基于估计熵确定心率变异信号中动力噪声强度

目前普遍的观点认为心率变异信号是确定性低维混沌系统产生的,同时该系统受到大量生理噪声的影响。研究了观测噪声和动力噪声对低维混沌系统的影响,提出了一种基于复杂性度量动力噪声强度刻划方法,表明随着动力噪声强度的增加,系统的复杂程度增加。该方法不需要对动力学系统完全重建,并对观测噪声具有一定鲁棒性。最后利用３类共５３只狗的心电图,每只狗的心电数据为１０００个Ｒ－Ｒ间期的微分序列检验了该算法。分析表明,估计出的动力噪声强度与不同的心脏功能状态相关联     

Metabolic cycles are linked to the cardiovascular diurnal rhythm in rats with essential hypertension

Background

The loss of diurnal rhythm in blood pressure (BP) is an important predictor of end-organ damage in hypertensive and diabetic patients. Recent evidence has suggested that two major physiological circadian rhythms, the metabolic and cardiovascular rhythms, are subject to regulation by overlapping molecular pathways, indicating that dysregulation of metabolic cycles could desynchronize the normal diurnal rhythm of BP with the daily light/dark cycle. However, little is known about the impact of changes in metabolic cycles on BP diurnal rhythm.

Methodology/Principal Findings

To test the hypothesis that feeding-fasting cycles could affect the diurnal pattern of BP, we used spontaneously hypertensive rats (SHR) which develop essential hypertension with disrupted diurnal BP rhythms and examined whether abnormal BP rhythms in SHR were caused by alteration in the daily feeding rhythm. We found that SHR exhibit attenuated feeding rhythm which accompanies disrupted rhythms in metabolic gene expression not only in metabolic tissues but also in cardiovascular tissues. More importantly, the correction of abnormal feeding rhythms in SHR restored the daily BP rhythm and was accompanied by changes in the timing of expression of key circadian and metabolic genes in cardiovascular tissues.

Conclusions/Significance

These results indicate that the metabolic cycle is an important determinant of the cardiovascular diurnal rhythm and that disrupted BP rhythms in hypertensive patients can be normalized by manipulating feeding cycles.     

Modelling insect diseases as functional predators

Abstract. Many larval diseases of insects allow no recovery once infected. Furthermore, infected individuals are not able to develop into adults and will not therefore reproduce. A simple modelling approach emphasizes the fact that, accordingly, the agents that cause these diseases are functionally predators. It is important to make this distinction and to be cautious in applying inference drawn from models of parasites to these diseases. Sublethal effects are well known in these insect larval diseases, and models show that they have important dynamical implications. Sublethal effects have received less attention in predator–prey interactions, but their functional relationship with insect diseases emphasizes that nonmortality effects of predators may have correspondingly important dynamical implications.     

Self-adaptive model-based ECG denoising using features extracted by mean shift algorithm

Denoising of electrocardiogram (ECG) is the fundamental technique for manual or automatic ECG diagnosis. Model-based denoising has attracted initial studies since the ECG dynamical model was established in 2003 and been demonstrated to outperform most model-less denoising methods. The focus of this paper is robust denoising of abnormal ECG signals, which do not satisfy the assumption in previous model-based studies that morphological or physiological variations are small from one beat to another. A mean shift based initializer is proposed to provide a much more robust estimation of initial model parameters for each heart beat. Together with physiological knowledge based wave sub-segmentation and enhanced strategies, the novel initializer has been demonstrated to achieve satisfactory performance for both normal and abnormal heart beats under both white and pink noises. Utilizing records from Massachusetts Institute of Technology (MIT)-Beth Israel Hospital (BIH) database, this paper also applies various filters to denoise noisy signals and the denoising performances verify the availability and efficacy of the proposed denoising method.     

Proteomic analysis of the Gallus gallus embryo at stage-29 of development

The chicken (Gallus gallus) is one of the primary models for embryological and developmental studies. In order to begin to understand the molecular mechanisms underlying the normal and abnormal development of the chicken, we used 2-DE to construct a whole-embryo proteome map. Proteins were separated by IEF on IPG strips, and by 11% SDS-PAGE) gels. Protein identification was performed by means of PMF with MALDI-TOF-MS. In all, 105 protein spots were identified, 35 of them implicated in embryo development, 10 related with some diseases, and 16, finally, being proteins that have never been identified, purified or characterized in the chicken before. This map will be updated continuously and will serve as a reference database for investigators, studying changes at the protein level under different physiological conditions.     

