Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation

BACKGROUND: X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1) repeats are relatively enriched on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes. RESULTS: Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could confer the capacity for relatively efficient chromosome-wide silencing. CONCLUSIONS: This study provides insight into the requirements for efficient Xist mediated silencing and specifically identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major influence on the ability of Xist-mediated silencing to be propagated in a continuous manner in cis

Fatty-acid uptake in prostate cancer cells using dynamic microfluidic raman technology

It is known that intake of dietary fatty acid (FA) is strongly correlated with prostate cancer progression but is highly dependent on the type of FAs. High levels of palmitic acid (PA) or arachidonic acid (AA) can stimulate the progression of cancer. In this study, a unique experimental set-up consisting of a Raman microscope, coupled with a commercial shear-flow microfluidic system is used to monitor fatty acid uptake by prostate cancer (PC-3) cells in real-time at the single cell level. Uptake of deuterated PA, deuterated AA, and the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were monitored using this new system, while complementary flow cytometry experiments using Nile red staining, were also conducted for the validation of the cellular lipid uptake. Using this novel experimental system, we show that DHA and EPA have inhibitory effects on the uptake of PA and AA by PC-3 cells

Antiferromagnetic Exchange Interaction between Electrons on Degenerate LUMOs in Benzene Dianion

We discuss the ground state of Benzene dianion (Bz$^{2-}$) on the basis of the numerical diagonalization method of an effective model of $\pi$ orbitals. It is found that the ground state can be the spin singlet state, and the exchange coupling between LUMOs can be antiferromagnetic.Comment: Accepted for publication in J. Phys. Soc. Jpn., 2 pages, 3 figure

Multi-Modes Phonon Softening in Two-Dimensional Electron-Lattice System

Phonon dispersion in a two-dimensional electron-lattice system described by a two-dimensional square-lattice version of Su-Schrieffer-Heeger's model and having the half-filled electronic band is studied theoretically at temperatures higher than the mean field critical temperature of the Peierls transition. When the temperature is lowered from the higher region down to the critical one, softening of multi phonon modes which have wave vectors equal to the nesting vector \vv{Q}=(\pi/a,\pi/a) with $a$ the lattice constant or parallel to \vv{Q} is observed. Although both of the transverse and longitudinal modes are softened at the critical temperature in the case of the wave vector equal to \vv{Q}, only the transverse modes are softened for other wave vectors parallel to \vv{Q}. This behavior is consistent with the Peierls distortions at lower temperatures.Comment: 10 pages, 5 Figure

COCO_TS Dataset: Pixel-level Annotations Based on Weak Supervision for Scene Text Segmentation

The absence of large scale datasets with pixel-level supervisions is a significant obstacle for the training of deep convolutional networks for scene text segmentation. For this reason, synthetic data generation is normally employed to enlarge the training dataset. Nonetheless, synthetic data cannot reproduce the complexity and variability of natural images. In this paper, a weakly supervised learning approach is used to reduce the shift between training on real and synthetic data. Pixel-level supervisions for a text detection dataset (i.e. where only bounding-box annotations are available) are generated. In particular, the COCO-Text-Segmentation (COCO_TS) dataset, which provides pixel-level supervisions for the COCO-Text dataset, is created and released. The generated annotations are used to train a deep convolutional neural network for semantic segmentation. Experiments show that the proposed dataset can be used instead of synthetic data, allowing us to use only a fraction of the training samples and significantly improving the performances

The Use of Gamma-ray Bursts as Direction and Time Markers in SETI Strategies

When transmitting a signal over a large distance it is more efficient to send a brief beamed signal than a continuous omni-directional transmission but this requires that the receiver knows where and when to look for the transmission. For SETI, the use of various natural phenomena has previously been suggested to achieve the desired synchronization. Here it is proposed that gamma-ray bursts may well the best ``synchronizers'' of all currently known phenomena due to their large intrinsic luminosities, high occurrence rate, isotropic sky distribution, large distance from the Galaxy, short duration, and easy detectability. For targeted searches, precise positions for gamma-ray bursts are required together with precise distance measurements to a target star. The required burst position determinations are now starting to be obtained, aided in large part by the discovery of optical afterglows. Good distance measurements are currently available from Hipparcos and even better measurements should be provided by spacecraft now being developed. For non-targeted searches, positional accuracies simply better than a detector's field of view may suffice but the time delay between the detection of a gamma-ray burst and the reception of the transmitted signal cannot be predicted in an obvious way.Comment: 8 pages, accepted for publication in PAS

An architecture for IEEE 802.16 MAC scheduler design

Copyright © 2007 IEEEThe scheduling algorithm for IEEE 802.16 broadband wireless access system has been left open in the standard. In this paper, we consider three criteria that we have identified as important criteria for an 802.16 scheduler: Service Type differentiation, dynamic sub-frame partition and Subscriber Station differentiation. We investigate the scheduler design from a general perspective, based on these three criteria

Symmetry and designability for lattice protein models

Native protein folds often have a high degree of symmetry. We study the relationship between the symmetries of native proteins, and their designabilities -- how many different sequences encode a given native structure. Using a two-dimensional lattice protein model based on hydrophobicity, we find that those native structures that are encoded by the largest number of different sequences have high symmetry. However only certain symmetries are enhanced, e.g. x/y-mirror symmetry and $180^o$ rotation, while others are suppressed. If it takes a large number of mutations to destabilize the native state of a protein, then, by definition, the state is highly designable. Hence, our findings imply that insensitivity to mutation implies high symmetry. It appears that the relationship between designability and symmetry results because protein substructures are also designable. Native protein folds may therefore be symmetric because they are composed of repeated designable substructures.Comment: 13 pages, 10 figure