Pub Date : 2025-08-29DOI: 10.1016/j.jtbi.2025.112250
Xuesong Bai, Thomas G. Fai
It has been observed that the growth of the nucleus and the cytoplasm is coordinated during cell growth, resulting in a nearly constant nuclear-to-cell volume ratio (N/C) throughout the cell cycle. Previous studies have shown that the N/C ratio is determined by the ratio between the number of proteins in the nucleus and the total number of proteins in the cell. These observations suggest the importance of the nucleocytoplasmic transport process in nuclear size by regulating protein concentrations in the nucleus and cytoplasm. This paper combines a biophysical model of Ran-mediated nucleocytoplasmic transport and a simple cell growth model to provide insights into several key aspects of the N/C ratio homeostasis in growing cells. Our model shows that the permeability of the nuclear envelope needs to grow in line with the cell to maintain a nearly constant N/C ratio, that several parameters involved in the nucleocytoplasmic transport mechanism and gene translation significantly affect the N/C ratio, and that Ran may potentially compensate for the lack of NTF2 in the nucleocytoplasmic transport mechanism to maintain a viable N/C ratio. However, this compensation is possible only if RanGDP is allowed to translocate through the nuclear envelope independently of NTF2.
{"title":"Mathematical model of nucleocytoplasmic transport and nuclear-to-cell ratio in a growing cell","authors":"Xuesong Bai, Thomas G. Fai","doi":"10.1016/j.jtbi.2025.112250","DOIUrl":"10.1016/j.jtbi.2025.112250","url":null,"abstract":"<div><div>It has been observed that the growth of the nucleus and the cytoplasm is coordinated during cell growth, resulting in a nearly constant nuclear-to-cell volume ratio (N/C) throughout the cell cycle. Previous studies have shown that the N/C ratio is determined by the ratio between the number of proteins in the nucleus and the total number of proteins in the cell. These observations suggest the importance of the nucleocytoplasmic transport process in nuclear size by regulating protein concentrations in the nucleus and cytoplasm. This paper combines a biophysical model of Ran-mediated nucleocytoplasmic transport and a simple cell growth model to provide insights into several key aspects of the N/C ratio homeostasis in growing cells. Our model shows that the permeability of the nuclear envelope needs to grow in line with the cell to maintain a nearly constant N/C ratio, that several parameters involved in the nucleocytoplasmic transport mechanism and gene translation significantly affect the N/C ratio, and that Ran may potentially compensate for the lack of NTF2 in the nucleocytoplasmic transport mechanism to maintain a viable N/C ratio. However, this compensation is possible only if RanGDP is allowed to translocate through the nuclear envelope independently of NTF2.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112250"},"PeriodicalIF":2.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979444","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 : 2025-08-28DOI: 10.1016/j.jtbi.2025.112253
Gideon A. Ngwa , Bime M. Ghakanyuy , Miranda I. Teboh-Ewungkem , Jacek Banasiak
A deterministic nonlinear ordinary differential equation model for mosquito dynamics in which the mosquitoes can quest for blood either within a human population or within non-human/vertebrate populations is derived and studied. The model captures both the mosquito’s aquatic and terrestrial forms and includes a mechanism to investigate the impact of mating on mosquito dynamics. The model uses a restricted form of homogeneous mixing based on the idea that the mosquito has a blood-feeding habit determined by its blood-feeding preferences and its gonotrophic cycle. This characterisation allows us to compartmentalise the total mosquito population into distinct compartments according to the spatial location of the mosquito (breeding site, resting places and questing places) as well as blood-fed status. Issues of overcrowding and intraspecific competition both within the aquatic and the terrestrial stages of the mosquito’s life forms are addressed and considered in the model. Results show that the inclusion of mating induces bistability, a phenomenon whereby locally stable trivial and non-trivial equilibria co-exist with an unstable non-zero equilibrium. The local nature of the stable equilibria is demonstrated by numerically showing that the long-term state of the system is sensitive to initial conditions. The bistability state is analogous to the phenomenon of the Allee effect that has been reported in population biology. The model’s results, including the derivation of the threshold parameter of the system, are comprehensively tested via numerical simulations. The output of our model has direct application to mosquito control strategies, for it clearly shows key points in the mosquito’s developmental pathway that can be targeted for control purposes.
