Pub Date : 2025-08-14DOI: 10.1016/j.jtbi.2025.112236
Andrew Francis
The rich and varied ways that genetic material can be passed between species has motivated extensive research into the theory of phylogenetic networks. Features that align with biological processes, or with desirable mathematical properties, have been used to define classes and prove results, with the goal of developing the theoretical foundations for network reconstruction methods. We may have now reached the point where a collection of recent results can be drawn together to make one class of network, the normal networks, a leading contender, sitting in the sweet spot between biological relevance and mathematical tractability.
{"title":"“Normal” phylogenetic networks may be emerging as the leading class","authors":"Andrew Francis","doi":"10.1016/j.jtbi.2025.112236","DOIUrl":"10.1016/j.jtbi.2025.112236","url":null,"abstract":"<div><div>The rich and varied ways that genetic material can be passed between species has motivated extensive research into the theory of phylogenetic networks. Features that align with biological processes, or with desirable mathematical properties, have been used to define classes and prove results, with the goal of developing the theoretical foundations for network reconstruction methods. We may have now reached the point where a collection of recent results can be drawn together to make one class of network, the <em>normal</em> networks, a leading contender, sitting in the sweet spot between biological relevance and mathematical tractability.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"614 ","pages":"Article 112236"},"PeriodicalIF":2.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862707","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 : 2025-08-10DOI: 10.1016/j.jtbi.2025.112237
George Booth , Christoforos Hadjichrysanthou , Keira L. Rice , Jacopo Frallicciardi , Zoltán Magyarics , Frank de Wolf , Jaap Goudsmit , Anna L. Beukenhorst , Roy Anderson
Introduction
Superspreading events are known to disproportionally contribute to onwards transmission of epidemic and pandemic viruses. Preventing infections in a small number of high-transmission settings is therefore an attractive public health goal.
Methods
We use deterministic and stochastic mathematical modelling to quantify the impact of intranasal sprays in containing outbreaks at a confirmed superspreading event (the 2020 SARS-CoV-2 outbreak at the Diamond Princess cruise ship) and a conference event that led to extensive transmission.
Results
In the Diamond Princess cruise ship case study, there exists a 7–14-day window of opportunity for widespread prophylactic intranasal spray usage to significantly impact the number of infections averted. Given an immediate response to a known SARS-CoV-2 outbreak, alongside testing and social distancing measures, prophylactic efficacy and coverage greater than 65% could reduce the average number of infections by over 90%. In the conference case study, in the absence of additional public health interventions, analyses suggest much higher prophylactic efficacy and coverage is required to achieve a similar outcome on a population level. However, prophylactic use can halve an individual’s probability of being infected, and significantly reduce the probability of developing a severe infection.
Conclusions
At a known potential superspreading event, early use of intranasal sprays can complement quarantining measures and significantly suppress a SARS-CoV-2 outbreak, even at suboptimal coverage. At a potential superspreading event of short duration, intranasal sprays can reduce individuals’ risk of infection, but in the absence of other interventions, they cannot prevent all infections or all onwards community transmission.
Plain language summary
Where crowds are in close contact in closed spaces, respiratory viruses like coronavirus spread easily. At such events, superspreading may occur: one person transmitting the virus to many other event-goers, fuelling the epidemic or pandemic. We used mathematical modelling to predict whether antiviral nose sprays which act immediately can prevent such superspreading events. We found that early use of nose sprays can suppress a SARS-CoV-2 outbreak, even if not everybody is treated with the nose spray, as long as people are also tested and use social distancing if infected. At a conference where people do not quarantine, it is more difficult to prevent spreading of the virus altogether with nose sprays alone. However, at an individual level, people who take the nose spray have lower chance of getting infected with the virus.
