Journal of Theoretical Biology最新文献_第6页

HIV transactivation: Stochastic modeling for studying the effects of BET inhibitors on the modulation of P-TEFb levels HIV交易激活：研究BET抑制剂对P-TEFb水平调节作用的随机模型。

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2024-12-04 DOI: 10.1016/j.jtbi.2024.112011

Miranda Harkess , Sudha Kumari , Trilochan Bagarti , Niraj Kumar

{"title":"HIV transactivation: Stochastic modeling for studying the effects of BET inhibitors on the modulation of P-TEFb levels","authors":"Miranda Harkess , Sudha Kumari , Trilochan Bagarti , Niraj Kumar","doi":"10.1016/j.jtbi.2024.112011","DOIUrl":"10.1016/j.jtbi.2024.112011","url":null,"abstract":"<div><div>Latency is the major obstacle in eradicating HIV from infected patients. Recent studies have shown that BET protein inhibitors can successfully reverse this latency by inhibiting the binding of BET proteins with positive cellular cofactor P-TEFb. Thus, availability of P-TEFbs plays an important role in HIV transactivation. However, in cells of our immune system which are primarily infected by the virus, number of P-TEFb is very low and is considered as one of the factors in inducing viral latency. At such small numbers of P-TEFb, the internal fluctuations can have a decisive role in the cell fate decision and fluctuations in the P-TEFb levels can switch the HIV to either a state of active replication or to a state of latency. Aimed at quantitative understanding of how BET inhibitors affect the statistics of P-TEFb level, we develop a coarse-grained stochastic model. However, the interaction between P-TEFb and BET proteins makes the problem analytically challenging. To address the nonlinearity arising due to such interactions, we use Langevin equation based approach to study the statistics of steady-state P-TEFb levels and explore the variations of some of the important quantities such as noise and fano factor associated with P-TEFb as well as correlations between BET and P-TEFb levels with model parameters. The analytic results derived exhibit that these quantities, in general, show non-monotonic response with respect to the parameters of the model. The results derived will be helpful in estimating the model parameters as well in identifying the pathways that can be intervened for effective HIV transactivation.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"599 ","pages":"Article 112011"},"PeriodicalIF":1.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792912","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

A hybrid approach to study and forecast climate-sensitive norovirus infections in the USA 研究和预测美国气候敏感诺如病毒感染的混合方法

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2024-11-26 DOI: 10.1016/j.jtbi.2024.112007

Juping Ji , Shohel Ahmed , Hao Wang

引用次数: 0

Optimal control of vaccination for an epidemic model with standard incidence rate 具有标准发病率的流行病模型的疫苗接种最优控制。

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2024-11-26 DOI: 10.1016/j.jtbi.2024.111993

Li Li , Na Zheng , Chen Liu , Zhen Wang , Zhen Jin

{"title":"Optimal control of vaccination for an epidemic model with standard incidence rate","authors":"Li Li , Na Zheng , Chen Liu , Zhen Wang , Zhen Jin","doi":"10.1016/j.jtbi.2024.111993","DOIUrl":"10.1016/j.jtbi.2024.111993","url":null,"abstract":"<div><div>A critical challenge for diseases spread is the development of effective prevention and control measures while minimizing costs, representing the foremost priority. Unfortunately, research in this crucial area remains inadequately explored. Consequently, this paper addresses the issue by leveraging an SI reaction–diffusion epidemic model incorporating a logistic birth rate and standard incidence rate. Employing vaccination as a control variable and integrating sparse optimal control theory, the study elucidates the achievement of epidemic prevention and control through the optimization of resource allocation, emphasizing a perspective rooted in pattern structure transformation. On the one hand, we theoretically prove the existence of the optimal solutions, first-order necessary optimality conditions, and the sparsity properties. On the other hand, we use numerical simulations to verify the rationality of the control method and the effectiveness of the control strategy from three aspects of control effect, control error and control cost. In addition, tailored targeting options are proposed based on the economic status of each region, specifying the required inoculum amount for each moment. Ultimately, the study demonstrates the effectiveness of input vaccination in controlling epidemics in a majority of areas. In summary, this work offers crucial insights into the prevention and control of a non-quasimonotonic reaction–diffusion epidemic model.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"598 ","pages":"Article 111993"},"PeriodicalIF":1.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741484","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

