1/2(0^+ --> 2^+_1) > 1.1 x 10^21 y (at 90% C.L.) and for the neutrinoless mode T^(0nu)_1/2(0^+ --> 2^+_1) > 1.6 x 10^23 y (at 90% C.L.).Comment: 23 pages, 7 figures, 4 tables, submitted to Nucl. Phy

Results of the BiPo-1 prototype for radiopurity measurements for the SuperNEMO double beta decay source foils

The development of BiPo detectors is dedicated to the measurement of extremely high radiopurity in $^{208}$Tl and $^{214}$Bi for the SuperNEMO double beta decay source foils. A modular prototype, called BiPo-1, with 0.8 $m^2$ of sensitive surface area, has been running in the Modane Underground Laboratory since February, 2008. The goal of BiPo-1 is to measure the different components of the background and in particular the surface radiopurity of the plastic scintillators that make up the detector. The first phase of data collection has been dedicated to the measurement of the radiopurity in $^{208}$Tl. After more than one year of background measurement, a surface activity of the scintillators of $\mathcal{A}$($^{208}$Tl) $=$ 1.5 $\mu$Bq/m$^2$ is reported here. Given this level of background, a larger BiPo detector having 12 m$^2$ of active surface area, is able to qualify the radiopurity of the SuperNEMO selenium double beta decay foils with the required sensitivity of $\mathcal{A}$($^{208}$Tl) $<$ 2 $\mu$Bq/kg (90% C.L.) with a six month measurement.Comment: 24 pages, submitted to N.I.M.

Spectral modeling of scintillator for the NEMO-3 and SuperNEMO detectors

We have constructed a GEANT4-based detailed software model of photon transport in plastic scintillator blocks and have used it to study the NEMO-3 and SuperNEMO calorimeters employed in experiments designed to search for neutrinoless double beta decay. We compare our simulations to measurements using conversion electrons from a calibration source of $\rm ^{207}Bi$ and show that the agreement is improved if wavelength-dependent properties of the calorimeter are taken into account. In this article, we briefly describe our modeling approach and results of our studies.Comment: 16 pages, 10 figure

Revised experimental upper limit on the electric dipole moment of the neutron

We present for the first time a detailed and comprehensive analysis of the experimental results that set the current world sensitivity limit on the magnitude of the electric dipole moment (EDM) of the neutron. We have extended and enhanced our earlier analysis to include recent developments in the understanding of the effects of gravity in depolarizing ultracold neutrons; an improved calculation of the spectrum of the neutrons; and conservative estimates of other possible systematic errors, which are also shown to be consistent with more recent measurements undertaken with the apparatus. We obtain a net result of dn=−0.21±1.82×10−26  e cm, which may be interpreted as a slightly revised upper limit on the magnitude of the EDM of 3.0×10−26  e cm (90% C.L.) or 3.6×10−26  e cm (95% C.L.)

Gravitational depolarization of ultracold neutrons: comparison with data

We compare the expected effects of so-called gravitationally enhanced depolarization of ultracold neutrons to measurements carried out in a spin-precession chamber exposed to a variety of vertical magnetic-field gradients. In particular, we have investigated the dependence upon these field gradients of spin-depolarization rates and also of shifts in the measured neutron Larmor precession frequency. We find excellent qualitative agreement, with gravitationally enhanced depolarization accounting for several previously unexplained features in the data

First detection of a VHE gamma-ray spectral maximum from a Cosmic source: H.E.S.S. discovery of the Vela X nebula

The Vela supernova remnant (SNR) is a complex region containing a number of sources of non-thermal radiation. The inner section of this SNR, within 2 degrees of the pulsar PSR B0833-45, has been observed by the H.E.S.S. gamma-ray atmospheric Cherenkov detector in 2004 and 2005. A strong signal is seen from an extended region to the south of the pulsar, within an integration region of radius 0.8 deg. around the position (RA = 08h 35m 00s, dec = -45 deg. 36' J2000.0). The excess coincides with a region of hard X-ray emission seen by the ROSAT and ASCA satellites. The observed energy spectrum of the source between 550 GeV and 65 TeV is well fit by a power law function with photon index = 1.45 +/- 0.09(stat) +/- 0.2(sys) and an exponential cutoff at an energy of 13.8 +/- 2.3(stat) +/- 4.1(sys) TeV. The integral flux above 1 TeV is (1.28 +/- 0.17 (stat) +/- 0.38(sys)) x 10^{-11} cm^{-2} s^{-1}. This result is the first clear measurement of a peak in the spectral energy distribution from a VHE gamma-ray source, likely related to inverse Compton emission. A fit of an Inverse Compton model to the H.E.S.S. spectral energy distribution gives a total energy in non-thermal electrons of ~2 x 10^{45} erg between 5 TeV and 100 TeV, assuming a distance of 290 parsec to the pulsar. The best fit electron power law index is 2.0, with a spectral break at 67 TeV.Comment: 5 pages, 4 figures, accepted for publication in Astronomy and Astrophysics letter