Cell-based mechanical models, such as the Cell Vertex Model (CVM), have proven useful for studying the mechanical control of epithelial tissue dynamics. We recently developed a statistical method called image-based parameter inference for formulating CVM model functions and estimating their parameters from image data of epithelial tissues. In this study, we employed Bayesian statistics to improve the utility and flexibility of image-based parameter inference. Tests on synthetic data confirmed that both our non-hierarchical and hierarchical Bayesian models provide accurate estimates of model parameters. By applying this method to Drosophila wings, we demonstrated that the reliability of parameter estimation is closely linked to the mechanical anisotropies present in the tissue. Moreover, we revealed that the cortical elasticity term is dispensable for explaining force-shape correlations in vivo. We anticipate that the flexibility of the Bayesian statistical framework will facilitate the integration of various types of information, thereby contributing to the quantitative dissection of the mechanical control of tissue dynamics.
{"title":"Bayesian parameter inference for epithelial mechanics","authors":"Xin Yan , Goshi Ogita , Shuji Ishihara , Kaoru Sugimura","doi":"10.1016/j.jtbi.2024.111960","DOIUrl":"10.1016/j.jtbi.2024.111960","url":null,"abstract":"<div><div>Cell-based mechanical models, such as the Cell Vertex Model (CVM), have proven useful for studying the mechanical control of epithelial tissue dynamics. We recently developed a statistical method called image-based parameter inference for formulating CVM model functions and estimating their parameters from image data of epithelial tissues. In this study, we employed Bayesian statistics to improve the utility and flexibility of image-based parameter inference. Tests on synthetic data confirmed that both our non-hierarchical and hierarchical Bayesian models provide accurate estimates of model parameters. By applying this method to <em>Drosophila</em> wings, we demonstrated that the reliability of parameter estimation is closely linked to the mechanical anisotropies present in the tissue. Moreover, we revealed that the cortical elasticity term is dispensable for explaining force-shape correlations <em>in vivo</em>. We anticipate that the flexibility of the Bayesian statistical framework will facilitate the integration of various types of information, thereby contributing to the quantitative dissection of the mechanical control of tissue dynamics.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111960"},"PeriodicalIF":1.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.jtbi.2024.111963
Mossa Merhi Reimert, Maya Katrin Gussmann, Anette Ella Boklund, Matt Denwood
Disease modelling at the livestock-wildlife interface is an important topic for which discrete-space models are used for the wildlife component. One prominent example is African Swine Fever, where wild boar play an influential role as reservoirs of disease spillover into domestic pig farms. In this paper, we present a simulation study that demonstrates the impact of seemingly arbitrary choices of landscape discretisation method on the inferred rate of spread within the model. We use an ordinary differential equation model to implement a simplified model of disease transmission between discrete groups of wild boar with spillover into domestic pig farms contained within a homogeneous landscape. We examine a range of scenarios whereby the landscape is discretised into wild boar patches of varying size and shape, and compare the rate of spread between domestic pig farms placed at fixed points on the landscape. Our results demonstrate a non-monotonic relationship between patch size and rate of spread, which is particularly unstable and unpredictable for square and triangular shaped patches. Discretisation of the landscape into hexagons appears to produce a more stable relationship between patch size and rate of spread for the three types of transmission kernel we investigated. Although the rate of disease spread does converge to a stable value, this occurs at patch sizes that are much smaller than would be used in practice for wild boar. We conclude that outputs of disease models containing a wildlife component should not be considered to be robust to arbitrary choices for patch size and placement, but rather as a source of uncertainty to be examined using sensitivity analysis. Furthermore, we strongly recommend the use of hexagons rather than squares or right triangles for landscape discretisation.
