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

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

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

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

Antifatigue Effect of Millettiae speciosae Champ (Leguminosae) Extract in Mice

Purpose: To evaluate whether Millettiae Speciosae Champ. (Leguminosae) can enhance exercise performance as well as ascertain if it a potential functional food material.Methods: The extract of Millettia speciosa Champ. (MSE) was orally administered to mice in 500, 1000, 2000 mg/kg doses to investigate its anti-fatigue effect in both forced swimming and climbing tests. Glycogen, triglyceride (TG), blood urea nitrogen (BUN) and creatine phosphokinase (CK) levels in plasma which can indicate alterations in energy utilization during exercise performance, were determined to analyze the operating exercise mechanisms.Results: The results showed that swimming time to exhaustion was longer in all treated groups (41.06 ± 1.92, 47.84 ± 1.60, 54.00 ± 2.45 min for 500, 10000 and 2000 mg/kg doses, respectively) than for control (19.45 ± 0.62 min, p < 0.05). The middle and high doses of MSE-treated groups significantly prolonged the climbing time compared with control (p < 0.05). Furthermore, MSE reduced the content of TG significantly by increasing fat utilization, delayed the accumulation of BUN and decreased the level of CK (p < 0.05). In addition, administration of MSE significantly protected the depletion of muscle glycogen when compared with control (p < 0.05).Conclusion: The results show for the first time that Millettia speciosa Champ. (Leguminosae) has significant anti-fatigue activity, and also suggest that it is a potential functional food material.Keywords: Radix millettiae speciosae, Anti-fatigue activity, Exercise performance, Serum urea nitrogen, Gastrocnemius muscle glycogen, Triglyceride, Functional foo

Overexpression of Forkhead Box Protein M1 (FOXM1) in Ovarian Cancer Correlates with Poor Patient Survival and Contributes to Paclitaxel Resistance

published_or_final_versio

Controlled motion of electrically neutral microparticles by pulsed direct current

A controlled motion of electrically neutral microparticles in a conductive liquid at high temperatures has not yet been realized under the uniform direct electric current field. We propose a simple method, which employs pulsed direct current to a conductive liquid metal containing low-conductivity objects at high temperature. The electric current enables the low-conductivity particles to pass from the centre towards the various surfaces of the high-conductivity liquid metal. Most interestingly, the directionality of microparticles can be controlled and their speed can be easily regulated by adjusting pulsed current density. We find that the movement may arise from the configuration of electrical domains which generates a driving force which exceeds the force of gravity and viscous friction. All of these features are of potential benefit in separating the particles of nearly equal density but distinctly different electrical conductivities, and also offer considerable promise for the precise and selective positioning of micro-objects or the controlled motion of minute quantities of surrounding fluids

Liquid crystalline behaviour of chitooligosaccharides

Two chitooligosaccharide samples (COS1 and COS2) were prepared by enzymatic degradation of chitosan. The molecular weight of the main component was determined by mass spectrometry to be 2340 and 4303, respectively. They showed cholesteric liquid crystal structures in concentrated solutions. The critical concentrations to form a lyotropic liquid crystalline phase in formic acid were measured by means of polarized optical microscopy, refractometry and Fourier transform infrared spectroscopy. The results from the three methods agreed with each other. The experimental value of COS2 was quantitatively consistent with that calculated according to Khokhlov and Semenov theory. But the experimental value of COS1 diverged from the theoretical one, which is explained by the inaccuracy at higher concentrations of the second virial approximation underlying this theory. (C) 2004 Elsevier Ltd. All rights reserved

Mild Hypothermia Attenuates Mitochondrial Oxidative Stress by Protecting Respiratory Enzymes and Upregulating MnSOD in a Pig Model of Cardiac Arrest

Mild hypothermia is the only effective treatment confirmed clinically to improve neurological outcomes for comatose patients with cardiac arrest. However, the underlying mechanism is not fully elucidated. In this study, our aim was to determine the effect of mild hypothermia on mitochondrial oxidative stress in the cerebral cortex. We intravascularly induced mild hypothermia (33°C), maintained this temperature for 12 h, and actively rewarmed in the inbred Chinese Wuzhishan minipigs successfully resuscitated after 8 min of untreated ventricular fibrillation. Cerebral samples were collected at 24 and 72 h following return of spontaneous circulation (ROSC). We found that mitochondrial malondialdehyde and protein carbonyl levels were significantly increased in the cerebral cortex in normothermic pigs even at 24 h after ROSC, whereas mild hypothermia attenuated this increase. Moreover, mild hypothermia attenuated the decrease in Complex I and Complex III (i.e., major sites of reactive oxygen species production) activities of the mitochondrial respiratory chain and increased antioxidant enzyme manganese superoxide dismutase (MnSOD) activity. This increase in MnSOD activity was consistent with the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and protein expressions, and with the increase of Nrf2 nuclear translocation in normothermic pigs at 24 and 72 h following ROSC, whereas mild hypothermia enhanced these tendencies. Thus, our findings indicate that mild hypothermia attenuates mitochondrial oxidative stress in the cerebral cortex, which may be associated with reduced impairment of mitochondrial respiratory chain enzymes, and enhancement of MnSOD activity and expression via Nrf2 activation

Spatiotemporal Structure of Molecular Evolution of H5N1 Highly Pathogenic Avian Influenza Viruses in Vietnam

BackgroundVietnam is one of the countries most affected by outbreaks of H5N1 highly pathogenic avian influenza viruses. First identified in Vietnam in poultry in 2001 and in humans in 2004, the virus has since caused 111 cases and 56 deaths in humans. In 2003/2004 H5N1 outbreaks, nearly the entire poultry population of Vietnam was culled. Our earlier study (Wan et al., 2008, PLoS ONE, 3(10): e3462) demonstrated that there have been at least six independent H5N1 introductions into Vietnam and there were nine newly emerged reassortants from 2001 to 2007 in Vietnam. H5N1 viruses in Vietnam cluster distinctly around Hanoi and Ho Chi Minh City. However, the nature of the relationship between genetic divergence and geographic patterns is still unclear.Methodology/Principal FindingsIn this study, we hypothesized that genetic distances between H5N1 viruses in Vietnam are correlated with geographic distances, as the result of distinct population and environment patterns along Vietnam's long north to south longitudinal extent. Based on this hypothesis, we combined spatial statistical methods with genetic analytic techniques and explicitly used geographic space to explore genetic evolution of H5N1 highly pathogenic avian influenza viruses at the sub-national scale in Vietnam. Our dataset consisted of 125 influenza viruses (with whole genome sets) isolated in Vietnam from 2003 to 2007. Our results document the significant effect of space and time on genetic evolution and the rise of two regional centers of genetic mixing by 2007. These findings give insight into processes underlying viral evolution and suggest that genetic differentiation is associated with the distance between concentrations of human and poultry populations around Hanoi and Ho Chi Minh City.Conclusions/SignificanceThe results show that genetic evolution of H5N1 viruses in Vietnamese domestic poultry is highly correlated with the location and spread of those viruses in geographic space. This correlation varies by scale, time, and gene, though a classic isolation by distance pattern is observed. This study is the first to characterize the geographic structure of influenza viral evolution at the sub-national scale in Vietnam and can shed light on how H5N1 HPAIVs evolve in certain geographic settings