Tissue-specific and neural activity-regulated expression of human BDNF gene in BAC transgenic mice

Background  

Brain-derived neurotrophic factor (BDNF) is a small secreted protein that has important roles in the developing and adult nervous system. Altered expression or changes in the regulation of the BDNF gene have been implicated in a variety of human nervous system disorders. Although regulation of the rodent BDNF gene has been extensively investigated, in vivo studies regarding the human BDNF gene are largely limited to postmortem analysis. Bacterial artificial chromosome (BAC) transgenic mice harboring the human BDNF gene and its regulatory flanking sequences constitute a useful tool for studying human BDNF gene regulation and for identification of therapeutic compounds modulating BDNF expression.     

Cocaine reward and locomotion stimulation in mice with reduced dopamine transporter expression

Background  

The dopamine transporter (DAT) plays a critical role in regulating dopamine neurotransmission. Variations in DAT or changes in basal dopaminergic tone have been shown to alter behavior and drug responses. DAT is one of the three known high affinity targets for cocaine, a powerful psychostimulant that produces reward and stimulates locomotor activity in humans and animals. We have shown that cocaine no longer produces reward in knock-in mice with a cocaine insensitive mutant DAT (DAT-CI), suggesting that cocaine inhibition of DAT is critical for its rewarding effect. However, in DAT-CI mice, the mutant DAT has significantly reduced uptake activity resulting in elevated basal dopaminergic tone, which might cause adaptive changes that alter responses to cocaine. Therefore, the objective of this study is to determine how elevated dopaminergic tone affects how mice respond to cocaine.     

生物体中的生物磁性纳米粒子及基因调控机制

生物磁性纳米粒子在所有三个生命领域的有机体中存在着,包括在原核生物、古细菌和真核生物中.这些生物体中的生物磁性纳米粒子具有相似的物理化学特性,也随着物种的不同存在着差别.在人体中的正常组织和病变组织中同样存在着生物磁性纳米粒子,这些粒子与其它物种中的生物磁性纳米粒子具有相似性和区别,人体病变组织中生物磁性纳米粒子数量的增多与人类神经退行性病变、癌症和动脉粥样硬化病等疾病有着密切的关系.基于比较基因组学研究方法,科学家认为生物体中生物磁性纳米粒子生物矿化过程有相似的基因调控机制,并给出了预测的基因调控机制模型.本文对以上内容做了简要描述,希望对有关研究提供借鉴.     

Exact solution of a model DNA-inversion genetic switch with orientational control

DNA inversion is an important mechanism by which bacteria and bacteriophage switch reversibly between phenotypic states. In such switches, the orientation of a short DNA element is flipped by a site-specific recombinase enzyme. We propose a simple model for a DNA-inversion switch in which recombinase production is dependent on the switch state (orientational control). Our model is inspired by the fim switch in E. coli. We present an exact analytical solution of the chemical master equation for the model switch, as well as stochastic simulations. Orientational control causes the switch to deviate from Poissonian behavior: the distribution of times in the on state shows a peak and successive flip times are correlated.     

Vibration suppression control of smart piezoelectric rotating truss structure by parallel neuro-fuzzy control with genetic algorithm tuning

The main goal of this paper is to develop a novel approach for vibration control on a piezoelectric rotating truss structure. This study will analyze the dynamics and control of a flexible structure system with multiple degrees of freedom, represented in this research as a clamped–free–free–free truss type plate rotated by motors. The controller has two separate feedback loops for tracking and damping, and the vibration suppression controller is independent of position tracking control. In addition to stabilizing the actual system, the proposed proportional–derivative (PD) control, based on genetic algorithm (GA) to seek the primary optimal control gain, must supplement a fuzzy control law to ensure a stable nonlinear system. This is done by using an intelligent fuzzy controller based on adaptive neuro-fuzzy inference system (ANFIS) with GA tuning to increase the efficiency of fuzzy control. The PD controller, in its assisting role, easily stabilized the linear system. The fuzzy controller rule base was then constructed based on PD performance-related knowledge. Experimental validation for such a structure demonstrates the effectiveness of the proposed controller. The broad range of problems discussed in this research will be found useful in civil, mechanical, and aerospace engineering, for flexible structures with multiple degree-of-freedom motion.     

The Rayleigh-Plesset equation in terms of volume with explicit shear losses

The most common nonlinear equation of motion for the damped pulsation of a spherical gas bubble in an infinite body of liquid is the Rayleigh-Plesset equation, expressed in terms of the dependency of the bubble radius on the conditions pertaining in the gas and liquid (the so-called ‘radius frame’). However over the past few decades several important analyses have been based on a heuristically derived small-amplitude expansion of the Rayleigh-Plesset equation which considers the bubble volume, instead of the radius, as the parameter of interest, and for which the dissipation term is not derived from first principles. So common is the use of this equation in some fields that the inherent differences between it and the ‘radius frame’ Rayleigh-Plesset equation are not emphasised, and it is important in comparing the results of the two equations to understand that they differ both in terms of damping, and in the extent to which they neglect higher order terms. This paper highlights these differences. Furthermore, it derives a ‘volume frame’ version of the Rayleigh-Plesset equation which contains exactly the same basic physics for dissipation, and retains terms to the same high order, as does the ‘radius frame’ Rayleigh-Plesset equation. Use of this equation will allow like-with-like comparisons between predictions in the two frames.     

