Journal of Theoretical Biology最新文献_第8页

A kinetic study of multi-substrate uniporters 多底物单转运体的动力学研究。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-09-09 DOI: 10.1016/j.jtbi.2025.112267

Ana S. de Pereda, Jihyun Park, Lily S. Cheung

Transporters play key roles in regulating the movement of molecules into and out of cells. Uniporters, the simplest class of transporters, use facilitated diffusion to translocate molecules across membranes down their concentration gradient. This process can be affected by the presence of additional substrates in the intra- and extracellular environment, which can either increase the net transport rate of a molecule via trans acceleration or decrease it via competitive inhibition. In this study, we derived mathematical models to describe the net transport rate of uniporters in the presence of multiple extracellular substrates or inhibitors. Analyses of these models identified four possible states for the system when two substrates are present, with two states leading to trans acceleration and the other two states resulting in inhibition. Finally, we found that the relation between kinetic constants that controls the fraction of transporters in the inward-facing open state is responsible for these behaviors. Our theoretical results provide a mathematical framework for understanding the dynamic response of uniporters in the presence of multiple substrates and inhibitors, which could have implications for various processes, from nutrient utilization to metabolic engineering.

转运蛋白在调节分子进出细胞的运动中起着关键作用。单转运蛋白是最简单的一类转运蛋白，它利用便利的扩散使分子沿着浓度梯度跨膜转移。这一过程可能受到细胞内和细胞外环境中存在的其他底物的影响，这些底物可以通过反加速增加分子的净运输速率，也可以通过竞争性抑制降低分子的净运输速率。在这项研究中，我们推导了数学模型来描述存在多种细胞外底物或抑制剂时单转运蛋白的净转运率。对这些模型的分析确定了两种底物存在时系统的四种可能状态，其中两种状态导致反加速，另外两种状态导致抑制。最后，我们发现控制向内开放态转运体比例的动力学常数之间的关系是这些行为的原因。我们的理论结果为理解单转运蛋白在多种底物和抑制剂存在下的动态响应提供了一个数学框架，这可能对从营养利用到代谢工程的各种过程产生影响。

{"title":"A kinetic study of multi-substrate uniporters","authors":"Ana S. de Pereda, Jihyun Park, Lily S. Cheung","doi":"10.1016/j.jtbi.2025.112267","DOIUrl":"10.1016/j.jtbi.2025.112267","url":null,"abstract":"<div><div>Transporters play key roles in regulating the movement of molecules into and out of cells. Uniporters, the simplest class of transporters, use facilitated diffusion to translocate molecules across membranes down their concentration gradient. This process can be affected by the presence of additional substrates in the intra- and extracellular environment, which can either increase the net transport rate of a molecule via trans acceleration or decrease it via competitive inhibition. In this study, we derived mathematical models to describe the net transport rate of uniporters in the presence of multiple extracellular substrates or inhibitors. Analyses of these models identified four possible states for the system when two substrates are present, with two states leading to trans acceleration and the other two states resulting in inhibition. Finally, we found that the relation between kinetic constants that controls the fraction of transporters in the inward-facing open state is responsible for these behaviors. Our theoretical results provide a mathematical framework for understanding the dynamic response of uniporters in the presence of multiple substrates and inhibitors, which could have implications for various processes, from nutrient utilization to metabolic engineering.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112267"},"PeriodicalIF":2.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenomenological modeling of gene transcription by approximating cooperativity of transcription factors improves prediction and reduces complexity in gene regulatory network models 通过近似转录因子的协同性来建立基因转录的现象学模型，可以提高预测能力，降低基因调控网络模型的复杂性。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-09-07 DOI: 10.1016/j.jtbi.2025.112264

Thiruvickraman Jothiprakasam, Siddharth Jhunjhunwala

Several computational models are available for representing the gene expression process, with each having their advantages and disadvantages. Phenomenological models are widely used as they make appropriate simplifications that aim to find a middle ground between accuracy and complexity. The existing phenomenological models compete in terms of how the transcription initiation process is approximated, to achieve high accuracy while having the lowest complexity possible. However, most current models still suffer from high parameter complexity in the case of complex promoters. Herein, we formally derive a phenomenological approach to model RNA polymerase recruitment, stating approximations on cooperativity between transcription factors that are applicable to promoters requiring multifactorial input, which reduces parameter complexity. We then apply this method to biologically relevant networks of varying complexities to show that the approximations improved predictive ability compared to existing models. In summary, our reduced parameter model (RPM) had lower complexity while maintaining high accuracy, which leads to better scalability for complex networks.

