Journal of Theoretical Biology最新文献_第2页

Spatio-temporal model of combining ADT and chemotherapy with senolytic treatment in metastatic prostate cancer

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2025-02-18 DOI: 10.1016/j.jtbi.2025.112069

Teddy Lazebnik , Avner Friedman

{"title":"Spatio-temporal model of combining ADT and chemotherapy with senolytic treatment in metastatic prostate cancer","authors":"Teddy Lazebnik , Avner Friedman","doi":"10.1016/j.jtbi.2025.112069","DOIUrl":"10.1016/j.jtbi.2025.112069","url":null,"abstract":"<div><div>Prostate cancer cells depend on androgen for their survival. A standard treatment of metastatic prostate cancer (mPC) is androgen deprivation treatment (ADT). However, after a period of remission, some cancer cells changed into androgen-independent cells, and then treatment proceeds with a combination of ADT and chemotherapy. Senescent cells are cells that stop dividing but sustain viability. Senescence cancer cells are common in cancer, and they affect cancer treatment negatively by secreting inflammatory cytokines and pro-cancer VEGF. In this paper, we include the effect of senescence in a model of mPC. We consider combinations of ADT, chemotherapy, and senolytic drug, which eliminate senescent cells, in a spatio-temporal partial differential equations model, and demonstrate that simulations of the model are in agreement with experimental results. We evaluate the synergy between different doses of chemotherapy and senolytic drugs, at different fixed doses of ADT. We also consider optimal scheduling of the drugs, and the hypothesis that, in optimal schedule, a senolytic drug is to be administered immediately following the chemotherapy drug.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"602 ","pages":"Article 112069"},"PeriodicalIF":1.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438209","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}

引用次数: 0

Optimal social distancing in pandemic preparedness and lessons from COVID-19: Intervention intensity and infective travelers

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2025-02-16 DOI: 10.1016/j.jtbi.2025.112072

Alberto Landi , Giulio Pisaneschi , Marco Laurino , Piero Manfredi

{"title":"Optimal social distancing in pandemic preparedness and lessons from COVID-19: Intervention intensity and infective travelers","authors":"Alberto Landi , Giulio Pisaneschi , Marco Laurino , Piero Manfredi","doi":"10.1016/j.jtbi.2025.112072","DOIUrl":"10.1016/j.jtbi.2025.112072","url":null,"abstract":"<div><div>Our analysis seeks best social distancing strategies optimally balancing the direct costs of a threatening outbreak with its societal-level costs by investigating the effects of different levels of restrictions’ intensity and of the continued importation of infective travellers, while controlling for the key dimensions of the response, such as early action, adherence and the relative weight of societal costs. We identify two primary degrees of freedom in epidemic control, namely the maximum intensity of control measures and their duration. In the absence of travellers, a lower (higher) maximum intensity requires a longer (shorter) duration to achieve similar control outcomes. However, uncontrollable external factors, like the importation of undetected infectives, significantly constrain these degrees of freedom so that the optimal strategy results to be one with low/moderate intensity but prolonged in time. These findings underscore the necessity for resilient health systems and coordinated global responses in preparedness plans.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"604 ","pages":"Article 112072"},"PeriodicalIF":1.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450990","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}

引用次数: 0

The effect of heterogeneity of relative vaccine costs on the mean population vaccination rate with mpox as an example

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2025-02-10 DOI: 10.1016/j.jtbi.2025.112062

Spalding Garakani , Luis Flores , Guillermo Alvarez-Pardo , Jan Rychtář , Dewey Taylor

引用次数: 0

Age-dependence of food allergy due to decreased supply of naïve T cells

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2025-02-08 DOI: 10.1016/j.jtbi.2025.112060

Yuna Kotsubo , Akane Hara , Rena Hayashi , Yoh Iwasa

{"title":"Age-dependence of food allergy due to decreased supply of naïve T cells","authors":"Yuna Kotsubo , Akane Hara , Rena Hayashi , Yoh Iwasa","doi":"10.1016/j.jtbi.2025.112060","DOIUrl":"10.1016/j.jtbi.2025.112060","url":null,"abstract":"<div><div>Food allergies to eggs and cow’s milk are common during infancy but often undergo desensitization during childhood. To investigate the age dependence of food allergies, we develop a simple mathematical model focusing on T helper 2 cells (Th2) causing allergies and induced regulatory T cells (iTreg) suppressing them. We assume as follows: Both types of cells differentiate from naïve T cells reactive to specific food allergens, with the rate of supply from the thymus decreasing with age. Naïve T cells are activated by allergens in peripheral tissues, differentiating into both Th2 and iTreg cells. The activation rate of Th2 cells is reduced by iTreg cells. Th2 cells promote allergies while iTreg cells help mitigate them. Analyses show that food allergies may develop at one age and resolve at a later age. Negative selection in the thymus reduces the number of naïve T cells that react to proteins resembling components of the body. As a result, allergies to these substances tend to start and resolve earlier in life than those to dissimilar materials. Food allergy starting at an older age tends to have a longer duration if the rate of naïve T cell supply decreases according to a hyperbolic (instead of exponential) function of age.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"602 ","pages":"Article 112060"},"PeriodicalIF":1.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392552","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}

