Alternative splicing produces structural and functional changes in CUGBP2

<p>Abstract</p> <p>Background</p> <p>CELF/Bruno-like proteins play multiple roles, including the regulation of alternative splicing and translation. These RNA-binding proteins contain two RNA recognition motif (RRM) domains at the N-terminus and another RRM at the C-terminus. CUGBP2 is a member of this family of proteins that possesses several alternatively spliced exons.</p> <p>Results</p> <p>The present study investigated the expression of exon 14, which is an alternatively spliced exon and encodes the first half of the third RRM of CUGBP2. The ratio of exon 14 skipping product (<it>R3δ</it>) to its inclusion was reduced in neuronal cells induced from P19 cells and in the brain. Although full length CUGBP2 and the CUGBP2 <it>R3δ </it>isoforms showed a similar effect on the inclusion of the smooth muscle (SM) exon of the <it>ACTN1 </it>gene, these isoforms showed an opposite effect on the skipping of exon 11 in the <it>insulin receptor </it>gene. In addition, examination of structural changes in these isoforms by molecular dynamics simulation and NMR spectrometry suggested that the third RRM of R3δ isoform was flexible and did not form an RRM structure.</p> <p>Conclusion</p> <p>Our results suggest that CUGBP2 regulates the splicing of <it>ACTN1 </it>and <it>insulin receptor </it>by different mechanisms. Alternative splicing of <it>CUGBP2 </it>exon 14 contributes to the regulation of the splicing of the <it>insulin receptor</it>. The present findings specifically show how alternative splicing events that result in three-dimensional structural changes in CUGBP2 can lead to changes in its biological activity.</p

Development of the reverse hybrid jig: Separation of polyethylene and cross-linked polyethylene from eco-cable wire

We have developed various types of jigs for resources recycling focusing primarily on plastic-plastic separation. The RETAC jig could be used to separate plastics heavier than water (specific gravity (SG) > 1.0) with different SGs while the hybrid jig-a process combining jig and flotation-was developed to separate plastics with similar SGs but different surface wettabilities. Meanwhile the reverse jig-a RETAC jig with a top screen-is used to separate plastics lighter than water with different SGs. In this study, a novel method that combines the principle of reverse and hybrid jigs, called "reverse hybrid jig separation" was developed to separate plastics lighter than water having similar SGs but different surface wettabilities. The tests were carried out with wastes from an eco-cable wire recycling facility in Japan, which is composed of polyethylene (PE) and cross-linked polyethylene (XLPE). The reverse hybrid jig separation results showed that bubble attachment to and detachment from plastic particles strongly influenced the separation efficiency. In addition, the effects of particle size on separation efficiency were also evaluated

Improvement of hybrid jig separation efficiency using wetting agents for the recycling of mixed-plastic wastes

We have developed the hybrid jig which combines the principles of jig separation and flotation. However, the selectivity of bubble attachment in water was poor because most plastics have inherently hydrophobic surfaces; so, development of surface modification techniques for plastic particles would expand the application of hybrid jig to the material recycling of plastics. In this study, hybrid jig separation of polypropylene using glass fiber and high impact polystyrene having similar specific gravities and surface wettability were investigated with three wetting agents [Di-2-ethylhexyl sodium sulfosuccinate (Aerosol OT, AOT), sodium lignin sulfonate, and tannic acid]. The results showed that the probability of bubble attachment was influenced by wetting agents because of their strong effects on the surface tension of solution and surface wettability of plastics. The results also suggest that wetting agents could be utilized to control the selectivity of bubble attachment and improve the hybrid jig separation efficiency. In addition, since the hybrid jig separation of polyvinyl chloride and polyamide (nylon-66) using AOT was imperfect, a two-step approach, composed of a pre-wetting step (first step) in a solution containing the wetting agent (AOT) and hybrid jig separation in water (second step), is proposed

Estimation of hybrid jig separation efficiency using a modified concentration criterion based on apparent densities of plastic particles with attached bubbles

The hybrid jig, which combines the principles of jig separation and flotation, was recently developed to separate mixed-plastics with similar specific gravities (SG) effectively. In this type of jig, air bubbles are introduced during water pulsation to modify the apparent SG (SG(apparent)) of plastics by the attachment of air bubbles to the particles so that the hybrid jig can separate materials having identical SGs if their surface wettabilities are different. Because the change in SG(apparent)-determined by the volume of attached bubbles on the particle surface-is critical for efficient separation in hybrid jigs, a method to estimate this parameter should be developed. In this study, a laser-assisted measurement apparatus was developed to quantify the attached-bubble volume on plastics during water pulsation. Hybrid jig separation was also conducted using three mixtures containing plastics of almost identical SGs: (i) polyvinyl chloride (PVC)/polyethylene terephthalate (PET), (ii) polypropylene with glass fiber (PPGF)/high-impact polystyrene (HIPS), and (iii) cross-linked polyethylene (XLPE)/polyethylene (PE). Finally, to estimate the separation efficiency of hybrid jig, a new index called the apparent concentration criterion (CCapparent) is proposed. The results showed that SG(apparent)and CC(apparent)calculated using the proposed methods could be used to estimate the hybrid jig separation efficiency

Bioinformatics and Functional Analyses Implicate Potential Roles for EOGT and <i>L</i>-fringe in Pancreatic Cancers

Notch signaling receptors, ligands, and their downstream target genes are dysregulated in pancreatic ductal adenocarcinoma (PDAC), suggesting a role of Notch signaling in pancreatic tumor development and progression. However, dysregulation of Notch signaling by post-translational modification of Notch receptors remains poorly understood. Here, we analyzed the Notch-modifying glycosyltransferase involved in the regulation of the ligand-dependent Notch signaling pathway. Bioinformatic analysis revealed that the expression of epidermal growth factor (EGF) domain-specific O-linked N-acetylglucosamine (EOGT) and Lunatic fringe (LFNG) positively correlates with a subset of Notch signaling genes in PDAC. The lack of EOGT or LFNG expression inhibited the proliferation and migration of Panc-1 cells, as observed by the inhibition of Notch activation. EOGT expression is significantly increased in the basal subtype, and low expression of both EOGT and LFNG predicts better overall survival in PDAC patients. These results imply potential roles for EOGT- and LFNG-dependent Notch signaling in PDAC

Bioinformatics and Functional Analyses Implicate Potential Roles for EOGT and L-fringe in Pancreatic Cancers

Notch signaling receptors, ligands, and their downstream target genes are dysregulated in pancreatic ductal adenocarcinoma (PDAC), suggesting a role of Notch signaling in pancreatic tumor development and progression. However, dysregulation of Notch signaling by post-translational modification of Notch receptors remains poorly understood. Here, we analyzed the Notch-modifying glycosyltransferase involved in the regulation of the ligand-dependent Notch signaling pathway. Bioinformatic analysis revealed that the expression of epidermal growth factor (EGF) domain-specific O-linked N-acetylglucosamine (EOGT) and Lunatic fringe (LFNG) positively correlates with a subset of Notch signaling genes in PDAC. The lack of EOGT or LFNG expression inhibited the proliferation and migration of Panc-1 cells, as observed by the inhibition of Notch activation. EOGT expression is significantly increased in the basal subtype, and low expression of both EOGT and LFNG predicts better overall survival in PDAC patients. These results imply potential roles for EOGT- and LFNG-dependent Notch signaling in PDAC