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    Tytuł:
    Sensitivity analysis of deterministic signaling pathways models
    Autorzy:
    Puszyński, K.
    Lachor, P.
    Kardyńska, M.
    Śmieja, J.
    Powiązania:
    https://bibliotekanauki.pl/articles/201589.pdf
    Data publikacji:
    2012
    Wydawca:
    Polska Akademia Nauk. Czytelnia Czasopism PAN
    Tematy:
    signaling pathways
    sensitivity analysis
    Opis:
    The paper is focused on application of sensitivity methods to analysis of signaling pathway models. Two basic methods are compared: local, based on standard sensitivity functions, and global, based on Sobol indices. Firstly, a general outline of modeling of signaling pathways by means of ordinary differential equations is briefly described. Afterwards, the methods of sensitivity analysis, known from literature, are introduced and illustrated with a simple example of a dynamical system of the second order. Subsequently, the analysis of the p53/Mdm2 regulatory module, which is a key element of any pathway involving p53 protein, is presented. The results of this analysis suggest that no single method should be chosen for investigation of any signaling pathway model but several of them should be applied to answer important questions about sources of heterogeneity in cells behavior, robustness of signaling pathways and possible molecular drug targets.
    Źródło:
    Bulletin of the Polish Academy of Sciences. Technical Sciences; 2012, 60, 3; 471-479
    0239-7528
    Pojawia się w:
    Bulletin of the Polish Academy of Sciences. Technical Sciences
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Sensitivity analysis of signaling pathway models based on discrete-time measurements
    Autorzy:
    Kardynska, M.
    Smieja, J.
    Powiązania:
    https://bibliotekanauki.pl/articles/229721.pdf
    Data publikacji:
    2017
    Wydawca:
    Polska Akademia Nauk. Czytelnia Czasopism PAN
    Tematy:
    sensitivity analysis
    signaling pathways
    measurement uncertainty
    discretetime measurements
    Opis:
    The paper is focused on sensitivity analysis of large-scale models of biological systems that describe dynamics of the so called signaling pathways. These systems are continuous in time but their models are based on discrete-time measurements. Therefore, if sensitivity analysis is used as a tool supporting model development and evaluation of its quality, it should take this fact into account. Such models are usually very complex and include many parameters difficult to estimate in an experimental way. Changes of many of those parameters have little effect on model dynamics, and therefore they are called sloppy. In contrast, other parameters, when changed, lead to substantial changes in model responses and these are called stiff parameters. While this is a well-known fact, and there are methods to discern sloppy parameters from the stiff ones, they have not been utilized, so far, to create parameter rankings and quantify the influence of single parameter changes on system time responses. These single parameter changes are particularly important in analysis of signalling pathways, because they may pinpoint parameters, associated with the processes to be targeted at the molecular level in laboratory experiments. In the paper we present a new, original method of creating parameter rankings, based on an Hessian of a cost function which describes the fit of the model to a discrete experimental data. Its application is explained with simple dynamical systems, representing two typical dynamics exhibited by the signaling pathways.
    Źródło:
    Archives of Control Sciences; 2017, 27, 2; 239-250
    1230-2384
    Pojawia się w:
    Archives of Control Sciences
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Coupled analytical and numerical approach to uncovering new regulatory mechanisms of intracellular processes
    Autorzy:
    Śmieja, J.
    Powiązania:
    https://bibliotekanauki.pl/articles/908134.pdf
    Data publikacji:
    2010
    Wydawca:
    Uniwersytet Zielonogórski. Oficyna Wydawnicza
    Tematy:
    ścieżka sygnalizacyjna
    punkt równowagi
    symulacja
    signaling pathways
    equilibrium points
    simulation
    Opis:
    The paper deals with the analysis of signaling pathways aimed at uncovering new regulatory processes regulating cell responses. First, general issues of comparing simulation and experimental data are discussed, and various aspects of data normalization are covered. Then, a model of a particular signaling pathway, induced by Interferon-\beta, is briefly introduced. It serves as an example illustrating how mathematical modeling can be used for inferring the structure of a regulatory system governing the dynamics of intracellular processes. In this pathway, experimental results suggest that a hitherto unknown process is responsible for a decrease in the levels of one of the important molecules used in the pathway. Then, equilibrium points of the model are analyzed, allowing the rejection of all but one explanation of the phenomena observed experimentally. Numerical simulations confirm that the model can mimic the dynamics of the processes in the pathway under consideration. Finally, some remarks about the applicability of the method based on an analysis of equilibrium points are made.