{"title":"Mating versus alternative blood sources as determinants to mosquito abundance and population resilience","authors":"Gideon A. Ngwa , Bime M. Ghakanyuy , Miranda I. Teboh-Ewungkem , Jacek Banasiak","doi":"10.1016/j.jtbi.2025.112253","DOIUrl":"10.1016/j.jtbi.2025.112253","url":null,"abstract":"<div><div>A deterministic nonlinear ordinary differential equation model for mosquito dynamics in which the mosquitoes can quest for blood either within a human population or within non-human/vertebrate populations is derived and studied. The model captures both the mosquito’s aquatic and terrestrial forms and includes a mechanism to investigate the impact of mating on mosquito dynamics. The model uses a restricted form of homogeneous mixing based on the idea that the mosquito has a blood-feeding habit determined by its blood-feeding preferences and its gonotrophic cycle. This characterisation allows us to compartmentalise the total mosquito population into distinct compartments according to the spatial location of the mosquito (breeding site, resting places and questing places) as well as blood-fed status. Issues of overcrowding and intraspecific competition both within the aquatic and the terrestrial stages of the mosquito’s life forms are addressed and considered in the model. Results show that the inclusion of mating induces bistability, a phenomenon whereby locally stable trivial and non-trivial equilibria co-exist with an unstable non-zero equilibrium. The local nature of the stable equilibria is demonstrated by numerically showing that the long-term state of the system is sensitive to initial conditions. The bistability state is analogous to the phenomenon of the Allee effect that has been reported in population biology. The model’s results, including the derivation of the threshold parameter of the system, are comprehensively tested via numerical simulations. The output of our model has direct application to mosquito control strategies, for it clearly shows key points in the mosquito’s developmental pathway that can be targeted for control purposes.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112253"},"PeriodicalIF":2.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979364","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 : 2025-08-24DOI: 10.1016/j.jtbi.2025.112248
Punya Alahakoon , Peter G. Taylor , James M. McCaw
COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people around the globe. We studied the spread of SARS-CoV-2 across six rural counties in North and South Dakota in the United States. The study period was from early March 2020 to mid-June 2021, during which non-pharmaceutical interventions (NPIs) were in place. The end of the study period coincided with the emergence of the Delta variant in the United States. We modelled the transmission dynamics in each county using a stochastic compartmental model and analysed the data within a Bayesian hierarchical statistical framework. We estimated key epidemiological and surveillance parameters including the reproduction number and reporting probability. We conducted a series of counterfactual analyses in which NPIs were lifted earlier and by varying degrees, modelled as an increase in the transmission rate. Under this range of plausible alternative responses, increases in case counts varied from negligible to substantial, underscoring the importance of timely public health measures and compliance with them. From a methodological perspective, our study demonstrates that despite the inherent high variability in epidemic behaviour in small rural communities, the combination of stochastic modelling and application of Bayesian hierarchical analyses enables the estimation of key epidemiological and surveillance parameters and consideration of the potential impact of alternative public health measures in small low population density communities.
{"title":"Stochastic modelling of early-stage COVID-19 epidemic dynamics in rural communities in the United States","authors":"Punya Alahakoon , Peter G. Taylor , James M. McCaw","doi":"10.1016/j.jtbi.2025.112248","DOIUrl":"10.1016/j.jtbi.2025.112248","url":null,"abstract":"<div><div>COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people around the globe. We studied the spread of SARS-CoV-2 across six rural counties in North and South Dakota in the United States. The study period was from early March 2020 to mid-June 2021, during which non-pharmaceutical interventions (NPIs) were in place. The end of the study period coincided with the emergence of the Delta variant in the United States. We modelled the transmission dynamics in each county using a stochastic compartmental model and analysed the data within a Bayesian hierarchical statistical framework. We estimated key epidemiological and surveillance parameters including the reproduction number and reporting probability. We conducted a series of counterfactual analyses in which NPIs were lifted earlier and by varying degrees, modelled as an increase in the transmission rate. Under this range of plausible alternative responses, increases in case counts varied from negligible to substantial, underscoring the importance of timely public health measures and compliance with them. From a methodological perspective, our study demonstrates that despite the inherent high variability in epidemic behaviour in small rural communities, the combination of stochastic modelling and application of Bayesian hierarchical analyses enables the estimation of key epidemiological and surveillance parameters and consideration of the potential impact of alternative public health measures in small low population density communities.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112248"},"PeriodicalIF":2.0,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979427","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 : 2025-08-24DOI: 10.1016/j.jtbi.2025.112252
Tadeas Priklopil , Kirsten Bomblies , Alex Widmer
Proper protein folding is essential for biological function, and its disruption can lead to disease, reduced fitness, or death. The ability of a protein to maintain its folded conformation is thus critical for life, making it a key target of adaptive evolution. However, protein stability is sensitive to environmental factors, particularly temperature, which can threaten phenotypic integrity and organismal survival under thermal changes. Despite its importance, the influence of complex thermal environments – characterized here by mean temperature, thermal fluctuations, and environmental heterogeneity – on the evolution of protein stability remains poorly understood. To address this, we developed a mathematical framework that combines two well-established models: a population genetic model describing species distributed across habitats with distinct thermal environments, and a thermodynamic model of protein stability incorporating temperature-dependent enthalpy and entropy contributions. We focus on two-state proteins that alternate between folded and unfolded states and assume that allelic fitness is maximized in proteins that achieve an optimal balance between flexibility and rigidity. Using this framework, we performed an invasion analysis of mutations (sensu adaptive dynamics framework) affecting three thermodynamic parameters that fully determine protein stability profiles. Where possible, we derived analytical expressions for evolutionarily optimal thermodynamic parameters and complemented these with numerical solutions. Our results show that mean temperature and thermal fluctuations have orthogonal effects on thermodynamic parameters, underscoring the need to consider both when studying protein stability adaptation. We further examined thermally heterogeneous environments, where subpopulations connected by migration experience different mean temperatures, identifying conditions that favor either local (specialist) or global (generalist) adaptation. Our results may explain why one thermodynamic parameter shows little association with thermal adaptation and suggest that local adaptation is more likely for proteins with stability profiles limited to narrow temperature ranges. Additionally, our analysis reveals whether a locally adapted protein originated in a colder or warmer habitat. Finally, we identified trade-offs in thermodynamic parameters that influence local or global adaptation. This study offers key predictions about protein evolution in complex thermal environments and lays the groundwork for developing practical tools to understand how temperature shapes adaptation and biodiversity.
