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Feed-forward loop improves the transient dynamics of an antithetic biological controller. 前馈回路改善了仿生生物控制器的瞬态动力学特性。
IF 3.7 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-01-01 Epub Date: 2025-01-22 DOI: 10.1098/rsif.2024.0467
Thales R Spartalis, Mathias Foo, Xun Tang

Integral controller is widely used in industry for its capability of endowing perfect adaptation to disturbances. To harness such capability for precise gene expression regulation, synthetic biologists have endeavoured in building biomolecular (quasi-)integral controllers, such as the antithetic integral controller. Despite demonstrated successes, challenges remain with designing the controller for improved transient dynamics and adaptation. Here, we explore and investigate the design principles of alternative RNA-based biological controllers, by modifying an antithetic integral controller with prevalently found natural feed-forward loops (FFL), to improve its transient dynamics and adaptation performance. With model-based analysis, we demonstrate that while the base antithetic controller shows excellent responsiveness and adaptation to system disturbances, incorporating the type-1 incoherent FFL into the base antithetic controller could attenuate the transient dynamics caused by changes in the stimuli, especially in mitigating the undesired overshoot in the output gene expression. Further analysis on the kinetic parameters reveals similar findings to previous studies that the degradation and transcription rates of the circuit RNA species would dominate in shaping the performance of the controllers.

积分控制器以其对扰动具有较好的自适应能力,在工业上得到了广泛的应用。为了利用这种能力进行精确的基因表达调控,合成生物学家一直在努力构建生物分子(准)积分控制器,例如对偶积分控制器。尽管取得了成功,但在设计控制器以改善瞬态动力学和自适应方面仍然存在挑战。在这里,我们探索和研究了基于rna的生物控制器的设计原则,通过使用普遍存在的自然前馈回路(FFL)修改反积分控制器,以改善其瞬态动力学和自适应性能。通过基于模型的分析,我们证明,虽然基本对偶控制器对系统干扰表现出出色的响应性和适应性,但将1型非相干FFL纳入基本对偶控制器可以减弱由刺激变化引起的瞬态动力学,特别是在减轻输出基因表达的非期望超调方面。对动力学参数的进一步分析揭示了与先前研究相似的发现,即电路RNA物种的降解和转录率将在塑造控制器的性能方面起主导作用。
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引用次数: 0
Skin adaptation in lower limb amputees assessed through Raman spectroscopy and mechanical characterization. 通过拉曼光谱和力学表征评估下肢截肢者的皮肤适应性。
IF 3.7 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-01-01 Epub Date: 2025-01-08 DOI: 10.1098/rsif.2024.0475
Jack Hayes, Jennifer Andrews, Omar Abdelwahab, Tomas Andriuskevicius, Tom Briggs, Ralph Gordon, Peter Worsley, Claire A Higgins, Marc Masen

Following lower limb amputation residuum skin from the lower leg is used to reconstruct the residual limb. Unlike skin on the sole of the foot (plantar skin), leg skin is not inherently load bearing. Despite this, leg skin is required to be load bearing in the prosthetic socket. Current hypotheses propose that lower limb amputee skin can adapt to become load bearing with repeated prosthesis use. Here, we show using confocal Raman spectroscopy, mechanical characterization and cytokine analysis that adaptations occur which actually result in impaired barrier function, higher baseline inflammation, increased coefficient of friction and reduced stiffness. Our results demonstrate that repeated frictional trauma does not confer beneficial adaptations in amputee skin. We hypothesize that non-plantar skin lacks the biological capabilities to respond positively to repeated mechanical trauma in the same manner observed in plantar skin. This finding highlights the need for improved therapies as opposed to current mechanical conditioning or product solutions that directly relate to improving load-bearing capacity on the skin of lower limb amputees. This study also highlights the importance of measuring multiple parameters of application-specific skin at different scales for skin tribology applications.

