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Search Results: 1 - 10 of 25 matches for " Eirikur Steingrimsson "
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C-KIT Signaling Depends on Microphthalmia-Associated Transcription Factor for Effects on Cell Proliferation
Bengt Phung, Jianmin Sun, Alexander Schepsky, Eirikur Steingrimsson, Lars R?nnstrand
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024064
Abstract: The development of melanocytes is regulated by the tyrosine kinase receptor c-KIT and the basic-helix-loop-helix-leucine zipper transcription factor Mitf. These essential melanocyte survival regulators are also well known oncogenic factors in malignant melanoma. Despite their importance, not much is known about the regulatory mechanisms and signaling pathways involved. In this study, we therefore sought to identify the signaling pathways and mechanisms involved in c-KIT mediated regulation of Mitf. We report that c-KIT stimulation leads to the activation of Mitf specifically through the c-KIT phosphorylation sites Y721 (PI3 kinase binding site), Y568 and Y570 (Src binding site). Our study not only confirms the involvement of Ras-Erk signaling pathway in the activation of Mitf, but also establishes that Src kinase binding to Y568 and Y570 of c-KIT is required. Using specific inhibitors we observe and verify that c-KIT induced activation of Mitf is dependent on PI3-, Akt-, Src-, p38- or Mek kinases. Moreover, the proliferative effect of c-KIT is dependent on Mitf in HEK293T cells. In contrast, c-KIT Y568F and Y721F mutants are less effective in driving cell proliferation, compared to wild type c-KIT. Our results reveal novel mechanisms by which c-KIT signaling regulates Mitf, with implications for understanding both melanocyte development and melanoma.
A detailed genome-wide reconstruction of mouse metabolism based on human Recon 1
Martin I Sigurdsson, Neema Jamshidi, Eirikur Steingrimsson, Ines Thiele, Bernhard ? Palsson
BMC Systems Biology , 2010, DOI: 10.1186/1752-0509-4-140
Abstract: We mapped the published, detailed reconstruction of human metabolism (Recon 1) to other mammals. By searching for genes homologous to Recon 1 genes within mammalian genomes, we were able to create draft metabolic reconstructions of five mammals, including the mouse. Each draft reconstruction was created in compartmentalized and non-compartmentalized version via two different approaches. Using gap-filling algorithms, we were able to produce all cellular components with three out of four versions of the mouse metabolic reconstruction. We finalized a functional model by iterative testing until it passed a predefined set of 260 validation tests. The reconstruction is the largest, most comprehensive mouse reconstruction to-date, accounting for 1,415 genes coding for 2,212 gene-associated reactions and 1,514 non-gene-associated reactions.We tested the mouse model for phenotype prediction capabilities. The majority of predicted essential genes were also essential in vivo. However, our non-tissue specific model was unable to predict gene essentiality for many of the metabolic genes shown to be essential in vivo. Our knockout simulation of the lipoprotein lipase gene correlated well with experimental results, suggesting that softer phenotypes can also be simulated.We have created a high-quality mouse genome-scale metabolic reconstruction, iMM1415 (Mus Musculus, 1415 genes). We demonstrate that the mouse model can be used to perform phenotype simulations, similar to models of microbe metabolism. Since the mouse is an important experimental organism, this model should become an essential tool for studying metabolic phenotypes in mice, including outcomes from drug screening.The first genome-scale reconstruction of metabolic networks emerged eleven years ago [1], four years after the first whole genome sequencing of an entire organism was published [2]. To date, 29 bacteria, 2 archaea and 5 eukaryotes have been reconstructed and for some organisms, up to 5 updates have been publ
Expression and Functional Role of Sprouty-2 in Breast Morphogenesis
Valgardur Sigurdsson, Saevar Ingthorsson, Bylgja Hilmarsdottir, Sigrun M. Gustafsdottir, Sigridur Rut Franzdottir, Ari Jon Arason, Eirikur Steingrimsson, Magnus K. Magnusson, Thorarinn Gudjonsson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060798
Abstract: Branching morphogenesis is a mechanism used by many species for organogenesis and tissue maintenance. Receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR) and the sprouty protein family are believed to be critical regulators of branching morphogenesis. The aim of this study was to analyze the expression of Sprouty-2 (SPRY2) in the mammary gland and study its role in branching morphogenesis. Human breast epithelial cells, breast tissue and mouse mammary glands were used for expression studies using immunoblotting, real rime PCR and immunohistochemistry. Knockdown of SPRY2 in the breast epithelial stem cell line D492 was done by lentiviral transduction of shRNA constructs targeting SPRY2. Three dimensional culture of D492 with or without endothelial cells was done in reconstituted basement membrane matrix. We show that in the human breast, SPRY2 is predominantly expressed in the luminal epithelial cells of both ducts and lobuli. In the mouse mammary gland, SPRY2 expression is low or absent in the virgin state, while in the pregnant mammary gland SPRY2 is expressed at branching epithelial buds with increased expression during lactation. This expression pattern is closely associated with the activation of the EGFR pathway. Using D492 which generates branching structures in three-dimensional (3D) culture, we show that SPRY2 expression is low during initiation of branching with subsequent increase throughout the branching process. Immunostaining locates expression of phosphorylated SPRY2 and EGFR at the tip of lobular-like, branching ends. SPRY2 knockdown (KD) resulted in increased migration, increased pERK and larger and more complex branching structures indicating a loss of negative feedback control during branching morphogenesis. In D492 co-cultures with endothelial cells, D492 SPRY2 KD generates spindle-like colonies that bear hallmarks of epithelial to mesenchymal transition. These data indicate that SPRY2 is an important regulator of branching morphogenesis and epithelial to mesenchymal transition in the mammary gland.
