Journal of Theoretical Biology最新文献

英文中文

Cell position-based evaluation of mechanical features of cells in multicellular systems

IF 1.9 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-02-18 DOI: 10.1016/j.jtbi.2025.112070

Hiroshi Koyama , Atsushi M. Ito , Hisashi Okumura , Tetsuhisa Otani , Kazuyuki Nakamura , Toshihiko Fujimori

Measurement of mechanical forces of cell–cell interactions is important for studying the emergence of diverse three-dimensional morphologies of multicellular organisms. We previously reported an image-based statistical method for inferring effective pairwise forces of cell–cell interactions (i.e., attractive/repulsive forces), where a cell particle model was fitted to cell tracking data acquired by live imaging. However, because the particle model is a coarse-grained model, it remains unclear how the pairwise forces relates to sub-cellular mechanical components including cell–cell adhesive forces. Here we applied our inference method to cell tracking data generated by vertex models that assumed sub-cellular components. Through this approach, we investigated the relationship between the effective pairwise forces and various sub-cellular components: cell–cell adhesion forces, cell surface tensions, cell–extracellular matrix (ECM) adhesion, traction forces between cells and ECM, cell growth, etc. We found that the cell–cell adhesion forces were attractive, and both the cell surface tensions and cell–ECM adhesive forces were repulsive, etc. These results indicate that sub-cellular mechanical components can contribute to the effective attractive/repulsive forces of cell–cell interactions. This comprehensive analysis provides theoretical bases for linking the pairwise forces to the sub-cellular mechanical components: this showcase is useful for speculating the sub-cellular mechanical components from the information of cell positions, and for interpreting simulation results based on particle models.

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引用次数: 0

Spatio-temporal model of combining ADT and chemotherapy with senolytic treatment in metastatic prostate cancer

IF 1.9 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-02-18 DOI: 10.1016/j.jtbi.2025.112069

Teddy Lazebnik , Avner Friedman

Prostate cancer cells depend on androgen for their survival. A standard treatment of metastatic prostate cancer (mPC) is androgen deprivation treatment (ADT). However, after a period of remission, some cancer cells changed into androgen-independent cells, and then treatment proceeds with a combination of ADT and chemotherapy. Senescent cells are cells that stop dividing but sustain viability. Senescence cancer cells are common in cancer, and they affect cancer treatment negatively by secreting inflammatory cytokines and pro-cancer VEGF. In this paper, we include the effect of senescence in a model of mPC. We consider combinations of ADT, chemotherapy, and senolytic drug, which eliminate senescent cells, in a spatio-temporal partial differential equations model, and demonstrate that simulations of the model are in agreement with experimental results. We evaluate the synergy between different doses of chemotherapy and senolytic drugs, at different fixed doses of ADT. We also consider optimal scheduling of the drugs, and the hypothesis that, in optimal schedule, a senolytic drug is to be administered immediately following the chemotherapy drug.

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引用次数: 0

Optimal social distancing in pandemic preparedness and lessons from COVID-19: Intervention intensity and infective travelers

IF 1.9 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-02-16 DOI: 10.1016/j.jtbi.2025.112072

Alberto Landi , Giulio Pisaneschi , Marco Laurino , Piero Manfredi

Our analysis seeks best social distancing strategies optimally balancing the direct costs of a threatening outbreak with its societal-level costs by investigating the effects of different levels of restrictions’ intensity and of the continued importation of infective travellers, while controlling for the key dimensions of the response, such as early action, adherence and the relative weight of societal costs. We identify two primary degrees of freedom in epidemic control, namely the maximum intensity of control measures and their duration. In the absence of travellers, a lower (higher) maximum intensity requires a longer (shorter) duration to achieve similar control outcomes. However, uncontrollable external factors, like the importation of undetected infectives, significantly constrain these degrees of freedom so that the optimal strategy results to be one with low/moderate intensity but prolonged in time. These findings underscore the necessity for resilient health systems and coordinated global responses in preparedness plans.