Development and validation of computational models for mammalian circadian oscillators

Circadian rhythms are endogenous rhythms with a cycle length of approximately 24 h. Rhythmic production of specific proteins within pacemaker structures is the basis for these physiological and behavioral rhythms. Prior work on mathematical modeling of molecular circadian oscillators has focused on the fruit fly, Drosophila melanogaster. Recently, great advances have been made in our understanding of the molecular basis of circadian rhythms in mammals. Mathematical models of the mammalian circadian oscillator are needed to piece together diverse data, predict experimental results, and help us understand the clock as a whole. Our objectives are to develop mathematical models of the mammalian circadian oscillator, generate and test predictions from these models, gather information on the parameters needed for model development, integrate the molecular model with an existing model of the influence of light and rhythmicity on human performance, and make models available in BioSpice so that they can be easily used by the general community. Two new mammalian models have been developed, and experimental data are summarized. These studies have the potential to lead to new strategies for resetting the circadian clock. Manipulations of the circadian clock can be used to optimize performance by promoting alertness and physiological synchronization.     

Physiological conditions can be reflected in human urine proteome and metabolome

Biomarkers are the measurable changes associated with physiological or pathophysiological processes. Urine, unlike blood, lacks mechanisms for maintaining homeostasis: it is therefore an ideal source of biomarkers that can reflect systemic changes. Urinary proteome and metabolome have been studied for their diagnostic capabilities, ability to monitor disease and prognostic utility. In this review, the effects of common physiological conditions such as gender, age, diet, daily rhythms, exercise, hormone status, lifestyle and extreme environments on human urine are discussed. These effects should be considered when biomarker studies of diseases are conducted. More importantly, if physiological changes can be reflected in urine, we have reason to expect that urine will become widely used to detect small and early changes in pathological and/or pharmacological conditions.     

Time-patterned drug administration: insights from a modeling approach

The physiological effects of a drug depend not only on its molecular structure but also on the time-pattern of its administration. One of the main reasons for the importance of temporal patterns in drug action is biological rhythms—particularly those of circadian period. These rhythms affect most physiological functions as well as drug metabolism, clearance, and dynamic processes that may alter drug availability and target cell responsiveness with reference to biological time. We present an overview of the importance of time-patterned signals in physiology focused on the insights provided by a modeling approach. We first discuss examples of pulsatile intercellular communication by hormones such as gonadotropin-releasing hormone, and by cyclic adenosine monophosphate (cAMP) signals in Dictyostelium amoebae. Models based on reversible receptor desensitization account in both cases for the existence of optimal patterns of pulsatile signaling. Turning to circadian rhythms, we examine how models can be used to account for the response of 24h patterns to external stimuli such as light pulses or gene expression, and to predict how to restore the physiological characteristics of altered rhythms. Time-patterned treatments of cancer involve two distinct lines of research. The first, currently evaluated in clinical trials, relies on circadian chronomodulation of anticancer drugs, while the second, mostly based on theoretical studies, involves a resonance phenomenon with the cell-cycle length. We discuss the implications of modeling studies to improve the temporal patterning of drug administration.     

睡眠2期脑电信号产生的生理机制模型仿真研究

目前慢波睡眠生理机制研究已有的理论及动物实验结果显示,慢波睡眠中,皮层-丘脑系统神经元存在三种不同节律的振荡:慢振荡(<1 HZ)、δ振荡(1-4Hz)和纺锤振荡(7-14Hz)。这些神经元电活动在皮层水平广泛同步化,产生慢波睡眠脑电。提出了能分别产生这三种节律的三种神经元环路模型,并将之组合简化成一个七细胞环路模型。由这样的大量环路组成的网络模型在合适的突触连接参数范围内,能在皮层处产生人类慢波睡眠脑电2期的完整波形。这一结果说明了如何将动物实验观察到的睡眠生理机制的结果与人自然睡眠活动的脑电结果联系起来,并提示脑信息处理中由微观神经元群放电特征整合为脑的宏观功能状态的主要环节。     

Time-patterned drug administration: insights from a modeling approach

The physiological effects of a drug depend not only on its molecular structure but also on the time-pattern of its administration. One of the main reasons for the importance of temporal patterns in drug action is biological rhythms—particularly those of circadian period. These rhythms affect most physiological functions as well as drug metabolism, clearance, and dynamic processes that may alter drug availability and target cell responsiveness with reference to biological time. We present an overview of the importance of time-patterned signals in physiology focused on the insights provided by a modeling approach. We first discuss examples of pulsatile intercellular communication by hormones such as gonadotropin-releasing hormone, and by cyclic adenosine monophosphate (cAMP) signals in Dictyostelium amoebae. Models based on reversible receptor desensitization account in both cases for the existence of optimal patterns of pulsatile signaling. Turning to circadian rhythms, we examine how models can be used to account for the response of 24h patterns to external stimuli such as light pulses or gene expression, and to predict how to restore the physiological characteristics of altered rhythms. Time-patterned treatments of cancer involve two distinct lines of research. The first, currently evaluated in clinical trials, relies on circadian chronomodulation of anticancer drugs, while the second, mostly based on theoretical studies, involves a resonance phenomenon with the cell-cycle length. We discuss the implications of modeling studies to improve the temporal patterning of drug administration.     

记忆水平依赖的海马-前额叶神经节律交互

海马(HPC)和前额叶皮层(PFC)的协同作用是记忆加工过程的关键,其相互作用对学习和记忆功能至关重要.大量证据表明,情景记忆的形成、巩固与检索依赖于特征神经节律在PFC和HPC脑区间的同步作用,这些节律包括theta节律、gamma节律和sharp wave ripples (SWRs)节律等.在精神类疾病中患者往往伴随出现学习记忆功能障碍,基于人类和动物的脑电研究均发现以上3种神经节律在HPC和PFC之间的同步性下降,可能作为反映精神病理下认知功能障碍的重要指标.本文从HPC-PFC网络中的神经节律研究出发,总结了theta节律、gamma节律和SWRs节律在两脑区间的协调交互模式在情景记忆中的作用,以及精神分裂症和抑郁症状态下HPC-PFC通路上神经节律的异常表现及其潜在损伤机制,为今后精神疾病的快速诊断提供客观依据.     

Modeling the influence of circadian rhythms on the acute inflammatory response

A wide variety of modeling techniques have been applied towards understanding inflammation. These models have broad potential applications, from optimizing clinical trials to improving clinical care. Models have been developed to study specific systems and diseases, but the effect of circadian rhythms on the inflammatory response has not been modeled. Circadian rhythms are normal biological variations obeying the 24-h light/dark cycle and have been shown to play a critical role in the treatment and progression of many diseases. Several of the key components of the inflammatory response, including cytokines and hormones, have been observed to undergo significant diurnal variations in plasma concentration. It is hypothesized that these diurnal rhythms are entrained by the cyclic production of the hormones cortisol and melatonin, as stimulated by the central clock in the suprachiasmatic nucleus. Based on this hypothesis, a mathematical model of the interplay between inflammation and circadian rhythms is developed. The model is validated by its ability to reproduce diverse sets of experimental data and clinical observations concerning the temporal sensitivity of the inflammatory response.     

A generalized mathematical model of biological oscillators

Biological rhythms such as circadian rhythms, biochemical rhythms and neural oscillators are based on the mathematical model of the theory of harmonic oscillators. These are solutions of certain second-order differential equations. They can also be viewed as spherical harmonics on the circle in the two-dimensional Euclidean space. The spherical harmonics on (n-1)-spheres and, more generally, the Stiefel harmonics can represent oscillatory phenomena, and we expect that they can serve as models for more complex biological rhythms.     

生物节律影响巨核细胞发育和血小板产生的研究进展

自然界中生物体的生命活动、生活习性都存在着一定的周期性变化。生物昼夜节律的产生是以内源性的生物钟系统为基础的。生物钟不仅易受到外界环境的影响,而且可以通过调控一系列特定的下游基因的表达,影响生物体的生理生化过程。巨核细胞是生成血小板的前体细胞,经过分化、增殖、成熟和裂解,最终生成血小板。血小板是一种没有细胞核的特殊细胞,在生理性止血和器官修复上发挥着重要作用,同时参与血栓等多种疾病的发生。近几年借助现代分子生物学和细胞生物学手段。证实了哺乳动物的巨核细胞和血小板的生成呈现明显的周期性的变化,利用生物钟基因缺失模型进一步发现了生物钟基因对巨核细胞和血小板的影响。本文概述了生物节律对巨核细胞和血小板的影响,为进一步研究巨核细胞的发育和血小板生成机制提供了参考。     

