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Search Results: 1 - 10 of 4689 matches for " Julia Krushkal "
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Parental ages and levels of DNA methylation in the newborn are correlated
Ronald M Adkins, Fridtjof Thomas, Frances A Tylavsky, Julia Krushkal
BMC Medical Genetics , 2011, DOI: 10.1186/1471-2350-12-47
Abstract: Using a genome-wide survey of 27,578 CpG dinucleotides in a cohort of 168 newborns, we examined the relationship between DNA methylation in newborns and a variety of parental and newborn traits. We found that methylation levels of 144 CpGs belonging to 142 genes were significantly correlated with maternal age. A weaker correlation was observed with paternal age. Among these genes, processes related to cancer were over-represented, as were functions related to neurological regulation, glucose/carbohydrate metabolism, nucleocytoplasmic transport, and transcriptional regulation. CpGs exhibiting gender differences in methylation were overwhelmingly located on the X chromosome, although a small subset of autosomal CpGs were found in genes previously shown to exhibit gender-specific differences in methylation levels.These results indicate that there are differences in CpG methylation levels at birth that are related to parental age and that could influence disease risk in childhood and throughout life.DNA methylation is a normal, heritable epigenetic modification that down-regulates the expression of approximately 1/3 of human genes [1-3] and is key to the allele-specific imprinting of genes [4]. DNA methylation also plays an important role in disease. For example, overall DNA hypomethylation accompanied by gene-specific hypermethylation is a hallmark of cancer [5]. Additionally, shifts in DNA methylation patterns appear to be involved in the normal aging process and increase in disease susceptibility [6]. Indeed, there is ample evidence for characteristic changes in the patterns of DNA methylation with age.The earliest data supporting progressive changes in DNA methylation patterns with age came from global studies of blood that demonstrated lower levels of methylation in older individuals [7] and greater differences in methylation in older monozygotic twins [8]. Christensen et al. [9] examined 217 tissues sampled from a range of non-diseased solid tissues and blood. In
Comparative genomics of Geobacter chemotaxis genes reveals diverse signaling function
Hoa T Tran, Julia Krushkal, Frances M Antommattei, Derek R Lovley, Robert M Weis
BMC Genomics , 2008, DOI: 10.1186/1471-2164-9-471
Abstract: The genomes of G. sulfurreducens, G. metallireducens, and G. uraniireducens contain multiple (~70) homologs of chemotaxis genes arranged in several major clusters (six, seven, and seven, respectively). Unlike the single gene cluster of E. coli, the Geobacter clusters are not all located near the flagellar genes. The probable functions of some Geobacter clusters are assignable by homology to known pathways; others appear to be unique to the Geobacter sp. and contain genes of unknown function. We identified large numbers of methyl-accepting chemotaxis protein (MCP) homologs that have diverse sensing domain architectures and generate a potential for sensing a great variety of environmental signals. We discuss mechanisms for class-specific segregation of the MCPs in the cell membrane, which serve to maintain pathway specificity and diminish crosstalk. Finally, the regulation of gene expression in Geobacter differs from E. coli. The sequences of predicted promoter elements suggest that the alternative sigma factors σ28 and σ54 play a role in regulating the Geobacter chemotaxis gene expression.The numerous chemoreceptors and chemotaxis-like gene clusters of Geobacter appear to be responsible for a diverse set of signaling functions in addition to chemotaxis, including gene regulation and biofilm formation, through functionally and spatially distinct signaling pathways.Chemotaxis is a trait shared by many bacteria that enables cells to move toward chemical attractants and away from repellents. The chemotaxis system of E. coli regulates flagellar-based motility; it has been studied in the great detail and has served as a paradigm for chemotactic motility [1,2]. However, it is now apparent from genomic, genetic and biochemical studies conducted with other bacteria that a diversity of pathway functions and purposes exist well beyond the E. coli paradigm [3-5].The E. coli chemotaxis pathway includes 11 genes, most of which are organized in a cluster near the flagellar genes [6
The genome sequence of Geobacter metallireducens: features of metabolism, physiology and regulation common and dissimilar to Geobacter sulfurreducens
Muktak Aklujkar, Julia Krushkal, Genevieve DiBartolo, Alla Lapidus, Miriam L Land, Derek R Lovley
BMC Microbiology , 2009, DOI: 10.1186/1471-2180-9-109
Abstract: The experimentally observed greater metabolic versatility of G. metallireducens versus G. sulfurreducens is borne out by the presence of more numerous genes for metabolism of organic acids including acetate, propionate, and pyruvate. Although G. metallireducens lacks a dicarboxylic acid transporter, it has acquired a second putative succinate dehydrogenase/fumarate reductase complex, suggesting that respiration of fumarate was important until recently in its evolutionary history. Vestiges of the molybdate (ModE) regulon of G. sulfurreducens can be detected in G. metallireducens, which has lost the global regulatory protein ModE but retained some putative ModE-binding sites and multiplied certain genes of molybdenum cofactor biosynthesis. Several enzymes of amino acid metabolism are of different origin in the two species, but significant patterns