下肢截肢后,残肢皮肤用于重建残肢。不像脚底的皮肤(足底皮肤),腿部皮肤不具有固有的承重能力。尽管如此,腿部皮肤仍需要在假肢窝中承受负荷。目前的假设认为,下肢截肢者的皮肤可以适应反复使用假肢的负荷。在这里,我们使用共聚焦拉曼光谱、力学表征和细胞因子分析表明,适应性的发生实际上导致屏障功能受损、基线炎症升高、摩擦系数增加和刚度降低。我们的研究结果表明,反复的摩擦创伤不会给截肢者的皮肤带来有益的适应。我们假设,非足底皮肤缺乏与足底皮肤相同的对重复机械创伤作出积极反应的生物学能力。这一发现强调了改进治疗方法的必要性,而不是目前的机械调节或产品解决方案,直接关系到提高下肢截肢者皮肤的承重能力。本研究还强调了在不同尺度上测量特定应用皮肤的多个参数对于皮肤摩擦学应用的重要性。
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引用次数: 0
State-space modelling using wastewater virus and epidemiological data to estimate reported COVID-19 cases and the potential infection numbers. 利用废水病毒和流行病学数据进行状态空间建模,以估计报告的COVID-19病例和潜在感染人数。
IF 3.7 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-01-01 Epub Date: 2025-01-08 DOI: 10.1098/rsif.2024.0456
Syun-Suke Kadoya, Yubing Li, Yilei Wang, Hiroyuki Katayama, Daisuke Sano

The current situation of COVID-19 measures makes it difficult to accurately assess the prevalence of SARS-CoV-2 due to a decrease in reporting rates, leading to missed initial transmission events and subsequent outbreaks. There is growing recognition that wastewater virus data assist in estimating potential infections, including asymptomatic and unreported infections. Understanding the COVID-19 situation hidden behind the reported cases is critical for decision-making when choosing appropriate social intervention measures. However, current models implicitly assume homogeneity in human behaviour, such as virus shedding patterns within the population, making it challenging to predict the emergence of new variants due to variant-specific transmission or shedding parameters. This can result in predictions with considerable uncertainty. In this study, we established a state-space model based on wastewater viral load to predict both reported cases and potential infection numbers. Our model using wastewater virus data showed high goodness-of-fit to COVID-19 case numbers despite the dataset including waves of two distinct variants. Furthermore, the model successfully provided estimates of potential infection, reflecting the superspreading nature of SARS-CoV-2 transmission. This study supports the notion that wastewater surveillance and state-space modelling have the potential to effectively predict both reported cases and potential infections.

由于报告率下降,COVID-19措施的现状使得难以准确评估SARS-CoV-2的流行情况,导致错过了最初的传播事件和随后的疫情。越来越多的人认识到,废水病毒数据有助于估计潜在感染,包括无症状和未报告的感染。了解隐藏在报告病例背后的COVID-19形势对于决策选择适当的社会干预措施至关重要。然而,目前的模型隐含地假设了人类行为的同质性,例如人群中的病毒脱落模式,这使得预测由于变体特异性传播或脱落参数而出现的新变体具有挑战性。这可能导致预测具有相当大的不确定性。在这项研究中,我们建立了一个基于废水病毒载量的状态空间模型来预测报告病例和潜在感染人数。我们使用废水病毒数据的模型显示出与COVID-19病例数的高拟合度,尽管数据集包括两种不同变体的波。此外,该模型成功地提供了潜在感染的估计,反映了SARS-CoV-2传播的超传播性质。这项研究支持了废水监测和状态空间模型有可能有效预测报告病例和潜在感染的观点。
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引用次数: 0
Can spatial self-organization inhibit evolutionary adaptation?
IF 3.7 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-01-01 Epub Date: 2025-01-29 DOI: 10.1098/rsif.2024.0454
B K Bera, O Tzuk, J J R Bennett, U Dieckmann, E Meron

Plants often respond to drier climates by slow evolutionary adaptations from fast-growing to stress-tolerant species. These evolutionary adaptations increase the plants' resilience to droughts but involve productivity losses that bear on agriculture and food security. Plants also respond by spatial self-organization, through fast vegetation patterning involving differential plant mortality and increased water availability to the surviving plants. The manners in which these two response forms intermingle and affect productivity and resilience have not been studied. Here we ask: can spatial patterning inhibit undesired evolutionary adaptation without compromising ecosystem resilience? To address this question, we integrate adaptive dynamics and vegetation pattern-formation theories and show that vegetation patterning can inhibit evolutionary adaptations to less productive, more stress-tolerant species over a wide precipitation range while increasing their resilience to water stress. This evolutionary homeostasis results from the high spatial plasticity of vegetation patterns, associated with patch thinning and patch dilution, which maintains steady local water availability despite decreasing precipitation. Spatial heterogeneity expedites the onset of vegetation patterning and induces evolutionary homeostasis at an earlier stage of evolutionary adaptation, thereby mitigating the productivity loss that occurs while the vegetation remains spatially uniform. We conclude by discussing our results in a broader context of evolutionary retardation.

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引用次数: 0
Quantifying the configurational complexity of biological systems in multivariate 'complexity space'.
IF 3.7 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-01-01 Epub Date: 2025-01-29 DOI: 10.1098/rsif.2024.0558
Tim Rock, Matthew A Wills

An increasing number of evolutionary studies seek to quantify the morphological complexity of organisms, particularly those comprising serially homologous elements at different hierarchical levels of organization. Numerous operational frameworks have been proposed for doing this, but most focus on one or multiple conflated aspects of what is really a multidimensional concept. Here, we advocate the use of 'complexity spaces': multidimensional spaces defined by different vectors of complexity. We explore their application to biological systems composed of homologous parts and identify three axes on which those systems differ: part number, part differentiation and the regularity of that differentiation. Such complexity spaces can be constructed for systems at different hierarchical levels of biological organization. To illustrate this, we explore the complexity spaces for trilobite body plans (comprising body segments of varying number and form), and for ant colonies (comprising differentiated worker polymorphisms of varying number and form within a 'superorganism'). Many different complexity spaces are possible, but all seek to distinguish different aspects of complexity within an information-theoretic framework, and thereby to clarify patterns of complexity evolution.

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引用次数: 0
Adaptive behaviour during epidemics: a social risk appraisal approach to modelling dynamics. 流行病期间的适应性行为:建模动力学的社会风险评估方法。
IF 3.7 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-01-01 Epub Date: 2025-01-15 DOI: 10.1098/rsif.2024.0363
David O'Gara, Matt Kasman, Laurent Hébert-Dufresne, Ross A Hammond

The interaction of infectious diseases and behavioural responses to them has been the subject of widespread study. However, limited attention has been given to how broader social context shapes behavioural response. In this work, we propose a novel framework which combines two well-studied dynamic processes into a 'social risk appraisal' mechanism. Our proposed framework has both theoretical and empirical support, occupying an important middle ground in the interacting contagions literature. Results indicate that a risk appraisal framework can express a wide range of epidemic outcomes, driven by simple interaction rules. This framework has implications for designing containment strategies in disease outbreaks, as well as equity considerations. Finally, the risk appraisal approach is well-posed to engage with a broad set of literature in epidemic management, decision-making and the adoption of social behaviours.

传染病的相互作用和对传染病的行为反应一直是广泛研究的主题。然而,人们对更广泛的社会背景如何影响行为反应的关注有限。在这项工作中,我们提出了一个新的框架,将两个经过充分研究的动态过程结合到“社会风险评估”机制中。我们提出的框架既有理论支持,也有实证支持,在相互作用传染文献中占据了重要的中间地带。结果表明,在简单的交互规则驱动下,风险评估框架可以表达广泛的疫情结果。这一框架对设计疾病暴发的遏制战略以及公平考虑具有影响。最后,风险评估方法可以很好地与流行病管理、决策和采取社会行为方面的广泛文献相结合。
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引用次数: 0
Improving influenza forecast in the tropics and subtropics: a case study of Hong Kong. 改善热带及亚热带地区的流感预报:以香港为例
IF 3.7 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-01-01 Epub Date: 2025-01-15 DOI: 10.1098/rsif.2024.0649
Haokun Yuan, Eric H Y Lau, Benjamin J Cowling, Wan Yang

Influenza forecasts could aid public health response as shown for temperate regions, but such efforts are more challenging in the tropics and subtropics due to more irregular influenza activities. Here, we built six forecast approaches for influenza in the (sub)tropics, with six model forms designed to model seasonal infection risk (i.e. seasonality) based on the dependence of virus survival on climate conditions and to flexibly account for immunity waning. We ran the models jointly with the ensemble adjustment Kalman filter to generate retrospective forecasts of influenza incidence in subtropical Hong Kong from January 1999 to December 2019 including the 2009 A(H1N1)pdm09 pandemic. In addition to short-term targets (one to four weeks ahead predictions), we also tested mid-range (one to three months) and long-range (four to six months) forecasts, which could be valuable for long-term planning. The largest improvement came from the inclusion of climate-modulated seasonality modelling, particularly for the mid- and long-range forecasts. The best-performing approach included a seasonal-trend-based climate modulation and assumed mixed immunity waning; the forecast accuracies, including peak week and intensity, were comparable to that reported for temperate regions including the USA. These findings demonstrate that incorporating mechanisms of climate modulation on influenza transmission can substantially improve forecast performance in the (sub)tropics.

