147 research outputs found

    A párbajozó úriember

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    Analysis of the botanical origins of monofloral honey types

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    At the Institute of Food Science of the University of Debrecen, we have been analyzing honey for ten years. In our study, the proline and phenolic compound contents of 70 types of monofloral honey (acacia, linden, rape, sunflower, milkweed, chestnut and forest) were examined. During the study, the answer was sought to the question whether it was possible, based on these two parameters, to differentiate monofloral honey types from each other or, in other words, was there an effect of the botanical origin on the amounts of these two compounds. With the help of linear discriminant analysis, it was determined that groups of monofloral honey could be clearly differentiated from each other. Differentiation of the two groups was not unambiguous in the case of forest and chestnut honey, so the analysis of a third characteristic could be necessary in the case of these two monofloral honeys

    Hypoxia-dependent sequestration of an oxygen sensor by a widespread structural motif can shape the hypoxic response - a predictive kinetic model

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    <p>Abstract</p> <p>Background</p> <p>The activity of the heterodimeric transcription factor hypoxia inducible factor (HIF) is regulated by the post-translational, oxygen-dependent hydroxylation of its α-subunit by members of the prolyl hydroxylase domain (PHD or EGLN)-family and by factor inhibiting HIF (FIH). PHD-dependent hydroxylation targets HIFα for rapid proteasomal degradation; FIH-catalysed asparaginyl-hydroxylation of the <it>C</it>-terminal transactivation domain (CAD) of HIFα suppresses the CAD-dependent subset of the extensive transcriptional responses induced by HIF. FIH can also hydroxylate ankyrin-repeat domain (ARD) proteins, a large group of proteins which are functionally unrelated but share common structural features. Competition by ARD proteins for FIH is hypothesised to affect FIH activity towards HIFα; however the extent of this competition and its effect on the HIF-dependent hypoxic response are unknown.</p> <p>Results</p> <p>To analyse if and in which way the FIH/ARD protein interaction affects HIF-activity, we created a rate equation model. Our model predicts that an oxygen-regulated sequestration of FIH by ARD proteins significantly shapes the input/output characteristics of the HIF system. The FIH/ARD protein interaction is predicted to create an oxygen threshold for HIFα CAD-hydroxylation and to significantly sharpen the signal/response curves, which not only focuses HIFα CAD-hydroxylation into a defined range of oxygen tensions, but also makes the response ultrasensitive to varying oxygen tensions. Our model further suggests that the hydroxylation status of the ARD protein pool can encode the strength and the duration of a hypoxic episode, which may allow cells to memorise these features for a certain time period after reoxygenation.</p> <p>Conclusions</p> <p>The FIH/ARD protein interaction has the potential to contribute to oxygen-range finding, can sensitise the response to changes in oxygen levels, and can provide a memory of the strength and the duration of a hypoxic episode. These emergent properties are predicted to significantly shape the characteristics of HIF activity in animal cells. We argue that the FIH/ARD interaction should be taken into account in studies of the effect of pharmacological inhibition of the HIF-hydroxylases and propose that the interaction of a signalling sensor with a large group of proteins might be a general mechanism for the regulation of signalling pathways.</p

    DEVELOPING A MATHEMATICAL MODEL FOR THE FISSION YEAST CELL CYCLE: SIMULATING MUTANTS OVEREXPRESSING EITHER CDC25 OR WEE1

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    During the last decade several mathematical models were constructed to describe the fission yeast cell cycle. In these models, fluctuations of MPF activity were responsible for cell cycle transitions, and they successfully explained the behaviour of wild-type fission yeast cells and many cell division cycle mutants as well. However, the mutants involved in these models were mainly loss-of-function mutants (either temperature-sensitive point mutants or gene deletion ones). By contrast, the phenotypes of several gene overproducing (op) mutants have been published during the last twenty years, like those of cdc25op and wee1op cells (in the case of the latter one, even the effects of different overexpression levels are known). Since Wee1 and Cdc25 is a kinase-phosphatase pair, regulating MPF activity and as a consequence, timing mitotic onset in fission yeast, a detailed mathematical model of the fission yeast cell cycle should be able to simulate these overexpression mutants. Within the framework of this paper, a formerly published model was tested for these mutants. In order to describe properly the behaviour of cdc25op and wee1op mutants, some alterations had to be made in the original model, both in the parameter values and in the equations. If these corrections have been involved, the newly developed model also maintained its capability to explain the phenotypes of all those mutants, for which the original model was made. Furthermore, the model predicts the phenotypes of two mutants not yet constructed by geneticists

    Dynamical Scenarios for Chromosome Bi-orientation

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    AbstractChromosome bi-orientation at the metaphase spindle is essential for precise segregation of the genetic material. The process is error-prone, and error-correction mechanisms exist to switch misaligned chromosomes to the correct, bi-oriented configuration. Here, we analyze several possible dynamical scenarios to explore how cells might achieve correct bi-orientation in an efficient and robust manner. We first illustrate that tension-mediated feedback between the sister kinetochores can give rise to a bistable switch, which allows robust distinction between a loose attachment with low tension and a strong attachment with high tension. However, this mechanism has difficulties in explaining how bi-orientation is initiated starting from unattached kinetochores. We propose four possible mechanisms to overcome this problem (exploiting molecular noise; allowing an efficient attachment of kinetochores already in the absence of tension; a trial-and-error oscillation; and a stochastic bistable switch), and assess their impact on the bi-orientation process. Based on our results and supported by experimental data, we put forward a trial-and-error oscillation and a stochastic bistable switch as two elegant mechanisms with the potential to promote bi-orientation both efficiently and robustly

