Truncated human endothelin receptor A produced by alternative splicing and its expression in melanoma

In this study, reverse transcriptase polymerase chain reaction was used to amplify human endothelin receptor A (ETA) and ETB receptor mRNA. A truncated ETA receptor transcript with exons 3 and 4 skipped was found. The skipping of these two exons results in 109 amino acids being deleted from the receptor. The truncated receptor was expressed in all tissues and cells examined, but the level of expression varied. In melanoma cell lines and melanoma tissues, the truncated receptor gene was the major species, whereas the wild-type ETA was predominant in other tissues. A 1.9-kb ETA transcript was identified in melanoma cell lines by Northern blot, which was much smaller than the transcript in heart and in other tissues reported previously (4.3 kb). The cDNA coding regions of the truncated and wild-type ETA receptors were stably transfected into Chinese hamster ovary (CHO) cells. The truncated ETA receptor-transfected CHO cells did not show binding affinity to endothelin 1 (ET-1) or endothelin 3 (ET-3). The function and biological significance of this truncated ETA receptor is not clear, but it may have regulatory roles for cell responses to ETs

A single meal has the potential to alter brain oxylipin content.

Our objective was to determine whether consumption of a single meal has the potential to alter brain oxylipin content. We examined the cerebrum of mice fed a single high-fat/high-sucrose Western meal or a low-fat/low-sucrose control meal, as well as fasted mice. We found no changes in fatty acid composition of cerebrum across the groups. The cerebral oxylipin profile of mice fed a Western meal is distinct from the profile of mice fed a low-fat/low-sucrose meal. Cerebral gene expression of cyclooxygenase 1, cyclooxygenase 2, and epoxide hydrolase 1 were elevated in Western meal-fed mice compared to low-fat/low-sucrose meal-fed mice. Mice that consumed either meal had lower gene expression of cytochrome P450, family 2, subfamily j, polypeptide 12 than fasted mice. Our data in this hypothesis-generating study indicates that the composition of a single meal has the potential to alter brain oxylipins and the gene expression of the enzymes responsible for their production

Additive resonances of a controlled van der Pol-Duffing oscillator

The trivial equilibrium of a controlled van der Pol-Duffing oscillator with nonlinear feedback control may lose its stability via a non-resonant interaction of two Hopf bifurcations when two critical time delays corresponding to two Hopf bifurcations have the same value. Such an interaction results in a non-resonant bifurcation of co-dimension two. In the vicinity of the non-resonant Hopf bifurcations, the presence of a periodic excitation in the controlled oscillator can induce three types of additive resonances in the forced response, when the frequency of the external excitation and the frequencies of the two Hopf bifurcations satisfy a certain relationship. With the aid of centre manifold theorem and the method of multiple scales, three types of additive resonance responses of the controlled system are investigated by studying the possible solutions and their stability of the four-dimensional ordinary differential equations on the centre manifold. The amplitudes of the free-oscillation terms are found to admit three solutions; two non-trivial solutions and the trivial solution. Of two non-trivial solutions, one is stable and the trivial solution is unstable. A stable non-trivial solution corresponds to a quasi-periodic motion of the original system. It is also found that the frequency-response curves for three cases of additive resonances are an isolated closed curve. It is shown that the forced response of the oscillator may exhibit quasi-periodic motions on a three-dimensional torus consisting of three frequencies; the frequencies of two bifurcating solutions and the frequency of the excitation. Illustrative examples are given to show the quasi-periodic motions. © 2008 Elsevier Ltd. All rights reserved

Nonlinear response of a forced van der Pol-Duffing oscillator at non-resonant bifurcations of codimension two

Non-resonant bifurcations of codimension two may appear in the controlled van der Pol-Duffing oscillator when two critical time delays corresponding to a double Hopf bifurcation have the same value. With the aid of centre manifold theorem and the method of multiple scales, the non-resonant response and two types of primary resonances of the forced van der Pol-Duffing oscillator at non-resonant bifurcations of codimension two are investigated by studying the possible solutions and their stability of the four-dimensional ordinary differential equations on the centre manifold. It is shown that the non-resonant response of the forced oscillator may exhibit quasi-periodic motions on a two- or three-dimensional (2D or 3D) torus. The primary resonant responses admit single and mixed solutions and may exhibit periodic motions or quasi-periodic motions on a 2D torus. Illustrative examples are presented to interpret the dynamics of the controlled system in terms of two dummy unfolding parameters and exemplify the periodic and quasi-periodic motions. The analytical predictions are found to be in good agreement with the results of numerical integration of the original delay differential equation. © 2008 Elsevier Ltd. All rights reserved

A Divergent Synthetic Route to the Vallesamidine and Schizozygine Alkaloids: Total Synthesis of (+)‐Vallesamidine and (+)‐14,15‐Dehydrostrempeliopine