有几种计算模型可用于表示基因表达过程，每种模型都有其优点和缺点。现象学模型被广泛使用，因为它们进行了适当的简化，旨在找到准确性和复杂性之间的中间地带。现有的现象学模型在如何近似转录起始过程方面存在竞争，以达到高精度，同时具有尽可能低的复杂性。然而，目前大多数模型在复杂启动子的情况下仍然存在较高的参数复杂度。在此，我们正式推导了一种现象学方法来模拟RNA聚合酶募集，说明了适用于需要多因子输入的启动子的转录因子之间的协同性的近似，从而降低了参数的复杂性。然后，我们将这种方法应用于不同复杂性的生物相关网络，以表明与现有模型相比，近似提高了预测能力。总之，我们的降参数模型（RPM）在保持高精度的同时具有较低的复杂性，这使得复杂网络具有更好的可扩展性。

{"title":"Phenomenological modeling of gene transcription by approximating cooperativity of transcription factors improves prediction and reduces complexity in gene regulatory network models","authors":"Thiruvickraman Jothiprakasam, Siddharth Jhunjhunwala","doi":"10.1016/j.jtbi.2025.112264","DOIUrl":"10.1016/j.jtbi.2025.112264","url":null,"abstract":"<div><div>Several computational models are available for representing the gene expression process, with each having their advantages and disadvantages. Phenomenological models are widely used as they make appropriate simplifications that aim to find a middle ground between accuracy and complexity. The existing phenomenological models compete in terms of how the transcription initiation process is approximated, to achieve high accuracy while having the lowest complexity possible. However, most current models still suffer from high parameter complexity in the case of complex promoters. Herein, we formally derive a phenomenological approach to model RNA polymerase recruitment, stating approximations on cooperativity between transcription factors that are applicable to promoters requiring multifactorial input, which reduces parameter complexity. We then apply this method to biologically relevant networks of varying complexities to show that the approximations improved predictive ability compared to existing models. In summary, our reduced parameter model (RPM) had lower complexity while maintaining high accuracy, which leads to better scalability for complex networks.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112264"},"PeriodicalIF":2.0,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mathematical model suggests current CAR-macrophage dosage is efficient to low pre-infusion tumour burden but refractory to high tumour burden 数学模型表明，目前的car -巨噬细胞剂量对低输注前肿瘤负荷有效，但对高肿瘤负荷难以耐受。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-09-04 DOI: 10.1016/j.jtbi.2025.112263

Shilian Xu , Maoxuan Liu

Chimeric antigen receptor (CAR)-macrophage therapy is a promising approach for tumour treatment due to antigen-specific phagocytosis and tumour clearance. However, the precise impact of tumour burden, dose and dosing regimens on therapeutic outcomes remains poorly understood. We developed ordinary differential equation (ODE) mathematical modelling and utilised parameter inference to analyse in vitro FACS-based phagocytosis assay data testing CD19-positive Raji tumour cell against CAR-macrophage, and revealed that phagocytosing efficiency of CAR-macrophage increases but saturates as both Raji cell and CAR-macrophage concentrations increase. This interaction resulted in bistable Raji cell kinetics; specifically, within a particular range of CAR-macrophage concentration, low tumour burdens are effectively inhibited, while high tumour burdens remain refractory. Furthermore, our model predicted that CAR-macrophage dosages typically suggested by current clinical trials yield favourable therapeutic outcomes only when tumour burden is low. For split CAR-macrophage infusion with fixed total dosage, the first infusion with high CAR-macrophage dose delivers superior treatment outcomes. Finally, we identified alternative infusion regimens: five billion cells administered monthly for three months, or seven billion cells every two months for six months, can efficiently suppress Raji cell replication irrespective of tumour burden. Our findings highlight CAR-macrophage therapeutic outcomes are strongly influenced by both tumour burden and different dosing regimens. This work underscores that reducing tumour burden, increasing CAR-macrophage dose in the first infusion and prolonging CAR-macrophage persistence are key strategies for achieving durable responses.