Optimisation of gene expression noise for cellular persistence against lethal events 优化基因表达噪音，使细胞持续对抗致死事件。

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2024-11-25 DOI: 10.1016/j.jtbi.2024.111996

Pavol Bokes , Abhyudai Singh

{"title":"Optimisation of gene expression noise for cellular persistence against lethal events","authors":"Pavol Bokes , Abhyudai Singh","doi":"10.1016/j.jtbi.2024.111996","DOIUrl":"10.1016/j.jtbi.2024.111996","url":null,"abstract":"<div><div>Bacterial cell persistence, crucial for survival under adverse conditions like antibiotic exposure, is intrinsically linked to stochastic fluctuations in gene expression. Certain genes, while inhibiting growth under normal circumstances, confer tolerance to antibiotics at elevated expression levels. The occurrence of antibiotic events lead to instantaneous cellular responses with varied survival probabilities correlated with gene expression levels. Notably, cells with lower protein concentrations face higher mortality rates. This study aims to elucidate an optimal strategy for protein expression conducive to cellular survival. Through comprehensive mathematical analysis, we determine the optimal burst size and frequency that maximise cell proliferation. Furthermore, we explore how the optimal expression distribution changes as the cost of protein expression to growth escalates. Our model reveals a hysteresis phenomenon, characterised by discontinuous transitions between deterministic and stochastic optima. Intriguingly, stochastic optima possess a noise floor, representing the minimal level of fluctuations essential for optimal cellular resilience.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"598 ","pages":"Article 111996"},"PeriodicalIF":1.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741485","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

An analytical, numerical and experimental study of in-vitro SARS-CoV-2 evolution in Vero B4 cells 体外 SARS-CoV-2 在 Vero B4 细胞中演变的分析、数值和实验研究。

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2024-11-23 DOI: 10.1016/j.jtbi.2024.112000

Matthew Nicol , Julian D.J. Sng , Yanshan Zhu , Sissy Therese Sonnleitner , Kirsty R. Short , Meagan Carney

{"title":"An analytical, numerical and experimental study of in-vitro SARS-CoV-2 evolution in Vero B4 cells","authors":"Matthew Nicol , Julian D.J. Sng , Yanshan Zhu , Sissy Therese Sonnleitner , Kirsty R. Short , Meagan Carney","doi":"10.1016/j.jtbi.2024.112000","DOIUrl":"10.1016/j.jtbi.2024.112000","url":null,"abstract":"<div><div>We derive a numerical model representing the emergence and evolution of SARS-CoV-2 variants, informed by data from in-vitro passaging experiments in Vero B4 cells. We compare our numerical simulation results against probabilistic derivations of the expected probability of and time until the fittest variant becomes fixed in the population. Contrary to literature surrounding DNA viruses and eukaryotes where probabilities of fitness extremes are often modelled by exponential decaying tail, we show that above wildtype fitness differences for SARS-CoV-2 are actually best modelled by a heavy-tailed Fréchet distribution. Furthermore, we find that SARS-CoV-2 variants evolve through an essentially deterministic process rather than a diffusional one, with the dynamics driven by the fitness difference between the top variants rather than by the sampling/dilution process. An interesting consequence of this setting is that the number of variant virions, rather than their proportion, is a better predictor of the probability of fixation for a given variant.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"598 ","pages":"Article 112000"},"PeriodicalIF":1.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717695","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

Noise-induced entrainment of the circadian clock by thermoperiods in tomato: A computational approach 番茄昼夜节律时钟在噪声诱导下受恒温周期影响：计算方法

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2024-11-22 DOI: 10.1016/j.jtbi.2024.111999

Ting Huang , Hengmin Lv , Yiting Shu , Jian Luo , Linxuan Yu , Bing Chen , Xin Sun , Xilin Hou , Xiong You , Tonghua Zhang

