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A memory access gate controlled by dynamic contexts 由动态上下文控制的内存访问门。
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-05-15 DOI: 10.1016/j.biosystems.2024.105232
Andrés Pomi , Juan Lin , Eduardo Mizraji

Temporary difficulties in accessing the contents of memories are a common experience in everyday life, for example, when we try to recognize a known person in an unusual context. In addition, recent experiments seem to indicate that retrograde amnesia in the early stages of Alzheimer's disease is due to disorders in accessing memories that were installed normally. These facts suggest the existence of an intermediate step between the stimulus arrival and the associative recognition. In this work, a multimodular neurocomputational model is presented postulating the existence of a neural gate that controls the access of the stimulus with its context to the consolidated memory. If recognition is not achieved, a random search is initiated in a contextual network aroused by the initial context. The search continues until the appropriate context that allows for recognition is found or until the process is turned off because the initial stimulus is no longer maintained in the working memory. The model is based on vector patterns of neural activity and context-dependent matrix memories. Simple Markov chain simulations are presented to exemplify possible search scenarios in the contextual network. Finally, we discuss some of the characteristics of the model and the phenomenon under study.

在日常生活中,获取记忆内容的暂时困难是一种常见的经历,例如,当我们试图在一个不寻常的环境中认出一个已知的人时。此外,最近的实验似乎表明,阿尔茨海默氏症早期的逆行性遗忘症是由于在获取正常安装的记忆时出现了障碍。这些事实表明,在刺激到达和联想识别之间存在一个中间环节。在这项工作中,提出了一个多模态神经计算模型,假定存在一个神经门,控制刺激物及其背景进入巩固记忆。如果没有实现识别,就会在由初始语境唤起的语境网络中启动随机搜索。这种搜索一直持续到找到可以识别的适当语境,或者由于工作记忆中不再保留初始刺激物而关闭搜索过程。该模型基于神经活动的矢量模式和与语境相关的矩阵记忆。我们将通过简单的马尔可夫链模拟来举例说明情境网络中可能出现的搜索情况。最后,我们将讨论该模型的一些特点和所研究的现象。
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引用次数: 0
A multi-objective optimisation approach for the linear modelling of cerebral autoregulation system 大脑自动调节系统线性建模的多目标优化方法。
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-05-14 DOI: 10.1016/j.biosystems.2024.105231
Felipe-Andrés Bello-Robles , Manuel Villalobos-Cid , Max Chacón , Mario Inostroza-Ponta

Objective:

Dynamic cerebral autoregulation (dCA) has been addressed through different approaches for discriminating between normal and impaired conditions based on spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CF). This work presents a novel multi-objective optimisation (MO) approach for finding good configurations of a cerebrovascular resistance-compliance model.

Methods:

Data from twenty-nine subjects under normo and hypercapnic (5% CO2 in air) conditions was used. Cerebrovascular resistance and vessel compliance models with ABP as input and CF velocity as output were fitted using a MO approach, considering fitting Pearson’s correlation and error.

Results:

MO approach finds better model configurations than the single-objective (SO) approach, especially for hypercapnic conditions. In addition, the Pareto-optimal front from the multi-objective approach enables new information on dCA, reflecting a higher contribution of myogenic mechanism for explaining dCA impairment.

目的:根据动脉血压(ABP)和脑血流量(CF)的自发波动,动态脑自动调节(dCA)通过不同的方法来区分正常和受损状态。本研究提出了一种新颖的多目标优化(MO)方法,用于寻找脑血管阻力-顺应性模型的良好配置:方法:使用了 29 名受试者在正常和高碳酸血症(5% CO2 空气)条件下的数据。使用 MO 方法拟合了以 ABP 为输入、CF 速度为输出的脑血管阻力和血管顺应性模型,并考虑了拟合皮尔逊相关性和误差:结果:MO 方法比单目标(SO)方法找到了更好的模型配置,尤其是在高碳酸血症条件下。此外,多目标方法的帕累托-极值前沿为 dCA 提供了新的信息,反映了肌源性机制在解释 dCA 损伤方面的更大贡献。
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引用次数: 0
From the principle of sustainable non-equilibrium to sustainable development 从可持续非均衡原则到可持续发展。
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-05-14 DOI: 10.1016/j.biosystems.2024.105233
Dmitry Ermakov , Alexander Ermakov

Ervin Bauer was Hungarian and Soviet scientist, who had a short, but bright and talented life. In 1935, working at the Institute of Experimental Medicine in the USSR, he published the book «Theoretical Biology», in which he proposed an idea of a special “non-equilibrium” state of living systems and the existence of internal machineries in the organism that work against thermodynamic equilibrium and increase the organism's capacity for work. Currently, this idea is called “the principle of sustainable non-equilibrium” or “Bauer's principle”. During the repressions of the 1930s in the USSR, Bauer was executed, the book « Theoretical Biology» was banned. Currently, his works are poorly known, especially outside the post-socialist region. We believe that his ideas could help in rethinking not only the biochemistry and bioenergetics of cells and tissues of living organisms, but also biogeochemical and civilizational processes on a planetary scale.