嵌合抗原受体(CAR)-巨噬细胞疗法是一种很有前途的治疗肿瘤的方法，由于抗原特异性吞噬和肿瘤清除。然而，肿瘤负荷、剂量和给药方案对治疗结果的确切影响仍然知之甚少。我们建立了常微分方程（ODE）数学模型，并利用参数推理分析了体外基于facs的吞噬实验数据，测试cd19阳性Raji肿瘤细胞对car -巨噬细胞的吞噬能力，发现car -巨噬细胞的吞噬效率随着Raji细胞和car -巨噬细胞浓度的增加而增加，但饱和。这种相互作用导致双稳态Raji细胞动力学；具体来说，在特定的car -巨噬细胞浓度范围内，低肿瘤负荷被有效抑制，而高肿瘤负荷仍然难以治愈。此外，我们的模型预测，当前临床试验通常建议的car -巨噬细胞剂量只有在肿瘤负荷较低时才能产生良好的治疗效果。对于总剂量固定的car -巨噬细胞分裂输注，首次高剂量car -巨噬细胞输注具有较好的治疗效果。最后，我们确定了替代输注方案：每月给药50亿个细胞，持续3个月，或每两个月给药70亿个细胞，持续6个月，可以有效抑制Raji细胞的复制，而不考虑肿瘤负荷。我们的研究结果强调了car -巨噬细胞治疗结果受到肿瘤负荷和不同给药方案的强烈影响。这项工作强调，减少肿瘤负担、增加首次输注car -巨噬细胞剂量和延长car -巨噬细胞持久性是实现持久反应的关键策略。

{"title":"Mathematical model suggests current CAR-macrophage dosage is efficient to low pre-infusion tumour burden but refractory to high tumour burden","authors":"Shilian Xu , Maoxuan Liu","doi":"10.1016/j.jtbi.2025.112263","DOIUrl":"10.1016/j.jtbi.2025.112263","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR)-macrophage therapy is a promising approach for tumour treatment due to antigen-specific phagocytosis and tumour clearance. However, the precise impact of tumour burden, dose and dosing regimens on therapeutic outcomes remains poorly understood. We developed ordinary differential equation (ODE) mathematical modelling and utilised parameter inference to analyse <em>in vitro</em> FACS-based phagocytosis assay data testing CD19-positive Raji tumour cell against CAR-macrophage, and revealed that phagocytosing efficiency of CAR-macrophage increases but saturates as both Raji cell and CAR-macrophage concentrations increase. This interaction resulted in bistable Raji cell kinetics; specifically, within a particular range of CAR-macrophage concentration, low tumour burdens are effectively inhibited, while high tumour burdens remain refractory. Furthermore, our model predicted that CAR-macrophage dosages typically suggested by current clinical trials yield favourable therapeutic outcomes only when tumour burden is low. For split CAR-macrophage infusion with fixed total dosage, the first infusion with high CAR-macrophage dose delivers superior treatment outcomes. Finally, we identified alternative infusion regimens: five billion cells administered monthly for three months, or seven billion cells every two months for six months, can efficiently suppress Raji cell replication irrespective of tumour burden. Our findings highlight CAR-macrophage therapeutic outcomes are strongly influenced by both tumour burden and different dosing regimens. This work underscores that reducing tumour burden, increasing CAR-macrophage dose in the first infusion and prolonging CAR-macrophage persistence are key strategies for achieving durable responses.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112263"},"PeriodicalIF":2.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Approximate Bayesian computation for Markovian binary trees in phylogenetics 系统发育中马尔可夫二叉树的近似贝叶斯计算。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-09-02 DOI: 10.1016/j.jtbi.2025.112246

Mingqi He , Sophie Hautphenne , Yao-ban Chan

Phylogenetic trees describe the relationships between species in the evolutionary process, and provide information about the rates of diversification. To understand the mechanisms behind macroevolution, we consider a class of multitype branching processes called Markovian binary trees (MBTs). MBTs allow for trait-based variation in diversification rates, and provide a flexible and realistic probabilistic model for phylogenetic trees. We develop an approximate Bayesian computation (ABC) scheme to infer the rates of MBT parameters by exploiting the information in the shapes of phylogenetic trees. We evaluate the accuracy of this inference method using simulation studies, and find that our method is able to detect variation in the diversification rates, with accuracy comparable to, and generally better than, likelihood-based methods. In an application to a real-life phylogeny of squamata, we reinforce conclusions drawn from earlier studies, in particular supporting the existence of ovi-/viviparity transitions in both directions. Our method demonstrates the potential for more complex models of evolution to be employed in phylogenetic inference, in conjunction with likelihood-free schemes.

系统发育树描述了进化过程中物种之间的关系，并提供了有关多样化速度的信息。为了理解宏观进化背后的机制，我们考虑了一类称为马尔可夫二叉树（mbt）的多类型分支过程。mbt允许基于性状的多样化率变化，并为系统发育树提供灵活和现实的概率模型。我们开发了一种近似贝叶斯计算（ABC）方案，利用系统发育树形状的信息来推断MBT参数的比率。我们通过模拟研究评估了这种推理方法的准确性，并发现我们的方法能够检测多样化率的变化，其准确性与基于似然的方法相当，并且通常优于基于似然的方法。在应用于现实生活中的鳞片系统发育中，我们加强了从早期研究中得出的结论，特别是支持卵/活两个方向上的过渡的存在。我们的方法展示了更复杂的进化模型与无似然方案一起用于系统发育推断的潜力。

{"title":"Approximate Bayesian computation for Markovian binary trees in phylogenetics","authors":"Mingqi He , Sophie Hautphenne , Yao-ban Chan","doi":"10.1016/j.jtbi.2025.112246","DOIUrl":"10.1016/j.jtbi.2025.112246","url":null,"abstract":"<div><div>Phylogenetic trees describe the relationships between species in the evolutionary process, and provide information about the rates of diversification. To understand the mechanisms behind macroevolution, we consider a class of multitype branching processes called Markovian binary trees (MBTs). MBTs allow for trait-based variation in diversification rates, and provide a flexible and realistic probabilistic model for phylogenetic trees. We develop an approximate Bayesian computation (ABC) scheme to infer the rates of MBT parameters by exploiting the information in the shapes of phylogenetic trees. We evaluate the accuracy of this inference method using simulation studies, and find that our method is able to detect variation in the diversification rates, with accuracy comparable to, and generally better than, likelihood-based methods. In an application to a real-life phylogeny of squamata, we reinforce conclusions drawn from earlier studies, in particular supporting the existence of ovi-/viviparity transitions in both directions. Our method demonstrates the potential for more complex models of evolution to be employed in phylogenetic inference, in conjunction with likelihood-free schemes.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112246"},"PeriodicalIF":2.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug dosing for cancer therapy: A stochastic model predictive control perspective 癌症治疗的药物剂量：一个随机模型预测控制的观点。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-08-31 DOI: 10.1016/j.jtbi.2025.112255

Andrés Hernández-Rivera , Pablo Velarde , Ascensión Zafra-Cabeza , José M. Maestre

Stochastic Model Predictive Control (SMPC) is an effective decision-making method in applications where uncertainties play a significant role. This work introduces a non-linear formulation of SMPC specifically designed for cancer therapy. The proposed method considers the stochastic nature of tumor growth, non-linear dynamics, and a potential side effect of the treatment. Through one-year simulations, the results showcase the effectiveness of this strategy in controlling drug dosing.

随机模型预测控制（SMPC）是一种有效的决策方法，适用于不确定性较大的应用场合。这项工作介绍了一种专门为癌症治疗设计的非线性SMPC配方。该方法考虑了肿瘤生长的随机性、非线性动力学和治疗的潜在副作用。通过一年的模拟，结果显示了该策略在控制药物剂量方面的有效性。

引用次数: 0

Emergent microtubule properties in a model of filament turnover and nucleation 细丝周转和成核模型中的涌现微管特性。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-08-30 DOI: 10.1016/j.jtbi.2025.112254

Anna C. Nelson , Scott A. McKinley , Melissa M. Rolls , Maria-Veronica Ciocanel

Microtubules (MTs) are dynamic protein filaments essential for intracellular organization and transport, particularly in long-lived cells such as neurons. The plus and minus ends of neuronal MTs switch between growth and shrinking phases, and the nucleation of new filaments is believed to be regulated in both healthy and injury conditions. We propose stochastic and deterministic mathematical models to investigate the impact of filament nucleation and length-regulation mechanisms on emergent properties such as MT lengths and numbers in living cells. We expand our stochastic continuous-time Markov chain model of filament dynamics to incorporate MT nucleation and capture realistic stochastic fluctuations in MT numbers and tubulin availability. We also propose a simplified partial differential equation (PDE) model, which allows for tractable analytical investigation into steady-state MT distributions under different nucleation and length-regulating mechanisms. We find that the stochastic and PDE modeling approaches show good agreement in MT length distributions, and that both MT nucleation and the catastrophe rate of large-length MTs regulate MT length distributions. In both frameworks, multiple mechanistic combinations achieve the same average MT length. The models proposed can predict parameter regimes where the system is scarce in tubulin, the building block of MTs, and suggest that low filament nucleation regimes are characterized by high variation in MT lengths, while high nucleation regimes drive high variation in MT numbers. These mathematical frameworks have the potential to improve our understanding of MT regulation in both healthy and injured neurons.

