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Search Results: 1 - 10 of 827 matches for " Gabor Jarai "
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Epithelial-mesenchymal transition in primary human bronchial epithelial cells is Smad-dependent and enhanced by fibronectin and TNF-α
Joana Camara, Gabor Jarai
Fibrogenesis & Tissue Repair , 2010, DOI: 10.1186/1755-1536-3-2
Abstract: Our data demonstrate that primary human bronchial epithelial cells (HBECs) are able to undergo EMT in response to transforming growth factor-beta 1 (TGF-β1), as revealed by typical morphological alterations and EMT marker progression at the RNA level by real-time quantitative polymerase chain reaction and, at the protein level, by western blot. By using pharmacological inhibitors we show that this is a Smad-dependent mechanism and is independent of extracellular signal-related kinase pathway activation. Additional cytokines and growth factors such as tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL1β) and connective tissue growth factor (CTGF) were also tested, alone or in combination with TGF-β1. TNF-α markedly enhances the effect of TGF-β1 on EMT, whereas IL1β shows only a very weak effect and CTGF has no significant effect. We have also found that cell-matrix contact, in particular to fibronectin, an ECM component upregulated in fibrotic lesions, potentiates EMT in both human alveolar epithelial cells and HBECs. Furthermore, we also show that the collagen discoidin domain receptor 1 (DDR1), generally expressed in epithelial cells, is downregulated during the EMT of bronchial epithelium whereas DDR2 is unaffected. Our results also suggest that bone morphogenetic protein-4 is likely to have a context dependent effect during the EMT of HBECs, being able to induce the expression of EMT markers and, at the same time, to inhibit TGF-β induced epithelial transdifferentiation.The results presented in this study provide additional insights into EMT, a potentially very important mechanism in fibrogenesis. We show that, in addition to alveolar epithelial type II cells, primary HBECs are also able to undergo EMT in vitro upon TGF-β1 stimulation via a primarily Smad 2/3 dependent mechanism. The effect of TGF-β1 is potentiated on fibronectin matrix and in the presence of TNF-α, representing a millieu reminiscent of fibrotic lesions. Our results can contribute to a
Discoidin domain receptors regulate the migration of primary human lung fibroblasts through collagen matrices
Pedro A Ruiz, Gabor Jarai
Fibrogenesis & Tissue Repair , 2012, DOI: 10.1186/1755-1536-5-3
Abstract: Transwell migration experiments showed that normal human lung fibroblast (NHLF) transmigration through collagen I-coated inserts is mediated by DDR2 and the DDR2-associated signaling kinases JAK2 and ERK1/2, but not DDR1. Additionally, experiments with specific small interfering (si)RNAs revealed that collagen I-induced expression of MMP-10 and MMP-2 is DDR2 but not DDR1 dependent in NHLFs. Our data showed that collagen I increases NHLF migration through collagen IV, the main component of basement membranes. Furthermore, basal and collagen I-induced NHLF migration through collagen IV-coated inserts was both DDR2 and DDR1 dependent. Finally, DDR2, but not DDR1 was shown to be involved in fibroblast proliferation.Our results suggest a mechanism by which the presence of collagen I in situations of excessive matrix deposition could induce fibroblast migration through basement membranes through DDR2 activation and subsequent DDR1 and MMP-2 gene expression. This work provides new insights into the role of DDRs in fibroblast function.Discoidin domain receptors (DDRs) are non-integrin collagen receptors that belong to the receptor tyrosine kinase family [1]. There are two related DDRs, DDR1 and DDR2. DDR1 is mainly expressed in epithelial cells, particularly of the lung, kidney, mammary gland and gastrointestinal tract, whereas DDR2 is primarily found in cells of mesenchymal origin, such as fibroblasts and smooth muscle cells [1,2]. DDR1 can be activated by most collagens including collagen I to IV and VIII, while DDR2 responds to collagen I and to a lesser extent to collagen II, III and V, but does not recognize collagen IV [3]. Collagen I is the most abundant protein of interstitial connective tissue, whereas the more flexible, network-forming collagen IV is the most important structural component of basement membranes [4].Studies with knockout mice and human carcinoma cells have shown that DDR1 and DDR2 play important roles in the expression of proinflammatory and profib