Statistics on ordered partitions of sets
Einar Steingrimsson
Mathematics , 2006,
Abstract: We introduce several statistics on ordered partitions of sets, that is, set partitions where the blocks are permuted arbitrarily. The distribution of these statistics is closely related to the q-Stirling numbers of the second kind. Some of the statistics are generalizations of known statistics on set partitions, but others are entirely new. All the new ones are sums of two statistics, inspired by statistics on permutations, where one of the two statistics is based on a certain partial ordering of the blocks of a partition.
Generalized permutation patterns -- a short survey
Einar Steingrimsson
Mathematics , 2008,
Abstract: An occurrence of a classical pattern p in a permutation \pi is a subsequence of \pi whose letters are in the same relative order (of size) as those in p. In an occurrence of a generalized pattern, some letters of that subsequence may be required to be adjacent in the permutation. Subsets of permutations characterized by the avoidance--or the prescribed number of occurrences--of generalized patterns exhibit connections to an enormous variety of other combinatorial structures, some of them apparently deep. We give a short overview of the state of the art for generalized patterns.
Some open problems on permutation patterns
Einar Steingrimsson
Mathematics , 2012,
Abstract: This is a brief survey of some open problems on permutation patterns, with an emphasis on subjects not covered in the recent book by Kitaev, \emph{Patterns in Permutations and words}. I first survey recent developments on the enumeration and asymptotics of the pattern 1324, the last pattern of length 4 whose asymptotic growth is unknown, and related issues such as upper bounds for the number of avoiders of any pattern of length $k$ for any given $k$. Other subjects treated are the M\"obius function, topological properties and other algebraic aspects of the poset of permutations, ordered by containment, and also the study of growth rates of permutation classes, which are containment closed subsets of this poset.
The Coloring Ideal and Coloring Complex of a Graph
Einar Steingrimsson
Mathematics , 2001,
Abstract: Let $G$ be a simple graph on $d$ vertices. We define a monomial ideal $K$ in the Stanley-Reisner ring $A$ of the order complex of the Boolean algebra on $d$ atoms. The monomials in $K$ are in one-to-one correspondence with the proper colorings of $G$. In particular, the Hilbert polynomial of $K$ equals the chromatic polynomial of $G$. The ideal $K$ is generated by square-free monomials, so $A/K$ is the Stanley-Reisner ring of a simplicial complex $C$. The $h$-vector of $C$ is a certain transformation of the tail $T(n)= n^d-k(n)$ of the chromatic polynomial $k$ of $G$. The combinatorial structure of the complex $C$ is described explicitly and it is shown that the Euler characteristic of $C$ equals the number of acyclic orientations of $G$.
Random Walks and Mixed Volumes of Hypersimplices
Eric Babson,Einar Steingrimsson
Mathematics , 2012,
Abstract: Below is a method for relating a mixed volume computation for polytopes sharing many facet directions to a symmetric random walk. The example of permutahedra and particularly hypersimplices is expanded upon.
Pattern avoidance in ascent sequences
Paul Duncan,Einar Steingrimsson
Mathematics , 2011,
Abstract: Ascent sequences are sequences of nonnegative integers with restrictions on the size of each letter, depending on the number of ascents preceding it in the sequence. Ascent sequences have recently been related to (2+2)-free posets and various other combinatorial structures. We study pattern avoidance in ascent sequences, giving several results for patterns of lengths up to 4, for Wilf equivalence and for growth rates. We establish bijective connections between pattern avoiding ascent sequences and various other combinatorial objects, in particular with set partitions. We also make a number of conjectures related to all of these aspects.
The Mobius Function of the Permutation Pattern Poset
Einar Steingrimsson,Bridget Eileen Tenner
Mathematics , 2009,
Abstract: A permutation \tau contains another permutation \sigma as a pattern if \tau has a subsequence whose elements are in the same order with respect to size as the elements in \sigma. This defines a partial order on the set of all permutations, and gives a graded poset P. We give a large class of pairs of permutations whose intervals in P have Mobius function 0. Also, we give a solution to the problem when \sigma occurs precisely once in \tau, and \sigma and \tau satisfy certain further conditions, in which case the Mobius function is shown to be either -1, 0 or 1. We conjecture that for intervals [\sigma,\tau] consisting of permutations avoiding the pattern 132, the magnitude of the Mobius function is bounded by the number of occurrences of \sigma in \tau. We also conjecture that the Mobius function of the interval [1,\tau] is -1, 0 or 1.
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