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引用次数: 0

The effect of heterogeneity of relative vaccine costs on the mean population vaccination rate with mpox as an example

IF 1.9 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-02-10 DOI: 10.1016/j.jtbi.2025.112062

Spalding Garakani , Luis Flores , Guillermo Alvarez-Pardo , Jan Rychtář , Dewey Taylor

Mpox (formerly known as monkeypox) is a neglected tropical disease that became notorious during its 2022–2023 worldwide outbreak. The vaccination was available, but there were inequities in vaccine access. In this paper, we extend existing game-theoretic models to study a population that is heterogeneous in the relative vaccination costs. We consider a population with two groups. We determine the Nash equilibria (NE), i.e., optimal vaccination rates, for each of the groups. We show that the NE always exists and that, for a narrow range of parameter values, there can be multiple NEs. We focus on comparing the mean optimal vaccination rate in the heterogeneous population with the optimal vaccination rate in the corresponding homogeneous population. We show that there is a critical size for the group with lower relative costs and the mean optimal vaccination in the heterogeneous population is more than in the homogeneous population if and only if the group is larger than the critical size.

天花（原名猴痘）是一种被忽视的热带疾病，在 2022-2023 年全球爆发期间臭名昭著。疫苗是可以接种的，但在疫苗接种方面存在不公平现象。在本文中，我们扩展了现有的博弈论模型，以研究在相对接种成本方面存在异质性的人群。我们考虑了有两个群体的人口。我们确定了每个群体的纳什均衡（NE），即最佳接种率。我们的研究表明，NE 始终存在，而且在参数值范围较小的情况下，可能存在多个 NE。我们主要关注异质人群的平均最佳接种率与相应同质人群的最佳接种率之间的比较。我们的研究表明，相对成本较低的群体存在一个临界规模，当且仅当该群体大于临界规模时，异质群体的平均最佳接种率高于同质群体。

引用次数: 0

Age-dependence of food allergy due to decreased supply of naïve T cells

IF 1.9 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-02-08 DOI: 10.1016/j.jtbi.2025.112060

Yuna Kotsubo , Akane Hara , Rena Hayashi , Yoh Iwasa

Food allergies to eggs and cow’s milk are common during infancy but often undergo desensitization during childhood. To investigate the age dependence of food allergies, we develop a simple mathematical model focusing on T helper 2 cells (Th2) causing allergies and induced regulatory T cells (iTreg) suppressing them. We assume as follows: Both types of cells differentiate from naïve T cells reactive to specific food allergens, with the rate of supply from the thymus decreasing with age. Naïve T cells are activated by allergens in peripheral tissues, differentiating into both Th2 and iTreg cells. The activation rate of Th2 cells is reduced by iTreg cells. Th2 cells promote allergies while iTreg cells help mitigate them. Analyses show that food allergies may develop at one age and resolve at a later age. Negative selection in the thymus reduces the number of naïve T cells that react to proteins resembling components of the body. As a result, allergies to these substances tend to start and resolve earlier in life than those to dissimilar materials. Food allergy starting at an older age tends to have a longer duration if the rate of naïve T cell supply decreases according to a hyperbolic (instead of exponential) function of age.

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引用次数: 0

Impact of evolutionary relatedness on species diversification and tree shape 进化相关性对物种多样性和树形的影响

IF 1.9 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-02-07 DOI: 10.1016/j.jtbi.2024.111992