Administration of Bleomycin via the Oropharyngeal Aspiration Route Leads to Sustained Lung Fibrosis in Mice and Rats as Quantified by UTE-MRI and Histology
Christine Egger, Catherine Cannet, Christelle Gérard, Elizabeth Jarman, Gabor Jarai, Agnès Feige, Thomas Suply, Arthur Micard, Andrew Dunbar, Bruno Tigani, Nicolau Beckmann
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063432
Abstract: Pulmonary fibrosis can be experimentally induced in small rodents by bleomycin. The antibiotic is usually administered via the intratracheal or intranasal routes. In the present study, we investigated the oropharyngeal aspiration of bleomycin as an alternative route for the induction of lung fibrosis in rats and mice. The development of lung injury was followed in vivo by ultrashort echo time magnetic resonance imaging (UTE-MRI) and by post-mortem analyses (histology of collagen, hydroxyproline determination, and qRT-PCR). In C57BL/6 mice, oropharyngeal aspiration of bleomycin led to more prominent lung fibrosis as compared to intranasal administration. Consequently, the oropharyngeal aspiration route allowed a dose reduction of bleomycin and, therewith, a model refinement. Moreover, the distribution of collagen after oropharyngeal aspiration of bleomycin was more homogenous than after intranasal administration: for the oropharyngeal aspiration route, fibrotic areas appeared all over the lung lobes, while for the intranasal route fibrotic lesions appeared mainly around the largest superior airways. Thus, oropharyngeal aspiration of bleomycin induced morphological changes that were more comparable to the human disease than the intranasal administration route did. Oropharyngeal aspiration of bleomycin led to a homogeneous fibrotic injury also in rat lungs. The present data suggest oropharyngeal aspiration of bleomycin as a less invasive means to induce homogeneous and sustained fibrosis in the lungs of mice and rats.
Cytokine Induced Phenotypic and Epigenetic Signatures Are Key to Establishing Specific Macrophage Phenotypes
Nicolai A. Kittan, Ronald M. Allen, Abhay Dhaliwal, Karen A. Cavassani, Matthew Schaller, Katherine A. Gallagher, William F. Carson, Sumanta Mukherjee, Jolanta Grembecka, Tomasz Cierpicki, Gabor Jarai, John Westwick, Steven L. Kunkel, Cory M. Hogaboam
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0078045
Abstract: Macrophages (MΦ) play an essential role in innate immune responses and can either display a pro-inflammatory, classically activated phenotype (M1) or undergo an alternative activation program (M2) promoting immune regulation. M-CSF is used to differentiate monocytes into MΦ and IFN-γ or IL-4+IL-13 to further polarize these cells towards M1 or M2, respectively. Recently, differentiation using only GM-CSF or M-CSF has been described to induce a M1- or M2-like phenotype, respectively. In this study, we combined both approaches by differentiating human MΦ in GM-CSF or M-CSF followed by polarization with either IFN-γ or IL-4+IL-13. We describe the phenotypic differences between CD14hi CD163hi CD206int FOLR2-expressing M-CSF MΦ and CD14lo CD163lo CD206hi GM-CSF MΦ but show that both macrophage populations reacted similarly to further polarization with IFN-γ or IL-4+IL-13 with up- and down-regulation of common M1 and M2 marker genes. We also show that high expression of the mannose receptor (CD206), a marker of alternative activation, is a distinct feature of GM-CSF MΦ. Changes of the chromatin structure carried out by chromatin modification enzymes (CME) have been shown to regulate myeloid differentiation. We analyzed the expression patterns of CME during MΦ polarization and show that M1 up-regulate the histone methyltransferase MLL and demethylase KDM6B, while resting and M2 MΦ were characterized by DNA methyltransferases and histone deacetylases. We demonstrate that MLL regulates CXCL10 expression and that this effect could be abrogated using a MLL-Menin inhibitor. Taken together we describe the distinct phenotypic differences of GM-CSF or M-CSF MΦ and demonstrate that MΦ polarization is regulated by specific epigenetic mechanisms. In addition, we describe a novel role for MLL as marker for classical activation. Our findings provide new insights into MΦ polarization that could be helpful to distinguish MΦ activation states.
