928 research outputs found

    The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease

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    The transcription factor REST silences neuronal gene expression in non-neuronal cells. In neurons, the protein is sequestered in the cytoplasm in part through binding to huntingtin. Polyglutamine expansions in huntingtin, which causes Huntington's disease (HD), abrogates REST-huntingtin binding. Consequently, REST translocates to the nucleus, occupies RE1 repressor sequences and decreases neuronal gene expression. In this work, we found that levels of several microRNAs (miRNAs) with upstream RE1 sites are decreased in HD patient cortices relative to healthy controls. Interestingly, one of these, the bifunctional brain enriched miR-9/miR-9*, targets two components of the REST complex: miR-9 targets REST and miR-9* targets CoREST. These data provide evidence for a double negative feedback loop between the REST silencing complex and the miRNAs it regulates

    Predicting Functional Alternative Splicing by Measuring RNA Selection Pressure from Multigenome Alignments

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    High-throughput methods such as EST sequencing, microarrays and deep sequencing have identified large numbers of alternative splicing (AS) events, but studies have shown that only a subset of these may be functional. Here we report a sensitive bioinformatics approach that identifies exons with evidence of a strong RNA selection pressure ratio (RSPR) —i.e., evolutionary selection against mutations that change only the mRNA sequence while leaving the protein sequence unchanged—measured across an entire evolutionary family, which greatly amplifies its predictive power. Using the UCSC 28 vertebrate genome alignment, this approach correctly predicted half to three-quarters of AS exons that are known binding targets of the NOVA splicing regulatory factor, and predicted 345 strongly selected alternative splicing events in human, and 262 in mouse. These predictions were strongly validated by several experimental criteria of functional AS such as independent detection of the same AS event in other species, reading frame-preservation, and experimental evidence of tissue-specific regulation: 75% (15/20) of a sample of high-RSPR exons displayed tissue specific regulation in a panel of ten tissues, vs. only 20% (4/20) among a sample of low-RSPR exons. These data suggest that RSPR can identify exons with functionally important splicing regulation, and provides biologists with a dataset of over 600 such exons. We present several case studies, including both well-studied examples (GRIN1) and novel examples (EXOC7). These data also show that RSPR strongly outperforms other approaches such as standard sequence conservation (which fails to distinguish amino acid selection pressure from RNA selection pressure), or pairwise genome comparison (which lacks adequate statistical power for predicting individual exons)

    Constraints on Spin-Independent Nucleus Scattering with sub-GeV Weakly Interacting Massive Particle Dark Matter from the CDEX-1B Experiment at the China Jin-Ping Laboratory

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    We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (mχm_{\chi}) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg⋅\cdotday exposure and 160 eVee threshold for TI analysis, and 1107.5 kg⋅\cdotday exposure and 250 eVee threshold for AM analysis. The sensitive windows in mχm_{\chi} are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σχNSI\sigma_{\chi N}^{\rm SI} at 90\% confidence level are derived as 2×2\times10−32∼7×^{-32}\sim7\times10−35^{-35} cm2\rm cm^2 for TI analysis at mχ∼m_{\chi}\sim 50−-180 MeV/c2c^2, and 3×3\times10−32∼9×^{-32}\sim9\times10−38^{-38} cm2\rm cm^2 for AM analysis at mχ∼m_{\chi}\sim75 MeV/c2−c^2-3.0 GeV/c2c^2.Comment: 5 pages, 4 figure

    Search for Light Weakly-Interacting-Massive-Particle Dark Matter by Annual Modulation Analysis with a Point-Contact Germanium Detector at the China Jinping Underground Laboratory

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    We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass pp-type point-contact germanium detector of the CDEX-1B experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2 yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ{\chi}-NN) spin-independent cross sections as function of WIMP mass (mχm_{\chi}) at 90\% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90\% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >>99.99\% and 98\% C.L., respectively. These results correspond to the best sensitivity at mχm_{\chi}<<6 GeV/c2~{\rm GeV}/c^2 among WIMP AM measurements to date.Comment: 5 pages, 4 figure

    Parallel momentum distribution of the 28^{28}Si fragments from 29^{29}P

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    Distribution of the parallel momentum of 28^{28}Si fragments from the breakup of 30.7 MeV/nucleon 29^{29}P has been measured on C targets. The distribution has the FWHM with the value of 110.5 ±\pm 23.5 MeV/c which is consistent quantitatively with Galuber model calculation assuming by a valence proton in 29^{29}P. The density distribution is also predicted by Skyrme-Hartree-Fock calculation. Results show that there might exist the proton-skin structure in 29^{29}P.Comment: 4 pages, 4 figure
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