The total synthesis of representative members of the schizozygine alkaloids, (+)‐vallesamidine and (+)‐14,15‐dehydrostrempeliopine, were completed from a late‐stage divergent intermediate. The synthesis took advantage of efficient nitro‐group reactions with the A/B/C ring skeleton constructed concisely on a gram scale through an asymmetric Michael addition, nitro‐Mannich/lactamisation, Tsuji–Trost allylation, and intramolecular C−N coupling reaction. Other key features of the synthesis are a novel [1,4] hydride transfer/Mannich‐type cyclisation to build ring E and a diastereoselective ring‐closing metathesis reaction to construct ring D. This approach gave access to a late‐stage C14,C15 alkene divergent intermediate that could be simply transformed into (+)‐vallesamidine, (+)‐14,15‐dehydrostrempeliopine, and potentially other schizozygine alkaloids and unnatural derivatives

Suppression of the primary resonance vibrations of a forced nonlinear system using a dynamic vibration absorber

In a single degree-of-freedom weakly nonlinear oscillator subjected to periodic external excitation, a small-amplitude excitation may produce a relatively large-amplitude response under primary resonance conditions. Jump and hysteresis phenomena that result from saddle-node bifurcations may occur in the steady-state response of the forced nonlinear oscillator. A simple mass-spring-damper vibration absorber is thus employed to suppress the nonlinear vibrations of the forced nonlinear oscillator for the primary resonance conditions. The values of the spring stiffness and mass of the vibration absorber are significantly lower than their counterpart of the forced nonlinear oscillator. Vibrational energy of the forced nonlinear oscillator is transferred to the attached light mass through linked spring and damper. As a result, the nonlinear vibrations of the forced oscillator are greatly reduced and the vibrations of the absorber are significant. The method of multiple scales is used to obtain the averaged equations that determine the amplitude and phases of the first-order approximate solutions to primary resonance vibrations of the forced nonlinear oscillator. Illustrative examples are given to show the effectiveness of the dynamic vibration absorber for suppressing primary resonance vibrations. The effects of the linked spring and damper and the attached mass on the reduction of nonlinear vibrations are studied with the help of frequency response curves, the attenuation ratio of response amplitude and the desensitisation ratio of the critical amplitude of excitation. © 2009 Elsevier Ltd. All rights reserved

Differing lifestyles of Staphylococcus epidermidis as revealed through Bayesian clustering of multilocus sequence types

Staphylococcus epidermidis is part of the normal bacterial flora of human skin and a leading cause of infections associated with indwelling medical devices. Previous phylogenetic analyses of subgenomic data have been unable to distinguish between S. epidermidis strains with nosocomial or commensal lifestyles, despite the identification of specific phenotypes and accessory genes that may contribute to such lifestyles. To attempt to better define the population structure of this species, the international S. epidermidis multilocus sequence typing database was analyzed with the Bayesian clustering programs STRUCTURE and BAPS. A total of six genetic clusters (GCs) were identified. A local population of S. epidermidis from clinical specimens was classified according to these six GCs, and further characterized for antibiotic susceptibilities, biofilm, and various genetic markers. GC5 was abundant and significantly enriched for isolates that were resistant to four classes of antibiotics, high biofilm production, and positive for the virulence markers icaA, IS256, and sesD/bhp, indicating its potential clinical relevance. In contrast, GC2 was rare and contained the only isolates positive for the putative commensal marker, fdh. GC1 and GC6 were abundant but not significantly associated with any of the examined characteristics, except for sesF/aap and GC6. GC3 was rare and identified as a potential genetic sink that received, but did not donate, core genetic material from other GCs. In conclusion, population genetics analyses were essential for identifying clusters of strains that may differ in their adaptation to nosocomial or commensal lifestyles. These results provide a new, population genetics framework for studying S. epidermidis

Steady-state response of fluid-structure interactions in hydraulic piping system of passive interconnected suspensions

Copyright © 2016 Inderscience Enterprises Ltd. Pressure changes in the liquid-filled fluid circuit of a hydraulically interconnected suspension (HIS) system can induce vibrations of the whole pipeline and the associated structure, and hence become a source of structural noise which degrades ride comfort. This paper presents a numerical and experimental investigation into the vibration of the hydraulic piping system of a passive interconnected suspension. The transfer matrix method (TMM) is used to develop a mathematical model, which consists of various pipe sections, hose sections, concentrated masses, spring supports, elbows, damper valves, and accumulators. Laboratory experiments are performed on two liquid-filled piping systems. The measured steady-state responses of the hydraulic circuits are compared with those obtained from numerical simulations of the developed model. It is found that the developed model of the hydraulic system has a reasonable accuracy in the frequency range of interest, and thus can be employed to optimise the design of the hydraulic system