Tianjian Qin , Luis Valente , Rampal S. Etienne

Slowdowns in lineage accumulation are often observed in phylogenies of extant species. One explanation is the presence of ecological limits to diversity and hence to diversification. Previous research has examined whether and how species richness (SR) impacts diversification rates, but rarely considered the evolutionary relatedness (ER) between species, although ER can affect the degree of interaction between species, which likely sets these limits. To understand the influences of ER on species diversification and the interplay between SR and ER, we present a simple birth–death model in which the speciation rate depends on the ER. We use different metrics of ER that operate at different scales, ranging from branch/lineage-specific to clade-wide scales. We find that the scales at which an effect of ER operates yield distinct patterns in various tree statistics. When ER operates across the whole tree, we observe smaller and more balanced trees, with speciation rates distributed more evenly across the tips than in scenarios with lineage-specific ER effects. Importantly, we find that negative SR dependence of speciation masks the impact of ER on some of the tree statistics. Our model allows diverse evolutionary trajectories for producing imbalanced trees, which are commonly observed in empirical phylogenies but have been challenging to replicate with earlier models.

在现存物种的系统发育过程中，经常可以观察到世系积累速度减慢的现象。一种解释是多样性存在生态限制，因此多样化也存在生态限制。以往的研究探讨了物种丰富度（SR）是否以及如何影响物种多样化率，但很少考虑物种之间的进化亲缘关系（ER），尽管ER会影响物种之间的相互作用程度，而物种之间的相互作用程度很可能设定了这些限制。为了了解ER对物种多样化的影响以及SR和ER之间的相互作用，我们提出了一个简单的出生-死亡模型，在这个模型中，物种的演化率取决于ER。我们使用了不同的ER指标，这些指标在不同的尺度上起作用，从特定的分支/系到整个类群的尺度。我们发现，ER效应在不同尺度上的作用会产生不同的树统计模式。当ER作用于整棵树时，我们观察到的树更小、更平衡，与特定世系的ER效应相比，树尖上的物种变异率分布更均匀。重要的是，我们发现物种演化的负SR依赖性掩盖了ER对某些树统计数据的影响。我们的模型允许不同的进化轨迹产生不平衡的树，这是在经验系统发生中经常观察到的现象，但在早期的模型中却很难复制。

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引用次数: 0

Possible regulatory mechanisms of typical and atypical absence seizures through an equivalent projection from the subthalamic nucleus to the cortex: Evidence in a computational model

IF 1.9 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-02-05 DOI: 10.1016/j.jtbi.2025.112059

Bing Hu, Yaqi Guo, JinDong Zhao, Xunfu Ma

The subthalamic nucleus (STN) is an important structure that regulates basal ganglia output and has been involved in the pathophysiology of epilepsy disease. In this paper, we propose an equivalent inhibitory pathway directly projecting from the STN to the cortex and systematically study its regulatory effect on absence seizures. Interestingly, we find that this equivalent inhibitory projection is a key factor for assisting in the development of atypical absence seizures. Through computational simulation and model analysis, we find that the enhancement of coupling strength on this equivalent STN-cortex projection can effectively suppress typical and atypical spike and wave discharges (TSWDs and ASWDs) during absence seizures. Furthermore, altering the activation level of STN through external stimuli can also control seizures, and the presence of equivalent STN-cortex projection makes the control effect more easier to achieve. Several direct and indirect pathways related to the STN can achieve inhibition of SWDs by regulating the activation level of STN, and relevant control strategies have high biological plausibility. Therefore, the STN may be an effective target for the deep brain stimulation (DBS) to control absence seizures. Importantly, we observe that the control effect of DBS-STN on SWDs is significantly superior to other basal ganglia targets in this model. Moreover, we find that the parameter range and value with high biological plausibility for the coupling weight in this equivalent STN-cortex projection can be effectively estimated in this model. Our results imply that the inhibitory effect from the STN to the cortex plays a crucial role in regulating both typical and atypical SWDs, and the STN might be a potential and reasonable DBS target for the treatment of absence epilepsy.

