47 research outputs found

    2020 North Carolina Election Protection Report

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    North Carolinians -- particularly our Black and Latiné neighbors -- have always faced an evolving array of barriers that prevented them from exercising their freedom to vote. Last century's literacy tests and poll taxes, used to keep Black and low-resourced voters away from the polls, have evolved into more insidious tactics like complex vote-by-mail procedures, intimidation, and felony disenfranchisement.Each year, Democracy North Carolina and the Southern Coalition for Social Justice (SCSJ) work to identify and remove voting barriers. The 2020 Election Protection report documents our work during one of the state's highest turnout and safest elections on record. Central to our report is an analysis of over 13,000 phone calls voters made to our statewide voter assistance hotline (888-OUR-VOTE) as well as from thousands of volunteers (also known as "Vote Protectors"), who observed polling places and helped voters during the 2020 elections

    A rare genomic duplication in 2p14 underlies autosomal dominant hearing loss DFNA58

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    Here we define a ~ 200Kb genomic duplication in 2p14 as the genetic signature that segregates with post-lingual progressive sensorineural autosomal dominant hearing loss in 20 affected individuals from the DFNA58 family, first reported in 2009. The duplication includes two entire genes, PLEK and CNRIP1, and the first exon of PPP3R1 (protein-coding), in addition to four uncharacterized long noncoding (lnc) RNA genes and part of a novel protein-coding gene. Quantitative analysis of mRNA expression in blood samples revealed selective overexpression of CNRIP1 and of two lncRNA genes (LOC107985892 and LOC102724389) in all affected members tested, but not in unaffected ones. Qualitative analysis of mRNA expression identified also fusion transcripts involving parts of PPP3R1, CNRIP1 and an intergenic region between PLEK and CNRIP1, in the blood of all carriers of the duplication, but were heterogeneous in nature. By in situ hybridization and immunofluorescence, we showed that Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea including the spiral ganglion neurons, suggesting changes in expression levels of these genes in the hearing organ could underlie the DFNA58 form of deafness. Our study highlights the value of studying rare genomic events leading to hearing loss such as copy number variations. Further studies will be required to determine which of these genes, either coding proteins or non-coding RNAs, is or are responsible for DFNA58 hearing loss

    Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity

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    Efficient transcriptional programming promises to open new frontiers in regenerative medicine. However, mechanisms by which programming factors transform cell fate are unknown, preventing more rational selection of factors to generate desirable cell types. Three transcription factors, Ngn2, Isl1 and Lhx3, were sufficient to program rapidly and efficiently spinal motor neuron identity when expressed in differentiating mouse embryonic stem cells. Replacement of Lhx3 by Phox2a led to specification of cranial, rather than spinal, motor neurons. Chromatin immunoprecipitation–sequencing analysis of Isl1, Lhx3 and Phox2a binding sites revealed that the two cell fates were programmed by the recruitment of Isl1-Lhx3 and Isl1-Phox2a complexes to distinct genomic locations characterized by a unique grammar of homeodomain binding motifs. Our findings suggest that synergistic interactions among transcription factors determine the specificity of their recruitment to cell type–specific binding sites and illustrate how a single transcription factor can be repurposed to program different cell types.Project ALS FoundationNational Institutes of Health (U.S.) (Grant P01 NS055923

    MEKK1-MKK4-JNK-AP1 Pathway Negatively Regulates Rgs4 Expression in Colonic Smooth Muscle Cells

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    Background: Regulator of G-protein Signaling 4 (RGS4) plays an important role in regulating smooth muscle contraction, cardiac development, neural plasticity and psychiatric disorder. However, the underlying regulatory mechanisms remain elusive. Our recent studies have shown that upregulation of Rgs4 by interleukin (IL)-1b is mediated by the activation of NFkB signaling and modulated by extracellular signal-regulated kinases, p38 mitogen-activated protein kinase, and phosphoinositide-3 kinase. Here we investigate the effect of the c-Jun N-terminal kinase (JNK) pathway on Rgs4 expression in rabbit colonic smooth muscle cells. Methodology/Principal Findings: Cultured cells at first passage were treated with or without IL-1b (10 ng/ml) in the presence or absence of the selective JNK inhibitor (SP600125) or JNK small hairpin RNA (shRNA). The expression levels of Rgs4 mRNA and protein were determined by real-time RT-PCR and Western blot respectively. SP600125 or JNK shRNA increased Rgs4 expression in the absence or presence of IL-1b stimulation. Overexpression of MEKK1, the key upstream kinase of JNK, inhibited Rgs4 expression, which was reversed by co-expression of JNK shRNA or dominant-negative mutants for MKK4 or JNK. Both constitutive and inducible upregulation of Rgs4 expression by SP600125 was significantly inhibited by pretreatment with the transcription inhibitor, actinomycin D. Dual reporter assay showed that pretreatment with SP600125 sensitized the promoter activity of Rgs4 in response to IL-1b. Mutation of the AP1-binding site within Rgs

    flame-cut discs and segments for Fix Iron Noses (FINs) prior to pre-machining

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    FINs discs and segments ready for pre-machining at Protvin

    COMPARISON OF FIELD CALCULATIONS AND MEASUREMENTS OF A SPECTROMETER MAGNET

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    The magnetic spectrometer of the CERN experiment NA48 uses a conventional dipole magnet with a gap of 2.40 m and a field integral of 0.83 Tm, equivalent to a transverse momentum change of charged particles of 250 MeV/c. This paper introduces the magnet and compares three-dimensional calculations of the magnetic field with the measured field map

    Images of CMS Superconducting Solonoid - Ancillaries

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    from the photo gallery on cmsinfo.cern.c
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