埃尔文-鲍尔是匈牙利和苏联科学家,一生短暂,但才华横溢。1935 年,在苏联实验医学研究所工作的他出版了《理论生物学》一书,在书中他提出了生命系统的特殊 "非平衡 "状态,以及生物体内存在违反热力学平衡、提高生物体工作能力的内部机制的观点。目前,这一观点被称为 "可持续非平衡原理 "或 "鲍尔原理"。20 世纪 30 年代苏联镇压期间,鲍尔被处决,《理论生物学》一书被禁。目前,他的著作鲜为人知,尤其是在后社会主义地区以外。我们相信,他的思想不仅有助于重新思考生物体细胞和组织的生物化学和生物能,而且有助于重新思考地球范围内的生物地球化学和文明进程。
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引用次数: 0
Ambush strategy enhances organisms’ performance in rock–paper–scissors games 伏击策略能提高生物在剪刀石头布游戏中的表现。
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-05-11 DOI: 10.1016/j.biosystems.2024.105229
R. Barbalho , S. Rodrigues , M. Tenorio , J. Menezes

We study a five-species cyclic system wherein individuals of one species strategically adapt their movements to enhance their performance in the spatial rock–paper–scissors game. Environmental cues enable the awareness of the presence of organisms targeted for elimination in the cyclic game. If the local density of target organisms is sufficiently high, individuals move towards concentrated areas for direct attack; otherwise, they employ an ambush tactic, maximising the chances of success by targeting regions likely to be dominated by opponents. Running stochastic simulations, we discover that the ambush strategy enhances the likelihood of individual success compared to direct attacks alone, leading to uneven spatial patterns characterised by spiral waves. We compute the autocorrelation function and measure how the ambush tactic unbalances the organisms’ spatial organisation by calculating the characteristic length scale of typical spatial domains of each species. We demonstrate that the threshold for local species density influences the ambush strategy’s effectiveness, while the neighbourhood perception range significantly impacts decision-making accuracy. The outcomes show that long-range perception improves performance by over 60%, although there is potential interference in decision-making under high attack triggers. Understanding how organisms’ adaptation their environment enhances their performance may be helpful not only for ecologists, but also for data scientists, aiming to improve artificial intelligence systems.

我们研究了一个五种生物的循环系统,在这个系统中,一种生物的个体会战略性地调整它们的运动,以提高它们在空间剪刀石头布游戏中的表现。通过环境线索,个体能够意识到循环游戏中需要消灭的目标生物的存在。如果目标生物在当地的密度足够高,个体就会向集中区域移动以进行直接攻击;否则,它们就会采用伏击战术,通过瞄准可能被对手占据的区域来最大限度地提高成功几率。通过随机模拟,我们发现与单独直接攻击相比,伏击策略提高了个体成功的可能性,从而导致以螺旋波为特征的不均匀空间模式。我们计算了自相关函数,并通过计算每个物种典型空间领域的特征长度尺度来衡量伏击策略如何使生物的空间组织失衡。我们证明,局部物种密度阈值会影响伏击策略的有效性,而邻域感知范围则会显著影响决策的准确性。研究结果表明,尽管在高攻击触发条件下决策可能会受到干扰,但远距离感知可将性能提高 60% 以上。了解生物如何适应环境以提高性能不仅对生态学家有帮助,对旨在改进人工智能系统的数据科学家也有帮助。
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引用次数: 0
Generation of genetic codes with 2-adic codon algebra and adaptive dynamics 利用 2-adic 密码子代数和自适应动力学生成遗传密码。
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-05-11 DOI: 10.1016/j.biosystems.2024.105230
Ekaterina Yurova Axelsson, Andrei Khrennikov

This is a brief review on modeling genetic codes with the aid of 2-adic dynamical systems. In this model amino acids are encoded by the attractors of such dynamical systems. Each genetic code is coupled to the special class of 2-adic dynamics. We consider the discrete dynamical systems, These are the iterations of a function F:Z2Z2, where Z2 is the ring of 2-adic numbers (2-adic tree). A genetic code is characterized by the set of attractors of a function belonging to the code generating functional class. The main mathematical problem is to reduce degeneration of dynamic representation and select the optimal generating function. Here optimality can be treated in many ways. One possibility is to consider the Lipschitz functions playing the crucial role in general theory of iterations. Then we minimize the Lip-constant. The main issue is to find the proper biological interpretation of code-functions. One can speculate that the evolution of the genetic codes can be described in information space of the nucleotide-strings endowed with ultrametric (treelike) geometry. A code-function is a fitness function; the solutions of the genetic code optimization problem are attractors of the code-function. We illustrate this approach by generation of the standard nuclear and (vertebrate) mitochondrial genetics codes.

