Journal of Theoretical Biology最新文献

{"title":"Optimal targeted therapy for multiple cancers based on contrastive Notch signaling networks","authors":"Tamaki Wakamoto ,&nbsp;Sungrim Seirin-Lee","doi":"10.1016/j.jtbi.2025.112143","DOIUrl":"10.1016/j.jtbi.2025.112143","url":null,"abstract":"<div><div>Over decades, cancer understanding has advanced significantly at molecular and cellular levels, leading to various therapies based on intra-/inter-cellular networks. Despite this, cancer still remains a leading cause of death globally. The Notch signaling pathway, a crucial intercellular network in many cancers, has been extensively studied and therapies targeting the Notch pathway also have been well-studied based on inhibiting various stages of Notch activation. Nonetheless, the unclear pathophysiological mechanisms of metastasis, responsible for about 90 % of cancer deaths, complicate treatment development. For example, the role of Notch signaling varies between cancers; in non-small cell lung cancer, Notch1 and Notch2 exhibit opposing effects compared to their roles in embryonal brain tumors. This suggests that a single targeted therapy to Notch signaling could produce opposing effects in the metastatic state, necessitating a more careful selection of therapies. To address this, we considered a scenario involving multiple cancers with contrasting Notch signaling pathways. We developed two mathematical models and explored optimal targeted therapies for reducing cancer cells in the metastatic state of two types of cancers with these contrasting pathways. From the <em>in silico</em> tests of existing Notch-targeted therapies and newly suggested therapies in this study, we found that multiple cancers with contrasting Notch networks can be controlled by one common targeted signal network. Furthermore, combination therapies enhancing Notch production may be most effective in early-stage cancer, whereas cleavage therapies may prove more effective in late-stage cancer. We also found that the order of multiple targeted therapies significantly affects treatment effectiveness and should be a key consideration. Our study proposes that optimal treatment should take into account the cancer stage, with careful selection and sequencing of medication therapies.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"610 ","pages":"Article 112143"},"PeriodicalIF":1.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082089","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}

{"title":"Synchronization transition in networks of Fractional-Order memristive Hindmarsh-Rose neurons","authors":"Sheida Ansarinasab ,&nbsp;Fahimeh Nazarimehr ,&nbsp;Farnaz Ghassemi ,&nbsp;Sajad Jafari","doi":"10.1016/j.jtbi.2025.112144","DOIUrl":"10.1016/j.jtbi.2025.112144","url":null,"abstract":"<div><div>Fractional-order neurons, which model memory effects in neural systems, are increasingly recognized for their importance in understanding complex neuronal dynamics. Despite extensive research on synchronization in networks of fractional-order neurons, the transition to synchronization in these networks, especially under electromagnetic radiation’s impact on neuron membranes, has been largely overlooked. This study addresses this gap by investigating synchronization transitions in small-world and scale-free networks composed of fractional-order and integer-order memristive Hindmarsh-Rose neurons. The results reveal that fractional-order neurons synchronize at smaller coupling strengths than integer-order neurons and exhibit more abrupt synchronization transitions, particularly in scale-free networks with dense connections. These findings underscore the critical role of memory effects and network topology in the emergence of synchronization behavior in neuronal networks.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"609 ","pages":"Article 112144"},"PeriodicalIF":1.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082091","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}

{"title":"Pillars of theoretical biology: ‘Mathematical models for cellular interaction in development, I and II’","authors":"Przemyslaw Prusinkiewicz","doi":"10.1016/j.jtbi.2025.112142","DOIUrl":"10.1016/j.jtbi.2025.112142","url":null,"abstract":"<div><div>This paper reviews the main idea and impact of the groundbreaking paper by Aristid Lindenmayer, ‘Mathematical models for cellular interaction in development, Parts I and II’, published in the <em>Journal of Theoretical Biology</em> <strong>18</strong>, 1968, pp. 280–299 and 300–315. The paper introduced the idea of L-systems, now the leading formalism for modeling plant development.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"609 ","pages":"Article 112142"},"PeriodicalIF":1.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071910","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}