引用次数: 0

Impact of evolutionary relatedness on species diversification and tree shape 进化相关性对物种多样性和树形的影响

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2025-02-07 DOI: 10.1016/j.jtbi.2024.111992

Tianjian Qin , Luis Valente , Rampal S. Etienne

{"title":"Impact of evolutionary relatedness on species diversification and tree shape","authors":"Tianjian Qin , Luis Valente , Rampal S. Etienne","doi":"10.1016/j.jtbi.2024.111992","DOIUrl":"10.1016/j.jtbi.2024.111992","url":null,"abstract":"<div><div>Slowdowns in lineage accumulation are often observed in phylogenies of extant species. One explanation is the presence of ecological limits to diversity and hence to diversification. Previous research has examined whether and how species richness (SR) impacts diversification rates, but rarely considered the evolutionary relatedness (ER) between species, although ER can affect the degree of interaction between species, which likely sets these limits. To understand the influences of ER on species diversification and the interplay between SR and ER, we present a simple birth–death model in which the speciation rate depends on the ER. We use different metrics of ER that operate at different scales, ranging from branch/lineage-specific to clade-wide scales. We find that the scales at which an effect of ER operates yield distinct patterns in various tree statistics. When ER operates across the whole tree, we observe smaller and more balanced trees, with speciation rates distributed more evenly across the tips than in scenarios with lineage-specific ER effects. Importantly, we find that negative SR dependence of speciation masks the impact of ER on some of the tree statistics. Our model allows diverse evolutionary trajectories for producing imbalanced trees, which are commonly observed in empirical phylogenies but have been challenging to replicate with earlier models.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"598 ","pages":"Article 111992"},"PeriodicalIF":1.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669395","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}

引用次数: 0

Possible regulatory mechanisms of typical and atypical absence seizures through an equivalent projection from the subthalamic nucleus to the cortex: Evidence in a computational model

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2025-02-05 DOI: 10.1016/j.jtbi.2025.112059

Bing Hu, Yaqi Guo, JinDong Zhao, Xunfu Ma

{"title":"Possible regulatory mechanisms of typical and atypical absence seizures through an equivalent projection from the subthalamic nucleus to the cortex: Evidence in a computational model","authors":"Bing Hu, Yaqi Guo, JinDong Zhao, Xunfu Ma","doi":"10.1016/j.jtbi.2025.112059","DOIUrl":"10.1016/j.jtbi.2025.112059","url":null,"abstract":"<div><div>The subthalamic nucleus (STN) is an important structure that regulates basal ganglia output and has been involved in the pathophysiology of epilepsy disease. In this paper, we propose an equivalent inhibitory pathway directly projecting from the STN to the cortex and systematically study its regulatory effect on absence seizures. Interestingly, we find that this equivalent inhibitory projection is a key factor for assisting in the development of atypical absence seizures. Through computational simulation and model analysis, we find that the enhancement of coupling strength on this equivalent STN-cortex projection can effectively suppress typical and atypical spike and wave discharges (TSWDs and ASWDs) during absence seizures. Furthermore, altering the activation level of STN through external stimuli can also control seizures, and the presence of equivalent STN-cortex projection makes the control effect more easier to achieve. Several direct and indirect pathways related to the STN can achieve inhibition of SWDs by regulating the activation level of STN, and relevant control strategies have high biological plausibility. Therefore, the STN may be an effective target for the deep brain stimulation (DBS) to control absence seizures. Importantly, we observe that the control effect of DBS-STN on SWDs is significantly superior to other basal ganglia targets in this model. Moreover, we find that the parameter range and value with high biological plausibility for the coupling weight in this equivalent STN-cortex projection can be effectively estimated in this model. Our results imply that the inhibitory effect from the STN to the cortex plays a crucial role in regulating both typical and atypical SWDs, and the STN might be a potential and reasonable DBS target for the treatment of absence epilepsy.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"602 ","pages":"Article 112059"},"PeriodicalIF":1.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143351002","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}

引用次数: 0

Efficient coupling of within-and between-host infectious disease dynamics

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2025-02-04 DOI: 10.1016/j.jtbi.2025.112061

Cameron A. Smith , Ben Ashby

{"title":"Efficient coupling of within-and between-host infectious disease dynamics","authors":"Cameron A. Smith , Ben Ashby","doi":"10.1016/j.jtbi.2025.112061","DOIUrl":"10.1016/j.jtbi.2025.112061","url":null,"abstract":"<div><div>Mathematical models of infectious disease transmission typically neglect within-host dynamics. Yet within-host dynamics – including pathogen replication, host immune responses, and interactions with microbiota – are crucial not only for determining the progression of disease at the individual level, but also for driving within-host evolution and onwards transmission, and therefore shape dynamics at the population level. Various approaches have been proposed to model both within- and between-host dynamics, but these typically require considerable simplifying assumptions to couple processes at contrasting scales (e.g., the within-host dynamics quickly reach a steady state) or are computationally intensive. Here we propose a novel, readily adaptable and broadly applicable method for modelling both within- and between-host processes which can fully couple dynamics across scales and is both realistic and computationally efficient. By individually tracking the deterministic within-host dynamics of infected individuals, and stochastically coupling these to continuous host state variables at the population-level, we take advantage of fast numerical methods at both scales while still capturing individual transient within-host dynamics and stochasticity in transmission between hosts. Our approach closely agrees with full stochastic individual-based simulations and is especially useful when the within-host dynamics do not rapidly reach a steady state or over longer timescales to track pathogen evolution. By applying our method to different pathogen growth scenarios we show how common simplifying assumptions fundamentally change epidemiological and evolutionary dynamics.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"602 ","pages":"Article 112061"},"PeriodicalIF":1.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143351000","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}

引用次数: 0

Simulations probe the role of space in the interplay between drug-sensitive and drug-resistant cancer cells

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2025-02-04 DOI: 10.1016/j.jtbi.2025.112048

Kira Pugh , Rhys D.O. Jones , Gibin Powathil , Sara Hamis

{"title":"Simulations probe the role of space in the interplay between drug-sensitive and drug-resistant cancer cells","authors":"Kira Pugh , Rhys D.O. Jones , Gibin Powathil , Sara Hamis","doi":"10.1016/j.jtbi.2025.112048","DOIUrl":"10.1016/j.jtbi.2025.112048","url":null,"abstract":"<div><div>The interplay between drug-sensitive and drug-resistant cancer cells has been observed to impact cell-to-cell interactions in experimental settings. However, the role that space plays in these interactions remains unclear. In this study, we develop mathematical models to investigate how spatial factors affect cell-to-cell competition between drug-sensitive and drug-resistant cancer cells in silico. We develop two baseline models to study cells from the epithelial FaDu cell line subjected to two drugs, specifically the ATR inhibitor ceralasertib and the PARP inhibitor olaparib, that target DNA damage response pathways. Our baseline models are: (1) a temporally resolved ordinary differential equation (ODE) model, and (2) a spatio-temporally resolved agent-based model (ABM). The models simulate cells in well-mixed and spatially structured cell systems, respectively. The ODE model is calibrated against in vitro data and is thereafter mapped onto the baseline ABM which, in turn, is extended to enable a simulation-based investigation on how spatial factors impact cell-to-cell competition. Simulation results from the extended ABMs demonstrate that the in silico treatment responses are simultaneously affected by: (i) the initial spatial cell configurations, (ii) the initial fraction of drug-resistant cells, (iii) the drugs to which cells express resistance, (iv) drug combinations, (v) drug doses, and (vi) the doubling time of drug-resistant cells compared to the doubling time of drug-sensitive cells. These results reveal that spatial structures of the simulated cancer cells affect both cell-to-cell interactions, and the impact that these interactions have on the ensuing population dynamics. This leads us to suggest that the role that space plays in cell-to-cell interactions should be further investigated and quantified in experimental settings.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"602 ","pages":"Article 112048"},"PeriodicalIF":1.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365920","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}

引用次数: 0

A mathematical model of microglia glucose metabolism and lactylation with positive feedback

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2025-01-30 DOI: 10.1016/j.jtbi.2025.112049

Kamila Larripa , Anca Rǎdulescu

引用次数: 0

Tradeoffs in the energetic value of neuromodulation in a closed-loop neuromechanical system

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2025-01-30 DOI: 10.1016/j.jtbi.2025.112050

Zhuojun Yu , Yangyang Wang , Peter J. Thomas , Hillel J. Chiel

{"title":"Tradeoffs in the energetic value of neuromodulation in a closed-loop neuromechanical system","authors":"Zhuojun Yu , Yangyang Wang , Peter J. Thomas , Hillel J. Chiel","doi":"10.1016/j.jtbi.2025.112050","DOIUrl":"10.1016/j.jtbi.2025.112050","url":null,"abstract":"<div><div>Rhythmic motor behaviors controlled by neuromechanical systems, consisting of central neural circuitry, biomechanics, and sensory feedback, show efficiency in energy expenditure. The biomechanical elements (e.g., muscles) are modulated by peripheral neuromodulation which may improve their strength and speed properties. However, there are relatively few studies on neuromodulatory control of muscle function and metabolic mechanical efficiency in neuromechanical systems. To investigate the role of neuromodulation on the system’s mechanical efficiency, we consider a neuromuscular model of motor patterns for feeding in the marine mollusk <em>Aplysia californica</em>. By incorporating muscle energetics and neuromodulatory effects into the model, we demonstrate tradeoffs in the energy efficiency of <em>Aplysia</em>’s rhythmic swallowing behavior as a function of the level of neuromodulation. A robust efficiency optimum arises from an intermediate level of neuromodulation, and excessive neuromodulation may be inefficient and disadvantageous to an animal’s metabolism. This optimum emerges from physiological constraints imposed upon serotonergic modulation trajectories on the energy efficiency landscape. Our results may lead to experimentally testable hypotheses of the role of neuromodulation in rhythmic motor control.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"604 ","pages":"Article 112050"},"PeriodicalIF":1.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076495","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}

引用次数: 0