of gene organization are conserved. Whereas most Geobacteraceae are predicted to obtain biosynthetic reducing equivalents from electron transfer pathways via a ferredoxin oxidoreductase, G. metallireducens can derive them from the oxidative pentose phosphate pathway. In addition to the evidence of greater metabolic versatility, the G. metallireducens genome is also remarkable for the abundance of multicopy nucleotide sequences found in intergenic regions and even within genes.The genomic evidence suggests that metabolism, physiology and regulation of gene expression in G. metallireducens may be dramatically different from other Geobacteraceae.Geobacter metallireducens is a member of the Geobacteraceae, a family of Fe(III)-respiring Delta-proteobacteria that are of interest for their role in cycling of carbon and metals in aquatic sediments and subsurface environments as well as the bioremediation of organic- and metal-contaminated groundwater and the harvesting of electricity from complex organic matter [1,2]. G. metallireducens is of particular interest because it was the first microorganism found to be capable of a number
Link groups of 4-manifolds
Vyacheslav Krushkal
Mathematics , 2005, DOI: 10.2140/gtm.2012.18.199
Abstract: The notion of a Bing cell is introduced, and it is used to define invariants, link groups, of 4-manifolds. Bing cells combine some features of both surfaces and 4-dimensional handlebodies, and the link group \lambda(M) measures certain aspects of the handle structure of a 4-manifold M. This group is a quotient of the fundamental group, and examples of manifolds are given with \pi_1(M) not equal to \lambda(M). The main construction of the paper is a generalization of the Milnor group, which is used to formulate an obstruction to embeddability of Bing cells into 4-space. Applications to the A-B slice problem and to the structure of topological arbiters are discussed.
Link groups and the A-B slice problem
Vyacheslav Krushkal
Mathematics , 2006,
Abstract: The A-B slice problem is a reformulation of the topological 4-dimensional surgery conjecture in terms of decompositions of the 4-ball and link homotopy. We show that link groups, a recently developed invariant of 4-manifolds, provide an obstruction for the class of model decompositions, introduced by M. Freedman and X.-S. Lin. This unifies and extends the previously known partial obstructions in the A-B slice program. As a consequence, link groups satisfy Alexander duality when restricted to the class of model decompositions, but not for general submanifolds of the 4-ball.
Graphs, links, and duality on surfaces
Vyacheslav Krushkal
Mathematics , 2009,
Abstract: We introduce a polynomial invariant of graphs on surfaces, $P_G$, generalizing the classical Tutte polynomial. Topological duality on surfaces gives rise to a natural duality result for $P_G$, analogous to the duality for the Tutte polynomial of planar graphs. This property is important from the perspective of statistical mechanics, where the Tutte polynomial is known as the partition function of the Potts model. For ribbon graphs, $P_G$ specializes to the well-known Bollobas-Riordan polynomial, and in fact the two polynomials carry equivalent information in this context. Duality is also established for a multivariate version of the polynomial $P_G$. We then consider a 2-variable version of the Jones polynomial for links in thickened surfaces, taking into account homological information on the surface. An analogue of Thistlethwaite's theorem is established for these generalized Jones and Tutte polynomials for virtual links.
A geometric proof of the Milnor conjecture
Vyacheslav Krushkal
Mathematics , 2012,
Abstract: A geometric argument is given to prove that the Seifert genus of a positive knot equals its slice genus. A combinatorial invariant, giving a lower bound for the slice genus, is formulated for arbitrary knots. Properties and applications of this invariant are discussed.
Dwyer's filtration and topology of 4-manifolds
Vyacheslav Krushkal
Mathematics , 2002,
Abstract: Topological 4-dimensional surgery is conjectured to fail, in general, for free fundamental groups. M. Freedman and P. Teichner have shown that surgery problems with an arbitrary fundamental group have a solution, provided they satisfy a certain condition on Dwyer's filtration on second homology. We give a new geometric proof of this result, and analyze its relation to the canonical surgery problems.
On disk embedding up to s-cobordism
Vyacheslav Krushkal
Mathematics , 2002,
Abstract: The disk embedding lemma is a technique underlying the topological classification results in 4-manifold topology for good fundamental groups. The purpose of this paper is to develop new tools for disk embedding that work up to s-cobordism, without restrictions on the fundamental group. As an application we show that a surgery problem gives rise to a collection of capped gropes that fit in the framework of control theory.
Robust 4-manifolds and robust embeddings
Vyacheslav Krushkal
Mathematics , 2008,
Abstract: A link in the 3-sphere is homotopically trivial, according to Milnor, if its components bound disjoint maps of disks in the 4-ball. This paper concerns the question of what spaces give rise to the same class of homotopically trivial links when used in place of disks in an analogous definition. We show that there are 4-manifolds for which this property depends on their embedding in the 4-ball. This work is motivated by the A-B slice problem, a reformulation of the 4-dimensional topological surgery conjecture. As a corollary this provides a new, secondary, obstruction in the A-B slice problem for a certain class of decompositions of D^4.
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