{"title":"Adaptation of protein stability to thermally heterogeneous environments","authors":"Tadeas Priklopil , Kirsten Bomblies , Alex Widmer","doi":"10.1016/j.jtbi.2025.112252","DOIUrl":"10.1016/j.jtbi.2025.112252","url":null,"abstract":"<div><div>Proper protein folding is essential for biological function, and its disruption can lead to disease, reduced fitness, or death. The ability of a protein to maintain its folded conformation is thus critical for life, making it a key target of adaptive evolution. However, protein stability is sensitive to environmental factors, particularly temperature, which can threaten phenotypic integrity and organismal survival under thermal changes. Despite its importance, the influence of complex thermal environments – characterized here by mean temperature, thermal fluctuations, and environmental heterogeneity – on the evolution of protein stability remains poorly understood. To address this, we developed a mathematical framework that combines two well-established models: a population genetic model describing species distributed across habitats with distinct thermal environments, and a thermodynamic model of protein stability incorporating temperature-dependent enthalpy and entropy contributions. We focus on two-state proteins that alternate between folded and unfolded states and assume that allelic fitness is maximized in proteins that achieve an optimal balance between flexibility and rigidity. Using this framework, we performed an invasion analysis of mutations (<em>sensu</em> adaptive dynamics framework) affecting three thermodynamic parameters that fully determine protein stability profiles. Where possible, we derived analytical expressions for evolutionarily optimal thermodynamic parameters and complemented these with numerical solutions. Our results show that mean temperature and thermal fluctuations have orthogonal effects on thermodynamic parameters, underscoring the need to consider both when studying protein stability adaptation. We further examined thermally heterogeneous environments, where subpopulations connected by migration experience different mean temperatures, identifying conditions that favor either local (specialist) or global (generalist) adaptation. Our results may explain why one thermodynamic parameter shows little association with thermal adaptation and suggest that local adaptation is more likely for proteins with stability profiles limited to narrow temperature ranges. Additionally, our analysis reveals whether a locally adapted protein originated in a colder or warmer habitat. Finally, we identified trade-offs in thermodynamic parameters that influence local or global adaptation. This study offers key predictions about protein evolution in complex thermal environments and lays the groundwork for developing practical tools to understand how temperature shapes adaptation and biodiversity.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112252"},"PeriodicalIF":2.0,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979374","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}
In the present work we propose a new nonlinear coupled 1D model to describe lung ventilation and the transport and diffusion of both oxygen and carbon dioxide in the bronchial tree through the blood. It takes into account the so-called Bohr-Haldane effect, which induces a strong coupling of oxygen and carbon dioxide, and is driven by the applied pleural pressure. The ability of this model to reproduce standard acknowledged values in healthy situations and normal breathing scenario is provided. One key aspect is that, contrary to its 0D counterpart, it naturally takes into account mixing of gases along the tree and a time delay as the gases have to be transported before reaching the alveoli. We investigate the sensitivity of the 1D model to model parameters, its behavior at exercise and recover standard washout carbon dioxide curves. We also investigate the sensitivity of both the 1D model and its 0D counterpart with respect to the breathing pattern by considering two types of pleural applied pressure: a piecewise constant one and a piecewise exponential one for various values of the breathing period, inspiratory ratio and pressure amplitude. We finally explore which cost functions the observed stereotypical breathing scenario for normal breathing in healthy situations may optimize, emphasizing the fact that it should be a combination of several criteria: low effort and small lung distension while maintaining average carbon dioxide arterial partial pressure at a given level. The paper concludes with a discussion on the proposed model, its limitations and further works.
{"title":"Sensitivity and optimality analysis of breathing scenarios for 1D or 0D models of gas diffusion in the lung","authors":"Céline Grandmont , Cyril Karamaoun , Sébastien Martin , Frédérique Noël","doi":"10.1016/j.jtbi.2025.112235","DOIUrl":"10.1016/j.jtbi.2025.112235","url":null,"abstract":"<div><div>In the present work we propose a new nonlinear coupled 1D model to describe lung ventilation and the transport and diffusion of both oxygen and carbon dioxide in the bronchial tree through the blood. It takes into account the <em>so-called</em> Bohr-Haldane effect, which induces a strong coupling of oxygen and carbon dioxide, and is driven by the applied pleural pressure. The ability of this model to reproduce standard acknowledged values in healthy situations and normal breathing scenario is provided. One key aspect is that, contrary to its 0D counterpart, it naturally takes into account mixing of gases along the tree and a time delay as the gases have to be transported before reaching the alveoli. We investigate the sensitivity of the 1D model to model parameters, its behavior at exercise and recover standard washout carbon dioxide curves. We also investigate the sensitivity of both the 1D model and its 0D counterpart with respect to the breathing pattern by considering two types of pleural applied pressure: a piecewise constant one and a piecewise exponential one for various values of the breathing period, inspiratory ratio and pressure amplitude. We finally explore which cost functions the observed stereotypical breathing scenario for normal breathing in healthy situations may optimize, emphasizing the fact that it should be a combination of several criteria: low effort and small lung distension while maintaining average carbon dioxide arterial partial pressure at a given level. The paper concludes with a discussion on the proposed model, its limitations and further works.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112235"},"PeriodicalIF":2.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913816","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 : 2025-08-15DOI: 10.1016/j.jtbi.2025.112247
Viktor Bezborodov , Tyll Krueger , Cornelia Pokalyuk , Piotr Szymański , Aurélien Velleret
This study examines the effectiveness of regional lockdown strategies in mitigating pathogen spread across regional units, termed cities hereinafter. We develop simplified models to analyze infection spread across cities within a country during an epidemic wave. Isolation of a city is initiated when infection numbers within the city surpass defined thresholds. We compare two strategies: strategy consists in prescribing thresholds proportionally to city sizes, while the same threshold is used for all cities under strategy . Given the heavy-tailed distribution of city sizes, strategy may result in more secondary infections from larger cities than strategy .