本文简要回顾了借助二元动力学系统建立遗传密码模型的过程。在这个模型中,氨基酸是由这种动力学系统的吸引子编码的。每个遗传密码都与特殊的 2-adic 动力系统相耦合。我们考虑的是离散动力系统,它们是函数 F:Z2→Z2 的迭代,其中 Z2 是 2-adic 数环(2-adic 树)。遗传密码的特征是属于密码生成函数类的函数的吸引子集。主要的数学问题是减少动态表示的退化和选择最优生成函数。这里的最优性有多种处理方法。一种方法是考虑在一般迭代理论中起关键作用的 Lipschitz 函数。然后,我们最小化 Lip 常量。主要问题是找到代码函数的适当生物学解释。我们可以推测,遗传密码的进化可以在核苷酸链的信息空间中用超对称(树状)几何来描述。代码函数是一种适应度函数;遗传密码优化问题的解就是代码函数的吸引子。我们通过生成标准的核遗传密码和(脊椎动物)线粒体遗传密码来说明这种方法。
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引用次数: 0
Thermodynamic analysis of energy coupling by determination of the Onsager phenomenological coefficients for a 3×3 system of coupled chemical reactions and transport in ATP synthesis and its mechanistic implications 通过确定 ATP 合成中 3×3 耦合化学反应和传输系统的 Onsager 现象系数进行能量耦合的热力学分析及其机理意义。
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-05-11 DOI: 10.1016/j.biosystems.2024.105228
Sunil Nath

The nonequilibrium coupled processes of oxidation and ATP synthesis in the fundamental process of oxidative phosphorylation (OXPHOS) are of vital importance in biosystems. These coupled chemical reaction and transport bioenergetic processes using the OXPHOS pathway meet >90% of the ATP demand in aerobic systems. On the basis of experimentally determined thermodynamic OXPHOS flux-force relationships and biochemical data for the ternary system of oxidation, ion transport, and ATP synthesis, the Onsager phenomenological coefficients have been computed, including an estimate of error. A new biothermokinetic theory of energy coupling has been formulated and on its basis the thermodynamic parameters, such as the overall degree of coupling, q and the phenomenological stoichiometry, Z of the coupled system have been evaluated. The amount of ATP produced per oxygen consumed, i.e. the actual, operating P/O ratio in the biosystem, the thermodynamic efficiency of the coupled reactions, η, and the Gibbs free energy dissipation, Φ have been calculated and shown to be in agreement with experimental data. At the concentration gradients of ADP and ATP prevailing under state 3 physiological conditions of OXPHOS that yield Vmax rates of ATP synthesis, a maximum in Φ of 0.5J(hmgprotein)1, corresponding to a thermodynamic efficiency of 60% for oxidation on succinate, has been obtained. Novel mechanistic insights arising from the above have been discussed. This is the first report of a 3 × 3 system of coupled chemical reactions with transport in a biological context in which the phenomenological coefficients have been evaluated from experimental data.

氧化磷酸化(OXPHOS)这一基本过程中的氧化和 ATP 合成的非平衡耦合过程在生物系统中至关重要。这些使用 OXPHOS 途径的耦合化学反应和运输生物能过程满足了有氧系统中超过 90% 的 ATP 需求。根据实验确定的热力学 OXPHOS 通量-力关系以及氧化、离子运输和 ATP 合成三元系统的生化数据,计算出了 Onsager 现象系数,包括误差估计值。在此基础上,对热力学参数,如耦合系统的总体耦合度和现象化学计量进行了评估。计算得出了每消耗一个氧气所产生的 ATP 量(即生物系统中实际运行的 P/O 比)、耦合反应的热力学效率以及吉布斯自由能耗散,并证明与实验数据一致。在产生 ATP 合成率的 OXPHOS 状态 3 生理条件下,ADP 和 ATP 的浓度梯度普遍存在,计算得出琥珀酸氧化反应的热力学效率最大值为 。研究人员还讨论了上述结果带来的新的机理启示。这是在生物背景下首次报道 3×3 的耦合化学反应与传输系统,其中的现象学系数是根据实验数据评估得出的。
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引用次数: 0
The cell as a semiotic system that realizes closure to efficient causation: The semiotic (M, R) system 细胞是一个实现有效因果关系闭合的符号系统:符号(m, r)系统。
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-05-08 DOI: 10.1016/j.biosystems.2024.105226
Federico Vega

Robert Rosen defines organisms as material systems closed to efficient causation, and proposes the replicative (M, R) system as a model for them. Recently, we presented a cell model that realizes Rosen's formal model, based on Hofmeyr's analysis of the functional organization of cell biochemistry and on Rosen's construction of the replication function. In this article we propose a cell model that, starting from the same biochemical processes, replaces the replication function with a set of semiotic relations between some of the elements that participate in cellular processes. The result is a cell model that constitutes a semiotic system that realizes closure to efficient causation: a semiotic (M, R) system. We compare the models of closure that correspond to the replicative (M, R) system and the semiotic (M, R) system. Additionally, we discuss the role that the genetic code and protein synthesis play in the semiotic closure to efficient causation. Finally, we outline the method to extend this analysis to more complex organisms.

罗伯特-罗森将有机体定义为封闭于有效因果关系的物质系统,并提出复制(M,R)系统作为有机体的模型。维加(2023)基于霍夫迈尔(2017)对细胞生化功能组织的分析和罗森对复制功能的构建,提出了一个实现罗森形式模型的细胞模型。在本文中,我们提出了一种细胞模型,从相同的生化过程出发,用参与细胞过程的一些元素之间的一系列符号关系取代了复制功能。结果,细胞模型构成了一个实现有效因果关系闭合的符号学系统:一个符号学(M,R)系统。我们比较了与复制(M,R)系统和符号(M,R)系统相对应的封闭模型。此外,我们还讨论了遗传密码和蛋白质合成在有效因果关系的符号学闭合中扮演的角色。最后,我们概述了将这一分析扩展到更复杂生物体的方法。
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引用次数: 0
Temporal multiscale modeling of biochemical regulatory networks: Calcium-regulated hepatocyte lipid and glucose metabolism 生化调控网络的时空多尺度建模:钙调控的肝细胞脂质和葡萄糖代谢
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-05-06 DOI: 10.1016/j.biosystems.2024.105227
Arina V. Martyshina, Anna G. Sirotkina, Irina V. Gosteva

Hepatocyte lipid and glucose metabolism is regulated not only by major hormones like insulin and glucagon but also by many other factors, including calcium ions. Recently, mitochondria-associated membrane (MAM) dysfunction combined with incorrect IP3-receptor regulation has been shown to result in abnormal calcium signaling in hepatocytes. This dysfunction could further lead to hepatic metabolism pathology. However, the exact contribution of MAM dysfunction, incorrect IP3-receptor regulation and insulin resistance to the calcium-insulin-glucagon interplay is not understood yet. In this work, we analyze the role of abnormal calcium signaling and insulin dysfunction in hepatocytes by proposing a model of hepatocyte metabolic regulatory network with a detailed focus on the model construction details besides the biological aspect. In this work, we analyze the role of abnormal calcium signaling and insulin dysfunction in hepatocytes by proposing a model of hepatocyte metabolic regulatory network. We focus on the model construction details, model validation, and predictions. We describe the dynamic regulation of signaling processes by sigmoid Hill function. In particular, we study the effect of both the Hill function slope and the distance between Hill function extremes on metabolic processes in hepatocytes as a model of nonspecific insulin dysfunction. We also address the significant time difference between characteristic time of glucose hepatic processing and a typical calcium oscillation period in hepatocytes. Our modeling results show that calcium signaling dysfunction results in an abnormal increase in postprandial glucose levels, an abnormal glucose decrease in fasting, and a decreased amount of stored glycogen. An insulin dysfunction of glucose phosphorylation, glucose dephosphorylation, and glycogen breakdown also cause a noticeable effect. We also get some insight into the so-called hepatic insulin resistance paradox, confirming the hypothesis regarding indirect insulin action on hepatocytes via dysfunctional adipocyte lipolysis.