{"title":"Choice of landscape discretisation method affects the inferred rate of spread in wildlife disease spread models","authors":"Mossa Merhi Reimert, Maya Katrin Gussmann, Anette Ella Boklund, Matt Denwood","doi":"10.1016/j.jtbi.2024.111963","DOIUrl":"10.1016/j.jtbi.2024.111963","url":null,"abstract":"<div><div>Disease modelling at the livestock-wildlife interface is an important topic for which discrete-space models are used for the wildlife component. One prominent example is African Swine Fever, where wild boar play an influential role as reservoirs of disease spillover into domestic pig farms. In this paper, we present a simulation study that demonstrates the impact of seemingly arbitrary choices of landscape discretisation method on the inferred rate of spread within the model. We use an ordinary differential equation model to implement a simplified model of disease transmission between discrete groups of wild boar with spillover into domestic pig farms contained within a homogeneous landscape. We examine a range of scenarios whereby the landscape is discretised into wild boar patches of varying size and shape, and compare the rate of spread between domestic pig farms placed at fixed points on the landscape. Our results demonstrate a non-monotonic relationship between patch size and rate of spread, which is particularly unstable and unpredictable for square and triangular shaped patches. Discretisation of the landscape into hexagons appears to produce a more stable relationship between patch size and rate of spread for the three types of transmission kernel we investigated. Although the rate of disease spread does converge to a stable value, this occurs at patch sizes that are much smaller than would be used in practice for wild boar. We conclude that outputs of disease models containing a wildlife component should not be considered to be robust to arbitrary choices for patch size and placement, but rather as a source of uncertainty to be examined using sensitivity analysis. Furthermore, we strongly recommend the use of hexagons rather than squares or right triangles for landscape discretisation.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"596 ","pages":"Article 111963"},"PeriodicalIF":1.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.jtbi.2024.111964
Junyuan Yang , Xinyi Duan , Guiquan Sun
Most of epidemic models assume that duration of the disease phase is distributed exponentially for the simplification of model formulation and analysis. Actually, the exponentially distributed assumption on the description of disease stages is hard to accurately approximate the interplay of drug concentration and viral load within host. In this article, we formulate an immuno-epidemiological epidemic model on complex networks, which is composed of ordinary differential equations and integral equations. The linkage of within- and between-host is connected by setting that the death caused by the disease is an increasing function in viral load within host. Mathematical analysis of the model includes the existence of the solution to the epidemiological model on complex networks, the existence and stability of equilibrium, which are completely determined by the basic reproduction number of the between-host system. Numerical analysis are shown that the non-exponentially distributions and the topology of networks have significant roles in the prediction of epidemic patterns.
{"title":"An immuno-epidemiological model with non-exponentially distributed disease stage on complex networks","authors":"Junyuan Yang , Xinyi Duan , Guiquan Sun","doi":"10.1016/j.jtbi.2024.111964","DOIUrl":"10.1016/j.jtbi.2024.111964","url":null,"abstract":"<div><div>Most of epidemic models assume that duration of the disease phase is distributed exponentially for the simplification of model formulation and analysis. Actually, the exponentially distributed assumption on the description of disease stages is hard to accurately approximate the interplay of drug concentration and viral load within host. In this article, we formulate an immuno-epidemiological epidemic model on complex networks, which is composed of ordinary differential equations and integral equations. The linkage of within- and between-host is connected by setting that the death caused by the disease is an increasing function in viral load within host. Mathematical analysis of the model includes the existence of the solution to the epidemiological model on complex networks, the existence and stability of equilibrium, which are completely determined by the basic reproduction number of the between-host system. Numerical analysis are shown that the non-exponentially distributions and the topology of networks have significant roles in the prediction of epidemic patterns.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111964"},"PeriodicalIF":1.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401942","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}
Pub Date : 2024-10-09DOI: 10.1016/j.jtbi.2024.111962
Boris P. Belotserkovskii, Philip C. Hanawalt
R-loops are structures containing an RNA-DNA duplex and an unpaired DNA strand. During R-loop formation an RNA strand invades the DNA duplex, displacing the homologous DNA strand and binding the complementary DNA strand. Here we analyze a model for transcription-dependent R-loop formation at double-stranded DNA breaks (DSBs). In this model, R-loop formation is preceded by detachment of the non-template DNA strand from the RNA polymerase (RNAP). Then, strand exchange is initiated between the nascent RNA and the non-template DNA strand. During that strand exchange the length of the R-loop could either increase, or decrease in a biased random-walk fashion, in which the bias would depend upon the DNA sequence. Eventually, the restoration of the DNA duplex would completely displace the RNA. However, as long as the RNAP remains bound to the template DNA strand it prevents that displacement. Thus, according to the model, RNAPs stalled at DSBs can increase the lifespan of R-loops, increasing their detectability in experiments, and perhaps enhancing their biological effects.