{"title":"Noise-induced entrainment of the circadian clock by thermoperiods in tomato: A computational approach","authors":"Ting Huang , Hengmin Lv , Yiting Shu , Jian Luo , Linxuan Yu , Bing Chen , Xin Sun , Xilin Hou , Xiong You , Tonghua Zhang","doi":"10.1016/j.jtbi.2024.111999","DOIUrl":"10.1016/j.jtbi.2024.111999","url":null,"abstract":"<div><div>The endogenous circadian rhythm (approximately 24 h) allows plants to adapt to daily light and temperature variations. Although the mechanism of photoperiod entrainment has been studied extensively, entrainment to diurnal temperature rhythms remains poorly understood. Here we investigate the stochastic entrainment of the circadian clock in the model crop tomato, subject to different thermoperiods. We first proposed the deterministic model of the thermoresponsive circadian clock. The expressions of the circadian clock genes under constant warm temperature (29 ℃) were quantified by RT-qPCR for basal parameters estimation through minimizing the cost function. Model simulations by the stochastic simulation algorithm showed warm temperatures resulting in an advanced phase for approximately 3–4 h. A few hundred molecules for the system size of the stochastic model were sufficient to engage the robust oscillations. Multiple temperature inputs and abnormal temperature cycles similarly showed the invariant robustness of the oscillations. In addition, phases of the core circadian elements were remarkably correlated linearly with periods under temperature cycles. Whereas, the phases were correlated with the duration of daily warm temperature stimuli in a polynomial mode.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"598 ","pages":"Article 111999"},"PeriodicalIF":1.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712030","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

Phase synchronization analysis of EEG functional connectivity in Parkinson’s disease 帕金森病脑电图功能连接的相位同步分析。

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2024-11-20 DOI: 10.1016/j.jtbi.2024.111997

Karthikeyan Rajagopal , Nafise Naseri , Fatemeh Parastesh , Farnaz Ghassemi , Sajad Jafari

{"title":"Phase synchronization analysis of EEG functional connectivity in Parkinson’s disease","authors":"Karthikeyan Rajagopal , Nafise Naseri , Fatemeh Parastesh , Farnaz Ghassemi , Sajad Jafari","doi":"10.1016/j.jtbi.2024.111997","DOIUrl":"10.1016/j.jtbi.2024.111997","url":null,"abstract":"<div><div>There is a growing need for research on Parkinson’s disease (PD), a neurological condition that often affects the elderly. By examining brain network connectivity, researchers are able to discover how different brain regions interact during various cognitive and behavioral tasks. They can also understand how changes in nonlinear connections may be linked to neurological and mental illnesses. In this paper, the synchrony levels of 59 EEG channels from 26 Parkinson’s patients and 13 healthy subjects is examined by utilizing Phase-Lag Index (PLI) during a motor task and resting-state conditions. Examining different EEG frequency bands shows that whole-brain synchronization in the delta band is significantly lower in PD patients compared to healthy subjects during the task. PD patients also exhibit a lower clustering coefficient and a higher shortest path length in this band during the task, which shows the higher small-worldness in Parkinson’s patients compared to healthy individuals. Moreover, the global efficiency in the delta band is significantly reduced in PD patients during the task. An analysis of local efficiency shows that PD and control groups differ in 57 channels. These results reveal that Parkinson’s patients appear to have considerable pathological abnormalities in their delta band connectivity and its characteristic features.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"598 ","pages":"Article 111997"},"PeriodicalIF":1.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689767","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

A stochastic population model for the impact of cancer cell dormancy on therapy success 癌细胞休眠对治疗成功率影响的随机群体模型。

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2024-11-19 DOI: 10.1016/j.jtbi.2024.111995

Jochen Blath , Anna Kraut , Tobias Paul , András Tóbiás

{"title":"A stochastic population model for the impact of cancer cell dormancy on therapy success","authors":"Jochen Blath , Anna Kraut , Tobias Paul , András Tóbiás","doi":"10.1016/j.jtbi.2024.111995","DOIUrl":"10.1016/j.jtbi.2024.111995","url":null,"abstract":"<div><div>Therapy evasion – and subsequent disease progression – is a major challenge in current oncology. An important role in this context seems to be played by various forms of cancer cell dormancy. For example, therapy-induced dormancy, over short timescales, can create serious obstacles to aggressive treatment approaches such as chemotherapy, and long-term dormancy may lead to relapses and metastases even many years after an initially successful treatment.</div><div>In this paper, we focus on individual cancer cells switching into and out of a dormant state both spontaneously as well as in response to treatment. We introduce an idealized mathematical model, based on stochastic agent-based interactions, for the dynamics of cancer cell populations involving individual short-term dormancy, and allow for a range of (multi-drug) therapy protocols. Our analysis – based on simulations of the many-particle limit – shows that in our model, depending on the specific underlying dormancy mechanism, even a small initial population (of explicitly quantifiable size) of dormant cells can lead to therapy failure under classical single-drug treatments that would successfully eradicate the tumour in the absence of dormancy. We further investigate and quantify the effectiveness of several multi-drug regimes (manipulating dormant cancer cells in specific ways, including increasing or decreasing resuscitation rates or targeting dormant cells directly). Relying on quantitative results for concrete simulation parameters, we provide some general basic rules for the design of (multi-)drug treatment protocols depending on the types and processes of dormancy mechanisms present in the population.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"597 ","pages":"Article 111995"},"PeriodicalIF":1.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683610","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