{"title":"Preventing SARS-CoV-2 superspreading events with antiviral intranasal sprays","authors":"George Booth , Christoforos Hadjichrysanthou , Keira L. Rice , Jacopo Frallicciardi , Zoltán Magyarics , Frank de Wolf , Jaap Goudsmit , Anna L. Beukenhorst , Roy Anderson","doi":"10.1016/j.jtbi.2025.112237","DOIUrl":"10.1016/j.jtbi.2025.112237","url":null,"abstract":"<div><h3>Introduction</h3><div>Superspreading events are known to disproportionally contribute to onwards transmission of epidemic and pandemic viruses. Preventing infections in a small number of high-transmission settings is therefore an attractive public health goal.</div></div><div><h3>Methods</h3><div>We use deterministic and stochastic mathematical modelling to quantify the impact of intranasal sprays in containing outbreaks at a confirmed superspreading event (the 2020 SARS-CoV-2 outbreak at the Diamond Princess cruise ship) and a conference event that led to extensive transmission.</div></div><div><h3>Results</h3><div>In the Diamond Princess cruise ship case study, there exists a 7–14-day window of opportunity for widespread prophylactic intranasal spray usage to significantly impact the number of infections averted. Given an immediate response to a known SARS-CoV-2 outbreak, alongside testing and social distancing measures, prophylactic efficacy and coverage greater than 65% could reduce the average number of infections by over 90%. In the conference case study, in the absence of additional public health interventions, analyses suggest much higher prophylactic efficacy and coverage is required to achieve a similar outcome on a population level. However, prophylactic use can halve an individual’s probability of being infected, and significantly reduce the probability of developing a severe infection.</div></div><div><h3>Conclusions</h3><div>At a known potential superspreading event, early use of intranasal sprays can complement quarantining measures and significantly suppress a SARS-CoV-2 outbreak, even at suboptimal coverage. At a <em>potential</em> superspreading event of short duration, intranasal sprays can reduce individuals’ risk of infection, but in the absence of other interventions, they cannot prevent all infections or all onwards community transmission.</div></div><div><h3>Plain language summary</h3><div>Where crowds are in close contact in closed spaces, respiratory viruses like coronavirus spread easily. At such events, superspreading may occur: one person transmitting the virus to many other event-goers, fuelling the epidemic or pandemic. We used mathematical modelling to predict whether antiviral nose sprays which act immediately can prevent such superspreading events. We found that early use of nose sprays can suppress a SARS-CoV-2 outbreak, even if not everybody is treated with the nose spray, as long as people are also tested and use social distancing if infected. At a conference where people do not quarantine, it is more difficult to prevent spreading of the virus altogether with nose sprays alone. However, at an individual level, people who take the nose spray have lower chance of getting infected with the virus.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112237"},"PeriodicalIF":2.0,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838612","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 : 2025-08-07DOI: 10.1016/j.jtbi.2025.112230
Simon F. Martina-Perez , Luke A. Heirene , Jennifer C. Kasemeier , Paul M. Kulesa , Ruth E. Baker
Neuroblastoma is a paediatric extracranial solid cancer that arises from the developing sympathetic nervous system and is characterised by an abnormal distribution of cell types in tumours compared to healthy infant tissues. In this paper, we propose a new mathematical model of cell differentiation during sympathoadrenal development. By performing Bayesian inference of the model parameters using clinical data from patient samples, we show that the model successfully accounts for the observed differences in cell type heterogeneity among healthy adrenal tissues and four common types of neuroblastomas. Using a phenotypically structured model, we show that alterations in healthy differentiation dynamics are related to cell malignancy, and tumour volume growth. We use this model to analyse the evolution of malignant traits in a tumour. Our findings suggest that normal development dynamics make the embryonic sympathetic nervous system more robust to perturbations and accumulation of malignancies, and that the diversity of differentiation dynamics found in the neuroblastoma subtypes lead to unique risk profiles for neuroblastoma relapse after treatment.