微管（MTs）是细胞内组织和运输所必需的动态蛋白丝，特别是在神经元等长寿细胞中。神经元MTs的正负两端在生长和萎缩阶段之间切换，新丝的成核被认为在健康和损伤条件下都受到调节。我们提出了随机和确定性的数学模型来研究丝成核和长度调节机制对活细胞中MT长度和数量等紧急特性的影响。我们扩展了长丝动力学的随机连续时间马尔可夫链模型，以纳入MT成核，并捕获MT数和微管蛋白可用性的实际随机波动。我们还提出了一个简化的偏微分方程（PDE）模型，该模型允许对不同成核和长度调节机制下的稳态MT分布进行易于处理的分析研究。我们发现随机和PDE建模方法在MT长度分布上表现出很好的一致性，并且MT成核和大长度MT的突变率都调节MT长度分布。在这两个框架中，多个机制组合实现相同的平均MT长度。所提出的模型可以预测系统缺乏微管蛋白（MT的组成部分）的参数体系，并表明低丝成核体系的特征是MT长度的高变化，而高成核体系驱动MT数的高变化。这些数学框架有可能提高我们对MT在健康和受伤神经元中的调节的理解。

{"title":"Emergent microtubule properties in a model of filament turnover and nucleation","authors":"Anna C. Nelson , Scott A. McKinley , Melissa M. Rolls , Maria-Veronica Ciocanel","doi":"10.1016/j.jtbi.2025.112254","DOIUrl":"10.1016/j.jtbi.2025.112254","url":null,"abstract":"<div><div>Microtubules (MTs) are dynamic protein filaments essential for intracellular organization and transport, particularly in long-lived cells such as neurons. The plus and minus ends of neuronal MTs switch between growth and shrinking phases, and the nucleation of new filaments is believed to be regulated in both healthy and injury conditions. We propose stochastic and deterministic mathematical models to investigate the impact of filament nucleation and length-regulation mechanisms on emergent properties such as MT lengths and numbers in living cells. We expand our stochastic continuous-time Markov chain model of filament dynamics to incorporate MT nucleation and capture realistic stochastic fluctuations in MT numbers and tubulin availability. We also propose a simplified partial differential equation (PDE) model, which allows for tractable analytical investigation into steady-state MT distributions under different nucleation and length-regulating mechanisms. We find that the stochastic and PDE modeling approaches show good agreement in MT length distributions, and that both MT nucleation and the catastrophe rate of large-length MTs regulate MT length distributions. In both frameworks, multiple mechanistic combinations achieve the same average MT length. The models proposed can predict parameter regimes where the system is scarce in tubulin, the building block of MTs, and suggest that low filament nucleation regimes are characterized by high variation in MT lengths, while high nucleation regimes drive high variation in MT numbers. These mathematical frameworks have the potential to improve our understanding of MT regulation in both healthy and injured neurons.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112254"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extinction and persistence in a temperature-driven, stage-structured stochastic model of Dalbulus maidis dynamics with nonlinear density-dependent regulation 具有非线性密度依赖调节的黄菖蒲动力学的温度驱动、阶段结构随机模型中的灭绝和持续。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-08-30 DOI: 10.1016/j.jtbi.2025.112256

F.E. Cornes , R.H. Barriga Rubio , M. Otero

We present an extension of a previously developed stochastic, stage-structured model of Dalbulus maidis (corn leafhopper), an important pest and vector in maize crops. The extended model introduces nonlinear density-dependent regulation on the nymphal stage, mediated by a carrying capacity that dynamically depends on the leaf area of maize plants. Both insect and host-plant dynamics are explicitly modeled, but the interaction is asymmetric, as the plant is not affected by the insect in the present formulation. Our main objective is to explore how the interplay between temperature-driven development and host-plant dynamics shapes the long-term behavior of the insect population, leading to either extinction or persistence. Using simulations parameterized with laboratory and field data, we analyze how temperature and maize development affect insect dynamics, and assess whether the model can reproduce observed abundance patterns under realistic conditions. This modeling framework provides a biologically grounded and flexible basis for future extensions, including pathogen transmission and bidirectional feedback between the maize and the insect.

我们提出了先前开发的玉米叶蝉（Dalbulus maidis）的随机阶段结构模型的扩展，玉米叶蝉是玉米作物的重要害虫和媒介。该扩展模型引入了若虫期的非线性密度依赖调节，由玉米植株叶面积动态依赖的承载能力介导。昆虫和寄主植物的动力学都被明确建模，但相互作用是不对称的，因为在本配方中植物不受昆虫的影响。我们的主要目标是探索温度驱动的发育和寄主植物动态之间的相互作用如何影响昆虫种群的长期行为，从而导致灭绝或持续存在。利用室内和野外数据进行参数化模拟，分析了温度和玉米发育对昆虫动态的影响，并评估了该模型是否能在现实条件下再现观测到的丰度模式。该模型框架为未来的扩展提供了生物学基础和灵活的基础，包括病原体传播和玉米与昆虫之间的双向反馈。