    Źródło:
    International Journal of Applied Mathematics and Computer Science; 2010, 20, 4; 781-788
    1641-876X
    2083-8492
    Pojawia się w:
    International Journal of Applied Mathematics and Computer Science
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Hypothetical orchestrated cooperation between dopaminergic and kinin receptors for the regulation of common functions
    Autorzy:
    Guevara-Lora, Ibeth
    Niewiarowska-Sendo, Anna
    Polit, Agnieszka
    Kozik, Andrzej
    Powiązania:
    https://bibliotekanauki.pl/articles/1038753.pdf
    Data publikacji:
    2016
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    kinin receptors
    dopamine receptors
    G protein-coupled receptors
    oligomerization
    signaling pathways
    Opis:
    The G protein-coupled receptors (GPCRs), one of the largest protein families, are essential components of the most commonly used signal-transduction systems in cells. These receptors, often using common pathways, may cooperate in the regulation of signal transmission to the cell nucleus. Recent scientific interests increasingly focus on the cooperation between these receptors, particularly in a context of their oligomerization, e.g. the formation of dimers that are able to change characteristic signaling of each receptor. Numerous studies on kinin and dopamine receptors which belong to this family of receptors have shown new facts demonstrating their direct interactions with other GPCRs. In this review, current knowledge on signaling pathways and oligomerization of these receptors has been summarized. Owing to the fact that kinin and dopamine receptors are widely expressed in cell membranes where they act as mediators of numerous common physiological processes, the information presented here sheds new light on a putative crosstalk of these receptors and provides more comprehensive understanding of possible direct interactions that may change their functions. The determination of such interactions may be useful for the development of new targeted therapeutic strategies against many disorders in which kinin and dopamine receptors are involved.
    Źródło:
    Acta Biochimica Polonica; 2016, 63, 3; 387-396
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Rak endometrium typu I i II – nowe spojrzenie na etiologię i przebieg kliniczny
    Type I and II endometrial cancer – a new look at the etiology and clinical course
    Autorzy:
    Markowska, Anna
    Pawałowska, Monika
    Korcyl, Małgorzata
    Markowska, Janina
    Powiązania:
    https://bibliotekanauki.pl/articles/1030431.pdf
    Data publikacji:
    2015
    Wydawca:
    Medical Communications
    Tematy:
    endometrial cancer
    molecular background
    signaling pathways
    podłoże molekularne
    rak endometrium
    ścieżki sygnałowe
    Opis:
    Endometrial cancer is the most frequent malignancy of female genital organs in more developed countries. It is a heterogeneous tumor with variable risk factors, precancerous conditions, clinical course and prognosis. The majority of cases are sporadic, however endometrial cancer develops in around 8–12% of women with Lynch syndrome, who are at increased risk of this disease. MLH1, MSH2 and MSH6 mutations are observed with equal frequency. Recent molecular studies on endometrial cancer indicate that the classic division into two types according to Bokhman is insufficient, particularly with respect to type II which is less common, and which includes both serous carcinomas and clear-cell carcinomas. Endometrial intraepithelial carcinoma is considered a precursor lesion for uterine serous carcinoma. In immunohistochemical tests (p53, Ki67, ER and PR) it resembles a precursor lesion for ovarian serous carcinoma, possibly indicating the clonal origin of both carcinomas. It is possible that cells from the foci of endometrial intraepithelial carcinoma migrate to the fallopian tube and lead to the peritoneal spread of the disease. Differential diagnosis of uterine serous carcinoma and ovarian serous carcinoma is difficult; testing ER and PR profiles and evaluation of WT1 expression can prove helpful. In recent years, it has been found that uterine serous carcinoma can be associated with the carrier state of mutated BRCA1. These studies are significant since in carriers of mutated BRCA1, apart from prophylactic adnexectomy, hysterectomy should be considered as well. Another important aspect in such cases is therapy with PARP inhibitors.
    Rak endometrium jest najczęstszym nowotworem złośliwym żeńskich narządów płciowych w krajach wysoko rozwiniętych. To heterogenny nowotwór o zróżnicowanych czynnikach ryzyka, stanach przedrakowych, przebiegu klinicznym i rokowaniu. Większość przypadków ma charakter sporadyczny, jednak kobiety z zespołem Lyncha mają rodzinne predyspozycje do powstania tego nowotworu, rozwijającego się u 8–12% z nich. Mutacje w MLH1, MSH2 i MSH6 występują z równą częstością. Najnowsze badania molekularne raka endometrium wskazują, że klasyczny podział według Bokhmana – na dwa typy – jest niewystarczający, zwłaszcza w obrębie rzadszego typu II, w którym stwierdzane są zarówno raki surowicze, jak i jasnokomórkowe. Za zmianę prekursorową raka surowiczego endometrium (uterine serous carcinoma) uznaje się śródnabłonkowego raka surowiczego (endometrial intraepithelial carcinoma). W badaniach immunohistochemicznych (p53, Ki67, ER i PR) wykazuje on podobieństwo do zmiany prekursorowej surowiczego raka jajnika (serous ovarian carcinoma), co może świadczyć o klonalnym pochodzeniu obu raków. Istnieje możliwość, że komórki z ognisk śródnabłonkowego raka surowiczego migrują do jajowodu i prowadzą do śródotrzewnowego rozsiewu choroby. Rozróżnienie raka surowiczego endometrium i surowiczego raka jajnika jest trudne; pomocne są badania profilu ER, PR i ocena ekspresji WT1. W ostatnich latach stwierdzono, iż rak surowiczy endometrium może mieć związek z nosicielstwem zmutowanego BRCA1. Badania te są istotne, gdyż u nosicieli zmutowanego BRCA1 oprócz profilaktycznej adneksektomii powinno się rozważyć również histerektomię. Innym ważnym aspektem byłaby w tych przypadkach terapia przy pomocy inhibitorów PARP.
