DNMTs are required for delayed genome instability caused by radiation

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited - Copyright @ 2012 Landes Bioscience.The ability of ionizing radiation to initiate genomic instability has been harnessed in the clinic where the localized delivery of controlled doses of radiation is used to induce cell death in tumor cells. Though very effective as a therapy, tumor relapse can occur in vivo and its appearance has been attributed to the radio-resistance of cells with stem cell-like features. The molecular mechanisms underlying these phenomena are unclear but there is evidence suggesting an inverse correlation between radiation-induced genomic instability and global hypomethylation. To further investigate the relationship between DNA hypomethylation, radiosensitivity and genomic stability in stem-like cells we have studied mouse embryonic stem cells containing differing levels of DNA methylation due to the presence or absence of DNA methyltransferases. Unexpectedly, we found that global levels of methylation do not determine radiosensitivity. In particular, radiation-induced delayed genomic instability was observed at the Hprt gene locus only in wild-type cells. Furthermore, absence of Dnmt1 resulted in a 10-fold increase in de novo Hprt mutation rate, which was unaltered by radiation. Our data indicate that functional DNMTs are required for radiation-induced genomic instability, and that individual DNMTs play distinct roles in genome stability. We propose that DNMTS may contribute to the acquirement of radio-resistance in stem-like cells.This study is funded by NOTE, BBSRC and the Royal Society Dorothy Hodgkin Research Fellowship

Long-lived driven solid-state quantum memory

We investigate the performance of inhomogeneously broadened spin ensembles as quantum memories under continuous dynamical decoupling. The role of the continuous driving field is two-fold: first, it decouples individual spins from magnetic noise; second and more important, it suppresses and reshapes the spectral inhomogeneity of spin ensembles. We show that a continuous driving field, which itself may also be inhomogeneous over the ensemble, can enhance the decay of the tails of the inhomogeneous broadening distribution considerably. This fact enables a spin ensemble based quantum memory to exploit the effect of cavity protection and achieve a much longer storage time. In particular, for a spin ensemble with a Lorentzian spectral distribution, our calculations demonstrate that continuous dynamical decoupling has the potential to improve its storage time by orders of magnitude for the state-of-art experimental parameters

Expression of a large LINE-1-driven antisense RNA is linked to epigenetic silencing of the metastasis suppressor gene TFPI-2 in cancer

LINE-1 retrotransposons are abundant repetitive elements of viral origin, which in normal cells are kept quiescent through epigenetic mechanisms. Activation of LINE-1 occurs frequently in cancer and can enable LINE-1 mobilization but also has retrotransposition-independent consequences. We previously reported that in cancer, aberrantly active LINE-1 promoters can drive transcription of flanking unique sequences giving rise to LINE-1 chimeric transcripts (LCTs). Here, we show that one such LCT, LCT13, is a large transcript (>300 kb) running antisense to the metastasis-suppressor gene TFPI- 2. We have modelled antisense RNA expression at TFPI-2 in transgenic mouse embryonic stem (ES) cells and demonstrate that antisense RNA induces silencing and deposition of repressive histone modifications implying a causal link. Consistent with this, LCT13 expression in breast and colon cancer cell lines is associated with silencing and repressive chromatin at TFPI-2. Furthermore, we detected LCT13 transcripts in 56% of colorectal tumours exhibiting reduced TFPI-2 expression. Our findings implicate activation of LINE-1 elements in subsequent epigenetic remodelling of surrounding genes, thus hinting a novel retrotransposition-independent role for LINE-1 elements in malignancy

Bound states and entanglement generation in waveguide quantum electrodynamics

We investigate the behavior of two quantum emitters (two-level atoms) embedded in a linear waveguide, in a quasi-one-dimensional configuration. Since the atoms can emit, absorb and reflect radiation, the pair can spontaneously relax towards an entangled bound state, under conditions in which a single atom would instead decay. We analyze the properties of these bound states, which occur for resonant values of the interatomic distance, and discuss their relevance with respect to entanglement generation. The stability of such states close to the resonance is studied, as well as the properties of non resonant bound states, whose energy is below the threshold for photon propagation

