Íz-kölcsönhatások elemzése elektronikus nyelvvel = Analysis of taste interactions with the electronic tongue

Munkámban az Alpha Astree elektronikus nyelv mérési eredményeit befolyásoló íz kölcsönhatásokat igyekeztem felderíteni a hatások globális és szenzor szintű elemzésével. Az elektronikus nyelvet érintő mintaösszetevő kölcsönhatások vizsgálata jelentősen hozzájárul az elektronikus nyelvről szerzett elméleti tudásunkhoz. Ezen túlmenően hasznos gyakorlati javaslatokkal szolgál mind kísérlettervezési, mind kiértékelési szempontból. A kölcsönhatások vizsgálatához az öt szabványosnak tekinthető, alapízeknek megfelelő vegyületből készített tiszta és kombinált oldatokat és élelmiszer mintákat vizsgáltam egy, az ismert zavaró hatásokat minimalizáló mérési módszerrel

Access Path to the Ligand Binding Pocket May Play a Role in Xenobiotics Selection by AhR.

Understanding of multidrug binding at the atomic level would facilitate drug design and strategies to modulate drug metabolism, including drug transport, oxidation, and conjugation. Therefore we explored the mechanism of promiscuous binding of small molecules by studying the ligand binding domain, the PAS-B domain of the aryl hydrocarbon receptor (AhR). Because of the low sequence identities of PAS domains to be used for homology modeling, structural features of the widely employed HIF-2alpha and a more recent suitable template, CLOCK were compared. These structures were used to build AhR PAS-B homology models. We performed molecular dynamics simulations to characterize dynamic properties of the PAS-B domain and the generated conformational ensembles were employed in in silico docking. In order to understand structural and ligand binding features we compared the stability and dynamics of the promiscuous AhR PAS-B to other PAS domains exhibiting specific interactions or no ligand binding function. Our exhaustive in silico binding studies, in which we dock a wide spectrum of ligand molecules to the conformational ensembles, suggest that ligand specificity and selection may be determined not only by the PAS-B domain itself, but also by other parts of AhR and its protein interacting partners. We propose that ligand binding pocket and access channels leading to the pocket play equally important roles in discrimination of endogenous molecules and xenobiotics

A komló és a sör aromajellemzőinek vizsgálata = Investigation of the aroma components of hop and beer

Vizsgálataink során két, különbözå fajtájú komló és a felhasználásukkal készült sör aromaösszetételét tanulmányoztuk. Igyekeztünk feltárni az egyes komlófajták aromatulajdonsága közötti eltérést, a komlónak a sör illatára gyakorolt hatását, valamint a sörök közötti illatkülönbségeket. Meglepådve tapasztaltuk, hogy a komló közvetlenül szinte alig vesz részt a sör illatának kialakításában. Látszólag tehát hiába használnak különbözå komlófajtákat a sörkészítéshez, a komlóforralás fázisában az illatkomponensek nagy része eltávozik, illetve átalakul, így a komló-eredet késåbb szinte észrevehetetlen marad az illat szempontjából. Az eredmények szemléletesebb interpretálására kifejlesztett aromaspektrum eljárással megállapítottuk, hogy a két sör aromaképe nagyon hasonlít egymásra a csaknem azonos összetevåknek megfelelåen, azonban bizonyos tartalmi különbségeket tárt fel a részletezå elemzés. A legjelentåsebb eltérés a fermentációs anyagcseretermékek arány különbségében mutatkozott. Egyes alkoholok és észterek esetében állt fenn ez a differencia. Mivel az erjesztés során ugyanazt az élesztå fajtát használják, a különbség nem ebbål adódik. A fermentáció vezetésében viszont van eltérés, és ez a tény befolyással van az erjedés során keletkezå illatanyagokra, ebbål adódik a fermentációs termékeket illetåen felmerülå különbözåség. Diverse hop cultivars and beers produced with them have been investigated. The difference between the aroma components of hop varieties, the effect this herb exerts on the fragrance of the beer and the variance among the beers’ odour have been attempted to reveal. Our results show that hop takes part in forming the fragrance of beer barely. Seemingly the use of different variants of hop for brewing is a futile attempt since the majority of the volatiles vaporizes and alters during the process. Thus the cultivated variety (of the herb) remains almost imperceptible in terms of fragrance. The scent pictures of the disparate beers examined closely resemble in compliance with their nearly identical constituents. Nevertheless, the detailed analysis found certain differences between the two beverages analysed. The main disparity showed up in the case of some fermentation products i.e. alcohols and esters. Since the same yeast strains were used for production the discrepancy derives from other causes, for instance from the distinctly conducted fermentation processes. They exert influence on the resulting odour structure that might induce the differences revealed