R 环是包含 RNA-DNA 双链和未配对 DNA 链的结构。在 R 环形成过程中，RNA 链侵入 DNA 双链，取代同源 DNA 链并结合互补 DNA 链。在这里，我们分析了双链DNA断裂（DSB）处依赖转录的R环形成模型。在该模型中，R 环形成之前，非模板 DNA 链会从 RNA 聚合酶（RNAP）上分离。然后，新生 RNA 和非模板 DNA 链之间开始进行链交换。在链交换过程中，R 环的长度可能会增加，也可能会以有偏差的随机漫步方式减少，而偏差取决于 DNA 序列。最终，DNA 双链的恢复将完全取代 RNA。但是，只要 RNAP 仍与模板 DNA 链结合，就会阻止这种位移。因此，根据该模型，停滞在 DSB 上的 RNAP 可以延长 R 环的寿命，提高它们在实验中的可检测性，或许还能增强它们的生物效应。
{"title":"A model for transcription-dependent R-loop formation at double-stranded DNA breaks: Implications for their detection and biological effects","authors":"Boris P. Belotserkovskii, Philip C. Hanawalt","doi":"10.1016/j.jtbi.2024.111962","DOIUrl":"10.1016/j.jtbi.2024.111962","url":null,"abstract":"<div><div>R-loops are structures containing an RNA-DNA duplex and an unpaired DNA strand. During R-loop formation an RNA strand invades the DNA duplex, displacing the homologous DNA strand and binding the complementary DNA strand. Here we analyze a model for transcription-dependent R-loop formation at double-stranded DNA breaks (DSBs). In this model, R-loop formation is preceded by detachment of the non-template DNA strand from the RNA polymerase (RNAP). Then, strand exchange is initiated between the nascent RNA and the non-template DNA strand. During that strand exchange the length of the R-loop could either increase, or decrease in a biased random-walk fashion, in which the bias would depend upon the DNA sequence. Eventually, the restoration of the DNA duplex would completely displace the RNA. However, as long as the RNAP remains bound to the template DNA strand it prevents that displacement. Thus, according to the model, RNAPs stalled at DSBs can increase the lifespan of R-loops, increasing their detectability in experiments, and perhaps enhancing their biological effects.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111962"},"PeriodicalIF":1.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395390","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}
Pub Date : 2024-10-05DOI: 10.1016/j.jtbi.2024.111957
Federica Padovano , Chiara Villa
We present a mathematical model of the evolutionary dynamics of a metastatic tumour under chemotherapy, comprising non-local partial differential equations for the phenotype-structured cell populations in the primary tumour and its metastasis. These equations are coupled with a physiologically-based pharmacokinetic model of drug administration and distribution, implementing a realistic delivery schedule. The model is carefully calibrated from the literature, focusing on BRAF-mutated melanoma treated with Dabrafenib as a case study. By means of long-time asymptotic and global sensitivity analyses, as well as numerical simulations, we explore the impact of cell migration from the primary to the metastatic site, physiological aspects of the tumour tissues and drug dose on the development of chemoresistance and treatment efficacy. Our findings provide a possible explanation for empirical evidence indicating that chemotherapy may foster metastatic spread and that metastases may be less impacted by the chemotherapeutic agent.
{"title":"The development of drug resistance in metastatic tumours under chemotherapy: An evolutionary perspective","authors":"Federica Padovano , Chiara Villa","doi":"10.1016/j.jtbi.2024.111957","DOIUrl":"10.1016/j.jtbi.2024.111957","url":null,"abstract":"<div><div>We present a mathematical model of the evolutionary dynamics of a metastatic tumour under chemotherapy, comprising non-local partial differential equations for the phenotype-structured cell populations in the primary tumour and its metastasis. These equations are coupled with a physiologically-based pharmacokinetic model of drug administration and distribution, implementing a realistic delivery schedule. The model is carefully calibrated from the literature, focusing on BRAF-mutated melanoma treated with Dabrafenib as a case study. By means of long-time asymptotic and global sensitivity analyses, as well as numerical simulations, we explore the impact of cell migration from the primary to the metastatic site, physiological aspects of the tumour tissues and drug dose on the development of chemoresistance and treatment efficacy. Our findings provide a possible explanation for empirical evidence indicating that chemotherapy may foster metastatic spread and that metastases may be less impacted by the chemotherapeutic agent.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111957"},"PeriodicalIF":1.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382450","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}
Pub Date : 2024-10-03DOI: 10.1016/j.jtbi.2024.111961
Paul Georgescu , Hong Zhang
We further pursue an investigation on an abstract model characterizing the dynamics of a general class of -species facultative mutualisms that was initiated in Georgescu et al. (2017), establishing biologically relevant sufficient conditions for the global asymptotic stability of the coexistence equilibria. These conditions are given in terms of per-species limits of growth-to-loss ratios computed at higher population densities, complemented by either monotonicity or sublinearity inequalities, and are observed to hold for -species versions of mutualistic models in current use. The specific modeling details that require either of these conditions being satisfied are outlined and discussed. As mutualisms can enhance species diversification and facilitate stable coexistence via a plethora of mechanisms, it is then important to understand the stability of speciose mutualisms, our results being of potential interest to theoretical ecologists studying the coexistence of many interacting species and to conservationists aiming for rare species preservation.