{"title":"Network modeling of the different SARS-CoV-2 spike protein infection points within the human hematopoietic network","authors":"Marni E. Cueno ,&nbsp;Noa Shintaku ,&nbsp;Noe Hayasaki ,&nbsp;Yuna Migita ,&nbsp;Kenichi Imai","doi":"10.1016/j.jtbi.2025.112139","DOIUrl":"10.1016/j.jtbi.2025.112139","url":null,"abstract":"<div><div>Hematopoiesis is a physiological process that mainly functions in both the formation and replenishment of varying types of blood cells. SARS-CoV-2 has been reported to affect the human hematopoietic system at multiple infection points leading to multiple types of blood disorders. However, the possible effects of the different SARS-CoV-2 infection points within the hematopoietic system were never fully understood. In this study, we designed and generated multiple human hematopoietic network models representing the varying known SARS-CoV-2 infection points within the human hematopoietic system. Subsequently, centrality measurement analyses were performed to identify significant nodes and edges within the models. We putatively generated human hematopoietic network models to represent the distinct, synergistic, and integrated SARS-CoV-2 spike protein infection points within the human hematopoietic system. Additionally, we potentially established that neither the discrete nor the synergistic network models showed any changes in the human hematopoietic network, which we attributed to the conserved nature of the hematopoietic system. Furthermore, we presumably demonstrated that the integrated network model indicated that erythropoiesis and thrombopoiesis were primarily affected. Overall, we propose that an integrated network model is putatively the more accurate representation of the human hematopoietic system in the presence of SARS-CoV-2 infection involving the spike protein.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"609 ","pages":"Article 112139"},"PeriodicalIF":1.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941643","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}

{"title":"Extinctions as a vestige of instability: The geometry of stability and feasibility","authors":"Stav Marcus,&nbsp;Ari M. Turner,&nbsp;Guy Bunin","doi":"10.1016/j.jtbi.2025.112141","DOIUrl":"10.1016/j.jtbi.2025.112141","url":null,"abstract":"<div><div>Species coexistence is a complex, multifaceted problem. At an equilibrium, coexistence requires two conditions: stability under small perturbations; and feasibility, meaning all species abundances are positive. Which of these two conditions is more restrictive has been debated for many years, with many works focusing on statistical arguments for systems with many species. Within the framework of the Lotka-Volterra equations, we examine the geometry of the region of coexistence in the space of interaction strengths, for symmetric competitive interactions and any finite number of species. We consider what happens when starting at a point within the coexistence region, and changing the interaction strengths continuously until one of the two conditions breaks. We find that coexistence generically breaks through the loss of feasibility, as the abundance of one species reaches zero. An exception to this rule - where stability breaks before feasibility - happens only at isolated points, or more generally on a lower dimensional subset of the boundary.</div><div>The reason behind this is that as a stability boundary is approached, some of the abundances generally diverge towards minus infinity, and so go extinct at some earlier point, breaking the feasibility condition first. These results define a new sense in which feasibility is a more restrictive condition than stability, and show that these two requirements are closely interrelated. We then show how our results affect the changes in the set of coexisting species when interaction strengths are changed: a system of coexisting species loses a species by its abundance continuously going to zero, and this new fixed point is unique. As parameters are further changed, multiple alternative equilibria may be found. Finally, we discuss the extent to which our results apply to asymmetric interactions.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"608 ","pages":"Article 112141"},"PeriodicalIF":1.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949023","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}

{"title":"Effect of inosine on recurrence of tumor after radiation therapy: A mathematical investigation","authors":"K.S. Yadav ,&nbsp;Gopinath Sadhu","doi":"10.1016/j.jtbi.2025.112138","DOIUrl":"10.1016/j.jtbi.2025.112138","url":null,"abstract":"<div><div>Tumor invasion that marks the transition from localized growth to aggressive spread is critical in cancer biology. It involves the breakdown of surrounding tissues through matrix degradation enzymes, such as urokinase plasminogen activator and matrix metalloproteinases, to promote cancer cells migration. Understanding invasion pathways is crucial for developing effective therapies and improving patient outcomes. There is a significant progress in cancer treatments; however, the treatments such as radiotherapy and chemotherapy are ineffective many times in the sense that some cancer cells survive, leading to tumor recurrence. It has been observed that dead cells play a key role in cancer recurrence. The dead cells, particularly due to treatments like radiation or chemotherapy, release signals and cellular components, including nucleotides like inosine, cytokines, and growth factors. These factors influence the tumor microenvironment and promote the survival and proliferation of nearby cancer cells. In this article, a novel mathematical model is proposed to investigate the effects of inosine on tumor recurrence and invasion. The simulated results are in very good agreement with the experimental and numerical results of the literature. The model simulated the inosine generation after some time of radiotherapy treatment withdrawal, and it achieves a log-normal profile. In line of experimental observations, it is obtained that the cancer cells proliferate with usual proliferation but once inosine gets generated from the dead cells, the proliferation intensity of cancer cells is enhanced significantly.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"609 ","pages":"Article 112138"},"PeriodicalIF":1.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000022","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}