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引用次数: 0

Efficient coupling of within-and between-host infectious disease dynamics

IF 1.9 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-02-04 DOI: 10.1016/j.jtbi.2025.112061

Cameron A. Smith , Ben Ashby

Mathematical models of infectious disease transmission typically neglect within-host dynamics. Yet within-host dynamics – including pathogen replication, host immune responses, and interactions with microbiota – are crucial not only for determining the progression of disease at the individual level, but also for driving within-host evolution and onwards transmission, and therefore shape dynamics at the population level. Various approaches have been proposed to model both within- and between-host dynamics, but these typically require considerable simplifying assumptions to couple processes at contrasting scales (e.g., the within-host dynamics quickly reach a steady state) or are computationally intensive. Here we propose a novel, readily adaptable and broadly applicable method for modelling both within- and between-host processes which can fully couple dynamics across scales and is both realistic and computationally efficient. By individually tracking the deterministic within-host dynamics of infected individuals, and stochastically coupling these to continuous host state variables at the population-level, we take advantage of fast numerical methods at both scales while still capturing individual transient within-host dynamics and stochasticity in transmission between hosts. Our approach closely agrees with full stochastic individual-based simulations and is especially useful when the within-host dynamics do not rapidly reach a steady state or over longer timescales to track pathogen evolution. By applying our method to different pathogen growth scenarios we show how common simplifying assumptions fundamentally change epidemiological and evolutionary dynamics.

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引用次数: 0

Simulations probe the role of space in the interplay between drug-sensitive and drug-resistant cancer cells

IF 1.9 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-02-04 DOI: 10.1016/j.jtbi.2025.112048

Kira Pugh , Rhys D.O. Jones , Gibin Powathil , Sara Hamis

The interplay between drug-sensitive and drug-resistant cancer cells has been observed to impact cell-to-cell interactions in experimental settings. However, the role that space plays in these interactions remains unclear. In this study, we develop mathematical models to investigate how spatial factors affect cell-to-cell competition between drug-sensitive and drug-resistant cancer cells in silico. We develop two baseline models to study cells from the epithelial FaDu cell line subjected to two drugs, specifically the ATR inhibitor ceralasertib and the PARP inhibitor olaparib, that target DNA damage response pathways. Our baseline models are: (1) a temporally resolved ordinary differential equation (ODE) model, and (2) a spatio-temporally resolved agent-based model (ABM). The models simulate cells in well-mixed and spatially structured cell systems, respectively. The ODE model is calibrated against in vitro data and is thereafter mapped onto the baseline ABM which, in turn, is extended to enable a simulation-based investigation on how spatial factors impact cell-to-cell competition. Simulation results from the extended ABMs demonstrate that the in silico treatment responses are simultaneously affected by: (i) the initial spatial cell configurations, (ii) the initial fraction of drug-resistant cells, (iii) the drugs to which cells express resistance, (iv) drug combinations, (v) drug doses, and (vi) the doubling time of drug-resistant cells compared to the doubling time of drug-sensitive cells. These results reveal that spatial structures of the simulated cancer cells affect both cell-to-cell interactions, and the impact that these interactions have on the ensuing population dynamics. This leads us to suggest that the role that space plays in cell-to-cell interactions should be further investigated and quantified in experimental settings.

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A mathematical model of microglia glucose metabolism and lactylation with positive feedback

IF 1.9 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-01-30 DOI: 10.1016/j.jtbi.2025.112049

Kamila Larripa , Anca Rǎdulescu

In this paper, we present and analyze a model for metabolism and lactylation in a single microglia. The model includes positive feedback from lactylation in the glycolytic pathway, and links metabolism and inflammation. Specific pathways include the transition of glucose to pyruvate to lactate in a microglia, as well as the gradient transport of glucose and lactate into and out of the cell. Additionally, the upregulation of certain pathways by either epigenetic modification or the inflammatory response are included. Bifurcation and sensitivity analyses demonstrate the importance of key parameters and pathways in the model, specifically the role of lactylation. Our model is validated by qualitatively reproducing recent in vitro experiments in which exogenous glucose and lactate are modified.

引用次数: 0

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