正如在温带地区所显示的那样,流感预报可以帮助公共卫生应对,但由于流感活动更加不规律,这种努力在热带和亚热带地区更具挑战性。在这里,我们建立了六种(亚)热带流感的预测方法,其中六种模型形式旨在基于病毒存活对气候条件的依赖来模拟季节性感染风险(即季节性),并灵活地考虑免疫力下降。我们将这些模型与集合平差卡尔曼滤波联合运行,以生成1999年1月至2019年12月包括2009年甲型H1N1流感大流行在内的亚热带香港流感发病率的回顾性预测。除了短期目标(提前一到四周的预测),我们还测试了中期(一到三个月)和长期(四到六个月)的预测,这对于长期规划可能是有价值的。最大的改进来自纳入了气候调节的季节性模式,特别是用于中长期预报的模式。效果最好的方法包括基于季节趋势的气候调节和假设混合免疫减弱;预报精度,包括高峰周和强度,与包括美国在内的温带地区的预报相当。这些发现表明,结合气候调节流感传播的机制可以大大提高(亚)热带地区的预测效果。
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引用次数: 0
Correction: 'Analytical approximation for invasion and endemic thresholds, and the optimal control of epidemics in spatially explicit individual-based models' (2021), by Suprunenko et al. 更正:“入侵和流行阈值的分析近似,以及空间明确的基于个体的模型中流行病的最佳控制”(2021年),Suprunenko等人。
IF 3.7 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-01-01 Epub Date: 2025-01-15 DOI: 10.1098/rsif.2024.0866
Yevhen F Suprunenko, Stephen J Cornell, Christopher A Gilligan
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引用次数: 0
Cooperative bots exhibit nuanced effects on cooperation across strategic frameworks.
IF 3.7 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-01-01 Epub Date: 2025-01-29 DOI: 10.1098/rsif.2024.0427
Zehua Si, Zhixue He, Chen Shen, Jun Tanimoto

The positive impact of cooperative bots on cooperation within evolutionary game theory is well-documented. However, prior studies predominantly use discrete strategic frameworks with deterministic actions. This article explores continuous and mixed strategic approaches. Continuous strategies use intermediate probabilities for varying degrees of cooperation and focus on expected payoffs, while mixed strategies calculate immediate payoffs from actions taken within these probabilities. Using the prisoner's dilemma game, this study examines the effects of cooperative bots on human cooperation in both well-mixed and structured populations across these strategic approaches. Our findings reveal that cooperative bots significantly enhance cooperation in both population types under weak imitation scenarios, where players are less concerned with material gains. Conversely, under strong imitation scenarios, cooperative bots do not alter the defective equilibrium in well-mixed populations but have varied impacts in structured populations. Specifically, they disrupt cooperation under discrete and continuous strategies but facilitate it under mixed strategies. These results highlight the nuanced effects of cooperative bots within different strategic frameworks and underscore the need for careful deployment, as their effectiveness is highly sensitive to how humans update their actions and their chosen strategic approach.

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引用次数: 0
Multicellular PID control for robust regulation of biological processes.
IF 3.7 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-01-01 Epub Date: 2025-01-29 DOI: 10.1098/rsif.2024.0583
Vittoria Martinelli, Davide Fiore, Davide Salzano, Mario di Bernardo

This article presents the first implementation of a proportional-integral-derivative (PID) biomolecular controller within a consortium of different cell populations, aimed at robust regulation of biological processes. By leveraging the modularity and cooperative dynamics of multiple engineered cell populations, we develop a comprehensive in silico analysis of the performance and robustness of P, PD, PI and PID control architectures. Our theoretical findings, validated through in silico experiments using the BSim agent-based simulation platform for bacterial populations, demonstrate the robustness and effectiveness of our multicellular PID control strategy. This innovative approach addresses critical limitations in current control methods, offering significant potential for applications in metabolic engineering, therapeutic contexts and industrial biotechnology. Future work will focus on experimental validation in vivo and further refinement of the control models.

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引用次数: 0
期刊
Journal of The Royal Society Interface
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