我们进一步研究了一个抽象模型，该模型描述了 Georgescu 等人（2017 年）提出的一般 n 种亲缘互惠关系的动态特征，为共存均衡的全局渐进稳定性建立了生物学相关的充分条件。这些条件是以在较高种群密度下计算的每物种生长-损失比的极限值给出的，并辅以单调性或亚线性不等式，据观察，这些条件在目前使用的 n 种互生模型中都是成立的。本文概述并讨论了需要满足上述任一条件的具体建模细节。由于互惠关系可以通过多种机制提高物种多样性并促进稳定共存，因此了解物种互惠关系的稳定性非常重要，我们的研究结果对于研究多种相互作用物种共存的理论生态学家和旨在保护稀有物种的保护主义者具有潜在的意义。
{"title":"Global stability of coexistence equilibria for n-species models of facultative mutualism","authors":"Paul Georgescu , Hong Zhang","doi":"10.1016/j.jtbi.2024.111961","DOIUrl":"10.1016/j.jtbi.2024.111961","url":null,"abstract":"<div><div>We further pursue an investigation on an abstract model characterizing the dynamics of a general class of <span><math><mi>n</mi></math></span>-species facultative mutualisms that was initiated in Georgescu et al. (2017), establishing biologically relevant sufficient conditions for the global asymptotic stability of the coexistence equilibria. These conditions are given in terms of per-species limits of growth-to-loss ratios computed at higher population densities, complemented by either monotonicity or sublinearity inequalities, and are observed to hold for <span><math><mi>n</mi></math></span>-species versions of mutualistic models in current use. The specific modeling details that require either of these conditions being satisfied are outlined and discussed. As mutualisms can enhance species diversification and facilitate stable coexistence via a plethora of mechanisms, it is then important to understand the stability of speciose mutualisms, our results being of potential interest to theoretical ecologists studying the coexistence of many interacting species and to conservationists aiming for rare species preservation.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111961"},"PeriodicalIF":1.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378625","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}
Pub Date : 2024-10-02DOI: 10.1016/j.jtbi.2024.111959
Nishnath Polavarapu , Madison Doty , Hana M. Dobrovolny
SARS-CoV-2 caused a global pandemic and is now an endemic virus that will require continued antiviral and vaccine development. A possible new treatment modality was recently suggested that would use vesicular stomatitis virus (VSV) modified to express the ACE2 receptor. Since the modified VSV expresses the cell surface receptor that is used by the SARS-CoV-2 spike protein, the thought is that SARS-CoV-2 virions would bind to the modified VSV and thus be neutralized. Additionally, since SARS-CoV-2 infected cells also express the spike protein, the modified VSV could potentially infect these cells, allowing for its own replication, but also potentially interfering with replication of SARS-CoV-2. This idea has not yet been tested experimentally, but we can investigate the feasibility of this possible treatment theoretically. In this manuscript, we develop a mathematical model of this suggested treatment and explore conditions under which it might be effective. We find that treatment with modified VSV does little to change the SARS-CoV-2 time course except when the treatment is applied at the onset of the SARS-CoV-2 infection at very high doses. In this case, VSV reduces the peak SARS-CoV-2 viral load, but lengthens the duration of the SARS-CoV-2 infection. Thus, we find that modified VSV treatment is unlikely to be effective largely because it does not prevent infection of cells by SARS-CoV-2.
