Time-periodic oscillations in a model for the respiratory process of a bacterial culture

Summary Deterministic (analytical), stochastic and computer-aided methods have been used to construct the time-periodic (limit cycle) solution of a model suggested by H. Degn to account for the qualitative features of the respiratory process in a Klebsiella Aerogenes bacterial culture.     

通过烟熏和间歇低氧构建大鼠COPD-OSAHS重叠综合征模型

目的构建大鼠COPD-OSAHS重叠综合征(OS)模型,为开展OS基础研究提供可行手段及实验平台。方法将14只SPF级雌性6周龄SD大鼠随机分为实验组和对照组,其中实验组(8只)予烟熏和间歇低氧暴露,对照组(6只)予假烟熏和正常氧暴露。8周后计算实验组大鼠的存活率,并对比两组大鼠的一般情况、血气分析、右心室肥厚指数、平均肺泡数、平均肺泡间隔、肺组织病理改变。结果间歇低氧箱氧浓度-时间变化曲线显示氧浓度均周期性降低及恢复正常,成功模拟出间歇低氧气体环境;实验组最终存活6只,存活率为75%,对照组6只大鼠全部存活。与对照组相比,实验组6只存活的SD大鼠一般情况较差,存在酸中毒、低氧血症、二氧化碳潴留、右心室肥厚、平均肺泡截距明显增大、平均肺泡数明显减少(P<0.05),差异有统计学意义;肺组织病理观察显示肺间质炎症浸润、支气管壁淋巴细胞增生、细支气管管壁平滑肌增生、管壁平滑肌部分断裂、杯状细胞增生及肺气肿。结论采用烟熏联合间歇低氧暴露方法成功建立了大鼠OS模型,更加有意义及客观的模型评价指标有待研究发现。     

New insights offered by a computational model of deep brain stimulation

Deep brain stimulation (DBS) is a standard neurosurgical procedure used to treat motor symptoms in about 5% of patients with Parkinson's disease (PD). Despite the indisputable success of this procedure, the biological mechanisms underlying the clinical benefits of DBS have not yet been fully elucidated. The paper starts with a brief review on the use of DBS to treat PD symptoms. The second section introduces a computational model based on the population density approach and the Izhikevich neuron model. We explain why this model is appropriate for investigating macroscopic network effects and exploring the physiological mechanisms which respond to this treatment strategy (i.e., DBS). Finally, we present new insights into the ways this computational model may help to elucidate the dynamic network effects produced in a cerebral structure when DBS is applied.     

An antioxidant treatment potentially protects myocardial energy metabolism by regulating uncoupling protein 2 expression in a chronic beta-adrenergic stimulation rat model

Excessive beta-adrenergic stimulation causes cardiac toxicity, which also contributes to cardiac oxidative stress. Although uncoupling protein 2 (UCP2), a member of the mitochondrial inner membrane carrier family, can regulate energy efficiency and oxidative stress in mitochondria, little data exist regarding interactions between UCP2 expression and beta-adrenergic stimulation induced cardiac oxidative damage. We investigated whether chronic beta-adrenergic stimulation induces myocardial energy metabolism abnormality via oxidative stress, including any role of UCP2. We also examined whether 3-methyl-1-phenyl-2-pyrazolin-5-one (MIC-186; edaravone), a potent free radical scavenger, has cardioprotective effects against beta-adrenergic stimulation. Male Sprague-Dawley rats received isoproterenol (1.2 mg/kg/day) subcutaneously or/and edaravone (30 mg/kg/day) orally. Isoproterenol increased the heart/body weight ratio, accompanied by an increase in the level of myocardial thiobarbituric acid reactive substances (TBARS) and a decreased phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. Isoproterenol also markedly increased expressions of UCP2 mRNA (1.74 fold vs. non-isoproterenol) and protein (1.93 fold vs. non-isoproterenol). Edaravone had no apparent effect in hypertrophic responses, but significantly prevented both increases in TBARS and decreases in the PCr/ATP ratio. Edaravone also prevented increases in UCP2 mRNA (0.76 fold vs. isoproterenol) and protein (0.62 fold vs. isoproterenol) expressions against isoproterenol administration. Our results suggest that chronic beta-adrenergic stimulation induces myocardial energy inefficiency via excessive oxidative stress. The antioxidant effect of edaravone has potential to improve energy metabolism abnormalities against beta-adrenergic stimulation. Adequate regulation of UCP2 expression through artificial reduction of oxidative stress may play an important role in protection of the myocardial energy metabolism.     

On the appearance of chaos in a model of the Belousov reaction

Summary A modified version of the Oregonator is analysed as a model of oscillations, bistability and chaos in the bromate-malonic acid-cerium reaction.This study was supported by the National Cancer Institute, USA, Grant No. 5 F32 CAO5152-02.     