{"title":"Modeling cell differentiation in neuroblastoma: Insights into development, malignancy, and treatment relapse","authors":"Simon F. Martina-Perez , Luke A. Heirene , Jennifer C. Kasemeier , Paul M. Kulesa , Ruth E. Baker","doi":"10.1016/j.jtbi.2025.112230","DOIUrl":"10.1016/j.jtbi.2025.112230","url":null,"abstract":"<div><div>Neuroblastoma is a paediatric extracranial solid cancer that arises from the developing sympathetic nervous system and is characterised by an abnormal distribution of cell types in tumours compared to healthy infant tissues. In this paper, we propose a new mathematical model of cell differentiation during sympathoadrenal development. By performing Bayesian inference of the model parameters using clinical data from patient samples, we show that the model successfully accounts for the observed differences in cell type heterogeneity among healthy adrenal tissues and four common types of neuroblastomas. Using a phenotypically structured model, we show that alterations in healthy differentiation dynamics are related to cell malignancy, and tumour volume growth. We use this model to analyse the evolution of malignant traits in a tumour. Our findings suggest that normal development dynamics make the embryonic sympathetic nervous system more robust to perturbations and accumulation of malignancies, and that the diversity of differentiation dynamics found in the neuroblastoma subtypes lead to unique risk profiles for neuroblastoma relapse after treatment.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"614 ","pages":"Article 112230"},"PeriodicalIF":2.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812680","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 : 2025-08-05DOI: 10.1016/j.jtbi.2025.112232
Keith L. Chambers , Mary R. Myerscough , Michael G. Watson , Helen M. Byrne
Atherosclerosis is a chronic inflammatory disease of the artery wall. The early stages of atherosclerosis are driven by interactions between lipids and monocyte-derived-macrophages (MDMs). The mechanisms that govern the spatial distribution of lipids and MDMs in the lesion remain poorly understood. In this paper, we develop a spatially-resolved and lipid-structured model for early atherosclerosis. The model development and analysis are guided by images of human coronary lesions by Nakashima et al. (2007). Consistent with their findings, the model predicts that lipid initially accumulates deep in the intima due to a spatially non-uniform LDL retention capacity. The model also qualitatively reproduces the global internal maxima in the Nakashima images only when the MDM mobility is sufficiently sensitive to lipid content, and MDM lifespan sufficiently insensitive. Introducing lipid content-dependence to MDM mobility and mean lifespan produced minimal impact on model behaviour at early times, but strongly impacted lesion composition at steady state. Increases to the sensitivity of MDM lifespan to lipid content yield lesions with fewer MDMs, less total lesion lipid content and reduced mean MDM infiltration depth. Increases to the sensitivity of MDM mobility to lipid content also reduces the MDM infiltration depth, but increases the proportion of lipid-laden MDMs. We find that MDM lipid content increases with spatial depth, regardless of blood LDL and HDL content. These results shed light on the mechanisms that drive spatial variation in the composition of early atherosclerotic lesions, and the role of macrophage lipid content in disease progression.
{"title":"A spatially resolved and lipid-structured model for macrophage populations in early human atherosclerotic lesions","authors":"Keith L. Chambers , Mary R. Myerscough , Michael G. Watson , Helen M. Byrne","doi":"10.1016/j.jtbi.2025.112232","DOIUrl":"10.1016/j.jtbi.2025.112232","url":null,"abstract":"<div><div>Atherosclerosis is a chronic inflammatory disease of the artery wall. The early stages of atherosclerosis are driven by interactions between lipids and monocyte-derived-macrophages (MDMs). The mechanisms that govern the spatial distribution of lipids and MDMs in the lesion remain poorly understood. In this paper, we develop a spatially-resolved and lipid-structured model for early atherosclerosis. The model development and analysis are guided by images of human coronary lesions by Nakashima et al. (2007). Consistent with their findings, the model predicts that lipid initially accumulates deep in the intima due to a spatially non-uniform LDL retention capacity. The model also qualitatively reproduces the global internal maxima in the Nakashima images only when the MDM mobility is sufficiently sensitive to lipid content, and MDM lifespan sufficiently insensitive. Introducing lipid content-dependence to MDM mobility and mean lifespan produced minimal impact on model behaviour at early times, but strongly impacted lesion composition at steady state. Increases to the sensitivity of MDM lifespan to lipid content yield lesions with fewer MDMs, less total lesion lipid content and reduced mean MDM infiltration depth. Increases to the sensitivity of MDM mobility to lipid content also reduces the MDM infiltration depth, but increases the proportion of lipid-laden MDMs. We find that MDM lipid content increases with spatial depth, regardless of blood LDL and HDL content. These results shed light on the mechanisms that drive spatial variation in the composition of early atherosclerotic lesions, and the role of macrophage lipid content in disease progression.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"614 ","pages":"Article 112232"},"PeriodicalIF":2.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790769","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 : 2025-07-31DOI: 10.1016/j.jtbi.2025.112228