{"title":"Mutant emergence timing and population immunisation status impact epidemiological dynamics","authors":"Bastien Reyné ,&nbsp;Ramsès Djidjou-Demasse ,&nbsp;Mircea T. Sofonea ,&nbsp;Samuel Alizon","doi":"10.1016/j.jtbi.2025.112140","DOIUrl":"10.1016/j.jtbi.2025.112140","url":null,"abstract":"<div><div>A key question in evolutionary epidemiology is to determine differences in the conditions that may allow some mutant strains to spread in a population where a resident strain is already circulating. Evolutionary invasion analyses assume that the immunity is long-lasting for previously infected individuals making it difficult to study traits such as immune escape. We relax this last assumption and allow the environment faced by the mutant to fluctuate outside of any epidemiological equilibrium. We introduce an original two-strains non-Markovian model that accounts for realistic immunity waning and cross-immunity, inspired by the case of SARS-CoV-2 variants. We show that mutants with increased contagiousness or with some immune escape abilities are more likely to invade the population. We also show that the timing of the introduction of mutant strain in the population is key because it is associated with the population’s immunisation status. Our results underline the importance of immune waning and non-equilibrium dynamics on infectious disease evolution.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"608 ","pages":"Article 112140"},"PeriodicalIF":1.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949024","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}

{"title":"Biased tertiary sex ratios enhance the efficacy of sex-ratio distorting genetic techniques to control invasive species","authors":"Michael L. Jones ,&nbsp;Ronald E. Thresher ,&nbsp;Nicholas J. Bax","doi":"10.1016/j.jtbi.2025.112137","DOIUrl":"10.1016/j.jtbi.2025.112137","url":null,"abstract":"<div><div>Genetic biocontrol strategies are increasingly being developed and tested for reducing the effects of invasive species, and are highly likely to be an important tool of integrated pest management in the future. Included among such strategies are those that distort the sex ratio of the target species. Models used to forecast the efficacy of such strategies generally assume, implicitly, that the tertiary sex ratio of the target population is 50:50. We present evidence that this assumption is important, and that if the tertiary sex ratio is biased towards females, a sex-distorting construct introduced into the population that produces phenotypic males will become fixed at a level determined by the magnitude of the bias, even after further introductions cease. We show, first using a simple logistic population model, and second using a realistic simulation of an important aquatic invasive species – the sea lamprey<!--> <em>Petromyzon marinus</em> <!-->– how this effect can greatly increase the effectiveness of a sex-distorting construct at population suppression, but also increase the risk of such strategies due to reduced reversibility. We also present evidence that biased tertiary sex ratios might be present in many invasive species, particularly when their population sizes are low relative to environmental carrying capacity.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"608 ","pages":"Article 112137"},"PeriodicalIF":1.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943679","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}

{"title":"Quantifying the effects of intraspecific trait variation and interspecific trait correlations on interacting populations—A nonlinear averaging approach","authors":"Koen J. van Benthem ,&nbsp;Rishabh Bagawade ,&nbsp;Chantal Blüml ,&nbsp;Peter Nabutanyi ,&nbsp;Frans M. Thon ,&nbsp;Meike J. Wittmann","doi":"10.1016/j.jtbi.2025.112134","DOIUrl":"10.1016/j.jtbi.2025.112134","url":null,"abstract":"<div><div>Interactions between two species, e.g. between a predator species and a prey species, can often be described as the sum of many individual-by-individual interactions whose outcomes depend on the traits of the interacting individuals. These traits often vary substantially among individuals in each species, and individuals do not always interact randomly, e.g. due to plastic responses to a shared environmental factor in a heterogeneous landscape. Here we investigate the impact of intraspecific trait variation (ITV) and such interspecific trait correlations on species interactions via nonlinear averaging. Building on past models that integrate over an interaction kernel to obtain the impacts of ITV, we develop a theoretical framework allowing the modeling of arbitrary species interactions, with interspecific trait correlations as a novel feature. Based on two key ingredients, a joint trait distribution and a two-dimensional interaction function, the average interaction parameters (e.g. average predation rate) can be quantified numerically, approximated using an insightful Taylor approximation, and compared to cases without ITV. We highlight two applications of our framework. First, we study the quantitative and qualitative effects of ITV and trait correlations in a simple predator-prey model and show that even in the absence of evolution, variation and trait correlations among interacting individuals can make or break the coexistence between species. Second, we use simulated field data for a predator-prey system to show how the impact of ITV on an ecological interaction can be estimated from empirical data.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"609 ","pages":"Article 112134"},"PeriodicalIF":1.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026825","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}