Impact of Ramadan intermittent fasting on cognitive function in trained cyclists: a pilot study

This study assessed selected measures of cognitive function in trained cyclists who observed daylight fasting during Ramadan. Eleven cyclists volunteered to participate (age: 21.6±4.8 years, VO₂max: 57.7±5.6 ml kg⁻¹·min⁻¹) and were followed for 2 months. Cognitive function (Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time index (RTI) and Rapid Visual Information Processing (RVP) tests) and sleep architecture (ambulatory EEG) were assessed: before Ramadan (BR), in the 1st week (RA1) and 4th week of Ramadan (RA4), and 2 weeks post-Ramadan (PR). Both cognitive tests were performed twice per day: before and after Ramadan at 8-10 a.m. and 4-6 p.m., and during Ramadan at 4-6 p.m. and 0-2 a.m., respectively. Training load (TL) by the rating of perceived exertion (RPE) method and wellness (Hooper index) were measured daily. If the TL increased over the study period, this variable was stable during Ramadan. The perceived fatigue and delayed onset muscle soreness (DOMS) increased at RA4. Sleep patterns and architecture showed clear disturbances, with significant increases in the number of awakenings and light sleep durations during Ramadan (RA1 and RA4), together with decreased durations of deep and REM sleep stages at PR. RTI (simple and multiple reaction index) reaction and movement times did not vary over the study period. The RVP test showed reduced false alarms during Ramadan, suggesting reduced impulsivity. Overall accuracy significantly increased at RA1, RA4 and PR compared to baseline. At RA4, the accuracy was higher at 0-2 a.m. compared to 4-6 p.m. Despite the observed disturbances in sleep architecture, Ramadan fasting did not negatively impact the cognitive performance of trained cyclists from the Middle East.     

间歇性低压低氧预处理对脑缺血大鼠海马p-p38 MAPK表达的影响

目的:本文旨在观察间歇性低压低氧(IH)预处理诱导脑缺血耐受过程中,大鼠海马CA1区磷酸化p38MAPK(p-p38 MAPK)的表达以及表达p-p38 MAPK的星形胶质细胞数量。方法:将30只健康雄性Wistar大鼠随机分为6组(n=5):假手术(sham)0 min组、IH+sham 0 min组、sham 7 d组、IH+sham 7 d组、损伤性缺血(Is)7 d组、IH+Is 7 d组。通过硫堇染色对各组大鼠海马CA1区锥体神经元进行神经病理学评价;免疫组织化学染色观察pp38 MAPK的表达;免疫荧光双标法观察表达p-p38 MAPK的星形胶质细胞数量。结果:IH预处理可以诱导脑缺血耐受,同时引起大鼠海马CA1区p-p38 MAPK的表达明显增加,且上调星形胶质细胞中p-p38 MAPK的表达。结论:低压低氧预处理促大鼠海马CA1区锥体神经元和星形胶质细胞中p-p38MAPK上调可能是IH预处理保护脑的一个途经。     

Reduction in cortical parvalbumin expression due to intermittent theta‐burst stimulation correlates with maturation of the perineuronal nets in young rats

We recently showed that intermittent theta‐burst stimulation (iTBS) using transcranial magnetic stimulation strongly reduces the number of rat neocortical interneurons expressing glutamic acid decarboxylase 67 kDa (GAD67) and parvalbumin (PV), indicating changed activity of fast‐spiking (FS) interneurons. In advance of in vitro studies intended to characterize changes in electrical properties of FS interneurons under these conditions, we tested whether the iTBS effect is age‐dependent. Conscious Sprague‐Dawley rats aged between 28 and 90 days received three blocks of iTBS at 15 min intervals. We found that iTBS‐related reduction in PV+ cells was absent up to an age of 32 days, then gradually increased, and approached a maximum of about 40% reduction at an age of about 40 days. The relative number of cells expressing PV (PV+, 8–9%) did not change with age in sham‐controls and also the increase in cortical c‐Fos expression induced by iTBS was not principally age‐dependent. However, a prominent growth of the perineuronal nets, typically surrounding the PV+ cells, exactly paralleled the increase in the iTBS effect. Based on these findings, we conclude that the functional development of the inhibitory network of PV+ interneurons with regard to intracortical synaptic connectivity is not sufficiently matured in rats younger than 35d to enable activity‐dependent modifications during iTBS. Outgrowth of the perineuronal nets and associated maturation of excitatory cortical inputs, as is characteristic for the critical cortical period, may take place before PV+ interneurons can be sufficiently activated via repetitive transcranial magnetic stimulation, allowing plastic changes of molecular phenotype and likely also synaptic plasticity. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 1–11, 2015     

Vagal nerve stimulation protects cardiac injury by attenuating mitochondrial dysfunction in a murine burn injury model