Sebastian J. Schreiber
A population exhibits an Allee effect when there is a critical density below which it goes extinct and above which it persists. Classical models with environmental stochasticity predict inevitable extinction, stemming from the assumption that environmental variation is normally distributed with rare but arbitrary large effect sizes. However, environmental fluctuations are bounded and often not normally distributed. To address this reality, I analyze piecewise deterministic Markov models (PDMPs) of populations experiencing Allee effects, where environmental dynamics are governed by a finite-state Markov chain. These models predict that populations can persist through the emergence of two threshold densities. Below the lower threshold, populations deterministically go extinct; above the higher threshold, they deterministically persist. At intermediate densities, populations experience stochastic bistability: with positive, complementary probabilities, they either go extinct or persist. Persistence becomes impossible when the carrying capacity in one environment falls below the Allee threshold in another. Such mismatch occurs only when the environmental state affects per-capita growth rates non-monotonically, as when environments supporting higher carrying capacities also produce higher predation levels or greater mate limitation. This work demonstrates that incorporating realistic bounded environmental fluctuations substantially alters predictions about population persistence, with important implications for conservation and management.
{"title":"Bounded environmental stochasticity generates secondary Allee thresholds","authors":"Sebastian J. Schreiber","doi":"10.1016/j.jtbi.2025.112228","DOIUrl":"10.1016/j.jtbi.2025.112228","url":null,"abstract":"<div><div>A population exhibits an Allee effect when there is a critical density below which it goes extinct and above which it persists. Classical models with environmental stochasticity predict inevitable extinction, stemming from the assumption that environmental variation is normally distributed with rare but arbitrary large effect sizes. However, environmental fluctuations are bounded and often not normally distributed. To address this reality, I analyze piecewise deterministic Markov models (PDMPs) of populations experiencing Allee effects, where environmental dynamics are governed by a finite-state Markov chain. These models predict that populations can persist through the emergence of two threshold densities. Below the lower threshold, populations deterministically go extinct; above the higher threshold, they deterministically persist. At intermediate densities, populations experience stochastic bistability: with positive, complementary probabilities, they either go extinct or persist. Persistence becomes impossible when the carrying capacity in one environment falls below the Allee threshold in another. Such mismatch occurs only when the environmental state affects per-capita growth rates non-monotonically, as when environments supporting higher carrying capacities also produce higher predation levels or greater mate limitation. This work demonstrates that incorporating realistic bounded environmental fluctuations substantially alters predictions about population persistence, with important implications for conservation and management.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"614 ","pages":"Article 112228"},"PeriodicalIF":2.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769359","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 : 2025-07-30DOI: 10.1016/j.jtbi.2025.112233
Adam H. Porter , Norman A. Johnson , Alexander Y. Tulchinsky
Although the regulation of gene expression is a fundamental link between genotype, phenotype, and fitness, little is known about how natural selection drives its evolution. To address this gap, we used a biophysical (thermodynamic) model of molecular interactions between allelic variants of transcription factors (TFs) and their cis-regulatory binding sites. We generated diploid genotype-phenotype maps for gene expression. We then applied a Gaussian fitness function to these maps, where the environment determines optimal expression level. The corresponding genotype-fitness landscapes are characterized by high ridges of heterozygote superiority. Heterozygote advantage occurs whenever the environmentally determined phenotypic optimum lies between the phenotypes of the two homozygotes.
To determine whether this superiority could lead to stable polymorphism, for each of 201 optimal expression levels we determined frequency-fitness landscapes (allele frequency vs. fitness) for all allelic combinations; maximized their population mean fitnesses; identified combinations with globally maximal mean fitness; and found their equilibrium allele frequencies. Globally stable polymorphisms occurred whenever the phenotypic optimum laid between the phenotypes of the best two homozygotes. Stable polymorphisms occupied 49–75% of the range of optimal expression levels, depending on biophysical and fitness parameters. Virtually all included TF polymorphism, with binding site co-polymorphisms across 33–55% of the range. Neutral polymorphisms were also widely distributed. Neither molecular complexity of the TF-cis interaction nor pleiotropic constraint had qualitative effects on polymorphism. However, genetic load was negatively correlated with molecular complexity, suggesting that reducing genetic load may be an important mechanism for increasing the complexity of regulatory genetic interactions.