    Źródło:
    Current Gynecologic Oncology; 2015, 13, 1; 5-10
    2451-0750
    Pojawia się w:
    Current Gynecologic Oncology
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Functional characteristic of PC12 cells with reduced microsomal glutathione transferase 1
    Autorzy:
    Sobczak, Monika
    Boczek, Tomasz
    Ferenc, Bozena
    Taha, Joanna
    Kozaczuk, Anna
    Wiktorska, Magdalena
    Sacewicz-Hofman, Izabela
    Niewiarowska, Jolanta
    Zylinska, Ludmila
    Powiązania:
    https://bibliotekanauki.pl/articles/1042731.pdf
    Data publikacji:
    2010
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    necrosis
    pc12 cells
    signaling pathways
    microsomal glutathione transferase 1
    pseudoneuronal phenotype
    metastatic potential
    Opis:
    Microsomal glutathione transferase 1 (MGST1) possesses glutathione transferase and peroxidase activities and is active in biotransformation of xenobiotics and in defense against oxidative stress. To assess MGST1 role in the development and functioning of PC12 cells, we constructed a cell line with reduced MGST1 (PC12_M). Real-time PCR and immunoblot assays showed MGST1 expression lowered to 60 % and immunocytochemical analyses demonstrated an altered concentration and distribution of the enzyme. PC12_M cells revealed a larger tendency to grow in clusters, weaker adhesion, irregular shape of bodies, short neurite outgrowth and higher percentage of necrotic cells (34 %). The total GSTs activity determined with non-specific substrate CDNB (1-chloro-2,4-dinitrobenzene) decreased by 15-20 %, whereas that with DCNB (2,4-dichloro-1-nitrobenzene), a substrate more specific for cytosolic GSTs, was similar to the one in control cells. This suggests that reduction of MGST1 cannot be compensated by other glutathione transferases. In PC12_M cells the total glutathione content was higher by 15-20 %, whereas the GSSG/GSH ratio was lower than in control cells. Moreover, the laminin-dependent migration rate was much faster in control cells than in PC12_M, suggesting some alterations in the metastatic potential of the line with suppressed MGST1. The amount of MAP kinases (p38, JNK, ERK1/2) was elevated in PC12_M cells but their phosphorylation level declined. Microarray analysis showed changed expression of several genes, which may be linked with differentiation and necrosis of PC12_M cells. Our data suggest that MGST1 could be an important regulator of PC12 cells development and might have significant effects on cell growth and proliferation, probably through altered expression of genes with different biological function.
    Źródło:
    Acta Biochimica Polonica; 2010, 57, 4; 589-596
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Model based analysis of signaling pathways
    Autorzy:
    Śmieja, J.
    Powiązania:
    https://bibliotekanauki.pl/articles/907948.pdf
    Data publikacji:
    2008
    Wydawca:
    Uniwersytet Zielonogórski. Oficyna Wydawnicza
    Tematy:
    ścieżka sygnalizacyjna
    układ dynamiczny
    biologia systemów
    interferon-beta
    signaling pathways
    dynamical system
    systems biology
    Opis:
    The paper is concerned with application of mathematical modeling to the analysis of signaling pathways. Two issues, deterministic modeling of gene transcription and model-driven discovery of regulatory elements, are dealt with. First, the biological background is given and the importance of the stochastic nature of biological processes is addressed. The assumptions underlying deterministic modeling are presented. Special emphasis is put on describing gene transcription. A framework for including unknown processes activating gene transcription by means of first-order lag elements is introduced and discussed. Then, a particular interferon-ß induced pathway is introduced, limited to early events that precede activation of gene transcription. It is shown how to simplify the system description based on the goals of modeling. Further, a computational analysis is presented, facilitating better understanding of the mechanisms underlying regulation of key components in the pathway. The analysis is illustrated by a comparison of simulation and experimental data.
    Źródło:
    International Journal of Applied Mathematics and Computer Science; 2008, 18, 2; 139-145
    1641-876X
    2083-8492
    Pojawia się w:
    International Journal of Applied Mathematics and Computer Science
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Planning identification experiments for cell signaling pathways: An NFκB case study
    Autorzy:
    Fujarewicz, K.
