The loopy world of cohesin

The cohesin complex spatially organizes interphase chromatin by bringing distal genomic loci into close physical proximity, looping out the intervening DNA. Mutation of cohesin complex subunits is observed in cancer and developmental disorders, but the mechanisms through which these mutations may contribute to disease remain poorly understood. Here, we investigate a recurrent missense mutation to the hinge domain of the cohesin subunit SMC1A, observed in acute myeloid leukemia. Engineering this mutation into murine embryonic stem cells caused widespread changes in gene expression, including dysregulation of the pluripotency gene expression program. This mutation reduced cohesin levels at promoters and enhancers, decreased DNA loops and interactions across short genomic distances, and weakened insulation at CTCF-mediated DNA loops. These findings provide insight into how altered cohesin function contributes to disease and identify a requirement for the cohesin hinge domain in three-dimensional chromatin structure.

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Integrated Fractional white Noise as an Alternative to Multifractional Brownian Motion

Journal of Applied Probability ◽

10.1017/s0021900200003041 ◽

2007 ◽

Vol 44 (02) ◽

pp. 393-408 ◽

Cited By ~ 1

Author(s):

Allan Sly

Keyword(s):

Stochastic Process ◽

Brownian Motion ◽

White Noise ◽

Gaussian Process ◽

Discrete Data ◽

Hölder Exponent ◽

Scaling Properties ◽

Multifractional Brownian Motion ◽

Local Properties

Multifractional Brownian motion is a Gaussian process which has changing scaling properties generated by varying the local Hölder exponent. We show that multifractional Brownian motion is very sensitive to changes in the selected Hölder exponent and has extreme changes in magnitude. We suggest an alternative stochastic process, called integrated fractional white noise, which retains the important local properties but avoids the undesirable oscillations in magnitude. We also show how the Hölder exponent can be estimated locally from discrete data in this model.

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Brownian motion with quadratic killing and some implications

Journal of Applied Probability ◽

10.1017/s0021900200116079 ◽

1986 ◽

Vol 23 (04) ◽

pp. 893-903 ◽

Cited By ~ 2

Author(s):

Michael L. Wenocur

Keyword(s):

Brownian Motion ◽

Weibull Distribution ◽

Special Function ◽

Function Theory ◽

Killing Rate

Brownian motion subject to a quadratic killing rate and its connection with the Weibull distribution is analyzed. The distribution obtained for the process killing time significantly generalizes the Weibull. The derivation involves the use of the Karhunen–Loève expansion for Brownian motion, special function theory, and the calculus of residues.

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Properties of Isolated Mitochondria of Agaricus Bisporus: Their Relationship to Dormancy and the Germination of Spores

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100072733 ◽

1973 ◽

Vol 31 ◽

pp. 458-459

Author(s):

K. S. McCarty ◽

R. F. Weave ◽

L. Kemper ◽

F. S. Vogel

Keyword(s):

Mitochondrial Dna ◽

Ethidium Bromide ◽

Microscopic Examination ◽

Agaricus Bisporus ◽

Osmotic Shock ◽

Electron Microscopic Examination ◽

Electron Microscopic ◽

Isolated Mitochondria ◽

Dna Strands ◽

Cytoplasmic Ribosomes

During the prodromal stages of sporulation in the Basidiomycete, Agaricus bisporus, mitochondria accumulate in the basidial cells, zygotes, in the gill tissues prior to entry of these mitochondria, together with two haploid nuclei and cytoplasmic ribosomes, into the exospores. The mitochondria contain prominent loci of DNA [Fig. 1]. A modified Kleinschmidt spread technique1 has been used to evaluate the DNA strands from purified whole mitochondria released by osmotic shock, mitochondrial DNA purified on CsCl gradients [density = 1.698 gms/cc], and DNA purified on ethidium bromide CsCl gradients. The DNA appeared as linear strands up to 25 u in length and circular forms 2.2-5.2 u in circumference. In specimens prepared by osmotic shock, many strands of DNA are apparently attached to membrane fragments [Fig. 2]. When mitochondria were ruptured in hypotonic sucrose and then fixed in glutaraldehyde, the ribosomes were released for electron microscopic examination.