Quantifying Genuine Multipartite Correlations and their Pattern Complexity

We propose an information-theoretic framework to quantify multipartite correlations in classical and quantum systems, answering questions such as what is the amount of seven-partite correlations in a given state of ten particles? We identify measures of genuine multipartite correlations, i.e., statistical dependencies that cannot be ascribed to bipartite correlations, satisfying a set of desirable properties. Inspired by ideas developed in complexity science, we then introduce the concept of weaving to classify states that display different correlation patterns, but cannot be distinguished by correlation measures. The weaving of a state is defined as the weighted sum of correlations of every order. Weaving measures are good descriptors of the complexity of correlation structures in multipartite systems

Oscillopsia in labyrinthine defective patients: Comparison of objective and subjective measures

Objective: To compare the oscillopsia sensation in vestibular defective patients, using a specific handicap questionnaire and a specific Visual Analog Scale, with objective measure of the vertical vestibulo-ocular reflex efficiency in the pitch plane, using the computerized Dynamic Visual Acuity (DVA) test and Gaze Stabilization Test (GST).Design: Controlled retrospective study.Setting: Day hospital in ENT Rehabilitation Unit.Subjects: Sixty-five subjects: 35 controls (12 men and 23 women; mean age, 50.77 +/- 13.39 years) and 30 patients with chronic dizziness: 18 with unilateral vestibular hypofunction (7 men and 11 women; mean age, 55.50 +/- 12.72 years) and 12 with bilateral hypofunction (7 men and 5 women; mean age, 57.25 +/- 9.18 years).Main measures: Computerize vertical DVA and GST; subjective Visual Analog Scale, Oscillopsia Score questionnaire.Results: Instrumental tests had different means between subject groups; vertical DVA results and subjective measures were significantly correlated.Conclusions: Vertical DVA and GST test in up and down direction are able to separate healthy and vestibular patients. Moreover, the DVA test in down direction differentiates patients with unilateral vestibular hypofunction and with bilateral vestibular hypofunction. These results show that vertical DVA test can be used for the assessment of the visual field instability referred to as disabling. (C) 2010 Elsevier Inc. All rights reserved

Dynamics of multipartite quantum correlations under decoherence

Quantum discord is an optimal resource for the quantification of classical and non-classical correlations as compared to other related measures. Geometric measure of quantum discord is another measure of quantum correlations. Recently, the geometric quantum discord for multipartite states has been introduced by Jianwei Xu [arxiv:quant/ph.1205.0330]. Motivated from the recent study [Ann. Phys. 327 (2012) 851] for the bipartite systems, I have investigated global quantum discord (QD) and geometric quantum discord (GQD) under the influence of external environments for different multipartite states. Werner-GHZ type three-qubit and six-qubit states are considered in inertial and non-inertial settings. The dynamics of QD and GQD is investigated under amplitude damping, phase damping, depolarizing and flipping channels. It is seen that the quantum discord vanishes for p>0.75 in case of three-qubit GHZ states and for p>0.5 for six qubit GHZ states. This implies that multipartite states are more fragile to decoherence for higher values of N. Surprisingly, a rapid sudden death of discord occurs in case of phase flip channel. However, for bit flip channel, no sudden death happens for the six-qubit states. On the other hand, depolarizing channel heavily influences the QD and GQD as compared to the amplitude damping channel. It means that the depolarizing channel has the most destructive influence on the discords for multipartite states. From the perspective of accelerated observers, it is seen that effect of environment on QD and GQD is much stronger than that of the acceleration of non-inertial frames. The degradation of QD and GQD happens due to Unruh effect. Furthermore, QD exhibits more robustness than GQD when the multipartite systems are exposed to environment.Comment: 15 pages, 4 figures, 4 table

Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation