1,553 research outputs found
Computational analysis of nucleosome positioning datasets
Chromatin is a complex of DNA and histone proteins that constitutes the elemental
material of eukaryotic chromosomes. The basic repeating sub-unit of chromatin, the
nucleosome core particle, is comprised of approximately 146 base pairs (bp) of DNA
wrapped around an octamer of core histones. Core particles are joined together by
variable lengths of linker DNA to form chains of nucleosomes that are folded into
higher-order structures. The specific distribution of nucleosomes along the DNA
fibre is known to influence this folding process. Furthermore, on a local level, the
positioning of nucleosomes can control access to DNA sequence motifs, and thus
plays a fundamental role in regulating gene expression. Despite considerable
experimental effort, neither the folding process nor the mechanisms for gene
regulation are currently well understood.Monomer extension (ME) is an established in vitro experimental technique which
maps the positions adopted by reconstituted core histone octamers on a defined DNA
sequence. It provides quantitative positioning information, at high resolution, over
long continuous stretches of DNA sequence. This technique has been employed to
map several genes: globin genes (8 kbp), the beta-lactoglobulin gene (10 kbp) and
various imprinting genes (4 kbp).This study explores and analyses this unique dataset, utilising computational and
stochastic techniques, to gain insight into the potential influence of nucleosomal
positioning on the structure and function of chromatin. The first section of this thesis
expands upon prior analyses, explores general features of the dataset using common
bioinformatics tools, and attempts to relate the quantitative positioning information
from ME to data from other commonly used competitive reconstitution protocols.
Finally, evidence of a correlation between the in vitro ME dataset and in vivo
nucleosome positions for the beta-lactoglobulin gene region is presented.The second section presents the development of a novel method for the analysis of
ME maps using Monte Carlo simulation methods. The goal was to use the ME
datasets to simulate a higher order chromatin fibre, taking advantage of the longrange and quantitative nature of the ME datasets.The Monte Carlo simulations have allowed new insights to be gleaned from the
datasets. Analysis of the beta-lactoglobulin positioning map indicates the potential
for discrete disruption of nucleosomal organisation, at specific physiological
nucleosome densities, over regions found to have unusual chromatin structure in
vivo. This suggests a correspondence between the quantitative histone octamer
positioning information in vitro and the positioning of nucleosomes in vivo.Further, the simulations demonstrate that histone density-dependent changes in
nucleosomal organisation, in both the beta-lactoglobulin and globin positioning
maps, often occur in regions involved in gene regulation. This implies that irregular
chromatin structures may form over certain biologically significant regions.Taken together, these studies lend weight to the hypothesis that nucleosome
positioning information encoded within DNA plays a fundamental role in directing
chromatin structure in vivo
Arithmetic patches, weak tangents, and dimension
The first named author is supported by a Leverhulme Trust Research Fellowship (RF-2016-500) and the second named author is supported by a PhD scholarship provided bythe School of Mathematics in the University of St AndrewsWe investigate the relationships between several classical notions in arithmetic combinatorics and geometry including the presence (or lack of) arithmetic progressions (or patches in dimensions at least 2), the structure of tangent sets, and the Assouad dimension. We begin by extending a recent result of Dyatlov and Zahl by showing that a set cannot contain arbitrarily large arithmetic progressions (patches) if it has Assouad dimension strictly smaller than the ambient spatial dimension. Seeking a partial converse, we go on to prove that having Assouad dimension equal to the ambient spatial dimension is equivalent to having weak tangents with non-empty interior and to ‘asymptotically’ containing arbitrarily large arithmetic patches. We present some applications of our results concerning sets of integers, which include a weak solution to the Erdös–Turán conjecture on arithmetic progressions.PostprintPeer reviewe
An update on nuclear calcium signalling
Over the past 15 years or so, numerous studies have sought to characterise how nuclear calcium (Ca2+) signals are generated and reversed, and to understand how events that occur in the nucleoplasm influence cellular Ca2+ activity, and vice versa. In this Commentary, we describe mechanisms of nuclear Ca2+ signalling and discuss what is known about the origin and physiological significance of nuclear Ca2+ transients. In particular, we focus on the idea that the nucleus has an autonomous Ca2+ signalling system that can generate its own Ca2+ transients that modulate processes such as gene transcription. We also discuss the role of nuclear pores and the nuclear envelope in controlling ion flux into the nucleoplasm
