2,687 research outputs found

    RXRΞ± acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells

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    Retinoid X receptor (RXR) plays a crucial role in the cross talk between retinoid receptors and other hormone receptors including the orphan receptor TR3, forming different heterodimers that transduce diverse steroid/thyroid hormone signaling. Here we show that RXRalpha exhibits nucleocytoplasmic shuttling in MGC80-3 gastric cancer cells and that RXRalpha, shuttling is energy-dependent through a nuclear pore complex (NPC)mediated pathway for its import and an intact DNA binding domain-mediated pathway for its export. In the presence of its ligand 9-cis retinoic acid, RXRalpha was almost exclusively located in the cytoplasm. More importantly, we also show that RXRalpha. acts as a carrier to assist translocation of TR3, which plays an important role in apoptosis. Both RXRalpha and TR3 colocalized in the nucleus; however, upon stimulation by 9-cis retinoic acid they cotranslocated to the cytoplasm and then localized in the mitochondria. TR3 export depends on RXRalpha as in living cells GFP-TR3 alone did not result in export from the nucleus even in the presence of 9-cis retinoic acid, whereas GFP-TR3 cotransfected with RXRalpha was exported out of the nucleus in response to 9-cis retinoic acid. Moreover, specific reduction of RXRalpha levels caused by anti-sense RXRalpha abolished TR3 nuclear export. In contrast, specific knockdown of TR3 by antisense-TR3 or TR3-siRNA did not affect RXRalpha shuttling. These results indicate that RXRalpha is responsible for TR3 nucleocytoplasmic translocation, which is facilitated by the RXRalpha ligand 9-cis retinoic acid. In addition, mitochondrial TR3, but not RXRalpha was critical for apoptosis, as TR3 mutants that were distributed in the mitochondria induced apoptosis in the presence or absence of 9-cis retinoic acid. These data reveal a novel aspect of RXRalpha function, in which it acts as a carrier for nucleocytoplasmic translocation of orphan receptors

    Effects of L-arginine on intestinal development and endogenous arginine-synthesizing enzymes in neonatal pigs

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    This study aimed to investigate the effects of dietary L-arginine supplementation on the intestinal development of neonatal piglets and the underlying mechanisms. 36 neonatal piglets were randomly allocated into three diet groups: control group (supplemented with 0% L-arginine), 0.4 and 0.8% Larginine groups. When compared with the control, dietary supplementation with L-arginine decreased (P<0.05) blood urea nitrogen (BUN), and improved (P<0.05) serum T3 and insulin level of the piglets on day 11. Arginine and its metabolites (citrulline and ornithine) were elevated, additionally, dietary supplementation with 0.8% L-arginine markedly enhanced jejunal villus height, villus area on day 11 and D-xylose absorption rate on day 19. Dietary supplementation with 0.8% L-arginine increased (P<0.05) activities of maltose and lactose on day 18, respectively. This effect correlated with profound change in enzyme activities as inducible nitric oxide synthetase (iNOS), glutamine synthetase (GS) and ornithine decarboxylase (ODC) were elevated on day 18. The concentrations of spermine was increased (P<0.05) by L-arginine supplementation on day 18. These results collectively suggest that dietaryΒ  Larginine supplementation improves protein synthesis and intestinal development of the neonatal pigs, the underlying mechanism includes dietary L-arginine supplementation which regulated the productions of intestinal polyamine in jejunum, and stimulated endogenous arginine-synthesizing enzymes in neonatal piglets.Key words: Neonatal pig, L-arginine, intestinal development, arginine-synthetases

    A resonance Raman spectroscopic and CASSCF investigation of the Franck-Condon region structural dynamics and conical intersections of thiophene

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    Resonance Raman spectra were acquired for thiophene in cyclohexane solution with 239.5 and 266 nm excitation wavelengths that were in resonance with ∼240 nm first intense absorption band. The spectra indicate that the Franck-Condon region photodissociation dynamics have multidimensional character with motion mostly along the reaction coordinates of six totally symmetry modes and three nontotally symmetry modes. The appearance of the nontotally symmetry modes, the CS antisymmetry stretch +C-C=C bend mode v 21 (B 2) at 754 cm-1 and the H 7 C 3 C 4 H 8 twist 9 (A 2) at 906 cm -1, suggests the existence of two different types of vibronic-couplings or curve-crossings among the excited states in the Franck-Condon region. The electronic transition energies, the excited state structures, and the conical intersection points 1B 1/ 1A 1 and 1B 2 / 1A 1 between 2 1A 1 and 1 1B 2 or 1 1B 1 potential energy surfaces of thiophene were determined by using complete active space self-consistent field theory computations. These computational results were correlated with the Franck-Condon region structural dynamics of thiophene. The ring opening photodissociation reaction pathway through cleavage of one of the C-S bonds and via the conical intersection point 1B/ 1A 1 was revealed to be the predominant ultrafast reaction channel for thiophene in the lowest singlet excited state potential energy hypersurface, while the internal conversion pathway via the conical intersection point 1B 2 / 1A 1 was found to be the minor decay channel in the lowest singlet excited state potential energy hypersurface. © 2010 American Institute of Physics.published_or_final_versio

    A New High-Level Reconfigurable Lossless Image Compression System for Space Applications

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    On board image data compression is an important feature of satellite remote sensing payloads. Reconfigurable Intellectual Property (IP) cores can enable change of functionality or modifications. A new and efficient lossless image compression scheme for space applications is proposed. In this paper, we present a lossless image compression IP core designed using AccelDSP, which gives users high level of flexibility. One typical configuration is implemented and tested on an FPGA prototyping board. Finally, it is integrated successfully into a System-on-Chip platform for payload data processing and control