{"title":"Extinction and persistence in a temperature-driven, stage-structured stochastic model of Dalbulus maidis dynamics with nonlinear density-dependent regulation","authors":"F.E. Cornes , R.H. Barriga Rubio , M. Otero","doi":"10.1016/j.jtbi.2025.112256","DOIUrl":"10.1016/j.jtbi.2025.112256","url":null,"abstract":"<div><div>We present an extension of a previously developed stochastic, stage-structured model of <em>Dalbulus maidis</em> (corn leafhopper), an important pest and vector in maize crops. The extended model introduces nonlinear density-dependent regulation on the nymphal stage, mediated by a carrying capacity that dynamically depends on the leaf area of maize plants. Both insect and host-plant dynamics are explicitly modeled, but the interaction is asymmetric, as the plant is not affected by the insect in the present formulation. Our main objective is to explore how the interplay between temperature-driven development and host-plant dynamics shapes the long-term behavior of the insect population, leading to either extinction or persistence. Using simulations parameterized with laboratory and field data, we analyze how temperature and maize development affect insect dynamics, and assess whether the model can reproduce observed abundance patterns under realistic conditions. This modeling framework provides a biologically grounded and flexible basis for future extensions, including pathogen transmission and bidirectional feedback between the maize and the insect.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112256"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mathematical model of nucleocytoplasmic transport and nuclear-to-cell ratio in a growing cell 生长细胞中核细胞质运输和核细胞比的数学模型。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-08-29 DOI: 10.1016/j.jtbi.2025.112250

Xuesong Bai, Thomas G. Fai

It has been observed that the growth of the nucleus and the cytoplasm is coordinated during cell growth, resulting in a nearly constant nuclear-to-cell volume ratio (N/C) throughout the cell cycle. Previous studies have shown that the N/C ratio is determined by the ratio between the number of proteins in the nucleus and the total number of proteins in the cell. These observations suggest the importance of the nucleocytoplasmic transport process in nuclear size by regulating protein concentrations in the nucleus and cytoplasm. This paper combines a biophysical model of Ran-mediated nucleocytoplasmic transport and a simple cell growth model to provide insights into several key aspects of the N/C ratio homeostasis in growing cells. Our model shows that the permeability of the nuclear envelope needs to grow in line with the cell to maintain a nearly constant N/C ratio, that several parameters involved in the nucleocytoplasmic transport mechanism and gene translation significantly affect the N/C ratio, and that Ran may potentially compensate for the lack of NTF2 in the nucleocytoplasmic transport mechanism to maintain a viable N/C ratio. However, this compensation is possible only if RanGDP is allowed to translocate through the nuclear envelope independently of NTF2.

在细胞生长过程中，细胞核和细胞质的生长是相互协调的，在整个细胞周期中，细胞核与细胞的体积比（N/C）几乎是恒定的。先前的研究表明，N/C比率是由细胞核中蛋白质数量与细胞中蛋白质总数之比决定的。这些观察结果表明，通过调节细胞核和细胞质中的蛋白质浓度，核胞质转运过程在细胞核大小中的重要性。本文结合了ran介导的核细胞质运输的生物物理模型和简单的细胞生长模型，以提供对生长细胞中N/C比稳态的几个关键方面的见解。我们的模型表明，核膜的通透性需要与细胞一致生长才能维持一个近乎恒定的N/C比，核胞质转运机制和基因翻译中涉及的几个参数显著影响N/C比，Ran可能潜在地弥补核胞质转运机制中NTF2的缺失，以维持一个可行的N/C比。然而，这种补偿只有在允许RanGDP独立于NTF2通过核包膜转运的情况下才有可能实现。

{"title":"Mathematical model of nucleocytoplasmic transport and nuclear-to-cell ratio in a growing cell","authors":"Xuesong Bai, Thomas G. Fai","doi":"10.1016/j.jtbi.2025.112250","DOIUrl":"10.1016/j.jtbi.2025.112250","url":null,"abstract":"<div><div>It has been observed that the growth of the nucleus and the cytoplasm is coordinated during cell growth, resulting in a nearly constant nuclear-to-cell volume ratio (N/C) throughout the cell cycle. Previous studies have shown that the N/C ratio is determined by the ratio between the number of proteins in the nucleus and the total number of proteins in the cell. These observations suggest the importance of the nucleocytoplasmic transport process in nuclear size by regulating protein concentrations in the nucleus and cytoplasm. This paper combines a biophysical model of Ran-mediated nucleocytoplasmic transport and a simple cell growth model to provide insights into several key aspects of the N/C ratio homeostasis in growing cells. Our model shows that the permeability of the nuclear envelope needs to grow in line with the cell to maintain a nearly constant N/C ratio, that several parameters involved in the nucleocytoplasmic transport mechanism and gene translation significantly affect the N/C ratio, and that Ran may potentially compensate for the lack of NTF2 in the nucleocytoplasmic transport mechanism to maintain a viable N/C ratio. However, this compensation is possible only if RanGDP is allowed to translocate through the nuclear envelope independently of NTF2.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112250"},"PeriodicalIF":2.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mating versus alternative blood sources as determinants to mosquito abundance and population resilience 交配与替代血液来源是蚊子数量和种群恢复力的决定因素。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-08-28 DOI: 10.1016/j.jtbi.2025.112253

