212 research outputs found

    DNMTs are required for delayed genome instability caused by radiation

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    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

    Quantifying Genuine Multipartite Correlations and their Pattern Complexity

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    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

    Expression of a SOX1 overlapping transcript in neural differentiation and cancer models

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    SOX1 is a member of the SOXB1 subgroup of transcription factors involved in early embryogenesis, CNS development and maintenance of neural stem cells. The structure and regulation of the human SOX1 locus has been less studied than that of SOX2, another member of the SOXB1 subgroup for which an overlapping transcript has been reported. Here we report that the SOX1 locus harbours a SOX1 overlapping transcript (SOX1-OT), and describe expression, splicing variants and detection of SOX1-OT in different stem and cancer cells. RT-PCR and RACE experiments were performed to detect and characterise the structure of SOX1-OT in neuroprogenitor cultures and across different cancer cell lines. SOX1-OT was found to present a complex structure including several unannotated exons, different transcript variants and at least two potential transcription start sites. SOX1-OT was found to be highly expressed in differentiated neural stem cells across different time points of differentiation, and its expression correlated with SOX1 gene expression. Concomitant expression of SOX1 and SOX1-OT was further observed in several cancer cell models. While the function of this transcript is unknown, the regulatory role reported for other lncRNAs strongly suggests a possible role for SOX1-OT in regulating SOX1 expression, as previously observed for SOX2. The elucidation of the genetic and regulatory context governing SOX1 expression will contribute to clarifying its role in stem cell differentiation and tumorigenesis

    Dynamics of spontaneous emission in a single-end photonic waveguide

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    We investigate the spontaneous emission of a two-level system, e.g. an atom or atomlike object, coupled to a single-end, i.e., semi-infinite, one-dimensional photonic waveguide such that one end behaves as a perfect mirror while light can pass through the opposite end with no back-reflection. Through a quantum microscopic model we show that such geometry can cause non-exponential and long-lived atomic decay. Under suitable conditions, a bound atom-photon stationary state appears in the atom-mirror interspace so as to trap a considerable amount of initial atomic excitation. Yet, this can be released by applying an atomic frequency shift causing a revival of photon emission. The resilience of such effects to typical detrimental factors is analyzed.Comment: 6 pages, 4 figure

    Quantum estimation of a two-phase spin rotation

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    We study the estimation of an infinitesimal rotation of a spin-j system, characterised by two unknown phases, and compare the estimation precision achievable with two different strategies. The first is a standard \u2018joint estimation\u2019 strategy, in which a single probe state is used to estimate both parameters, while the second is a \u2018sequential\u2019 strategy in which the two phases are estimated separately, each on half of the total number of system copies. In the limit of small angles we show that, although the joint estimation approach yields in general a better performance, the two strategies possess the same scaling of the total phase sensitivity with respect to the spin number j, namely ' 1/j. Finally, we discuss a simple estimation strategy based on spin squeezed states and spin measurements, and compare its performance with the ultimate limits to the estimation precision that we have derived above

    Quantum Correlations in Multipartite Quantum Systems

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    We review some concepts and properties of quantum correlations, in particular multipartite measures, geometric measures and monogamy relations. We also discuss the relation between classical and total correlationsComment: to be published as a chapter of the book "Lectures on general quantum correlations and their applications" edited by F. Fanchini, D. Soares-Pinto, and G. Adesso (Springer, 2017

    Differences in the pattern and regulation of mineral deposition in human cell lines of osteogenic and non-osteogenic origin

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    Bone marrow-derived mesenchymal stem cells (MSCs) are widely used as a cellular model of bone formation, and can mineralize in vitro in response to osteogenic medium (OM). It is unclear, however, whether this property is specific to cells of mesenchymal origin. We analysed the OM response in 3 non-osteogenic lines, HEK293, HeLa and NTera, compared to MSCs. Whereas HEK293 cells failed to respond to OM conditions, the 2 carcinoma-derived lines NTera and HeLa deposited a calcium phosphate mineral comparable to that present in MSC cultures. However, unlike MSCs, HeLa and NTera cultures did so in the absence of dexamethasone. This discrepancy was confirmed, as bone morphogenetic protein inhibition obliterated the OM response in MSCs but not in HeLa or NTera, indicating that these 2 models can deposit mineral through a mechanism independent of established dexamethasone or bone morphogenetic protein signalling. © 2011 S. Karger AG, Basel

    Effects of Dietary Extruded Linseed (Linum usitatissimum) and Oregano (Origanum vulgare) on Growth Traits, Carcass Composition and Meat Quality of Grigia di Potenza Suckling Kids

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    The aim of this trial was to compare the influence of supplementing diets with extruded linseed and oregano on growth parameters and meat qualitative traits in Grigia di Potenza breed suckling kids. Twenty-four male kids, exclusively fed milk from their dams, were assigned to the following diets: C) group control fed without any supplement; L) group fed control feed containing 3% extruded linseed (Linum usitatissimum L.); and LO) group fed control diet with 0.6% dried oregano (Origanum vulgare) and 3% extruded linseed. Growth performance as well as slaughtering traits and meat cuts of kids were not significantly influenced (P > 0.05) by dietary treatments. Conversely, kids in linseed group reported the lower (P < 0.05) percentage of dissectible fat in leg and loin. The meat from Longissimus lumborum and Semimembranosus muscles of kids in linseed diet had the lowest (P < 0.05) cooking loss percentage, whereas the proximate chemical composition of both meat muscles did not vary among treatments (P > 0.05). The experimental diets partially modulated the kid meat fatty acid composition in both muscles, where feeding linseed and oregano improved (P < 0.05) the content of DPA and reduced MUFA. Based on the current findings, it can be concluded that linseed and oregano supplementation can be used in goat diet as no significant detrimental effects on productive performance and meat quality of suckling kids were observed

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

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    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

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    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
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