Random graph models are constructed to represent infection spread as a percolation process. In particular, we consider a model in which mobility between cities only depends on city sizes. We assess the relative efficiency of the two strategies by comparing the ratios of the number of individuals under isolation to the total number of infections by the end of the epidemic wave under strategy and . Additionally, we derive analytical formulas for disease prevalence and basic reproduction numbers.
Our models are calibrated using mobility data from France, Poland and Japan, validated through simulation. The findings indicate that mobility between cities in France and Poland is mainly determined by city sizes. However, a poor fit was observed with Japanese data, highlighting the importance to include other factors like e.g. geography for some countries in modeling. Our analysis suggest similar effectiveness for both strategies in France and Japan, while strategy demonstrates distinct merits in Poland.
{"title":"Inter-city infections and the role of size heterogeneity in containment strategies","authors":"Viktor Bezborodov , Tyll Krueger , Cornelia Pokalyuk , Piotr Szymański , Aurélien Velleret","doi":"10.1016/j.jtbi.2025.112247","DOIUrl":"10.1016/j.jtbi.2025.112247","url":null,"abstract":"<div><div>This study examines the effectiveness of regional lockdown strategies in mitigating pathogen spread across regional units, termed cities hereinafter. We develop simplified models to analyze infection spread across cities within a country during an epidemic wave. Isolation of a city is initiated when infection numbers within the city surpass defined thresholds. We compare two strategies: strategy <span><math><mrow><mo>(</mo><mi>P</mi><mo>)</mo></mrow></math></span> consists in prescribing thresholds proportionally to city sizes, while the same threshold is used for all cities under strategy <span><math><mrow><mo>(</mo><mi>U</mi><mo>)</mo></mrow></math></span>. Given the heavy-tailed distribution of city sizes, strategy <span><math><mrow><mo>(</mo><mi>P</mi><mo>)</mo></mrow></math></span> may result in more secondary infections from larger cities than strategy <span><math><mrow><mo>(</mo><mi>U</mi><mo>)</mo></mrow></math></span>.</div><div>Random graph models are constructed to represent infection spread as a percolation process. In particular, we consider a model in which mobility between cities only depends on city sizes. We assess the relative efficiency of the two strategies by comparing the ratios of the number of individuals under isolation to the total number of infections by the end of the epidemic wave under strategy <span><math><mrow><mo>(</mo><mi>P</mi><mo>)</mo></mrow></math></span> and <span><math><mrow><mo>(</mo><mi>U</mi><mo>)</mo></mrow></math></span>. Additionally, we derive analytical formulas for disease prevalence and basic reproduction numbers.</div><div>Our models are calibrated using mobility data from France, Poland and Japan, validated through simulation. The findings indicate that mobility between cities in France and Poland is mainly determined by city sizes. However, a poor fit was observed with Japanese data, highlighting the importance to include other factors like e.g. geography for some countries in modeling. Our analysis suggest similar effectiveness for both strategies in France and Japan, while strategy <span><math><mrow><mo>(</mo><mi>U</mi><mo>)</mo></mrow></math></span> demonstrates distinct merits in Poland.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112247"},"PeriodicalIF":2.0,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876886","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 : 2025-08-14DOI: 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}
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