While this analysis assumes environmental homogeneity, the results suggest that this phenomenon may enhance the role of environmental heterogeneity in maintaining regulatory polymorphism. Selection favors the maintenance of polymorphism not just because different homozygotes have higher fitness in different environments, but also because heterozygote advantage can act as a ‘storage effect’ by promoting regulatory polymorphism during the transitions between environmental states.
We use the model to make predictions about future evolutionary trajectories in a well-documented case of regulatory heterozygote advantage involving flower color in an Alpine orchid. More empirical research on the extent and maintenance of regulatory polymorphism within populations is needed.
{"title":"Fitness landscapes of simple regulatory genetic interactions show pervasive heterozygote advantage and support stable polymorphism","authors":"Adam H. Porter , Norman A. Johnson , Alexander Y. Tulchinsky","doi":"10.1016/j.jtbi.2025.112233","DOIUrl":"10.1016/j.jtbi.2025.112233","url":null,"abstract":"<div><div>Although the regulation of gene expression is a fundamental link between genotype, phenotype, and fitness, little is known about how natural selection drives its evolution. To address this gap, we used a biophysical (thermodynamic) model of molecular interactions between allelic variants of transcription factors (TFs) and their <em>cis</em>-regulatory binding sites. We generated diploid genotype-phenotype maps for gene expression. We then applied a Gaussian fitness function to these maps, where the environment determines optimal expression level. The corresponding genotype-fitness landscapes are characterized by high ridges of heterozygote superiority. Heterozygote advantage occurs whenever the environmentally determined phenotypic optimum lies between the phenotypes of the two homozygotes.</div><div>To determine whether this superiority could lead to stable polymorphism, for each of 201 optimal expression levels we determined frequency-fitness landscapes (allele frequency vs. fitness) for all allelic combinations; maximized their population mean fitnesses; identified combinations with globally maximal mean fitness; and found their equilibrium allele frequencies. Globally stable polymorphisms occurred whenever the phenotypic optimum laid between the phenotypes of the best two homozygotes. Stable polymorphisms occupied 49–75% of the range of optimal expression levels, depending on biophysical and fitness parameters. Virtually all included TF polymorphism, with binding site co-polymorphisms across 33–55% of the range. Neutral polymorphisms were also widely distributed. Neither molecular complexity of the TF-<em>cis</em> interaction nor pleiotropic constraint had qualitative effects on polymorphism. However, genetic load was negatively correlated with molecular complexity, suggesting that reducing genetic load may be an important mechanism for increasing the complexity of regulatory genetic interactions.</div><div>While this analysis assumes environmental homogeneity, the results suggest that this phenomenon may enhance the role of environmental heterogeneity in maintaining regulatory polymorphism. Selection favors the maintenance of polymorphism not just because different homozygotes have higher fitness in different environments, but also because heterozygote advantage can act as a ‘storage effect’ by promoting regulatory polymorphism during the transitions between environmental states.</div><div>We use the model to make predictions about future evolutionary trajectories in a well-documented case of regulatory heterozygote advantage involving flower color in an Alpine orchid. More empirical research on the extent and maintenance of regulatory polymorphism within populations is needed.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"614 ","pages":"Article 112233"},"PeriodicalIF":2.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765800","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 : 2025-07-29DOI: 10.1016/j.jtbi.2025.112227
Danish A. Ahmed , Sergei V. Petrovskii , Joseph D. Bailey , Michael B. Bonsall , Phillip J. Haubrock
Random walks (RW) provide a useful modelling framework for the movement of animals at an individual level. If the RW is uncorrelated and unbiased such that the direction of movement is completely random, the dispersal is characterised by the statistical properties of the probability distribution of step lengths, or the dispersal kernel. Whether an individual exhibits short- or long-distance dispersal can be distinguished by the rate of asymptotic decay in the end-tail of the distribution of step-lengths. If the decay is exponential or faster, referred to as a thin-tail, then the step length variance is finite – as occurs in Brownian motion. On the other hand, inverse power-law step length distributions have a heavy end-tail with slower decay, resulting in an infinite step length variance, which is the hallmark of a Lévy walk. In theoretical studies of individual animal movement, various approaches have been employed to connect these dispersal mechanisms, yet they are often ad hoc. We provide a more robust method by ensuring that the survival probability, that is the probability of occurrence of steps longer than a certain threshold is the same for both distributions. Furthermore, the dispersal kernels are then standardised by adjusting the probability to minimise disparities between these distributions. By assuming the same survival probability for movement paths with commonly used thin- and heavy-tailed step length distributions, we form a relationship between the short- and long-distance dispersal of animals in different spatial dimensions. We also demonstrate how our findings can be applied in different ecological contexts, to relate dispersal kernels within theoretical models for boundary effects and spatio-temporal population dynamics. Moreover, we show that the relationship between these dispersal kernels can drastically affect the outcomes across various ecological scenarios.