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Small Angle Electron Scattering From Vacuum Condensed Metallic Films

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100101657 ◽

1968 ◽

Vol 26 ◽

pp. 380-381

Author(s):

J. Silcox ◽

R. H. Wade

Keyword(s):

Electron Scattering ◽

Small Angle ◽

Ring Structure ◽

Two Dimensional ◽

Metallic Films ◽

Micro Structure ◽

Angle Scattering ◽

The Fourier Transform ◽

Source Of Information ◽

Kinematical Theory

Recent work has drawn attention to the possibilities that small angle electron scattering offers as a source of information about the micro-structure of vacuum condensed films. In particular, this serves as a good detector of discontinuities within the films. A review of a kinematical theory describing the small angle scattering from a thin film composed of discrete particles packed close together will be presented. Such a model could be represented by a set of cylinders packed side by side in a two dimensional fluid-like array, the axis of the cylinders being normal to the film and the length of the cylinders becoming the thickness of the film. The Fourier transform of such an array can be regarded as a ring structure around the central beam in the plane of the film with the usual thickness transform in a direction normal to the film. The intensity profile across the ring structure is related to the radial distribution function of the spacing between cylinders.

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Parathyroid gland before and after cisplatin treatment

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128584 ◽

1987 ◽

Vol 45 ◽

pp. 860-861

Author(s):

S.K. Aggarwal ◽

J.M. Fadool

Keyword(s):

Parathyroid Gland ◽

Wistar Rats ◽

Antitumor Agent ◽

The Body ◽

Cross Linking ◽

Limiting Factor ◽

Hormonal Changes ◽

Primary Mechanism ◽

Before And After ◽

Dna Strands

Cisplatin (CDDP) a potent antitumor agent suffers from severe toxic side effects with nephrotoxicity being the major dose-limiting factor, The primary mechanism of its action has been proposed to be through its cross-linking DNA strands. It has also been shown to inactivate various transport enzymes and induce hypocalcemia and hypomagnesemia that may be the underlying cause for some of its toxicities. The present is an effort to study its influence on the parathyroid gland for any hormonal changes that control calcium levels in the body.Male Swiss Wistar rats (Crl: (WI) BR) weighing 200-300 g and of 60 days in age were injected (ip) with cisplatin (7mg/kg in normal saline). The controls received saline injections only. The animals were injected (iv) with calcium (0.5 ml of 10% calcium gluconate/day) and were killed by decapitation on day 1 through 5. Trunk blood was collected in heparinized tubes.

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Immunoelectron microscope detection of C-type natriuretic peptide in normal human atrial tissue

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100147776 ◽

1993 ◽

Vol 51 ◽

pp. 388-389

Author(s):

Chi-Ming Wei ◽

Margaret Hukee ◽

Christopher G.A. McGregor ◽

John C. Burnett

Keyword(s):

Amino Acid ◽

Natriuretic Peptide ◽

Vascular Tone ◽

Cardiac Tissue ◽

Ring Structure ◽

Terminal Amino Acid ◽

Amino Acid Peptide ◽

Normal Human ◽

Terminal Amino ◽

The Brain

C-type natriuretic peptide (CNP) is a newly identified peptide that is structurally related to atrial (ANP) and brain natriuretic peptide (BNP). CNP exists as a 22-amino acid peptide and like ANP and BNP has a 17-amino acid ring formed by a disulfide bond. Unlike these two previously identified cardiac peptides, CNP lacks the COOH-terminal amino acid extension from the ring structure. ANP, BNP and CNP decrease cardiac preload, but unlike ANP and BNP, CNP is not natriuretic. While ANP and BNP have been localized to the heart, recent investigations have failed to detect CNP mRNA in the myocardium although small concentrations of CNP are detectable in the porcine myocardium. While originally localized to the brain, recent investigations have localized CNP to endothelial cells consistent with a paracrine role for CNP in the control of vascular tone. While CNP has been detected in cardiac tissue by radioimmunoassay, no studies have demonstrated CNP localization in normal human heart by immunoelectron microscopy.

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