Classification and Identification of Three Vintage Designated Hungarian Spirits by Their Volatile Compounds

The quality of fruit based spirits varies year to year; therefore, the identification of the vintage of a distilled alcoholic beverage is necessary, but requires highly sensitive analytics. The interpretation of the gathered data requires a well-adapted chemometric method. In this study, Hungarian apple, sour cherry and plum distillates (pálinka’s) from different vintages were analyzed, classified and identified using volatile composition analyzed by GC-MS. The fruit’s origin, fermentation technique and distillation were the same at all the fruits; the only differences in the samples were their vintages (2010, 2011 and 2012). Analysis of variance (ANOVA) and Linear discriminant analysis (LDA) was applied for classification and components’ identification related to the vintage effect. The samples were successfully classified (correct classification rate ranging from 75 to 100%), three components are found to be related to the vintage effect regardless the fruit type: propanol, butanol and ethyl-propionate. GC-MS data proved to be a promising tool for classification of fruit distillate vintages

Factors Influencing the Long-Term Stability of Electronic Tongue and Application of Improved Drift Correction Methods

Temperature, memory effect, and cross-contamination are suspected to contribute to drift in electronic tongue (e-tongue) sensors, therefore drift corrections are required. This paper aimed to assess the disturbing effects on the sensor signals during measurement with an Alpha Astree e-tongue and to develop drift correction techniques. Apple juice samples were measured at different temperatures. pH change of apple juice samples was measured to assess cross-contamination. Different sequential orders of model solutions and apple juice samples were applied to evaluate the memory effect. Model solutions corresponding to basic tastes and commercial apple juice samples were measured for six consecutive weeks to model drift of the sensor signals. Result showed that temperature, cross-contamination, and memory effect influenced the sensor signals. Three drift correction methods: additive drift correction based on all samples, additive drift correction based on reference samples, and multi sensor linear correction, were developed and compared to the component correction in literature through linear discriminant analysis (LDA). LDA analysis showed all the four methods were effective in reducing sensor drift in long-term measurements but the additive correction relative to the whole sample set gave the best results. The results could be explored for long-term measurements with the e-tongue

Thallium Labeled Citrate-Coated Prussian Blue Nanoparticles as Potential Imaging Agent

Background. The aim of this study was to develop and characterize a nanoparticle-based image-contrast platform which is biocompatible, chemically stable, and accessible for radiolabeling with 201Tl. We explored whether this nanoparticle enhanced the T1 signal which might make it an MRI contrast agent as well. Methods. The physical properties of citrate-coated Prussian blue nanoparticles (PBNPs) (iron(II);iron(III);octadecacyanide) doped with 201Tl isotope were characterized with atomic force microscopy, dynamic light scattering, and zeta potential measurement. PBNP biodistribution was determined by using SPECT and MRI following intravenous administration into C57BL6 mice. Activity concentrations (MBq/cm3) were calculated from the SPECT scans for each dedicated volume of interest (VOI) of liver, kidneys, salivary glands, heart, lungs, and brain. Results. PBNP accumulation peaked at 2 hours after injection predominantly in the kidneys and the liver followed by a gradual decrease in activity in later time points. Conclusion. We synthetized, characterized, and radiolabeled a Prussian blue-based nanoparticle platform for contrast material applications. Its in vivo radiochemical stability and biodistribution open up the way for further diagnostic applications

Discrete molecular dynamics can predict helical prestructured motifs in disordered proteins.