{"title":"Bridging short- and long-distance dispersal in individual animal movement","authors":"Danish A. Ahmed , Sergei V. Petrovskii , Joseph D. Bailey , Michael B. Bonsall , Phillip J. Haubrock","doi":"10.1016/j.jtbi.2025.112227","DOIUrl":"10.1016/j.jtbi.2025.112227","url":null,"abstract":"<div><div>Random walks (RW) provide a useful modelling framework for the movement of animals at an individual level. If the RW is uncorrelated and unbiased such that the direction of movement is completely random, the dispersal is characterised by the statistical properties of the probability distribution of step lengths, or the dispersal kernel. Whether an individual exhibits short- or long-distance dispersal can be distinguished by the rate of asymptotic decay in the end-tail of the distribution of step-lengths. If the decay is exponential or faster, referred to as a thin-tail, then the step length variance is finite – as occurs in Brownian motion. On the other hand, inverse power-law step length distributions have a heavy end-tail with slower decay, resulting in an infinite step length variance, which is the hallmark of a Lévy walk. In theoretical studies of individual animal movement, various approaches have been employed to connect these dispersal mechanisms, yet they are often ad hoc. We provide a more robust method by ensuring that the survival probability, that is the probability of occurrence of steps longer than a certain threshold is the same for both distributions. Furthermore, the dispersal kernels are then standardised by adjusting the probability to minimise disparities between these distributions. By assuming the same survival probability for movement paths with commonly used thin- and heavy-tailed step length distributions, we form a relationship between the short- and long-distance dispersal of animals in different spatial dimensions. We also demonstrate how our findings can be applied in different ecological contexts, to relate dispersal kernels within theoretical models for boundary effects and spatio-temporal population dynamics. Moreover, we show that the relationship between these dispersal kernels can drastically affect the outcomes across various ecological scenarios.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"614 ","pages":"Article 112227"},"PeriodicalIF":2.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762277","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 : 2025-07-29DOI: 10.1016/j.jtbi.2025.112234
Seyed-Saleh Hosseini-Yazdi , John EA Bertram
Human gait control involves regulating multiple parameters, particularly when navigating uneven terrain. Terrain perturbations can introduce substantial challenges. While the regulation of total step mechanical work across multiple steps has been studied, other observed measures of gait adjustment remain less explored. Using an analytical model, we examined the center of mass (COM) mechanical work and step frequency cost to evaluate the mechanistic implications of transitory step adjustment strategies reported in the literature. Since COM work represents most walking energetics, mechanical analysis shows a specific threshold for which the cost of going atop a perturbation and extending the step length are equal. The same could be observed when the total cost (work and frequency) is examined. Thus, beyond the point of equilibrium, the strategy with less metabolic cost must be favorable. As this evaluation is based on a Just-in-Time walking strategy, extended lookahead horizon on less complicated terrains may change the preference. Our simulations reveal that transient step length reduction with nominal push-off has less collisional dissipation and, as such, elevated walking momentum post step transition. This strategy can compensate for lost momentum atop terrain perturbations yet, it is costlier than push-off regulation. Hence, it might instead be for foothold selection. An extended step may also be utilized when momentum reduction is needed. Additionally, simulations showed that effective leg length adjustment can not only alter the step length but may also limit COM elevation changes. It in turn limits the work against gravity or perhaps limb loading due to elevated collisions. Therefore, step length adjustments, achieved either by adopting different gait strategies or by controlling the effective leg length, are noted as possible complementary approaches to modulating the magnitude of the push-off and preparation to vault atop a perturbation. We also evaluated the anticipatory control traits of older adults, who are more vulnerable to falls on uneven terrain. Older adults demonstrated a transitory speed decrease before encountering perturbation. This might be an indication that older adults require extra time to select a secure foothold. Even without penalty for the lost time of deceleration, to achieve the average speed after a terrain perturbation encounter, we observe materially increased total mechanical work when the walker slows down just before a perturbation. This added cost likely contributes to the higher mechanical work observed in older adults when walking. Elevated mechanical work demand may contribute to fall incidents in older adults when they are not able to perform adequately.