肝细胞的脂质和葡萄糖代谢不仅受胰岛素和胰高血糖素等主要激素的调节,还受包括钙离子在内的许多其他因素的调节。最近的研究表明,线粒体相关膜(MAM)功能障碍与不正确的 IP3 受体调节相结合,导致肝细胞中的钙信号异常。这种功能障碍可能会进一步导致肝脏代谢病变。然而,MAM 功能障碍、不正确的 IP3 受体调节和胰岛素抵抗对钙-胰岛素-胰高血糖素相互作用的确切贡献尚不清楚。在这项工作中,我们通过提出肝细胞代谢调控网络模型来分析异常钙信号传导和胰岛素功能障碍在肝细胞中的作用,除了生物学方面,我们还详细关注了模型构建的细节。在这项工作中,我们通过提出一个肝细胞代谢调控网络模型,分析了异常钙信号传导和胰岛素功能障碍在肝细胞中的作用。我们重点讨论了模型构建细节、模型验证和预测。我们用西格玛希尔函数描述了信号传导过程的动态调控。作为非特异性胰岛素功能障碍模型,我们特别研究了希尔函数斜率和希尔函数极值之间的距离对肝细胞代谢过程的影响。我们还研究了葡萄糖肝处理特征时间与肝细胞典型钙振荡周期之间的显著时间差。我们的建模结果表明,钙信号传导功能障碍会导致餐后血糖水平异常升高、空腹血糖异常下降以及糖原储存量减少。胰岛素对葡萄糖磷酸化、葡萄糖去磷酸化和糖原分解的功能障碍也会造成明显的影响。我们还对所谓的肝脏胰岛素抵抗悖论有了一些了解,证实了关于胰岛素通过脂肪细胞脂肪分解功能障碍间接作用于肝细胞的假设。
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引用次数: 0
Editorial: Systems bioinformatics for medicine 社论:医学系统生物信息学
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-05-01 DOI: 10.1016/j.biosystems.2024.105211
Yoshiyuki Asai, Masahiko Nakatsui, Hiroshi Matsuno
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引用次数: 0
Buckling forces and the wavy folds between pleural epithelial cells 胸膜上皮细胞之间的屈曲力和波浪褶皱。
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-04-29 DOI: 10.1016/j.biosystems.2024.105216
Joseph Sutlive , Betty S. Liu , Stacey A. Kwan , Jennifer M. Pan , Kun Gou , Rongguang Xu , Ali B. Ali , Hassan A. Khalil , Maximilian Ackermann , Zi Chen , Steven J. Mentzer

Cell shapes in tissues are affected by the biophysical interaction between cells. Tissue forces can influence specific cell features such as cell geometry and cell surface area. Here, we examined the 2-dimensional shape, size, and perimeter of pleural epithelial cells at various lung volumes. We demonstrated a 1.53-fold increase in 2-dimensional cell surface area and a 1.43-fold increase in cell perimeter at total lung capacity compared to residual lung volume. Consistent with previous results, close inspection of the pleura demonstrated wavy folds between pleural epithelial cells at all lung volumes. To investigate a potential explanation for the wavy folds, we developed a physical simulacrum suggested by D'Arcy Thompson in On Growth and Form. The simulacrum suggested that the wavy folds were the result of redundant cell membranes unable to contract. To test this hypothesis, we developed a numerical simulation to evaluate the impact of an increase in 2-dimensional cell surface area and cell perimeter on the shape of the cell-cell interface. Our simulation demonstrated that an increase in cell perimeter, rather than an increase in 2-dimensional cell surface area, had the most direct impact on the presence of wavy folds. We conclude that wavy folds between pleural epithelial cells reflects buckling forces arising from the excess cell perimeter necessary to accommodate visceral organ expansion.

组织中的细胞形状受到细胞间生物物理相互作用的影响。组织力会影响特定的细胞特征,如细胞几何形状和细胞表面积。在这里,我们研究了不同肺容量下胸膜上皮细胞的二维形状、大小和周长。我们发现,与残肺量相比,总肺活量时细胞的二维表面积增加了 1.53 倍,细胞周长增加了 1.43 倍。与之前的结果一致,仔细观察胸膜可发现,在所有肺容量下,胸膜上皮细胞之间都存在波浪状褶皱。为了研究波浪状褶皱的潜在解释,我们开发了达西-汤普森(D'Arcy Thompson)在《论生长与形态》(On Growth and Form)一书中提出的物理模拟模型。该模拟图表明,波浪状褶皱是多余的细胞膜无法收缩的结果。为了验证这一假设,我们进行了数值模拟,以评估二维细胞表面积和细胞周长的增加对细胞-细胞界面形状的影响。模拟结果表明,细胞周长的增加,而不是二维细胞表面积的增加,对波浪形褶皱的出现有最直接的影响。我们的结论是,胸膜上皮细胞之间的波浪状褶皱反映了为适应内脏器官扩张所需的过大细胞周长所产生的屈曲力。
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引用次数: 0
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