{"title":"Unification of alpha, mu, and tau rhythms and their beta-band harmonics via eigenmodes: spectral peaks, topography, and reactivity","authors":"P.A. Robinson,&nbsp;Rawan Khalil El Zghir","doi":"10.1016/j.jtbi.2025.112136","DOIUrl":"10.1016/j.jtbi.2025.112136","url":null,"abstract":"&lt;div&gt;&lt;div&gt;&lt;em&gt;Objective:&lt;/em&gt;The alpha, mu, and tau rhythms all have frequencies of around 10 Hz in normal adult humans, with a range of 7–13 Hz. The beta rhythm, mu-associated activity, and tau-associated activity, are found at around twice those frequencies. The present objective is to use neural field theory (NFT) to explain the observed frequency structure and spatial topography, and to suggest a mechanism of reactivity, of all these rhythms in a unified way, and to predict other features not yet reported experimentally.&lt;/div&gt;&lt;div&gt;&lt;em&gt;Methods:&lt;/em&gt; NFT averages over the activity of large numbers of neurons to predict mean firing rates and EEG characteristics. It predicts the existence of natural modes of activity, each with characteristic spatial structure and frequencies. The lowest modes dominate large-scale activity and the first four are used here to predict spectra, topography, and reactivity of alpha, mu, and tau rhythms and their second harmonics, including split peaks.&lt;/div&gt;&lt;div&gt;&lt;em&gt;Results:&lt;/em&gt; Corticothalamic loop delays determine the basic &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mo&gt;∼&lt;/mo&gt;&lt;mn&gt;10&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; Hz frequency of the alpha rhythm, the &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mo&gt;∼&lt;/mo&gt;&lt;mn&gt;20&lt;/mn&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; Hz frequency of the beta rhythm, and explain their frequency correlations on an individual-subject level. Differential effects of cortical geometry on individual modes cause observed frequency splitting of the alpha and beta rhythms and we predict analogous splitting of mu and tau and their harmonics. Spatial topographies of alpha, mu, and tau are explained by modal structure, with amplitudes superposed rather than powers, and we predict that the harmonic of each rhythm will tend to have similar topography to its fundamental, although specific exceptions can occur. Similar results are obtained when modal eigenfrequencies differ sufficiently to give rise to split peaks. Dynamics of rotating patterns and wavefronts are also explained in terms of pairs of modes. Blocking or “desynchronization” of each rhythm can be accounted for by modest decreases in corticothalamic loop gains, magnified by proximity to a critical state, and we predict that fundamental and harmonic will tend to be blocked in tandem, an effect that has already been observed for alpha and beta. Paradoxically, modal analysis implies that blocking in one region can correlate with enhancement in another, which may account for the phenomenon of event-related synchronization.&lt;/div&gt;&lt;div&gt;&lt;em&gt;Conclusions:&lt;/em&gt; A unified explanation of alpha, mu, tau, and their harmonics is obtained in terms of just four corticothalamic eigenmodes. The results are consistent with a wide variety of experimental observations and experimentally testable predictions of new features are made.&lt;/div&gt;&lt;div&gt;&lt;em&gt;Significance:&lt;/em&gt; A century after the first observations of human EEG, this work explains and unifies alpha, the earliest detected rhythm, with its relatives and their harmonics to form a single family.","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"608 ","pages":"Article 112136"},"PeriodicalIF":1.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943585","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}