Deficiency of Capicua disrupts bile acid homeostasis

Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type 1 and cancer in mammals; however, the in vivo physiological functions of CIC remain largely unknown. Here we show that Cic hypomorphic (Cic-L-/-) mice have impaired bile acid (BA) homeostasis associated with induction of proinflammatory cytokines. We discovered that several drug metabolism and BA transporter genes were down-regulated in Cic-L-/- liver, and that BA was increased in the liver and serum whereas bile was decreased within the gallbladder of Cic-L-/- mice. We also found that levels of proinflammatory cytokine genes were up-regulated in Cic-L-/- liver. Consistent with this finding, levels of hepatic transcriptional regulators, such as hepatic nuclear factor 1 alpha (HNF1 alpha), CCAAT/enhancer-binding protein beta (C/EBP beta), forkhead box protein A2 (FOXA2), and retinoid X receptor alpha (RXR alpha), were markedly decreased in Cic-L-/- mice. Moreover, induction of tumor necrosis factor alpha (Tnf alpha) expression and decrease in the levels of FOXA2, C/EBP beta, and RXRa were found in Cic-L-/- liver before BA was accumulated, suggesting that inflammation might be the cause for the cholestasis in Cic-L-/- mice. Our findings indicate that CIC is a critical regulator of BA homeostasis, and that its dysfunction might be associated with chronic liver disease and metabolic disorders.open11810Ysciescopu

Subwavelength localization and toroidal dipole moment of spoof surface plasmon polaritons

We experimentally and theoretically demonstrate subwavelength scale localization of spoof surface plasmon polaritons at a point defect in a two-dimensional groove metal array. An analytical expression for dispersion relation of spoof surface plasmon polaritons substantiates the existence of a band gap where a defect mode can be introduced. A waveguide coupling method allows us to excite localized spoof surface plasmon polariton modes and measure their resonance frequencies. Numerical calculations confirm that localized modes can have a very small modal volume and a high Q factor both of which are essential in enhancing light-matter interactions. Interestingly, we find that the localized spoof surface plasmon polariton has a significant toroidal dipole moment, which is responsible for the high Q factor, as well as an electric quadrupole moment. In addition, the dispersion properties of spoof surface plasmon polaritons are analyzed using a modal expansion method and numerical calculations

Noncommunicating Isolated Enteric Duplication Cyst in the Abdomen in Children: Report of One Case and Review of the Literature

Noncommunicating isolated enteric duplications in the abdomen are an extremely rare variant of enteric duplications with their own blood supply. We report a case of a noncommunicating isolated ileal duplication in a 10-month-old boy. He was admitted because of severe abdominal distension and developed irritability abruptly. Abdominal ultrasound and computed tomography scan revealed a closed loop of small bowel that was dilated severely. A large tubular cyst hanging on the narrow vascular pedicle arising from the base of the terminal ileum mesentery was found with torsion of the pedicle in the right upper quadrant of the abdomen. Laparoscopic excision was performed successfully. Here, we will also review the previously reported cases to raise awareness of noncommunicating isolated enteric duplications in the literature.Keywords: Abdomen, Children, Duplication, Isolated, Noncommunicatin

Modulation of hole-injection in GaInN-light emitting triodes and its effect on carrier recombination behavior

The effects of the hole injection modulated by using a three-terminal GaInN-based light emitter, light-emitting triode (LET), on carrier recombination behavior and efficiency droop are investigated. It was found that the lateral electric field created by applying voltage bias between the two anodes effectively reduces efficiency droop as well as dynamic conductance of LETs. Detailed analyses of LETs under various operation conditions by APSYS simulations reveal that the asymmetry in carrier transport between electrons and holes is alleviated by promoted injection of hot holes over the potential barrier, increasing the hole concentration as well as the radiative recombination rate in the multiple quantum well active region. (C) 2015 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.110Ysciescopu

Bioreducible Polymer-delivered siRNA Targeting MMP-9: Suppression of Granulation Tissue Formation after Bare Metallic Stent Placement in a Rat Urethral Model

To evaluate the effectiveness of small interfering RNA (siRNA) targeting matrix metalloproteinase 9 (MMP-9) in suppressing granulation tissue formation caused by bare metallic stent placement in a rat urethral model. All experiments were approved by the committee of animal research. In 20 Sprague-Dawley male rats (weight range, 300-350 g), a self-expanding metallic bare stent was inserted in the urethra with fluoroscopic guidance. One group of 10 rats (group A) was treated with MMP-9 siRNA/bioreducible branched polyethylenimine-disulfide cross-linked-indocyanine green (bioreducible BPEI-SS-ICG), while the other group of 10 rats (group B) received control siRNA/bioreducible BPEI-SS-ICG treatment. All rats were sacrificed at 4 weeks. The therapeutic effectiveness of the MMP-9 siRNA/bioreducible BPEI-SS-ICG complex was assessed by comparing the two results of retrograde urethrography, histologic examination, and quantification of MMP-9 by using zymography and Western blot analysis between the two groups. The Mann-Whitney U test was used to evaluate differences. Stent placement was successful in all rats without a single case of migration at follow-up. Retrograde urethrography performed 4 weeks after stent placement demonstrated significantly larger luminal diameters of the urethra within the stents in group A compared with those in group B (P = .011). Histologic analysis revealed that the mean percentage of granulation tissue area (P < .001), mean number of epithelial layers (P < .001), and mean thickness of submucosal fibrosis (P < .001) were significantly decreased in group A compared with group B. Meanwhile, the mean density of inflammatory cell infiltration did not significantly differ between the two groups (P = .184). Quantitative analysis disclosed MMP-9 levels to be lower in group A relative to group B, indicating positive inhibition of MMP-9 by MMP-9 siRNA/bioreducible BPEI-SS-ICG. MMP-9 siRNA/bioreducible BPEI-SS-ICG is effective for inhibiting granulation tissue formation after bare metallic stent placement in a rat urethral model.X1143Ysciescopu

Protein Degradation of RNA Polymerase II-Association Factor 1(PAF1) Is Controlled by CNOT4 and 26S Proteasome

The PAF complex (PAFc) participates in various steps of the transcriptional process, from initiation to termination, by interacting with and recruiting various proteins to the proper locus for each step. PAFc is an evolutionarily conserved, multi-protein complex comprising PAF1, CDC73, CTR9, LEO1, yRTF1 and, in humans, hSKI8. These components of PAFc work together, and their protein levels are closely interrelated. In the present study, we investigated the mechanism of PAF1 protein degradation. We found that PAF1 protein levels are negatively regulated by the expression of CNOT4, an ortholog of yNOT4 and a member of the CCR4-NOT complex. CNOT4 specifically controls PAF1 but not other components of PAFc at the protein level by regulating the polyubiquitination of PAF1 and its subsequent degradation by the 26S proteasome. The degradation of PAF1 was found to require nuclear localization, as no PAF1 degradation by CNOT4 and the 26S proteasome was observed with NLS (nucleus localization signal)-deficient PAF1 mutants. However, chromatin binding by PAF1 was not necessary for 26S proteasome- or CNOT4-mediated degradation. Our results suggest that CNOT4 controls the degradation of chromatin-unbound PAF1 via the 26S proteasome.open1184Ysciescopu