H2O2-mediated modulation of cytosolic signaling and organelle function in rat hippocampus

Reactive oxygen species (ROS) released from (dys-)functioning mitochondria contribute to normal and pathophysiological cellular signaling by modulating cytosolic redox state and redox-sensitive proteins. To identify putative redox targets involved in such signaling, we exposed hippocampal neurons to hydrogen peroxide (H2O2). Redox-sensitive dyes indicated that externally applied H2O2 may oxidize intracellular targets in cell cultures and acute tissue slices. In cultured neurons, H2O2 (EC50 118 µM) induced an intracellular Ca2+ rise which could still be evoked upon Ca2+ withdrawal and mitochondrial uncoupling. It was, however, antagonized by thapsigargin, dantrolene, 2-aminoethoxydiphenyl borate, and high levels of ryanodine, which identifies the endoplasmic reticulum (ER) as the intracellular Ca2+ store involved. Intracellular accumulation of endogenously generated H2O2—provoked by inhibiting glutathione peroxidase—also released Ca2+ from the ER, as did extracellular generation of superoxide. Phospholipase C (PLC)-mediated metabotropic signaling was depressed in the presence of H2O2, but cytosolic cyclic adenosine-5′-monophosphate (cAMP) levels were not affected. H2O2 (0.2–5 mM) moderately depolarized mitochondria, halted their intracellular trafficking in a Ca2+- and cAMP-independent manner, and directly oxidized cellular nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2). In part, the mitochondrial depolarization reflects uptake of Ca2+ previously released from the ER. We conclude that H2O2 releases Ca2+ from the ER via both ryanodine and inositol trisphosphate receptors. Mitochondrial function is not markedly impaired even by millimolar concentrations of H2O2. Such modulation of Ca2+ signaling and organelle interaction by ROS affects the efficacy of PLC-mediated metabotropic signaling and may contribute to the adjustment of neuronal function to redox conditions and metabolic supply

Tailoring the Antibody Response to Aggregated Aß Using Novel Alzheimer-Vaccines

Recent evidence suggests Alzheimer-Disease (AD) to be driven by aggregated Aß. Capitalizing on the mechanism of molecular mimicry and applying several selection layers, we screened peptide libraries for moieties inducing antibodies selectively reacting with Aß-aggregates. The technology identified a pool of peptide candidates; two, AFFITOPES AD01 and AD02, were assessed as vaccination antigens and compared to Aβ1-6, the targeted epitope. When conjugated to Keyhole Limpet Hemocyanin (KLH) and adjuvanted with aluminum, all three peptides induced Aß-targeting antibodies (Abs). In contrast to Aß1-6, AD01- or AD02-induced Abs were characterized by selectivity for aggregated forms of Aß and absence of reactivity with related molecules such as Amyloid Precursor Protein (APP)/ secreted APP-alpha (sAPPa). Administration of AFFITOPE-vaccines to APP-transgenic mice was found to reduce their cerebral amyloid burden, the associated neuropathological alterations and to improve their cognitive functions. Thus, the AFFITOME-technology delivers vaccines capable of inducing a distinct Ab response. Their features may be beneficial to AD-patients, a hypothesis currently tested within a phase-II-study

Towards Biochar and Hydrochar Engineering—Influence of Process Conditions on Surface Physical and Chemical Properties, Thermal Stability, Nutrient Availability, Toxicity and Wettability

The impact of conversion process parameters in pyrolysis (maximum temperature, inert gas flow rate) and hydrothermal carbonization (maximum temperature, residence time and post-washing) on biochar and hydrochar properties is investigated. Pine wood (PW) and corn digestate (CD), with low and high inorganic species content respectively, are used as feedstock. CD biochars show lower H/C ratios, thermal recalcitrance and total specific surface area than PW biochars, but higher mesoporosity. CD and PW biochars present higher naphthalene and phenanthrene contents, respectively, which may indicate different reaction pathways. High temperatures (>500 °C) lead to lower PAH (polycyclic aromatic hydrocarbons) content (<12 mg/kg) and higher specific surface area. With increasing process severity the biochars carbon content is also enhanced, as well as the thermal stability. High inert gas flow rates increase the microporosity and wettability of biochars. In hydrochars the high inorganic content favor decarboxylation over dehydration reactions. Hydrochars show mainly mesoporosity, with a higher pore volume but generally lower specific surface area than biochars. Biochars present negligible availability of NO −3 and NH +4 , irrespective of the nitrogen content of the feedstock. For hydrochars, a potential increase in availability of NO −3 , NH +4 , PO 3−4 , and K + with respect to the feedstock is possible. The results from this work can be applied to “engineer” appropriate biochars with respect to soil demands and certification requirements