    Dual pulse shaping transmission with complementary nyquist pulses

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    Β© 2019 IEEE. The concept of complementary Nyquist pulse is introduced in this paper. Making use of a half rate Nyquist pulse and its complementary one, a dual pulse shaping transmission scheme is proposed, which achieves full Nyquist rate transmission with only a half of the sampling rate required by conventional Nyquist pulse shaping. This is essential for realizing high-speed digital communication systems with available and affordable data conversion devices. The condition for cross-symbol interference free transmission with the proposed dual pulse shaping is proved in theory, and two classes of ideal complementary Nyquist pulses are formulated assuming raised-cosine pulse shaping. Simulation results are also presented to demonstrate the improved spectral efficiency with dual pulse shaping and compare other system performance against conventional Nyquist pulse shaping

    Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer

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    Conceived and designed the experiments: XFL GAC RCB. Performed the experiments: XFL MIA WM RS MSN SZ. Analyzed the data: XFL SR. Contributed reagents/materials/analysis tools: YW GAC. Wrote the paper: XFL RCB.Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 oncoprotein, can effectively target HER2-positive breast cancer through several mechanisms. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis and apoptosis have been investigated in depth, the effect of trastuzumab on microRNA (miRNA) has not been extensively studied. We have performed miRNA microarray profiling before and after trastuzumab treatment in SKBr3 and BT474 human breast cancer cells that overexpress HER2. We found that trastuzumab treatment of SKBr3 cells significantly decreased five miRNAs and increased three others, whereas treatment of BT474 cells significantly decreased two miRNAs and increased nine. The only change in miRNA expression observed in both cell lines following trastuzumab treatment was upregulation of miRNA-194 (miR-194) that was further validated in vitro and in vivo. Forced expression of miR-194 in breast cancer cells that overexpress HER2 produced no effect on apoptosis, modest inhibition of proliferation, significant inhibition of cell migration/invasion in vitro and significant inhibition of xenograft growth in vivo. Conversely, knockdown of miR-194 promoted cell migration. Increased miR-194 expression markedly reduced levels of the cytoskeletal protein talin2 and specifically inhibited luciferase reporter activity of a talin2 wild-type 39-untranslated region, but not that of a mutant reporter, indicating that talin2 is a direct downstream target of miR-194. Trastuzumab treatment inhibited breast cancer cell migration and reduced talin2 expression in vitro and in vivo. Knockdown of talin2 inhibited cell migration/invasion. Knockdown of trastuzumab-induced miR-194 expression with a miR-194 inhibitor compromised trastuzumab-inhibited cell migration in HER2-overexpressing breast cancer cells. Consequently, trastuzumab treatment upregulates miR-194 expression and may exert its cell migration-inhibitory effect through miR-194-mediated downregulation of cytoskeleton protein talin2 in HER2-overexpressing human breast cancer cells.This work was supported by the Anne and Henry Zarrow Foundation, kind gifts from Stuart and Gaye Lynn Zarrow and from Mrs. Delores Wilkenfeld, the Laura and John Arnold Foundation, the RGK Foundation, and the MD Anderson NCI CCSG P30 CA16672. G.A.C. is supported as a Fellow at the University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar and by the CLL Global Research Foundation

    Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet

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    A low-grade pro-inflammatory state is at the pathogenic core of obesity and type 2 diabetes. We tested the hypothesis that the plant terpenoid compound ginsenoside Rb1 (Rb1), known to exert anti-inflammatory effects, would ameliorate obesity, obesity-associated inflammation and glucose intolerance in the high-fat diet-induced obese mouse model. Furthermore, we examined the effect of Rb1 treatment on central leptin sensitivity and the leptin signaling pathway in the hypothalamus. We found that intraperitoneal injections of Rb1 (14 mg/kg, daily) for 21 days significantly reduced body weight gain, fat mass accumulation, and improved glucose tolerance in obese mice on a HF diet compared to vehicle treatment. Importantly, Rb1 treatment also reduced levels of pro-inflammatory cytokines (TNF-Ξ±, IL-6 and/or IL-1Ξ²) and NF-ΞΊB pathway molecules (p-IKK and p-IΞΊBΞ±) in adipose tissue and liver. In the hypothalamus, Rb1 treatment decreased the expression of inflammatory markers (IL-6, IL-1Ξ² and p-IKK) and negative regulators of leptin signaling (SOCS3 and PTP1B). Furthermore, Rb1 treatment also restored the anorexic effect of leptin in high-fat fed mice as well as leptin pSTAT3 signaling in the hypothalamus. Ginsenoside Rb1 has potential for use as an anti-obesity therapeutic agent that modulates obesity-induced inflammation and improves central leptin sensitivity in HF diet-induced obesity. Β© 2014 Public Library of ScienceAcquired from the Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 2014 Wu et al

    Multi-pipe string electromagnetic detection tool and its applications

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    The MID-K, a new kind of multi-pipe string detection tool is introduced. This tool provides a means of evaluating the condition of in-place pipe string, such as tubing and casino. It is capable of discriminating the defects of the inside and outside, and estimating the thickness of tubing and casing. It is accomplished by means of a low frequency eddy current to detect flaws on the inner surface and a magnetic flux leakage to inspect the full thickness. The measurement principle, the technology and applications are presented in this paper
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