2,446 research outputs found

    Long noncoding RNAs in organogenesis: Making the difference

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    A large proportion of the cellular transcriptome of higher vertebrates consists of non-protein coding transcripts, among them the long noncoding RNAs (lncRNAs). Although lncRNAs are functionally extremely divergent, many ncRNAs have been shown to interact with chromatin modifying complexes and/or with transcriptional regulators. Via such interactions, many lncRNAs are involved in controlling the activity and expression level of target genes, including important regulators of embryonic processes, and thereby fine-tune gene regulatory networks controlling cell fate, lineage balance, and organogenesis. Intriguingly, an increase in organ complexity during evolution parallels a rise in lncRNA abundance. The current data suggest that lncRNAs support the generation of cell diversity and organ complexity during embryogenesis, and thereby have promoted the evolution of more complex organisms

    The long non-coding RNA Fendrr links epigenetic control mechanisms to gene regulatory networks in mammalian embryogenesis

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    Epigenetic control mechanisms determine active and silenced regions of the genome. It is known that the Polycomb Repressive Complex 2 (PRC2) and the Trithorax group/Mixed lineage leukemia (TrxG/Mll) complex are able to set repressive and active histone marks, respectively. Long non-coding RNAs (lncRNAs) can interact with either of these complexes and guide them to regulatory elements, thereby modifying the expression levels of target genes. The lncRNA Fendrr is transiently expressed in lateral mesoderm of mid-gestational mouse embryos and was shown to interact with both PRC2 and TrxG/Mll complexes in vivo. Gene targeting revealed that loss of Fendrr results in impaired differentiation of tissues derived from lateral mesoderm, the heart and the body wall, ultimately leading to embryonic death. Molecular data suggests that Fendrr acts via dsDNA/RNA triplex formation at target regulatory elements, and directly increases PRC2 occupancy at these sites. This, in turn, modifies the ratio of repressive to active marks, adjusting the expression levels of Fendrr target genes in lateral mesoderm. We propose that Fendrr also mediates long-term epigenetic marks to define expression levels of its target genes within the descendants of lateral mesoderm cells. Here we discuss approaches for lncRNA gene knockouts in the mouse, and suggest a model how Fendrr and possibly other lncRNAs act during embryogenesis

    Optimal time-domain combination of the two calibrated output quadratures of GEO 600

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    GEO 600 is an interferometric gravitational wave detector with a 600 m arm-length and which uses a dual-recycled optical configuration to give enhanced sensitivity over certain frequencies in the detection band. Due to the dual-recycling, GEO 600 has two main output signals, both of which potentially contain gravitational wave signals. These two outputs are calibrated to strain using a time-domain method. In order to simplify the analysis of the GEO 600 data set, it is desirable to combine these two calibrated outputs to form a single strain signal that has optimal signal-to-noise ratio across the detection band. This paper describes a time-domain method for doing this combination. The method presented is similar to one developed for optimally combining the outputs of two colocated gravitational wave detectors. In the scheme presented in this paper, some simplifications are made to allow its implementation using time-domain methods

    Physical instrumental vetoes for gravitational-wave burst triggers

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    We present a robust strategy to \emph{veto} certain classes of instrumental glitches that appear at the output of interferometric gravitational-wave (GW) detectors.This veto method is `physical' in the sense that, in order to veto a burst trigger, we make use of our knowledge of the coupling of different detector subsystems to the main detector output. The main idea behind this method is that the noise in an instrumental channel X can be \emph{transferred} to the detector output (channel H) using the \emph{transfer function} from X to H, provided the noise coupling is \emph{linear} and the transfer function is \emph{unique}. If a non-stationarity in channel H is causally related to one in channel X, the two have to be consistent with the transfer function. We formulate two methods for testing the consistency between the burst triggers in channel X and channel H. One method makes use of the \emph{null-stream} constructed from channel H and the \emph{transferred} channel X, and the second involves cross-correlating the two. We demonstrate the efficiency of the veto by `injecting' instrumental glitches in the hardware of the GEO 600 detector. The \emph{veto safety} is demonstrated by performing GW-like hardware injections. We also show an example application of this method using 5 days of data from the fifth science run of GEO 600. The method is found to have very high veto efficiency with a very low accidental veto rate.Comment: Minor changes, To appear in Phys. Rev.

    Antagonistic Activities of Sox2 and Brachyury Control the Fate Choice of Neuro-Mesodermal Progenitors

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    The spinal cord and mesodermal tissues of the trunk such as the vertebral column and skeletal musculature derive from neuro-mesodermal progenitors (NMPs). Sox2, Brachyury (T), and Tbx6 have been correlated with NMP potency and lineage choice; however, their exact role and interaction in these processes have not yet been revealed. Here we present a global analysis of NMPs and their descending lineages performed on purified cells from embryonic day 8.5 wild-type and mutant embryos. We show that T, cooperatively with WNT signaling, controls the progenitor state and the switch toward the mesodermal fate. Sox2 acts antagonistically and promotes neural development. T is also involved in remodeling the chromatin for mesodermal development. Tbx6 reinforces the mesodermal fate choice, represses the progenitor state, and confers paraxial fate commitment. Our findings refine previous models and establish molecular principles underlying mammalian trunk development, comprising NMP maintenance, lineage choice, and mesoderm formation

    Benchmarking of 3D space charge codes using direct phase space measurements from photoemission high voltage DC gun

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    We present a comparison between space charge calculations and direct measurements of the transverse phase space for space charge dominated electron bunches after a high voltage photoemission DC gun followed by an emittance compensation solenoid magnet. The measurements were performed using a double-slit setup for a set of parameters such as charge per bunch and the solenoid current. The data is compared with detailed simulations using 3D space charge codes GPT and Parmela3D with initial particle distributions created from the measured transverse and temporal laser profiles. Beam brightness as a function of beam fraction is calculated for the measured phase space maps and found to approach the theoretical maximum set by the thermal energy and accelerating field at the photocathode.Comment: 11 pages, 23 figures. submitted to Phys Rev ST-A

    Physical activity and sedentary behavior from 6 to 11 years

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    OBJECTIVES: Physical activity (PA) is presumed to decline during childhood and adolescence, but only few long-term studies about PA development during this period of life exist. We assessed PA and sedentary behavior (SB) over a 5-year period to gain a better understanding of the extent of change in activity and potential influencing factors. METHODS: PA and SB of 600 children from the Childhood Obesity Project were objectively measured with the SenseWear Armband 2 at the ages of 6, 8, and 11 years, resulting in 1254 observations. Longitudinal changes of total PA, moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and SB were modeled with mixed-effects models. RESULTS: Total PA revealed a significant quadratic decline with age (P < .001), resulting in a change of total PA by -75.3 minutes per day from 6 to 11 years. LPA linearly declined (P < .001) by 44.6 minutes per day, MVPA quadratically declined (P < .001) by an overall 30.7 minutes, whereas SB increased significantly (+107 minutes; P = .001). Boys showed a steeper decline in LPA (P = .003) and MVPA (P < .001) than did girls. Higher fat mass index and BMI z scores were associated with lower levels of total PA and MVPA and higher levels of SB (all P < .001). CONCLUSIONS: We showed that PA decreased, and SB increased in earlier years than previously thought. MVPA remained relatively stable until 8 years, but revealed a drop-off at 11 years, identifying this period as a crucial time for intervention
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