Mitochondria play a central role in the integration and execution of a wide variety of apoptotic signals. In the present study, we examined the deleterious effects of burn injury on heart tissue. We explored the effects of vagal nerve stimulation (VNS) on cardiac injury in a murine burn injury model, with a focus on the protective effect of VNS on mitochondrial dysfunction in heart tissue. Mice were subjected to a 30% total body surface area, full‐thickness steam burn followed by right cervical VNS for 10 min. and compared to burn alone. A separate group of mice were treated with the M₃‐muscarinic acetylcholine receptor (M₃‐AchR) antagonist 4‐DAMP or phosphatidylinositol 3 Kinase (PI3K) inhibitor LY294002 prior to burn and VNS. Heart tissue samples were collected at 6 and 24 hrs after injury to measure changes in apoptotic signalling pathways. Burn injury caused significant cardiac pathological changes, cardiomyocyte apoptosis, mitochondrial swelling and decrease in myocardial ATP content at 6 and 24 hrs after injury. These changes were significantly attenuated by VNS. VNS inhibited release of pro‐apoptotic protein cytochrome C and apoptosis‐inducing factor from mitochondria to cytosol by increasing the expression of Bcl‐2, and the phosphorylation level of Bad (pBad¹³⁶) and Akt (pAkt³⁰⁸). These protective changes were blocked by 4‐DAMP or LY294002. We demonstrated that VNS protected against burn injury–induced cardiac injury by attenuating mitochondria dysfunction, likely through the M₃‐AchR and the PI3K/Akt signalling pathways.     

Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model

Vagus nerve stimulation (VNS) is an effective adjunctive treatment for medically refractory epilepsy. In this study, we measured VNS-induced changes in hippocampal neurotransmitter levels and determined their potential involvement in the anticonvulsive action of VNS, to elucidate the mechanism of action responsible for the seizure suppressing effect of VNS in an animal model for limbic seizures. We used in vivo intracerebral microdialysis to measure VNS-induced changes in hippocampal extracellular concentrations of noradrenaline, dopamine, serotonin and GABA in freely moving, male Wistar rats. During the same experiment, the effect of VNS on pilocarpine-induced limbic seizures was assessed using video-EEG monitoring. The involvement of VNS-induced increases in hippocampal noradrenaline in the mechanims of action of VNS was evaluated by blocking hippocampal α(2)-receptors. VNS produced a significant increase in hippocampal noradrenaline concentration (69 ± 16% above baseline levels). VNS also increased the latency between pilocarpine infusion and the onset of epileptiform discharges, and reduced the duration and severity of pilocarpine-induced limbic seizures. A strong positive correlation was found between the noradrenergic and anticonvulsive effects of VNS. Blockade of hippocampal α(2 -receptors reversed the seizure-suppressing effect of VNS. VNS induces increases in extracellular hippocampal noradrenaline, which are at least partly responsible for its seizure-suppressing effect in a model for limbic seizures, and constitute a potential biomarker for the efficacy of VNS in temporal lobe epilepsy.     

Yeast glycolytic oscillations that are not controlled by a single oscillophore: a new definition of oscillophore strength

Biochemical oscillations, such as glycolytic oscillations, are often believed to be caused by a single so-called ‘oscillophore’. The main characteristics of yeast glycolytic oscillations, such as frequency and amplitude, are however controlled by several enzymes. In this paper, we develop a method to quantify to which extent any enzyme determines the occurrence of oscillations. Principles extrapolated from metabolic control analysis are applied to calculate the control exerted by individual enzymes on the real and imaginary parts of the eigenvalues of the Jacobian matrix. We propose that the control exerted by an enzyme on the real part of the smallest eigenvalue, in terms of absolute value, quantifies to which extent that enzyme contributes to the emergence of instability. Likewise the control exerted by an enzyme on the imaginary part of complex eigenvalues may serve to quantify the extent to which that enzyme contributes to the tendency of the system to oscillate. The method was applied both to a core model and to a realistic model of yeast glycolytic oscillations. Both the control over stability and the control over oscillatory tendency were distributed among several enzymes, of which glucose transport, pyruvate decarboxylase and ATP utilization were the most important. The distributions of control were different for stability and oscillatory tendency, showing that control of instability does not imply control of oscillatory tendency nor vice versa. The control coefficients summed up to 1, suggesting the existence of a new summation theorem. These results constitute proof that glycolytic oscillations in yeast are not caused by a single oscillophore and provide a new, subtle, definition for the oscillophore strength of an enzyme.     