Cooperative SIR dynamics as a model for spontaneous blood clot initiation 作为自发血凝块形成模型的合作 SIR 动力学。

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2024-11-17 DOI: 10.1016/j.jtbi.2024.111991

Philip Greulich

{"title":"Cooperative SIR dynamics as a model for spontaneous blood clot initiation","authors":"Philip Greulich","doi":"10.1016/j.jtbi.2024.111991","DOIUrl":"10.1016/j.jtbi.2024.111991","url":null,"abstract":"<div><div>Blood clotting is an important physiological process to suppress bleeding upon injury, but when it occurs inadvertently, it can cause thrombosis, which can lead to life threatening conditions. Hence, understanding the microscopic mechanistic factors for inadvertent, spontaneous blood clotting, in absence of a vessel breach, can help in predicting and averting such conditions. Here, we present a minimal model – reminiscent of the SIR model – for the initiating stage of spontaneous blood clotting, the collective activation of blood platelets. This model predicts that in the presence of very small initial activation signals, collective activation of the platelet population is possible, but requires a sufficient degree of heterogeneity of platelet sensitivity. To propagate the activation signal and achieve collective activation of the bulk platelet population, it requires the presence of, possibly only few, hyper-sensitive platelets, but also a sufficient proportion of platelets with intermediate, yet higher-than-average sensitivity. A comparison with experimental results demonstrates a qualitative agreement for high platelet signalling activity.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"598 ","pages":"Article 111991"},"PeriodicalIF":1.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676877","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

Enlightening the blind spot of the Michaelis–Menten rate law: The role of relaxation dynamics in molecular complex formation 揭示迈克尔-门顿速率定律的盲点：弛豫动力学在分子复合物形成中的作用。

IF 1.9 4区数学

Journal of Theoretical Biology Pub Date : 2024-11-16 DOI: 10.1016/j.jtbi.2024.111989

Junghun Chae , Roktaek Lim , Thomas L.P. Martin , Cheol-Min Ghim , Pan-Jun Kim

{"title":"Enlightening the blind spot of the Michaelis–Menten rate law: The role of relaxation dynamics in molecular complex formation","authors":"Junghun Chae , Roktaek Lim , Thomas L.P. Martin , Cheol-Min Ghim , Pan-Jun Kim","doi":"10.1016/j.jtbi.2024.111989","DOIUrl":"10.1016/j.jtbi.2024.111989","url":null,"abstract":"<div><div>The century-long Michaelis–Menten rate law and its modifications in the modeling of biochemical rate processes stand on the assumption that the concentration of the complex of interacting molecules, at each moment, rapidly approaches an equilibrium (quasi-steady state) compared to the pace of molecular concentration changes. Yet, in the case of actively time-varying molecular concentrations with transient or oscillatory dynamics, the deviation of the complex profile from the quasi-steady state becomes relevant. A recent theoretical approach, known as the effective time-delay scheme (ETS), suggests that the delay from the relaxation time of molecular complex formation contributes to the substantial breakdown of the quasi-steady state assumption. Here, we systematically expand this ETS and inquire into the comprehensive roles of relaxation dynamics in complex formation. Through the modeling of rhythmic protein–protein and protein–DNA interactions and the mammalian circadian clock, our analysis reveals the effect of the relaxation dynamics beyond the time delay, which extends to the dampening of changes in the complex concentration with a reduction in the oscillation amplitude compared to the quasi-steady state. Interestingly, the combined effect of the time delay and amplitude reduction shapes both qualitative and quantitative oscillatory patterns such as the emergence and variability of the mammalian circadian rhythms. These findings highlight the downside of the routine assumption of quasi-steady states and enhance the mechanistic understanding of rich time-varying biomolecular processes.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"597 ","pages":"Article 111989"},"PeriodicalIF":1.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668951","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