Journal of Theoretical Biology最新文献_第7页

Network reciprocity turns cheap talk into a force for cooperation 网络互惠将廉价的谈话转化为合作的力量

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2026-01-21 Epub Date: 2025-11-07 DOI: 10.1016/j.jtbi.2025.112303

Zhao Song , Chen Shen , The Anh Han

Non-binding communication is common in daily life and crucial for fostering cooperation, even though it has no direct payoff consequences. However, despite robust empirical evidence, its evolutionary basis remains poorly understood. Here, we develop a game-theoretic model in which individuals can signal an intention to cooperate before playing a Donation game. Strategies differ in how they respond to these signals, ranging from unconditional to conditional types, with the latter incurring a cognitive cost for deliberation. Through evolutionary analysis, we show that non-binding communication alone cannot sustain cooperation in well-mixed, anonymous populations, consistent with empirical observations. In contrast, structured populations support the emergence of cooperation, with conditional cooperators acting as catalysts that protect unconditional cooperators through context-dependent patterns of cyclic dominance. These findings offer an evolutionary explanation for how non-binding communication promotes cooperation and provide a modelling framework for exploring its effects in diverse social settings.

非约束性沟通在日常生活中很常见，对促进合作至关重要，尽管它没有直接的回报结果。然而，尽管有强有力的经验证据，其进化基础仍然知之甚少。在这里，我们开发了一个博弈论模型，其中个人可以在玩捐赠游戏之前发出合作意愿的信号。策略的不同在于它们对这些信号的反应方式，从无条件的到有条件的，后者会产生考虑的认知成本。通过进化分析，我们表明，在混合良好的匿名群体中，仅靠非约束性交流无法维持合作，这与经验观察一致。相比之下，结构化种群支持合作的出现，有条件的合作者作为催化剂，通过环境依赖的循环优势模式保护无条件的合作者。这些发现为非约束性交流如何促进合作提供了一种进化解释，并为探索其在不同社会环境中的影响提供了一个建模框架。

引用次数: 0

The role of colony size on activity rhythms of ants 蚁群大小对蚁群活动节律的影响。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2026-01-21 Epub Date: 2025-10-17 DOI: 10.1016/j.jtbi.2025.112286

Michael Napoli , Rifat Sipahi , Maurizio Porfiri

Thirty years of research into activity rhythms of ant colonies have contributed an improved understanding of this fascinating form of collective behavior. Yet, little is known about how the colony size influences the intensity and tempo of the rhythms. Here, we address this knowledge gap through a two-pronged approach, combining the re-evaluation of published experimental observations on California ant, Temnothorax rudis, with the formulation of a novel mathematical model. From the analysis of published data, we discover that the period of the activity bursts is nearly independent of the colony size, while the number of ants activated during the bursts scales hypometrically with the colony size. In search of the biological mechanisms underpinning this evidence, we put forward a compartmental model consisting of three classes: active, inactive, and refractory ants. The study of the resulting system of nonlinear delay-differential equations explains the emergence of activity rhythms as stable limit cycles. The period of these limit cycles is controlled by the refractory delay for the resting phase, independently of the colony size, but their amplitude allometrically varies with the colony size due to social deactivation. During activity rhythms, ants spontaneously deactivate when socially interacting with active individuals.

三十年来对蚁群活动节奏的研究使我们对这种令人着迷的集体行为形式有了更好的理解。然而，人们对蜂群大小如何影响节奏的强度和节奏知之甚少。在这里，我们通过双管齐下的方法来解决这一知识差距，结合对加利福尼亚蚂蚁Temnothorax rudis的已发表实验观察结果的重新评估，以及一个新的数学模型的制定。从已发表的数据分析中，我们发现活动爆发的周期几乎与群体规模无关，而在爆发期间被激活的蚂蚁数量与群体规模呈低计量关系。为了寻找支持这一证据的生物学机制，我们提出了一个由三类蚂蚁组成的区室模型：活性蚂蚁、非活性蚂蚁和难降解蚂蚁。由此产生的非线性时滞微分方程组的研究解释了活动节律作为稳定极限环的出现。这些极限环的周期是由静止阶段的耐火延迟控制的，独立于群体大小，但它们的振幅随群体大小而异速变化，这是由于社会的失活。在活动节律期间，蚂蚁在与活跃的个体进行社交互动时，会自发地停止活动。

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引用次数: 0

Intraspecific competition can stabilize asymmetric nursery pollination mutualisms 种内竞争可以稳定苗圃授粉的不对称共生关系。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2026-01-21 Epub Date: 2025-10-17 DOI: 10.1016/j.jtbi.2025.112300

Jian-Zhong Gao , Feng Zhang , Derek W. Dunn , Hao Wang , K.Charlotte Jandér , Rui-Wu Wang

A fundamental problem in ecology is to understand how mutualisms remain stable. The density-dependent regulations within interacting species potentially impact the persistence of these interspecific relationships. Yet few studies explore such intraspecific regulations’ role in stabilizing mutualisms. In addition, partner species often gain unequal benefits in mutualisms. To what extent such an interspecific asymmetry affects the stability of mutualisms is also poorly understood. We here developed a dynamic model for the asymmetric interaction between plants and their pollinators in nursery mutualisms, considering the intraspecific competition of each mutualist. We found that (i) a mutualism can be stabilized only if both mutualists are subject to the regulation of intraspecific competition; (ii) stabilizing the system also requires that the degree of asymmetry in benefits between mutualists must be limited to a range of ‘tolerance’, which narrows as intraspecific competition increases and even fades away with strong competition within both mutualistic species; (iii) when intraspecific competition within a species increases, the tolerant range is compressed from the side beneficial for it, with thus its partner species gaining relatively more benefit allocation; (iv) if the plant-pollinator interaction initiates from a small host plant population, these host plants must offer pollinators high levels of benefits, that can be subsequently reduced to favor plants once the mutualism has been successfully established. The agreement of empirical data to theoretical predictions suggests model reliability. These results highlight the role of intraspecific competition and the degree of benefit asymmetry between host plants and symbionts in stabilizing mutualisms.

生态学的一个基本问题是了解共生关系如何保持稳定。相互作用物种内部的密度依赖规则可能会影响这些种间关系的持久性。然而，很少有研究探讨这种种内调控在稳定共生关系中的作用。此外，伴侣物种往往在互惠关系中获得不平等的利益。这种种间不对称在多大程度上影响了共生关系的稳定性，人们也知之甚少。本文建立了苗圃共生中植物与传粉者之间不对称相互作用的动态模型，考虑了每个共生者的种内竞争。我们发现：(1)只有当双方都受到种内竞争的调节时，互惠共生才能稳定；（ii）稳定系统还要求互惠者之间利益的不对称程度必须限制在一个“容忍”范围内，这个范围随着种内竞争的增加而缩小，甚至随着两个互惠物种内部的激烈竞争而消失；(3)当种内竞争加剧时，从有利的方面压缩了物种的容忍度范围，从而使其伴侣物种获得相对较多的利益分配；（iv）如果植物与传粉者的相互作用是从一个小的寄主植物种群开始的，这些寄主植物必须为传粉者提供高水平的利益，一旦互惠关系成功建立，这种利益随后可以减少到有利于植物。经验数据与理论预测的一致性表明模型的可靠性。这些结果强调了种内竞争和寄主植物与共生体之间的利益不对称程度在稳定共生关系中的作用。

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引用次数: 0

Threshold behavior of a social norm in response to error proneness 社会规范对错误倾向反应的阈值行为。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2026-01-21 Epub Date: 2025-11-04 DOI: 10.1016/j.jtbi.2025.112305

Quang Anh Le , Seung Ki Baek

A social norm defines what is good and what is bad in social contexts, as well as what to do based on such assessments. A stable social norm should be maintained against errors committed by its players. In addition, individuals may have different probabilities of errors in following the norm, and a social norm would be unstable if it benefited those who do not follow the norm carefully. In this work, we show that Simple Standing, which has been known to resist errors and mutants successfully, actually exhibits threshold behavior. That is, in a population of individuals playing the donation game according to Simple Standing, the residents can suppress the invasion of mutants with higher error proneness only if the residents’ own error proneness is sufficiently low. Otherwise, the population will be invaded by mutants that commit assessment errors more frequently, and a series of such invasions will eventually undermine the existing social norm. This study suggests that the stability analysis of a social norm may have a different picture if the probability of error itself is regarded as an individual attribute.

社会规范定义了在社会环境中什么是好的，什么是坏的，以及在这种评估的基础上应该做什么。应该维持稳定的社会规范，防止参与者犯下错误。此外，个体在遵循规范时可能会有不同的错误概率，如果一种社会规范有利于那些不认真遵守规范的人，那么它就会不稳定。在这项工作中，我们证明了简单站立，它已经被认为可以成功地抵抗错误和突变，实际上表现出阈值行为。即在进行简单站立捐赠博弈的个体群体中，只有当居民自身的错误倾向足够低时，居民才能抑制高错误倾向突变体的入侵。否则，种群将被更频繁地犯评估错误的突变体入侵，而一系列这样的入侵最终将破坏现有的社会规范。这项研究表明，如果错误概率本身被视为个体属性，那么对社会规范的稳定性分析可能会有不同的结果。

引用次数: 0

Human papillomavirus driving cervical cancer: A mathematical model with persistent infection, cancer progression, and spontaneous remission 人乳头瘤病毒驱动子宫颈癌：持续感染、癌症进展和自发缓解的数学模型。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2026-01-21 Epub Date: 2025-10-06 DOI: 10.1016/j.jtbi.2025.112289

Rena Hayashi , Akane Hara , Yoh Iwasa

Human papillomavirus (HPV), a DNA virus, causes cervical cancer, which is the most common cancer among Japanese women in their forties. Upon infection, HPV temporarily proliferates but is usually eliminated by the immune system. However, if the virus enters the nuclei of epithelial cells, it can evade immune detection and establish a persistent infection. In this state, HPV inhibits apoptosis and allows genomic mutations to accumulate. Over many years, this can lead to dysplasia, genetic abnormalities, and eventually, invasive cancer with metastasis. While many individuals with persistent HPV infections experience spontaneous remission, a small proportion develop cervical cancer. In this study, we aim to understand the sharp contrast between cervical cancer and other solid tumors (cancers of epithelial tissues). We analyze a mathematical model for stochastic transitions between infection states, where the likelihood of persistent infection is proportional to the cumulative viral load, influenced by viral dynamics, immune effectors, and immune memory. We derive formulas for total cancer incidence, mean age at diagnosis, and age variance. Key parameters were estimated from data using the MCMC method. We conclude that major characteristics of cervical cancer arise from the strong age-dependence of viral genome incorporated into the epithelial tissue — shaped by the human sexual behavior — and from the very high rate of spontaneous remission.

人类乳头瘤病毒（HPV）是一种DNA病毒，它会导致宫颈癌，这是日本40多岁女性中最常见的癌症。感染后，HPV会暂时增殖，但通常会被免疫系统消除。然而，如果病毒进入上皮细胞的细胞核，它可以逃避免疫检测并建立持续感染。在这种状态下，HPV抑制细胞凋亡并允许基因组突变积累。多年来，这可能导致发育不良、遗传异常，并最终导致转移的侵袭性癌症。虽然许多持续HPV感染的个体会自发缓解，但一小部分会发展为宫颈癌。在本研究中，我们旨在了解宫颈癌与其他实体瘤（上皮组织癌）之间的鲜明对比。我们分析了感染状态之间随机转换的数学模型，其中持续感染的可能性与累积病毒载量成正比，受病毒动力学，免疫效应器和免疫记忆的影响。我们推导出癌症总发病率、平均诊断年龄和年龄方差的公式。利用MCMC方法从数据中估计关键参数。我们得出结论，宫颈癌的主要特征源于病毒基因组合并到上皮组织的强烈年龄依赖性——由人类性行为形成——以及非常高的自发缓解率。

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引用次数: 0

The effect of oxidative stress on the leading edge of the a-wave in retinitis pigmentosa 氧化应激对视网膜色素变性a波前缘的影响。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2026-01-21 Epub Date: 2025-10-30 DOI: 10.1016/j.jtbi.2025.112306

Deepak K Pattanaik , Nachieketa K Sharma , Vasudevan Lakshminarayanan

Background

The development of an oxidative stress model has been used to explain the decrease in the ERG’s a-wave amplitude in the presence of iron ions. Reactive oxygen species (ROS), which are produced by iron ions, are thought to reduce photoreceptor hyperpolarization. In Retinitis Pigmentosa (RP), oxygen builds up inside the cells of the rods, where superoxide radicals are produced. This provides an explanation for the decrease in scotopic a-wave amplitude in RP patients.

Methods

The oxidative stress model is applied here since oxygen buildup produces ROS (superoxide radicals) that are comparable to those produced by iron ions. The loss of rod photoreceptors is a further consequence of ROS. A component denoting the fraction of rods present is incorporated into the formula for the a-wave voltage to account for the effect of rod deaths on amplitude.

Results

The ROS generated in RP eyes were able to draw calcium ions, increasing the calcium influx. The voltage vs. time graph can be determined with the aid of a factor that represents the percentage of rods present. The loss of rod photoreceptors and calcium ions both result in a decrease in the amplitude of the a-wave at any time t. The theoretical results compare well with experimental results.

Conclusion

Due to oxidative stress, which causes rod photoreceptors to die and cause tunnel vision and peripheral visual field loss, the decline in scotopic a-wave amplitude in RP patients’ eyes is explained.

背景：氧化应激模型的发展已被用来解释铁离子存在时ERG a波振幅的下降。由铁离子产生的活性氧（ROS）被认为可以减少光感受器的超极化。在色素性视网膜炎（RP）中，氧在杆状细胞内积聚，在那里产生超氧自由基。这解释了RP患者暗位a波振幅降低的原因。方法：氧化应激模型被应用于这里，因为氧的积累产生ROS（超氧自由基），与铁离子产生的ROS相当。杆状光感受器的丧失是ROS的另一个后果。表示存在棒的分数的分量被纳入A波电压的公式中，以说明棒的死亡对振幅的影响。结果：RP眼产生的活性氧能够吸引钙离子，增加钙的内流。电压与时间的关系图可以借助于一个表示存在的棒的百分比的因子来确定。棒状光感受器和钙离子的损失都会导致a波在任意时刻的振幅减小，理论结果与实验结果比较吻合。结论：RP患者眼部暗斑a波振幅下降的原因是氧化应激导致视杆光感受器死亡，导致隧道视觉和周围视野丧失。

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引用次数: 0

Strategic synergies: Dispersal and resource allocation in mitigating tipping cascades 战略协同效应：缓解引爆级联的分散和资源分配。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2026-01-21 Epub Date: 2025-10-14 DOI: 10.1016/j.jtbi.2025.112281

Saswati Biswas, Sudeshna Sinha

While ecosystems may experience sudden transitions to a degraded state under intensified exploitation, the impact of additional food provision in exploited patchy environments remains largely unexplored. This study investigates the trade-off between connectivity and resource allocation in mitigating tipping points that could lead to metacommunity-level population collapse. We first explore predator-prey dynamics within an isolated patch, investigating the effects of predator harvesting and additional food provision on population persistence. Our results reveal that, while additional food can rescue predators in scarcity, excessive provisioning may disrupt the trophic balance. Strategic harvesting helps mitigate this risk, but multistability across harvesting intensities complicates ecological management. Extending our analysis to a two-patch system with diffusive coupling, we find that a carefully calibrated food share ratio between patches is essential for long-term steady-state coexistence, with the required ratio modulated by coupling strength. However, beyond a critical dispersal threshold, stability can be maintained without strict adherence to a specific supply ratio. While dispersal aids in local predator rescue, higher flow can trigger a tipping point, resulting in catastrophic predator collapses across the metacommunity. Our findings reveal a potential rescue mechanism in which maintaining adequate food quality – ensuring uniformity across patches – is crucial to preventing abrupt population extinction, especially under strong connectivity. Overall, our study underscores the importance of integrating dispersal dynamics and the resource allocation mechanism in shaping ecosystem resilience, providing insight into strategies to mitigate population collapses in fragmented habitats.

在集约化开发的情况下，生态系统可能会突然过渡到退化状态，但在被开发的零散环境中增加粮食供应的影响在很大程度上仍未得到探索。本研究探讨了连接性和资源分配之间的权衡，以减轻可能导致元社区水平人口崩溃的临界点。我们首先在一个孤立的斑块内探索捕食者-猎物动态，研究捕食者捕获和额外食物供应对种群持久性的影响。我们的研究结果表明，虽然额外的食物可以在稀缺的情况下拯救捕食者，但过度供应可能会破坏营养平衡。战略性采伐有助于减轻这种风险，但采伐强度之间的多重稳定性使生态管理复杂化。将我们的分析扩展到具有扩散耦合的两个斑块系统，我们发现斑块之间精心校准的食物份额比例对于长期稳态共存至关重要，所需比例由耦合强度调节。然而，超过临界扩散阈值后，可以在不严格遵守特定供应比例的情况下保持稳定性。虽然分散有助于局部捕食者的救援，但更高的流量可能引发临界点，导致整个元群落的灾难性捕食者崩溃。我们的发现揭示了一种潜在的救援机制，在这种机制中，保持足够的食物质量——确保各个斑块的均匀性——对于防止种群突然灭绝至关重要，尤其是在强连通性的情况下。总体而言，我们的研究强调了整合分散动力学和资源分配机制在塑造生态系统恢复力方面的重要性，为减轻碎片化栖息地中种群崩溃的策略提供了见解。

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引用次数: 0

Antigenic cooperation in viral populations: Maximal load on viruses and self-sufficiency of persistent viruses 病毒群体中的抗原合作：病毒的最大负荷和持久性病毒的自给自足。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2026-01-21 Epub Date: 2025-10-14 DOI: 10.1016/j.jtbi.2025.112282

Leonid Bunimovich , Athulya Ram

The paper continues the study of the phenomenon of local immunodeficiency in viral cross-immunoreactivity networks, with a focus on the roles and interactions between central and persistent viral variants. As usual, only the state of stable (i.e. observable) local immunodeficiency is analyzed. First, we show that a single central viral variant has an upper limit for the number of persistent viral variants that it can support. Our findings reveal that in viral cross-immunoreactivity networks, central viruses act essentially autonomously from each other. Namely, connections between central viruses change neither their qualitative roles nor the quantitative values of the strengths of their connections in the cross-immunoreactivity networks. In other words, each central virus does exactly the same actions, and has the same strengths with or without specific structural features such as central viruses. This indicates that local immunodeficiency can arise purely from the network structure. However, having more central viruses allows to keep the sizes of populations of persistent viruses at higher levels. Likewise, the strength of the immune response against any central virus remains at the same constant level regardless of how many persistent viruses this central virus supports (i.e. shields from the immune response of the host’s immune system). It is also shown that viruses strongly compete with each other in order to become persistent in the state of stable local immunodeficiency. We also present an (quite unexpected) example of a cross-immunoreactivity network with stable local immunodeficiency that only consists of persistent viral variants, which shows that persistent viruses may demonstrate a kind of self-consistency.

本文继续研究病毒交叉免疫反应网络中的局部免疫缺陷现象，重点关注中心型和持续性病毒变体之间的作用和相互作用。通常，只分析稳定的（即可观察的）局部免疫缺陷状态。首先，我们证明了一个单一的中心病毒变体对它所能支持的持续病毒变体的数量有上限。我们的研究结果表明，在病毒交叉免疫反应网络中，中心病毒基本上是相互自主地起作用的。也就是说，中心病毒之间的连接既不会改变它们的定性作用，也不会改变它们在交叉免疫反应性网络中连接强度的定量值。换句话说，每个中心病毒都有完全相同的行为，并且有或没有特定的结构特征（如中心病毒）具有相同的强度。这表明局部免疫缺陷可能纯粹由网络结构引起。然而，拥有更多的中心病毒可以使持久性病毒的种群规模保持在较高的水平。同样，对任何中心病毒的免疫反应强度保持在相同的恒定水平，无论该中心病毒支持多少持久性病毒（即屏蔽宿主免疫系统的免疫反应）。研究还表明，病毒之间存在着激烈的竞争，以维持稳定的局部免疫缺陷状态。我们还提出了一个（相当出乎意料的）具有稳定局部免疫缺陷的交叉免疫反应网络的例子，该网络仅由持久性病毒变体组成，这表明持久性病毒可能表现出一种自我一致性。

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引用次数: 0

Evolution of hunting efficiency of predator and hiding efficiency of prey in a stage-structured prey-predator model 阶段结构捕食者-捕食者模型中捕食效率和猎物隐藏效率的演化。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2026-01-21 Epub Date: 2025-10-31 DOI: 10.1016/j.jtbi.2025.112302

Santana Mondal , Ludek Berec , Subhas Khajanchi

The predator-prey interaction is likely the most studied relationship in ecology. Predator consumption rate is modulated by more efficient hunting of prey by predators or, conversely, by more efficient hiding from predators by prey. Here, we study predator and prey adaptations in these traits using a common modeling framework, consisting of juvenile prey, adult prey, and an unstructured predator. What distinguishes the cases with predator and prey adaptations is the trade-offs. While more efficient predator hunting is assumed to be negatively correlated to its mortality rate (hunting trade-off), more efficient prey hiding is assumed to reduce prey reproduction (hiding trade-off). Natural selection benefits predators with high hunting efficiency if the hunting trade-off is strongly concave. For prey hiding efficiency, concave trade-offs give rise to a continuously stable strategy, whereas evolutionary branching is observed for convex trade-offs. In the latter case, the distance separating two branches on the evolutionary tree grows with increasing prey maturation rate; one branch eventually develops toward maximal hiding efficiency and minimal reproduction rate, while the other branch evolves towards minimal hiding efficiency and maximal reproduction rate. The concave trade-off thus serves a dual function in prey and predator evolution. For prey-hiding evolution, it increases prey protection. For predator-hunting evolution, it decreases hunting efficiency and thus promotes prey protection, too. Thus, the trade-off form proves to be a crucial determinant of evolutionary outcomes.

捕食者-猎物的相互作用可能是生态学中研究最多的关系。捕食者更有效地捕食猎物，或者相反，猎物更有效地躲避捕食者，会调节捕食者的消耗率。在这里，我们使用一个共同的模型框架来研究捕食者和猎物在这些特征中的适应性，该模型框架由幼年猎物、成年猎物和非结构化捕食者组成。捕食者和猎物适应的区别在于权衡。虽然更有效的捕食者被认为与其死亡率呈负相关（狩猎权衡），但更有效的猎物隐藏被认为可以减少猎物繁殖（隐藏权衡）。自然选择有利于捕猎效率高的捕食者，如果狩猎权衡是强凹的。对于猎物隐藏效率而言，凹形权衡会产生连续稳定的策略，而凸形权衡则会产生进化分支。在后一种情况下，进化树上两个分支之间的距离随着猎物成熟率的增加而增加；一个分支最终向最大隐藏效率和最小繁殖率发展，而另一个分支向最小隐藏效率和最大繁殖率发展。因此，凹形权衡在猎物和捕食者的进化中起着双重作用。对于隐藏猎物的进化，它增加了对猎物的保护。对于捕食进化来说，它降低了捕猎效率，从而也促进了猎物的保护。因此，权衡形式被证明是进化结果的关键决定因素。

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引用次数: 0

Mathematical models for the EP2 and EP4 signaling pathways and their crosstalk EP2和EP4信号通路及其串扰的数学模型。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2026-01-21 Epub Date: 2025-10-15 DOI: 10.1016/j.jtbi.2025.112287

Alessandra Cambi , Diane S. Lidke , Mariya Ptashnyk , Willemijn Smit , Stefanie Sonner

G protein-coupled receptors EP2 and EP4 are both activated by the lipid messenger Prostaglandin E2 (PGE2) and induce the intracellular production of cyclic AMP (cAMP), ultimately affecting gene expression. Changes in cellular responses to PGE2 can have important consequences on immunity and disease, yet a detailed understanding of the EP2-EP4 signaling network is lacking. EP2 and EP4 are often co-expressed in cells but their specific contribution to cAMP production is poorly understood. Experimental data have shown that cAMP levels differ depending on whether PGE2 triggers EP2 or EP4, or both. To better understand the underlying mechanisms and predict cellular responses to PGE2, we developed mathematical models for EP2 and EP4 cAMP signaling, including receptor crosstalk. The mathematical models qualitatively reproduce the experimentally observed cAMP levels and provide mechanistic insight into both the differences and commonalities in EP2/EP4 signaling. We found that ligand binding dynamics play a crucial role for both single-receptor signaling and inter-receptor crosstalk. Inhibition of PGE2 signaling via receptor antagonists is gaining increasing attention in tumor immunology. These mathematical models could therefore contribute to the design of more effective anti-tumor therapies targeting EP2 and EP4.

G蛋白偶联受体EP2和EP4均被脂质信使前列腺素E2 （PGE2）激活，诱导细胞内产生环AMP (cAMP)，最终影响基因表达。细胞对PGE2反应的改变可能对免疫和疾病产生重要影响，但对EP2-EP4信号网络的详细了解尚缺乏。EP2和EP4通常在细胞中共表达，但它们对cAMP产生的具体贡献尚不清楚。实验数据表明，cAMP水平的不同取决于PGE2是否触发EP2或EP4，或两者兼而有之。为了更好地理解潜在的机制并预测细胞对PGE2的反应，我们建立了EP2和EP4 cAMP信号传导的数学模型，包括受体串扰。数学模型定性地再现了实验观察到的cAMP水平，并提供了EP2/EP4信号传导差异和共性的机制见解。我们发现配体结合动力学在单受体信号传导和受体间串扰中起着至关重要的作用。通过受体拮抗剂抑制PGE2信号在肿瘤免疫学中越来越受到关注。因此，这些数学模型有助于设计更有效的针对EP2和EP4的抗肿瘤疗法。

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引用次数: 0