Minimal configurations and sandpile measures
Antal A. Jarai,Nicolas Werning
Mathematics , 2011, DOI: 10.1007/s10959-012-0446-z
Abstract: We give a new simple construction of the sandpile measure on an infinite graph G, under the sole assumption that each tree in the Wired Uniform Spanning Forest on G has one end almost surely. For, the so called, generalized minimal configurations the limiting probability on G exists even without this assumption. We also give determinantal formulas for minimal configurations on general graphs in terms of the transfer current matrix.
Infinite volume limit of the Abelian sandpile model in dimensions d >= 3
Antal A. Jarai,Frank Redig
Mathematics , 2004, DOI: 10.1007/s00440-007-0083-0
Abstract: We study the Abelian sandpile model on Z^d. In dimensions at least 3 we prove existence of the infinite volume addition operator, almost surely with respect to the infinite volume limit mu of the uniform measures on recurrent configurations. We prove the existence of a Markov process with stationary measure mu, and study ergodic properties of this process. The main techniques we use are a connection between the statistics of waves and uniform two-component spanning trees and results on the uniform spanning tree measure on Z^d.
Electrochemical Migration in Thick-Film IC-S
Gabor Ripka,Gabor Harsanyi
Active and Passive Electronic Components , 1985, DOI: 10.1155/apec.11.281
Nonsmooth geometry and collapse of flexible structures under smooth loads
Gabor Csanyi,Gabor Domokos
Physics , 2012,
Abstract: While static equilibria of flexible strings subject to various load types (gravity, hydrostatic pressure, Newtonian wind) is well understood textbook material, the combinations of the very same loads can give rise to complex spatial behaviour at the core of which is the unilateral material constraint prohibiting compressive loads. While the effects of such constraints have been explored in optimisation problems involving straight cables, the geometric complexity of physical configurations has not yet been addressed. Here we show that flexible strings subject to combined smooth loads may not have smooth solutions in certain ranges of the load ratios. This non-smooth phenomenon is closely related to the collapse geometry of inflated tents. After proving the nonexistence of smooth solutions for a broad family of loadings we identify two alternative, critical geometries immediately preceding the collapse. We verify these analytical results by dynamical simulation of flexible chains as well as with simple table-top experiments with an inflated membrane.
Local chromatic number, Ky Fan's theorem, and circular colorings
Gabor Simonyi,Gabor Tardos
Mathematics , 2004,
Abstract: The local chromatic number of a graph was introduced by Erdos et al. in 1986. It is in between the chromatic and fractional chromatic numbers. This motivates the study of the local chromatic number of graphs for which these quantities are far apart. Such graphs include Kneser graphs, their vertex color-critical subgraphs, the Schrijver (or stable Kneser) graphs; Mycielski graphs, and their generalizations; and Borsuk graphs. We give more or less tight bounds for the local chromatic number of many of these graphs. We use an old topological result of Ky Fan which generalizes the Borsuk-Ulam theorem. It implies the existence of a multicolored copy of the balanced complete bipartite graph on t points in every proper coloring of many graphs whose chromatic number t is determined via a topological argument. (This was in particular noted for Kneser graphs by Ky Fan.) This yields a lower bound of t/2+1 for the local chromatic number of these graphs. We show this bound to be tight or almost tight in many cases. As another consequence of the above we prove that the graphs considered here have equal circular and ordinary chromatic numbers if the latter is even. This partially proves a conjecture of Johnson, Holroyd, and Stahl and was independently attained by F. Meunier. We also show that odd chromatic Schrijver graphs behave differently, their circular chromatic number can be arbitrarily close to the other extreme.
Borel oracles. An analytical approach to constant-time algorithms
Gabor Elek,Gabor Lippner
Mathematics , 2009,
Abstract: Nguyen and Onak constructed the first constant-time algorithm for the approximation of the size of the maximum matching in bounded degree graphs. The Borel oracle machinery is a tool that can be used to convert some statements in Borel graph theory to theorems in the field of constant-time algorithms. In this paper we illustrate the power of this tool to prove the existence of the above mentioned constant-time approximation algorithm.
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