Cell cycle-dependent phosphorylation of Theileria annulata schizont surface proteins

The invasion of Theileria sporozoites into bovine leukocytes is rapidly followed by the destruction of the surrounding host cell membrane, allowing the parasite to establish its niche within the host cell cytoplasm. Theileria infection induces host cell transformation, characterised by increased host cell proliferation and invasiveness, and the activation of anti-apoptotic genes. This process is strictly dependent on the presence of a viable parasite. Several host cell kinases, including PI3-K, JNK, CK2 and Src-family kinases, are constitutively activated in Theileria-infected cells and contribute to the transformed phenotype. Although a number of host cell molecules, including IkB kinase and polo-like kinase 1 (Plk1), are recruited to the schizont surface, very little is known about the schizont molecules involved in host-parasite interactions. In this study we used immunofluorescence to detect phosphorylated threonine (p-Thr), serine (p-Ser) and threonine-proline (p-Thr-Pro) epitopes on the schizont during host cell cycle progression, revealing extensive schizont phosphorylation during host cell interphase. Furthermore, we established a quick protocol to isolate schizonts from infected macrophages following synchronisation in S-phase or mitosis, and used mass spectrometry to detect phosphorylated schizont proteins. In total, 65 phosphorylated Theileria proteins were detected, 15 of which are potentially secreted or expressed on the surface of the schizont and thus may be targets for host cell kinases. In particular, we describe the cell cycle-dependent phosphorylation of two T. annulata surface proteins, TaSP and p104, both of which are highly phosphorylated during host cell S-phase. TaSP and p104 are involved in mediating interactions between the parasite and the host cell cytoskeleton, which is crucial for the persistence of the parasite within the dividing host cell and the maintenance of the transformed state

The effects of the small t properties of hadronic scattering amplitude on the determination its real part

Taking into account the different forms of the Coulomb-hadron interference phase and the possible spin-flip contribution the new analysis of the experimental data of the proton-antiproton elastic scattering at $3.8 < p_L <6.0 \$GeV/c and small momentum transfer is carried out. It is shown that the size of the spin-flip amplitude can be determined from the form of the differential cross sections at small $t$, and the deviation of $\rho(s,t)$ obtained from the examined experimental data of the $p\bar{p}$ scattering from the analysis \cite{Kroll}, based on the dispersion relations, is conserved in all xamined assumptions. The analysis of the proton-proton elastic scattering at $9 < p_L < 70 \$GeV/c also shows the impact of the examined effects on the form of the differential cross sections.Comment: 13 pages, 3 figure

Li/MgO with spin sensors as catalyst for the oxidative coupling of methane

Co-doping of Li/MgO, a well-known catalyst for the oxidative coupling of methane, was investigated. It is demonstrated that Gd3+ and Fe3+ can be used as spin sensors in these solids to investigate the structure via EPR spectroscopy. These aliovalent ions occupy Mg2+ sites in the lattice; the expected coupling with charge-compensating neighboring Li+ was detected. A strong increase of the activity was observed. However, all samples suffered from deactivation. The solubility of Gd3+ in MgO turned out to be inhibited. No such restriction was observed for Fe3+

Evidence for electronically-driven ferroelectricity in the family of strongly correlated dimerized BEDT-TTF molecular conductors

By applying measurements of the dielectric constants and relative length changes to the dimerized molecular conductor $\kappa$-(BEDT-TTF)$_2$Hg(SCN)$_2$Cl, we provide evidence for order-disorder type electronic ferroelectricity which is driven by charge order within the (BEDT-TTF)$_2$ dimers and stabilized by a coupling to the anions. According to our density functional theory calculations, this material is characterized by a moderate strength of dimerization. This system thus bridges the gap between strongly dimerized materials, often approximated as dimer-Mott systems at 1/2 filling, and non- or weakly dimerized systems at 1/4 filling exhibiting charge order. Our results indicate that intra-dimer charge degrees of freedom are of particular importance in correlated $\kappa$-(BEDT-TTF)$_2$X salts and can create novel states, such as electronically-driven multiferroicity or charge-order-induced quasi-1D spin liquids.Comment: 6 pages, 4 figures + Supplementary Information (8 pages, 8 figures

The MGDO software library for data analysis in Ge neutrinoless double-beta decay experiments

The GERDA and Majorana experiments will search for neutrinoless double-beta decay of germanium-76 using isotopically enriched high-purity germanium detectors. Although the experiments differ in conceptual design, they share many aspects in common, and in particular will employ similar data analysis techniques. The collaborations are jointly developing a C++ software library, MGDO, which contains a set of data objects and interfaces to encapsulate, store and manage physical quantities of interest, such as waveforms and high-purity germanium detector geometries. These data objects define a common format for persistent data, whether it is generated by Monte Carlo simulations or an experimental apparatus, to reduce code duplication and to ease the exchange of information between detector systems. MGDO also includes general-purpose analysis tools that can be used for the processing of measured or simulated digital signals. The MGDO design is based on the Object-Oriented programming paradigm and is very flexible, allowing for easy extension and customization of the components. The tools provided by the MGDO libraries are used by both GERDA and Majorana.Comment: 4 pages, 1 figure, proceedings for TAUP201

Safety, tolerability, and impact on allergic inflammation of autologous E.coli autovaccine in the treatment of house dust mite asthma - a prospective open clinical trial

Background: Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. Methods: Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. Results: Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p=0.334) compared to initial values (from 32.6 to 42.2 ppb; p=0.046) (p=0.034). In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, B-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. Conclusion: The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. EudraCT Nr. 2005-005534-12 ClinicalTrials.gov ID NCT0067720

Myrtucommulone from Myrtus communis: metabolism, permeability, and systemic exposure in rats

Nonsteroidal anti-inflammatory drug intake is associated with a high prevalence of gastrointestinal side effects, and severe cardiovascular adverse reactions challenged the initial enthusiasm in cyclooxygenase-2 inhibitors. Recently, it was shown that myrtucommulone, the active ingredient of the Mediterranean shrub Myrtus communis, dually and potently inhibits microsomal prostaglandin E₂ synthase-1 and 5-lipoxygenase, suggesting a substantial anti-inflammatory potential. However, one of the most important prerequisites for the anti-inflammatory effects in vivo is sufficient bioavailability of myrtucommulone. Therefore, the present study was aimed to determine the permeability and metabolic stability in vitro as well as the systemic exposure of myrtucommulone in rats. Permeation studies in the Caco-2 model revealed apparent permeability coefficient values of 35.9 · 10⁻⁶ cm/s at 37 °C in the apical to basolateral direction, indicating a high absorption of myrtucommulone. In a pilot rat study, average plasma levels of 258.67 ng/mL were reached 1 h after oral administration of 4 mg/kg myrtucommulone. We found that myrtucommulone undergoes extensive phase I metabolism in human and rat liver microsomes, yielding hydroxylated and bihydroxylated as well as demethylated metabolites. Physiologically-based pharmacokinetic modeling of myrtucommulone in the rat revealed rapid and extensive distribution of myrtucommulone in target tissues including plasma, skin, muscle, and brain. As the development of selective microsomal prostaglandin E₂ synthase-1 inhibitors represents an interesting alternative strategy to traditional nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for the treatment of chronic inflammation, the present study encourages further detailed pharmacokinetic investigations on myrtucommulone