Analysis of oscillations in yeast continuous cultures by a new simplified model

The autonomous oscillations in yeast continuous cultures are investigated analytically and related to the behaviour of the single cell by means of a suitable modified version of Monod’s classical chemostat model. Two main cell phases or states are considered to account for the experimentally observed changes occurring in the cell growth course: the budded phase and the unbudded one. Thus, a sort of two compartment structure is given to the total biomass. The model so far obtained allows one to analyse the local properties of the predicted steady states under various assumptions, both on the yield coefficients and the specific growth rates. Necessary conditions for the local instability are derived and the existence of stable limit cycles is shown by computer simulation. With respect to the qualitative changes in the metabolic parameters, this analysis agrees with the results obtained by simulation of complex structured and segregated models. However, the oscillation period is too long compared with the experimental one and this fact may be mainly due to the strong simplifying assumptions on the dynamic evolution of the transfer rates between the two compartments. The model’s usefulness seems until now restricted to the identification of the relationships between the cell cycle regulation and the oscillation triggering.     

无线遥测和刺激技术建立兔房颤模型的探索

目的探索一种在无线遥测和刺激技术基础上的兔房颤模型的制作。方法新西兰兔皮下植入自主研发的植入式遥测刺激器,植入式遥测刺激器的制作是以TI公司（德州仪器）的MSP单片机和TI公司的RF无线收发芯片CC2250为核心开发设计。优化植入系统设计以满足新西兰兔房颤模型建立的探索实验;植入子植入新西兰兔腹部皮下,采集电极留置于左上肢和右上肢腋下皮下,两个刺激电极分别缝合于左心耳和左心房上,通过无线收发采集和刺激信号;实现利用Powerlab生理记录仪连续监测体表I导联心电信号,并通过专用计算机程序刺激软件,发放间歇（刺激2 s,暂停2 s）高频（频率20 Hz）阈上（强度2 mA,脉宽1 ms）刺激,若间歇期内出现房颤,则人为干预中止刺激,若转为窦性心律,则继续刺激。结果植入式遥测刺激器在体内可稳定工作（包括采集模拟心电信号和发放刺激）30 d,植入新西兰兔体内刺激3周后可诱导出房颤,持续时间〉48 h。结论用新西兰兔代替比格犬建立基于无线遥测和刺激基础上的房颤模型是完全可行的,同时也体现了动物福利优化和替代原则。     

Oscillating signals in the sensory pathway of halobacteria induced by periodic light stimuli

The swimming behaviour of Halobacterium salinarium can be modulated by light. Changes of the light intensity that induce reversals of the swimming direction are called repellent stimuli, those that suppress reversals, which otherwise would occur spontaneously from time to time, are called attractant stimuli. Bacteria were stimulated by periodic pulse-like stimuli, and the frequency of induced reversals was recorded. Stimulation with a period length between 16 and 6.5 s let the cells reverse periodically with the frequency of the external force. After the stimulation had been stopped, the cells continued to reverse periodically for 3 to 9 periods which, however, switched to a value of about 6 to 8 s, independent of the frequency of preceding stimulation. This endogeneous oscillation was most distinct when the stimulation period either equalled the endogeneous period or was twice or half of its length. During the endogeneous oscillation, the responsiveness to an attractant stimulus showed a pronounced phase-dependence. These results point to the oscillation of a signal in the sensory pathway which, different from our former assumption, seems to be not self-sustained but has to be set going by external stimulation. Received: 14 January 1998 / Revised version: 9 April 1998 / Accepted: 17 May 1998     

Long-lasting H-reflex inhibition evoked by stimulation of a nerve to the antagonist muscles and vibrational stimulation of the muscle receptors in humans

In testing of healthy subjects, we studied the influence of conditioning stimulation of then.peroneus communis on the H-reflex EMG discharge recorded from them. soleus. Two waves of inhibition separated by a period of relative facilitation of the reflex were observed. The first wave,D ₁, was not longer than 50 msec. The intensity of later inhibition (D ₂ wave) within a 500 to 4000 msec time segment linearly depended on the logarithm of the interval between the conditioning and test stimuli. Extrapolation showed that the duration of this wave could be evaluated as equal to 6.3 msec, on average. We also studied the temporal course of H-reflex inhibition after conditioning vibrational stimulation of the receptors of them. tibialis ant. andm. biceps femori. Within a 500 to 4000 msec test interval, it could also be fitted with a logarithmic dependence similar to that observed after electrical stimulation of then. peroneus comm. The duration of inhibition after vibrational stimulation of them. tibialis ant. andm. biceps femori was 6.2 and 8.9 sec, respectively. Inhibition evoked by both conditioning influences was not removed after a voluntary plantar flexion of the foot. Our observations support the statement that in humans stimulation of the afferent fibers from the antagonist muscles, as well of the muscle receptors, evokes in two-neuron reflex arcs presynaptic inhibition, whose duration reaches several seconds; this phenomenon can play a significant role in the control of muscle tone in the course of muscle performance.