A Toxoplasma gondii Oxopurine Transporter Binds Nucleobases and Nucleosides Using Different Binding Modes

Toxoplasma gondii is unable to synthesize purines de novo, instead salvages them from its environment, inside the host cell, for which they need high affinity carriers. Here, we report the expression of a T. gondii Equilibrative Nucleoside Transporter, Tg244440, in a Trypanosoma brucei strain from which nucleobase transporters have been deleted. Tg244440 transported hypoxanthine and guanine with similar affinity (K_m ~1 µM), while inosine and guanosine displayed K_i values of 4.05 and 3.30 µM, respectively. Low affinity was observed for adenosine, adenine, and pyrimidines, classifying Tg244440 as a high affinity oxopurine transporter. Purine analogues were used to probe the substrate-transporter binding interactions, culminating in quantitative models showing different binding modes for oxopurine bases, oxopurine nucleosides, and adenosine. Hypoxanthine and guanine interacted through protonated N1 and N9, and through unprotonated N3 and N7 of the purine ring, whereas inosine and guanosine mostly employed the ribose hydroxy groups for binding, in addition to N1H of the nucleobase. Conversely, the ribose moiety of adenosine barely made any contribution to binding. Tg244440 is the first gene identified to encode a high affinity oxopurine transporter in T. gondii and, to the best of our knowledge, the first purine transporter to employ different binding modes for nucleosides and nucleobases.     

Zur Reaktion der N-Sulfinylamine mit Isocyaniden und die Synthese von 2,5-Diaryl-3,4-diarylimino-1,2,5-thiadiazolidin-S-oxiden

The Reaction of N-Sulfinylamines with Isocyanides and Synthesis of 2,5-Diaryl-3,4-diarylimino-1,2,5-thiadiazolidin-S-oxides N-Sulfinylamines 1 react with isocyanides 2 to give isocyanates 3 , isothiocyanates 6 , and especially 2,5-diaryl-3,4-diarylimino-1,2,5-thiadiazolidin-S-oxides 7 . This new heterocyclic ring system 7 can also be synthesized in high yields by a cyclization reaction of tetraarylated oxalic amidines 9 with thionyl chloride. The acid catalyzed hydrolysis of the heterocyclic compounds 7 leads to oxalic anilides 8 , the hydrolysis with alkali forms amidines 9 . The amidine 9a reacts with N-sulfinyl-p-toluenesulfonamide 11 to give an open chained adduct 12 .     

Development of gluten-free fresh egg pasta based on oat and teff flour

Due to increased awareness of consumers about the relationship between food and health as well as the requirements of people following a gluten-free diet, the production of cereal products from raw materials other than wheat is of interest. However, the elimination of the visco-elastic gluten protein represents a technological challenge. During this study, response surface methodology was applied to determine optimal formulations for the production of egg pasta from oat and teff flour. Wheat flour was used as a control. The resulting products were characterised regarding firmness and elasticity, stickiness and cooking loss. The results showed that the mechanical texture of oat and teff pasta was comparable to wheat pasta, however, elasticity was significantly reduced. Compositional analysis was carried out on flour raw materials as well as on the final pasta products, showing that regarding fibre and mineral content, oat and teff samples are nutritionally superior to wheat. In addition, the microstructure was investigated by means of scanning electron microscopy, allowing also the observation of structural changes occurring during cooking. Upon cooking, a distinct outer layer can be observed, resulting from protein denaturation and starch gelatinisation. This structural feature is clearly visible for cooked wheat pasta and but is less apparent for teff and oat pasta.     

Analytical and Numerical Calculation of the Energy Release Rate for the Microbond-Test

The energy release rate for interface crack propagation for the Microbond-Test specimen is calculated by using several stress analysis methods. For the corresponding finite element calculation an axisymmetrical model (elliptical droplet) and linear elastic material properties are used. The analytical approximations use several stress analysis methods to obtain the energy release rate.

The resulting energy release rate curves suggest that the debonding process can be described at least partially as a stable crack propagation along the interface. Some experiments confirm this prediction. The matrix droplet contribution to the energy release rate can be considerable. Because of the very complex stress fields in the droplet a simple analytical approximation cannot be given. The qualitative dependences on the material properties and on the geometry can be explained from the presented analysis. The remaining correction factor can be obtained from a numerical calculation.     

Applications of one-cycle control to improve the interconnection of a solid oxide fuel cell and electric power system with a dynamic load

Adding distributed generation (DG) is a desirable strategy for providing highly efficient and environmentally benign services for electric power, heating, and cooling. The interface between a solid oxide fuel cell (SOFC), typical loads, and the electrical grid is simulated in Matlab/Simulink and analyzed to assess the interactions between DG and the electrical grid. A commercial building load profile is measured during both steady-state and transient conditions. The load data are combined with the following models that are designed to account for physical features: a One-Cycle Control grid-connected inverter, a One-Cycle Control active power filter, an SOFC, and capacitor storage. High penetration of DG without any power filter increases the percentage of undesirable harmonics provided by the grid, but combined use of an inverter and active power filter allows the DG system interconnection to improve the grid tie-line flow by lowering total harmonic distortion and increasing the power factor to unity.     

Quantenchemische Untersuchungen zur Molekül- und Elektronenstruktur einfacher Azomethinimine und verwandter Verbindungen

Quantum Chemical Investigations of the Molecular and Electronic Structure of Simple Azomethine Imines and Related Compounds The molecular and electronic structure of simple azomethinimines are investigated by means of MINDO/3 and CNDO/2 calculations. The calculated molecular geometry is compared with X-ray results obtained for these compounds. Except for the NN-bond lengths MINDO/3 satisfactorily describes the molecular structure of azomethinimine and related π-electronic systems. The charges at the atoms along the conjugated chain are alternating as in polymethines. The terminal carbon atom carries a negative charge. This charge brings about an appreciable shielding of this carbon atom such as found in the ¹³C-n.m.r. spectrum. This result does not contradict a stabilization of azomethinimines in the crystal via = CH…︁OC interactions.     

Ex vivo and in vivo Evaluation of [18F]PR04.MZ in Rodents: A Selective Dopamine Transporter Imaging Agent

N‐4‐Fluorobut‐2‐yn‐1‐yl‐2β‐carbomethoxy‐3β‐phenyltropane (PR04.MZ) has been developed as dopamine transporter (DAT) ligand for molecular imaging. It contains a terminally fluorinated, conformationally constrained nitrogen substituent that is well suited for the introduction of fluorine‐18. The present report describes the pharmacological characterisation of [¹⁸F]PR04.MZ. The ligand shows an IC₅₀ value of 2 nM against human DAT, whereas the IC₅₀ value against human serotonin transporter and human noradrenalin transporter are lower (110 nM and 22 nM , respectively). Furthermore, its ex vivo organ distribution, its binding profile in the rat brain and reversibility of binding were examined. A μPET study illuminates a fast kinetic profile and specific binding to rat DAT.