{"title":"The consequence of uneven walking transitory modulation strategies: A simulation-based approach","authors":"Seyed-Saleh Hosseini-Yazdi , John EA Bertram","doi":"10.1016/j.jtbi.2025.112234","DOIUrl":"10.1016/j.jtbi.2025.112234","url":null,"abstract":"<div><div>Human gait control involves regulating multiple parameters, particularly when navigating uneven terrain. Terrain perturbations can introduce substantial challenges. While the regulation of total step mechanical work across multiple steps has been studied, other observed measures of gait adjustment remain less explored. Using an analytical model, we examined the center of mass (COM) mechanical work and step frequency cost to evaluate the mechanistic implications of transitory step adjustment strategies reported in the literature. Since COM work represents most walking energetics, mechanical analysis shows a specific threshold for which the cost of going atop a perturbation and extending the step length are equal. The same could be observed when the total cost (work and frequency) is examined. Thus, beyond the point of equilibrium, the strategy with less metabolic cost must be favorable. As this evaluation is based on a Just-in-Time walking strategy, extended lookahead horizon on less complicated terrains may change the preference. Our simulations reveal that transient step length reduction with nominal push-off has less collisional dissipation and, as such, elevated walking momentum post step transition. This strategy can compensate for lost momentum atop terrain perturbations yet, it is costlier than push-off regulation. Hence, it might instead be for foothold selection. An extended step may also be utilized when momentum reduction is needed. Additionally, simulations showed that effective leg length adjustment can not only alter the step length but may also limit COM elevation changes. It in turn limits the work against gravity or perhaps limb loading due to elevated collisions. Therefore, step length adjustments, achieved either by adopting different gait strategies or by controlling the effective leg length, are noted as possible complementary approaches to modulating the magnitude of the push-off and preparation to vault atop a perturbation. We also evaluated the anticipatory control traits of older adults, who are more vulnerable to falls on uneven terrain. Older adults demonstrated a transitory speed decrease before encountering perturbation. This might be an indication that older adults require extra time to select a secure foothold. Even without penalty for the lost time of deceleration, to achieve the average speed after a terrain perturbation encounter, we observe materially increased total mechanical work when the walker slows down just before a perturbation. This added cost likely contributes to the higher mechanical work observed in older adults when walking. Elevated mechanical work demand may contribute to fall incidents in older adults when they are not able to perform adequately.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"614 ","pages":"Article 112234"},"PeriodicalIF":2.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762279","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 : 2025-07-27DOI: 10.1016/j.jtbi.2025.112229
Anahí Flores-Pérez , Marcos A. González-Olvera , Gustavo Chávez-Peña , Ana G. Gallardo-Hernández , Lizeth Torres
In this work, we analyze the progression of COVID-19 across six distinct epidemic waves in Mexico using a time-delay SIR model, focusing specifically on whether the inclusion of incubation and recovery delays into the classical SIR framework enhances the model’s ability to capture the complex dynamics observed in epidemic data. To achieve robust and reliable estimation of both model parameters and time delays despite the inherent uncertainties present in pandemic data, we employ Particle Swarm Optimization (PSO) and Genetic Algorithms (GA). The performance of these optimization methods is assessed by examining their effectiveness in accurately reconstructing parameters across varying data with noise and uncertainties. Our findings indicate that both PSO and GA yield robust parameter and time-delay estimations even under scenarios where data have uncertainties, highlighting the critical role that time delays play in realistically modeling epidemic dynamics. The obtained results provide valuable insights into COVID-19 transmission patterns in Mexico and demonstrate the practical advantages of evolutionary algorithms for epidemic model calibration.
