45 research outputs found

    Tissue-specific splicing regulator Fox-1 induces exon skipping by interfering E complex formation on the downstream intron of human F1γ gene

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    Fox-1 is a regulator of tissue-specific splicing, via binding to the element (U)GCAUG in mRNA precursors, in muscles and neuronal cells. Fox-1 can regulate splicing positively or negatively, most likely depending on where it binds relative to the regulated exon. In cases where the (U)GCAUG element lies in an intron upstream of the alternative exon, Fox-1 protein functions as a splicing repressor to induce exon skipping. Here we report the mechanism of exon skipping regulated by Fox-1, using the hF1γ gene as a model system. We found that Fox-1 induces exon 9 skipping by repressing splicing of the downstream intron 9 via binding to the GCAUG repressor elements located in the upstream intron 8. In vitro splicing analyses showed that Fox-1 prevents formation of the pre-spliceosomal early (E) complex on intron 9. In addition, we located a region of the Fox-1 protein that is required for inducing exon skipping. Taken together, our data show a novel mechanism of how RNA-binding proteins regulate alternative splicing

    Usefulness of Simple Diffusion Kurtosis Imaging for Head and Neck Tumors: An Early Clinical Study

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    Diffusion kurtosis (DK) imaging (DKI), a type of restricted diffusion-weighted imaging, has been reported to be useful for tumor diagnoses in clinical studies. We developed a software program to simultaneously create DK images with apparent diffusion coefficient (ADC) maps and conducted an initial clinical study. Multi-shot echo-planar diffusion-weighted images were obtained at b-values of 0, 400, and 800 sec/mm2 for simple DKI, and DK images were created simultaneously with the ADC map. The usefulness of the DK image and ADC map was evaluated using a pixel analysis of all pixels and a median analysis of the pixels of each case. Tumor and normal tissues differed significantly in both pixel and median analyses. In the pixel analysis, the area under the curve was 0.64 for the mean kurtosis (MK) value and 0.77 for the ADC value. In the median analysis, the MK value was 0.74, and the ADC value was 0.75. The MK and ADC values correlated moderately in the pixel analysis and strongly in the median analysis. Our simple DKI system created DK images simultaneously with ADC maps, and the obtained MK and ADC values were useful for differentiating head and neck tumors from normal tissue

    Characteristic Mean Kurtosis Values in Simple Diffusion Kurtosis Imaging of Dentigerous Cysts

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    We evaluated the usefulness of simple diffusion kurtosis (SD) imaging, which was developed to generate diffusion kurtosis images simultaneously with an apparent diffusion coefficient (ADC) map for 27 cystic disease lesions in the head and neck region. The mean kurtosis (MK) and ADC values were calculated for the cystic space. The MK values were dentigerous cyst (DC): 0.74, odontogenic keratocyst (OKC): 0.86, ranula (R): 0.13, and mucous cyst (M): 0, and the ADC values were DC: 1364 × 10−6 mm2/s, OKC: 925 × 10−6 mm2/s, R: 2718 × 10−6 mm2/s, and M: 2686 × 10−6 mm2/s. The MK values of DC and OKC were significantly higher than those of R and M, whereas their ADC values were significantly lower. One reason for the characteristic signal values in diffusion-weighted images of DC may be related to content components such as fibrous tissue and exudate cells. When imaging cystic disease in the head and neck region using SD imaging, the maximum b-value setting at the time of imaging should be limited to approximately 1200 s/mm2 for accurate MK value calculation. This study is the first to show that the MK values of DC are characteristically higher than those of other cysts

    SPF45/RBM17-dependent splicing and multidrug resistance to cancer chemotherapy

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    The early splicing complex A occupies at least eighty nucleotides of intron, in which U2AF covers the polypyrimidine tract. SPF45 (RBM17) functionally substitutes for U2AF on a subset of short introns. Since SPF45 expression confers resistance to various anticancer drugs, SPF45-dependent splicing may play a critical role in multidrug resistance

    Practical production of 61Cu using natural Co target and its simple purification with a chelating resin for 61Cu-ATSM

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    Copper-61 (T-1/2 = 3.41 h) produced via the Co-59(alpha, 2n)Cu-61 nuclear reaction using natural Co target was isolated from the irradiated target by two methods developed here and applied for preparation of (Cu-61-ATSM) (Cu-61-diacetyl-bis(N-4-methylthiosemicarbazone)), known as an imaging agent of hypoxic tissue. A commercially available cobalt disk (thickness: 125 mum) was irradiated with 40 MeV (37.9 MeV on target) a particles, then treated with conc. HNO3, and the Cu-61 was separated by two different methods, i.e. a two column method using a cation and an anion exchange column; and a one Column method using a column packed with chelating resin, Chelex 100. Both separation methods gave satisfactory results, though the latter method was superior because of the simplicity of the apparatus, the separation procedure and somewhat shorter processing time. Around 1.1 GBq of 61Cu(2+) were obtained with >95% yield (decay corrected) from Co target at 10 I-LA for 1 h irradiation, and with the radionuclidic purity of >98% (EOS). The only radionuclidic impurity in the isolated Cu-61(2+) solution was identified to be Cu-60 at EOS but no radionuclidic impurity was observed after 50 hours. The solution of Cu-61-ATSM was prepared in >85% radiochemical yield with >95% radiochemical purity.\nDo you want to read the rest of this article?Request full-text \nPractical production of 61Cu using natural Co target and its simple purification with a chelating resin for 61CU-ATSM. Available from: https://www.researchgate.net/publication/244745391_Practical_production_of_61Cu_using_natural_Co_target_and_its_simple_purification_with_a_chelating_resin_for_61CU-ATSM [accessed Mar 27, 2017]
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