207 research outputs found

    Achieving Functionality Through Modular Build-up: Structure and Size Selection of Serine Oligopeptidases

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    Enzymes of the prolyl oligopeptidase family (S9 family) recognize their substrates not only by the specificity motif to be cleaved but also by size - they hydrolyze oligopeptides smaller than 30 amino acids. They belong to the serine-protease family, but differ from classical serine-proteases in size (80 kDa), structure (two domains) and regulation system (size selection of substrates). This group of enzymes is an important target for drug design as they are linked to amnesia, schizophrenia, type 2 diabetes, trypanosomiasis, periodontitis and cell growth. By comparing the structure of various members of the family we show that the most important features contributing to selectivity and efficiency are: (i) whether the interactions weaving the two domains together play a role in stabilizing the catalytic triad and thus their absence may provide for its deactivation: these oligopeptidases can screen their substrates by opening up, and (ii) whether the interaction-prone β-edge of the hydrolase domain is accessible and thus can guide a multimerization process that creates shielded entrance or intricate inner channels for the size-based selection of substrates. These cornerstones can be used to estimate the multimeric state and selection strategy of yet undetermined structures

    Erdőlátogatási szokások felmérése és a fizikai aktivitás vizsgálata az észak-magyarország régió 55 év feletti lakosságának körében = The study regarding forest visit habit and physical activity status for the population over 55 years in the North Hungarian Region

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    Hazánk természeti adottságai potenciális lehetőségnek tekinthetők az egészségvédelem és az egészségi állapot javításának vonatkozásában. Az erdők közjóléti ren del te té sé nek hasznos befektetésével támogathatják idősödő társadalmunkban a közép- és időskorúak öregedési folyamatának lassítását. A kutatási internetes, önkitöltős, validált kérdőívet az International Physical Activity Questionnaire kérdései és módszerei alapján állítottuk össze, melyben szerepeltek saját kérdések is. Az eredmények alapján elmondható, hogy a minta legnagyobb részét az Észak-magyaroszág régió nyugdíjasklubjainak tagjai töltötték ki (n=103 fő; m=65,05). Az adatfeldolgozást Excel és SPSS 20.0 program segítségével végeztük. Összefoglalásként elmondható, hogy a tudományos megközelítések alátámasztják azt a tényt, hogy a testmozgás jelentős preventív hatással bír. Az erdő kínálta rekreációs lehetőségek – mint a túrázás, a kerékpározás vagy a futás – kiváló eszközként jól beilleszthetőek az idősödő korosztály életmódjába, és támogathatják, hogy a nyugdíjasok is fizikailag aktív tagjai maradhassanak a társadalomnak. Kulcsszavak: erdőlátogatási szokások, fizikai aktivitás, 55 év feletti lakosság, International Physical Activity Questionnaire, észak-Magyarország régió The touristic habit in the forests of the North Hungarian region may give a good and healthy turistical programmes for the population over 55 years. The green forest may give a remarkable possibility to slow the elderly people’s typical progressive disease status. The sample was sampled from some North Hungarian retired People’s clubs (n=103; m=65.0). result was measured by the basis of a validated, International Physical Activity Questionnaire. Data were analysed by Excel and SPSS.20.0 programmes. Conclusion is, that the trip in the green forest, like a hiking or cycling have a positive effect on the elderlies’ health and physical activity status. Key words: touristic habits in the forest, physical activity, population over 55 years, International Physical Activity Questionnaire, North Hungarian Regio

    Identification and quantitative determination of pinoresinol in Taxus ×media Rehder needles, cell suspension and shoot cultures

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    The aim of our study was to investigate the presence and quantitative contents of lignans in the tissues of Taxus ×media. The presence of the lignans: pinoresinol, matairesinol and secoisolariciresinol was assessed in needles, shoots cultures and suspension culture. Pinoresinol was the only lignan found in the tissue of T. ×media. The total pinoresinol content in the needles and in the shoots was 1.24 mg/g dry weight (dw) and 0.69 mg/g dw, respectively. Most of the pinoresinol identified was appeared glycosidically bound. In needles, the amount of glycosidically bound pinoresinol (0.81 mg/g dw) was about twice as high as that of free pinoresinol (0.43 mg/g dw). The content of free and glycosidically bound pinoresinol showed the level of 0.18 mg/g dw and 0.51 mg/g dw, respectively in the in vitro shoot cultures. In the cell culture, no pinoresinol was found