Gideon A. Ngwa , Bime M. Ghakanyuy , Miranda I. Teboh-Ewungkem , Jacek Banasiak

A deterministic nonlinear ordinary differential equation model for mosquito dynamics in which the mosquitoes can quest for blood either within a human population or within non-human/vertebrate populations is derived and studied. The model captures both the mosquito’s aquatic and terrestrial forms and includes a mechanism to investigate the impact of mating on mosquito dynamics. The model uses a restricted form of homogeneous mixing based on the idea that the mosquito has a blood-feeding habit determined by its blood-feeding preferences and its gonotrophic cycle. This characterisation allows us to compartmentalise the total mosquito population into distinct compartments according to the spatial location of the mosquito (breeding site, resting places and questing places) as well as blood-fed status. Issues of overcrowding and intraspecific competition both within the aquatic and the terrestrial stages of the mosquito’s life forms are addressed and considered in the model. Results show that the inclusion of mating induces bistability, a phenomenon whereby locally stable trivial and non-trivial equilibria co-exist with an unstable non-zero equilibrium. The local nature of the stable equilibria is demonstrated by numerically showing that the long-term state of the system is sensitive to initial conditions. The bistability state is analogous to the phenomenon of the Allee effect that has been reported in population biology. The model’s results, including the derivation of the threshold parameter of the system, are comprehensively tested via numerical simulations. The output of our model has direct application to mosquito control strategies, for it clearly shows key points in the mosquito’s developmental pathway that can be targeted for control purposes.

本文推导并研究了蚊子在人类种群或非人/脊椎动物种群中吸血的确定性非线性常微分方程模型。该模型捕获了蚊子的水生和陆地形态，并包括一种机制来研究交配对蚊子动力学的影响。该模型使用了一种有限形式的均匀混合，其基础是蚊子的吸血习惯是由它的吸血偏好和淋养循环决定的。这种特征使我们能够根据蚊子的空间位置（繁殖地点、休息地点和探索地点）以及吸血状况将蚊子总数划分为不同的区域。该模型解决并考虑了蚊子在水生和陆地生命形式阶段的过度拥挤和种内竞争问题。结果表明，配合的包含引起双稳定性，即局部稳定的平凡平衡和非平凡平衡与不稳定的非零平衡共存的现象。用数值方法证明了系统的长期状态对初始条件敏感，从而证明了系统稳定平衡的局部性质。双稳状态类似于种群生物学中报道的Allee效应现象。通过数值模拟对模型结果进行了全面验证，包括系统阈值参数的推导。我们的模型的输出可以直接应用于蚊子控制策略，因为它清楚地显示了蚊子发育途径中的关键点，可以用于控制目的。

{"title":"Mating versus alternative blood sources as determinants to mosquito abundance and population resilience","authors":"Gideon A. Ngwa , Bime M. Ghakanyuy , Miranda I. Teboh-Ewungkem , Jacek Banasiak","doi":"10.1016/j.jtbi.2025.112253","DOIUrl":"10.1016/j.jtbi.2025.112253","url":null,"abstract":"<div><div>A deterministic nonlinear ordinary differential equation model for mosquito dynamics in which the mosquitoes can quest for blood either within a human population or within non-human/vertebrate populations is derived and studied. The model captures both the mosquito’s aquatic and terrestrial forms and includes a mechanism to investigate the impact of mating on mosquito dynamics. The model uses a restricted form of homogeneous mixing based on the idea that the mosquito has a blood-feeding habit determined by its blood-feeding preferences and its gonotrophic cycle. This characterisation allows us to compartmentalise the total mosquito population into distinct compartments according to the spatial location of the mosquito (breeding site, resting places and questing places) as well as blood-fed status. Issues of overcrowding and intraspecific competition both within the aquatic and the terrestrial stages of the mosquito’s life forms are addressed and considered in the model. Results show that the inclusion of mating induces bistability, a phenomenon whereby locally stable trivial and non-trivial equilibria co-exist with an unstable non-zero equilibrium. The local nature of the stable equilibria is demonstrated by numerically showing that the long-term state of the system is sensitive to initial conditions. The bistability state is analogous to the phenomenon of the Allee effect that has been reported in population biology. The model’s results, including the derivation of the threshold parameter of the system, are comprehensively tested via numerical simulations. The output of our model has direct application to mosquito control strategies, for it clearly shows key points in the mosquito’s developmental pathway that can be targeted for control purposes.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112253"},"PeriodicalIF":2.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stochastic modelling of early-stage COVID-19 epidemic dynamics in rural communities in the United States 美国农村社区早期COVID-19流行动态的随机建模