    Toxikus és nehézfém ionok hatása modellmembrán rendszerekre = Effects of toxic molecules and heavy metal ions on modelmembran systems

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    A szerves és toxikus hatással rendelkező molekulák közül a diklór- és dibrómfenol, szulfadiazin, szteptomicin, tobramicin, spektinomicin, a Salmonella minnesota Re 595 mutáns törzséből előállított endotoxin, valamint a fémionok közül a Cu, Zn és Cd ionok szerkezetmódosító és szerkezetromboló hatását tanulmányoztuk a humán valamint a baktérimok membránjának lipidösszetételét megközelítő liposzómákban valamint szintén réteges szerkezetű nemionos/víz rendszerű modellrendszerekben. A vizsgálatok során kis és nagyszögű röntgenszórást, anomális röntgenszórást, kalorimetriát (DSC), fagyasztva törést követő transzmissziós elektronmikroszkópiát, valamint az eredmények interpretálásához kvantumkémiai, molekuladinamikai és szóráselméleti számításokat használtunk fel. Azonosítottuk a fenntiekben felsorolt molekulák koncentrációjának és a hőmérsékletnek a függvényében indukált, a vezikulák természetes kettősrétegétől való eltérő szerkezeti formáit (interdigitated =''egymásba tolt '' fázis, köbös és hexagonális, vagy ezek keverékeit, amorf formáit). Az anomális kisszögű szórás adta kivételes lehetőséget kihasználva megállapítottuk a fémionok liposzómákon belüli inhomogén eloszlását, valamint új típusú, a liposzómák interlamelláris terében való nanorészecske előállítási módot fedtünk fel. | The effects of the toxic 2,4-dichlorophenol, 2,4-dibromophenol, sulfadiazine, streptomycin, tobramycin, spectinomycin, LPS prepared from the rough mutant Salmonella minnesota Re 595 and the bivalent copper, zinc and cadmium ions on the different vesicle system consisting of phospholipids corresponding to the natural biomembranes were studies by means of small and wide angle X-ray scattering, anomalous small angle X-ray scattering , calorimetry (DSC), and freeze-fracture combined by transmission electronmicroscopy. Moreover, the interpretation of the results were completed with quantumchemical, molecular dynamical and scattering theoretical calculations. The different non-bilayer structures of lipids induced by LPS were identified. Using the unique possibility of the anomalous small angle X-ray scattering the inhomogeneous location of the bivalent metal ions was described and characterized. Applying the knowledge of the special location of the metal ions a new pathway of preparation for nanoparticles was revealed and proposed

    Fajtamézek botanikai eredetének vizsgálata

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    A Debreceni Egyetem Élelmiszertudományi Intézetében tizedik éve foglalkozunk mézek vizsgálatával. Tanulmányunkban 70 darab fajtaméz (akác, hárs, repce, napraforgó, selyemfű, gesztenye és erdei) prolin- és összes fenolos vegyülettartalmát vizsgáltuk. Vizsgálataink során arra kerestük a választ, hogy e két paraméter alapján lehetséges-e a fajtamézeket elkülöníteni egymástól, tehát hogy a botanikai eredetnek van-e hatása ennek a két vegyület mennyiségére. Lineáris diszkriminancia-elemzés segítségével megállapítottuk, hogy a vizsgált fajtamézek csoportjai egyértelműen elkülönülnek egymástól. Az erdei és gesztenyemézeknél a két csoport elkülönülése nem volt egyértelmű, tehát ennek a két fajtaméznek az esetében egy harmadik jellemző vizsgálatára is szükség lehet

    Mitotic exit in mammalian cells

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    This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution and reproduction in any medium, provided the original author and source are credited. Creation of derivativeworks is permitted but the resultingworkmay be distributed only under the same or similar licence to this one. This licence does not permit commercial exploitation without specific permission. © 2009 EMBO and Macmillan Publishers Limited All rights reserved

    Time scale and dimension analysis of a budding yeast cell cycle model

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    BACKGROUND: The progress through the eukaryotic cell division cycle is driven by an underlying molecular regulatory network. Cell cycle progression can be considered as a series of irreversible transitions from one steady state to another in the correct order. Although this view has been put forward some time ago, it has not been quantitatively proven yet. Bifurcation analysis of a model for the budding yeast cell cycle has identified only two different steady states (one for G1 and one for mitosis) using cell mass as a bifurcation parameter. By analyzing the same model, using different methods of dynamical systems theory, we provide evidence for transitions among several different steady states during the budding yeast cell cycle. RESULTS: By calculating the eigenvalues of the Jacobian of kinetic differential equations we have determined the stability of the cell cycle trajectories of the Chen model. Based on the sign of the real part of the eigenvalues, the cell cycle can be divided into excitation and relaxation periods. During an excitation period, the cell cycle control system leaves a formerly stable steady state and, accordingly, excitation periods can be associated with irreversible cell cycle transitions like START, entry into mitosis and exit from mitosis. During relaxation periods, the control system asymptotically approaches the new steady state. We also show that the dynamical dimension of the Chen's model fluctuates by increasing during excitation periods followed by decrease during relaxation periods. In each relaxation period the dynamical dimension of the model drops to one, indicating a period where kinetic processes are in steady state and all concentration changes are driven by the increase of cytoplasmic growth. CONCLUSION: We apply two numerical methods, which have not been used to analyze biological control systems. These methods are more sensitive than the bifurcation analysis used before because they identify those transitions between steady states that are not controlled by a bifurcation parameter (e.g. cell mass). Therefore by applying these tools for a cell cycle control model, we provide a deeper understanding of the dynamical transitions in the underlying molecular network
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