Uniform scaling limits for ergodic measures
J. M. Fraser and M. Pollicott were financially supported in part by the EPSRC grant EP/J013560/1.We provide an elementary proof that ergodic measures on one-sided shift spaces are ‘uniformly scaling’ in the following sense: at almost every point the scenery distributions weakly converge to a common distribution on the space of measures. Moreover, we show how the limiting distribution can be expressed in terms of, and derived from, a 'reverse Jacobian’ function associated with the corresponding measure on the space of left infinite sequences. Finally we specialise to the setting of Gibbs measures, discuss some statistical properties, and prove a Central Limit Theorem for ergodic Markov measures.PostprintPeer reviewe
Editorial: If the settler never came
If the settler never came and the (Australian) continent developed herself, what kinds of conversations would we consider? Perhaps, we would highlight the fact that the Country and Island landscape did not have an estimated number of languages but significantly more than the speculated 250 (or “over 300”, or “hundreds of”) Aboriginal and Torres Strait Islander languages across the island and continental landscape. It would be a given continuance that every year across the Country, and not just 2019 declared by the United Nations General assembly, as the year to celebrate the Indigenous languages. Perhaps the ways we define, discuss and distinguish these numerous, living languages would be very different from our current forensic approaches
Effects of supply and demand disturbances on real commodity prices: the US, UK and Japanese experience
Using forty-one years of monthly data, this paper assesses the impact of economy-wide supply and demand shocks on commodity prices in three of the world?s major economies. Utilising a small theoretical macro model, empirical results support the hypothesis that the relationship between real commodity prices and inflation can be either positive or negative depending on the relative importance of supply and demand shocks in the national economy. Our results also show that differences occur across economies with the UK commodity returns registering more sensitivity to demand shocks than those of US and Japanese markets. Supply and demand components of commodity prices have also varied over time and across economies, suggesting that commodity markets are not fully globally integrated but are highly sensitive to national influences
The dimensions of inhomogeneous self-affine sets
Funding: SAB thanks the Carnegie Trust for financially supporting this work. JMF was financially supported by a Leverhulme Trust Research Fellowship (RF-2016-500) and an EPSRC Standard Grant (EP/R015104/1).We prove that the upper box dimension of an inhomogeneous self-affine set is bounded above by the maximum of the affinity dimension and the dimension of the condensation set. In addition, we determine sufficient conditions for this upper bound to be attained, which, in part, constitutes an exploration of the capacity for the condensation set to mitigate dimension drop between the affinity dimension and the corresponding homogeneous attractor. Our work improves and unifies previous results on general inhomogeneous attractors, low-dimensional affine systems, and inhomogeneous self-affine carpets, while providing inhomogeneous analogues of Falconer’s seminal results on homogeneous self-affine sets.Publisher PDFPeer reviewe
MELANESIA BURNING: RELIGIOUS REVOLUTION IN THE WESTERN PACIFIC
In the history of Pacific Christianity, the explosion of revival activity within Melanesia during the 1970s remains an untold story. Within this regional spiritual upheaval, ecstatic Pentecostalist phenomena spread with unprecedented rapidity, intensity and geographical scope. As a result of these movements, Christianity assumed an importance in Melanesia in a way it never had before, as local congregations redefined their church life and spirituality over and against mission Christianity. This article documents a major branch of this regional revivalism. A detailed description of this series of interconnected movements transitions to an explanation of their success in terms of four factors: the mutual ramification of the revivals with political independence movements; the fact that despite being built on theologies of world breaking, the revivals dovetailed with traditional Melanesian religious experiences; the existence of interdenominational organisations that expedited the movement of people, practices and ideas across local, regional and national frontiers; and, finally, the personal dimensions of Melanesian revivalism, whereby the genesis, uptake and diffusion of revival movements often depended crucially upon the persuasive capabilities of influential Christian leaders in each society
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