{"title":"Exploring the treatment of SARS-CoV-2 with modified vesicular stomatitis virus","authors":"Nishnath Polavarapu , Madison Doty , Hana M. Dobrovolny","doi":"10.1016/j.jtbi.2024.111959","DOIUrl":"10.1016/j.jtbi.2024.111959","url":null,"abstract":"<div><div>SARS-CoV-2 caused a global pandemic and is now an endemic virus that will require continued antiviral and vaccine development. A possible new treatment modality was recently suggested that would use vesicular stomatitis virus (VSV) modified to express the ACE2 receptor. Since the modified VSV expresses the cell surface receptor that is used by the SARS-CoV-2 spike protein, the thought is that SARS-CoV-2 virions would bind to the modified VSV and thus be neutralized. Additionally, since SARS-CoV-2 infected cells also express the spike protein, the modified VSV could potentially infect these cells, allowing for its own replication, but also potentially interfering with replication of SARS-CoV-2. This idea has not yet been tested experimentally, but we can investigate the feasibility of this possible treatment theoretically. In this manuscript, we develop a mathematical model of this suggested treatment and explore conditions under which it might be effective. We find that treatment with modified VSV does little to change the SARS-CoV-2 time course except when the treatment is applied at the onset of the SARS-CoV-2 infection at very high doses. In this case, VSV reduces the peak SARS-CoV-2 viral load, but lengthens the duration of the SARS-CoV-2 infection. Thus, we find that modified VSV treatment is unlikely to be effective largely because it does not prevent infection of cells by SARS-CoV-2.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111959"},"PeriodicalIF":1.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376324","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}
Pub Date : 2024-10-01DOI: 10.1016/j.jtbi.2024.111958
Christopher W. Rodriguez, Peter W. Reddien
Although demographic studies have failed to find evidence of aging in certain animal species, classic evolutionary theories of aging struggle to explain how evolution could favor agelessness in such cases. Here, we develop mathematical models of the disposable soma theory to identify conditions in which agelessness would be evolutionarily favored. For any given type of damage that could accumulate and cause age-accelerating mortality risk, we find that evolution could select for its complete removal if the mortality risk it poses is severe enough and its repair does not pose too large of a penalty to reproduction. Environmental factors such as extrinsic mortality and the form of population density-dependent regulation also play a large role in determining the optimal rate of aging and whether agelessness should be evolutionarily favored. However, in a system with multiple sources of damage and multiple independent repair processes, avoiding aging is rarely evolutionarily favorable. Pleiotropic repair processes, such as those that could be present in asexual fissioning organisms, make agelessness more likely but do not guarantee it. Our results indicate that agelessness could be favored by evolution in narrow contexts but that multiple types of damage and repair make agelessness unlikely to arise in sufficiently complex organisms.
{"title":"Agelessness is possible under the disposable soma theory but system complexity makes it unlikely","authors":"Christopher W. Rodriguez, Peter W. Reddien","doi":"10.1016/j.jtbi.2024.111958","DOIUrl":"10.1016/j.jtbi.2024.111958","url":null,"abstract":"<div><div>Although demographic studies have failed to find evidence of aging in certain animal species, classic evolutionary theories of aging struggle to explain how evolution could favor agelessness in such cases. Here, we develop mathematical models of the disposable soma theory to identify conditions in which agelessness would be evolutionarily favored. For any given type of damage that could accumulate and cause age-accelerating mortality risk, we find that evolution could select for its complete removal if the mortality risk it poses is severe enough and its repair does not pose too large of a penalty to reproduction. Environmental factors such as extrinsic mortality and the form of population density-dependent regulation also play a large role in determining the optimal rate of aging and whether agelessness should be evolutionarily favored. However, in a system with multiple sources of damage and multiple independent repair processes, avoiding aging is rarely evolutionarily favorable. Pleiotropic repair processes, such as those that could be present in asexual fissioning organisms, make agelessness more likely but do not guarantee it. Our results indicate that agelessness could be favored by evolution in narrow contexts but that multiple types of damage and repair make agelessness unlikely to arise in sufficiently complex organisms.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111958"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1016/j.jtbi.2024.111953
J. Innerarity Imizcoz , W. Djema , F. Mairet , J.-L. Gouzé
