2,030 research outputs found
DNA bubble dynamics as a quantum Coulomb problem
We study the dynamics of denaturation bubbles in double-stranded DNA on the
basis of the Poland-Scheraga model. We demonstrate that the associated
Fokker-Planck equation is equivalent to a Coulomb problem. Below the melting
temperature the bubble lifetime is associated with the continuum of scattering
states of the repulsive Coulomb potential, at the melting temperature the
Coulomb potential vanishes and the underlying first exit dynamics exhibits a
long time power law tail, above the melting temperature, corresponding to an
attractive Coulomb potential, the long time dynamics is controlled by the
lowest bound state. Correlations and finite size effects are discussed.Comment: 4 pages, 3 figures, revte
Dynamics of DNA-breathing: Weak noise analysis, finite time singularity, and mapping onto the quantum Coulomb problem
We study the dynamics of denaturation bubbles in double-stranded DNA on the
basis of the Poland-Scheraga model. We show that long time distributions for
the survival of DNA bubbles and the size autocorrelation function can be
derived from an asymptotic weak noise approach. In particular, below the
melting temperature the bubble closure corresponds to a noisy finite time
singularity. We demonstrate that the associated Fokker-Planck equation is
equivalent to a quantum Coulomb problem. Below the melting temperature the
bubble lifetime is associated with the continuum of scattering states of the
repulsive Coulomb potential; at the melting temperature the Coulomb potential
vanishes and the underlying first exit dynamics exhibits a long time power law
tail; above the melting temperature, corresponding to an attractive Coulomb
potential, the long time dynamics is controlled by the lowest bound state.
Correlations and finite size effects are discussed.Comment: 12 pages, 10 figures, revte
Pulling a polymer out of a potential well and the mechanical unzipping of DNA
Motivated by the experiments on DNA under torsion, we consider the problem of
pulling a polymer out of a potential well by a force applied to one of its
ends. If the force is less than a critical value, then the process is activated
and has an activation energy proportinal to the length of the chain. Above this
critical value, the process is barrierless and will occur spontaneously. We use
the Rouse model for the description of the dynamics of the peeling out and
study the average behaviour of the chain, by replacing the random noise by its
mean. The resultant mean-field equation is a nonlinear diffusion equation and
hence rather difficult to analyze. We use physical arguments to convert this in
to a moving boundary value problem, which can then be solved exactly. The
result is that the time required to pull out a polymer of segments
scales like . For models other than the Rouse, we argue that Comment: 11 pages, 6 figures. To appear in PhysicalReview
Dynamical scaling of the DNA unzipping transition
We report studies of the equilibrium and the dynamics of a general set of
lattice models which capture the essence of the force-induced or mechanical DNA
unzipping transition. Besides yielding the whole equilibrium phase diagram in
the force vs temperature plane, which reveals the presence of an interesting
re-entrant unzipping transition for low T, these models enable us to
characterize the dynamics of the process starting from a non-equilibrium
initial condition. The thermal melting of the DNA strands displays a model
dependent time evolution. On the contrary, our results suggest that the
dynamical mechanism for the unzipping by force is very robust and the scaling
behaviour does not depend on the details of the description we adopt.Comment: 6 pages, 4 figures, A shorter version of this paper appeared in Phys.
Rev. Lett. 88, 028102 (2002
Quantitative test of the barrier nucleosome model for statistical positioning of nucleosomes up- and downstream of transcription start sites
The positions of nucleosomes in eukaryotic genomes determine which parts of
the DNA sequence are readily accessible for regulatory proteins and which are
not. Genome-wide maps of nucleosome positions have revealed a salient pattern
around transcription start sites, involving a nucleosome-free region (NFR)
flanked by a pronounced periodic pattern in the average nucleosome density.
While the periodic pattern clearly reflects well-positioned nucleosomes, the
positioning mechanism is less clear. A recent experimental study by Mavrich et
al. argued that the pattern observed in S. cerevisiae is qualitatively
consistent with a `barrier nucleosome model', in which the oscillatory pattern
is created by the statistical positioning mechanism of Kornberg and Stryer. On
the other hand, there is clear evidence for intrinsic sequence preferences of
nucleosomes, and it is unclear to what extent these sequence preferences affect
the observed pattern. To test the barrier nucleosome model, we quantitatively
analyze yeast nucleosome positioning data both up- and downstream from NFRs.
Our analysis is based on the Tonks model of statistical physics which
quantifies the interplay between the excluded-volume interaction of nucleosomes
and their positional entropy. We find that although the typical patterns on the
two sides of the NFR are different, they are both quantitatively described by
the same physical model, with the same parameters, but different boundary
conditions. The inferred boundary conditions suggest that the first nucleosome
downstream from the NFR (the +1 nucleosome) is typically directly positioned
while the first nucleosome upstream is statistically positioned via a
nucleosome-repelling DNA region. These boundary conditions, which can be
locally encoded into the genome sequence, significantly shape the statistical
distribution of nucleosomes over a range of up to ~1000 bp to each side.Comment: includes supporting materia
The role of protein tyrosine phosphorylation in integrin-mediated gene induction in monocytes.