Water activity in liquid food systems : A molecular scale interpretation

Water activity has historically been and continues to be recognised as a key concept in the area of food science. Despite its ubiquitous utilisation, it still appears as though there is confusion concerning its molecular basis, even within simple, single component solutions. Here, by close examination of the well-known Norrish equation and subsequent application of a rigorous statistical theory, we are able to shed light on such an origin. Our findings highlight the importance of solute-solute interactions thus questioning traditional, empirically based “free water” and “water structure” hypotheses. Conversely, they support the theory of “solute hydration and clustering” which advocates the interplay of solute-solute and solute-water interactions but crucially, they do so in a manner which is free of any estimations and approximations

Measurement of the Beam Asymmetry Σ\Sigma in the Forward Direction for pi0 Photoproduction

Photoproduction of neutral pions has been studied with the CBELSA/TAPS detector for photon energies between 0.92 and 1.68~GeV at the electron accelerator ELSA. The beam asymmetry~$\Sigma$ has been extracted for $115^\circ < \theta_{\rm c.m.} < 155^\circ$ of the $\pi^0$~meson and for $\theta_{\rm c.m.} < 60^\circ$. The new beam asymmetry data improve the world database for photon energies above 1.5~GeV and, by covering the very forward region, extend previously published data for the same reaction by our collaboration. The angular dependence of $\Sigma$ shows overall good agreement with the SAID parameterization.Comment: 11 pages, 10 figures, published in Phys. Rev. C, included LEPS data and MAID 2007 predictions for comparison with our dat

Measurement of polarisation observables in Ks0Σ+K^0_s\Sigma^+ photoproduction off the proton

The reaction $\gamma \, p \rightarrow K^0_S\,\Sigma^+$ is studied in the photon energy range from threshold. Linearly polarised photon beams from coherent bremsstrahlung enabled the first measurement of photon beam asymmetries in this reaction up to $E_\gamma = 2250$ MeV. In addition, the recoil hyperon polarisation was determined through the asymmetry in the weak decay $\Sigma^+ \rightarrow p \pi^0$ up to $E_\gamma = 1650$ MeV. The data are compared to partial wave analyses, and the possible impact on the interpretation of a recently observed cusp-like structure near the $K^*$ thresholds is discussed.Comment: 6 pages, 5 figures. References [8,9,10,11] which were not on the original submission are now include

Photoproduction of Neutral Pions off Protons

Photoproduction of neutral pions has been studied with the CBELSA/TAPS detector in the reaction $\gamma p\to p\pi^0$ for photon energies between 0.85 and 2.50 GeV. The $\pi^0$ mesons are observed in their dominant neutral decay mode: $\pi^0\to\gamma\gamma$. For the first time, the differential cross sections cover the very forward region, $\theta_{\rm c.m.}<60^\circ$. A partial-wave analysis of these data within the Bonn-Gatchina framework observes the high-mass resonances $G_{17}$(2190), $D_{13}$(2080), and $D_{15}$(2070).Comment: 12 pages, 9 figures, minor modifications to PWA sectio

Photoproduction of {\omega} Mesons off the Proton

The differential cross sections and unpolarized spin-density matrix elements for the reaction $\gamma p\to p\omega$ were measured using the CBELSA/TAPS experiment for initial photon energies ranging from the reaction threshold to 2.5 GeV. These observables were measured from the radiative decay of the $\omega$ meson, $\omega\to\pi^0\gamma$. The cross sections cover the full angular range and show the full extent of the $t$-channel forward rise. The overall shape of the angular distributions in the differential cross sections and unpolarized spin-density matrix elements are in fair agreement with previous data. In addition, for the first time, a beam of linearly-polarized tagged photons in the energy range from 1150 MeV to 1650 MeV was used to extract polarized spin-density matrix elements. These data were included in the Bonn-Gatchina partial wave analysis (PWA). The dominant contribution to $\omega$ photoproduction near threshold was found to be the $3/2^+$ partial wave, which is primarily due to the sub-threshold $N(1720)\,3/2^+$ resonance. At higher energies, pomeron-exchange was found to dominate whereas $\pi$-exchange remained small. These $t$-channel contributions as well as further contributions from nucleon resonances were necessary to describe the entire dataset: the $1/2^-$, $3/2^-$, and $5/2^+$ partial waves were also found to contribute significantly.Comment: 8 pages, 5 figures, accepted for publication in Physics Letters