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-08-24 DOI: 10.1016/j.jtbi.2025.112248

Punya Alahakoon , Peter G. Taylor , James M. McCaw

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people around the globe. We studied the spread of SARS-CoV-2 across six rural counties in North and South Dakota in the United States. The study period was from early March 2020 to mid-June 2021, during which non-pharmaceutical interventions (NPIs) were in place. The end of the study period coincided with the emergence of the Delta variant in the United States. We modelled the transmission dynamics in each county using a stochastic compartmental model and analysed the data within a Bayesian hierarchical statistical framework. We estimated key epidemiological and surveillance parameters including the reproduction number and reporting probability. We conducted a series of counterfactual analyses in which NPIs were lifted earlier and by varying degrees, modelled as an increase in the transmission rate. Under this range of plausible alternative responses, increases in case counts varied from negligible to substantial, underscoring the importance of timely public health measures and compliance with them. From a methodological perspective, our study demonstrates that despite the inherent high variability in epidemic behaviour in small rural communities, the combination of stochastic modelling and application of Bayesian hierarchical analyses enables the estimation of key epidemiological and surveillance parameters and consideration of the potential impact of alternative public health measures in small low population density communities.

由严重急性呼吸系统综合征冠状病毒2 （SARS-CoV-2）引起的COVID-19已影响到全球数百万人。我们研究了SARS-CoV-2在美国北达科他州和南达科他州六个农村县的传播。研究期间为2020年3月初至2021年6月中旬，在此期间实施了非药物干预措施（npi）。研究期结束时，美国出现了Delta变异。我们使用随机区隔模型模拟了每个县的传播动态，并在贝叶斯分层统计框架内分析了数据。我们估计了关键的流行病学和监测参数，包括繁殖数和报告概率。我们进行了一系列反事实分析，在这些分析中，npi被提前解除，并在不同程度上被建模为传播率的增加。在这一系列合理的备选对策下，病例数的增加从微不足道到大量不等，强调了及时采取公共卫生措施和遵守这些措施的重要性。从方法学的角度来看，我们的研究表明，尽管小型农村社区的流行病行为具有固有的高度可变性，但随机建模和贝叶斯分层分析的应用相结合，可以估计关键的流行病学和监测参数，并考虑在小型低人口密度社区中替代公共卫生措施的潜在影响。

{"title":"Stochastic modelling of early-stage COVID-19 epidemic dynamics in rural communities in the United States","authors":"Punya Alahakoon , Peter G. Taylor , James M. McCaw","doi":"10.1016/j.jtbi.2025.112248","DOIUrl":"10.1016/j.jtbi.2025.112248","url":null,"abstract":"<div><div>COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people around the globe. We studied the spread of SARS-CoV-2 across six rural counties in North and South Dakota in the United States. The study period was from early March 2020 to mid-June 2021, during which non-pharmaceutical interventions (NPIs) were in place. The end of the study period coincided with the emergence of the Delta variant in the United States. We modelled the transmission dynamics in each county using a stochastic compartmental model and analysed the data within a Bayesian hierarchical statistical framework. We estimated key epidemiological and surveillance parameters including the reproduction number and reporting probability. We conducted a series of counterfactual analyses in which NPIs were lifted earlier and by varying degrees, modelled as an increase in the transmission rate. Under this range of plausible alternative responses, increases in case counts varied from negligible to substantial, underscoring the importance of timely public health measures and compliance with them. From a methodological perspective, our study demonstrates that despite the inherent high variability in epidemic behaviour in small rural communities, the combination of stochastic modelling and application of Bayesian hierarchical analyses enables the estimation of key epidemiological and surveillance parameters and consideration of the potential impact of alternative public health measures in small low population density communities.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112248"},"PeriodicalIF":2.0,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0