Integrin-mediated cell adhesion, or cross-linking of integrins using antibodies, often results in the enhanced tyrosine phosphorylation of certain intracellular proteins, suggesting that integrins may play a role in signal transduction processes. In fibroblasts, platelets, and carcinoma cells, a novel tyrosine kinase termed pp125FAK has been implicated in integrin-mediated tyrosine phosphorylation. In some cell types, integrin ligation or cell adhesion has also been shown to result in the increased expression of certain genes. Although it seems reasonable to hypothesize that integrin-mediated tyrosine phosphorylation and integrin-mediated gene induction are related, until now, there has been no direct evidence supporting this hypothesis. In the current report, we explore the relationship between integrin- mediated tyrosine phosphorylation and gene induction in human monocytes. We demonstrate that monocyte adherence to tissue culture dishes or to extracellular matrix proteins is followed by a rapid and profound increase in tyrosine phosphorylation, with the predominant phosphorylated component being a protein of 76 kD (pp76). Tyrosine phosphorylation of pp76 and other monocyte proteins can also be triggered by incubation of monocytes with antibodies to the integrin beta 1 subunit, or by F(ab')2 fragments of such antibodies, but not by F(ab) fragments. The ligation of beta 1 integrins with antibodies or F(ab')2 fragments also induces the expression of immediate-early (IE) genes such as IL-1 beta. When adhering monocytes are treated with the tyrosine kinase inhibitors genistein or herbimycin, both phosphorylation of pp76 and induction of IL-1 beta message are blocked in a dose-dependent fashion. Similarly, treatment with genistein or herbimycin can block tyrosine phosphorylation of pp76 and IL-1 beta message induction mediated by ligation of beta 1 integrin with antibodies. These observations suggest that protein tyrosine phosphorylation is an important aspect of integrin-mediated IE gene induction in monocytes. The cytoplasmic tyrosine kinase pp125FAK, although important in integrin signaling in other cell types, seems not to play a role in monocytes because this protein could not be detected in these cells
Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of beta 1 integrins.
The integrin family of cell adhesion receptors mediates many of the interactions between cells and the extracellular matrix. Because the extracellular matrix has profound influences on cell behavior, it seems likely that integrins transduce biochemical signals across the cell membrane. The nature of these putative signals has, thus far, remained elusive. Antibody-mediated clustering of integrin receptors was used to mimic the integrin clustering process that occurs during formation of adhesive contacts. Human epidermal carcinoma (KB) cells were incubated with an anti-beta 1 integrin monoclonal antibody for 30 min on ice followed by incubation at 37 degrees C with anti-rat IgG. This treatment, which induced integrin clustering, stimulated the phosphorylation on tyrosine residues of a 115- to 130-kDa complex of proteins termed pp130. When integrins were clustered in the presence of the phosphatase inhibitor sodium orthovanadate, pp130 showed a substantial increase in phosphorylation compared to the case in which integrins were clustered in the absence of vanadate. Maximal pp130 phosphorylation was observed 10-20 min after initiation of integrin clustering in the absence of vanadate or after 5-10 min in its presence. These time courses roughly parallel the formation of integrin clusters on the cell surface as observed by fluorescence microscopy. pp130 phosphorylation depended on the amount of anti-integrin antibody present. Additionally, the tyrosine phosphorylation of pp130 showed specificity since it was stimulated by antibodies to the integrin alpha 3 and beta 1 subunits but not by antibodies to other integrin alpha subunits or to nonintegrin cell surface proteins. Immunoprecipitation experiments clearly demonstrated that pp130 is not itself a beta 1 integrin. It is postulated, therefore, that the integrin-stimulated tyrosine phosphorylation of pp130 may reflect part of an important signal transduction process between the extracellular matrix and the cell interior
The role of religion in the longer-range future, April 6, 7, and 8, 2006
This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This conference that took place during April 6, 7, and 8, 2006. Co-organized by David Fromkin, Director, Frederick S. Pardee Center for the Study of the Longer-Range Future, and Ray L. Hart, Dean ad interim Boston University School of TheologyThe conference brought together some 40 experts from various disciplines to ponder upon the “great dilemma” of how science, religion, and the human future interact. In particular, different panels looked at trends in what is happening to religion around the world, questions about how religion is impacting the current political and economic order, and how the social dynamics unleashed by science and by religion can be reconciled.Carnegie Council on Ethics and International Affair
The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes
To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance
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