A history of recent advancements on <Emphasis Type="Italic">Nephrops norvegicus</Emphasis> behavioral and physiological rhythms

Biological rhythms are a widespread feature of living organisms, being expressed at any level of their organization. Behavioral and physiological rhythms can affect the results on species stock assessment when the timing of sampling is not taken into account. That timing is of importance since animals may be present or not in a certain area of sampling depending on their activity cycle. As an example of this, the rhythmic behavior and physiology of one of the most commercially important European decapods, the Norway lobster (Nephrops norvegicus) was studied. These rhythms affect its commercial catchability at a diel and at a seasonal scale. Nephrops inhabits muddy bottoms where animals dig burrows that save them from the trawl tow capture when occupied. Catch patterns have been widely used as proxy of activity rhythms of populations of different depths. Catches show a modulation upon the day-night cycle since animals emerge under optimum environmental illumination in order to feed. Emergence is also affected in a not fully clarified manner by other variables of environmental and demographic nature (e.g. food presence, hunger state, sex, size, reproductive stage, territorialism and mating). All these features make Nephrops a good model of reference for studies on biological rhythms of other commercially important deep water decapods in relation to their ecological context. In this review, we summarize the actual knowledge on Nephrops behavioral and physiological rhythms. We will compare data obtained from laboratory tests on single individuals with data obtained from trawling of populations of different depths. We will also describe some new hypotheses on the rhythmic regulation of the species behaviour, as well as potential scenarios for future research.     

Mpl ligand or thrombopoietin: Biological activities

Thrombopoietin (TPO) or Mpl ligand is the primary physiological regulator of platelet production. This cytokine is the most potent stimulator of the proliferation and differentiation of MK progenitor and precursor cellsin vitro. It also acts additively or synergistically with several cytokines on progenitor cells from various hematopoietic lineages, including the primitive stem cells. The factor is an extremely potent thrombocytopoietic agent when administrated to normal animals, and it accelerates platelet and erythropoietic recovery in several models of myelosuppression. Phase I/II clinical trials are ongoing with no detectable adverse effects. Mpl ligand does not induce platelet aggregation, but it lowers the platelet sensitivity to physiological dose of agonists. In experimental mouse models, high and chronic dose of Mpl ligand results in myelofibrosis. TPO is constantly produced by the liver and the kidney; its plasmatic clearance occurs by binding to its receptor expressed on megakaryocytes and platelets. However, the full spectrum of the biological effects of this new cytokine is not fully understood, in particular its the role in the terminal stage of platelet production. In the near future, it is likely that new insights will be obtained in the physiopathological mechanisms underlying abnormal platelet production in human.     

遗忘的神经机制及其与神经系统疾病的相关性

遗忘是记忆系统的重要组成部分.一方面,生理条件下,正常的遗忘有助于维持大脑记忆系统稳态;另一方面,异常的遗忘与多种病理条件下记忆障碍的发生发展密切相关.或者说,遗忘是为了更好的记忆.对不愉快或者不必要记忆的遗忘有利于机体及时地获取新信息以适应环境的变化;而遗忘出现异常很可能会导致相关记忆障碍.例如,阿尔茨海默症(Alz...     

Autophagy,a guardian against neurodegeneration

Autophagy is an intracellular degradation process responsible for the clearance of most long-lived proteins and organelles. Cytoplasmic components are enclosed by double-membrane autophagosomes, which subsequently fuse with lysosomes for degradation. Autophagy dysfunction may contribute to the pathology of various neurodegenerative disorders, which manifest abnormal protein accumulation. As autophagy induction enhances the clearance of aggregate-prone intracytoplasmic proteins that cause neurodegeneration (like mutant huntingtin, tau and ataxin 3) and confers cytoprotective roles in cell and animal models, upregulating autophagy may be a tractable therapeutic strategy for diseases caused by such proteins. Here, we will review the molecular machinery of autophagy and its role in neurodegenerative diseases. Drugs and associated signalling pathways that may be targeted for pharmacological induction of autophagy will also be discussed.