Intrinsically disordered proteins (IDPs) lack a stable tertiary structure, but their short binding regions termed Pre-Structured Motifs (PreSMo) can form transient secondary structure elements in solution. Although disordered proteins are crucial in many biological processes and designing strategies to modulate their function is highly important, both experimental and computational tools to describe their conformational ensembles and the initial steps of folding are sparse. Here we report that discrete molecular dynamics (DMD) simulations combined with replica exchange (RX) method efficiently samples the conformational space and detects regions populating alpha-helical conformational states in disordered protein regions. While the available computational methods predict secondary structural propensities in IDPs based on the observation of protein-protein interactions, our ab initio method rests on physical principles of protein folding and dynamics. We show that RX-DMD predicts alpha-PreSMos with high confidence confirmed by comparison to experimental NMR data. Moreover, the method also can dissect alpha-PreSMos in close vicinity to each other and indicate helix stability. Importantly, simulations with disordered regions forming helices in X-ray structures of complexes indicate that a preformed helix is frequently the binding element itself, while in other cases it may have a role in initiating the binding process. Our results indicate that RX-DMD provides a breakthrough in the structural and dynamical characterization of disordered proteins by generating the structural ensembles of IDPs even when experimental data are not available

Evaluation of Brain Nuclear Medicine Imaging Tracers in a Murine Model of Sepsis-Associated Encephalopathy

PURPOSE: The purpose of this study was to evaluate a set of widely used nuclear medicine imaging agents as possible methods to study the early effects of systemic inflammation on the living brain in a mouse model of sepsis-associated encephalopathy (SAE). The lipopolysaccharide (LPS)-induced murine systemic inflammation model was selected as a model of SAE. PROCEDURES: C57BL/6 mice were used. A multimodal imaging protocol was carried out on each animal 4 h following the intravenous administration of LPS using the following tracers: [(99m)Tc][2,2-dimethyl-3-[(3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(3E)-3-hyd roxyiminobutan-2-yl]azanide ([(99m)Tc]HMPAO) and ethyl-7-[(125)I]iodo-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carbox ylate ([(125)I]iomazenil) to measure brain perfusion and neuronal damage, respectively; 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) to measure cerebral glucose uptake. We assessed microglia activity on another group of mice using 2-[6-chloro-2-(4-[(125)I]iodophenyl)-imidazo[1,2-a]pyridin-3-yl]-N-ethyl-N-methyl -acetamide ([(125)I]CLINME). Radiotracer uptakes were measured in different brain regions and correlated. Microglia activity was also assessed using immunohistochemistry. Brain glutathione levels were measured to investigate oxidative stress. RESULTS: Significantly reduced perfusion values and significantly enhanced [(18)F]FDG and [(125)I]CLINME uptake was measured in the LPS-treated group. Following perfusion compensation, enhanced [(125)I]iomazenil uptake was measured in the LPS-treated group's hippocampus and cerebellum. In this group, both [(18)F]FDG and [(125)I]iomazenil uptake showed highly negative correlation to perfusion measured with ([(99m)Tc]HMPAO uptake in all brain regions. No significant differences were detected in brain glutathione levels between the groups. The CD45 and P2Y12 double-labeling immunohistochemistry showed widespread microglia activation in the LPS-treated group. CONCLUSIONS: Our results suggest that [(125)I]CLINME and [(99m)Tc]HMPAO SPECT can be used to detect microglia activation and brain hypoperfusion, respectively, in the early phase (4 h post injection) of systemic inflammation. We suspect that the enhancement of [(18)F]FDG and [(125)I]iomazenil uptake in the LPS-treated group does not necessarily reflect neural hypermetabolism and the lack of neuronal damage. They are most likely caused by processes emerging during neuroinflammation, e.g., microglia activation and/or immune cell infiltration