{"title":"Time-delay enhanced SIR model for COVID-19 waves in Mexico: Parameter estimation using evolutionary algorithms","authors":"Anahí Flores-Pérez , Marcos A. González-Olvera , Gustavo Chávez-Peña , Ana G. Gallardo-Hernández , Lizeth Torres","doi":"10.1016/j.jtbi.2025.112229","DOIUrl":"10.1016/j.jtbi.2025.112229","url":null,"abstract":"<div><div>In this work, we analyze the progression of COVID-19 across six distinct epidemic waves in Mexico using a time-delay SIR model, focusing specifically on whether the inclusion of incubation and recovery delays into the classical SIR framework enhances the model’s ability to capture the complex dynamics observed in epidemic data. To achieve robust and reliable estimation of both model parameters and time delays despite the inherent uncertainties present in pandemic data, we employ Particle Swarm Optimization (PSO) and Genetic Algorithms (GA). The performance of these optimization methods is assessed by examining their effectiveness in accurately reconstructing parameters across varying data with noise and uncertainties. Our findings indicate that both PSO and GA yield robust parameter and time-delay estimations even under scenarios where data have uncertainties, highlighting the critical role that time delays play in realistically modeling epidemic dynamics. The obtained results provide valuable insights into COVID-19 transmission patterns in Mexico and demonstrate the practical advantages of evolutionary algorithms for epidemic model calibration.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"613 ","pages":"Article 112229"},"PeriodicalIF":2.0,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745913","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 : 2025-07-26DOI: 10.1016/j.jtbi.2025.112220
Josué Manik Nava-Sedeño , Abraham Martínez , Haralampos Hatzikirou
The emergence of multicellular invasive behavior is a key characteristic of various biological processes, including wound healing, development, and tissue regeneration. In this study, we develop a lattice-gas cellular automaton (LGCA) model to explore the role of inhibitory feedback in the invasive behavior of a hierarchical lineage composed of stem cells and differentiated cells. We consider both non-spatial and spatial stochastic models to investigate how spatial interactions influence invasion dynamics. Our findings suggest that inhibitory feedback from differentiated cells significantly impacts the invasive potential of stem cells. In addition, local fluctuations induce unstable fronts that move with relatively low speed. Finally, we explore the implications of our work for understanding the regulation of multicellular dynamics in various pathophysiological contexts.
{"title":"On the onset of multicellular invasive behavior in hierarchical lineage: The role of inhibitory feedback and local fluctuations","authors":"Josué Manik Nava-Sedeño , Abraham Martínez , Haralampos Hatzikirou","doi":"10.1016/j.jtbi.2025.112220","DOIUrl":"10.1016/j.jtbi.2025.112220","url":null,"abstract":"<div><div>The emergence of multicellular invasive behavior is a key characteristic of various biological processes, including wound healing, development, and tissue regeneration. In this study, we develop a lattice-gas cellular automaton (LGCA) model to explore the role of inhibitory feedback in the invasive behavior of a hierarchical lineage composed of stem cells and differentiated cells. We consider both non-spatial and spatial stochastic models to investigate how spatial interactions influence invasion dynamics. Our findings suggest that inhibitory feedback from differentiated cells significantly impacts the invasive potential of stem cells. In addition, local fluctuations induce unstable fronts that move with relatively low speed. Finally, we explore the implications of our work for understanding the regulation of multicellular dynamics in various pathophysiological contexts.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"613 ","pages":"Article 112220"},"PeriodicalIF":2.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735457","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号