    Powiązania:
    https://bibliotekanauki.pl/articles/908137.pdf
    Data publikacji:
    2010
    Wydawca:
    Uniwersytet Zielonogórski. Oficyna Wydawnicza
    Tematy:
    komórka
    ścieżka sygnalizacyjna
    projektowanie eksperymentu
    estymacja parametrów
    cell signaling pathways
    experiment design
    parameter estimation
    Opis:
    Mathematical modeling of cell signaling pathways has become a very important and challenging problem in recent years. The importance comes from possible applications of obtained models. It may help us to understand phenomena appearing in single cells and cell populations on a molecular level. Furthermore, it may help us with the discovery of new drug therapies. Mathematical models of cell signaling pathways take different forms. The most popular way of mathematical modeling is to use a set of nonlinear ordinary differential equations (ODEs). It is very difficult to obtain a proper model. There are many hypotheses about the structure of the model (sets of variables and phenomena) that should be verified. The next step, fitting the parameters of the model, is also very complicated because of the nature of measurements. The blotting technique usually gives only semi-quantitative observations, which are very noisy and collected only at a limited number of time moments. The accuracy of parameter estimation may be significantly improved by a proper experiment design. Recently, we have proposed a gradient-based algorithm for the optimization of a sampling schedule. In this paper we use the algorithm in order to optimize a sampling schedule for the identification of the mathematical model of the NF[...]B regulatory module, known from the literature. We propose a two-stage optimization approach: a gradient-based procedure to find all stationary points and then pair-wise replacement for finding optimal numbers of replicates of measurements. Convergence properties of the presented algorithm are examined.
    Źródło:
    International Journal of Applied Mathematics and Computer Science; 2010, 20, 4; 773-780
    1641-876X
    2083-8492
    Pojawia się w:
    International Journal of Applied Mathematics and Computer Science
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Sensitivity Analysis Aimed at Finding Potential Molecular Drug Targets
    Analiza wra»liwo±ci ukierunkowana na poszukiwanie molekularnych celów dla leków
    Autorzy:
    Smieja, Jaroslaw
    Kardyńska, Małgorzata
    Pudlo, Marta
    Powiązania:
    https://bibliotekanauki.pl/articles/953271.pdf
    Data publikacji:
    2019
    Wydawca:
    Polskie Towarzystwo Matematyczne
    Tematy:
    sensitivity analysis
    signaling pathways
    molecular drug
    targets
    molekularne cele leków
    analiza wrażliwości
    szlaki sygnałowe
    Opis:
    Sensitivity analysis has become one of the standard tools in analysis of models of intracellular processes. Various methods have been proposed, developed for either local or global sensitivity of systems under investigation. In this work, we propose a method that may be used to find potential molecular drug targets, taking into account heterogeneity of population of cells with respect to their responses to a particular drug agent.
    Źródło:
    Mathematica Applicanda; 2019, 47, 2
    1730-2668
    2299-4009
    Pojawia się w:
    Mathematica Applicanda
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Protein-protein interaction and coarse grained simulation study of glioblastoma multiforme reveals novel pathways of Gpr17
    Autorzy:
    Gnanavel, M.
    Yli-Harja, O.
    Kandhavelu, M.
    Powiązania:
    https://bibliotekanauki.pl/articles/1935822.pdf
    Data publikacji:
    2014
    Wydawca:
    Politechnika Gdańska
    Tematy:
    signaling network
    RNA-Seq
    coarse-grain
    Glioblastoma Multiforme
    pathways
    Opis:
    Studies of receptor mediated signaling networks in neuronal cells provide a unique opportunity to uncover the basis of many diseases. Receptor signaling cascades proceed from the cell surface, where extra cellular factors interact with their specific receptors e.g. G-Protein Coupled Receptors (GPR). Recent studies have shown that the activation or suppression of GPR 17 in diseased neuronal cells has potential impact in altering the tumor con ditions. We identified many hundred times expressions of GPR 17 in Glioblastoma Multiforme (GBM) from the RNA -Seq data. We also observed many other genes having similar expression patterns with GPR 17, indicating possible connections of this receptor with diverse gene products. We performed a coarse-grained simulation of ∼500 proteins inside a cytoplasm like a box with solvent water molecules. The summarized protein interaction networks resulted from a coarse grained simulation and large scale protein-protein docking reveals novel molecular connections and pathways.
    Źródło:
    TASK Quarterly. Scientific Bulletin of Academic Computer Centre in Gdansk; 2014, 18, 4; 321--325
    1428-6394
    Pojawia się w:
    TASK Quarterly. Scientific Bulletin of Academic Computer Centre in Gdansk
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
      Wyświetlanie 1-10 z 10

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