Although microorganisms often live in dynamic environments, most studies, both experimental and theoretical, are carried out under static conditions. In this work, we investigate the issue of optimal resource allocation in bacteria growing in periodic environments. We consider a dynamic model describing the microbial metabolism under varying conditions, involving a control variable quantifying the protein precursors allocation. Our objective is to determine the optimal strategies maximizing the long-term growth of cells under a piecewise-constant periodic environment. Firstly, we perform a theoretical analysis of the resulting optimal control problem (OCP), based on the application the Pontryagin’s Maximum Principle (PMP). We determine that the structure of the optimal control must be bang–bang, with possibly some singular arcs corresponding to optimal equilibria of the system. If the control presents singular arcs, then these can only be reached and left through chattering arcs. We also use a direct optimization method, implemented in the BOCOP software, to solve the studied OCP. Our study reveals that the optimal solution over a large time horizon is related to the one over a single period of the varying environment with periodic constraints. Moreover, we observe that the maximal average growth rate attainable under periodic conditions can be higher than the one under a constant environment. We further extend our analysis to conduct a qualitative comparison between the predictions from our model and some recent biological experiments on E. coli. This analysis particularly highlights the mechanisms of action of the ppGpp signaling molecule, thus providing relevant explanations of the experimental observations. In conclusion, our study corroborates previous research indicating that this molecule plays a crucial role in the regulation of resource allocation of protein precursors in E. coli.
{"title":"Optimal resource allocation in micro-organisms under periodic nutrient fluctuations","authors":"J. Innerarity Imizcoz , W. Djema , F. Mairet , J.-L. Gouzé","doi":"10.1016/j.jtbi.2024.111953","DOIUrl":"10.1016/j.jtbi.2024.111953","url":null,"abstract":"<div><div>Although microorganisms often live in dynamic environments, most studies, both experimental and theoretical, are carried out under static conditions. In this work, we investigate the issue of optimal resource allocation in bacteria growing in periodic environments. We consider a dynamic model describing the microbial metabolism under varying conditions, involving a control variable quantifying the protein precursors allocation. Our objective is to determine the optimal strategies maximizing the long-term growth of cells under a piecewise-constant periodic environment. Firstly, we perform a theoretical analysis of the resulting optimal control problem (OCP), based on the application the Pontryagin’s Maximum Principle (PMP). We determine that the structure of the optimal control must be bang–bang, with possibly some singular arcs corresponding to optimal equilibria of the system. If the control presents singular arcs, then these can only be reached and left through chattering arcs. We also use a direct optimization method, implemented in the <span>BOCOP</span> software, to solve the studied OCP. Our study reveals that the optimal solution over a large time horizon is related to the one over a single period of the varying environment with periodic constraints. Moreover, we observe that the maximal average growth rate attainable under periodic conditions can be higher than the one under a constant environment. We further extend our analysis to conduct a qualitative comparison between the predictions from our model and some recent biological experiments on <em>E. coli</em>. This analysis particularly highlights the mechanisms of action of the ppGpp signaling molecule, thus providing relevant explanations of the experimental observations. In conclusion, our study corroborates previous research indicating that this molecule plays a crucial role in the regulation of resource allocation of protein precursors in <em>E. coli</em>.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111953"},"PeriodicalIF":1.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-29DOI: 10.1016/j.jtbi.2024.111956
Takeshi Miki , Po-Ju Ke
Microbes in the dark oceans are a key determinant of remineralization of sinking carbon particles. However, most marine ecosystem models overlook how microbes aggregate on particles and the microscale interactions between particle-associated microbes, making it difficult to obtain mechanistic insights on their vertical power-law decay pattern. Here, we present a spatial population model where the attachment and detachment processes of bacterial cells depend on local density of particle-associated bacteria. We show that the power-law relationship can emerge when the non-random aggregated distribution of bacteria is considered without any depth-specific environmental parameters. Furthermore, the comparison between model behavior and empirical patterns in the Pacific and Southern Ocean indicated that temperature-dependent hydrolysis rate and nutrient-dependent sinking rate of particles are key parameters to explain the regional variations of the power-law exponent. The mechanistic approach developed here provides a pathway to link micro-scale interactions between individuals to macro-scale food chain structures and carbon cycle.
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