From simple to complex oscillatory behavior in metabolic and genetic control networks

We present an overview of mechanisms responsible for simple or complex oscillatory behavior in metabolic and genetic control networks. Besides simple periodic behavior corresponding to the evolution toward a limit cycle we consider complex modes of oscillatory behavior such as complex periodic oscillations of the bursting type and chaos. Multiple attractors are also discussed, e.g., the coexistence between a stable steady state and a stable limit cycle (hard excitation), or the coexistence between two simultaneously stable limit cycles (birhythmicity). We discuss mechanisms responsible for the transition from simple to complex oscillatory behavior by means of a number of models serving as selected examples. The models were originally proposed to account for simple periodic oscillations observed experimentally at the cellular level in a variety of biological systems. In a second stage, these models were modified to allow for complex oscillatory phenomena such as bursting, birhythmicity, or chaos. We consider successively (1) models based on enzyme regulation, proposed for glycolytic oscillations and for the control of successive phases of the cell cycle, respectively; (2) a model for intracellular Ca(2+) oscillations based on transport regulation; (3) a model for oscillations of cyclic AMP based on receptor desensitization in Dictyostelium cells; and (4) a model based on genetic regulation for circadian rhythms in Drosophila. Two main classes of mechanism leading from simple to complex oscillatory behavior are identified, namely (i) the interplay between two endogenous oscillatory mechanisms, which can take multiple forms, overt or more subtle, depending on whether the two oscillators each involve their own regulatory feedback loop or share a common feedback loop while differing by some related process, and (ii) self-modulation of the oscillator through feedback from the system's output on one of the parameters controlling oscillatory behavior. However, the latter mechanism may also be viewed as involving the interplay between two feedback processes, each of which might be capable of producing oscillations. Although our discussion primarily focuses on the case of autonomous oscillatory behavior, we also consider the case of nonautonomous complex oscillations in a model for circadian oscillations subjected to periodic forcing by a light-dark cycle and show that the occurrence of entrainment versus chaos in these conditions markedly depends on the wave form of periodic forcing. (c) 2001 American Institute of Physics.     

Phase-matched enhancements of high-harmonic soft X-rays by adaptive wave-front control with a genetic algorithm

We demonstrate the enhancement of high-harmonic soft-X-ray generation by adaptive wave-front control of a 745-nm Ti:sapphire laser by use of a 59-channel membrane deformable mirror, combined with a genetic algorithm, for the first time to our knowledge. The harmonics ranging from 17 nm to 28 nm were enhanced by factors up to 13. The numerical calculations illustrate that the enhancements of the plateau harmonics are due to macroscopic phase-matching effect, whereas those of the cutoff harmonics are due to the increase in focal intensity. PACS 42.65.Ky     

Analytical results for a non-Markovian process of gene expression with positive and negative feedbacks

Gene expression is a very complex process and involves many small biochemical reaction steps, resulting in a non-Markovian discrete stochastic process due to molecular memory between individual reactions. At present, this process is successfully investigated by generalized chemical master equation models. However, these models do not consider the role of feedback networks in gene expression. How the interaction between feedbacks and molecular memory affects gene expression still remains not well understood. Here, we establish generalized chemical master equation models of gene expression with positive and negative feedbacks. Assuming that the process of producing proteins follows an Erlang probability distribution, we obtain the analytical expression for this model in a steady state, as well as the measure of the noise of protein numbers. We further find that molecular memory competes with the positive feedback in suppressing the noise of the protein number. For our model with a negative feedback, molecular memory can strengthen the intensity of suppressing this noise. These interesting results imply that molecular memory are as important as the feedbacks to affect gene expression.     

Influence of body posture and lung volume on subglottal pressure control during singing

The role of different breathing muscles during singing was investigated by synchronously recording EMG, pressure, and sound signals, using lung volume and gravity as experimental parameters. Surface EMG signals from the external and internal intercostals, the diaphragm, and the abdominal oblique muscles were recorded, while two singer subjects performed various singing tasks associated with rapid and precise changes of subglottal pressure. Esophageal and gastric pressures were measured by pressure transducers, and lung volume by means of impedance plethysmography. The results show that the breathing system efficiently compensates for drastic differences in the mechanics of the breathing apparatus, caused by differences in lung volume and gravity induced by changes of body posture.     

Qualitative assessment of gene expression in affymetrix genechip arrays

Affymetrix Genechip microarrays are used widely to determine the simultaneous expression of genes in a given biological paradigm. Probes on the Genechip array are atomic entities which by definition are randomly distributed across the array and in turn govern the gene expression. In the present study, we make several interesting observations. We show that there is considerable correlation between the probe intensities across the array which defy the independence assumption. While the mechanism behind such correlations is unclear, we show that scaling behavior and the profiles of perfect match (PM) as well as mismatch (MM) probes are similar and immune-to-background subtraction. We believe that the observed correlations are possibly an outcome of inherent non-stationarities or patchiness in the array devoid of biological significance. This is demonstrated by inspecting their scaling behavior and profiles of the PM and MM probe intensities obtained from publicly available Genechip arrays from three eukaryotic genomes, namely: Drosophila melanogaster (fruit fly), Homo sapiens (humans) and Mus musculus (house mouse) across distinct biological paradigms and across laboratories, with and without background subtraction. The fluctuation functions were estimated using detrended fluctuation analysis (DFA) with fourth-order polynomial detrending. The results presented in this study provide new insights into correlation signatures of PM and MM probe intensities and suggests the choice of DFA as a tool for qualitative assessment of Affymetrix Genechip microarrays prior to their analysis. A more detailed investigation is necessary in order to understand the source of these correlations.