    1,2,3,4,6 penta-O -galloyl-β-D-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension

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    Background and Purpose: Hypertension is a multifactorial disease, manifested by vascular dysfunction, increased superoxide production and perivascular inflammation. In this study, we have hypothesized that 1,2,3,4,6 Penta‐O‐Galloyl‐β‐D‐Glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension. Experimental Approach: PGG was administered every two days in a dose of 10 mg·kg‐1 i.p during 14‐days of Ang II infusion and was used in a final concentration of 20 μM for in vitro studies. Key Results: Ang II administration increased leukocyte and T cell content in perivascular adipose tissue (pVAT) and administration of PGG significantly decreased total leukocyte and T cell infiltration in pVAT (1640±150 vs. 1028±57, p<0.01; 321±22 vs 158±18, cells/mg; p<0.01, respectively). This effect was observed in relation to all T cell subsets. PGG also decreased the content of T cells bearing CD25, CCR5 and CD44 receptors and the expression of both MCP‐1 in aorta and RANTES in pVAT. PGG administration decreased the content of TNF+ and IFN‐γ+ CD8 T cells and IL‐17A+ CD4+ and CD3+CD4‐CD8‐ cells. Importantly, these effects of PGG were associated with improved vascular function and decreased ROS production in the aortas of Ang II‐infused animals independently of blood pressure increase. Mechanistically, PGG (20 μM) directly inhibited CD25 and CCR5 expression in cultured T cells. It also decreased the content of IFN‐γ+ by CD8+ and CD3+CD4‐CD8‐ cells and IL‐17A+ by CD3+CD4‐CD8‐ cells. Conclusion and Implication: PGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension

    A self-compartmentalizing hexamer serine protease from Pyrococcus Horikoshii: Substrate selection achieved through multimerization

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    Oligopeptidases impose a size limitation on their substrates, the mechanism of which has long been in debate. Here we present the structure of a hexameric serine protease, an oligopeptidase from Pyrococcus horikoshii (PhAAP), revealing a complex, self-compartmentalized inner space, where substrates may access the monomer active sites passing through a double-gated "check-in" system: first passing through a pore on the hexamer surface, then turning to enter through an even smaller opening at the monomers' domain-interface. This substrate screening strategy is unique within the family. We found that among oligopeptidases a member of catalytic apparatus is positioned near an amylogenic beta-edge, which needs to be protected to prevent aggregation and found different strategies applied to such end. We propose that self-assembly within the family results in characteristically different substrate selection mechanisms coupled to different multimerization states

    Stable carbon and nitrogen isotopes identify nuanced dietary changes from the Bronze and Iron Ages on the Great Hungarian Plain

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    The Great Hungarian Plain (GHP) served as a geographic funnel for population mobility throughout prehistory. Genomic and isotopic research demonstrates non-linear genetic turnover and technological shifts between the Copper and Iron Ages of the GHP, which influenced the dietary strategies of numerous cultures that intermixed and overlapped through time. Given the complexities of these prehistoric cultural and demographic processes, this study aims to identify and elucidate diachronic and culture-specific dietary signatures. We report on stable carbon and nitrogen isotope ratios from 74 individuals from nineteen sites in the GHP dating to a ~ 3000-year time span between the Early Bronze and Early Iron Ages. The samples broadly indicate a terrestrial C 3 diet with nuanced differences amongst populations and through time, suggesting exogenous influences that manifested in subsistence strategies. Slightly elevated δ 15 N values for Bronze Age samples imply higher reliance on protein than in the Iron Age. Interestingly, the Füzesabony have carbon values typical of C 4 vegetation indicating millet consumption, or that of a grain with comparable δ 13 C ratios, which corroborates evidence from outside the GHP for its early cultivation during the Middle Bronze Age. Finally, our results also suggest locally diverse subsistence economies for GHP Scythians
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